Studies Proving Essentiality of Omega-3

  1. People and Pet Glow Information. ENRECO. 1997.
    In 1994, the American Institute of Nutrition (AIN), who publish the Journal of Nutrition, declared that Omega-3 was essential for laboratory rats and mice. The truth is that Omega-3 is essential for all mammals, which include dogs, cats, ferrets, horses, humans, etc. The reason AIN declared Omega-3 essential was that in some experiments, some of the rats were very susceptible to cancer, AIDS, arthritis, and other diseases; but other rats were very resistant to these diseases. Most of these researchers were ignorant of the connection between Omega-3 deficiency and immune-related diseases. When this connection became common knowledge because of research by Lands, Holman, Crawford, Bourre, Sinclair, Lee, and many others, the ad hoc committee on Diets for Laboratory Animals decided that Omega-3, in the form of alpha-linolenic acid, would be a required nutrient for all rodent diets. Flax is nature's richest source of Omega-3. It also contains many other important, beneficial compounds, such as lignans, fiber, trace minerals, and essential amino acids. You'll also uncover millions of dollars of research work that the U.S. Food and Drug Administration, the National Cancer Institute, the U.S. Department of Agriculture, the National Institute of Alcohol Abuse, and the Canadian Food Protection Branch have done on flax. Look for it under You and all your animal friends can obtain many wonderful benefits, such as beautiful, shiny hair and more energy just by adding flax to your diet. For Glowing Good Health, look for flax labelled, &quotPeople and Pet Glow" in pet food stores and &quotFortified Flax" in health food stores and pet foods made with ENRECO's Stabilized Flax. May you and your furry friends be ever as healthy as laboratory rats and mice. For more information on essentiality of linolenic acid, check out the rest of the abstracts in this section.


  2. Using flax to get benefit of fish oils (Patent). A method to process flax as food additive source of omega 3 has been developed by Paul Stitt of Essential Nutrient Research Company of Manitowoc. U.S Patent No.4,857,326.
    . New York Times (National Edition). August 19, 1989;16.
    (c) 1996 Information Access Co. All rts. reserv.
    A method to process flax for a food additive source of omega 3 has been developed and patented (US 4,857,326) by PA Stitt. Omega 3, a fatty acid, has been cited as treatment for symptoms of heart disease, such as angina, and as a way to for prevent cancer. In its fish liver oil form, however, it is too unpalatable for use as a dietary supplement. The new process involves the use of flax, which contains omega 3-rich oil, into a wide variety of foods. The flax seed, treated with zinc and vitamin B-6 to keep the linseed oil from becoming rancid, yields a stable product that is not bad tasting. Flax seed filled products, including breads, cookies muffins and drink mixes now being sold in the Midwest, account for 65% of the $5.5 mil in sales for Natural Ovens of Manitowoc (Manitowoc, WI), a new company formed by the inventor.


  3. Fatty acids: their biochemical and functional classification. Agostoni C, Bruzzese MG., V Clinica Pediatrica, Universita degli Studi di Milano, Italia. Pediatr Med Chir. 1992;14:473-479.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Fatty acids (FA) constitute the main component of phospholipids, triglycerides and cholesterol esters. FA are acidic, monocarboxylic linear chains of variable length: short-chain FA (2-4 carbon atoms), medium-chain FA (6-12 carbon atoms), long-chain FA (14-18 carbon atoms), very long-chain FA (derived from parental 18-carbon molecules). They can be further subdivided into saturated (no double bond), monounsaturated (one double bond) and polyunsaturated (two or more double bonds). They are all involved in energetic, metabolic and structural activities. Short-chain FA act as growth factors; medium chain FA are readily available as energy source; saturated long-chain FA constitute a source of energy but may be implicated in the development of the atherosclerotic process; unsaturated long-chain FA include oleic acid and the essential fatty acids (linoleate and linolenate), and are all implicated in fundamental metabolic processes; very-long chain FA are the most characteristic molecules in biologic membranes. From recent works it is clearly established that the physiological role of FA depends on the chain length, and that the very-long chain molecules could determine the quality of human development. A functional classification of FA today must be based not only on the rate of unsaturation, but also (and most importantly) on the chain length.


  4. Polyunsaturated fatty acids status in blood, heart, liver, intestine, retina and brain of newborn piglets fed either sow milk or a milk replacer diet. Alessandri JM, Goustard B, Guesnet P, Durand G. Reprod Nutr Dev. 1996;36:95-109.
    Docosahexaenoic (DHA) and arachidonic acids (20:4n-6) are deposited in large amounts in the developing neural tissues of the fetus and neonate. The suckling infants receive both fatty acids via the maternal milk, whereas formula-fed infants must synthesize them de novo from their respective precursors, linoleic (18:2n-6) and alpha-linolenic (18:3n-3) acids. We compared the lipid status of 14- and 21-day-old piglets fed either natural milk or infant formula, with special emphasis on the resulting DHA and 20:4n-6 levels in the neural tissues. The two diets presented similar ratios of precursors (18:2n-6/18:3n-3 = 14-16). The sow milk contained 20:4n-6 (0.6% of total fatty acids) and very low levels of DHA (< 0.1%). Formula feeding resulted in higher deposition of DHA in the brain than sow milk feeding, whereas the brain content of 20:4n-6 was not altered. The brain DHA level was negatively correlated with the 18:2n-6/18:3n-3 ratio in the red blood cells (RBC). In contrast, it was not correlated with the DHA concentration in the circulating lipids. The results indicate that the very low amount of DHA in sow milk has no effect on the accumulation of DHA in the piglet's brain, and that natural milk and formula are not equivalent with respect to precursor bio-availability and processing. This difference could be the result of a higher absorption rate and/or the metabolic sparing of formula 18:3n-3. The data support the view that the balance between the essential precursors in the circulating lipids is of vital importance for optimal deposition of DHA in the developing neural tissues.


  5. Accretion of n-3 fatty acids in the brain and retina of chicks fed a low-linolenic acid diet supplemented with docosahexaenoic acid. Anderson GJ, Connor WE., Oregon Health Sciences University, Portland, OR. Am J Clin Nutr. 1994;59:1338-1346.
    Includes references.
    Diets low in alpha-linolenic acid may not support normal brain accretion of n-3 fatty acids. An n-3 fatty acid-deficient diet was fed to laying hens and the resulting deficient chicks were fed a low-linolenic acid diet based on corn oil, or the same diet supplemented with docosahexaenoic acid. Control chicks from soybean oil-fed hens were fed a soybean oil-based diet. The fatty acid composition of the chick brains, retinas, livers, and serum was determined after 0-4 wk. The corn oil diet did not reverse the deficiency but the combination of corn oil and docosahexaenoic acid rapidly restored brain and retinal concentrations of docosahexaenoic acid. Supplemented chicks, however, showed a slight lowering of arachidonic acid in the brain and serum. This study demonstrates that a low-linolenic acid diet without docosahexaenoic acid fails to support accretion of n-3 fatty acids in the nervous tissue of chicks.


  6. On the demonstration of omega-3 essential-fatty-acid deficiency. Anderson GJ, Connor WE. Am J Clin Nutr. 1989;49:585-587. charts.
    Includes 25 references.
    Abstract: In the few reported cases of human omega-3 fatty acid deficiency, the clinical conditions described probably resulted from either combined omega-3 and omega-6 fatty acid deficiencies (leading to skin lesions) or from complications arising from special medical situations, such as long-term total parental nutrition with an omega-3-deficient fat preparation, such as safflower oil. These reports plus the experimental animal studies do call attention to the fact that those who devise enteral formula diets or parenteral fluids should always consider that both series of fatty acids (omega-6 and omega-3) must be included in the total diet as essential nutrients. This consideration is especially important if the feeding period is months or even years or if in the short-term continuous glucose infusion blocks the release of these essential fatty acids from adipose tissue stores. The deficient state, biochemically identifiable, can arise in a few days under the latter circumstance.


  7. Alterations in triacylglycerols and free fatty acids of plasma and adipose tissue of lambs dispensed with various essential fatty acids. Angelov A, Dimov V. Zhivotnovud Nauki. 1990;27:81-88.
    (c) 1996 American Chemical Society. All rts. reserv.


  8. Effects of alpha-linolenic acid deficiency and age on oxidative phosphorylation and fatty acid composition of rat liver mitochondria. Angulo-Monroy O, Guesent P, Durand GA., I.N.R.A., Jouy-en-Josas, France . The J Of Nutr Biochem. 1991;2:484-491.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv. Includes references.
    Two weeks before mating, female rats from n-3 PUFA deficient lineage were divided into two groups; the first group continued to get the n-3 PUFA deficient diet (peanut oil) and the second one received a control diet (peanut and rapeseed oil mixture). Total phospholipid fatty acid composition, respiration, and succinic dehydrogenase (SDH) activity were studied in liver mitochondria from 14-, 30-, and 90-day-old male rats delivered by these two experimental groups. Moreover, the principal phospholipid classes PC, PE, CL) content and F1F0 ATPase activity were studied in liver submitochondrial (inner) membrane from 30-day-old rats. The results showed that dietary n-3 PUFA deficiency did not modify cholesterol and phospholipid levels in total mitochondrial lipids whatever the animal age. However, 22:6 n-3 (DHA) level in phospholipids was considerably reduced by this deficiency; this reduction was compensated by an increase in 22:5 n-6 and 20:4 n-6 so that the total polyunsaturated fatty acid sum (n-6 + n-3) was not modified. it did not alter basal and stimulated succinic dehydrogenase specific activity, state 3, state 4, neither respiratory control ratio. However, the rate of oxidative phosphorylation pathway was doubled between 14- and 30-day-old animals independently of diet. The relative proportions of the major phospholipid classes in submitochondrial membrane were not altered. Also, there was no significant effect on F1F0 ATPase activity in submitochondrial membrane. Finally, the considerable reduction of DHA level and the parallel increase of the n-6/n-3 ratio in mitochondrial membrane phospholipids Ad not influence mitochondrial physiological activity, at least with regard to experimental conditions used and to the parameters studied.


  9. Exclusion of alpha -linolenic acid from the diet of rats for several generations. Araya J, Cagalj A., Departamento de Nutricion, Facultad de Medicina, Universidad de Chile, Santiago, Chile. Arch Latinoam Nutr. 1993;43:123-131.
    (c) 1995 CAB International. All rts. reserv.
    During 3 successive generations female Wistar rats were given a diet with 10% sunflower oil deficient in alpha -linolenic acid (C18:3 omega 3) or a control diet with 10% soyabean oil as source of fat. Rats given sunflower oil showed a decrease in fecundity, fertility and postnatal growth as well as high rates of mortality for offspring from birth to 3 days old. Perinatal mortality increased with successive generations from 14.6 to 16.9 to 18.6% compared with control values. The fatty acid composition of placental phospholipids and milk lipids reflected the nature of the dietary oil. The possibility that C18:3 omega 3 might function in a different way from the essential fatty acid role of C18:2 omega 6 in reproduction in rats is discussed.


  10. Formula alpha-linolenic (18:3(n - 3)) and linoleic (18:2(n - 6)) acid influence neonatal piglet liver and brain saturated fatty acids, as well as docosahexaenoic acid (22:6(n - 3). Arbuckle LD, Rioux FM, MacKinnon MJ, Innis SM., Department of Human Nutrition, University of British Columbia, Vancouver, Canada. Biochim Biophys Acta. 1992;1125:262-267.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Saturated fatty acids can be synthesized de novo and play a role in determining properties of structural membranes. The effect of dietary essential fatty acids, linoleic acid (18:2(n - 6)) and alpha-linolenic acid (18:3(n - 3)), on the saturated fatty acid content of membrane phospholipid has not previously been considered in newborn nutrition. The studies report the effect of low (1% fatty acids) or high (4%) formula 18:3(n - 3) with low (16%) or high (30-35%) formula 18:2(n - 6) on the saturated and unsaturated fatty acid composition of liver and brain structural lipid of piglets fed formula from birth for 15 days. A significant inverse relationship between the formula % 18:3(n - 3), but not 18:2(n - 6), and the liver phospholipid palmitic acid (16:0) was found. This may indicate a possible effect of dietary 18:3(n - 3) on de novo synthesis of 16:0 and requires further investigation. Monounsaturated fatty acids in both liver and brain were significantly lower in response to high 18:3(n - 3) and to high 18:2(n - 6) plus low 18:1(n - 9) in the formula. Liver phospholipid and brain total lipid % docosahexaenoic acid (22:6(n - 3)) were significantly higher when formula containing 4% rather than 1% 18:3(n - 3) was fed, suggesting that 1% 18:3(n - 3) may not saturate Omega-3 fatty acids in various tissues. These results suggest that future studies of essential fatty acid requirements, specifically 18:3(n - 3), should consider possible influences on the saturated fatty acids which also play a functional role in tissue structural lipids.


  11. Effects of selenium and vitamin e status on plasma creatine kinase activity in calves. Arthur JR., Biochemistry Division, Rowett Research Institute, Bucksburn, Aberdeen, United Kingdom. J Nutr. 1988;118:747-755.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv.
    In four experiments, attempts were made to induce nutritional myopathy in calves given a selenium- and vitamin E-deficient diet (less than 0.01 mg Se/kg, less than 2 mg total vitamin E/kg). In housed calves, combined selenium and vitamin E deficiency was insufficient to provoke the large increase in plasma creatine kinase activity typical of muscle damage. Such increases were only obtained when selenium- and vitamin E-deficient calves were turned out from indoor housing in small pens to open pasture. The rises in plasma creatine kinase activity on turnout were prevented when the calves had consumed diets supplemented with 0.1 mg Se/kg (as Na2SeO3). The percentage of the polyunsaturated fatty acid, linolenic acid (18:3 omega 3), in plasma total fatty acids was up to 10-fold higher in calves consuming fresh grass at pasture or indoors than in those housed indoors and fed purified diet. However, in the housed calves there were no rises in plasma creatine kinase activity, whereas large increases occurred in those turned out to pasture. Thus, because increased dietary polyunsaturated fatty acid at turnout is not the sole trigger for the development of myopathy in selenium- and vitamin E-deficient calves, additional unidentified dietary or environmental factors must also be involved.


  12. Occurrence of long and very long polyenoic fatty acids of the n-9 series in rat spermatozoa. Aveldano MI, Rotstein NP, Vermouth NT., Instituto de Investigaciones Bloquimicas, Universidad Nacional del Sur, Bahia Blanca, Argentina. Lipids. 1992;27:676-80.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Dietary deficiency of essential fatty acids of the n-3 and n-6 series is known to promote a compensatory increase in polyenoic fatty acids of the n-9 series in the lipids of mammalian tissues. In the present study long-chain n-9 polyenes were found to be normal components of the epididymis and especially of sperm isolated from that tissue, in healthy, well-fed, fertile rats maintained on essential fatty acid-sufficient diets. The n-9 polyenes occurred in large concentrations in the choline glycerophospholipids (CGP), the major phospholipid class of spermatozoa in epididymal cauda, and were highly concentrated in plasmenylcholine, the major subclass of CGP. The uncommon polyene 22:4n-9 was found in the highest proportion, followed in order of relative abundance by 22:3n-9, 20:3n-9 and 24:4n-9. These polyenes were probably derived from oleate (18:1n-9) in much the same way as long-chain polyenes of the n-6 and n-3 series are derived from linoleate (18:2n-6) and linolenate (18:3n-3), respectively.


  13. Effect of dietary flaxseed on fatty acid composition, superoxide, nitric oxide generation and antilisterial activity of peritoneal macrophages from female Sprague-Dawley rats. Babu US, Bunning VK, Weisenfield P, Raybourne RB, O'Donnell M. Life Sci. 1997;V 60:545-554.
    The impact of ground flaxseed (FS) or flaxseed mean (FSM) diets on the fatty acid composition and functions of rat peritoneal exudate cells (PEC) was determined. Female weanling Sprague-Dawley rats (10/group) were fed isocaloric AIN-76 diets supplemented with 0.0, 10.0% (w/w) FS or 6.2% (w/w) FSM. At the end of 56-days, rat serum and thioglycollate-elicted PEC were analyzed for total lipid fatty acids. Production of nitric oxide (NO) and superoxide (O2), Listeria monocytogenes (LM) phagocytic index and antilisterial activity of resident PEC were also assessed. A significant increase in a-linolenic (C18:3), eicosapentanoic (C20:5) and docosahexanoic (22:6) acids, as well as a significant reduction in arachidonic acid (C20:4) was observed in the serum of rats fed 10% FS. Dietary FS caused a significant reduction in palmitic acid (C16:0) and an increase in stearic acid (C18:0) of PEC. Defatted FSM produced a significant increase in long chain fatty acids, which included eicosadienoic acid (C20:2) in PEC and C22:6 in serum. PEC from rats fed 10.0% FS produced significantly less (about 50%) O2 in response to phorbol myristate acetate (PMA), than did PEC from control animals, dietary treatment had no effect on O2 in response to LM. FSM had no impact on the O2 production by PEC in response to PMA or LM. Antilisterial activity of PEC was determined by comparing bacterial uptake after 1 hr with recovery 24 hrs later. Despite comparably equivalent bacterial uptake, few viable intracellular LM were recovered at T=24 for all test samples, indicating that, regardless of the dietary treatment, PEC were able to handle the in vitro LM infection. This bacterial clearance was accompanied by equivalent NO generation by PEC from each dietary group in response to LM. Summarily, dietary FS produced significant changes in fatty acid composition of serum and PEC, inhibited O2 generation by PEC, and was ineffectual to both NO production by and antilisterial activity of PEC. There are conflicting reports on the impact of dietary a-linolenic acid (C18:3) on structure and function of peritoneal macrohages. Some reports showed an increase in n-3 fatty acids (first double bond occurs at the 3rd carbon atom from the methyl end of the fatty acid molecule) and a decrease in n-6 (first double bond occurs at the 6th carbon atom from the methyl end of the fatty acid molecule) to n-3 fatty acid ratios in macrophages and neutrophils by either in vivo or in vitro supplementation of C18:3 (1-6). Others reported a change in inflammatory response by macrophages and neutrophils. These effects were ovserved in various species (e.g. rats, mice and horses). Among the antiinflammatory responses noted were reductions in leukotrienes (LTB, LTC4, LYE4) (3,4,7), prostaglandin E2 (2,7), tumor necrosis factor (8), thromboxane B2 (9,10) and platelet activating factor (1). Other reports suggested proinflammatory effects (increased production of tumor necrosis factor and superoxide generation) in response to C18:3 exposure (5,11,12). Macrophages play multiple roles in the immune response. Apart from an involvement in inflammatory reactions (13), macrophages present antigen to lymphocytes during the development of specific immunity (14) and serve as supportive cells to lymphocytes by releasing soluble factors (cytokines). Macrophages also carry out protective functions of ingesting and killing invading pathogens and parasites by oxidative and non-oxidative mechanisms (15). Previous studies have focused mainly on the effects of flaxseed oil and other oils enriched in C18:3 on antiiflammatory activites of macrophages. In our study, dietary flaxseed, in its commonly consumed from (bread and cereal) (16), was used to assess total lipid fatty composition and some immunologic functions of PEC. Ground flaxseed was the main source of C18:3, and defatted flaxseed meal was used to determine if any effects were related to the lipid portion of flaxseed. We observed that dietary flaxseed had no negative influence on the in vitro survival of Listeria monocytogenes or the production of nitric oxide and O2 by peritoneal exudate cells. These results suggest potential health benefits conferred by dietary flaxseed, which include anti-inflammatory properties, without compromising the ability of phagocytic cells to kill bacteria.

  14. Time course of omega-3 fatty acid incorporation into serum lipid subfractions in dogs fed whole ground flax seed. Bauer JE, Stitt PA. To Be Published.
    The purpose f the study, was to examine, in dogs, the time course of the nutritional effects of a diet of 3% whole ground flax seed on serum lipid subfractions.
    Results showed that the linolenic acid from ground flax seed was rapidly absorbed and converted to long chain Omega-3 compounds. In four days the level of linolenic acid in phospholipids tripled and stayed at that same level during the entire 84 days of the study. DPA increased 75% and achieved steady state levels in 14 days. DHA levels in the serum did not increase during the 84 days.
    The control diet contained 0.15% linolenic acid. The experimental diet contained 1.1% linolenic acid. Both diets contained 3.5% linoleic acid. The control diet certainly did not saturate the level in the serum. Higher levels than 3% flax in the diet may lead to higher levels in the serum.


  15. Bazan NG, Murphy MG, Toffano G; Neurobiology of essential fatty acids. New York : Plenum Press; 444 p.
    &quotProceedings of a symposium on the Neurobiology of Essential Fatty Acids, held July 10-12, 1991, in Palm Cove, Far North Queensland, Australia"--T.p. verso.


  16. Influence of dietary n-6/n-3 polyunsaturated fatty acid balance on the development of tolerance during chronic ethanol intoxication in rats. Beauge F, Zerouga M, Durand G, Bourre JM., INSERM U 26, Hopital Fernand Widal, Paris, France. Alcohol. 1992;27:257-265.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The present study addresses the possible interacting effects of dietary n-6/n-3 polyunsaturated fatty acid (PUFA) balance and chronic ethanol intoxication on the synaptic membrane responses to ethanol and the development of tolerance in rats. Wistar rats were fed either a standard lab chow or various semi-synthetic diets: rich in PUFA (from soya oil: SO), deficient in linolenate (from sunflower oil: SFO) or rich in long-chain (n-3) PUFA (cod liver oil: CLO). Male adult rats from the second specially fed generation were submitted to a 3-week alcoholization by daily intubation. Functional tolerance was quantified by the hypothermic response to a challenge dose of ethanol. Synaptic fluidity and sensitivity to ethanol (variations after acute ethanol addition) were assessed by fluorescence polarization (FP) of DPH, TMA-DPH or PROP-DPH. Membrane fatty acid composition was determined by GLC. The fatty acid composition of the synaptic membranes was influenced by the diet, but rearrangements among the lipids occurred, resulting in an apparent stability in brain membrane fluidity parameters. Nevertheless, clear-cut differences were noted in response to ethanol intoxication according to the diet. In the same period of time, rats fed SFO or CLO diets were unable to develop tolerance to ethanol at the membrane level as well as functionally, contrarily to the rats fed SO or standard diets. The structurally specific roles of PUFA are suggested by the negative membrane effects of the alpha-linolenate deficient diet (SFO) and the positive ones of a diet (SO) rich and well balanced in (n-3 + n-6) PUFA. Furthermore, the n-6/n-3 PUFA balance in the synaptic membrane needs to be kept within very narrow limits to allow normal development of the adaptive response to ethanol.


  17. The metabolism and availability of essential fatty acids in animal and human tissues. Bezard J, Blond JP, Bernard A, Clouet P. Reprod Nutr Dev. 1994;34:539-568.
    Essential fatty acids (EFA), which are not synthesized in animal and human tissues, belong to the n-6 and n-3 families of polyunsaturated fatty acids (PUFA), derived from linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (LNA, 18:3n-3). Optimal requirements are 3-6% of ingested energy for LA and 0.5-1% for LNA in adults. Requirements in LNA are higher in development. Dietary sources of LA and LNA are principally plants, while arachidonic acid (AA, 20:4n-6) is found in products from terrestrian animals, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in products from marine animals. EFA are principally present in dietary triacylglycerols, which should be hydrolyzed by lipases in gastric and intestinal lumen. DHA seems to be released more slowly than the others. Its intestinal absorption is delayed but not decreased. Long-chain PUFAs are incorporated in noticeable amounts in chylomicron phospholipids. However, their uptake by tissues is no more rapid than uptake of shorter chain PUFA. In tissues, LA and LNA, which constitute the major part of dietary EFA, should be converted into fatty acids of longer and more unsaturated chain by alternate desaturation (delta 6, delta 5, delta 4)-elongation reactions. Animal tissues are more active in this biosynthesis than human tissues. Liver is one of the most active organs and its role is critical in providing less active tissues, particularly the brain, with long-chain PUFA secreted in VLDL (very low density lipoprotein). In liver, many nutritional, hormonal and physiological factors act on the PUFA biosynthesis. Dietary fatty acids exert a great influence and are often inhibitory. Dietary LNA inhibits delta 6 desaturation of LA. The desaturation products AA, EPA, and DHA inhibit delta 6 desaturation of LA and delta 5 desaturation of DGLA (dihomo-gamma-linolenic acid). With regard to hormones, insulin and thyroxin are necessary to delta 6 and delta 5 desaturation activities, whereas other hormones (glucagon, epinephrine, ACTH, glucocorticoids) inhibit desaturation. Concerning the physiological factors, the age of individuals is critical. In the fetus, the liver and the brain are capable of converting LA and LNA into longer-chain EFA, but these are also delivered by the mother, after synthesis in the maternal liver and placenta. Just after birth, in animals, the delta 6 desaturation activity increases in the liver and decreases in the brain. In aging, the capacity of the whole liver to desaturate LA and DGLA is equal at 1.5 and 25 months of age in rats fed a balanced diet throughout their life and the AA and DHA content of tissue phospholipids is unchanged in aging.


  18. Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids. Birch DG, Birch EE, Hoffman DR, Uauy RD., Anderson Vision Research Center, Retina Foundation of the Southwest, Dallas, Texas 75231. Invest Ophthalmol Vis Sci. 1992;33:2365-2376.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Full-field electroretinograms (ERGs) were obtained from very-low-birth-weight (VLBW) neonates to determine whether omega-3 (omega-3) fatty acids are essential for normal human retinal development. Eighty-one infants born at 30.4 (standard deviation, +/- 1.5) wk gestation were, within 10 d of birth, either enrolled to receive mother's milk (naturally containing both omega-6 and omega-3 essential fatty acids) or randomized to receive one of the infant formulas. Corn oil-based Formula A contained mainly linoleic acid (18:2 omega-6) and was low in all omega-3 fatty acids. Soy oil-based Formula B contained ample alpha-linolenic acid (18:3 omega-3) but no long-chain omega-3. Formula C, supplemented with both alpha-linolenic acid and marine oils, was comparable to human milk in long-chain omega-3. Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception. Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception. Significant differences were found among groups in rod ERG function. Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain omega-3 (human milk, Formula C, and intrauterine). Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition. Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level. Differences were not present in infants at 57 wk postconception. No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception. Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk. These findings suggest that retinal function varies with the dietary supply of omega-3 fatty acids in VLBW infants.


  19. Dietary essential fatty acid supply and visual acuity development. Birch EE, Birch DG, Hoffman DR, Uauy R., Retina Foundation of the Southwest, Dallas, TX 75231. Invest Ophthalmol Vis Sci. 1992;33:3242-3253.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The influence of dietary omega-3 fatty acid supply on visual acuity development was evaluated in very low birth weight (VLBW) infants using visual-evoked potential (VEP) and forced-choice preferential-looking (FPL) procedures at 36 and 57 wk postconception. The VLBW infants born at 27-33 wk postconception were randomized to one of three diet groups: corn oil, which provided solely linoleic acid; soy oil, which provided linoleic and alpha-linolenic acids; or soy/marine oil; which was similar to the soy oil formula but also provided preformed long chain omega-3 fatty acids. The VLBW infants in the soy/marine oil group had higher omega-3 levels in erythrocyte membranes and better VEP and FPL acuities at 36 and 57 wk than infants in the corn oil group. The soy oil group had intermediate omega-3 levels in erythrocyte membranes and significantly poorer VEP acuity at 57 wk compared with the soy/marine oil group. Only the soy/marine oil group had acuities comparable to the &quotgold standards" of VLBW infants fed human milk and preterm infants who were born and tested at 35-36 wk postconception. In addition, VEP and FPL acuity were poorer in a nonrandomized group of formula-fed full-term infants than in breast-fed full-term infants. The results suggest that dietary omega-3 fatty acid supply may play an important role in early human visual development.


  20. Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. A population-based intervention trial from the Tromso study. Bonaa KH, Bjerve KS, Straume B, Gram IT, Thelle D. N Engl J Med. 1990;322:795-801.
    Studies of whether polyunsaturated fatty acids in fish oil--in particular, eicosapentaenoic and docosahexaenoic acids--lower blood pressure have varied in design and results. We conducted a population-based, randomized, 10-week dietary-supplementation trial in which the effects of 6 g per day of 85 percent eicosapentaenoic and docosahexaenoic acids were compared with those of 6 g per day of corn oil in 156 men and women with previously untreated stable, mild essential hypertension. The mean systolic blood pressure fell by 4.6 mm Hg (P = 0.002), and diastolic pressure by 3.0 mm Hg (P = 0.0002) in the group receiving fish oil; there was no significant change in the group receiving corn oil. The differences between the groups remained significant for both systolic (6.4 mm Hg; P = 0.0025) and diastolic (2.8 mm Hg; P = 0.029) pressure after control for anthropometric, lifestyle, and dietary variables. The decreases in blood pressure were larger as concentrations of plasma phospholipid n-3 fatty acids increased (P = 0.027). Dietary supplementation with fish oil did not change mean blood pressure in the subjects who ate fish three or more times a week as part of their usual diet, or in those who had a base-line concentration of plasma phospholipid n-3 fatty acids above 175.1 mg per liter. We conclude that eicosapentaenoic and docosahexaenoic acids reduce blood pressure in essential hypertension, depending on increases in plasma phospholipid n-3 fatty acids.


  21. Combined treatment with concentrated essential fatty acids and prednisolone in the management of canine atopy. Bond R, Lloyd DH. Vet Rec. 1994;134:30-32.
    Includes references.


  22. Margarines and coronary artery disease. Booyens J, van der Merwe CF., Department of Internal Medicine, Medical University of Southern Africa, Medunsa. Med Hypotheses. 1992;37:241-244.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    In a previous paper we predicted that health effects of dietary fats in humans would require half a century or more to be understood, instead of the decade or so predicted during 1956 by an Editorial in The Lancet. It would seem that our prediction may have been optimistic since it has now been reported that trans unsaturated fatty acids present in high concentrations in margarines promote hypercholesterolemia in humans. Consequently, there has been a call for the reclassification of dietary fats upon the basis of their hypercholesterolemic properties. Using the latter criterion, therefore, many margarine brands would be classified as coronary artery disease risk foods. The primary adverse metabolic action of trans unsaturated fatty acids is the competitive inhibition of delta-6-desaturase, the hepatic enzyme responsible for the initial metabolic desaturation of the essential fatty acids cis linoleic and cis alpha-linolenic acid. In addition to margarines, many other common foods such as deep-fried foods, many convenience foods and bakery products contain relatively high levels of trans fatty acids. Therefore, since it has become virtually impossible to avoid a consistent, daily dietary intake of trans fatty acids, it would appear that a precautionary, preventative supplementation of the diet with supplements containing the direct metabolic products of delta-6-desaturation of the essential fatty acids, would be prudent. Such supplements are readily available.


  23. Metabolism of linoleic and alpha-linolenic acids in cultured cardiomyocytes: effect of different N-6 and N-3 fatty acid supplementation. Bordoni A, Lopez Jimenez JA, Spano C, Biagi PL, Horrobin DF, Hrelia S., University of Bologna, Bologna, Italy. Mol Cell Biochem. 1996;157:217-222.
    Includes references.
    The metabolites of linoleic (LA) and alpha-linolenic (ALA) acids are involved in coronary heart disease. Both n-6 and n-3 essential fatty acids (EFAs) are likely to be important in prevention of atherosclerosis since the common risk factors are associated with their reduced 6-desaturation. We previously demonstrated the ability of heart tissue to desaturate LA. In this study we examined the ability of cultured cardiomyocytes to metabolize both LA and ALA in vivo, in the absence and in the presence of gamma linolenic acid (GLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) alone or combined together. In control conditions, about 25% of LA and about 90% of ALA were converted in PUFAs. GLA supplementation had no influence on LA conversion to more unsaturated fatty acids, while the addition of n-3 fatty acids, alone or combined together, significantly decreased the formation of interconversion products from LA. Using the combination of n-6 and n-3 PUFAs, GLA seemed to counterbalance partially the inhibitory effect of EPA and DHA on LA desaturation/elongation. The conversion of ALA to more unsaturated metabolites was greatly affected by GLA supplementation. Each supplemented fatty acid was incorporated to a significant extent into cardiomyocyte lipids, as revealed by gas chromatographic analysis. The n-6/n-3 fatty acid ratio was greatly influenced by the different supplementations; the ratio in GLA+EPA+DHA supplemented cardiomyocytes was the most similar to that recorded in control cardiomyocytes. Since important risk factors for coronary disease may be associated with reduced 6-desaturation of the parent EFAs, administration of n-6 or n-3 EFA metabolites alone. metabolites is likely to achieve optimum results.


  24. Fats in the diet. Bosch V, Pantin EL., Instituto de Medicina Experimental, Universidad Central de Venezuela, Caracas. Arch Latinoam Nutr. 1988;38:506-518.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Fats are important constituents of the human diet since on the one hand, they contribute to the caloric density of the diet, and on the other, they serve as vehicles of essential nutrients such as linoleic and alpha-linolenic acids, as well as fat-soluble vitamins. The existence of human populations subsisting on diets with values as low as 10% or more than 50% of the calories represented by fats, has been documented, demonstrating the great adaptability of man to a wide availability of this type of food. Nevertheless, extensive epidemiological and experimental research in relation to a frequent degenerative diseases of man, arteriosclerosis, have consistently demonstrated that the proportion of saturated fats in the diet has a positive correlation with the frequency of these alterations. Mortality and fat availability in Latin America is consistent with these results. In consequence, and taking into consideration the present level of fat availability in the Region, we propose that no more than 25% of the caloric requirement should be covered by fats. Additionally, this amount of fat should have equal proportions of saturated, monounsaturated and polyunsaturated fatty acids. Cholesterol, which is contained in animal fats, is not a necessary nutrient for humans, so that no minimum consumption needs to be established. Daily ingestion of cholesterol should be restrained to no more than 100 mg/1,000 calories. Introduction of new fatty foods for human consumption should be preceded by a thorough investigation of the metabolic consequences.


  25. Alpha-linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer. Bougnoux P, Koscielny S, Chajes V, Descamps P, Couet C, Calais G. Br J Cancer. 1994;70:330-334.
    The association between the levels of various fatty acids in adipose breast tissue and the emergence of visceral metastases was prospectively studied in a cohort of 121 patients with an initially localised breast cancer. Adipose breast tissue was obtained at the time of initial surgery, and its fatty acid content analysed by capillary gas chromatography. A low level of alpha-linolenic acid (18:3n-3) in adipose breast tissue was associated with positive axillary lymph node status and with the presence of vascular invasion, but not with tumour size or mitotic index. After an average 31 months of follow-up, 21 patients developed metastases. Large tumour size, high mitotic index, presence of vascular invasion and low level of 18:3n-3 were single factors significantly associated with an increased risk of metastasis. A Cox proportional hazard regression model was used to identify prognostic factors. Low 18:3n-3 level and large tumour size were the two factors predictive of metastases. These results suggest that host alpha-linolenic acid has a specific role in the metastatic process in vivo. Further understanding of the biology of this essential fatty acid of the n-3 series is needed in breast carcinoma.


  26. Structural and functional importance of dietary polyunsaturated fatty acids in the nervous system. Bourre JM, Bonneil M, Chaudiere J, et al., INSERM Unite 26, Hopital Fernand Widal, Paris, France. Adv Exp Med Biol. 1992;318:211-229.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The nervous system is the organ with the second greatest concentration of lipids. These lipids participate directly in membrane functioning. Brain development is genetically programmed. It is therefore necessary to ensure that nerve cells receive an adequate supply of nutrients, especially of lipids, during their differentiation and multiplication, and throughout their lives. The effects of polyunsaturated fatty acid deficiency have been extensively studied; prolonged deficiency leads to death in animals. Linoleic acid is now universally recognized to be an essential nutrient. Until recently, however, alpha-linolenic acid was considered non-essential. Feeding animals with oils that have a low alpha-linolenic content results in all brain cells and organelles and various organs having reduced amounts of 22:6n-3, which is compensated for by an increase in 22:5n-6. The speed of recuperation from these anomalies is extremely slow for brain cells, organelles, and microvessels, in contrast to other organs. A decrease in alpha-linolenic series acids in the membranes results in a 40% reduction in the Na(+)-K(+)-ATPase of nerve terminals and a 20% reduction in 5'-nucleotidase. Some other enzymatic activities are not affected, although membrane fluidity is altered. A diet low in alpha-linolenic acid induces alterations in the electroretinogram which disappear with age; motor function and activity are little affected, but learning behavior is markedly altered. The presence of alpha-linolenic acid in the diet confers a greater resistance to certain neurotoxic agents (triethyl-lead). During the period of cerebral development, there is a linear relationship between brain content of n-3 acids and the n-3 content of the diet up to the point where alpha-linolenic levels reach 200 mg for 100 g of food intake. Beyond that level there is a plateau. For other organs, such as the liver, the relationship is also linear up to 200 mg/100 g, but then there is merely an abrupt change in slope and not a plateau. When dietary 18:2n-6 content was varied, it was noted that 20:4n-6 optimum values were obtained at 150 mg/100 g for all nerve structures, 300 mg for testicle and muscle, 800 mg for kidney, and 1200 mg for liver, lung and heart. A deficiency in alpha-linolenic acid and an excess of linoleic acid have the same main effect: an increase in 22:5n-6 levels.


  27. Function of dietary polyunsaturated fatty acids in the nervous system. Bourre JM, Bonneil M, Clement M, et al. Prostaglandins Leukot Essent Fatty Acids. 1993:5-15.
    The brain is the organ with the second greatest concentration of lipids; they are directly involved in the functioning of membranes. Brain development is genetically programmed; it is therefore necessary to ensure that nerve cells receive an adequate supply of lipids during their differentiation and multiplication. Indeed the effects of polyunsaturated fatty acid (PUFA) deficiency have been extensively studied; prolonged deficiency leads to death in animals. Linoleic acid (LA) is now universally recognized to be an essential nutrient. On the other hand, alpha-linolenic acid (LNA) was considered non-essential until recently, and its role needs further studies. In our experiments, feeding animals with oils that have a low alpha-linolenic content results in all brain cells and organelles and various organs in reduced amounts of 22:6(n-3), compensated by an increase in 22:5(n-6). The speed of recuperation from these anomalies is extremely slow for brain cells, organelles and microvessels, in contrast with other organs. A decrease in alpha-linolenic series acids in the membranes results in a 40% reduction in the Na-K-ATPase of nerve terminals and a 20% reduction in 5'-nucleotidase. Some other enzymatic activities are not affected, although membrane fluidity is altered. A diet low in LNA induces alterations in the electroretinogram which disappear with age: motor function and activity are little affected but learning behaviour is markedly altered. The presence of LNA in the diet confers a greater resistance to certain neurotoxic agents, i.e. triethyl-lead. We have shown that during the period of cerebral development, there is a linear relationship between brain content of (n-3) acids and the (n-3) content of the diet up to the point where alpha-linolenic levels reach 200 mg for 100 g food intake. Beyond that level there is a plateau. For the other organs, such as the liver, the relationship is also linear up to 200 mg/100 g, but then there is merely an abrupt change in slope and not a plateau. By varying the dietary 18:2(n-6) content, it was noted that 20:4(n-6) optimum values were obtained at 150 mg/100 g for all nerve structures, at 300 mg for testicle and muscle, 800 mg for the kidney, and 1200 mg for the liver, lung and heart. A deficiency in LNA or an excess of LA has the same main effect: an increase in 22:5(n-6) levels.


  28. Fatty acids of the alpha-linolenic family and the structures and functions of the brain - their nature, role, origin and dietary importance - animal model. Bourre JM, Dumont O, Clement M, Durand G., Hop Fernand Widal,Inserm,U26,200 Rue Faubourg St Denis/F-75475 Paris 10//France/ (Reprint) . Corps Gras Lipides. 1995;2:254-263.
    (c) 1996 Inst for Sci Info. All rts. reserv.
    Dietary alpha-linolenic acid deficiency alters dramatically fatty acids profiles of all organs, including brain. In the nervous tissue 22:6 n-3 is replaced by 22:5 n-6. Membrane fluidity is changed (as well as nerve endings and red cell membranes); the fluidizing effect of ethanol is changed. Major enzymatic activities are altered by alpha-linolenic deficiency : na+k+ atp ase is dramatically reduced and its isoforms activities are changed 5'-nucleotidose activity in membranes is modified by the fatty acid profile and more specifically by alpha-linolenic acid family fatty acids from the nuclear membranes ore changed by dietary lipids and nte activity is controled by n-3 fatty acids. The efficiency of blood brain barrier is controled by dietary alpha-linolenic acid electroretinogram is dramatically affected especially in young animal. Learning performances are reduced. The minimum level of alpha-linolenic acid to provide in the rat diet as been determined during the gestational-lactating period (0.4% Of calories) and for maintening n-3 fatty acids in adult (0.26% Of calories). Brain phospholipids given in the diet are providing polyinsaturated fatty acids more efficiently than triglycerides. Fish oils changed brain fatty acids composition. Delta-6-desaturase; a key enzyme in the polyunsaturated fatty acids biosynthesis is very low rapidly after birth. Thus, brain very long chain polyunsaturated fatty acids ore provided by the liver synthesis or directly by the diet brain cell cultures differenciate, divide, release neuromediators only when cultivated in the presence of 22:6 n-3 and 20:4 n-6. Moreover delta-6-desaturase is reduced during aging. Thus, polyunsaturated very long chains forty acids ore conditionaly essential at certain periods of life. All the datas obtained in young animals (biochemical, electrophysiological and learning ability) have been confirmed in the human newborns. Thus, formula now contains alpha-linolenic acids. As human milk contains 20:4 n-6 and 22:6 n-3, these acids must be also added in the formulas. Polyunsaturated forty acids in membranes must be protected against peroxidation. Only alpha-d-tocopherol isomer of vitamin e is efficient. Moreover, this vitamin controls delta-6-desaturase.


  29. Does an increase in dietary linoleic acid modify tissue concentrations of cervonic acid and consequently alter alpha-linolenic requirements? Minimal requirement of linoleic acid in adult rats. Bourre JM, Dumont O, Durand G., INSERM, Paris, France. Biochem Mol Biol Int. 1996;39:607-619.
    Includes references.
    Rats were fed a control diet containing both linoleic and alpha-linolenic acid. When 60-days-old they were divided into 8 groups, each receiving the same amount of alpha-linolenic acid, but varying amounts of linoleic acid. When the (n-6)/(n-3) ratio in the diet varied from 2 to 32 (with a constant amount of 150 mg alpha-linolenic acid per 100 g diet), tissue levels of the (n-3) series fatty acids were not significantly modified, except in the liver, heart and testes. In all organs studied, the saturated and monounsaturated fatty acids were practically unchanged. For the (n-6) series fatty acids, arachidonic acid was not significantly affected, in muscle, kidney, brain, myelin, nerve-endings or sciatic nerve, whatever the quantity of linoleic acid in the diet. In liver, arachidonic acid plateaued at 2400 mg linoleic acid/ 100 g diet and at 400 mg/100g diet in heart. Results for 22:5(n-6) showed a marked increase in heart, a moderate increase in liver and kidney, and no effect in muscle, testes, brain, myelin, nerve- endings or sciatic nerve. This experiment defined the minimum amount of linoleic acid required in the diet to maintain fatty acids of the linoleic family in the young adult rat. For the first time it was demonstrated that 1200 mg/100 g diet are sufficient for the liver, as evidenced by maintenance of the arachidonic acid concentration. For the other organs, there is either a very marked preservation of this acid, or the dietary level is less than 300 mg/100 g diet. For the essential fatty acid precursors (i.e. linoleic and alpha-linolenic acids), the recommended optimal (n-6)/(n-3) ratio required in the diet is about 8.


  30. Brain cell and tissue recovery in rats made deficient in n-3 fatty acids by alteration of dietary fat. Bourre JM, Durand G, Pascal G, Youyou A. J Nutr. 1989;119:15-22.
    Includes references.
    Rats were fed a purified diet containing either 1.5% sunflower oil [940 mg linoleic acid[18:2(n-6)]/100 g diet; 6 mg alpha-linolenic acid [18:3(n-3)]/100 g diet] or 1.9% soybean oil [940 mg 18:2(n-6)/100 g diet; 130 mg 18:3(n-3)/100 g diet]. In all cells and tissues examined 22:6(n-3) was lower and 22:5(n-6) was higher in rats fed sunflower oil than in rats fed soyben oil. Levels of 22:4(n-6) and 20:4(n-6) were largely unaffected. Expressed as a percentage of that in soybean oil-fed rats, 22:6(n-3) in sunflower oil-fed rats was as follows: neurons, 49; astrocytes, 47; oligodendrocytes, 10; lung, 27; testes, 32; retina, 36; liver, 35 and kidneys, 45. Ten wk after the change in diet of 60-d-old rats from one containing sunflower oil to one containing soybean oil, the fatty acid composition of the brain cells had not reached control values, e.g., that obtained in animals continuously fed soybean oil; 22:6(n-3) was 77, 65 and 80% of control levels for astrocytes, oligodendrocytes and neurons, respectively. In contrast, the recovery measured by the decay of 22:5(n-6) was complete within 10 wk. For 22:6(n-3), it took approximately 2 wk for liver and kidney to recover to the control value, 3 wk for lung, 6 wk for retina and 10 wk for testes. The decrease of 22:5(n-6) was rapid: the control values were reached within 2 wk for kidney, liver and lung and within 6 wk for retina. Because the recovery of the content of 22:6(n-3) by brain cells was very slow, the optimal ratioof long-chain fatty acid precursors must be determined very carefully.


  31. Effect of polyunsaturated fatty acids on fetal mouse brain cells in culture in a chemically defined medium. Bourre JM, Faivre A, Dumont O, et al. J Neurochem. 1983;41:1234-42.
    The biochemical and morphological effects of polyunsaturated fatty acids on fetal brain cells grown in a chemically defined medium were studied. Fetal brain cells were dissociated from mouse cerebral hemispheres taken on the 16th day of gestation. After cells had grown in chemically defined medium for 8 days, the proportion of polyunsaturated fatty acids of cultured cells was only one-half of that observed at day 0 and about 1.5 times less than that of cells grown in serum-supplemented medium. Fatty acid 20:3(n-9) was present in cultured cells grown in either chemically defined or serum-supplemented medium, demonstrating the deficiency of essential fatty acids. The reduced amount of polyunsaturated fatty acids in cells grown in the chemically defined medium was balanced by an increase in monounsaturated fatty acids. The saturated fatty acids were not affected. When added at the seeding time, linoleic, linolenic, arachidonic, or docosahexaenoic acid stimulated the proliferation of small dense cells. Besides, we demonstrate that each of the four fatty acids studied was incorporated into phospholipids. Adding fatty acids of the n-6 series increased the content of n-6 fatty acids in the cells, but also provoked an increase in the n-3 fatty acids.


  32. Alterations in the fatty acid composition of rat brain cells (neurons, astrocytes, and oligodendrocytes) and of subcellular fractions (myelin and synaptosomes) induced by a diet devoid of n-3 fatty acids. Bourre JM, Pascal G, Durand G, Masson M, Dumont O, Piciotti M. J Neurochem. 1984;17:342-348.
    Includes references.
    Rats were fed through four generations with a linolenic acid deficient, semisynthetic diet containing 1.0% sunflower oil (6.7 mg/g n-6 fatty acids, 0.04 mg/g n-3 fatty acids). When comparing 60 day-old animals fed with soya oil or sunflower oil, the n-3/n-6 fatty acid ratio was reduced 16-fold in dendrocytes, 12-fold in myelin, 2-fold in neurons, 6-fold in synaptosomes, and 3-fold in astrocytes.


  33. Nature, origin and role of fatty acids in the nervous system: an essential fatty acid, alpha-linolenic acid, controls the structure and the function of the brain. Bourre JM. Bull Acad Natl Med (Paris). 1989;173:1137-1151.
    (c) 1996 American Chemical Society. All rts. reserv.


  34. Bouziane M, Belleville J, Prost J&lt03 Author Affiliation>. Hepatic storage and transport of n-3 and n-6 polyunsaturated fatty acids by very-low-density lipoproteins in growing rats fed low- or adequate-protein diets with sunflower, coconut, and salmon oils. Am J Clin Nutr. 1997;65:750-760.
    Protein and essential fatty acid (EFA) deficiencies may both occur in chronic malnutrition and have common symptoms. To determine the interactions between dietary protein intake and EFA availability, rats were fed purified diets containing 20% or 2% casein and 5% as one of four fats (sunflower, soybean, coconut, or salmon oil) that differed particularly in their n-6 and n-3 polyunsaturated fatty acids (PUFAs). Protein malnutrition enhanced hepatic triacyglycerol and cholesterol concentrations while decreasing hepatic protein and phospholipid contents and mass and components of very-low-density lipoproteins (VLDL). The ratio of PUFAs to saturated fatty acids (SFAs) was consistently depressed by protein malnutrition in liver and VLDL triacylglycerol and phospholipid. Total n-6 and n-3 fatty acids were diminished by protein malnutrition, except with salmon oil, which a decrease of 20:5n-3 was compensated for by an increase in 22:6n-3. The ratio of 20:4n-6 to 18:2n-6 was enhanced in liver phospholipid and VLDL triacylglycerol, and modified little in liver triacylglycerol. Generally, the ratio of 20:3n-9 to 20:4n-6, an index for EFA deficiency, was raised with protein malnutrition in liver triacylglycerol and phospholipid and in VLDL triacyglycerol. The extent of changes in each fatty acid proportion varied according to the oil ffed. Overall, VLDL-apolipoprotein concentrations were, in general, strongly reduced with protein malnutrition. In conclusion, protein malnutrition may accelerate marginal EFA deficiency and decrease long-chain PUFA bioavilability and thus increase EFA requirement.


  35. Changes in serum and lipoprotein fatty acids of growing rats fed protein-deficient diets with low or adequate linoleic acid concentrations. Bouziane M, Prost J, Belleville J., Unite de Recherches de Nutrition Cellulaire et Metabolique, Universite de Bourgogne, Faculte des Sciences Mirande, BP 138, 21004, Dijon Cedex, France. J Nutr. 1992;122:2037-2046.
    (c) 1995 CAB International. All rts. reserv.
    The effects of a protein-deficient diet associated with sunflower oil (adequate in 18:2(n-6), poor in 18:3(n-3)) or soyabean oil (adequate in both 18:2(n-6) and 18:3(n-3)) on lipid serum and lipoprotein compositions were studied in growing rats. Groups of rats were fed on diets containing 20% casein + 5% sunflower oil (SFC); 2% casein + 5% sunflower oil (SFd); 20% casein + 5% soyabean oil (SC); 2% casein + 5% soyabean oil (Sd). After 28 days, both protein-deficient groups showed low concentrations of protein, phospholipid, triacylglycerol and total cholesterol in serum and very low density lipoprotein (VLDL). Compared with rats fed on 20% casein diets, those fed on low-protein diets had lower 18:2(n-6) and 20:4(n-6) in phospholipids of serum, VLDL and high density lipoprotein (HDL)2-3, and the 20:4(n-6)/18:2(n-6) ratio was 2-fold higher in triacylglycerols of serum and VLDL. In the SFd-group, 22:5(n-6) was higher than in the SFC-fed group for both triacylglycerols and phospholipids in overall lipoprotein fractions studied. In addition, the 20:3(n-9)/20:4(n-6) ratio was 0.1 in HDL2-3 phospholipids of the SFd-fed group. Sunflower oil-fed rats compared with soyabean oil-fed rats had greater monounsaturated fatty acids and lower total (n-3) fatty acids in both triacylglycerols and phospholipids of serum, VLDL and HDL2-3, as well as lower total (n-6) fatty acids in serum and VLDL triacylglycerols. Apolipoproteins (apo) of VLDL were drastically depressed in rats fed on protein-deficient diets, whereas apo-AI of HDL2-3 showed a particular resistance. Likewise, sunflower oil-fed rats had enhanced apo-B48 of VLDL and apo-C, apo-AII and apo-AIV of HDL2-3. The findings show that some effects of protein malnutrition were enhanced by alpha -linolenic acid deficiency, in particular reduced (n-6) and (n-3) fatty acid bioavailability.


  36. Unsaturated fatty acid bioavailability in growing rats fed low or adequate protein diets with sunflower or soybean oils. Bouziane M, Prost J, Belleville J. J Nutr Biochem. 1993;4:399-408.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv. Includes references.
    The relationship of serum very low density lipoproteins (VLDL) to hepatic lipid composition was studied after 28 days of protein depletion to determine the interactions between dietary protein levels and the essential fatty acid (EFA) availability. This was examined in rats using a dietary combination of 20% or 2% casein with 5% vegetable oils, variable in their n-6:n-3 fatty acid ratios. Rats were divided into four groups, SFC (20% casein + 5% sunflower oil); SFd (2% casein + 5% sunflower oil); SC (20% casein + 5% soybean oil); Sd (2% casein + 5% soybean oil). Dietary protein depletion decreased phospholipid and protein concentrations in liver and VLDL, whereas triacylglycerol amounts were enhanced in liver, but lowered in VLDL. Dietary protein depletion strongly depressed VLDL apolipoproteins. Protein-deficient groups (SFd and Sd) exhibited, in both liver and VLDL, decreased linoleic acid in triacylglycerol fractions and depressed both arachidonic and linoleic acids in phospholipid fractions. In spite of short periods of dietary treatment, protein depletion involved an impairment in EFA availability. Total n-6 polyunsaturated fatty acids contents were diminished in liver and VLDL lipids, while total n-3 polyunsaturated fatty acids contents were diminished in only VLDL triacylglycerol and phospholipid. Furthermore, sunflower oil amplified this impairment, and the lack of alpha-linolenic acid involved a greater diminution in n-3 polyunsaturated fatty acids and enhanced 20:3 n-9 and 22:5 n-6, especially in phospholipid fractions. In this experiment, in spite of a short period of dietary treatment, protein depletion strongly impairs EFA metabolism and accentuates the alpha-linolenic acid deficiency.


  37. Red blood cell and tissue phospholipid fatty acid profiles of weanling rats fed infant formula fat blends containing soy and/or corn oil. Boyle FG, Yuhas RJ, Lien EL. Ann Nutr Metab. 1996;40:234-242.
    Soy oil or corn oil may be employed to provide essential fatty acids in infant formulas. Both of these sources are high in linoleic acid; soy oil contains modest levels of alpha-linolenic acid, while corn oil contains very low levels of this essential omega 3 fatty acid. We examined the omega 3 long-chain polyunsaturated fatty acid (LCP) accretion in red blood cells, liver, and brain phospholipids of rats on diets containing infant formula fat blends with essential fatty acids provided from soy and/or corn oil. Although modest alterations occurred in the red blood cell omega 3 LCP fatty acid status, substantially larger changes were noted in liver LCP profiles. Due to the relatively mature nature of the rats employed in this experiment, no alterations were noted in brain fatty acid profiles. In conclusion, we have observed substantial tissue differences in animals fed soy or corn oil containing diets. It appears that corn oil is inappropriate for use in infant formulas.


  38. Alterations in cerebral and microvascular prostaglandin synthesis by manipulation of dietary essential fatty acids. Brown ML, Marshall LA, Johnston PV. J Neurochem. 1984;43:1392-1400.
    Includes references.


  39. The prevention of experimental nephrocalcinosis with eicosapentaenoic acid (EPA) and evening primrose oil (GLA). Buck AC, Smellie WS, James A, Horrobin D, Marko M. Urolithiasis 2, (Proc. Int. Symp.), 7th: 1994:333-334.
    (c) 1996 American Chemical Society. All rts. reserv.


  40. Alpha-linolenic acid as a regulator of the metabolism of arachidonic acid: dietary implications of the ratio, n-6:n-3 fatty acids. Budowski P, Crawford MA. Proc Nutr Soc. 1985;44:221-229.


  41. Nutritional encephalomalacia in the chick: an exposure of the vulnerable period for cerebellar development and the possible need for both omega 6- and omega 3-fatty acids. Budowski P, Leighfield MJ, Crawford MA. Br J Nutr. 1987;58:511-20.
    1. Cockerels (1-d-old) received over a period of 4 weeks, a balanced diet containing either safflower oil (diet S) or linseed oil (diet L) as a source of polyunsaturated fatty acids (PUFA). Body-weight, and weights of cerebrum and cerebellum increased at similar rates in the two dietary groups. The total fatty acids (FA) of the cerebellum differed from the cerebral FA by their higher PUFA and oleic acid contents and their lower stearic acid level. During the 3rd week of life there was a spurt in accretion of PUFA in the cerebellum, but not in the cerebrum. At the end of the experimental period phosphatidylethanolamine was present at twice the concentration in the cerebellum, compared with the cerebrum. 2. Diets S and L resulted in extensive mutual replacement of omega 6- and omega 3-FA in brain, without any significant change in the total PUFA. Brain oleic acid concentration was higher in the diet-L group than in the diet-S group, but saturated FA were not affected by the dietary treatments. 3. These results may be relevant to basic brain biology and to chick nutritional encephalomalacia (NE). This disease, which specifically affects the cerebellum and is readily induced by diets supplying linoleic acid but deficient in vitamin E, usually reaches its highest incidence during the 3rd week of life and may thus be related to the cerebellar PUFA spurt that occurs at that time. The fact that NE was induced by linoleic acid, while alpha-linolenic acid exerted a protective action, points to an overproduction of arachidonic-derived eicosanoids as a factor in the etiology of the cerebellar lesion and possibly a structural change due to a loss of docosahexaenoic acid and gain of arachidonic acid in the chicks given diet S.


  42. Relevance of N-3 fatty acids in human infant nutrition. A critical review. Cardace G, Berra B., Univ. Milano, fac. farmacia, ist. fisiologia gen. chimica biologica, Italy . Rivista Italiana Delle Sostanze Grasse. 1993;70:471-476.
    (c) 1995 INIST/CNRS. All rts. reserv.
    Alpha-linolenic acid is the parent fatty acid of the n-3 series and it is essential for human beings as they are not able to insert a double bond in the n-3 position. In adults alpha-linolenic acid originates longer chain fatty acids of peculiar biological activities; among these docosahexaenoic acid which is essential in the retina for normal visual function. Differently from adults, the newborn infant has limited capability to synthesize docosahexaenoic acid, naturally supplied by human milk. The available data suggest that infant formulas too, particularly if intended for preterm neonates, be enriched with docosahexaenoic acid and other long chain polyunsaturated fatty acids at levels similar to those found in human milk.


  43. Digestion and absorption of polyunsaturated fatty acids. Carlier H, Bernard A, Caselli C., Departement de Nutrition, ENS.BANA, Universite de Bourgogne, Dijon, France. Reprod Nutr Dev. 1991;31:475-500.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Polyunsaturated fatty acids play an important part in the structure and function of cellular membranes and are precursors of lipid mediators which play a key role in cardiovascular and inflammatory diseases. Dietary sources of essential fatty acids are vegetable oils for either linoleic or alpha-linolenic acids, and sea fish oils for eicosapentaenoic and docosahexaenoic acids. Because of the specificity of the pancreatic lipid hydrolases, triglyceride fatty acid distribution is an essential parameter in the digestibility of fats. The efficiency of the intestinal uptake depends on the hydrolysis and especially on their micellarization. n-3 polyunsaturated fatty acid ethyl ester digestion is recognized to be impaired, but n-3 polyunsaturated fatty acid triglyceride hydrolysis remains a controversial point, and to some authors explains differences observed between vegetable and fish oil absorption. So additional studies are required to investigate this intestinal step. In enterocytes, morphological and biochemical absorption processes involve reesterification of long-chain fatty acids and lipoprotein formation. At this level, specific affinity of I- and L-FABPc (cytosolic fatty acid binding proteins) to polyunsaturated fatty acids requires further investigation. A better understanding of the role of these FABPc might bring to light the esterification step, particularly the integration of polyunsaturated fatty acids into phospholipids. With reference to differences published between fish and vegetable oil absorption, longer-term absorption studies appear essential to some authors. Polyunsaturated fatty acid absorption is thought to be not very dissimilar to that of long-chain mono-unsaturated fatty acid absorption. However, several digestion and absorption specific steps are worth studying with reference to the crucial role of polyunsaturated fatty acids in the organism, and for example adaptation of possible dietary supplements.


  44. Medium-chain triacylglycerols in formulas for preterm infants: effect on plasma lipids, circulating concentrations of medium-chain fatty acids, and essential fatty acids. Carnielli VP, Rossi K, Badon T, et al. Am J Clin Nutr. 1996;64:152-158.
    Limited information is available on the metabolic fate of medium-chain triacylglycerols (triglycerides) after intestinal absorption and on their influence on essential fatty acid metabolism. We studied in preterm infants the effect of two infant formulas, one with a high (HMCT) and one with a low (LMCT) medium-chain triacylglycerol content, on plasma fatty acids. The HMCT formula contained 46 mol% 8:0 + 10:0 and the LMCT formula (4.8 mol% 8:0 + 10:0) had approximately twice the amount of long-chain saturated and monounsaturated fatty acids as the HMCT. Both formulas had similar contents of linoleic and linolenic acids. Plasma lipids and fatty acids were determined at birth and on day 24 of life in 20 infants fed the LMCT (n = 12) or HMCT (n = 8) formula. Significant amounts of medium-chain fatty acids were found in the systemic circulation of the infants fed the HMCT formula, mainly in plasma fatty acids and triacylglycerols. Despite striking dietary differences, palmitic and stearic acids were not different between groups, indicating de novo synthesis of long-chain fatty acids with the HMCT formula. Plasma phospholipid docosahexaenoic acid was significantly lower in the HMCT group than in the LMCT infants (1.38 +/- 0.07 compared with 1.73 +/- 0.07 mol%, P = 0.002). Our data indicate that a high MCT intake in preterm infants increases lipogenesis, and dietary nonessential fatty acids interfere with the metabolism of docosahexaenoic acid.


  45. Summation: which fat/how much fat--animals. Carroll KK. Prev Med. 1987;16:510-515.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv.
    Promotion of carcinogenesis in rats by dietary fat depends on the amount and type of fatty acids ingested, mainly as triglycerides. A certain amount of essential fatty acid of the linoleate type (n-6) is required for promotion of mammary cancer and pancreatic cancer and probably also for colon cancer. Promotion is also enhanced by a high level of dietary fat, and this additional effect seems to be relatively independent of the type of fat. Saturated fatty acids, either medium or long chain, and cis and trans monoenoic fatty acids appear to have no specific promoting effects. Fish oils containing long-chain polyunsaturated fatty acids of the linolenate type (n-3) are inhibitory, and this may also be true for rapeseed oil high in erucic acid, a long-chain monoenoic fatty acid. The promoting action of dietary fat can be modified by other components of the diet, such as starch, sugar, and fiber. Promotion is also dependent on the length of time animals are exposed to the high-fat diet. The overall tumor yield can be decreased by reducing the level and degree of unsaturation of the dietary fat after a period of feeding a high polyunsaturated-fat diet.


  46. Estimation of essential fatty acid intake in swine. Caster WO, Hill EG, Holman RT. J Animal Sc. 1963;22:389-392.


  47. Reappraisal of the essential fatty acids. Chapkin RS. Food Sci Technol (N. Y.). 1992;53:429-436.
    (c) 1996 American Chemical Society. All rts. reserv.


  48. Trans mono- and polyunsaturated fatty acids in human milk. Chardigny JM, Wolff RL, Mager E, Sebedio JL, Martine L, Juaneda P., INRA, Dijon, France. Eur J Clin Nutr. 1995;49:523-531.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv. Includes references.
    Objective: The aim of the present study was to identify the transisomers of C18 fatty acids in some human milk samples. Subjects: Ten human milk samples from French women were collected in a local milk bank in order to assess their trans mono and polyunsaturated fatty acids (PUFA) content. Intervention: The fatty acid profile was examined using methyl and isopropyl ester derivatives. The combination of gas-liquid chromatography, high-performance liquid chromatography and silver nitrate thin-layer chromatography was needed to describe the detailed fatty acid compositions, including the trans isomers of unsaturated C18 fatty acids. Results: All the samples contained trans isomers of C18:1 acid (mean level 1.9 +/- 0.2% of total fatty acids), with trans vaccenic acid being the major isomer. The samples also contained various isomers of linoleic and alpha-linolenic acid, but at lower levels. Trans isomers of PUFA are the same as those present in deodorised or deep-fried oils. One sample presented an abnormally high degree of isomerisation of alpha-linolenic acid (almost 50%). This was related to the dietary habit or consuming foods that were deep-fried in rapeseed oil. This milk sample also contained some cyclic fatty acid monomers. Conclusion: The human milk samples collected in this study contained some trans fatty acids, including isomers of essential fatty acids. This should be taken into account in the dietary intake of the newborn.


  49. Dietary polyunsaturated fatty acids and aging modulate glutathione-related antioxidants in rat liver. Christon R, Haloui RB, Durand G. J Nutr. 1995;125:3062-3070.
    The effects of dietary polyunsaturated fatty acids (PUFA) on the age-dependent changes in liver glutathione antioxidant system were investigated in male Wistar rats fed diets supplying either balanced amounts of linoleic acid and alpha-linolenic acids (control) or deficient in alpha-linolenic acid [n-3) deficient]. The animals were studied at the age of 6 or 24 mo. Glutathione antioxidative metabolism was markedly affected by aging. Cytosolic concentration of reduced glutathione (GSH) was lower (P < 0.01), whereas that of oxidized glutathione (GSSG) as well as the GSSG:GSH ratio were greater (P&lt0.001) in the 24-mo-old as compared with the 6-mo-old rats, regardless of the diet. Glutathione peroxidase activities were lower (P < 0.001) in 24-mo-old rats, though more markedly in those fed the control diet. The lipid composition of rat liver microsomal membranes was strongly modified by both diet and aging. The age-related changes mainly involved the polyunsaturated fatty acids. These results suggest that the nature of dietary PUFA and not only their degree of unsaturation affects the cellular glutathione-dependent antioxidant system and thus may modify the age-related changes in metabolic reactions.


  50. The effect of different n-6/n-3 essential fatty acid ratios on calcium balance and bone in rats. Claassen N, Coetzer H, Steinmann CM, Kruger MC. Prostaglandins Leukot Essent Fatty Acids. 1995;53:13-19.
    Prostaglandins (PGs) are known to have various effects on bone metabolism. The supplementation of essential fatty acids (EFAs), the precursors of PGs, leads to increased intestinal calcium absorption and calcium balance. It is, however, not known whether increased calcium absorption and calcium balance will enhance the calcium content in bone. Male Sprague-Dawley rats (n = 40) aged 5-12 weeks were supplemented with EFAs. The main dietary EFAs, linoleic acid (LA) and alpha-linolenic acid (ALA) were administered in a ratio of 3:1 as a control group. The conversion of LA to ALA to the PG precursors is slow, with the first step, delta-6-desaturation being rate limiting. Fatty acids beyond this rate-limiting step, gamma-linolenic acid (GLA, n-6) and eicoapentaenioc acid (EPA, n-3), were administered to different groups in the ratios 3:1, 1:1 and 1:3 to explore the impact of different ratios of n-6 and n-3 EFAs. Intestinal calcium absorption (mg/24 h) increased by 41.5% in the 3:1 supplemented group, compared with the control group. The decrease in urinary calcium (mg/24 h) correlated with the increase in n-3 level. The calcium balance (mg/24 h) and bone calcium (mg/g bone ash) increased significantly in the 3:1 (41.5% and 24.7%) group, compared with the control. The increase in bone calcium might be attributed to an EFA-induced increase in circulating PGs. An increased synthesis of PGs acting on target bone cells, as well as changes in membrane fluidity, may underlie these observations.


  51. Supplemented gamma-linolenic acid and eicosapentaenoic acid influence bone status in young male rats: effects on free urinary collagen crosslinks, total urinary hydroxyproline, and bone calcium content. Claassen N, Potgieter HC, Seppa M, et al. Bone. 1995;16:385S-392S.
    The effect of different ratios of the prostaglandin precursors gamma-linolenic (GLA) and eicosapentaenoic (EPA) acids on bone status in growing rats measured as a function of free urinary pyridinium crosslinks and hydroxyproline levels was investigated. Male Sprague-Dawley rats were weaned onto an essential fatty acid deficient diet and from their fifth week, different groups of rats received a balanced, semisynthetic diet, supplemented with different ratios of GLA:EPA supplied as a mixture of evening primrose oil (EPO) and fish oil (FO). Controls were supplemented with linoleic (LA; sunflower oil) and alpha-linolenic (ALA; linseed oil) acids (3:1) or a commercially available rat chow. Animals were terminated at 84 days and femur length, ash weight, calcium content, free urinary pyridinium crosslinks (Pyd and Dpyd), total hydroxyproline (Hyp), and creatinine levels measured. Free urinary Pyd and Dpyd are good indicators of bone status and they correlated well with Hyp. Pyd and Dpyd excretion were significantly decreased in the higher GLA:EPA dietary groups and correlated well (r = 0.7) with Hyp levels. Concomitantly, bone calcium content increased significantly in the same dietary groups. These results suggest that diet supplementation with relatively high GLA:EPA ratios are more effective in inhibiting bone resorption than LA:ALA.


  52. Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas. Clark KJ, Makrides M, Neumann MA, Gibson RA., Department of Paediatrics and Child Health, Flinders Medical Centre, Adelaide, South Australia. J Pediatr. 1992;120:S151-158.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The fatty acid composition of erythrocyte total lipids taken from a group of term infants 10 weeks after being fed a commercial infant formula with a high ratio of linoleic acid (18:2n-6) (LA) to alpha-linolenic acid (18:3n-3) (ALA) (19:1; LA, 14%; ALA, 0.7%; group A, n = 10) was compared with the fatty acid composition of erythrocytes from infants fed formulas that contained LA/ALA ratios reduced by either increasing ALA (4:1; LA, 13%; ALA, 3.3%; group B, n = 11) or decreasing LA (3:1; LA, 3.5%; ALA, 1.1%; group C, n = 8). Results were compared with those in an age-controlled group (n = 9) of breast-fed infants. Decreasing the LA/ALA ratio increased n-3 C20 and C22 fatty acid incorporation (formula B = 8.98% +/- 0.65%; formula C = 9.30% +/- 0.95%) relative to formula A (5.97% +/- 0.76%; p less than 0.05). Although docosahexaenoic acid (22:6n-3) (DHA) incorporation was highest in infants fed formulas B and C (4.78% +/- 0.45% and 4.48% +/- 0.49%, respectively) relative to formula A (3.47% +/- 0.46%; p less than 0.05), it did not reach levels found in breast-fed infants (6.55% +/- 1.23%; p less than 0.05). In addition, levels of arachidonic acid (20:4n-6) (AA) were lower in all formula-fed groups (p less than 0.05) relative to those in breast-fed infants. Based on some equations, it is predicted that AA levels in tissues of infants fed lower LA/ALA ratios would be reduced even further. Because both AA and DHA are probably essential for normal neural development of the infant, formulas with LA/ALA ratios below 4:1 are likely to result in fatty acid profiles notably different from those of breast-fed infants.


  53. Specific inhibition of hepatic fatty acid synthesis exerted by dietary linoleate and linolenate in essential fatty acid adequate rats. Clarke SD, Romsos DR, Leveille GA., (Dep. Food Sci. and Hum. Nutr., Michigan State Univ., East Lansing, MI 48824, USA) . Lipids. 1976;11:485-490.
    (c) 1995 Cambridge Sci Abs. All rts. reserv.


  54. Dietary deprivation of linolenic acid in rhesus monkeys: effects on plasma and tissue fatty acid composition and on visual function. Conner W, Neuringer M, Barstad L, Lin D. Transactions From the Association of American Physicians. 1989;97:1-9.
    In 1929, Bur and Burr discovered that rats reared on a fat-free, deficient diet failed to grow, developed renal desease and necrosis of the tails, and subsequently died. Our findings provide the first experimental evidence for a dietary requrement for omega-3 fatty acids in primates. Omega-3 fatty acids may be essential nutrients for retinal and brain function, expecially during fetal and postnatal development.


  55. Essentiality of omega 3 fatty acids: evidence from the primate model and implications for human nutrition. Connor WE, Neuringer M, Reisbick S. World Rev Nutr Diet . 1991;66:188-132.
    A diet deficient in omega-3 fatty acids leads to a triad of signs in the rhesus monkey: visual impairment, abnormalities of the electroretinogram, and polydipsia [1-4]. Profound biochemical changes in the fatty acid composition of the membranes of the retina, brain and other organs accompany these other disturbances[4-5]. Low concentrations of omega-3 fatty acids accur at birth in the plasma, red blood cells, and neural tissues of infants born from mothers fed an omega-3 deficient diet [1]. Docosahexaenoic acid (DHA,22:6 omega-3), an omega-3 fatty acid which is uniquely rich in neural membranes, is found in very low concentrations in these infant monkeys. These concentrations even become lower as the deficient diet is continued postnatally. By 4 weeks of age, visual impairment can be demonstrated and shortly after that abnormalities of the electretinogram occur [1-4]. Polydipsia develops later in life.


  56. Brain metabolism of alpha-linolenic acid during development. Cook HW., Atlantic Research Centre for Mental Retardation, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada. Nutrition. 1991;7:440-442.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    To date, experimental models for evaluation of the relative contribution of conversion of 18:3n-3 to 22:6n-3 in brain, particularly during crucial stages of rapid brain growth, have limitations that preclude a definitive resolution of the relative contribution of conversion in brain per se compared with dependence on extracerebral sources of 22:6n-3. Clearly, brain in the neonatal period has substantial capacity for delta 6- and delta 5-desaturation that equals or surpasses that of immature liver. Furthermore, activity in brain is much less susceptible than that in liver to dietary fluctuations. Studies with cultured cells of neural origin provide valuable insight into relative contributions of alternate pathways and into molecular mechanisms of regulation of desaturation and chain elongation but obviously have limitations when trying to extrapolate this to the intact animal. Some investigators have concluded that 22:6n-3 for brain phospholipids may be derived primarily from liver and dietary sources; at the same time, brain has the capacity for formation of 22:6n-3 should 18:3n-3 be the primary dietary component of the n-3 family. Whereas 18:3n-3 itself appears not to be essential for esterification to brain membrane phospholipids, 22:6n-3 is clearly a vital and quantitatively significant component. Potentially, brain can convert 18:3n-3 to more polyunsaturated derivates during the growth period when the products are most needed and other sources such as diet or conversion by liver may be restrictive.


  57. Interaction of (n-3) and (n-6) fatty acids in desaturation and chain elongation of essential fatty acids in cultured glioma cells. Cook HW, Spence MW. 1987;22:613-9.
    Recent research in various biological systems has revived interest in interactions between the (n-6) and (n-3) essential fatty acids. We have utilized cultured glioma cells to show that linolenic acid, 18:3(n-3), is rapidly desaturated and chain elongated; 20:5(n-3) is the major product and accumulates almost exclusively in phospholipids. We examined effects of various (n-6), (n-3), (n-9) and (n-7) fatty acids at 40 microM concentration on desaturation and chain elongation processes using [1-14C]18:3(n-3) as substrate. In general, monoenoic fatty acids were without effect. The (n-6) fatty acids (18:2, 18:3, 20:3, 20:4 and 22:4) had little effect on total product formed. There was a shift of labeled product to triacylglycerol, and in phospholipids, slightly enhanced conversion of 20:5 to 22:5 was evident. In contrast, 22:6(n-3) was inhibitory, whereas 20:3(n-3) and 20:5(n-3) had much less effect. At concentrations less than 75 microM, all acids were inhibitory. Most products were esterified to phosphatidylcholine, but phosphatidylethanolamine also contained a major portion of 20:5 and 22:5. We provide a condensed overview of how the (n-6) and (n-3) fatty acids interact to modify relative rates of desaturation and chain elongation, depending on the essential fatty acid precursor. Thus, the balance between these dietary acids can markedly influence enzymes providing crucial membrane components and substrates for biologically active oxygenated derivatives.


  58. Biological effects on premature infants of a milk formula enriched with alpha -linolenic acid: a multicentre study. Crastes de Paulet A, Babin F, Billeaud C, Bougle D, Sarda P, Mendy F., Lab. Biochimie A, Institut de Biologie, Faculte de Medecine, Bd. Henri IV, 34000 Montpellier, France. Bull Acad Natl Med. 1994;178:267-278.
    (c) 1995 CAB International. All rts. reserv.
    Nervous tissues and the retina are rich in docosahexaenoic acid (DHA, C22:6 (n-3)), an essential fatty acid which is the product of the elongation and desaturation of alpha -linolenic acid ( alpha -LnA, C18:3 (n-3)). Lower plasma and membrane DHA levels as well as impaired nervous function (psychomotor development and visual disturbances) have been observed in premature infants receiving standard milk-based formulae when compared with breast-fed infants; these have been related to the lack of long-chain (&gtC20) fatty acids in these products. In this study, the possibility of increasing the plasma and erythrocyte DHA level in premature infants by giving a milk formula enriched with alpha -LnA (1.95% vs. 0.55%) was investigated. Results showed that, after 15 days of feeding, alpha -LnA supplementation significantly increased plasma DHA availability (2.20 vs. 1.54% (P&lt0.001) in the plasma phospholipids) and increased DHA level in erythrocyte membranes (3.02 vs. 2.54% (non-significant) in the red blood cell phosphatidylethanolamines). At the LA/ alpha -LnA ratio used (6:1), there was only a limited impact on the n-6 pathway which was reflected in a slight decrease in the arachidonic acid (AA) of the plasma phospholipids (6.88 vs. 7.53% (P&lt0.05) after 15 days). Furthermore, the AA content of the red blood cell phosphatidylethanolamines was perfectly preserved even after a mean period of 4-5 weeks of feeding ((15.70 vs. 14.86% (non-significant))). The observed enhancement in fatty acids of the n-3 series indicates the need for a prospective study to investigate whether these improvements will be associated with changes in the kinetics of psychomotor development and in the visual function of enriched-formula-fed vs. breast-fed infants.


  59. Background to essential fatty acids and their prostanoid derivatives. Crawford MA. Br Med Bull. 1983;39:210-213.


  60. Essential fatty acids and brain development. Crawford MA. Nestle Nutr Workshop Ser. New York, N.Y. 1987:67-78.
    Papers presented at the Second Nestle Nutrition Research Symposium, Sept 26-27, 1985, Vevey, Switzerland.
    Abstract: A technical review discusses some of the aspects of the involement of essential fatty acids (EFA's) in brain development in infants. Attention is given to: the absorption of dietary fats and factors affecting such absorption; the in vivo utilization of fats and their role in infant nutrition; fat consumption patterns of school children from school meals; associations between dietary lipids and protein-calorie malnutrition; the effect of food policy in developing countries on the balance between dietary protein and EFA's; and the utility of long-chain derivatives of EFA's. A factorial approach to the calculation of the requirements of EFA's by infants and children is detailed.(wz).


  61. Essential fatty acids in early development. Crawford MA, Costeloe K, Doyle W, et al., Hackney Hospital, London. Nestle Nutr Workshop Ser. New York, N.Y. 1992;28:93-110.
    In the series analytic: Polyunsaturated fatty acids in human nutrition / edited by U. Bracco and R.J. Deckelbaum. Discussion by workshop participants, p. 109-110.
    This article examines the possibility that arachidonic and docosahexaenoic acids delivered during fetal development and in the postnatal period may be related to low birthweight and offer a route for the prevention of neurodevelopmental damage. Arachidonic acid concentrations in cord blood and umbilical artery blood are shown to be correlated with birthweight and head circumference, while negative correlations were found between these growth variables and the triene/tetraene ratio; and the pentaene/tetraene ratio in umbilical artery endothelium.


  62. N-6 and n-3 fatty acids during early human development. Crawford MA, Doyle W, Drury P, Lennon A, Costeloe K, Leighfield M. J Intern Med Suppl. 1989;225:159-169.
    The food intakes of pregnant women were analysed from two contrasting socio-economic areas in London. There were significant differences in mean calorie and EFA intakes. Analysis of maternal and cord blood essential fatty acids (EFAs) in relation to birth weight, placental weight and head circumference were consistent with the dietary data. To assess the EFA tissue status of the low birth weight babies, the umbilical arteries from 14 separate babies of different birth weights were studied. Surprisingly high levels of the Mead acid (20:3 n-9) were found, with the highest appearing in the artery from the baby with the lowest birth weight. This data may not necessarily imply an EFA deficiency, but at the least it probably indicates a remarkable thirst for long chain n-6 and n-3 fatty acids for fetal brain development.


  63. Biochemical background to the integrity of the brain. Crawford MA, Harbige L S. Rose FC, Editor. Multiple Sclerosis: Immunological , Diagnostic, and Therapeutic Aspects. London: John Libbey; 1987:165-177.
    In a normal human pregnancy some 70% of the brain cells divide before birth, and a significant part of the remainder do so in the first few months of life. The brain uses arachidonic and docosahexaenoic acids in its cell membranes and not linoleic or alpha-linolenic acids. The mechanism for delivering these long-chain polyunsaturated fatty acids depends on selective uptake and delivery by the placenta. During early development, loss of integrity and retardation of brain development can be induced by deprivation of essential fatty acids in a manner which distorts the lipids of the neural membranes. Studies using experimental allergic encephalomyelitis to mimic an auto-immune effect have demonstrated the protective effect of linoleic acid, whilst experimental nutritional encephaelomalacia demonstrates the need for the w3 essential fatty acids. There is a separate library of data demonstrating the effect of saturated fatty acids in distorting vascular integrity. The concordance of multiple sclerosis (MS) from country to country with cardio-vascular disease, together with the evidence of a vascular involvement in MS offers a simple explanation for the perivascular pathology, lymphocyte infiltration and demyelination, based on the dietary distortion of fats which has led to the parallel and astonishingly high incidence of vascular disease in technically advanced societies.


  64. Essential fatty acid requirements in pregnancy and lactation with special reference to brain development. Crawford MA, Hassam AG, Stevens PA. Prog Lipid Res . 1981;20:31-40.
    Lipids account for some 50-60% of the solid matter in the brain and lipids also play a major role in maintaining the integrity of the vascular system on which it depends.


  65. Essential fatty acids and fetal brain growth. Crawford MA, Hassam AG, Williams G. Lancet. 1976;1:452-453.
    The fetal brain accumulates long-chain (C20 and 22) polyunsaturated fatty acids--arachidonic and docosahexaenoic--during cell division. De-novo synthesis of these acids does not occur and they are thought to be either directly derived from food or by metabolism from linoleic and linolenic acids, respectively. Administration of isotopically labelled linoleic and linolenic acids to pregnant guineapigs showed that only a small proportion of the label was converted to their respective long-chain polyunsaturated derivatives in the maternal liver. The proportion was increased within the phospholipids (structural lipids) by what appeared to be amultiple processing system which increased chain length and degree of polyunsaturation from maternal liver to placenta, fetal liver, and to fetal brain. Observations in man suggest a similar trend. The porportion of long-chain polyunsaturated acids increased in the phospholipids from maternal blood, cord blood, fetal liver, and fetal brain. These data show that the placenta and fetus are radically modifying the maternal phospholipids so as to achieve the high proportions of the C20 and C22 polyunsaturated fatty acids in the structural lipids of the developing brain.


  66. A study on essential fatty acids and multiple sclerosis. Crawford MA, Stevens P. Prog Lipid Res 1981. 1981;20.


  67. Quantitative changes in long-chain fatty acids during fetal and early postnatal development in rats. Cunnane SC, Chen ZY., Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada. Am J Physiol. 1992;262:R14-R19.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The quantitative importance of triacylglycerol as a source of total essential fatty acids during early postnatal development is reported in the accompanying article. Our objective here was to measure the quantitative changes in individual long-chain fatty acids in specific lipid classes of the carcass, liver, and brain of the developing rat mainly to describe the relative accumulation of long-chain vs. precursor fatty acids. Fatty acids in carcass phosphatidylcholine (micrograms/g) were lower at fetal days 18-21 than at either fetal day 15 or postnatal days +3 to +9. Individual long-chain fatty acids in liver phosphatidylcholine and phosphatidylethanolamine increased markedly by day +3 postnatally, whereas in brain phosphatidylethanolamine, the postnatal increase was delayed to between days +6 and +9. Fatty acids in carcass and liver triacylglycerols increased quantitatively by 10- to 300-fold from fetal day 21 to postnatal day +3 with amounts of both arachidonic and docosahexaenoic acid equaling linoleic acid. The ratios of linoleic and alpha-linolenic acids to respective long-chain products were significantly higher in triacylglycerols, whereas that of stearic to oleic acid was higher in phospholipids. We conclude that, during early postnatal life, oleic, linoleic, and alpha-linolenic acids are required in quantitatively greater amounts in triacylglycerols, whereas stearic acid and long-chain essential fatty acids are required in phospholipids.


  68. Omega-3 essential fatty acids decrease weight gain in genetically obese mice. Cunnane SC, McAdoo KR, Horrobin DF. Br J Nutr. 1986;56:87-95.
    Includes references.


  69. Zinc deficiency impairs whole body accumulation of polyunsaturates and increases the utilization of [1-c-14]linoleate for de novo lipid synthesis in pregnant rats. Cunnane SC, Yang J., Univ Toronto,Fac Med,Dept Nutr Sci/Toronto/On M5s 1a8/Canada/ (Reprint) . Can J Physiol Pharmacol. 1995;73.
    (c) 1996 Inst for Sci Info. All rts. reserv.
    Zinc deficiency impairs the metabolism of polyunsaturates, but the degree to which its effects are independent of food intake are still in question. Identical amounts of a semiliquid control diet (26.4 Mg zinc/kg) or moderately zinc deficient diet (3.2 Mg zinc/kg) were tube fed to rats for 11 days during the second half of pregnancy to evaluate the specific effects of zinc deficiency on maternal utilization and fetal accumulation of polyunsaturates. The whole body fatty acid balance method was used to determine net accumulation of polyunsaturates and their whole-body disappearance. Incorporation of c-14 from [l-c-14]linoleate into maternal and fetal lipid classes was also studied on days 20-21. At term, zinc-deficient rats had significantly higher whole-body disappearance of linoleate and alpha-linolenate and lower accumulation of n-6 and n-3 long-chain polyunsaturates. Zinc-deficient rats had higher c-14 activity in free cholesterol, saturates, and monounsaturates in several maternal organs but not in the fetuses. We conclude that during pregnancy, moderate zinc deficiency not affecting food intake or weight gain still alters whole-body metabolism of linoleate and alpha-linolenate towards increased beta-oxidation and also increases the utilization of carbon from linoleate for de novo lipid synthesis.


  70. Third Toronto essential fatty acid workshop on alpha -linolenic acid in human nutrition and disease. Cunnane S. Nutrition : (Burbank). 1992;8:129-138.
    (c) 1995 INIST/CNRS. All rts. reserv. part. II.


  71. Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease. Das UN. Prostaglandins Leukot Essent Fatty Acids. 1995;52:387-391.
    Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential hypertension (HTN) are higher in people of South Asian descent than in other groups. There is evidence to believe that essential fatty acids (EFAs) and their metabolites may have a role in the pathobiology of CHD, DM and HTN. Fatty acid analysis of the plasma phospholipid fraction revealed that in CHD the levels of gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low, in patients with HTN linoleic acid (LA) and AA are low, and in patients with non-insulin dependent diabetes mellitus (NIDDM) and diabetic nephropathy the levels of dihomo-gamma-linolenic acid (DGLA), AA, alpha-linolenic acid (ALA) and DHA are low, all compared to normal controls. These results are interesting since DGLA, AA and EPA form precursors to prostaglandin E1, (PGE1), prostacyclin (PGI2), and PGI3, which are potent platelet anti-aggregators and vasodilators and can prevent thrombosis and atherosclerosis. Further, the levels of lipid peroxides were found to be high in patients with CHD, HTN, NIDDM and diabetic nephropathy. These results suggest that increased formation of lipid peroxides and an alteration in the metabolism of EFAs are closely associated with CHD, HTN and NIDDM in Indians.


  72. Nutrients, essential fatty acids and prostaglandins interact to augment immune responses and prevent genetic damage and cancer. Das UN. Nutrition. 1989;5:106-10.
    Micronutrients, vitamins A, C, and E, beta-carotene, and selenium can decrease the incidence of cancer, possibly due to their antioxidant action(s). These nutrients prevent lipid peroxidation, especially that of gamma-linolenic, dihomo-gamma-linolenic and arachidonic acids, the precursors of prostaglandins. Gammma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA), prostaglandin E1 (PGE1) and prostacyclin can prevent genetic damage in vitro and in vivo. They augment immune responses and tumoricidal actions of macrophages. Prostacyclin also has anti-metastatic properties. Zinc, magnesium, calcium and pyridoxine are cofactors in the formation of GLA, DGLA, PGE1 and PGI2. Hence, in situations where there is a reduced intake of trace elements and vitamins, there may be a decrease in the synthesis of GLA, DGLA, PGE1 and PGI2, leading to immune suppression and genetic damage that cannot be reversed or prevented. In the presence of adequate amounts of selenium, beta-carotene and Vitamin A and E, peroxidation of GLA/DGLA/AA would not occur, so that they are available for the synthesis of PGE1 and PGI2. This interaction between nutrients, essential fatty acids and prostaglandins can be exploited to develop new preventive and therapeutic strategies in cancer.


  73. Essential fatty acid metabolism in south Indians. Das UN, Kumar KV, Ramesh G., Department of Medicine, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India. Prostaglandins Leukot Essent Fatty Acids. 1994;50:253-255.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Coronary artery disease (CAD), hypertension and diabetes mellitus are more common in Indians compared to their incidence in the Western population. The exact reason for this is not known. One of the risk factors for the development of and complications due to CAD, hypertension and diabetes mellitus could be hyperinsulinemia and insulin resistance and low plasma levels of arachidonic acid and eicosapentaenoic acid, metabolites of dietary essential fatty acids (EFAs), cis-linoleic and alpha-linolenic acids. Fatty acid analysis of the plasma phospholipid (PL) fraction of normal Indians showed that they have low concentrations of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid in comparison to those seen in Canadian and Minnesota (USA) normals. Since insulin can activate EFA metabolism, this alteration in the EFA metabolism may, at least, in part explain the high incidence of CAD, hypertension and diabetes mellitus and insulin resistance and hyperinsulinemia that are common in Indians.


  74. Omega-3 fatty acids and cardiovascular diseases: update to 1996. De Caterina R, Gianetti J, Endres S. G Ital Cardiol. 1996;26:563-578.
    N-3 Fatty acids (mostly eicosapentaenoic and docosahexaenoic acid) continue to elicit research interest as dietary or pharmacological agents able to prevent or retard the progression of atherosclerosis and its clinical manifestations. Significant advances have occurred over the past five years in understanding their mechanism of action, including anti-atherogenic, anti-thrombotic and anti-arrhythmic properties. In parallel, clinical studies have continued the evaluation of these compounds in the prevention of cardiovascular disease. Recent epidemiological studies have in general confirmed the hypothesis of a relevant anti-atherogenic effect, although this has not necessarily translated into clinical benefits in selected, relatively low-risk populations. Recent negative studies in trials of restenosis prevention after coronary angioplasty have tempered the initial enthusiasm as a possible preventive strategy in this subset, although reasons for discrepancies among past trials still await conclusive explanations. A recent dietary intervention trial in post-myocardial infarction patients has renewed the interest for alpha-linolenic acid, both as the metabolic precursor of eicosapentaenoic and docosahexaenoic acid, and as a fatty acid with direct specific properties.


  75. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. de Lorgeril M, Renaud S, Mamelle N, et al. Lancet. 1994;343:1454-1459.
    Comment in: Lancet 1994 Jun 11;343(8911):1445. Comment in: Lancet 1994 Aug 6;344(8919):407. Comment in: Lancet 1994 Aug 27;344(8922):622. Comment in: Lancet 1994 Sep 24;344(8926):893-4. Comment in: ACP J Club 1994 Nov-Dec;121(3):59.
    In a prospective, randomised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infarct prudent diet. After a first myocardial infarction, patients were randomly assigned to the experimental (n = 302) or control group (n = 303). Patients were seen again 8 weeks after randomisation, and each year for 5 years. The experimental group consumed significantly less lipids, saturated fat, cholesterol, and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma. Serum lipids, blood pressure, and body mass index remained similar in the 2 groups. In the experimental group, plasma levels of albumin, vitamin E, and vitamin C were increased, and granulocyte count decreased. After a mean follow up of 27 months, there were 16 cardiac deaths in the control and 3 in the experimental group; 17 non-fatal myocardial infarction in the control and 5 in the experimental groups: a risk ratio for these two main endpoints combined of 0.27 (95% CI 0.12-0.59, p = 0.001) after adjustment for prognostic variables. Overall mortality was 20 in the control, 8 in the experimental group, an adjusted risk ratio of 0.30 (95% CI 0.11-0.82, p = 0.02). An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death.


  76. Essential fatty acids in full term infants fed breast milk or formula. Decsi T, Thiel I, Koletzko B., Kinderpoliklinik, Ludwig-Maximilians-Universitat, Munich, Germany. Arch Dis Child Fetal Neonatal Ed. 1995;72:F23-28.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    To determine the biochemical effects of the fatty acid composition of plasma lipids, two groups of 10 healthy full term infants who were either exclusively breast fed or received a formula with similar contents of linoleic and alpha linolenic acids, but without long chain polyunsaturated (LCP) fatty acids, were studied prospectively. Plasma phospholipid, triglyceride, and sterol ester fatty acids were determined at the age of 2, 4, and 8 weeks by high resolution capillary gas chromatography. Breast fed infants maintained stable LCP fatty acid concentrations throughout the study. Formula fed infants had significantly lower median values of arachidonic acid (AA) at the ages of 2 (6.9 v 9.5% wt/wt) and 4 weeks (5.9 v 7.9%) and docosahexaenoic acid (DHA) at the ages of 4 (1.1 v 1.7%) and 8 weeks (1.0 v 1.7%) in plasma phospholipids. Median AA values in triglycerides were also significantly lower in the infants receiving formula at the ages of 2 (0.4 v 0.6%) and 4 weeks (0.3 v 0.6%). It is concluded that formula fed full term infants are unable to match the omega-3 and omega-6 LCP status of breast fed full term infants until at least two months after birth.


  77. Alpha-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex. Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G. J Neurochem. 1996;66:1582-1591.
    The effects of alpha-linolenic acid diet deficiency on rat dopaminergic and serotoninergic neurotransmission systems were investigated in the frontal cortex, striatum, and cerebellum of male rats 2,6,12, and 24 months of age. The diet deficiency induced severe decrease in the 22:6n-3 fatty acid levels in all regions and a compensatory increase in n-6 fatty acid levels. A recovery in the levels of 22:6n-3 was observed in deficient rats between 2 and 12 months of age; however, this recovery was lower in frontal cortex than in striatum and cerebellum. In the striatum and cerebellum, dopaminergic and serotoninergic receptor densities and endogenous dopamine and serotonin levels were affected by aging regardless of the diet. In contrast, a 40-75% lower level of endogenous dopamine in the frontal cortex occurred in deficient rats according to age. The deficiency also induced an 18-46% increase in serotonin 5-HT2 receptor density in the frontal cortex during aging, without variation in endogenous serotonin level, and a 10% reduction in density of dopaminergic D2 receptors. Monoamine oxidase-A and -B activities showed specific age-related variations but regardless of the diet. Our results suggest that a chronically alpha-linolenic-deficient diet specifically affects the monoaminergic systems in the frontal cortex.


  78. Chronic dietary alpha -linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmissions in rats. Delion S, Chalon S, Herault J, Guilloteau D, Besnard JC, Durand G., INSERM U 316, Laboratoire de Biophysique Medicale et Pharmaceutique et Laboratoire de Biochimie, 37200 Tours Cedex, France. J Nutr. 1994;124:2466-2476.
    (c) 1995 CAB International. All rts. reserv.
    This study examined the effects of dietary alpha -linolenic acid (LNA) deficiency on dopaminergic and serotoninergic neurotransmission systems in 60-day-old male Wistar rats. Rats were fed on semipurified diets containing peanut oil (the (n-3)-deficient group) or peanut plus rapeseed oil (control group). Densities of the serotonin-2 (5-HT2) receptors and the dopamine-2 (D2) receptors were estimated by autoradiography and membrane-binding assays in relation to the fatty acid composition and levels of endogenous monoamines in 3 cerebral regions: the frontal cortex, the striatum and the cerebellum. Long-term feeding of the (n-3)-deficient diet induced a significantly higher 5-HT2 receptor density in the frontal cortex compared with the control rats without any difference in the endogenous serotonin concentrations. Results also showed some modification of dopaminergic neurotransmission specifically in the frontal cortex in the rats deficient in alpha -LNA with a significantly lower density of D2 receptors and a significantly lower concentration of endogenous dopamine than in control rats. Moreover, there were lower levels of (n-3) fatty acids in all the regions studied in the deficient rats, balanced by greater levels of (n-6) fatty acids. It is suggested that chronic consumption of an alpha -LNA deficient diet could induce modification of the neurotransmission pathways; this might induce the behavioural disturbances previously described in this fatty acid-deficient animal model.


  79. Essential fatty acids and prematurity: a triple experimental approach. Descomps B, Rodriguez A. C R Seances Soc Biol Fil. 1995;189:781-796.
    Previous studies in our laboratory have shown that in fetal plasma arachidonic (AA) and docosahexaenoic acid (DHA) levels are higher (about two fold) than in maternal plasma whereas the reverse situation was observed for the levels of their C18 precursors linoleic acid (AL) and alpha-linolenic acid (AAL) (13). This paradoxical situation raises the questions of the origin of the long chain polyunsaturated fatty acids (PUFAs) and of the ability of fetal liver to desaturate and elongate C18 precursors since placenta was shown not to be able to desaturate fatty acids. This question should be answered for the rationale of formula feeding supplementation either with long chain PUFAs or with their C18 precursors. Three experimental approaches can contribute to elucidate this dilemna: nutritional studies with formula supplementation, investigations on hepatic enzymes in vitro, in vivo experiments using stable isotopes. Supplementation of formulas with AAL in precise conditions (AL/AAL ratio: 6.4/1 and AL intake: 4.95% of total energetic supply) was done in a multicentric study including 88 premature newborns (32 weeks post conceptional age) for five weeks. The plasma phospholipid and red blood cell DHA status was found to be closer to human milk feeding than with standard formula feeding and most of the n-6 pathway was preserved. The data suggests that in premature newborns a significant conversion of AAL into DHA is possible provided an equilibrium is respected between AL and AAL supplies. This conversion is confirmed both by in vitro and in vivo studies: in fetal livers (obtained from therapeutic abortion) significant delta 6 and delta 5 desaturase activities were measured by a radiochemical method using reverse phase HPLC separation of [1-14C] labelled substrates and products in the n-6 and in the n-3 series. Substrate inhibition was observed especially at delta 5 desaturation and the maximum velocities were relatively limited mainly in the n-6 pathway which was slower than in the n-3 serie. These data are in agreement with recent preliminary data obtained in different laboratories with stable isotopes in vivo but in infants born in term: experiments using either 13C or deuterium labelled fatty acids concluded to the conversion of C18 essential fatty acids into AA and DHA justifying (AAL) formula supplementation for sustaining DHA status in preterm newborns.


  80. Contrasting effects of treatment with .omega.-3 and omega.-6 essential fatty acids on peripheral nerve function and capillarization in streptozotocin-diabetic rats. Dines KC, Cotter MA, Cameron NE. Diabetologia. 1993;36:1132-138.
    (c) 1996 American Chemical Society. All rts. reserv.


  81. Comparison of recovery of previously depressed hepatic delta 6 desaturase activity in adult and old rats. Dinh L, Bourre JM, Dumont O, Durand G., Laboratoire de Nutrition et de Securite Alimentaire, INRA, Jouy-en-Josas, France. Ann Nutr Metab. 1995;39:117-123.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The ability to recover hepatic delta 6 desaturase (delta 6D) activity with linoleic acid as substrate was compared in adult and old rats. Male rats fed a diet deficient in alpha-linolenic acid were used either at 6 or 21 months. From these two ages onward, animals were fed a diet containing 10% fish oil for 3 months to reduce delta 6D activity. After this period, some of the animals were killed. The other animals were returned to the original diet deficient in alpha-linolenic acid. Fatty acid composition in liver and brain and hepatic delta 6D activity were analysed 3 and 7 days after the change in diet. When rats were fed the diet containing 10% fish oil, delta 6D activity was lower than in those fed the diet deficient in alpha-linolenic acid. The liver fatty acid composition was altered with disappearance of 22:5 n-6 and a decrease in 18:2 n-6, 20:4 n-6 and 22:4 n-6 accompanied by an increase in 20:5 n-3, 22:5 n-3 and 22:6 n-3. When rats were re-fed the original diet, delta 6D activity returned after 3 days to its initial level in the 9-month-old rats; in 24-month-old animals, recuperation was incomplete. The level of 20:4 n-6 and 18:2 n-6 increased in the liver concurrently with a decrease in levels of 20:5 n-3, 22:5 n-3 and 22:6 n-3. In both age groups, the brain fatty acid profile remained unchanged 7 days after returning to the diet deficient in alpha-linolenic acid.


  82. Comparison of liver microsome enzyme and fatty acid compositionrecovery in adult and old rats deficient in 18:3n-3 refed a dietcontaining 18:3n-3. Dinh L, Dumont O, Durand G., Laboratoire de Neurotoxicologie, INSERM U26, 200 Rue du Fg Saint-Denis, 75010 Paris, France. Biochem Mol Biol Int. 1994;32:869-877.
    (c) 1995 CAB International. All rts. reserv.
    The effect of dietary n-3 polyunsaturated fatty acid (PUFA) deficiency on liver microsome enzymes activities and fatty acid composition was studied in adult (3 months old) and old rats (18 months old). At both ages, deficient rats were refed with alpha -linolenic acid (18:3n-3) diet for 1 or 2 months and the recovery of these parameters was investigated. Cytochrome P-450 was decreased by n-3 PUFA deficiency. After refeeding, it returned to control values after 1 month. NADH-cytochrome b5 reductase activity was decreased, the activities of NADPH cytochrome c reductase, aminopyrine demethylase, aniline hydroxylase were also decreased, but in old rats they were increased by refeeding. n-3 PUFA deficiency caused a decrease of 18:2n-6 and 22:6n-3 and an increase in 20:4n-6, 22:5n-6 and 18:1n-9. After refeeding, in adult rats, the PUFA level remained lower, in old rats, the monounsaturated fatty acid and PUFA levels returned to control values. Liver microsomal enzyme activities depend on the degree of unsaturation of fatty acids rather than the specific species of PUFA.


  83. The incorporation of (1-14C)linolenate into lipids of developing rat brain during essential fatty acid deprivation. Dwyer B, Bernsohn J., (Dep. Biochem. and Biophys., Loyola Univ. Med. Cent., Maywood, IL, USA) . J Neurochem . 1979;32:833-838.
    (c) 1995 Cambridge Sci Abs. All rts. reserv.
    Twenty-one-day old essential fatty acid (EFA) deprived rats incorporated about twice the radioactivity from (1-14C)linolenate into brain lipid fractions as did controls. At 5 min after injection, 2/3 of the radioactivity was associated with the less polar lipid fraction of both control and EFA deprived animals. By 30 min after injection, 70% of the radioactivity was in the phospholipid fraction. This value increased to 90% at later time points. The specific activity of brain phospholipids from EFA deprived rats was always greater than that of controls. Phosphatidylcholine was usually labeled most rapidly. With increasing time intervals, radioactivity was transferred to phosphatidylethanolamine and phosphatidylserine + phosphatidylinositol. The transfer of fatty acid radioactivity into phospholipid and the distribution of radioactivity among individual phosphatides did not appear to be affected by the dietary state. The total amount of radioactivity incorporated was related to the amount initially retained by brain after injection. These data suggest that one or more components of the less polar lipid fraction may act as a 'trap' or reservoir for fatty acids which are required for phospholipid synthesis.


  84. Neural 22-carbon fatty acids in the weanling rat respond rapidly and specifically to a range of dietary linoleic to alpha-linolenic fatty acid ratios. Dyer JR, Greenwood CE., Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada. J Neurochem. 1991;56:1921-1931.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Changing the dietary ratio of the essential fatty acids (EFA), 18:2n6 and 18:3n3, while keeping the amounts of other fatty acids in the diet constant can rapidly and specifically alter the proportions of n6 and n3 22-carbon fatty acids in the brain of the weanling rat. A dietary 18:2n6/18:3n3 ratio of 165 versus 1.8 caused higher n6 and lower n3 22-carbon fatty acid levels, without changing total 22-carbon fatty acid levels, in phosphatidylethanolamine and phosphatidylcholine from several neural membrane fractions. This was apparent after only 2 weeks and showed no sign of plateauing after 12 weeks. Other neural fatty acids were essentially unaffected. The three most abundant 22-carbon fatty acids responded somewhat differently to increments in the dietary 18:2n6/18:3n3 ratio (1.8, 9, 36, and 165). Levels of 22:4n6 increased by similar absolute amounts for each four-fold increase in dietary 18:2n6/18:3n3 ratio; in contrast, the largest absolute changes in 22:5n6 and 22:6n3 levels occurred as the 18:2n6/18:3n3 ratio increased from 36 to 165. This study shows that the 18:2n6/18:3n3 ratio of diets high in fat (40% of energy) and adequate in EFA, both typical of diets in developed countries, can substantially and relatively quickly affect the 22-carbon fatty acids in the brain, even after the rapid accumulation of these fatty acids during neural growth has ceased.


  85. Activities of liver microsomal fatty acid desaturases in zinc-deficientrats force-fed diets with a coconut oil/safflower oil mixture of flaxseed oil. Eder K, Kirchgessner M., Institut fur Ernahrungsphysiologie der Technischen Universitat Munchen-Weihenstephan, 85350 Freising, Germany. Biol Trace Elem Res. 1995;48:215-229.
    (c) 1995 CAB International. All rts. reserv.
    A study was conducted to investigate the effect of zinc deficiency on fatty acid desaturation in Sprague-Dawley rats fed on Zn-deficient diets containing 2 types of dietary fat, a mixture of coconut oil and safflower oil (7:1, weight/weight, &quotcoconut oil diet") or linseed oil (&quotlinseed oil diet"). In order to ensure an adequate food intake, rats were force-fed by gastric tube. Zn deficiencies caused significant reduction of DELTA 9-desaturase activity in liver microsomes of rats fed on coconut oil diet and tendential reduction (P&lt0.15) in rats fed on linseed oil diet compared with control rats fed on diets with the same type of fat. In agreement with this effect, Zn deficiency in the rats fed on both types of dietary fat increased the ratio between total saturated and total monounsaturated fatty acid in liver phospholipids and liver microsomes. Zn deficient rats on the coconut oil diet had unchanged DELTA 6-desaturase activity with linoleic acid as substrate and lowered activity with alpha -linolenic acid as substrate. In contrast, Zn deficient rats on the linseed oil diet had increased DELTA 6-desaturase activity with linoleic acid as substrate and unchanged activity with alpha -linolenic acid. Because linoleic acid is the main substrate for DELTA 6-desaturase in the rats fed on coconut oil diet, it is concluded that in vivo DELTA 6 desaturation was not changed by Zn deficiency in rats fed on both types of dietary fat. Activity of DELTA 5-desaturase was also not changed by Zn deficiency in rats fed on both dietary fats. Levels of fatty acids in liver phospholipids and liver microsomes derived by DELTA 4-, DELTA 5- and DELTA 6-desaturation were not consistently changed by Zn deficiency in rats fed on both types of fat. Thus, enzyme studies and also fatty acid composition data of liver phospholipids and microsomes indicate that Zn deficiency does not considerably disturb desaturation of linoleic and alpha -linolenic acid. Therefore, it is suggested that similarities between deficiencies of Zn and essential fatty acids described in the literature are not due to disturbed desaturation of linoleic acid in Zn deficiency. This study also indicates that Zn deficiency enhances incorporation of eicosapentaenoic acid into phosphatidylcholine of rats fed on diets with large amounts of n-3 polyunsaturated fatty acids.


  86. Influence of dietary polyunsaturated fatty acids on aortic and platelet fatty acid composition in the rat. Engler MM, Karanian JW, Salem NJr., Univ Cal., San Francisco, Dept. Physiological Nursing, Room N611Y, Lab, Cardiovascular Physiol, San Francisco, CA 94143-0610 . Nutrition Research. 1991;11:753-764.
    (c) 1996 BIOSIS. All rts. reserv.
    The effects of 18-carbon chain w-9, w-6 and w-3 fatty acid enriched diets on aortic and platelet fatty acid composition were studied in male Sprague-Dawley rats. Purified diets containing 11 wt% of either sesame oil (SES) rich in 18:1w9, borage oil (BOR) rich in 18:3w6 or a blend of linseed and safflower oils (LSO/SFO) rich in 18:3w3 were administered for 7 weeks. All diets provided comparable amounts of the essential fatty acid 18:2w6. Total lipids from aortic tissue and platelets were extracted, methylated and analyzed by gas chromatography. In general, the tissue fatty aicd composition reflected the type of dietary fat. The SES diet resulted in increased levels of 18:1w9 whereas the BOR diet increased 18:3w6 and the LSO/SFO diet increased 18:3w3 in aortic and platelet lipids. However, the BOR diet also LSO/SFO diet increased 18:3w3 in aortic and platelet lipids. However, the BOR diet also resulted in an increase in the longer chain metabolites 20:3w6 and 20:4w6. The LSO/SFO-based diet elevated the levels of 20:5w3 and 22:6w3. These results suggest that the profile of 20-carbon chain polyunsaturated fatty caids can be modified in vascular tissue and platelets by diets enriched with 18-carbon w-6 and w-3 fatty acids.


  87. Dietary lipid modulation of immune responsiveness. Erickson KL, Adams DA, McNeill CJ. Lipids. 1983;18:468-74.
    The influence of dietary fat concentration and saturation on blastogenesis, cytotoxicity, antibody response and fatty acid composition of murine splenic lymphocytes was studied. Blastogenesis of lymphocytes from dietarily manipulated mice in response to alloantigens from control mice was significantly greater for those mice fed a diet containing minimal essential fatty acids (EFA) as the only fat source (EFA control) than those fed an EFA-deficient diet. When the dietary fat concentration was increased, blastogenic response decreased compared to the EFA control diet. Lymphocyte-mediated cytotoxicity against allogeneic melanoma cells was greater for mice receiving diets with EFA only than for those deficient in EFA. However, cytotoxicity responses of mice fed additional polyunsaturated fat (PUF) decreased as concentration increased, whereas responses of mice fet the saturated fat (SF) diets decreased only when the dietary fat concentration was greater than 8%. As compared to diets with EFA control, direct plaque-forming cell (PFC) response was decreased for mice fed high levels of PUF and increased for mice fed high levels of SF; however, no difference in the percentage of IgM-positive cells was observed. These changes in PFC response were inversely related to the levels of linoleic acid in the lymphocyte. Thus, high levels of dietary fat, and particularly PUF, suppress lymphocyte functions when EFA requirements are met, whereas low levels (EFA control) intensify these responses. EFA deficiency, however, suppress some lymphocyte responses. Thus, dietary lipids differentially modulate the levels of T- and B-cell responsiveness.


  88. Age- and dietary-related distributions of hepatic arachidonic and docosahexaenoic acid in early infancy. Farquharson J, Jamieson EC, Logan RW, Patrick WJ, Howatson AG, Cockburn F. Pediatr Res. 1995;38:361-365.
    A dietary-related deficiency of docosahexaenoic acid [C22:6(n-3)] in infant cerebral cortex has been identified. Absence or very low rates of hepatic synthesis from the essential fatty acid precursor, alpha-linolenic acid [C18:3(n-3)], in early life may have been a contributory factor. We have analyzed liver total lipid fatty acid compositions in 27 term (37-42 wk gestation) and 4 preterm (30-33 wk gestation) infants who died within the first 6 mo of life from sudden infant death syndrome. The infants were fed exclusively either human or formula milks. Formula-fed infants were subdivided into two groups, one receiving SMA milk with an alpha-linolenic acid content at 1.5% of total fatty acids and the other a composite group fed milks with low alpha-linolenic acid concentrations (< 0.1% to 0.4%). The hepatic content of arachidonic acid [C20:4(n-6)] and docosahexaenoic acid was generally lower in both formula-fed groups than in the human milk-fed group. The age-related distributions of docosahexaenoic acid showed that coincident minimum levels were present in both formula groups in the third month of life. This may indicate that the hepatic enzymes involved in the final stage (delta 4-desaturation) conversion of alpha-linolenic acid to docosahexaenoic acid could be inactive in the first months of life. Emphasis must be on provision of preformed dietary docosahexaenoic acid and possibly arachidonic acid as well as their essential fatty acid precursors, to both term and preterm infants for at least the first 16 wk of life.


  89. Dietary alpha-linolenic acid deficiency and early uterine development in female rats. Fayard JM, Timouyasse L, Guesnet P, Durand G, Pascal G, Laugier C., Laboratoire de Physiologie Pharmacodynamie, INSERM U 352, INSA Villeurbanne, France. J Nutr. 1992;122:1529-1535.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Feeding rats a purified diet containing peanut oil with a low alpha-linolenic acid [18:3(n-3)] content resulted in lower amounts of (n-3) polyunsaturated fatty acids, mainly docosahexaenoic acid [22:6(n-3)], greater amounts of docosapentaenoic acid [22:5(n-6)] in uterus phospholipids, and altered postnatal uterus development when compared with rats fed a diet containing peanut and rapeseed oils. Maximal differences in uterine growth, as measured by uterine weight, protein and DNA content, occurred between d 24 and 30 postpartum and disappeared near the end of sexual development (d 40). The induction of the progesterone receptor was not affected, and serum estradiol concentrations were not significantly reduced in deficient animals. Moreover, growth response of the uterus to low doses of 17 beta-estradiol (less than 5 micrograms/kg) was significantly reduced in ovariectomized animals fed the diet containing only peanut oil. However, the maximal response of the uterus, observed with higher 17 beta-estradiol doses (5-50 micrograms/kg), was not affected. Because the two diets used differed in the content of alpha-linolenic acid, it is likely that alpha-linolenic acid deficiency in animals fed the diet containing only peanut oil was the cause of the affected uterine development.


  90. Antithromboxane activity of dietary alpha-linolenic acid: a pilot study. Ferretti A, Flanagan VP. Prostaglandins Leukot Essent Fatty Acids. 1996;54:451-455.
    Two decades of research conclusively demonstrated the antithrombotic properties of the long-chain n-3 polyunsaturated fatty acids (PUFA) present in lipids from marine fishes. Most American consumers, however, given their preference for meat, will not realize the benefits of a fish-rich diet. Could alpha-linolenic acid (18:3, n-3) be similarly effective via modulation of the synthesis of vasoactive eicosanoids, i.e., thromboxane and prostacyclin? The present pilot study is a contribution toward answering this question. We determined that the urinary excretion of 11-dehydrothromboxane B2 declined by 34% from baseline level 7 weeks after the n-6/n-3 ratio of dietary PUFA was reduced from 28:1 to 1:1. The excretion of 2,3-dinor-6-oxo-prostaglandin F1 alpha was similarly affected. The dietary adjustment was brought about by substituting measured amounts of canola and flaxseed oils (3:1) for measured amounts of olive and corn oils (3:1) in an otherwise fat-free basal diet. This study demonstrates that dietary alpha-linolenic acid is an effective modulator of thromboxane and prostacyclin biosynthesis. Therefore, we can expect that the eicosanoid-mediated effects of alpha-linolenic acid are similar to those elicited by marine lipids.


  91. Schizophrenic patients treated with high dose phenothiazine or thioxanthene become deficient in polyunsaturated fatty acids in their thrombocytes. Fischer S, Kissling W, Kuss HJ., Department of Medicine II, University of Munich, Federal Republic of Germany. Biochem Pharmacol. 1992;44:317-23.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Total fatty acids were analysed in thrombocytes of schizophrenic patients treated with a &quothigh dose" or &quotlow dose" monotherapy of neuroleptic drugs phenothiazine or thioxanthene. The ratio of the very long chain fatty acid hexacosanoic acid to the long chain fatty acid docosanoic acid (C26:0/C22:0) increased in the &quothigh dose" and &quotlow dose" groups as compared to healthy untreated controls (P less than 0.05). The polyunsaturated fatty acid arachidonic acid decreased in the &quothigh" and &quotlow dose" groups (P less than 0.01 and P less than 0.05). The polyunsaturated fatty acids alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid were not detectable in most of the &quothigh dose" schizophrenic patients, however, they were found in the &quotlow dose" group and in the controls. There was a negative correlation between the daily dosage of phenothiazine and the percentages of the polyunsaturated fatty acids arachidonic acid and alpha-linolenic acid+eicosapentaenoic acid+docosahexaenoic acid in thrombocytes (r = -0.87, P less than 0.01 and r = -0.81, P less than 0.01). Two patients of the &quothigh dose" group with an especially high and long lasting monotherapy of neuroleptics were nearly devoid of polyunsaturated fatty acids in their thrombocytes. Untreated schizophrenic patients exhibited a fatty acid pattern in their thrombocytes not markedly different from that of the healthy untreated control group. We conclude that neuroleptic drugs phenothiazine or thioxanthene can alter the fatty acid pattern of thrombocytes.


  92. Influence of a dietary alpha-linolenic acid deficiency on learning in the Morris water maze and on the effects of morphine. Frances H, Coudereau JP, Sandouk P, Clement M, Monier C, Bourre JM. Eur J Pharmacol. 1996;298:217-225.
    Female OF1 mice were fed on a diet deficient in alpha-linolenic acid or on a control diet 3 weeks before mating and throughout pregnancy and lactation. Pups fed on the same diet as their mothers were used for experiments. The effects of dietary alpha-linolenic acid deficiency were studied in a model of learning, the Morris water maze, and on the following effects of morphine: increase in locomotor activity, modifications of rectal temperature and analgesia. In the place and in the cue versions of the Morris water maze, learning occurred at the same speed in the two diet groups; however, in the place version of the test, the level of the performance was significantly lower in the deficient mice. The probe trial and the extinction procedure did not show any difference between the two diet groups. The morphine-induced increase in locomotor activity occurred significantly earlier and was greater in the deficient diet group. Morphine induced an early hypothermia followed by a late hyperthermia; the hypothermia was significantly greater and the hyperthermia significantly smaller in the deficient mice. The pain thresholds and the morphine-induced analgesia were unmodified by the dietary deficiency. The plasma levels of morphine were similar in the two diet groups.


  93. Effects of dietary alpha-linolenic acid deficiency on neuromuscular and cognitive functions in mice. Frances H, Monier C, Bourre JM., INSERM U.26 - Hopital Fernand Widal 200, rue du Fbg St Denis 75010 Paris, France. Life Sci. 1995;57:1935-1947.
    (c) 1995 CAB International. All rts. reserv.
    Female OF1 mice were fed on a diet deficient in alpha -linolenic acid or a control diet and the effect of this deficiency was assessed by behavioural and pharmacological measurements. 3 weeks before mating mice were fed on a diet containing peanut oil poor in alpha-linolenic acid ((n-3)-) or peanut + rapeseed oil rich in alpha-linolenic acid ((n-3)+, controls). Pups, aged 47 to 61 days, fed on the same diet as their dams, were used for behavioural experiments. Muscular function and neuromuscular coordination assessed by the traction test, the elevated rotarod test and swimming endurance were unchanged by the (n-3)- deficiency. The level of anxiety assessed by the elevated plus-maze (anxiety protocol), the light-dark transition and the neophobia tests did not differ between (n-3)- and control mice. Defensive behaviour was not changed by the diet. The pentobarbital-induced loss of the righting reflex had the same duration in males, females and controls as in (n-3) deficient mice; the latency to pentobarbital-induced loss of the righting reflex was significantly shorter in females than in males but did not differ according to the diet. Mice fed on the (n-3)- deficient diet showed less efficient learning in the elevated plus-maze (learning protocol) and poorer understanding of the situation (or less motivation to escape) in the low rotarod test than mice fed on the control (n-3)+ diet.


  94. The influence of dietary fatty acids and vitamin E on plasma prostanoids and liver microsomal alkane production in broiler chickens with regard to nutritional encephalomalacia. Fuhrmann H, Sallmann HP. J Nutr Sci Vitaminol. 1995;41:553-561.
    Nutritional encephalomalacia (NE) in broiler chicken is considered as a peroxidative dysfunction caused by vitamin E-deficient diets. A feeding experiment was performed to investigate the consequences of feeding different fats in combination with increasing amounts of vitamin E on liver lipid peroxidation and plasma prostanoid pattern. Newly hatched chicks from hens on a vitamin E-poor diet were fed with either mainly linolenic, linoleic or oleic acid-rich oils in a vitamin E-deficient (5 ppm) basic diet. The animals were supplemented with vitamin E on three levels (0, 20 or 120 ppm). On appearance of the first symptoms of NE after 8 days post-hatching, the animals were examined. Typical symptoms with a high incidence only occurred in the group fed linoleic acid and 5 ppm vitamin E. Plasma prostanoids and microsomal alkane production in liver as a measure of endogenous lipid peroxidation were determined. The dietary conditions affected plasma prostaglandin E2 and thromboxane A2, but not prostacyclin. However, it seems unlikely that the prostanoids are involved in the pathogenesis of NE. Liver lipid peroxidation increased in vitamin E deficiency. The level of alkanes depended on the type of fat supplied. The consequences of the different dietary fats in combination with vitamin E deficiency on peroxidative metabolism of broiler chickens are evident, indicating that a high level of oxidative stress is imposed by the linoleic acid-rich fat.


  95. Arachidonic acid stimulates cell growth in an osteoblastic cell line, MC3T3-E1, by noneicosanoid mechanism. Fujimori A, Tsutsumi M, Yamada H, Fukase M, Fujita T., Third Div., Dep. Med., Kobe Univ. Sch. Med., Kusunoki-cho, Chuo-ku, Kobe 650, Japan . Calcif Tissue Int. 1989;44:186-191.
    (c) 1995 Cambridge Sci Abs. All rts. reserv.
    Arachidonic acid, added to .alpha.-minimum essential medium containing 10% fetal bovine serum at the final concentration of 10-4 M, significantly increased DNA content of an osteoblastic cell line, MC3T3-E1, along with an increase of DNA synthesis. .alpha.-Linolenic acid, which cannot be converted to arachidonic acid, also increased DNA content at 10-4 M. The stimulatory effects of these fatty acids were not inhibited by simultaneous addition of indomethacin. Indomethacin also significantly increased DNA content of MC3T3-E1 cells. These results suggest that arachidonic acid may potentiate the growth-stimulatory effect of serum-derived growth factors probably via noneicosanoid mechanism.


  96. Increased requirements for essential fatty acids in atopic individuals: a review with clinical descriptions. Galland L. J Am Coll Nutr. 1986;5:213-28.
    Patients with atopic eczema and a mixture of allergic illnesses show biochemical evidence suggesting impairment in the desaturation of linoleic acid and linolenic acid by the enzyme delta-6 dehydrogenase. Consequences of this enzyme defect are 1) diminished synthesis of the 20-carbon polyunsaturated fatty acids, which are prostaglandin precursors and 2) a reduction in the concentration of double bonds in the cell membrane. A distortion in the production of prostaglandins and leukotrienes, which might result from this block, can account for the immunological defects of atopy and a variety of clinical symptoms experienced by atopic individuals. Dietary supplementation with essential fatty acids relieves the signs and symptoms of atopic eczema, may improve other types of allergic inflammation, and may also correct coexisting symptoms as diverse as excessive thirst and dysmenorrhea. Further research is suggested to test the hypothesis that some atopic states represent a condition of essential fatty acid dependency owing to defective desaturation of dietary fatty acids.


  97. Fatty acid composition of breast milk lipids of Nigerian women. Glew RH, Omene JA, Vignetti S, D'amico M, Evans RW., Health sci. cent. univ. New Mexico, dep. biochemistry, Albuquerque NM 87131, USA . Nut Res. 1995;15:477-489.
    (c) 1995 INIST/CNRS. All rts. reserv.
    Breast milk lipids from 13 lactating women in Southern Nigeria who were moderate to severely malnourished and whose mean body mass index (BMI) was 20.2 ( +- 1.9) and (16.4 ( +- 1.2)), respectively were separated into various neutral lipid and phospholipid fractions and analyzed for their fatty acid compositions. There were no differences in the content of free fatty acids, diglycerides, triglycerides or the major phospholipid classes between the two groups of women. Three saturated fatty acids (12:0, 14:0, and 16:0) and oleic acid accounted for more than three-fourths of the total fatty acids in the triglyceride fractions. Lauric acid (12:0) and myristic acid (14:0), intermediate-chain length fatty acids which are readily digested, absorbed and oxidized by newborn infants, comprised an unusually high proportion (approximately 40%) of the fatty acids of the total breast milk lipids. While the breast milk of all the mothers we studied contained moderate levels of linoleic acid (18:2(n-6)), they were markedly deficient in another essential fatty acid, namely alpha -linolenic acid (18:3(n-3)). A lack of alpha -linolenic acid could result in a deficiency of docosahexaenoic acid (22:6(n-3)) in the central nervous system of the infants being nursed by these mothers.


  98. Linolenic acid transport in hamster intestinal cells is carrier-mediated. Gore J, Hoinard C., Laboratoire de Physiologie et Biophysique Cellulaires, Faculte des Sciences Pharmaceutiques, Tours, France. J Nutr. 1993;123:66-73.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The intestinal uptake of [1-14C]linolenic acid [18:3(n-3)], an essential fatty acid, was investigated in isolated hamster intestinal cells using a rapid filtration method and 20 mmol/L taurocholate as solubilizing agent. Under these conditions, the initial rate of alpha-linolenic acid uptake was not a linear function of external monomer concentrations in the range of 2 to 2250 nmol/L, but rather the transport system was characterized by saturation kinetics with Vmax = 11.37 protein-1.min-1 and Km = 382 nmol/L. Temperature and metabolic poisons (2,4-dinitrophenol, antimycin A) drastically decreased the initial rate of uptake, as did replacement of Na+. The presence of excess unlabeled alpha-linolenic acid in the incubation medium significantly inhibited the uptake of [1-14C]linolenic acid, whereas L-alanine and D-glucose had no effect. Other long-chain fatty acids (saturated or unsaturated), as well as cholesterol, inhibited the uptake of [1-14C]linolenic acid. We concluded that an active, carrier-mediated mechanism was involved in the intestinal transport of alpha-linolenic acid. Inhibition data are compatible with the hypothesis that intestinal uptake of alpha-linolenic acid is mediated by a carrier common to long-chain fatty acids.


  99. Linoleic acid uptake by isolated enterocytes: influence of alpha-linolenic acid on absorption. Gore J, Hoinard C, Couet C. Lipids. 1994;29:701-706.
    In a previous study we showed that intestinal uptake of alpha-linolenic acid (18:3n-3) was carrier-mediated and we suggested that a plasma membrane fatty acid protein was involved in the transport of long-chain fatty acids. To further test this hypothesis, the mechanism of linoleic acid (18:2n-6) uptake by isolated intestinal cells was examined using a rapid filtration method and 20 mM sodium taurocholate as solubilizing agent. Under these experimental conditions transport of [1-14C]linoleic acid monomers in the concentration range of 2 to 2220 nM was saturable with a Vm of 5.1 +/- 0.6 nmol/mg protein/min and a Km of 183 +/- 7 nM. Experiments carried out in the presence of metabolic inhibitors, such as 2,4-dinitrophenol and antimycin A, suggested that an active, carrier-mediated mechanism was involved in the intestinal uptake of this essential fatty acid. The addition of excess unlabeled linoleic acid to the incubation medium led to a 89% decrease in the uptake of [1-14C]linoleic acid, while D-glucose did not compete for transport into the cell. Other long-chain polyunsaturated fatty acids added to the incubation mixture inhibited linoleic acid uptake by more than 80%. The presence of alpha-linolenic acid (18:3n-3) in the incubation medium caused the competitive inhibition (Ki = 353 nM) of linoleic acid uptake. The data are compatible with the hypothesis that intestinal uptake of both linoleic, and alpha-linolenic acid is mediated by a membrane carrier common to long-chain fatty acids.


  100. Loss of fatty acid Delta 6 desaturating ability in human mammary epithelial cells that express an activated c-Ha-ras oncogene. Grammatikos SI, Harvey MJ, Subbaiah PV, Victor TA, Miller WM., Department of Chemical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3120. USA . Int J Onc. 1995;6:1039-1046.
    (c) 1996 Elsevier Science B.V. All rts. reserv.
    The synthesis of essential fatty acids (EFAs) that have been shown to inhibit breast cancer cell growth in vitro and tumor growth in animals requires desaturation at C-6 of linoleic or alpha-linolenic acid. This observation, combined with reports that many tumors and tumor cell lines are deficient in Delta6 desaturation and/or contain low levels of 6-desaturated EFAs, has led to the suggestion that loss of Delta6 desaturating ability is relevant to the process of malignant transformation. This study was undertaken in search of direct evidence that malignant transformation of mammary epithelial cells alters EFA metabolism. We used two cell lines derived from the spontaneously immortalized human mammary epithelial cell line MCF-10A and expressing either the c-Ha-ras protooncogene (MCF-10AneoN) or an activated c-Ha-ras oncogene (MCF-10AneoT), and a cell line immortalized by transfection of human mammary epithelial cells with SV40 T antigen. We compared these cell lines in terms of ability to convert EFAs (30 microM) to other EFAs of the same family. MCF-10AneoT cells lose the ability to perform Delta6 and Delta4 desaturations, whereas MCF-10AneoN cells and the SV40 T antigen-transformed cell line do not. No significant changes in growth response to culture with 6-desaturated EFAs were noted for MCF-10AneoT cells compared with MCF-10AneoN and parental MCF-10A cells, suggesting that FA metabolism alone cannot account for the effects of EFAs on the growth of neoplastic and non-neoplastic mammary epithelial cells.


  101. Diversity in the ability of cultured cells to elongate and desaturate essential (n-6 and n-3) fatty acids. Grammatikos SI, Subbaiah PV, Victor TA, Miller WM. Ann N Y Acad Sci. 1994;745:92-105.
    Essential fatty acids (EFAs) cannot be synthesized by mammalian cells. Once taken in with the diet, they can undergo desaturations/saturations and chain elongations/shortenings to yield a variety of polyunsaturated fatty acids of the same family. Cells in vitro from a variety of tissues are capable of processing EFAs to varying extents. Conversion of the parent EFAs, linoleic (LA, n-6) and alpha-linolenic (LNA, n-3) acids, to the 20-carbon polyunsaturated fatty acids, arachidonic (AA, n-6) and eicosapentanoic (EPA, n-3), requires chain elongation and delta 6 and delta 5 desaturations. AA and EPA are required by many tissues for optimal biological function and are precursors of biologically active eicosanoid hormones. All cultured cells are able to elongate exogenous LA and LNA, and most can perform delta 5 desaturation, so delta 6 desaturation is the limiting step in AA and EPA production. Longer fatty acids that have more double bonds than AA or EPA are less frequently produced due to a deficiency in delta 4 desaturating ability. The process of retroconversion (chain shortening) is less extensively studied, but evidence from a variety of cells suggests that this type of metabolic conversion is normally active. The example of MCF-7 (human breast cancer cell line) and MCF-10A cells (human noncancerous breast cell line) is discussed in order to emphasize the diversity in EFA processing ability of cultured cells. Under identical culture conditions, MCF-10A cells perform extensive desaturations, elongations, and retroconversions, whereas MCF-7 cells can only elongate and retroconvert exogenous EFAs. Given the great diversity in the ability of cultured cells to process EFAs, no conclusions can be drawn regarding the mechanisms responsible for the effects of exogenous EFAs on a particular cell until that cell's EFA processing patterns have been evaluated.


  102. N-3 and n-6 fatty acid processing and growth effects in neoplastic and non-cancerous human mammary epithelial cell lines. Grammatikos SI, Subbaiah PV, Victor TA, Miller WM. Br J Cancer. 1994;70:219-227.
    The type rather than the amount of dietary fat may be more important in breast carcinogenesis. While animal studies support this view, little is known about the effects of essential fatty acids (EFAs) at the cellular level. The MCF-7 breast cancer and the MCF-10A non-cancerous human mammary epithelial cell lines are compared in terms of growth response to EFAs and ability to incorporate and process the EFAs. Eicosapentaenoic (EPA, n-3) and docosahexaenoic (DHA, n-3) acids, presented bound to albumin, inhibited the growth of MCF-7 cells by as much as 50% in a dose-dependent manner (6-30 microM) in medium containing 0.5% serum. alpha-Linolenic (LNA, n-3) and arachidonic (AA, n-6) acids inhibited growth less extensively, while linoleic acid (LA, n-6) had no effect. In contrast, MCF-10A cells were not inhibited by any of the EFAs at levels below 24 microM. The differential effects of AA, EPA and DHA on MCF-7 and MCF-10A cells support a protective role of highly unsaturated essential fatty acids against breast cancer. The EFAs were primarily incorporated into phosphoglycerides. MCF-7 cells showed chain elongations and possibly delta 8 desaturation, but no AA was formed from LA, nor EPA or DHA from LNA. In contrast, MCF-10A cells desaturated and elongated the exogenous EFAs via all the known pathways. These findings suggest defects in the desaturating enzymes of MCF-7 cells. LNA, DHA and AA presented to MCF-7 cells in phospholipid liposomes inhibited growth as extensively as albumin-bound free acids, but were less extensively incorporated, suggesting different mechanisms of inhibition for the two methods.


  103. Effects of essential fatty acids on epidermal growth factor receptor tyrosine autophosphorylation. Grammatikos SI, Webb MD, Harvey MJ, Victor TA, Milller WM. Dep. Chem. Eng., Northwestern U., Evanston, Il 60208, Usa. Proceedings Of The American Association For Cancer Research Annual Meeting. Eighty-Sixth Annual Meeting Of The American Association For Cancer Research, March 18, 1995-March 22, 1995; Toronto, Ontario, Canada. 1995:54.
    Toronto, Ontario, Canada, March 18-22, 1995.


  104. Incorporation of trans long-chain n-3 polyunsaturated fatty acids in rat brain structures and retina. Grandgirard A, Bourre JM, Julliard F, et al., INRA, Station de Recherches sur la Qualite des Aliments de l'Homme, Unite de Nutrition Lipidique, Dijon, France. Lipids. 1994;29:251-258.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    During heat treatment, polyunsaturated fatty acids and specifically 18:3n-3 can undergo geometrical isomerization. In rat tissues, 18:3 delta 9c,12c,15t, one of the trans isomers of linolenic acid, can be desaturated and elongated to give trans isomers of eicosapentaenoic and docosahexaenoic acids. The present study was undertaken to determine whether such compounds are incorporated into brain structures that are rich in n-3 long-chain polyunsaturated fatty acids. Two fractions enriched in trans isomers of alpha-linolenic acid were prepared and fed to female adult rats during gestation and lactation. The pups were killed at weaning. Synaptosomes, brain microvessels and retina were shown to contain the highest levels (about 0.5% of total fatty acids) of the trans isomer of docosahexaenoic acid (22:6 delta 4c,7c,10c,13c,16c,19t). This compound was also observed in myelin and sciatic nerve, but to a lesser extent (0.1% of total fatty acids). However, the ratios of 22:6 trans to 22:6 cis were similar in all the tissues studied. When the diet was deficient in alpha-linolenic acid, the incorporation of trans isomers was apparently doubled. However, comparison of the ratios of trans 18:3n-3 to cis 18:3n-3 in the diet revealed that the cis n-3 fatty acids were more easily desaturated and elongated to 22:6n-3 than the corresponding trans n-3 fatty acids. An increase in 22:5n-6 was thus observed, as has previously been described in n-3 fatty acid deficiency. These results encourage further studies to determine whether or not incorporations of such trans isomers into tissues may have physiological implications.


  105. Elongation, desaturation, and esterification of essential fatty acids by fetal rat brain in vivo. Green P, Yavin E., Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel. J Lipid Res. 1993;34:2099-2107.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Tracer amounts of either [1-14C]linolenic (18:3n-3, LNA), or [1-14C]linoleic (18:2n-6, LA) acids were intracranially injected into 19- to 20-day-old rat fetuses, and the time course of the in vivo formation and esterification of their long chain polyenoic metabolites was determined for up to 20 h. A rapid disappearance of free LNA and LA, with apparent half-lives of 60 and 40 min, respectively, was noticed. One hour after LNA injection, 32.3% and 14.3% of the total brain radioactivity was found in the neutral glyceride (NG) and phospholipid (PL) fractions, respectively. After 20 h, PL radioactivity attained a level of 75%. Phosphatidylcholine (PC), diacylglycerol (DG), and triacylglycerol (TG) constituted 40%, 23%, and 9% of the total brain label at 1 h, and 35%, 10% and 14% at 20 h, respectively. Ethanolamine-containing PL (including plasmalogen) radioactivity accounted for about 10% up to 6 h and increased nearly 3-fold at 20 h, primarily due to an increase in the amount of labeled docosapentaenoic and docosahexaenoic acids (DHA), the elongation-desaturation products of LNA. A similar pattern of incorporation into NG and PL fraction was observed after the administration of [1-14C]LA. After 1 h, PC, DG, and TG species constituted 23%, 10%, and 23% of the total brain radioactivity, whereas after 20 h it accounted for 44%, 6%, and 10%, respectively. Although radioactivity in the ethanolamine PL also increased substantially from 4% at 1 h to 29% at 20 h, the main labeled fatty acid in this fraction was LA. Labeled arachidonic acid (AA) constituted 42.7% of the total radioactivity in phosphatidylinositol (PI) at 20 h. At this time, it comprised 12.5% and 14% of the total radioactivity in PC and ethanolamine PL, respectively, suggesting a high degree of esterification selectivity. Comparison of the total amounts of LA and LNA and their corresponding labeled AA and DHA metabolites in brain and liver after 3 and 6 h indicated that the contribution of liver metabolism to the elongation-desaturation under these conditions was negligible. One hour after intracerebral injection of [3H]DHA (22:6n-3) or [3H]AA (20:4n-6), 29.2% and 12% of total radioactivity, respectively, was found in the ethanolamine PL while 20% and 40% was incorporated in PC, respectively. PI labeling by [3H]AA was 6- to 8-fold higher than that seen in the presence of DHA. A high percent of radioactivity (26.9% and 18.2%) was found in DG and TG species.(ABSTRACT TRUNCATED AT 400 WORDS).


  106. Protein kinase c and phagocytic activity in amitriptyline-exposed primary cultures of glial cells. Grundt IK, Nyland H, Mork S. Alternatives To Laboratory Animals . 1993;21:181-186.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv. Paper presented at the tenth annual Scandinavian Society of Cell Toxicology conference on in vitro toxicology, Sept 10-13, 1992, Visby, Gotland, Sweden. Includes references.
    Factors which can have either an aggravating or a protective effect on glial cell activation, as found in the early stages of multiple sclerosis and other neurological disorders, are not well known. Enzyme analyses and time-lapse video film were used to study the mechanisms underlying glial cell activation as induced by exposure to amitriptyline (AT). When the effects on the two enzymes protein kinase C (PKC) and 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNP) were compared, PKC activity was increased by 49% and CNP activity was not affected. The addition of the essential fatty acids arachidonic acid (Ara) and alpha-linolenic acid (Lin), revealed that Lin alone activated PKC by 59%, and when Lin was co-exposed with AT, by 67%. The activation of astroglial and microglial cells and phagocytosis of oligodendroglial cells in an AT-exposed culture was recorded by video film. Further studies on AT-induced events in primary cultures of glial cells and the modulating effects of fatty acids, are in progress.


  107. Dietary alpha-linolenic acid deficiency in the rat. I. Effects on reproduction and postnatal growth. Guesnet P, Pascal G, Durand G. Reprod Nutr Dev. 1986;26:969-985.
    The effects of a dietary alpha-linolenic acid (18 : 3 n-3) deficiency on reproduction and postnatal growth in rats were studied during 3 successive gestations and 4 successive generations. Female rats received respectively a semi-synthetic diet in which the lipids were incorporated either as sunflower oil at 1.5% (deficient diet) or as soya oil at 1.87% (control diet). Both diets supplied the same amount of linoleic acid (18 : 2 n-6) (940 mg/100 g of diet), but the sunflower oil supplied 22 times less alpha-linolenic acid than the soya diet (6 mg vs 130 mg/100 g of diet). The results showed that, in our experimental conditions, the alpha-linolenic acid deficiency had no effect on fecundity (% of pregnant females), fertility (number of pups/litter), pup birth weight, food intake and weight of pregnant or lactating females, or pup growth during suckling. However, this deficiency did cause abnormally high rates of perinatal mortality from birth to postpartum day 3, namely on the average, for successive gestations: 18.5% in deficient pups vs 5.2% in the controls, and for successive generations: 16.6% in deficient pups vs 5.3% in the controls. Rat n-3 PUFA requirement during reproduction has been discussed; it appears to be more than 100 mg/100 g of feed. But this need should also be estimated in relation to n-6 PUFA supply; for female rats during reproduction, the ratio n-6: n-3 should be less than 10.


  108. Effects of dietary alpha-linolenic acid deficiency during pregnancy and lactation on lipid fatty acid composition of liver and serum in the rat. Guesnet P, Pascal G, Durand G. Reprod Nutr Dev. 1988;28:275-292.
    The effects of a dietary alpha-linolenic acid (18:3 n-3) deficiency on lipid fatty acid composition of the liver and serum of lactating rats have been studied during three gestations and over three generations. These females were compared to corresponding females which remained sterile. Two lots of female rats received, respectively, a diet containing lipids either in the form of 1.50 g of sunflower oil per 100 g of diet (deficient diet) or as 1.87 g of soya oil per 100 g of diet (control diet). Both diet contained the same amount of linoleic acid (18:2 n-6), i.e. 940 mg/100 g of diet, but the sunflower diet supplied 43 times less 18:3 n-3 than the soja diet, or 3 mg vs 130 mg/100 g of diet. Results show that successive gestations appeared to be more efficient means of depleting material n-3 PUFA stores than successive generations. The 18:3 n-3 deficient diet caused a considerable decrease in the level of n-3 polyunsaturated fatty acids (n-3 PUFA) in liver and serum lipids, and particularly of 22:6 n-3. This decline was compensated by an increase in the level of n-6 polyunsaturated fatty acids (n-6 PUFA), and particularly by a very high augmentation of 22:5 n-6. The ratio n-6 PUFA/n-3 PUFA in liver phospholipids and in serum lipids was a good index of the adequacy of dietary n-3 PUFA supply. However, the ratio 22:5 n-6/22:6 n-3 was a finer index. This ratio appeared to be a reliable index of dietary n-3 PUFA deficiency when it was higher than 1 in serum lipids of a fasting animal. The proportion of 22:5 n-6 as well as the ratios n-6/n-3 and 22:5 n-6/22:6 n-3, were also increased in the liver phospholipids of lactating females receiving the soya oil diet; this suggested that a supply of 130 mg/100 g of diet, corresponding to a ratio of n-6/n-3 = 7.2, was not sufficient for these rats during pregnancy and lactation. A supply of 200 mg of n-3 PUFA/100 g of diet, corresponding to a ratio of n-6/n-3 = 5, is recommended for these animals.


  109. Aldehydes in food and its relation with the tea test for rancidity. Guillensans R, Guzmanchozas M., Univ Sevilla,Fac Pharm,Dept Nutr & Food Sci, Strprof Garcia Gonzalez W-N/E-41012 Seville, Spain . Fett Wiss Technol. 1995;97:7-8.
    (c) 1996 Inst for Sci Info. All rts. reserv.
    Aldehydes have been found in fruits and essential oils. But their presence in the off-flavor compounds (rancidity of foods) is well known. Aldehydes are characteristic compounds of secondary oxidation in the autoxidative process of fats, oils, lipidic foods and biological membranes. Malonaldehyde and other aldehydes responsible for rancidity can be evaluated through the thiobarbituric acid (tea) assay. Alkanals, alkenals and dienals give characteristic pigments (yellow, orange, red pigments) with tea reagent, which could be spectrophotometrically evaluated.


  110. Essential fatty acids and human nutrition. Hansen AE, Burr GO. JAMA. 1946;132:855-859.


  111. A comparison of evening primrose oil and sunflower oil for the management of papulocrustous dermatitis in cats. Harvey RG. Vet Rec. 1993;133:571-573.
    Includes references.


  112. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Hibbeln JR, Salem NJ. Am J Clin Nutr
    Recent studies have both offered and contested the proposition that lowering plasma cholesterol by diet and medications increases suicide, homicide, and depression. Significant confounding factors include the quantity and distribution of dietary n-6 and n-3 polyunsaturated essential fatty acids that influence serum lipids and alter the biophysical and biochemical properties of cell membranes. Epidemiological studies in various countries and in the United States in the last century suggest that decreased n-3 fatty acid consumption correlates with increasing rates of depression. This is consistent with a well-established positive correlation between depression and coronary artery disease. Long-chain n-3 polyunsaturate deficiency may also contribute to depressive symptoms in alcoholism, multiple sclerosis, and post-partum depression. We postulate that adequate long-chain polyunsaturated fatty acids, particularly docosahexaenoic acid, may reduce the development of depression just as n-3 polyunsaturated fatty acids may reduce coronary artery disease.


  113. Essentiality of dietary omega 3 fatty acids for premature infants: plasma and red blood cell fatty acid composition. Hoffman DR, Uauy R., University of Texas Southwestern Medical Center, Department of Pediatrics, Dallas. Lipids. 1992;27:886-95.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Pre-term infants, that are not breast-fed, are deprived of vital intrauterine fat accretion during late pregnancy and must rely on formula to obtain fatty acids essential for normal development, particularly of the visual system. Preterm infants (30 wk postconception) receiving human milk were compared to infants given one of the following formulae: Formula A was a commercial preterm formula with predominantly 18:2 omega 6 (24.2%) and low (0.5%) 18:3 omega 3; Formula B was based on soy oil and contained similar 18:2 omega 6 levels (20%) and high 18:3 omega 3 (2.7%); Formula C was also a soy oil-based formula (20% 18:2, 1.4% 18:3) but was supplemented with marine oil to provide omega 3 long-chain polyunsaturated fatty acids (LCP) at a level (docosahexaenoic acid, DHA, 0.35%) equivalent to human milk. At entry (10 days of age), the fatty acid composition of plasma and red blood cell (RBC) membrane lipids of the formula groups were identical. By 36 wk postconception, the DHA content in lipids of group A was significantly reduced compared to that in the human milk and marine oil formula groups. Omega-3 LCP results were further amplified by 57 wk with compensatory increases in 22:5 omega 6 in both plasma and RBC lipids. Provision of 2.7% alpha-linolenic acid in formula group B was sufficient to maintain 22:6 omega 3 levels equivalent to those in human milk-fed infants at 36 wk but not at 57 wk. Effects on the production of thiobarbituric acid reactive substances and fragility of RBC attributable to the marine oil supplementation were negligible. The results support the essentiality of omega 3 fatty acids for preterm infants to obtain fatty acid profiles comparable to infants receiving human milk. Formula for preterm infants should be supplemented with omega 3 fatty acids including LCP.


  114. Control of polyunsaturated acids in tissue lipids. Holman RT. J Am Coll Nutr. 1986;5:183-211 (REF: 90).
    (c) format only 1995 Knight-Ridder Info. All rts. reserv.
    Since the discovery in 1929 that certain polyunsaturated fatty acids (PUFA) are essential for life and health, intense investigation has revealed the multiplicity of members in each of several families of PUFA, no two of which are equivalent. The quantified nutrient requirements for the essential dietary precursors of the two dominant families of PUFA have been estimated, and the general functions of these families are slowly becoming known. The PUFA are essential components of structural membrane lipids. The functions of the individual members are not yet differentiated, except as they act as precursors of synthesis of unique octadecanoid, eicosanoid, and docosanoid products of oxidation that have potent biological properties. The PUFA occur in animals and higher plants as ubiquitous and essential components of structural lipid that are in a dynamic equilibrium with the pool of dietary acyl groups. Many human diseases have been found to involve unique essential fatty acid (EFA) deficiencies or distortions of the normal equilibrium pattern. The equilibrium is influenced by the level of dietary intake or precursors, by the presence of competing essential and nonessential acyl groups, by nonoptimum intake of other essential nutrients, by hormonal effects, by drug therapy, and by other effects upon physiological condition. With the many variables already known to modulate or control the equilibrium, it should be possible with more precise understanding of each variable to shift abnormal equilibria in the direction of normalcy. This perhaps will be the next area of intensive investigation in this field of nutrition and metabolism.


  115. Essential fatty acid deficiency profiles in idiopathic immunoglobulin A nephropathy. Holman RT, Johnson SB, Bibus D, Spencer DC, Donadio JVJ., Hormel Institute, University of Minnesota, Austin. Am J Kidney Dis. 1994;23:648-54.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The profiles of fatty acids (FAs) of plasma phospholipids (the compartment reflecting the essential FA status of tissue lipids), nonesterified FAs (the precursor pool for autacoid synthesis), urine protein excretion, and glomerular filtration rate were measured before and after supplementation with fish oil in 15 patients with immunoglobulin A nephropathy. In the FA profiles, there was deficient 18:3 omega 3 (alpha-linolenic acid), the parent compound of omega 3 polyunsaturated FA, and deficient chain elongation products of both omega 3 and omega 6 polyunsaturated FAs with replacement by saturated and monounsaturated short-chain, odd-chain, and branched-chain FAs, producing significant loss of omega 3 FA. These alterations indicate nutritional or functional (omega 3) and metabolic (omega 6) deficiencies. Additionally, the mean melting point of the FAs was significantly increased, implying an inherent decrease in cell membrane fluidity. Enhancement of 20: 5 omega 3 (eicosapentaenoic acid) and 22:6 omega 3 (docosahexaenoic acid) and suppression of 20:4 omega 6 (arachidonate) after supplementation with fish oil were accompanied by important decreases in proteinuria and improved glomerular filtration rate. Omega-3 polyunsaturated FAs may favorably influence immunoglobulin A nephropathy through a modulation of the pathologic actions of the omega 6 eicosanoids and other diverse actions on various mediators produced by an initial immune injury.


  116. Deficiency of essential fatty acids and membrane fluidity during pregnancy and lactation. Holman RT, Johnson SB, Ogburn PL. Proc Natl Acad Sci U S A. 1991;88:4835-4839.
    In a group of 19 normal pregnant women, plasma lipids were extracted, phospholipids were isolated, and the fatty acid (FA) compositions were measured by capillary gas chromatography. The changes seen in phospholipid profiles suggest a significant transfer of omega 3 and omega 6 polyunsaturated FA from the mother to the fetus. These FA are essential for normal fetal growth and development; their relative deficiency in maternal circulation suggests that dietary supplementation may be indicated.


  117. Alteration in fatty acid composition of adult rat brain capillaries and choroid plexus induced by a diet deficient in n-3 fatty acids: slow recovery after substitution with a nondeficient diet. Homayoun P, Durand G, Pascal G, Bourre JM. J Neurochem. 1988;51:45-48.
    Wistar rats were fed for three generations with a semisynthetic diet containing either 1.5% sunflower oil (940 mg% of C18:2n-6, 6 mg% of C18:3n-3) or 1.9% soya oil (940 mg% of C18:2n-6, 130 mg% of C18:3n-3). At 60 days of age, the male offspring of the third generation were killed. The fatty acyl composition of isolated capillaries and choroid plexus was determined. The major changes noted in the fatty acid profile of isolated capillaries were a reduction (threefold) in the level of docosahexaenoic acid and, consequently, a fourfold increase in docosapentaenoic acid in sunflower oil-fed animals. The total percentage of polyunsaturated fatty acids was close to that in the soya oil-fed rats, but the ratio of n-3/n-6 fatty acids was reduced by threefold. In the choroid plexus, the C22:6n-3 content was also reduced, but by 2.6-fold, whereas the C22:5n-6 content was increased by 2.3-fold and the ratio of n-3/n-6 fatty acids was reduced by 2.4-fold. When the diet of sunflower oil-fed rats was replaced with a diet containing soya oil at 60 days of age, the recovery in content of n-6 and n-3 fatty acids started immediately after diet substitution; it progressed slowly to reach normal values after 2 months for C22:6n-5 and 2.5 months for C22:6n-3. The recovery in altered fatty acids of choroid plexus was also immediate and very fast. Recovery in content of C22:5n-6 and C22:6n-3 was complete by 46 days after diet substitution.


  118. Effect of dietary essential fatty acids on pulmonary metastasis of ascites tumor cells in rats. Hori T, Moriuchi A, Okuyama H, Sobajima T, Tamiya-Koizumi K, Kojima K. Chem Pharm Bull (Toyko). 1987;35:3925-3927.


  119. Essential fatty acid metabolism in cultured rat cardiomyocytes in response to either N-6 or N-3 fatty acid supplementation. Hrelia S, Lopez Jimenez JA, Bordoni A, et al. Biochem Biophys Res Commun. 1995;216:11-19.
    In this study we demonstrate that cultured rat cardiomyocytes possess the capacity to desaturate/elongate essential fatty acids (EFAs). Alpha-linolenic acid (ALA) conversion to higher metabolites was greater than linoleic acid (LA) conversion, according to the higher affinity of the delta-6-desaturase enzyme for the n-3 than for the n-6 EFAs. Gamma-linolenic acid (GLA) supplementation to the culture medium had no influence on LA conversion; but the addition of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids significantly decreased the formation of interconversion products from LA. The conversion of ALA to higher metabolites was greatly affected by GLA; EPA had no effect on ALA conversion, while DHA significantly inhibited it. Both GLA (converted mostly to dihomo-gamma-linolenic acid) and EPA can be removed from phospholipids and addressed to prostanoid biosynthesis, so avoiding their potential accumulation and the inhibition of their own production. Our data clearly indicate that supplementation of the culture medium with either n-6 or n-3 fatty acids can cause reduced levels of the other series of fatty acids. This effect may be undesirable, since both n-6 and n-3 fatty acids are important in the prevention of coronary diseases.

  120. Changes in abdominal and gluteal adipose-tissue fatty acid compositions in obese subjects after weight gain and weight loss. Hudgins LC, Hirsch J., Rockefeller Univ,Human Behav & Metab Lab,1230 York Ave/New York//Ny/10021 (Reprint) . Am J Clin Nutr. 1991;53:1372-1377.
    (c) 1996 Inst for Sci Info. All rts. reserv.
    The fatty acid compositions of abdominal and gluteal subcutaneous adipose tissues of eight obese subjects were measured after an initial 5-10-wk period of weight maintenance on a liquid-formula diet (40% of calories as corn oil, 45% as carbohydrate, and 15% as protein), after a 10% increase in weight (11-20 kg) on a solid-food diet of each subject's choice (n = 5) or after a 20% decrease in weight (26-37 kg) on 800 kcal/d of the same corn-oil-formula diet (n = 5). After weight gain or weight loss, all subjects maintained their new weights for 2-10 wk on the same corn-oil-formula diet. As hypothesized, there were minimal changes in the concentrations of 41 fatty acids identified in both abdominal and gluteal tissues after all dietary phases, and small site-specific differences in the levels of saturated and monounsaturated fatty acids were not altered. The largest change was a 15% decrease (p < 0.05) In 18:3n-3 in both abdominal and gluteal tissues during weight loss, despite higher levels in the diet than in the baseline adipose tissue. This decrease occurred without coexisting decreases in 22:5n-3 and 22:6n-3, two elongase-desaturase products of 18:3n-3 that were not detectable in the diet.


  121. N-3 fatty acids from vegetable oils. Hunter JE., Procter & Gamble Company, Cincinnati, OH. Am J Clin Nutr. 1990;51:809-814. charts.
    Includes 25 references.
    Abstract: Principal food sources of the n-3 fatty acid alpha-linolenic acid are salad and cooking oil, salad dressing, shortening, margarine, and food-service fat and oil products made from canola oil or soybean oil. Using food production data provided by US trade associations and by Statistics Canada, I estimated the per capita availability of alpha-linolenic acid from vegetable-oil products in the United States to be approximately 1.2 g/d and in Canada, approximately 2 g/d. The higher alpha-linolenic acid availability in Canada is largely accounted for by widespread use of canola oil there. Emerging research has suggested possible health benefits associated with modest increases in dietary alpha-linolenic acid, including reduced blood-clotting tendency and reduced blood pressure.


  122. Decreased formation of prostaglandins derived from arachidonic acid by dietary linolenate in rats. Hwang DH, Carroll AE. Am J Clin Nutr. 1980;33:590-597.
    Accumulated evidence now suggests that availability of precursor acid is an important factor controlling the biosynthesis of prostaglandins (PG's). Since linolenic acid inhibits the conversion of linoleic acid to arachidonic acid, rats receiving more linolenic acid are expected to have less arachidonic acid and thus less PG's synthesized from arachidonic acid than those receiving linoleic acid alone. Essential fatty acid-deficient rats, induced by feeding hydrogenated coconut oil diet for 15 weeks, were divided into six groups and fed graded amounts of purified methyl linolenate for 6 weeks. Each group of rats except essential fatty acid-deficient group received the same amount of linoleate. The results showed that the level of arachidonic acid in serum lipids and serum concentrations of PG's synthesized from arachidonic acid by platelets decreased as the amount of dietary linolenate increased. This indicated that biosynthesis of PG's in platelets can be influenced by the availability of precursors, and thus it can be modified by the manipulation of dietary fatty acids.


  123. N-3 fatty acid requirements of the newborn. Innis SM., Univ British Columbia,Res Ctr,Dept Paediat,950 W 28th Ave/Vancouver V5z 4h4/Bc/Canada/ (Reprint) . Lipids. 1992;27:879-885.
    (c) 1996 Inst for Sci Info. All rts. reserv.
    Whether docosahexaenoic acid (22:6n-3) is an essential nutrient for term or preterm infants, or if not, the quantity of dietary linolenic acid (18:3n-3) needed to support sufficient synthesis of 22:6n-3 for assimilation in the central nervous system is unknown. Infants fed formulas have lower plasma and red blood cell (rbc) levels of 22:6n-3 than breast fed infants. No relationship between the intake of 18:3n-3 in formula (0.8 Or 4.5% Of fatty acids, 18:2n-6/18:3n-3 ratio 35:1 or 7:1, respectively) and the infant's rbc 22:6n-3 was found. Premature infants (&lt33 wk gestation) also showed a decrease in rbc 22:6n-3 during feeding with formula containing 18:3n-3 as the only n-3 fatty acid. However, a marked decrease in plasma and rbc 22:6n-3 occurred between premature birth and the start of full enteral feeding at 1-2 wk of age. This was not reversed by breast milk or formula feeding. Piglets, which are appropriate for studies of infant lipid metabolism, had decreased brain synaptic plasma membrane, retina and liver 22:6n-3 and increased 22:5n-6 when fed formula with 0.8% Fatty acids (0.3% Of kcal) as 18:3n-3. Formula with 4.0% Fatty acids (1.7% Of kcal) as 18:3n-3 resulted in similar accretion of 22:6n-3 in the organs compared to milk fed animals. The studies suggest the dietary requirement for 18:3n-3 in term animals in energy balance exceeds 0.3% Diet kcal. Studies in the premature infants suggest 18:3n-3 may be oxidized rather than desaturated to 22:6n-3 if energy requirements are not met, and that due to early lipid restriction and later rapid growth, premature infants may have higher dietary n-3 requirements than term infants.


  124. Dietary docosahexaenoic acid is not essential for development of preferential look (visual) acuity in term gestation infants fed infant formula with adequate alpha linolenic acid. Innis SM, Nelson CM, Rioux MF, Waslen P., Dep. Pediatr., Ubc, Vancouver V5z 4h4, Can . 104th Annual Meeting Of The American Pediatric Society And The 63rd Annual Meeting Of The Society For Pediatric Research, Seattle, Washington, Usa, May 2-5, 1994. Pediatric Research. 1994;35:313a.


  125. Adipose-tissue fatty acid composition in recipients of long-term total parenteral nutrition (tpn). Ito Y, Hudgins LC, Hirsch J, Shike M., Mem Sloan Kettering Canc Ctr,Dept Med,1275 Yorkave/New York//Ny/10021 (Reprint); Mem Sloan Kettering Canc Ctr,Dept Med,1275 Yorkave/New York//Ny/10021; Cornell Univ,Med Ctr,Coll Med/New York//Ny/10021; Rockefeller Univ,Human Behav & Metab Lab/New York//Ny/10021 . Am J Clin Nutr. 1991;53:1487-1492.
    (c) 1996 Inst for Sci Info. All rts. reserv.
    Adipose-tissue fatty acid composition was studied in nine patients requiring long-term total parenteral nutrition (tpn). The patients received 17 +/- 8% of total energy as soybean-oil emulsion (intralipid(r)) and 66 +/- 8% as glucose. Despite low intake of 9c-16:1, 11c-18:1, and 13c-18:1, adipose-tissue concentrations of these monounsaturated fatty acids were higher in the tpn patients than in free-living control subjects (p < 0.05) And inversely correlated with the percent energy from fat (r = -0.56, P = 0.11; R = -0.64, P = 0.06; R = -0.81, P = 0.008, Respectively). This suggests that these fatty acids accumulated from endogenous synthesis from carbohydrate and thus may be markers of the percent fat in the diet. The essential fatty acids, 18:2 and 18:3n-3, positively correlated with the percent energy from fat (r = 0.79, P = 0.01; R = 0.80, P = 0.01, Respectively). Linear-regression analysis suggests that normal adipose-tissue stores of 18:2 and 18:3n-3 are maintained when intravenous soybean-oil emulsion provides 11-20% and 4-12%, respectively, of total energy.


  126. Does the fatty acid profile of dietary fat influence its trophic effect on the small intestinal mucosa? Jenkins AP, Thompson RP., Gastrointestinal Laboratory, Rayne Institute, St Thomas's Hospital, London. Gut. 1993;34:358-64.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    To compare the enterotrophic effects of different triglycerides, five groups of eight rats were fed mixed diets giving 50% of calories as oils rich in either essential fatty acids (EFA), alpha-linolenic acid, fully saturated fatty acids, oleic acid, or medium chain fatty acids. After 21-24 days there were no significant differences between the groups in overall small intestinal whole gut weight, mucosal weight, or mucosal DNA; overall mucosal protein showed slight variation (p < 0.05) that was compatible with differences in food intake between the groups. However, long chain triglycerides (LCT) and medium chain triglycerides (MCT) differed in their regional effects on cell proliferation; all four LCT rich diets increased mucosal mass and cell proliferation maximally in the mid small intestine, while MCT had their greatest effect proximally. Subsequently, two groups of eight rats were fed diets in which EFA or MCT were given as twice daily boluses (29% of dietary calories) for 20 to 23 days and compared with a third group of eight rats receiving a glucose rich, low fat diet. EFA and MCT boluses increased the overall parameters of small intestinal mucosal mass and for both oils the effects were now maximal in the mid small intestine. Thus different triglycerides have similar effects on overall small intestinal mucosal mass, but MCT differ from LCT in their regional effects on mucosal cell proliferation when they are given in mixed diets, although not when given as boluses.


  127. Flavonoids increase tissue essential fatty acids in vitamin E-deficient chicks. Jenkins KJ, Atwal AS., Cent. Food Animal Res., Res. Branch, Agriculture Agri-Food Canada, Ottawa, ON K1A 0C6, Canada . J Nut Biochem. 1995;6:97-103.
    (c) 1996 BIOSIS. All rts. reserv.
    This study assessed the effect of dietary flavonoids (quercetin, morin, rutin, silymarin), a simple phenolic (ferulic acid), and vitamin E on lipid composition of selected tissues taken from chicks fed a low vitamin E, low essential fatty acid (EFA) diet. Dietary supplementation with vitamin E had no influence on lipid classes in blood plasma, liver, or breast muscle or on their fatty acid composition. Similarly, the phenolics had no effect on lipid classes in these tissues but quercetin, morin, and ferulic acid had marked effects on the fatty acid composition of tissue lipids, notably by reducing 18:1 and 20:3 n-9(triene indicator of EFA deficiency), and increasing 18:2 n-6, 20:4 n-6, and total n-6 fatty acids. These phenolic antioxidants appear to have promoted the production and/or the conservation of EFA in the EFA- and vitamin E-deficient chicks.

  128. Flavonoids increase tissue essential fatty acids in vitamin E-deficient chicks. Jenkins KJ, Atwal AS., Cent. Food Animal Res., Res. Branch, Agriculture Agri-Food Canada, Ottawa, ON K1A 0C6, Canada . J Nut Biochem. 1995;6:97-103.
    (c) 1996 BIOSIS. All rts. reserv.
    This study assessed the effect of dietary flavonoids (quercetin, morin, rutin, silymarin), a simple phenolic (ferulic acid), and vitamin E on lipid composition of selected tissues taken from chicks fed a low vitamin E, low essential fatty acid (EFA) diet. Dietary supplementation with vitamin E had no influence on lipid classes in blood plasma, liver, or breast muscle or on their fatty acid composition. Similarly, the phenolics had no effect on lipid classes in these tissues but quercetin, morin, and ferulic acid had marked effects on the fatty acid composition of tissue lipids, notably by reducing 18:1 and 20:3 n-9(triene indicator of EFA deficiency), and increasing 18:2 n-6, 20:4 n-6, and total n-6 fatty acids. These phenolic antioxidants appear to have promoted the production and/or the conservation of EFA in the EFA- and vitamin E-deficient chicks.


  129. Essential fatty acid deficiency in patients with sever fat malabsorption. Jeppesen PB, Christensen MS, Hoy C-E, Mortensen PB. Am J of Clin Nutr. 1997;65:837-843.
    Essential fatty acid deficiency is commonly described in patients receiving parenteral nutrition, but the occurence in patients with severe fat malabsorption not receiving parenteral nutrition is uncertain. One hundred twelve patients were grouped according to their degree of fat malabsorption: group 1, &lt10% (n=52); group 2, 10-25% (n=21); group 3, 25-50% (n=24); and group 4, &gt50% (n=15). Fecal fat was measured by the method Van de Kamer the last 2 of 5 d of a 75-g fat diet. Serum fatty acids in the phospholipid fraction were measured by gas-liquid chromatography after separation by thin-layer chromatography and expressed as a percentage of total fatty acids. The concentration of linoleic acid in groups 1,2,3, and 4 was 21.7%, 19.4%. 16.4%, and 13.4% respectively (P&lt0.001). The concentration of linolenic acid in groups 1,2,3, and 4 was 0.4%, 0.4%, 0.3%, and 0.3% respectively (p=0.017). Evidence of essential fatty acid deficiency, defined as a serum concentration of linoleic acid less than the lower limit if the 95% CI in patients without fat malabsorption (group 1), was 5% (1/21), 38% (9/24), and 67% (10/15) in groups 2,3,and 4, respectively. A considerable proportion of patients with gastrointestinal diseases resulting in malabsorption of &gt25-50% of dietary fat intake and not treated with parenteral nutrition have biochemical signs of essential fatty acid deficiency. The clinical effect of the changes are yet to be elucidated.


  130. Dietary fat, prostaglandins and the immune. Johnston DV, Marshall LA. Prog Food Nutr Sci. 1984;8:3-25. ill., charts.
    Supported by a grant from the Science and Education Administration of the U.S. Department of Agriculture.
    Abstract: A comprehensive critical literature review addresses key aspects of the interrelationships among dietary fat, immunity, and the role of prostaglandins (PG). Topics include the chronological development of research associating dietary fat (particularly, essential fatty acids (EFA)) with immunity; possible functions of PG (and other eicosanoids) in the immune response; the effect of the quality and quantity of dietary fat on immune response (including histopathological studies of lymphoid organs); the effect of an EFA deficiency on immunity and of the linoleic/linolenic EFA ratio on PG synthesis by immunocompetent cells and on immune function; the effect of dietary fat on leukotriene synthesis; and problems encountered in studies of the effect of dietary fat on immune function. Recommendations concerning experimental design and research conduct relevant to this topic also are discussed. (wz). ¤.


  131. Flaxseed rich in essential fatty acids, good protein source as well. Johnston IMJJR. Health News & Review. 1989:6(1).
    (c)1996 Inform Access Co. All rts. reserv.


  132. The effects of clofibrate and 3-amino-1,2,4-triazole on liver catalase and lipid metabolism in mice. Jones GL, Neill AR. Biochim Biophys Acta. 1982;712:420-426.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv.
    Clofibrate-treated mice showed a significant decrease in plasma triacylglycerols and a parallel elevation of liver catalase. Repeated administration of aminotriazole to clofibrate-treated mice effectively abolished the elevated catalase activity, but had no significant effect on the reduced plasma triacylglycerol levels. In mice, the hypolipidemic effect of clofibrate may be dissociated from its capacity to elevate liver catalase. Repeated administration of aminotriazole to control mice resulted in significantly lowered carcass fat and plasma triacylglycerol levels even though the liver catalase activity was greatly depressed. The livers of clofibrate-treated mice showed an increase in phospholipid content. Livers of aminotriazole-treated mice showed a decrease in total lipid content, with a profound decrease in free fatty acids and triacylglycerols and a slight increase in phospholipids. The composition of the individual free fatty acids of the liver triacylglycerols showed a shift towards the shorter fatty acids and the nutritionally essential alpha-linolenic acid in clofibrate-treated mice.


  133. Histopathologic and ultrastructural myocardial alterations in calves deficient in vitamin E and selenium and fed polyunsaturated fatty acids. Kennedy S, Rice DA., Veterinary Research Laboratories, Stormont, Belfast, Northern Ireland. Vet Pathol. 1992;29:129-138.
    Includes references.
    We developed an experimental model of nutritional degenerative myopathy in ruminant cattle. Fourteen experimental calves were fed a diet low in vitamin E and selenium for 127 to 137 days. Six of these calves were then euthanatized. After 127 days, a dietary additive of linseed oil that had been treated to protect it against ruminal hydrogenation was added to the low vitamin E and selenium diet of the eight remaining calves as a source of polyunsaturated fatty acids. Six of these animals were euthanatized after 6 to 11 days of polyunsaturated fatty acid feeding; the other two died after 6 and 8 days. Macroscopic myocardial alterations were seen in five polyunsaturated fatty acid fed calves but not in any other experimental calf. Microscopic lesions, comprising multifocal or diffuse cardiocyte degeneration and necrosis, were seen in atrial and ventricular myocardium of all experimental calves. These changes were more severre in polyunsaturated fatty acid-fed calves than in animals that did not receive polyunsaturates. Ultrastructurally, sublethally damaged cardiocytes had lysed contractile material; vacuolated sarcoplasm; altered mitochondria, sarcoplasmic myelin figures, and lipofuscin granuels; and multiple nuclei. Necrotic cardiocytes had contracted myofibrils, pyknotic nuclei, mieralized mitochondria, and plasmalemmal disruption; the external lamina remained largely intact. necrosis was followed by macrophage invasion and phagocytosis of necrotic debris. Repair of the lesions was by deposition of collagen and elastin fibers. No alterations were seen in the hearts of control calves fed vitamin E and selenium-supplemented diet. The induced myocardial lesions are similar to those of spontaneous nutritional degenerative myopathy in ruminant cattle.


  134. Influence of dietary fat mixtures on platelet adhesiveness, atherosclerosis and plasma cholesterol content in rabbits. Kloeze J, Houtsmuller UM, Vles RO. J Atheroscler Res. 1969;9:319-334.


  135. Long chain polyunsaturated fatty acids in the diets of premature infants. Koletzko B., Kinderpoliklinik der Ludwig-Maximilians-Universitat, Munich, Germany . Nestle Nutrition Workshop Series. 1992; v. 28 :135-146.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv. In the series analytic: Polyunsaturated fatty acids in human nutrition / edited by U. Bracco and R.J. Deckelbaum. Discussion by workshop participants, p. 144-146. Includes references.
    This chapter examines guidelines on the feeding of premature infants which recommend dietary supply of linoleic and partly also of alpha-linolenic acid but not of any other essential fatty acids. It examines biosynthesis of long chain polyunsaturated fatty acids in the human neonate and the intrauterine supply; intake from human milk and formulas; and the use of fish oil supplements.


  136. Trans fatty acids may impair biosynthesis of long-chain polyunsaturates and growth in man. Koletzko B., Kinderklinik Heinrich-Heine-Universitat, Dusseldorf, Germany. Acta Paediatr. 1992;81:302-6.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Human diet contains large amounts of trans fatty acids originating primarily from hydrogenated fats. Consumption of trans fatty acids is considered safe for man, but side effects, including impaired biosynthesis of long-chain polyunsaturated fatty acids with 20 and 22 carbon atoms and reduced growth have been observed in animals. We studied whether or not there are indications of untoward effects of trans fatty acids in 29 premature infants (birth weight 1700 +/- 127 g, gestational age 33.6 +/- 1.4 weeks, mean +/- SD). Plasma samples obtained on day 4 of life were analysed for fatty acid composition. Trans octadecenoic acid and total trans fatty acids in plasma lipid fractions (% wt/wt) were not related to the precursor essential fatty acids linoleic and alpha-linolenic acids but correlated inversely to n - 3 and n - 6 long-chain polyunsaturated fatty acids and to the product/substrate ratios of long-chain polyunsaturate biosynthesis. Trans fatty acids were also inversely correlated to birth weight but not to gestational age. These data indicate a potential impairment of essential fatty acid metabolism and early growth by trans isomers in man, and question the safety of high dietary trans isomer intakes during pregnancy and the perinatal period.


  137. Arachidonic acid and early human growth: is there a relation? Koletzko B, Braun M., Kinderklinik, Heinrich-Heine-Universitat, Dusseldorf, BRD. Ann Nutr Metab. 1991;35:128-31.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Growth failure is a classical sign of essential fatty acid deficiency. We investigated whether birth weight correlates with the postnatal essential fatty acid status in a group of 29 premature infants. A significant and positive correlation between body weight and plasma triglyceride content of arachidonic acid (20:4n-6) (r = 0.47, p = 0.01) and total omega-6 long-chain polyunsaturated fatty acids (r = 0.49, p less than 0.01) was found. In contrast, there was no positive relation to linoleic acid (18:2n-6) or any omega-3 fatty acid but a significant inverse correlation to alpha-linolenic acid (18:3n-3). We propose that during early life arachidonic acid may have a growth-promoting effect which could be related to its role as an eicosanoid precursor or to its structural function in membrane lipids.


  138. The role of lipids in feeding low-birth-weight infants. &ltOriginal> FETTE IN DER ERNAHRUNG VON NEUGEBORENEN MIT NIEDRIGEM GEBURTSGEWICHT. Koletzko B, Keicher U, Saule H, Wawatschek S, Bohles H, Bervoets K., Kinderpoliklinik, Ludwig-Maximilians-Universitat, Pettenkoferstrasse 8a, D-80336 Munchen. Germany . Monatsschrift Fur Kinderheilkunde. 1995;143:S99-S104.
    (c) 1996 Elsevier Science B.V. All rts. reserv.
    The importance of dietary supply and metabolism of fats for growth and development of premature infants is receiving increased attention. Low-birth-weight infants have only minor body stores of lipids at birth, but very high demands for tissue deposition due to their rapid growth. A high dietary fat supply of 40-55% of energy intake, as it is found in human milk, is preferred today for low-birth-weight infant formulas, primarily because of advantages for energy balance. Medium chain triglycerides (MCT) have a higher rate of absorption, but because of their lower energy content they do not improve energy balance and growth. MCT may have beneficial effects on calcium absorption and prevention of hypoglycemia. A limitation of MCT intake to a maximum of 40% of total fat intake is recommended to avoid potential metabolic disadavantages. Polyunsaturated fatty acids of the omega-6 and omega-3 series cannot be synthesized by man and must be supplied with the diet in adequate amounts and relative ratios (linoleic acid: 4,5-10,8% of energy intake, linoleic acid/alpha-linolenic acid ratio: 5-15). In addition, long-chain polyunsaturated fatty acids (LCP) are conditionally essential substrates for low-birth-weight infants, because the activity of endogenous LCP synthesis from supplied precursors is not sufficient to meet the high demand for growth. The availability of the omega-6 LCP arachidonic acid correlates with weight gain, and the supply of preformed docosahexaenoic acid (omega-3 LCP) can modulate development of infantile visual acuity and mental functions. Recently, low-birth-weight infant fomulae enriched with metabolites of the classical essential fatty acids have become available and allow an effective improvement of infantile LCP status.


  139. A possible essential role for dietary linolenic acid in the development of the young rat. Lamptey MS, Walker BL. J Nutr. 1976;106:86-93.
    Female rats were fed semi-purified diets containing 10% safflower oil or 10% soybean oil for six weeks prior to mating and through-out pregnancy and lactation. The progeny were weaned to the diet of the dam. Physical, neuromotor and reflex development was monitored in the progeny prior to weaning and learning ability of the mature progeny was assessed in a simple Y-maze test. Brain lipid analyses were conducted in the progeny at birth, 21 and 210 days of age. Inclusion of soybean oil in the diet resulted in higher levels of 22:6omega3 and lower levels of 22:5omega6 in the brain ethanolamine glycerophosphatides. The nature of the dietary fat exerted no effect on the physical development, onset of reflexologic responses or onset of neuromotor co-ordination in the pups. The soybean oil-fed animals spent more time in certain neuromotor activities possibly associated with explorative drive than did their safflower oil-fed counterparts. The performance of the mature soybean oil-fed progeny in the discrimination-learning test was superior to that of progeny fed safflower oil. The association of superior learning capacity with dietary soybean oil-induced incorporation of omega3 fatty acids into the brain glycerophosphatides is offered as support for an essential role for dietary linolenic acid for the young rat.

  140. Biochemistry and physiology of n-3 fatty acids. Lands WE. Faseb J. 1992;6:2530-2536.
    Considering the n-3 fatty acids to be partial agonists relative to n-6 fatty acids helps consolidate into a unified interpretation the many diverse reports and controversies on the actions of these two types of essential fatty acids. Some research reports illustrate the similarities between these two types and some emphasize the differences, leaving readers to evaluate the status of n-3 fatty acids from a viewpoint that is conceptually similar to regarding a glass of water as half empty or half full. Both n-3 and n-6 types of fatty acids must be obtained through the diet because they are not synthesized de novo by vertebrates. Both types can support important physiological and developmental processes, can form eicosanoids (prostaglandins, leukotrienes, lipoxins, etc.), can be esterified to and hydrolyzed from tissue glycerolipids, and can be metabolically elongated and desaturated to a variety of highly unsaturated fatty acids. However, some nonesterified n-6 acids are vigorously converted to potent n-6 eicosanoids that exert intense agonist actions at eicosanoid receptors, whereas the n-3 acids less vigorously form n-3 eicosanoids that often produce less intense (partial) actions. Because both types owe their presence in vertebrate tissues to dietary intake, important physiological consequences follow the inadvertent selection of deficient dietary supplies of these two types of polyunsaturated fatty acids.

  141. Biosynthesis of prostaglandins. Lands WE. Annu Rev Nutr . 1991;11:41-60.


  142. Renewed questions about polyunsaturated fatty acids. Lands WE. Nutr Rev. 1986;44:189-195.


  143. Polyunsaturated fatty acid effects on cellular interactions. Lands WEM. Bendich A, Butterworth CE. Micronutrients in Health and in Disease Prevention. New York: Dekker; 1991:9-34.
    Much of the important nutritional research on the essential fatty acids was completed before we knew of their biosynthetic conversion to the highly potent homrone-like compounds called eicosanoids (which include prostaglandins, thromboxane, leukotrienes, and fatty acid epoxides). Now the current awareness of the importance of prostaglandins and leukotrienes as signaling agents mediating the actions of polyunsaturated fatty acids in mammalian physiology makes it important to reexamine the early evidence for the need for the essential fatty acids and reevaluate the appropriate limits of the term &quotdeficiency" in the context of preventive nutrition. The different types of polyunsaturated fatty acids are known to have competitive interactions in biochemical processes that influence eicosanoid-mediated events. To detect and interpret important competitive interactions between the n-3 and n-6 types of fatty acids, we need to identify physiological criteria for designating when either of these types of fatty acid might be in either inadequate or excessive supply. The purpose of this chapter is to examine the limits of the evidence for human needs in the context of the probable physiological mechanisms involved and to provide a basis for selecting the proportions of dietary n-3 and n-6 polyunsaturated fatty acids suitable for attaining goals in preventive nutrition.

  144. Effects of different dietary intake of essential fatty acids on C20:3 omega 6 and C20:4 omega 6 serum levels in human adults. Lasserre M, Mendy F, Spielmann D, Jacotot B. Lipids. 1985;20:227-233.
    Four diets which differed in fatty acid composition were provided for five months each to a group of 24 healthy nun volunteers. The diets contained 54% carbohydrates, 16% proteins and 30% lipids. One-third of the lipid part remained unchanged during the whole study, and two-thirds were modified during each period. For this latter portion, one of the following dietary fats was used: sunflower oil, peanut oil, low erucic acid rapeseed (LEAR) oil or milk fats. This procedure allowed an evaluation of the effects of various amounts of dietary linoleic acid (C18:2 omega 6) and alpha-linolenic acid (C18:3 omega 3) on the serum level of their metabolites. A diet providing a large amount of linoleic acid (14% of the total caloric intake) resulted in low levels of dihomo-gamma-linolenic acid (C20:3 omega 6) and arachidonic acid (C20:4 omega 6) in serum phospholipids and cholesteryl esters. A diet providing a small amount of linoleic acid (0.6% to 1.3% of the total caloric intake) induced high levels of omega 6 fatty acid derivatives. Intermediate serum levels of C20:3 omega 6 and C20:4 omega 6 were found with a linoleic acid supply of about 6.5% of the total caloric intake. Serum levels of omega 6 metabolites were not different after two diets providing a similar supply of C18:2 omega 6 (4.5% to 6.5% of the total caloric intake), although in one of them the supply of C18:3 omega 3 was higher (1.5% for LEAR oil versus 0.13% for peanut oil).


  145. Retinal function in rats and guinea-pigs reared on diets low in essential fatty acids and supplemented with linoleic or linolenic acids. Leat WM, Curtis R, Millichamp NJ, Cox RW. Ann Nutr Metab. 1986;30:166-174.
    Rats were reared into a third generation on diets deficient in essential fatty acids supplemented with linoleic acid (18:2 n-6) or linolenic acid (18:3 n-3) with the object of depleting the retina of n-6 or n-3 fatty acids. In the rats fed 18:2 n-6 the percentage by weight of 22:6 n-3 in retinal fatty acids fell from 22.5 to 8.5% in first-generation animals but then remained unchanged in second and third generations. There was no difference in b-wave amplitudes of the electroretinogram between the rats fed 18:2 n-6 and those fed 18:3 n-3. In guinea-pigs fed purified diets low in 18:3 n-3 the percentage by weight of 22:6 n-3 in retinas fell from 8 to less than 0.5% by the third generation. However, there were no statistical differences in the b-wave amplitudes between these animals and those reared on a commercial diet. It is concluded that if n-3 fatty acids are involved in retinal function their role is too subtle to be detected by standard electroretinographic techniques.


  146. Protective effect of ground flaxseed or ethyl linolenate in a vitamin E-deficient diet against murine malaria. Levander OA, Ager ALJr, Morris VC, May RG., USDA/ARS Human Nutrition Research Center, Vitamin Mineral Nutrition Laboratory, Beltsville, MD. 20705U . Nutrition Research. 1991;11:941-948.
    (c) 1996 BIOSIS. All rts. reserv.
    Vitamin E-deficient diets containing 5 to 20% ground flaxseed or 2.75% ethyl linolenate protected mice against the malarial parasite Plasmodium voelii as shown by decreased parasitemia and enhanced survival. Although the biochemical mechanism of these dietary effects is not established, the high intake of linolenic acid coupled with the oxidant stress generated by the parasite presumably destabilize the red blood cell of the vitamin E-deficient host leading to premature erythrocyte lysis and destruction of the parasite. Continued investigation into the response of the malarial parasite to dietary pro-oxidant stress may provide leads to new approaches in the control of this disease.


  147. Comparative antimalarial effects on n-3 fatty acid ethyl esters in vitamin e-deficient mice. Levander OA, Ager AL, Morris VC, May RG., Usda, Human Nutrition Res. Cent., Beltsville, Md. 20705. 75th Annual Meeting Of The Federation Of American Societies For Experimental Biology, Atlanta, Georgia, Usa, April 21-25, 1991. Faseb (Fed Am Soc Exp Biol) J. 1991;5:A1080.


  148. Transport of n-3 fatty acids from the intestine to the retina in rats. Li J, Wetzel MG, O'Brien PJ. J Lipid Res. 1992;33:539-548.
    (c) 1996 American Chemical Society. All rts. reserv.


  149. The ratio of linoleic acid to alpha-linolenic acid in infant formulas: current facts and future research directions. Lien EL. World Rev Nutr Diet. 1994;75:92-95.


  150. The incorporation of n-3 and n-6 essential fatty acids into the chick embryo from egg yolks having vastly different fatty acid compositions. Lin DS, Connor WE, Anderson GJ., Oregon Hlth Sci Univ,Dept Med,Div Endocrinol Diabet & Clin Nutr,L465/Portland//Or/97201 (Reprint); Oregon Hlth Sci Univ,Dept Med,Div Endocrinol Diabet & Clin Nutr,L465/Portland//Or/97201 . Pediatr Res. 1991;29:601-605.
    (c) 1996 Inst for Sci Info. All rts. reserv. = (Reprint).
    The effect of egg yolk fatty acid composition on essential fatty acid utilization by the developing chick embryo was studied by feeding laying hens a fat-free diet supplemented with oils containing widely divergent contents of the essential n-6 and n-3 fatty acids. A control hen was fed a commercial feed for laying hens. The diets contained 20 to 4370 mg/100 g n-3 fatty acids and 360 to 8020 mg/100 g n-6 fatty acids. Fertile eggs were collected in pairs: one was incubated and the other served as an unincubated control. The fatty acid content of the unincubated egg and the newly hatched chick from each pair was compared. Some 50% of the total fatty acids in the egg yolk were incorporated into the tissues of the newly hatched chick. Regardless of diet, more yolk n-6 fatty acids were incorporated into the chick compared to saturated or monounsaturated fatty acids. The percentage of incorporation especially increased from the eggs containing relatively low amounts of n-6 fatty acids. The percentage of incorporation of n-3 fatty acids was similar to that of saturated and monounsaturated fatty acids when n-3 fatty acids were plentiful in the egg yolk, but increased significantly when n-3 fatty acids were low in the eggs. There was a generally linear relationship between essential fatty acids in the egg and in the chick, although levels of docosahexaenoic acid [dha; 22:6(n-3)] in the brain did not respond proportionally. The developing chick preferentially removed dha from the yolk, but did not synthesize more dha when the amount of the dha precursor, 18:3(n-3), in the yolk was increased. We concluded that the developing chick embryo requires 0.4-1.1% Of egg energy as n-3 fatty acids and 4.8-6.2% As n-6 fatty acids, or a &quotdietary" ratio of n-6/n-3 of 5 to 14. This requirement may have relevance for humans as well.


  151. Essential fatty acid requirement of juvenile red drum (Sciaenopsocellatus). Lochmann RT, Gatlin DMI., Department of Wildlife and Fisheries Sciences, Texas A&ampM University System, College Station, TX 77843-2258, USA. Fish Physiology and Biochemistry. 1993;12:221-235.
    (c) 1995 CAB International. All rts. reserv.
    The essential fatty acid (EFA) requirement of juvenile red drum (Sciaenops ocellatus) maintained in aquaria at about 25 deg C supplied with brackish water (5 plus or minus 2 ppt) was investigated in 2, 6-week experiments. Fish were fed at 5-7% of body weight on diets containing a total of 7% lipid consisting of different combinations of tristearin (predominantly 18:0) and oleate, linoleate, linolenate, and a mixture of highly unsaturated fatty acids (HUFA) containing about 60% eicosapentaenoate plus docosahexaenoate. EFA-deficient diets (containing only tristearin or oleate) rapidly reduced fish growth and feed conversion efficiency, and increased mortality. Fin erosion and a &quotshock syndrome" also occurred in association with EFA deficiency. Diets containing 0.5-1% n-3 HUFA (0.3-0.6% eicosapentaenoate plus docosahexaenoate) promoted the best growth, survival and feed conversion efficiency; however, the control diet containing 7% menhaden fish oil provided the best performance. Excess n-3 HUFA suppressed fish weight gain; suppression became evident at 1.5% n-3 HUFA, and was pronounced at 2.5%. Fatty acid compositions of whole-body, muscle and liver tissues from red drum fed on the various diets reflected dietary fatty acids, but modifications of these patterns also were evident. Levels of saturated fatty acids appeared to be regulated independent of diet. In fish fed on EFA-deficient diets (containing only tristearin or oleate), monoenes increased and n-3 HUFA were preferentially conserved in polar lipid fractions. Eicosatrienoic acid (20:3 n-9) was not increased in EFA-deficient red drum, apparently due to their limited ability to transform fatty acids. Red drum had some limited ability to elongate and desaturate linoleic acid (18:2 n-6) and linolenic acid (18:3 n-3); however, metabolism of 18:3 n-3 did not increase tissue levels of n-3 HUFA. Based on these responses the red drum required about 0.5% n-3 HUFA in the diet (about 7% of dietary lipid) for proper growth and health.


  152. The effect of dietary vitamin E and beta-carotene on oxidation processes in the rat testis. Lomnitski L, Bergman M, Schon I, Grossman S., Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel. Biochim Biophys Acta. 1991;1082:101-7.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The effects of dietary vitamin E and beta-carotene were studied on enzymes involved in arachidonic acid metabolism and other related enzymes in the rat testis. Groups of rats were fed various soybean oil-based semi purified diets. Group 1 was fed a vitamin E-supplemented diet (+E - beta); Group 2 was fed a beta-carotene-supplemented diet (-E + beta); Group 3, the control group (-E - beta) was fed a vitamin E-deficient diet; and Group 4, the standard diet group (S), was fed vitamin E plus beta-carotene-standard diet. Soybean oxidized oil was added to the three diet groups - (+E - beta), (- E + beta) and (- E - beta), whereas the diet of S group contained non-oxidized oil. After 8 weeks rats were killed, blood and testis samples were collected for biochemical determinations. Vitamin E deficiency caused significant increase in testis thiobarbituric acid value and activities of testis NADPH oxidase, testis 15-lipoxygenase and in plasma pyruvate kinase. In contrast, significant decreases were observed in activity of testis prostaglandin synthetase, compared with antioxidant-supplemented diet groups. We also found a significant increase in 15-lipoxygenase activity in (- E + beta) diet group, compared with (- E - beta) diet group. Fatty acid analysis of testis parenchyma indicated decrease in palmitate (16:0) and arachidonate (20:4(n - 6)), and increase in oleate (18:1(n-6)) linoleate (18:2(n - 6)) and linolenate (18:3(n - 3)), when compared (-E - beta) diet group with vitamin E-supplemented diet groups. The results suggest that dietary vitamin E has a role in both enzymatic and non-enzymatic peroxidation of polyunsaturated fatty acids in the testis.


  153. Utilization of precursor essential fatty acids in culture by skin fibroblasts from schizophrenic patients and normal controls. Mahadik SP, Shendarkar NS, Scheffer RE, Mukherjee S, Correnti EE. Prostaglandins Leukot Essent Fatty Acids. 1996;55:65-70.
    Based on the lower levels of long-chain polyunsaturated analogs of essential fatty acids (EPUFAs) in plasma membrane phospholipids of red blood cells, brain and cultured skin fibroblasts from schizophrenic patients, a defective utilization (uptake, conversion to EPUFAs and incorporation into membrane phospholipids) of precursor EFAs has been suggested. Utilization of radiolabeled linoleic (LA, 18:2(n-6)) and alpha-linolenic (ALA, 18:3(n-3)) acids was studied in cultured skin fibroblasts from patients with established schizophrenia and at the first episode of psychosis, and normal controls. Uptake and incorporation of both the EFAs were similar in fibroblasts from both groups of patients studied compared with normal controls. However, although the utilization of LA into arachidonic acid (AA, 20:4n-6) was similar in patients and controls, the utilization of eicosapentaenoic acid (EPA, 20:5(n-3)) into docosahexaenoic acid (DHA, 22:6(n-3)) was significantly lower in first-episode psychotic patients (patients, 96.33 +/- 27.16 versus normals, 161.66 +/- 26.33 nmoles per mg total protein; P = < 0.001). This data indicates that the level of delta 6- as well as delta 5-desaturase may be normal. However, the levels of delta 4-desaturase may be lower in fibroblasts from schizophrenic patients even at the first episode of psychosis.


  154. Are long-chain polyunsaturated fatty acids essential nutrients in infancy. Makrides M, Neumann M, Simmer K, Pater J, Gibson R., Flinders Medical Centre, Bedford Park, Adelaide, SA, Australia. Lancet. 1995;345:1463-1468.
    Includes references.
    We investigated whether the disparity in neural maturation between breastfed and formula-fed term infants could be corrected by the addition of fish oil, a source of docosahexaenoic acid (DHA, 22:6 omega 3), to infant formula. Healthy, term infants were randomised at birth to receive either a supplemented or placebo formula If their mothers had chosen to bottle feed. Breastfed term infants were enrolled as a reference group. Infant erythrocyte fatty acids and anthropometry were assessed on day 5 and at 6, 16, and 30 weeks of age. Visual evoked potential (VEP) acuity was determined at 16 and 30 weeks. VEP acuities of breastfed and supplemented-formula-fed infants were better than those of placebo-formula-fed infants at both 16 and 30 weeks of age (p < 0.001 and p < 0.01). Erythrocyte DHA in breastfed and supplemented-formula-fed infants was maintained near birth levels throughout the 30-week study period but fell in placebo-formula-fed infants (p < 0.001). Erythrocyte DHA was the only fatty acid that consistently correlated with VEP acuity in all infants at both ages tested. A continuous supply of DHA may be required to achieve optimum VEP acuity since infants breastfed for short periods (< 16 weeks) had slower development of VEP than infants receiving a continuous supply of DHA from either breastmilk or supplemented formula. Erythrocyte arachidonic acid (20:4 omega 6) in supplemented-formula-fed infants was reduced below that of infants fed breastmilk or placebo formula at 16 and 30 weeks (p < 0.001), although no adverse effects were noted, with growth of all infants being similar. DHA seems to be an essential nutrient for the optimum neural maturation of term infants as assessed by VEP acuity. Whether.


  155. Interaction between vitamin B6 deficiency and low EFA dietary intake on kidney phospholipids and PGE2 in the rat. Maranesi M, Barzanti V, Coccheri S, Marchetti M, Tolomelli B., Centro Ricerche sulla Nutrizione, Dipartimento di Biochimica, Bologna, Italia. Prostaglandins Leukot Essent Fatty Acids. 1993;49:531-536.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Vitamin B6 is involved in the metabolism of long chain polyunsaturated fatty acids and phospholipids. We have studied the interaction between pyridoxine deficiency and low amounts of dietary essential fatty acids (EFA) in the rat. The fatty acid composition of kidney phospholipids of pyridoxine deficient animals shows a decrease of 20:3 n9 and an increase of 20:4 n6 in comparison with control and pair fed animals. This variation of fatty acid composition could be due to the simultaneous effect of vitamin B6 deficiency, which reduces the oxidation of linolenate, and of a low intake of EFAs which stimulates delta-6-desaturase. The dietary treatment also influences kidney Prostaglandin E2 (PGE2) levels which are higher in vitamin B6 deficient animals. This effect could be correlated with a higher response to sympathetic stimulation caused by the simultaneous presence of vitamin B6 deficiency and low EFA availability. Also the higher level of arachidonate could be involved in promoting PGE2 synthesis.


  156. Essential fatty acid composition of human colostrum triglycerides: its relationship with adipose tissue composition. Martin JC, Niyongabo T, Moreau L, et al., Laboratoire de Biologie des Tumeurs, Hopital Bretonneau, Tours, France, Paris. Am J Clin Nutr. 1991;54:829-835.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The relationships between essential fatty acid (EFA) composition of colostrum and white adipose tissue (WAT) were examined on day 5 after delivery in 69 healthy women. Fatty acid composition was assessed by capillary gas chromatography, and 33 fatty acids were detected in colostrum and in WAT. Total polyunsaturated fatty acid (PUFA) content was similar in colostrum and in WAT (15.7 +/- 3.1% and 16.1 +/- 3.8%, respectively), but long-chain PUFA content was higher in colostrum than in WAT (2.9 +/- 0.6% and 1 +/- 0.2%, respectively; P less than 0.001). The concentrations of linoleic acid were significantly correlated between colostrum and WAT (r = 0.77, P less than 0.0001). No correlation was found for alpha-linolenic acid. The relationships between long-chain PUFA composition of colostrum and WAT suggested that individual factors along with tissue specificity of the mammary gland are involved in either the capacity of desaturating and chain-elongating pathways and/or incorporation of long-chain PUFAs into colostrum.


  157. Influence of dietary fish oil on mitochondrial function and response to ischemia. McMillin JB, Bick RJ, Benedict CR. Am J Physiol. 1992;263:H1479-H1485.
    Dietary supplementation with marine oils may reduce the incidence of thromboembolism and decrease cardiac arrhythmias during myocardial ischemia. However, function of subcellular organelles isolated from hearts of these animals is impaired. In contrast to studies where marine oil was the sole source of dietary lipid in rats, menhaden oil was used to supplement standard canine laboratory chow. In mitochondria isolated from hearts of dogs fed this diet for 60 wk, the phospholipid content of arachidonic acid was replaced by the n-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Mitochondrial levels of linoleic and linolenic acids were not altered. The mitochondrial membrane phospholipid from the menhaden oil-fed dogs demonstrated increased cardiolipin. The respiratory function of heart mitochondria from the menhaden oil-supplemented dogs was not decreased from that of dogs on standard chow only. Increased succinate-supported respiration paralleled increased cytochrome oxidase in mitochondria from menhaden oil-fed dogs. The activity of the cardiolipin-dependent carnitine acylcarnitine translocase was unaffected. Myocardial ischemia decreased mitochondrial respiration in menhaden-fed dogs. Decreased palmitoylcarnitine-carnitine exchange following ischemia resulted from decreased matrix carnitine rather than decreased translocase activity. Normal levels of the essential fatty acids in the n-3-enriched mitochondrial membrane phospholipids appear to eliminate the mitochondrial dysfunction observed in essential fatty acid-deficient membranes.


  158. Lipid utilization during fish development. Mellinger J., Univ Reims,Fac Sci,Biol Anim Lab,Bp 347/F-51062reims France . Annee Biologique. 1995;34:137-168.
    (c) 1996 Inst for Sci Info. All rts. reserv.
    A series of three review articles on the role of lipids in fish development ends up with this paper on lipid utilization. Essential fatty acids (efa) requirements in juveniles and larvae differ according to species. The majority of farmed fish species only require n-3 highly unsaturated fatty acids (n-3 hufa), specifically eicosapentaenoate (epa) and docosohexaenoate (dha). One species of tilapia only needs linoleate (18:2n-6). Several species need a mixture of linoleate and linolenate (18:3n-3). These differences seem to be only quantitative. They remain unexplained. Some experiments carried on with gilthead sea bream (sparus aurata) larvae suggested that n-3 hufa, particularly dha, promote growth by stimulating feeding through some external action (chemosensory effect?). Large differences in the percentage of various lipid classes are typical of teleost eggs. It is shown that eggs with a predominant phospholipid content use large amounts of phosphatidylcholine as a source of energy, while others use chiefly neutral lipids. Whenever neutral lipids are present under the form of large oil droplets, these are resorbed after hatching. This can be explained by the need for keeping the eggs of many teleosts buoyant. Even if oil does not provide the main uplift to marine planktonic eggs, its small contribution may be vital, until the dense chorion is shed. This constraint is also shown by species that produce planktonic larvae from demersal eggs. It is concluded that every fish species, particularly in teleosts, uses egg lipids in an integrated manner, according to its own << developmental stategy >>. By contrast, the fatty acid profile of lipids in the larval body remains very similar to the profile established during vitellogenesis in egg lipids.


  159. Effect of essential fatty acid deficiency on maternal, placental, and fetal rat tissues. Menon NK, Moore C, Dhopeshwarkar GA. J Nutr. 1981;111:1602-1610.
    Prolonged dietary deprivation is needed to produce essential fatty acid (EFA) deficiency. But lack of EFA also impairs reproductive function. Inclusion of small amounts of linoleic acid in the diet can overcome this difficulty; further, if large amounts of oleic acid are included in the diet, this competes with the utilization of 18:2 producing EFA deficiency. Using this approach, female rats were fed a fat-free diet containing 5% oleic acid w/w (with 2-3% 18:2) as the only source of fat for 4 months. They were mated and on the 21st day of gestation, the fatty acids of fetal tissues, placenta, maternal liver and plasma were analyzed and compared to controls on a stock diet. Fetuses from the experimental group were smaller and contained higher amounts of 18:1 and 20:3 omega 9 indicating EFA deficiency. The omega 6 fatty acids in the polar lipids of placenta of the EFA-deficient group were not significantly lower than the controls, in spite of lower concentrations in the maternal plasma, suggesting a unique capacity of the placenta to concentrate omega 6 fatty acids, which in turn may be utilized for prostaglandin synthesis needed for inducing labor and other vascular changes in the fetus.


  160. Effect of Linolenic Acid Upon the Metabolism of Linoleic Acid. Mohrauer HaRTH., Univ. of Minn., Hormel Res. Inst. J. Nutrition. 1963;81:67-74.
    Weanling rats were fed a fat free diet supplemented with highly purified linolearte and linolenate combined in several ratios. The fatty acid composition of liver, heart and adipose tissue was analyzed by gas chromatography. Increased amounts of dietary linolenate suppressed the levels of arachidonate in tissue lipids, thus showing thet the conversion of linoleate is inhibited by dietary linolenate. One percent linolenate lowered the triene:pentaene ratio to less than one.


  161. The effect of dietary essential fatty acids upon composition of polyunsaturated fatty acids in depot fat and erythrocytes of the rat. Mohrauer H, Holman RT. J of Lip Research. 1963;4:346-350.
    The fatty acid compostion of lipids from erythrocytes and depot fat of rats whose diet was supplemented with various levels of linoleate, arachidonate, or linolenate has been investigated. The ratio of eicosatrienoic acid to eicosatetraenoic acid, derived from the analysis of depot fat, decreases with increasing amounts of all three dietary essential fatty acids (EFA) in the same manner as observed in organ lipids. The composition of the unsaturated fatty acids of erythrocyte lipids is altered readily by increasing amounts of dietary EFA. The concentration of 20:3 is lowered extensively by all three EFA. The synthesis of arachidonate is inhibited by dietary linolenate and 20:5 and 22:5w3 (double bond between third and fourth carbons from w end) can be detected only in animals given linolenate.


  162. The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver. Mohrhauer H, Holman R. J Lipid Research. 1963;4:151-59.
    Rats were fed various levels of either ethyl linoleate, ethyl arachidonate, or ethyl linolenate. Weight gain, fat deficiency status, and fatty acid composition of the liver lipids were determined. Dietary linoleate, fed in excess of 1% of calories, maintained good growth and cured fat deficiency. Increasing amounts of dietary linoleate were stored in the liver lipids and converted into fatty acids of the linoleate family - 20:4 and 22:4. The concentration of 20:3 was decreased. Dietary arachidonate cured fat deficiency three times more effectively than linoleate. Increasing amounts of dietary arachidonate were stored in liver lipids and converted to 22:5w6. The level of 20:3 was lowered three times more effectively than when linoleate was fed. No fatty acids of the linoleante family were synthesized from linoleate or arachidonate. Dietary linolenate did not support weight gain as efficiently as did linoleate or arachidonate. Fat deficiency symptoms could not be cured completely. Increasing amounts of dietary linolenate increased the levels of fatty acids of the linolenate family; linolenic acid was stored, and 20:5, 22:5w3, and 22:6 were synthesized from linolenate. The level of 20:3 was lowered in the same fashion as when linoleate or arachidonate was fed. The level of 20:4 was decreased with increasing amounts of dietary linolenate.


  163. Metabolism of linoleic acid in relation to dietary saturated fatty acids in the rat. Mohrhauer H, Holman T. J Nutr. 1967;91:528-534.
    To study the interactions of dietary saturated fatty acids with the metabolism of essential fatty acids, triglycerides of saturated fatty acids of chain lengths C4 to C16 were fed in a semipurified diet to groups of weanling rats at 20% of calories for 80 days. All groups were given a daily oral supplement of ethyl linoleate at a level of 0.5% of total calories. The fatty acid composition of liver lipids was determined by gas chromatography. The conversion of linoleic to arachidonic acid was not hindered by the dietary triglycerides of saturated fatty acids. Levels of 20:4w6 were, in fact, higher in rats fed the triglycerides of saturated fatty acids than in rats fed linoleic acid only. The content of 20:3w9 was slightly lowered by triglycerides of even-numbered saturated fatty acids of chain lengths up through C14, wheras it is significantly diminished by dietary triglycerides of fatty acids with chain lengths C5 and C11. Weight gain data revealed that triglycerides of dietary saturated fatty acids enhanced growth if minimal levels of linoleic acid were provided. Odd-numbered fatty acids affected growth adversely.


  164. Metabolism of linoleic acid in relation to dietary monoenoic fatty acids in the rat. Mohrhauer H, Rahm JJ, Seufert J, Holamn RT. J Nutr. 1967;91.
    To study the interaction of dietary monoenoic fatty acids with the metabolism of essential fatty acids, weanling rats were fed a fat-free diet supplemented with oleic and linoleic acids in several rations. The fatty acid composition of liver lipids was determined by gas-liquid chromatography. The conversion of oleic to eicosatrienoic acid was inhibited by dietary linoleic acid at all dietary levels of oleic acid investigated. The metabolism of linoleic acid could be influenced only when extremely high ratios of oleic to linoleic acid were fed. Petroselinic and erucic acids, representing isomers and homologues of oleic acid, were also fed as possible inhibitors of the metabolism of linoleic acid. Petroselinic acid interfered with the metabolism of linoleic and oleic acids, wheras erucic acid had little effect.


  165. Role of the blood-brain barrier in the formation of long-chain omega-3 and omega-6 fatty acids from essential fatty acid precursors. Moore SA, Yoder E, Spector AA. J Neurochem. 1990;55:391-402.
    Elongated, more highly polyunsaturated derivatives of linoleic acid (18:2 omega-6) and linolenic acid (18:3 omega-3) accumulate in brain, but their sites of synthesis and mechanism of entry are not well characterized. To investigate the role of the blood-brain barrier in this process, cultured murine cerebromicrovascular endothelia were incubated with [1-14C]18:2 omega-6 or [1-14C]18:3 omega-3 and their elongation/desaturation products determined. The major metabolite of 18:2 omega-6 was 20:4 omega-6, whereas the primary product from 18:3 omega-3 was 20:5 omega-3. Although these products were found primarily in cell lipids, they were also released from the cells and gradually accumulated in the extracellular fluid. Eicosanoid production was observed from the 20:4 omega-6 and 20:5 omega-3 that were formed. No 22:5 omega-6 or 22:6 omega-3 fatty acids were detected, suggesting that these endothelial cells are not the site of the final desaturation step. Although the uptake of 18:3 omega-3 and 18:2 omega-6 was nearly identical, 18:3 omega-3 was more extensively elongated and desaturated. Competition experiments demonstrated a preference for 18:3 omega-3 by the elongation/desaturation pathway. These findings suggest that the blood-brain barrier can play an important role in the elongation and desaturation of omega-3 and omega-6 essential fatty acids during their transfer from the circulation into the brain.


  166. Comparative antimalarial activity of linseed oil (LO) and ground flaxseed (GF) in Vitamin E-Deficient (-VE) mice. Morris VC, Ager AL, May RG, Levander OA., USDA Human Nutrition Research Center, Beltsville, MD., USA . Am J Clin Nutr. 51 (Suppl.):519.
    (c) 1996 BIOSIS. All rts. reserv.


  167. Essential fatty acids in soybean products. Part 3. Effects of the addition of .alpha.-linolenic acid on oxidation of lipid in frozen tofu. Muramatsu N, Karasawa H, Ohike T. Nagano-Ken Shokuhin Kogyo Shikenjo Kenkyu Hokoku. 1992;20.
    (c) 1996 American Chemical Society. All rts. reserv.


  168. Nagasaka Y, Ito M, Tanaka Y, inventors; Nippon Oils & Fats Co Ltd, assignee. Nutritious Oil Compositions Containing .Alpha.-Linolenic Acid and Aliphatic AlcoholsJapan Kokai Tokkyo Koho ; JP 9470717 A2 ; JP 0670717. 1994 Mar 15.
    (c) 1996 American Chemical Society. All rts. reserv.


  169. A controlled trial of the effect of linolenic acid on incidence of coronary heart disease. The Norwegian vegetable oil experiment of 1965-66. Natvig H, Borchgrevink CF, Dedichen J, Owren PA, Schiotz EH, Westlund K. Scand J Clin Lab Invest Suppl. 1968;105:1-20.


  170. Are n-3 fatty acids essential nutrients for fetal and infant development? Nettleton JA., Office of Scientific Public Affairs, Institute of Food Technologists, Chicago, IL 60601. J Am Diet Assoc. 1993;93:58-64.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Recent research indicates that n-3 fatty acids (FAs) are essential nutrients in early human development. In human infants, nonhuman primates, and animal models, the n-3 FA, docosahexaenoic acid (DHA, 22:6n-3) is highly concentrated in brain and retinal tissues and accumulates during late fetal and early neonatal life. Diets deficient in n-3 FAs are associated with reduced levels of DHA in erythrocytes and brain and retinal tissues and with abnormalities in retinal function that may be irreversible. The precursor of DHA, alpha-linolenic acid (LNA, 18:3n-3), may be an inadequate substitute for DHA because LNA may not be converted to DHA in sufficient amounts to meet an infant's needs. Premature infants lose DHA from their tissues unless they are fed human milk or formula supplemented with DHA. Fish and shellfish are the main food sources of DHA. Women who consume fish have more DHA in their breast milk than do those who do not eat seafood. Infant formulas contain only LNA as a source of n-3 FAs. Pregnant and nursing women should be encouraged to consume seafood on a regular basis during pregnancy and lactation to furnish DHA for their infants.


  171. Omega-3 fatty acids: comparison of plant and seafood sources in human nutrition. Nettleton JA. J Am Diet Assoc. 1991;91:331-337.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Omega-3 Fatty acids (omega-3FAs) are found in seafoods, some plants, and some livestock rations. Fish oils are the only concentrated source of eicosapentaenoic acid (EPA; 20:5 omega-3) and docosahexaenoic acid (DHA; 22:6 omega-3). The major omega-3FA in plants is alpha-linolenic acid (LNA; 18:3 omega-3). LNA must be converted to EPA before it exerts biological effects similar to EPA, such as reduced platelet aggregation. Human beings convert LNA to EPA to a small extent only. LNA may be more readily oxidized than incorporated into tissues. The effects of consuming LNA-rich oils are more modest than the effects of EPA-rich oils. Evidence suggests that omega-3FAs are essential and highly desirable for brain and eye development and heart health. LNA is the only source of omega-3FAs for vegetarians. Because LNA and EPA are not biologically equivalent, food composition data or product claims mentioning total omega-3FA content must clarify the individual omega-3FAs present.


  172. N-3 fatty acids in the brain and retina: evidence for their essentiality. Neuringer M, Connor WE. Nutr Rev. 1986;44:285-294. charts.
    Literature review.
    Abstract: A technical review summarizes and discusses current evidence concerning the significance of the role played by n-3 polyunsaturated fatty acids (n-3 FA's) in brain and retina function. Topics include: the distribution of n-3 FA's in the retina, brain, and other tissues; the essentiality of these n-3 FA's and the effects of their deficiency on the retina, the brain, and on behavior in animals and humans; and the reversibility of such deficiency. It is concluded that, despite the lack of a clear demonstration of a deficiency of n-3 FA's in humans, evidence from animal (including non- human primates) studies is growing that n-3 FA's are essential for normal development and functioning of the retina and brain.(wz).

  173. Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys. Neuringer M, Connor WE, Van Petten C, Barstad L. J Clin Invest. 1984;73:272-276.
    Linolenic acid (18:3 omega 3) is a dietary precursor of docosahexaenoic acid (22:6 omega 3), the major fatty acid in the photoreceptor membranes of the retina. We hypothesized that rhesus monkeys deprived of dietary omega-3 fatty acids during prenatal and postnatal development would show plasma depletion of these fatty acids and visual impairment. Semipurified diets deficient in omega-3 fatty acids were fed to one group of adult female rhesus monkeys throughout pregnancy and to their infants from birth. A control group of mothers and infants received similar diets but supplying ample linolenic acid. In the plasma phospholipids of deficient infants, linolenic acid was generally undetectable and 22:6 omega 3 levels became progressively depleted, falling from 42% of control values at birth to 21% at 4 wk, 9% at 8 wk, and 6% at 12 wk of age. In the other plasma lipid classes, 22:6 omega 3 was undetectable by 12 wk. The visual acuity of the deprived infants, as measured by the preferential looking method, was reduced by one-fourth at 4 wk (P less than 0.05) and by one-half at 8 and 12 wk (P less than 0.0005) compared with control infants. These results suggest that omega-3 fatty acids may be an essential nutrient, and that 22:6 omega 3 may have a specific function in the photoreceptor membranes of the retina.

  174. Changes in the fatty acid patterns of brain phospholipids during development of rats fed peanut or rapeseed oil, taking into account differences between milk and maternal food. Nouvelot A, Bourre JM, Sezille G, Dewailly P, Jaillard J. Ann Nutr Metab. 1983;27:173-181.
    The nature and amount of essential fatty acids in dietary fat play a leading part in the repartition of brain polyunsaturated fatty acids (n-3 and n-6). In order to determine precisely the respective roles of linolenic and linoleic acids in the diet on rat brain development, we used two diets in which the percentage of linolenic acid (18:3 n-3) was different. The animals were fed peanut oil (group A) or rapeseed oil (group B) during pregnancy and throughout lactation. The study of the fatty acid composition of gastric milk showed that the levels of linoleic acid (18:2 n-6) and more so linolenic acid (18:3 n-3) were much lower than in dietary fats. In group B, the 18:3 n-3 level of gastric content was about four times lower (2.4%) than in the maternal diet (8.5%) at the beginning of the suckling period and significantly increased until weaning. Analysis of the fatty acid composition of ethanolamine phosphoglycerides showed that docosapentaenoic acid delta 7-10-13-16-19 (22:5 n-3) and docosahexaenoic acid delta 4-7-10-13-16-19 (22:6 n-3) levels increased in group B in relation to group A and, on the other hand, the docosapentaenoic acid delta 4-7-10-13-16 (22:5 n-6) level decreased in group B. The sum of (n-3 + n-6) fatty acids did not change in either group B or group A. In our experimental conditions, we found no marked effect of diet composition upon conversion of linoleic acid to arachidonic acid. In summary, linolenic acid can be utilized in the brain (rather than linoleic acid) to provide long-chain polyunsaturated fatty acids and the amount of n-3 fatty acids would correlate with the desaturation activity of docosatetraenoic acid delta 7-10-13-16 (22:4 n-6) to docosapentaenoic acid delta 4-7-10-13-16 (22:5 n-6).


  175. Effects of dietary essential fatty acid balance on behavior and chronic diseases. Okuyama H., Nagoya City University, Nagoya, Japan . Nestle Nutrition Workshop Series. 1992;128:19-175.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv. In the series analytic: Polyunsaturated fatty acids in human nutrition / edited by U. Bracco and R.J. Deckelbaum. Discussion by workshop participants, p. 177-178. Includes references.
    This chapter examines evidence that the dietary alpha-linolenate/linoleate balance has effects both on aspects of behavior and learning and on the development of chronic diseases such as cancer, allergy, thrombotic diseases, cerebral vascular disease, hypertension, and aging. Among the specific topics examined are: 1) desaturation-elongation activity; 2) alpha-linolenic acid function in brain and nerve functions; 3) omega-3 fatty acid requirements; 4) allergic hyperactivity; 5) the success and failure of nutritional guidelines for the prevention of chronic diseases; 6) carcinogenesis; and 7) an optimal omega-3/omega-6 ratio.


  176. Minimum requirements of n-3 and n-6 essential fatty acids for the function of the central nervous system and for the prevention of chronic disease. Okuyama H. Proc Soc Exp Biol Med. 1992;200:174-176.
    General behavioral patterns of rats or mice fed a deficient diet of 5 wt% safflower oil (75% linoleate [n-6] and less than 0.1% alpha-linolenate [n-3]) for two generations were significantly different from those of animals fed 5 wt% perilla oil (15% n-6 and 55% n-3). Also, brightness-discrimination learning ability and retinal function were higher in the perilla group than in the group fed 5 wt% soybean oil (53% n-6 and 4.7% n-3) or safflower oil, indicating that the requirement of n-3 for the maximum responses of the nervous system is above 0.6 en% when there is 6.8 en% linoleate n-6. Perilla oil has been found to be beneficial for the suppression of carcinogenesis, allergic hyperreactivity, thrombotic tendency, apoplexy, hypertension, and aging in animals, as compared with soybean oil and safflower oil. These results are against a lipid peroxide theory of aging, carcinogenesis, and chronic diseases. Animal experiments and epidemiological studies lead to a recommendation that the intake of n-6 should be decreased to as low as 2-4 en% and that of n-3 be increased to levels higher than linoleate n-6 for the prevention of chronic diseases prevailing in the industrialized countries.


  177. Effect of maternal fatty acid deficiency on lipid content and composition of rat liver during prenatal development. Omodeo Sale F, Mariani C, Berra B. Cell Mol Biol 1989. 1989;35:379-390.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv.
    Two groups of female rats were fed a diet with high (5.9 cal % of linoleate + linolenate) or low (0.78 cal % of linoleate + linolenate) essential fatty acid (EFA) concentration. The effects of the EFA concentration during gestation on liver lipid and fatty acid composition were studied in the fetuses at 15 and 20 days of intrauterine life. Fetal and liver weights were identical in the two groups; at day 20 the contents of proteins, total cholesterol, phospholipids and glycolipids were significantly decreased (p less than 0.01) with the low EFA diet while at day 15 only total cholesterol was affected (p less than 0.05). At both gestational ages the triacylglycerol content was increased in the low EFA group (day 15 p less than 0.05, day 20 p less than 0.01). The maternal EFA deficiency resulted in higher levels of 16:1 n-7 in the phospholipid fractions and 16:1 n-7 and 18:1 n-7 in the neutral lipids. The increase in these monoenoic derivatives partially compensated the decrease of the polyunsaturated species 18:2 n-6 and 20:4 n-6. In conclusion the low EFA diet results in important modifications of the fetal hepatic lipids during intrauterine development.


  178. Rod outer segment lipids in vitamin A-adequate and -deficient rats. Organisciak DT, Wang HM, Noell WK, Plantner JJ, Kean EL. Exp Eye Res. 1986;42:73-82.
    Weanling albino rats were fed a vitamin-A-adequate diet or vitamin-A-deficient diet and maintained in a cyclic light or dark environment for up to 14 weeks. One half of the rats were supplemented with additional dietary linolenic acid in the form of linseed oil. The lipid composition and rhodopsin-opsin contents of isolated rod outer segments were determined after 6-7 weeks or 12-14 weeks on diet. This study shows that feeding rats a standard vitamin A-adequate or -deficient diet results in an age-dependent loss of omega three docosahexaenoic acid and a concomitant increase in omega six docosapentanoic acid in the rod outer segments. The loss of docosahexaenoate appears to be caused by insufficient dietary omega three fatty acids. The increase in omega six docosapentanoic acid appears to arise from the high concentration of linoleic acid in standard diets containing either cottonseed, or peanut oil or supplemental corn oil. Feeding rats diets supplemented with linseed oil, however, results in a rod outer-segment lipid profile which is the same as for chow-fed animals. The same effects were seen in the fatty-acid profile of lipids from liver, although the content of polyunsaturates was much lower than in rod outer segments. Vitamin A deficiency, itself, does not lead to changes in the fatty-acid composition of either the rod outer segments or liver. After 6-7 weeks on A+ or A- diet, rhodopsin levels were, as expected, higher in dark-reared rats than in cyclic-light animals. Although the rhodopsin levels in dark-reared vitamin A-adequate rats were significantly higher than in vitamin A-deficient animals, measurements of the lipid to opsin ratio of rod outer segments indicate that the rods of vitamin A-deficient rats are not markedly different than those of vitamin A-adequate rats. It is concluded that these diets may be useful in providing a means for evaluating the role of docosahexaenoic acid in visual cell death from damaging light.


  179. Metabolic utilization of linoleate and alpha-linolenate in cultured peritubular cells. Oulhaj H, Oulhaj N, Bichoualne L, Ouahabi A, Huynh S., Departement De Biologie, Faculte De Sciences, Universite Moulay Ismail, B. P. 4010, Beni M'hamed, Meknes, Maroc, France . C R Seances Soc Biol Fil. 1994;188:259-275.
    The capacity of cultured peritubular cells to synthesize long-chain polyunsaturated fatty acids (PUFA) from the essential fatty acid (EFA) precursors 18:2n-6 and 18:3n-3 was tested, and compared to the PUFA biosynthesis in Sertoli cells. The concentrations of each EFA required to obtain maximal incorporation into membrane lipids were determined. The two EFA were added to the culture medium as free fatty acids complexed to albumin in a molar ratio of 12:1. When the substrates were added individually, the maximal levels of biosynthesis in peritubular cells were obtained with 0.70 mu-g/ml of 18:2n-6 or 18:3n-3 in culture medium. With Sertoli cells, the concentration of 0.70 mu-g/ml linoleate or of 2.00 mu-g/ml alpha-linolenate in culture medium appeared to correspond to levels required for maximal incorporation and utilization of the n-6 PUFA or n-3 PUFA. Incorporation and metabolic utilization were always more important in cultured Sertoli cells than in cultured peritubular cells. The peritubular cell appeared to incorporate linoleate less efficiently than alpha-linolenate at identical concentrations. In agreement with observations in other cell systems (15), we found a preferential utilization of 18:3n-3 over 18:2n-6 by the DELTA-6 desaturase in the peritubular cell and in the Sertoli cell.


  180. Abnormal essential fatty acid metabolism in Darier's disease. Oxholm A, Oxholm P, da Cunha Bang F, Horrobin DF., Department of Dermatology, University of California, San Francisco. Arch Dermatol. 1990;126:1308-1311.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Fatty acid levels in plasma and erythrocyte cell membranes were determined in 13 Danish patients with Darier's disease and 21 Danish controls. Concentrations of the main dietary essential fatty acids, linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), were consistently modestly above normal; concentrations of the delta 6-desaturase metabolites of both linoleic and alpha-linolenic acids, however, were consistently and often significantly below normal. These results suggest that the capacity of the enzyme delta 6-desaturase activity is inadequate in patients with Darier's disease.


  181. Ischemia myocardial damage in spontaneously hypertensive rats (SHR) is enhanced after lonbg-term feeding of an alpha-linolenic acid enriched diet. Papies B, Schmike I, Moritz V, Massow S, Foerster D, Wagenknecht C., Humboldt univ., dep. pathology clin. biochemistry, Berlin, Federal Republic of Germany . Prostaglandins Leukot Essent Fatty Acids. 1991;43:111-117.
    (c) 1995 INIST/CNRS. All rts. reserv.


  182. Ethanol exposure causes a decrease in docosahexaenoic acid and an increase in docosapentaenoic acid in feline brains and retinas. Pawlosky RJ, Salem N Jr. Am J Clin Nutr. 1995;61:1284-1289.
    Alcohol altered the fatty acyl composition of the liver, brain, and retina of domestic felines that were maintained on a diet having low, but adequate, amounts of essential fatty acids. For 8 mo, seven adult cats were provided a diet with 10% fat (by wt), consisting of 9:1 ratio of hydrogenated coconut oil:corn oil. During 6 of these 8 mo, four of the cats were given oral daily doses of a 95% ethanol solution (1.2 Cats were killed and the fatty acyl composition of tissues were determined. In the plasma and livers of the alcohol-exposed animals, there were significant decreases in the concentrations of 18:2 omega 6, 20:4 omega 6, 22:5 omega 3, and 22:6 omega 3 and increases in the concentrations of the nonessential fatty acids 16:1 omega 7, 18:1 omega 9, and 20:3 omega 9. In the brains and retinas of the alcohol-exposed animals, 22:6 omega 3 decreased by 17% and there was a compensatory increase in 22:5 omega 6. In the retinas, the concentration of 22:5 omega 6 increased by 250%. The reciprocal change in the ratio of 22:6 omega 3 to 22:5 omega 6 is known to be associated with a loss in nervous system function and may provide a biochemical mechanism underlying some of the neuropathology associated with alcoholism.


  183. Essential fatty acid uptake and metabolism in the developing rodent brain. Pawlosky RJ, Ward G, Salem N Jr. Lipids. 1996:31 Suppl:S103-7.
    Studies were carried out to determine whether the brain takes up and metabolizes essential fatty acids during early postnatal development in rodents. Rats and mice were dosed with deuterium-labeled linoleic and linolenic acids either by intraperitoneal injection or by gavage. Animals were killed at different times thereafter, and organs were removed. Brains, livers, and blood were analyzed by gas chromatography--negative-ion-mass spectrometry for labeled fatty acids. To determine whether fatty acids were present in the brain apart from cerebral blood, a subset of animals was exsanguinated by perfusion with buffered saline, and the brain was then fractionated into subcellular components. Results demonstrated that the brain took up both labeled essential fatty acids within 8 h from the time of dosing. There was on average a greater uptake of linolenic acid into the cerebellum than into the cerebral cortex during the first 8 d of life in rats. The amount of linoleic acid taken into either region was similar, however. Docosahexaenoic acid intermediates, 20:5n-3 and 22:5n-3, were also found labeled in the brain. Time-course labeling experiments indicated that these intermediates may be converted to 22:6n-3 within the brain. A rise of labeled 22:6n-3 in the brain at 24 h appeared to be due to uptake of this fatty acid from the blood. The amount of labeled 22:6n-3 in the brain continued to increase beyond 24 h, and this did not appear to be correlated with its blood concentration. These results suggest that, during development in the rodent, different regions within the brain may vary in their capacity to synthesize 22:6n-3, and this may be correlated with regional growth rates.


  184. Essential fatty acid metabolism in the feline: relationship between liver and brain production of long-chain polyunsaturated fatty acids. Pawlosky R, Barnes A, Salem NJ., Laboratory of Membrane Biochemistry and Biophysics, DICBR, National Institute on Alcoholism and Alcohol Abuse, Rockville, MD 20852. J Lipid Res. 1994;35:2032-2040.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    A comparison was made between the liver and brain conversion of linoleic acid, 18:2n-6, and linolenic acid, 18:3n-3, to long chain polyunsaturated fatty acids in domestic felines. This report demonstrates that 6-desaturase activity does exist in the feline. The liver produced deuterium-labeled polyunsaturated fatty acids up to 22:4n-6 and 22:5n-3. The brain was found to accumulate the deuterium-labeled polyunsaturated fatty acids, 22:5n-6, 22:6n-3, 24:4n-6, 24:5n-6, 24:5n-3, and 24:6n-3. Adult felines were provided a diet consisting of either 10% fat (hydrogenated coconut oil-corn oil 9:1) containing no 20- or 22-carbon n-6 or n-3 fatty acids or a chow diet with meat and meat by-products that contained these long chain polyunsaturated fatty acids for a 6-month period. During this time, the in vivo production of long chain polyunsaturated fatty acids was evaluated in these animals. The cats were given oral doses of both [17,17,18,18,18,2H]18:3n-3 and [9,10,12,13-2H]18:2n-6 and the deuterium-labeled fatty acid metabolites were measured in the blood, liver, and brain using a highly sensitive and specific gas chromatography-mass spectrometry technique. Contrary to previous claims, 6-desaturase activity was shown to exist in the feline. The evidence for this was the detection of [9,10,12,13-2H] 18:3n-6 which was converted from [9,10,12,13-2H]18:2n-6 and observed in the plasma.(ABSTRACT TRUNCATED AT 250 WORDS).


  185. Reduced arachidonate in serum phospholipids and cholesteryl esters associated with vegetarian diets in humans. Phinney SD, Odin RS, Johnson SB, Holman RT. Am J Clin Nutr. 1990;51:385-392.
    Lipid fractions such as phospholipids (PLs), cholesteryl esters (CEs), and free fatty acids (FFAs) represent source pools for eicosanoid synthesis. To determine whether dietary habits affect the enrichment of 20:4n-6 in these precursor pools, we studied humans with partial or complete arachidonate restriction resulting from chronic avoidance of animal fat and tissue. Fasting serum was obtained from omnivorous control subjects (Omni, n = 100), semivegetarians (Semiveg, n = 16), and vegetarians (Veg, n = 25). PLs, CEs, FFAs, and triglyceride (TG) fatty acids were quantitated by thin-layer and gas chromatography. Serum 20:4n-6 was lower in the PL fraction in both Veg (p less than 0.01) and Semiveg groups (p less than 0.05) than in the Omni group and lower in the CE fraction in the Veg group (p less than 0.05). Serum 18:2n-6 did not differ between groups for any serum lipid fraction. 18:3n-3 was elevated in PLs and CEs of both Veg (p less than 0.05 and 0.01) and Semiveg groups (p less than 0.05 and 0.01) compared with the Omni group but did not result in differences in 20:5n-3 in PLs or CEs between diet groups. The lower concentration of 20:4n-6 in serum PLs and CEs of the Veg group indicates that dietary arachidonic acid enriches its circulating pool in humans; however, 20:5n-3 is not similarly responsive to dietary restriction.


  186. Estimation of essential fatty acid requirements of common carp larvae using semi-purified artificial diets. Radunz-Neto J, Corraze G, Bergot P, Kaushik SJ. Arch Tierernahr. 1996;49:41-48.
    Two trials were conducted with duplicate groups of (first feeding) carp larvae fed artificial dry diets based on casein and dextrin over 21 or 25 days. One control diet based on yeast was also tested. Survival, growth and fatty acid profiles of larvae were studied. In trial 1, (n-3) fatty acid requirement was estimated using diets supplemented or not with methyl linolenate or cod liver oil. After 21 days, the best survival and growth were observed in larvae fed the unsupplemented diet [(n-3) fatty acid level: 0.05%]. Survival and growth were not improved by higher levels of (n-3) fatty acids. In trial 2, (n-6) fatty acid requirement was estimated using diets with graded levels of methyl linolenate or peanut oil. After 25 days, the best survival and growth were obtained with diets supplemented with 0.25% methyl linolenate (total (n-6) fatty acid level: 1%) or with 1.25% peanut oil (total (n-6) fatty acid level: 0.89%). Survival and growth were not improved by higher levels of (n-6) fatty acids. Fatty acid composition of carp reflected that of the diets and also showed that carp larvae are capable of elongating and desaturating linolenic acid and linoleic acid in longer chain fatty acids.


  187. The influence of maternal vegetarian diet on essential fatty acid status of the newborn. Reddy S, Sanders TA, Obeid O., Department of Nutrition and Dietetics, King's College London, UK. Eur J Clin Nutr. 1994;48:358-68.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    OBJECTIVES: To evaluate whether a maternal vegetarian diet influences the essential fatty acid status of the newborn and whether this is related to outcome of pregnancy. DESIGN: Dietary intake and the fatty acid composition of plasma phospholipids were determined in 24 South Asian vegetarian and 24 white omnivore non-pregnant premenopausal women randomly selected from the general population of North London. Umbilical cords and cord blood were collected at delivery from 48 South Asian vegetarian women and 98 white omnivores from the same catchment area along with details of antenatal history and the outcome of pregnancy. The fatty acid composition of the cord arteries and that of cord plasma phospholipids were analysed in a subset of 32 pairs of subjects, who were matched for maternal age, gestational age, parity and sex of infant. RESULTS: Intakes of linoleic acid (18:2n-6) expressed as proportion of the dietary energy and the ratio of linoleic to alpha-linolenic acid (18:3n-3) were higher in the vegetarian women, and eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were absent from their diets. The proportion of linoleic acid, as well as the absolute concentration, was greater and those of EPA and DHA were lower in plasma phospholipids, plasma free fatty acid and total plasma lipids of the vegetarians compared with the white subjects. The proportion of DHA was lower (P > 0.001) but that of docosapentaenoic acid (22:5n-6) was greater (P < 0.001) in cord those from the omnivores. The ratio of 20:3n-9/20:4n-6 was elevated in cord artery but not in cord plasma phospholipids in both groups. Early onset of labour and the duration of gestation was 5.6 days shorter. Birth weight, head circumference and length were lower in the infants born to South Asian vegetarians even after adjusting for maternal height, duration of gestation, parity, gender of infants and smoking habits. Multivariate analysis did not reveal any relationship between the proportions of DHA in plasma or cord artery phospholipids and the birthweight or head circumference of the infants. CONCLUSION: This study demonstrates that vegetarians give birth to infants with less DHA in their plasma and cord artery phospholipids but this did not appear to be independently related to the outcome of pregnancy.


  188. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. Reeves PG, Niesen FH, Fahey GCJr. J Nut. 1993;123:1939-1951.
    Includes references.
    For sixteen years, the American institute of Nutrition Rodent Diets, AIN-76 and AIN-76A, have been used extensively around the world. Because of numerous nutritional and technical problems encountered with the diet during this period, it was revised. Two new formulations were derived: AIN-93G for growth, pregnancy and lactation, and AIN-93m for adult maintenance. Some major differences in the new formulation of AIN-93G compared with AIN-76A are as follows: 7 g soybean oil (0.5 g. linolenic acid)/100 g diet was substituted for 5 g corn oil/100 g diet to increase the amount of linolenic acid; cornstarch was substituted for sucrose; the amount of phosphorus was reduced to help eliminate the problem of kidney calcification in female rats; L-cystine was substituted for DL-methionine as the amino acid supplement for casein, know to be deficient in the sulfur amino acids; manganese concentration was lowered to one-fifth the amount in the old diet; the amounts of vitamin E, vitamin K and vitamin B-12 were increased; and molybdenum, sillicon, fluoride, nickel, boron, lithium and vanadium were added to the mineral mix. for the AIN-93M maintenance diet, the amount of fat was lowered to 40g/kg diet from 70 g/kg diet, and the amount of casein to 140 g/kg from 200 g/kg in the AIN-93G diet. Because of a better balance of essential nutrients, the AIN-93 diets may prove to be a better choice than AIN-76A for long-term as well as short-term studies with laboratory rodents.


  189. Lipid intake during pregnancy in developing countries: possible effect of essential fatty acid deficiency on fetal growth. Robillard PY, Christon R., Service de neonatologie, Centre Hospitalier Universitaire de Pointe-a-Pitre, France. Prostaglandins Leukot Essent Fatty Acids. 1993;48:139-42.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    There is a strong epidemiological association between poor nutritional status and low-birthweight (LBW) newborns. According to the World Health Organization (WHO), 95% of total LBW in the world are born in developing countries. Nevertheless, the nutritional etiology of intra uterine growth retardation (IUGR) is still controversial and not yet established largely because of contradictory nutritional studies in pregnancy. In 1981 Menon et al described an animal model of IUGR due to mild deficiency in essential fatty acids (EFA, linoleic and alpha linolenic acids), with a strong correlation between EFA intake during pregnancy and fetal growth. According to the WHO reports in the last decade, there was a dramatic deficiency of lipid intakes (less than 10% of total caloric amounts) in the majority of developing countries while the EFA requirements alone of normal nourished women are evaluated at 6% of total caloric amounts during pregnancy. A mild deficiency in dietary EFA may be a limiting factor in fetal growth processes in humans as it has been shown in animals. Such a mechanism could be easily verified. Research proposals are made in an attempt to test this hypothesis in developing countries with possible applications in further nutritional interventions in pregnancy.


  190. Liver subcellular fatty acid profiles of chicks fed diets containing hydrogenated fats and varying linoleate levels. Rogel AM, Watkins BA., Department of Animal Sciences, Washington State University, Pullman 99164-6320. Lipids. 1987;22:637-42.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv.
    Day-old male broiler chickens were fed semipurified diets containing 5% lipid from one of four different lipid sources: corn oil (CO), partially hydrogenated soybean oil (HSBO), a spent restaurant grease (SRG) and a purified mixture of triolein, tripalmitin and tristearin (OPS). Diets CO and HSBO contained adequate amounts of linoleic acid, but diets SRG and OPS were deficient in linoleate. In addition, SRG and HSBO contained trans isomers of 16:1 and 18:1. The diets were fed for 3 wk to determine the effects of low linoleate levels and trans isomers on fatty acid profiles in liver microsomes, mitochondria and cytosol. Chicks fed HSBO had the highest body weights, while those fed SRG and OPS had the lowest. The incidence and severity of dermatitis were similar for all treatments. The proportions of linoleate and arachidonate in lipids from liver subcellular fractions were reduced significantly in chicks fed OPS and SRG; however, levels of 20:3 omega 9 were not increased. Feeding HSBO, which is high in both linoleate and linolenate, resulted in higher levels of 18:3 omega 3 and 20:5 omega 3 in liver subcellular fractions and lower levels of 20:4 omega 6 than those seen in chicks fed CO. The isomeric forms of 18:1 present in the partially hydrogenated fats (HSBO and SRG) appeared to be incorporated into the lipids of liver fractions. The results of this study show that dietary lipids influence fatty acid profiles of chick liver microsomes, mitochondria and cytosol. Decreases in linoleate and arachidonate in these organelles occur before overt essential fatty acid (EFA), deficiency signs in chicks fed EFA-deficient diets.


  191. Essential polyunsaturated nutrients in the development of striated muscle in rats. Rondinone R., Istituto di Fisiologia Umana, Facolta di Medicina, Universita di Genova, Genova, Italy. Bollettino Societa Italiana Di Biologia Sperimentale. 1990;66:67-74.
    (c) 1995 CAB International. All rts. reserv.
    During development and maturation of striated muscle in rats short chain fatty acids and monounsaturated fatty acids increased progressively and unsaturated and polyunsaturated fatty acids (PUFA) decreased. Content of hyperunsaturated fatty acids (eicosapentaenoic and docosahexaenoic acids) was high. Feeding growing and adult rats on diets supplemented with linoleic and alpha -linolenic acids improved the balance of PUFA to hypersaturated fatty acids without affecting other fatty acids.


  192. Influence of different unsaturated fatty acids on stability of raterythrocyte membranes. Roth HP, Kirchgessner M., Technische Universitat Munchen, Institut fur Ernahrungsphysiologie, 8050 Freising-Weihenstephan, Germany. Ann Nutr Metab. 1992;36:113-120.
    (c) 1995 CAB International. All rts. reserv.
    Restrictive feeding of 54 Sprague-Dawley rats on a semi-synthetic diet, with coconut fat as the dietary fat, caused an essential fatty acid deficiency with increased osmotic fragility of erythrocytes against hypotonic saline solutions. A 60% replacement of the coconut fat in the basal diet by pure oleic acid (18:1 n-9) or linoleic acid (18:2 n-6) by 0.6% alpha -linolenic acid (18:3 n-3), eicosatrienoic acid (20:3 n-3) or eicosapentaenoic acid (20:5 n-3) led, in the case of linoleic acid and eicosapentaenoic acid, to a significant decrease in the fragility of rat erythrocytes in comparison with the basal diet. The inefficacy of the alpha -linolenic acid treatment is possibly the consequence of a too low dietary supplementation.


  193. Rudin D, Felix C. Omega-3 Oils: to Improve Mental Health, Fight Degenerative Diseases and Extend Your Life. Garden City Park, NY: Avery Publishing Group; 1996.
    Flaxseed is a good source of crucial &quotgood fats", though opinions differ on what role they should play in a healthy diet. According to Omega-3 Oils, by Donald Rudin, M.D., and Clara Felix, the current American diet, while higher in polyunsaturated oils (such as corn oil) containing Omega-6, still leaves the population dangerously deficient in Omega-3. Rudin calls Omega-3 oils such as flaxseed &quotultrapolyunsaturated" and contends that both kinds of fatty acids are needed in the correct ratio for a healthy diet, since each produces distinctive &quotprostaglandins" which in turn regulate key hormonal functions involging the reproductive, digestive, and nervous systems. In a perliminary study, Rudin found that flaxseed oil supplements helped ease a wide variety of ailments in his patients, including rheumatoid arthritis, stomach ailments, and even mental illness. The best source of Omega-3 is flaxseed. Aside from being ideal for vegetarians, flaxseed has a major advantage over fish oil. It takes better, and can be used both for cooking and for salad dressing. In addition, flaxseed contains lignan, an excellent plant fiber associated with lower cancer rates. Fish oil, on the other hand, may contain DDT and mercury, which may produce dangerous &quotfree radicals.".


  194. Failure of topical vegetable oils to prevent essential fatty acid deficiency in a critically ill patient receiving long-term parenteral nutrition. Sacks GS, Brown RO, Collier P, Kudsk KA., Department of Clinical Pharmacy, University of Tennessee, Memphis. J Parenter Enteral Nutr. 1994;18:274-277.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    This case report describes the failure of topical vegetable oils containing esters of linoleic acid to prevent essential fatty acid deficiency in a critically ill patient with trauma. A 40-year-old black man injured in a motor vehicle accident developed essential fatty acid deficiency after being maintained on long-term, fat-free parenteral nutrition plus topical vegetable oil application because of the presence of severe hypertriglyceridemia. Biochemical evidence of this deficiency included a decrease in serum linoleic, a-linolenic, and arachidonic acid levels with a corresponding increase in oleic and palmitoleic acid levels. Cutaneous manifestations consistent with this syndrome were also present. After 3 weeks of daily topical treatments with vegetable oils rich in linoleic acid, biochemical abnormalities of deficiency were still evident. Over the following 2 1/2 months, 4% to 22% of the total caloric intake was delivered as intravenous fat in addition to continued topical administration of vegetable oil. Only after supplementation with intravenous fat did the patient demonstrate clinical and biochemical signs of improvement. The results show that cutaneous administration of vegetable oils as the sole source of linoleic acid may be unable to prevent or treat essential fatty acid deficiency in a critically ill surgical patient.


  195. Effect of maternal fatty acid deficiency on lipid content and composition of rat liver during prenatal development. Sale FO, Mariani C, Berra B., Istituto di Fisiologia Generale e Chimica Biologica, Facolta di Farmacia, via Saldini 50, 20133 Milan, Italy. Cell Mol Biol (Noisy-Le-Grand). 1989;35:379-390.
    (c) 1995 CAB International. All rts. reserv.
    Female rats were given a diet high (5.9 energy % of linoleate plus linolenate) or low (0.78 energy % of linoleate plus linolenate) in essential fatty acids (EFA). Foetuses were studied at 15 and 20 days of intrauterine life. Foetal and liver weights were identical in the 2 groups; at day 20 the contents of protein, total cholesterol, phospholipids and glycolipids were significantly decreased with the low EFA diet whereas at day 15 only total cholesterol was affected. At both gestational ages the triacylglycerol content was increased in the low EFA group. The maternal EFA deficiency resulted in higher 16:1 n-7 values in the phospholipid fractions and 16:1 n-7 and 18:1 n-7 in the neutral lipids. The increase in these monoenoic derivatives partly compensated the decrease of the polyunsaturated species 18:2 n-6 and 20:4 n-6.


  196. Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Salem N, Wegher B, Mena P, Uauy R. Proc Natl Acad Sci USA. 1996;93:49-54.
    It is becoming clear that an adequate level of long-chain highly unsaturated fatty acids in the nervous system is required for optimal function and development; however, the ability of infants to biosynthesize long-chain fatty acids is unknown. This study explores the capacity of human infants to convert 18-carbon essential fatty acids in their elongated and desaturated forms, in vivo. A newly developed gas chromatography/negative chemical ionization/mass spectrometry method employing 2H-labeled essential fatty acids allowed assessment of ths in vivo conversion with very high sensitivity and selectivity. Our results demonstrate that human infants have the capacity to convert dietary essential fatty acids administered enterally as 2H-labeled ethyl estrs to their longer-chain derivatives, transport them to plasma, and incorporate them into membrane lipids. The in vivo conversion of linoleic acid (18:2n6) to arachidonic acid (20:4n6) is demonstrated in human beings. All elongases/desaturases necessary for the conversion of linolenic acid (18:3n3) to docosahexaenoic acid (22:6n3) are also active in the first week after birth. Although the absolute amounts of n-3 fatty acid metabolites accumulated in plasma are greater than those of the n-6 family, estimats for the endogenous pools of 18:2n6 and 18:3n3 indicate that n-6 fatty acid conversion rates are greater than those of the n-3 family. While these data clearly demonstrate the capability of infants to biosynthesize 22:6n3, a lipid that is required for optimal neural development, the amounts produced in vivo from 18:3n3 may be inadequate to support the 22:6n3 level observed in breast-fed infants.


  197. The growth and development of vegan children. Sanders TAB, Manning J., King's College London, London . Journal Of Human Nutrition And Dietetics. 1992;5:11-21.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv. Includes references.
    The results of prospective study on the growth and diets, estimated from 7-day weighed food intake records, of 20 life vegan children (aged 5.8-12.8 years) are presented. The growth and development of the children were normal but they tended to be lighter in weight and exceptionally lean compared with standards. Heights were around the median of the Tanner-Whitehouse standards but were lower than the medians recently proposed by the Department of Health. Energy intakes were similar to those reported in children of the same age in the general population, but dietary fibre intakes were very high which may have influenced the digestible energy. Sugar provided an average 15.6% of the dietary energy and this was supplied mainly by fruit and fruit juice. Mean fat intakes were close to the dietary reference values. Daily intakes of essential nutrients generally met the amounts recommended, with the exceptions of calcium and vitamin B12. Many children received supplementary sources of vitamin B12 and only two children had intakes below the lower recommended nutrient intake. Intakes of saturated fatty acids were low and those of linoleic acid were high. The ratio of linoleic/alpha-linolenic acid was high. As docosahexaenoic acid is absent from vegan diets, it is suggested that vegans should use oils with a lower ratio of linoleic/alpha-linolenic acid. Future studies should also consider the influence of a vegan diet on retinal function. None of the children was immunized against whooping cough and 11 had not been immunized against polio; 16 of the children had suffered from whooping cough. Future studies need to take into account factors other than diet when assessing the health of vegans. The results of this study show that children can be successfully reared on a vegan diet providing sufficient care is taken to avoid the known pitfalls of a bulky diet and vitamin B12 deficiency.


  198. The influence of a vegetarian diet on the fatty acid composition of human milk and the essential fatty acid status of the infant. Sanders TA, Reddy S., Department of Nutrition and Dietetics, King's College, University of London. J Pediatr. 1992;120:S71-7.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Vegan and vegetarian diets supply higher amounts of linoleic acid than those of omnivores. Intakes of alpha-linolenic acid (18:3n-3) are variable, depending on the oils used, but are generally high in vegans. Docosahexaenoic acid (22:6n-3) (DHA) is absent from vegan and many vegetarian diets. Cord plasma and cord artery phospholipid levels of Hindu vegetarians contained less DHA and more docosapentaenoic acid (22:5n-6) compared with those of omnivore control subjects. These differences in fatty acid composition were not statistically related to differences in birth weight, head circumference, or length. In human milk from vegans, vegetarians, and omnivores, the mean percentage in total fatty acids of 18:2n-6 was 23.8%, 19.7%, and 10.9%, respectively; that of 18:3n-3 was 1.36%, 1.25%, and 0.49%, respectively; and that of 22:6n-3 was 0.14%, 0.30%, and 0.37%, respectively. The proportion of DHA in erythrocyte total lipids of infants breast-fed by vegans was 1.9% compared with 3.7% in infants fed a milk formula containing butterfat as the sole source of fat and 6.2% in infants breast-fed by omnivores at 14 weeks postpartum. The ratio of linoleic/alpha-linolenic acid in the diet was predictive of the proportion of eicosapentaenoic acid but not that of DHA in infant red blood cell lipids. It is concluded that the intakes of linoleic acid and DHA are the major determinants of the proportion of DHA in plasma and red blood cell lipids.


  199. Nutritional role of polyunsaturated fatty acids. Sardesai VM., University Health Center, Detroit, MI . J Nut Biochem. 1992;3:154-166.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv. Literature review. Includes references.
    In mammalian tissues there are four families of polyunsaturated fatty acids derived from the parent fatty acids: palmitoleic and oleic acids, which can be synthesized endogenously, and linoleic and linolenic acids, which must be obtained from the diet and are known as essential fatly acids. These four precursors are desaturated and chain elongated to form the long chain highly unsaturated fatty acids. The principal products of linoleic acid are arachidonic, with four double bonds (tetraene), and dihomogamma linolenic acids; those of linolenic acid are eicosapentaenoic and docosahexaenoic acids. These polyunsaturated acids derived from essential fatty acids when incorporated into membrane phospholipids can alter membrane fluidity, which determines the permeability of membranes and the behavior of membrane-bound enzymes and receptors. The dihomogammalinolenic, arachidonic, and eicosapentaenoic acids are also the precursors of eicosanoids, which influence many cellular processes. When the dietary amounts of linoleic and linolenic acids are inadequate, palmitoleate and oleate are desaturated and chain elongated to give rise to eicosatrienoic acids (triene). An elevated tissue triene/tetraene ratio is, therefore, used as a marker for essential fatty acid deficiency. The essential fatty acid deficiency symptoms include reduced growth rate, scaly dermatitis, impaired reproduction, and susceptibility to infection. The intake of 1 to 2% of the daily calories as linoleate and 0.2 to 0.5% as linolenate is widely acknowledged as the approximate amounts to meet the needs of essential fatty acids in humans.


  200. Interconversion of alpha-linolenate and docosahexaenoate in fetal rhesus monkey. Sheaff RC, Nathanielsz PW, Brenna JT. Cornell Univ., Ithaca, Ny 14853, Usa. Experimental Biology 95, Part I, Atlanta, Georgia, Usa, April 9-13, 1995. Faseb Journal: 1995:A464.


  201. Conversion of alpha-linolenate to docosahexaenoate in young rats maintained on low essential fatty acid (efa) or high 18:2-omega-6-18:3-omega-3 diets. Sheaff R, Su H-M, Keswick L, Brenna JT. Div. Nutr. Sci., Cornell Univ., Ithaca, Ny 14853, Usa. Experimental Biology 94, Parts I And Ii, Anaheim, California, Usa, April 24-28, 1994. Faseb Journal: 1994:A730.


  202. The relevance of fats to human health. Shorland FB., School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand. Proceedings of the Nutrition Society of New Zealand. 1990;15:118-129.
    (c) 1995 CAB International. All rts. reserv.
    Aside from the need to provide traces of the essential linoleic acid, fats have not been traditionally considered necessary dietary components. However, their use as wholesome dietary constituents was recommended without limitation. Contemporary interest in fats has been stimulated by the suggestion that their presence in the diet correlates with the occurrence of chronic diseases, especially coronary heart disease and cancer, with the result that national committees have begun to recommend that the current intakes in western countries of about 40% of energy as fat should be substantially reduced. Developments taking place within the past decade have been reviewed and, in particular, it has been shown that in addition to the physiological effects of linoleic (18:2 omega 6) acid, alpha -linolenic (18:3 omega 3) acid and its long chain C20 and C22 metabolites have physiological functions that are very different from those of linoleic acid. Docosahexaenoic (22:6 omega 3) acid, for example, is involved in vision and in brain function. Of still greater significance has been the recognition that the prostaglandins and leukotrienes (eicosanoids) produced from linoleic and alpha -linolenic acids in nanogram quantities have powerful physiological properties involving blood pressure, blood coagulation, inflammation, tumorigenesis and immune response. In many cases the adverse effects from the eicosanoids derived from linoleic ( omega 6) acid are balanced by the beneficial effects of those derived from alpha -linolenic ( omega 3) acid; a matter of considerable potential in the control of chronic diseases.


  203. Essential and trans fatty acid metabolism in health and disease. Siguel EN. Compr Ther. 1994;20:500-510.


  204. Altered fatty acid metabolism in patients with angiographically documented coronary artery disease. Siguel EN, Lerman RH. Metabolism. 1994;43:982-993.
    Plasma lipids and fatty acids have been linked to coronary artery disease (CAD), and linoleic acid deficiency has been proposed as a risk factor for cardiovascular disease, but few studies have considered their multivariate effects or found the biochemical shifts associated with abnormal fatty acid metabolism or essential fatty acid (EFA) deficiency. We studied fatty acid patterns associated with CAD using high-resolution capillary column gas-liquid chromatography to analyze fasting plasma from 47 patients with angiographically documented CAD and 56 reference subjects. CAD patients exhibited a shift in fatty acid metabolism similar to that associated with EFA-deficient patients. Compared with reference subjects, CAD patients had (1) reduced percentages of polyunsaturated fatty acids ([PUFA] 45% v 50%, P < .001), (2) increased monounsaturated fatty acids (26% v 22%, P < .001), (3) higher ratios of Mead (20:3 omega 9) to arachidonic (20:4 omega 6) acid (0.016 v 0.013, P < .04), (4) increased levels of 16:1 omega 7 (2.10% v 1.55%, P < .001), and (5) higher concentrations of total fatty acids (356 v 284 mg/dL, P < .001), saturated fatty acids (101 v 75 mg/dL, P < .001), monounsaturated fatty acids (91 v 63 mg/dL, P < .001), PUFA (159 v 143 mg/dL, P < .01), 20:3 omega 9 (0.5 v 0.3 mg/dL, P < .01) and 16:1 omega 7 (7.7 v 4.5 mg/dL, P < .01). On indices of EFA status that depend on percentages or ratios of fatty acids or on the production of abnormal fatty acids, CAD patients were between severely EFA-deficient patients and healthy subjects, a state referred to as EFA insufficiency. Patients had metabolic shifts toward increased production of monounsaturated fatty acids and increased ratios of derivatives to precursors of omega 6 fatty acids, shifts that occur when cells are EFA-deficient. Levels of EFAs were negatively correlated with levels of saturated and monounsaturated fatty acids. The percentage of 18:2 omega 6 was positively correlated with high-density lipoprotein (HDL) cholesterol and the ratio of HDL to total cholesterol (r = .58, P < .001, and r = .61, P < .001, respectively) and negatively correlated with triglycerides and total cholesterol (r = .61, P < .001, and r = -.24, P < .01, respectively). Opposite correlations with these parameters were observed with saturated and monounsaturated fatty acids. Saturated fatty acids, total cholesterol, and indicators of EFA deficiency increased and the HDL to total cholesterol ratio and PUFA decreased the probability of CAD as measured by multivariate linear regression.(ABSTRACT TRUNCATED AT 400 WORDS).


  205. Alpha-linolenic acid metabolism: the chicken and the egg. Sim JS, Cherian G, Jiang Z., Department of Animal Sciences, University of Alberta, Edmonton, Canada. Nutrition. 1992;8:221-222.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The pioneering discovery that n-3 fatty acids protect against coronary heart disease in Greenland Eskimos consuming fish has generated much research over the past decade about the various health benefits of dietary n-3 fatty acids from fish oils. It was thus suggested that 800-1100 mg/day of 18:3n-3 and 300-400 mg/day of a combination of 20:5n-3 and 22:6n-3 are needed to meet the n-3 fatty acid requirement of the elderly. Recently, the Canadian Government adopted a recommendation that n-3 polyunsaturated fatty acids (PUFAs) are essential nutrients, and dietary supply should be at least o.5% of energy intake, and the ratio of dietary n-6 to n-3 PUFA should be reduced.


  206. Serum fatty acids and the risk of stroke. Simon JA, Fong J, Bernert JTJr, Browner WS. Stroke. 1995;26:778-782.
    BACKGROUND AND PURPOSE: To examine the relationship between serum fatty acids, which reflect dietary intake, and stroke, we conducted a nested case-control study of 96 men with incident stroke and 96 control subjects matched by age, clinical center, treatment group, and date of randomization who were enrolled in the Multiple Risk Factor Intervention Trial. METHODS: After confirming the stability of the stored serum samples, we measured serum cholesterol ester and phospholipid fatty acid levels as the percentage of total fatty acids by gas-liquid chromatography and examined their association with incident stroke. Using stepwise conditional logistic regression that controlled for risk factors for stroke, we determined which fatty acids were independent correlates of stroke. RESULTS: In univariate models, a standard deviation (SD) increase (1.37%) in phospholipid stearic acid (18:0) was associated with a 37% increase in the risk of stroke, whereas an SD increase (0.06%) in phospholipid omega-3 alpha-linolenic acid (18:3) was associated with a 28% decrease in the risk of stroke (all P < .05). Only alpha-linolenic acid in the cholesterol ester fraction was associated with the risk of stroke in multivariate models: an SD increase (0.13%) in the serum level of alpha-linolenic acid was associated with a 37% decrease in the risk of stroke (P < .05). Systolic blood pressure and cigarette smoking were also independently associated with stroke risk. CONCLUSIONS: Our findings suggest that higher serum levels of the essential fatty acid alpha-linolenic acid are independently associated with a lower risk of stroke in middle-aged men at high risk for cardiovascular disease.


  207. Omega-3 fatty acids in health and disease and in growth and development. Simopoulos AP. Am J Clin Nutr. 1991;54:438-463.
    Comment in: Am J Clin Nutr 1992 Mar;55(3):760-1.
    Several sources of information suggest that man evolved on a diet with a ratio of omega 6 to omega 3 fatty acids of approximately 1 whereas today this ratio is approximately 10:1 to 20-25:1, indicating that Western diets are deficient in omega 3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. Omega-3 fatty acids increase bleeding time; decrease platelet aggregation, blood viscosity, and fibrinogen; and increase erythrocyte deformability, thus decreasing the tendency to thrombus formation. In no clinical trial, including coronary artery graft surgery, has there been any evidence of increased blood loss due to ingestion of omega 3 fatty acids. Many studies show that the effects of omega 3 fatty acids on serum lipids depend on the type of patient and whether the amount of saturated fatty acids in the diet is held constant. In patients with hyperlipidemia, omega 3 fatty acids decrease low-density-lipoprotein (LDL) cholesterol if the saturated fatty acid content is decreased, otherwise there is a slight increase, but at high doses (32 g) they lower LDL cholesterol; furthermore, they consistently lower serum triglycerides in normal subjects and in patients with hypertriglyceridemia whereas the effect on high-density lipoprotein (HDL) varies from no effect to slight increases. The discrepancies between animal and human studies most likely are due to differences between animal and human metabolism. In clinical trials eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oils along with antirheumatic drugs improve joint pain in patients with rheumatoid arthritis; have a beneficial effect in patients with ulcerative colitis; and in combination with drugs, improve the skin lesions, lower the hyperlipidemia from etretinates, and decrease the toxicity of cyclosporin in patients with psoriasis. In various animal models omega 3 fatty acids decrease the number and size of tumors and increase the time elapsed before appearance of tumors. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. Because omega 3 fatty acids are essential in growth and development throughout the life cycle, they should be included in the diets of all humans. Omega-3 and omega 6 fatty acids are not interconvertible in the human body and are important components of practically all cell membranes. Whereas cellular proteins are genetically determined, the polyunsaturated fatty acid (PUFA) composition of cell membranes is to a great extent dependent on the dietary intake.(ABSTRACT TRUNCATED AT 400 WORDS).


  208. John Rivers (1945-1989): his contribution to research on polyunsaturated fatty acids in cats. Sinclair AJ., Royal Melbourne Institute of Technology, Melbourne, Victoria, Australia. J Nutr. 1994;124:2513S-2519S.
    Paper presented at the &quotWaltham Symposium on the Nutrition of Companion Animals," September 23-25, 1993, Adelaide, South Australia.
    John Rivers was a remarkable person, with enormous courage and a very generous spirit. He made a significant and long-lasting impact on the science of nutrition, disaster relief and the lives of those with whom he worked. His contribution to the understanding of the essential fatty acid requirements and metabolism in the cat while working at the Nuffield Institute of Comparative Medicine is described in this paper, together with background information on the polyunsaturated fatty acid research undertaken in the Biochemistry Department at the Institute.


  209. Sinclair HM&lt03 Author Affiliation>. Deficiency of essential fatty acids and artherosclerosis, et cetera (letter). Lancet. 1956;381-383.
    The thesis is that the dietaries of the more highly civilised countries are becoming increasingly deficient in the essential polyethenoid fatty acids (the vitamin arachidonic acid which in presence of vitamin B6 can be formed in the body from the vitamin linoleic acid) and increasingly rich in more saturated fatty acids and unnatural fatty acids which may act as antivitamins. This disastrous change arises partly from processes of manufacture such as the hardening of fats, and partly from the use of low-extraction flour &quotimproved" with oxidising agents. Since the requirement of males for EFA is much greater than that of females, the consquences are more serious in males.


  210. The relative importance of essential fatty acids of the linoleic and linolenic families: studies with an Eskimo diet. Sinclair HM. Prog Lipid Res . 1981;20:897-899.


  211. Essentiality of n-3 polyunsaturated fatty acids. Singer P., Heckmannufer 6A, 1000 Berlin 36. Aktuelle Ernahrungsmedizin. 1989;14:293-303.
    (c) 1995 CAB International. All rts. reserv.
    So far, the essentiality of polyunsaturated fatty acids (PUFA) was mainly accepted for n-6 PUFA (linoleic and arachidonic acids), abundantly found in several vegetable oils. New data from clinical and experimental studies provide evidence that n-3 PUFA ( alpha -linolenic, eicosapentaenoic and docosahexaenoic acids) should be classified as essential. This is based mainly on the correction of deficiency symptoms and biochemical results in man. Long-chain n-3 PUFA (eicosapentaenoic and docosahexaenoic acids) seem particularly effective. Whereas the daily requirement of linoleic acid is 8 to 10 g, the requirement of n-3 PUFA is considerably lower. The estimated minimal requirement of alpha -linolenic acid is 0.3 to 0.4 g daily and that of long-chain n-3 PUFA 0.1 to 0.2 g daily. The optimal requirements are assumed to be 0.9 to 1.0 g daily of alpha -linolenic acid and 0.3 to 0.4 g daily of long-chain n-3 PUFA, respectively. Probably, at least for a short time, the requirement is higher in deficiency conditions. In a balanced diet the ratio of n-6 to n-3 PUFA should be about 10:1.


  212. N-6 and N-3 PUFA in liver lipids, thromboxane formation and bloodpressure from SHR during diets supplemented with evening primrose,sunflower seed or fish oil. Singer P, Berger I, Moritz V, Forster D, Taube C., Central Institute of Cardiovascular Research, 1115 Berlin-Buch, Germany. Prostaglandins Leukot Essent Fatty Acids. 1990;39:207-211.
    (c) 1995 CAB International. All rts. reserv.
    Spontaneously hypertensive rats (SHR) after weaning (at 4 weeks of age) were fed diets supplemented with either sunflower oil (SO), evening primrose oil (EPO), fish oil (FO) or EPO + FO (50:50%, v/v) for 22 weeks. A diet with commercially available pellets served as a control. Systolic blood pressure was significantly lower in the dietary groups receiving FO, EPO and FO + EPO, the former being most effective. In liver triacylglycerols (TG) EPO resulted in a markedly increased percentage of linoleic acid (LA; C18:2, n-6), alpha -linolenic acid ( alpha -LNA; C18:3, n-6) and especially of arachidonic acid (AA; C20:4, n-6), whereas eicosapentaenoic acid (EPA; C20:5, n-3) and docosahexaenoic acid (DHA: C22:6 n-3) were depressed to undetectable and significantly lower levels, respectively. In liver phosphatidylcholine (PC) and phosphatidylethanolamine (PE) only slight changes of LA and AA were observed. Feeding of FO led to a significant rise of EPA and DHA in liver TG, PC and PE at the expense of n-6 polyunsaturated fatty acids (PUFA), (except LA in PC and PE). With a combination EPO and FO, a significant increase of EPA and DHA, but on lower levels as compared with FO alone, was associated with a significant rise of LA, but with a slight decline of AA as compared with control rats. Nevertheless, the levels of AA in the group fed EPO + FO were still higher than in the FO-group. In the SO-group the increase of LA was even higher when compared with the EPO-group. The concomitant rise of AA in liver was, however, minor and of similar magnitude in liver PC and PE in comparison with the EPO-group. The thromboxane B2-formation in serum from SHR appeared markedly depressed during FO feeding, but was augmented during EPO- and SO-rich diet. Although the diets were not adjusted to equimolar amounts of n-6 and n-3 PUFA, the data indicate that the highest supply of the prostaglandin precursors AA and EPA can be obtained when the long-chain n-6 and n-3 PUFA, which are able to by-pass the delta-6-desaturase level, are provided.


  213. Aging and nutritional requirements of essential fatty acids. Siquel N, Schaefer EJ. Beare-Rogers J. Dietary Fat Requirements in Health and Development . Champaign, Ill: American Oil Chemists' Society; 1988:163-189.
    Literature review.


  214. The effect of iron fortification on the fatty acid composition of plasma and erythrocyte membranes in primary school children with and without iron deficiency. Smuts CM, Tichelaar HY, van Jaarsveld PJ, et al., Medical Research Council, Tygerberg, South Africa. Prostaglandins Leukot Essent Fatty Acids. 1995;52:59-67.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    An intervention study was designed to evaluate the fatty acid (FA) status of children aged 6-11 years before and after iron fortification. Iron-deficient (ID) and matched controls without ID (n = 30) were selected. All children received soup (160 ml) fortified with 20 mg iron and 100 mg vitamin C for 15 weeks on school days. Measurements before and after intervention included dietary intake, haematological and iron status and FA composition of plasma and erythrocyte membranes (EMBs). The prevalence of low plasma ferritin concentration and transferrin saturation decreased in the ID children by 40% and 56%, respectively, with intervention. Plasma FAs reflected dietary FA intake. In comparison with controls, the ID group presented with increased percentage total saturated FAs (SFAs; p = 0.0002) in their EMB phosphatidylcholine (PC) and reduced percentage total polyunsaturated FAs (PUFAs; p = 0.0037) before intervention. Lower total n-3 FAs (p = 0.0070), including eicosapentenoic acid (EPA; p = 0.0034), docosapentenoic acid (DPA; p = 0.0048) and docosahexenoic acid (DHA; p = 0.0058), were observed in the ID group. The EMB phosphatidylethanol-amine (PEA) of the ID children presented with lower percentages of alpha-linolenic acid (ALA; p = 0.0001), EPA (p = 0.0051) and DHA (p = 0.0084) compared to controls before intervention. Iron intervention was associated with an increase (p < 0.05) in the percentage of n-3 FAs in the EMB-PC and EMB-PEA of the ID group to percentages comparable to that in the control group. It appears that iron status can influence FA metabolism of specific n-3 FAs in the EMBs of young children.


  215. Flax as a source of alpha-linolenic acid. Stitt PA., Essential Nutrient Research Co., Manitowoc, WI . Nato Asi Series : Series A : Life Sciences. 1989. 389-390.
    (c) format only 1995 Knight-Ridder Info. All rts. reserv. In series analytic: Dietary omega 3 and omega 6 fatty acids: biological effects and nutritional essentiality / edited by C. Galli and A.P. Simopoulos. Proceedings of a NATO Advanced Research Workshop, June 20-23, 1988, Belgirate, Italy.


  216. Nutritional advantages of flax. Stitt PA., Essential Nutr. Res. Co., Manitowoc, Wi 54220, Usa . 34th Annual Meeting Of The American College Of Nutrition On Advances In Clinical Nutrition, Chicago, Illinois, Usa, October 8-11, 1993. Journal Of The American College Of Nutrition. 1993;12:611.


  217. Efficacy of feeding flax to humans and other animals. Stitt P. 1988 Flax Institute Conference: 1988; Fargo, North Dakota. 1988.
    Flax is nature's richest and safest source of Omega-3. Flax contains 18 to 24 percent Omega-3 compared to fish at 0 to 2%. The Omega-3 from flax is also metabolized more slowly so that a nutritional imbalance is prevented, and flax does not contain any undesiraeble fats such as cholesterol or trans fatty acids.
    We have found that by feeding flax to animals, we have been able to increase the Omega-3 content in such animal products as chicken, pork, milk, and eggs, and we have been able to increase bone strength, egg shell strength, and the strength of hooves. Flax has also been found to improve the silkiness and sheen of animals' fur. Flax has also been found to improve the quantity and quality of mother's milk and helps to reduce high blood pressure, cholesterol, and serum triglyceride levels.
    Flax seed has been used for over 5,000 years, but in the last few years it has been ignored because some people used it unwisely. Some fed it to animals at very high levels without being ground or nutritionally balanced and it caused diarrhea and a nutritional imbalance which led to death in a few cases. When one uses flax, one should use it at 10 to 20% of the diet, balanced with other essential nutrients and grind it so that the nutrients in the flax are available.
    Flax seed contains an anti-B-6 factor which must be balanced with a surplus of B-6 in the diet and it contains a small amount of cyanide, which is easily handled in an acid stomach. Flax is low in zinc, pantothenic acid, and copper, so these should also be consumed with the flax. Otherwise, no other drawbacks have been found.
    In one experiment, which was done at the University of Wisconsin, day old chicks were fed a nutritionally balanced formula that contained 20% flax seed. The animals grew at a healthy rate. Upon testing, the fat in the thigh contained 12% Omega-3 versus 1% for control, breast meat contained 11% versus 2.3% for control and the liver contained 13% versus 3% for control. Fatty acid analysis was done at the University of Minnesota. See table 1. Bone breaking experiment on the ulna showed 29.7 pounds for the flax fed chickens versus 23.8 for the control. The controls were also much more brittle.
    Ground fortified flax seed was given to horses. In three weeks the coats developed a beautiful sheen and dandruff was greatly diminished. In 9 months, the cracked hooves were completely healed. A pregnant mare was fed flax and out of seven colts with the same stallion on her, this colt was the largest, had the best conformation and grew the fastest. At 30 days of age she was 49" tall and her hair was very silky.
    Mink and fox were also fed the normal diet with 10% fortified flax (dry weight basis) added. The mink and fox ate their food better when it contained flax; they grew faster and their coats were shinier.
    Another experiment was doen with chickens to seek to maximize growth rate with flax in the diet. The protein level was raised to 21%, vitamin levels were raised, and extra methionine was added to the diet. In 21 days, the fortified flax-fed chickens weighed 680 grams, the control diet fed chickens weighed 360 grams. This showed that fortification of the flax with zinc, B-6, copper, and pantothenic acid is very important and that flax can boost the growth rate.
    Nursing mothers were also fed the fortified flax and bread and cookies that contained flax. After 4 weeks, the Omega-3 content of the milk increased 55% and their milk flow also increased. The mothers noted their skin was softer and the babies were more content.
    Four men who had high blood pressure were given the flax at a rate of 45 grams per day. The average blood pressure decreased 16% in six weeks. There were no other changes in the diet.
    A double blind crossover diet study was done with free living individuals who had elevated triglycerides. Neither the doctor or patient knew if they were consuming Omega-3 or not. The individuals were under the supervision of Dr. Thelma Newby at the Milwaukee Wellness Clinic during the study. Several months before entering the study, most of the individuals had been counselled to limit their intake of fatty foods and to increase consumption of fruits, vegetables, and whole grain breads. Diets were not changed during the three weeks of this study.
    After three weeks on Fortified Flax, the subjects were given sunflower seeds for three weeks as a natural source of polyunsaturated fat in place of flax. Sunflower seeds were used because they contain about the same amount of total fat. Sunflower fat contains a different essentail fatty acid, linoleic, which has Omega-6 activity, but it contains virtually no linolenic acid content or Omega-3 activity.
    The results are shown on Table II.
    The results show a 49.8% drop after taking Fortified Flax for three weeks in subjects with above normal (153 mg/dl) serum triglyceride levels. It shows a 16% increase in three weeks after the subjects went off the flax and were on a high polyunsaturated (sunflower seed) diet. This demonstrated that Fortified Flax may be effective at reducing triglyceride levels better than a normal low fat diet and even better than a polyunsaturated fat diet, without the use of medication. However, these are preliminary results. The study should be repeated in a setting with more patients and with better control of the overall diet.
    The foregoing examples demonstrate that flax is safe, highly beneficial, and deserve further study. While not a cure-all, flax had demonstrated it's effectiveness at improving general health.
    Table I
    Omega-3 Content of Chicken
    Thigh Meat(note 1)
    18.3 (note 2) 20.5(note 3) 22.6 (note 4) Control .89 0 0

    Flax seed 11.35 .44 .36
    fed chickens

    Percentage increase 1270%
    Average increase in Omega-3 1305%

    Breast Meat
    18.3 20.5 22.6
    Control .98 .38 1.00

    Flax seed 8.95 1.33 1.07
    fed chickens

    Percentage 910% 350% 7%

    Average increase in Omega-3 501%

    10.3 20.5 22.5
    Control .61 .44 1.83

    Flax seed 4.16 3.85 4.97
    fed chickens

    Percentage 680% 875% 271%

    Average increase in Omega-3 450%

    note 1: results are expressed as percent by weight of total fat.
    note 2: 18.3=alpha linolenic acid
    note 3: 20.5=ecosopentenoic acid
    note 4: 22.6=docusohexenoic acid

    Table II
    Serum triglyceride level of 10 patients after consuming flax or sunflower for 3 weeks

    Serium Triglyceride levels (normal is 25 to 153 mg/dl)

    Patient number Before flax After 3 wks After sunflower for 3 wks
    1 1443 129 no data
    2 372 168 120
    3 446 211 322
    4 238 194 136
    5 196 97 264
    6 166 250 209
    7 468 440 430
    8 461 42 78
    9 1119 930 790
    10 160 81 no data

    avg. 507 254 293
    49.8% drop 16% increase.


  218. Flax: the wonder food. Stitt PA. 15th Annual Proceedings of the Flax Growers of Western Canada: February 4, 1989; Regina, Sask.
    Flaxseed was first used by humans during the Stone Age. We know it was used as a food source because archeologists have found evidence of flax seeds in posts made during the Stone Age. Flaxseed was also used as food during the Iron Age. There was a group of people from that time we refer to as the Bog People, because of their custom of burying their dead in bogs. The tannic acid in these bogs preserved the bodies perfectly, down to the contents of their stomaches. Archeologists have found that some of the Bog People made flaxseed part of their final meal. Coming into the historical era, evidence has been found that the original Olympic runners were vegetarians, and used a lot of flaxseed in their diets. It was used in bread in Israel, and its oil was used in cooking. Some cultures still use a lot of flaxseed. It is currently used in breads in parts of Germany, Greece and Italy.


  219. Stitt PA. 1988.
    The major nutritional discovery of the 1980's, the importance of essential fatty acids, was started in 1929 in the research laboratories at the University of Minnesota by Burr and Burr.

    Doctors Burr discovered the importance of Vitamin E in animal nutrition and they later discovered it to be very important in humans, too. Later they discovered the importance of Omega-6, an essential fatty acid (a close relative of Omega-3). From there, the thread of discovery of the importance of Omega-3 dispersed worldwide with many particpants. H.O. Bang at the Dept. of Clinical Chemistry in Alborg, Denmark, found that Eskimos in Greenland on high fat diets had only three cases of heart trouble in four years among 2,400 people. Two of the cases were over 78 years old, the other had rheumatic fever. They did not find a single case of diabetes. This was at the height of public perception that all fats were bad and, especially, cholesterol. Sinclair also noticed that Eskimos were consuming large amounts of cholesterol in a diet that was 60% fat. To prove that a high fat diet was safe, Sinclair put himself on the Eskimo's fat diet. He noticed striking changes in his body. First of all, he lost weight (gulp!), his blood became so thin that it took a long time to clot, his energy level increased and he experienced more vitality than ever! Totally unexpected results- at least according to the dogma prevelant in the US during the 1970's.

    Further studies showed that when the Eskimos in Greenland moved to Denmark and adopted Danish food, they experienced a much higher heart attack rate, even though the fat content of the diet decreased. Further studies showed that it wasn't the quantity of fat in the diet that was doing the harm, but the quality. Scientists discovered that if the diet contained reasonable levels of Omega-3, heart attack rates would decrease; but if Omega-3 was scarce, heart attack rates would increase. He concludes &quotthat a relative deficiency of essential fatty acids is common on western diets and that it plays an important part in the causation of atherosclerosis, diabetes, hypertension, and certain forms of malignant diseases." B.R. Culp did work with electric shock induced heart attacks in dogs, and found that Omega-3 would reduce heart attacks by 80% and reduce the size of clots by 75%. W.S. Harris, at Oregon Health Sciences University, discovered that taking 10 grams of Omega-3 per day would reduce serum triglycerides by 61% in three days, and has shown that the Omega-3 level in mother's milk can be increased ten fold within five days by consuming 20 grams flax seed oil per day. Dr. Neuringer has shown that a deficiency of Omega-3 leads to poor vision in monkeys due to poor development of the vitreous humour in the eye.

    Dr. Crawford has shown that if baby's formula is deficient in Omega-3 on top of the mother's diet being deficient (teenage mothers?), this can lead to poor mental development, poor vision, dry, scaly skin that is deep red and highly inflamed. They also found that just rubbing the Omega-3 oil on the skin would correct the problem faster than consuming it through the stomach. Nowadays, baby formula is fortified with Omega-3. Unfortunately, this was discovered after millions of babies had been fed formula or worse, cows milk, both of which were very deficient in Omega-3. The Nobel prize in medicine, awarded in 1982 to Dr. J.R. Vane, had to do with the metabolism of Omega-3 and how it helped prevent heart problems.

    Dr. Holman at the University of Minnesota, found that an Omega-3 deficiency in a patient on total parenteral nutrition led to seizures, sepsis (a reaction to bacteria) cheilosis (dry, cracking skin), and dermatitis (inflamation of the skin). The patient was also weak and lethargic. By adding to the diet 5 grams of Omega-6 plus 1 gram of Omega-3 for two months she was discharged improved. Then they removed the Omega-3 from the diet and in 5 months, she was again experiencing numbness, weakness, vague pains and visual blurring. Over the following 12 weeks with Omega-3 added to the diet, she experienced gradual and complete resolution of her symptons. Dr. Holman has published over 300 scientific papers in the last 30 years dealing with the importance and metabolism of essential fatty acids-Omega-3 and Omega-6.

    Dr. M.S. Lamptey has noted that differences in physical activity and ability to learn have been related to the low content of Omega-3 in the diet of test animals.

    Mechanism of Action

    Dr. Needleman found that the ways in which Omega-3 prevent heart trouble is very complex. His findings were published in the proceedings of the National Academy of Science. So far, they have found that it prevents agglutination of the platelets. This mechanism is being actively researched at the present time. Dr. Patricia Johnston, at the University of Illinois, has found that Omega-3 is transformed into a cellular hormone called PGI-3 that acts in some way to keep the platelets from sticking to each other and causing clots. Dr. Johnston published many papers every year on the metabolism of essential fatty acids.

    The advantages of consuming Omega-3 are not limited to its effect on just the heart and circulation system. It also has many profound effects on the immune system.

    Omega-3 and the Immune System

    Cell walls, the vitreous humour of the eye, and brain cells, are mostly fat. Fat is used as an insulating material to keep the electrical impulses of nerves separate so that they don't &quotshort" out and the fat in cell walls are used to control the inward and outward migration of water molecules of the cell and thus the water soluble nutrients.

    The quality of the fat in such application is all important. If the fat molecules are not perfectly aligned, miscroscopic pin holes will develop that will allow migration of undigested food particles directly into the blood stream and will allow shorting out of electrical impulses around nerves. Unfortunately, the body will use any fats for building cells. If insufficient Omega-3 is present, it will use Omega-6 fatty acids. If they're insufficient, it'll use hydrogenated or saturated fats. The result will be imperfect membranes and sheathes around the nerves. These defects can result in a wide variety of diseases according to Dr. Donald Rudin.

    One result would be allergic reactions to any number of foods because the undigested food particles go directly into the blood stream.

    Another would be almost any neurological problem such as schizophrenia, paranoia, depression, numbness, parethesia, and even inability to walk. The medical profession is just beginning to see this connection and hopefully in the future they will use the proper nutrient in the right place to correct such problems rather than throwing a drug into the system that acts in a totally different way. Dr. Rudin has deeply researched this area and he has published volumes on this problem. Hopefully, his new book (soon to be out) will catch the ear of a good many lay people as well as professionals.

    The ability of Omega-3 to influence the course of an immune reaction goes even deeper, because Omega-3 is converted by the body into a myriad of shortlived cellular hormones called prostaglandins, that influence immune antibody production. Even though some of these hormones exist for only five seconds in the body, their effect is tremendous. The hormones are generated within each and every cell and are used within that cell to control the direction of its intracellular activities. Prostaglandins control the activity of thousands of enzymes, that also utilize B-vitamins, in each cell to produce thousands of products. Oh! if only we could see and understand the many mysterious ways in which these things happen, we would never abuse our bodies in any way ever again.

    Sources of Omega-3

    What's happened in the last 100 years to the supply of Omega-3 in the American diet? A lot! The common sources of Omega-3 were the fats in whole grains, green leafy vegetables, and nuts and seeds grown in northern climates. What's happened to whole grains, vegetables, nuts and seeds? I think you know. During the 1900's, it became old-fashioned to eat such foods. The &quotin" foods became overly processed, &quotrefined" foods, white bread, salty puffed snacks, skinned potatoes, sugary drinks, milk and red meat. Only nerds ate vegetables and brown bread. Fats, as in nuts and seeds became &quotfattening", but the fats in french fries and potato chips were &quotfun foods" because they were &quotconvenient".

    To add insult to injury, after the processors removed as much Omega-3 from the foods as possible (because they cause foods to become rancid quickly), they then destroyed the slight traces of Omega-3 remaining. Perhaps not intentionally, but that is what happened. The processors called it &quothydrogenation." The end product was a shortening or oleo-margerine (depending if yellow color was added). The end result is that the average American gets less than 1 gram per day of Omega-3 and the consensus of opinion is that one needs 3 to 8 grams per day. According to Dr. Farris, the process of hydrogenation produced high levels of trans fatty acids and saturated fats. Dr. Hill and Dr. holman discovered that trans fatty acids intensifies essential fatty acid deficiencies and produces &quotweird" prostaglandins. This is another good reason to avoid all margarines and shortenings. What to use in cooking? An article recently in the New England Journal of Medicine recommends olive oil and peanut oil because they are mono-unsaturated.

    Fish oils can certainly help individuals with heart problems, but it's rather difficult to apply this to the whole American culture. One problem is the supply of fish oils or fatty fish like mackerel, salmon, and sardines and the other is the taste of fish oils. Also fish oils generally contain only 10% Omega-3. The other 90% represents large amounts of unneeded calories. Other sources of Omega-3 are dark green, leafy vegetables. These are good sources if one consumes large dark green salads every day but the concentration of Omega-3 is low. Another good source is walnuts, but the total nationwide supply is inadequate. Sea vegetables are an excellent source, but few people in the U.S. and Canada eat many sea vegetables.

    Another excellent source of essential fatty acids is flax seed - LINUM USITATISSIMUM. The oil in flax contains about 55% Omega-3. The body can easily metabolize the type of Omega-3 found in flax into the same type found in fish oil by elongation. Flax is also a good source of Omega-6, the other essential fatty acid, and of vegetable protein and soluble fiber which is good for humans to consume.

    The flavor of flax is highly desirable. It &quotfits" right into people's taste preferences and can easily be used in baked goods, cereals, soups, and blended juices.

    There are a couple of draw backs to the use of flax in the diet. First, it contains an anti-B-6 factor, which draws B-6 away from other foods. Secondly, it requires zinc to be metabolized. According to Klostermann, the first problem can be overcome by using 100 PPM B-6 in ground flax seed. The second problem, zinc, can be overcome by being sure that each person that uses flax consumes at least 15 mg per day of zinc in a highly usable form. This is another example of how nutrients must be consumed &quotin balance" with one another to be most effective.

    How Much to Take?

    One heaping tablespoon of whole or ground flax contains about four grms of Omega-3. For one with a long term deficiency of Omega-3, probably three heaping tablespoons a day would be sufficient. After the deficiency is satisified, probably three grams (rounded tablespoon) a day is enough.

    Side Benefits

    One will usually notice several side benefits. One is that bowel movements will become larger and more often, but NO diarrhea has been observed. Another is that the skin will become softer and more sensitive. At higher dosages, chapped lips and dry skin will disappear in three days and blood triglyceride levels will drop to normal in a few weeks. However, whenever consumption drops below the minimum daily requirement, the dry skin and chapped lips and higher triglyceride levels will return. Dozens of other subtle changes happen that are too numerous to mention - like improved whole body sensitivity!

    World Wide Implications

    American farmers can easily grown enough flax to satisfy the need for Omega-3. As a matter of fact, growing more flax could keep many farmers in business. Flax is the only crop in America that isnot presently available in great surplus. This may provide a needed alternative to help solve the farm crisis occuring in the United States today.


  220. Stitt PA, inventor; Stable Nutritive and Therapeutic Flax Seed Compositions, Methods of Preparing the Same, and Therapeutic Methods Employing the Same. USA 4,857,326. 1989 Aug 15.
    A method for producing a stable dry composition of flax seed comprising grinding the flax seed in the presence of vitamin B-6 and zinc ion at a temperature of about 160 degrees F. to just above freezing. A stable dry composition of flax seed producted by the aforementioned method. A method for producing a stable emulsion or suspension of flax seed comprising: (1) grinding the flax seed in the presence of vitamin B-6 and zinc ion at a temperature of about 160 degrees F. to just above freezing; (2) soaking the flax seed in an aqueous solution for about 10 minutes to overnight at a temperature of about 160 degrees F. to just above freezing; and (3) blending or homogenizing said soaked, ground flax seed, with or without further additives, to form a stable emulsion or suspension; provided that the steps (1) and (2) can be conducted in any order. A stable emulsion or suspension of flax seed. A method of lowering serum triglycerides and/or cholesterol comprising administering a therapeutically effective amount of the stable emulsion or suspension of flax seed. A method of treating the symptoms of psoriasis comprising administering topically to an affected area the stable emulsion or suspension of flax seed.


  221. Stitt PA, inventor; Therapeutic and Nutritive Flax Seed Composition and Methods Employing the Same. USA 5,069,903. 1993 Dec 3.
    A stable dry edible flax seed composition comprising ground raw flax seed. An animal feed blend comprising (1) animal feed, and (2) the above-described flax seed composition. A method for improving the general health and appearance of animals, increasing Omega-3 content of animal tissue and decreasing the cholesterol content of animal tissue comprising adnimistering orally to a subject a biologically effective amount of the above-described flax seed and composition. A method for improving the general health and appearance of human beings and Omega-3 content of human being tissue comprising adminisstering orally to a human being a biologically effective amount of the above-described flax seed composition. A method for producing the above described stable dry edible flax seed composition comprising grinding raw flax seed at a temperature of from about 160 degrees F. to just above freezing. The flax seed composition can additionally comprise zinc and/or vitamin B-6.


  222. Essential fatty acids. Sugano M, Ikeda I., Lab. Nutrition Chem., Kyusyu Univ. Sch. Agric., 6-10-1 Hakozaki, Higashi-Ku, Fukuoka-Shi 812. J Jpn Oil Chem Soc. 1991;40:831-837.
    Essential fatty acids (EFAs) are linoleic acid (18: 2n-6) and .alpha.-linolenic (18: 3n-3) acid, and a series of polyunsaturated fatty acids (PUFAs) derived from them. The desaturation-elongation products appear to have more potent functions than the parent molecules. Since minimum requirement of EFAs is 1 .apprx. 1.2% of energy intake as linoleic acid and 0.4% as .alpha.-linolenic acid, the EFA deficiency rarely happens insofar as we eat regular meals. The main functions of EPAs include structural constituents of the membranes, precursors of eicosanoids and a barrier of skin permeability. When considering the physiological effects, intake of EFAs should be far more than the minimum requirement. EFAs appreciably relate to the development of various degenerative diseases such as atherosclerosis, immune dysfunction and carcinogenesis. The amount and the balance of dietary n-6 and N-3 PUFAs are indeed important to prevent and improve these diseases. Desaturation of linoleic and .alpha.-linolenic acids are regulated ingeniously and influenced by a number of factors. In addition, there is a strong interference in the metabolism between n-6 and n-3 PUFAs. Although enormous efforts have been paid to acknowledge the optimum balance and composition of dietary n-6 and n-3 PUFAs, many questions still remain to be solved.


  223. Relationship between dietary supply of long-chain fatty acids and membrane composition of long- and very long chain essential fatty acids in developing rat photoreceptors. Suh M, Wierzbicki AA, Lien E, Clandinin MT., University of Alberta, Edmonton, Canada. Lipids. 1996;31:61-64.
    Paper presented at the symposium &quotDietary Fat and Neural Development," May 7-11, 1995, San Antonio, Texas.
    The present study was designed to determine if dietary supply of long-chain fatty acid (LCFA, C20:4n-6, and/or C22:6n-3) , reflecting levels that might be incorporated into infant formulas, influences the fatty acid composition of the visual cell membrane. The rod outer segment (ROS) of the retina was analyzed from rats fed diets varying in the ratio of 18:2n-6 to 18:3n-3 with or without 20:4n-6 [arachidonic acid (AA)] and 226n-3 (docosahexaenoic acid) from birth to six weeks of age. This study suggests that dietary fat containing small amounts of AA or DHA is an important factor influencing membrane fatty acid composition of the visual cell during development.


  224. Dietary levels of methyl laurate and essential fatty acid requirement of rainbow trout.|. Takeuchi T, Watanabe T., (Lab.Fish Nutr., Tokyo Univ.Fish., Konan 4, Minato-ku, Tokyo, Japan) . Bull Jap Soc Sci Fish. 1977;43:893-898.
    (c) 1995 Cambridge Sci Abs. All rts. reserv.
    The present study was conducted to investigate whether in trout (Salmo gairdneri) there is an increased requirement for dietary methyl linolenate as the lipid levels in the diet are increased. Feeding a diet containing 1% linolenate with 4% laurate resulted in a good growth rate, while the same diet containing 1% linolenate with 9% or 14% laurate resulted in reduced growth. With such elevated lipid levels, more than 2% linolenate was required for maximum growth. This result indicates that the elevated dietary laurate levels increase the requirement of rainbow trout for linolenate. On the other hand, dietary laurate levels exerted no significant effects on fatty acid composition, while there were marked changes in fatty acid distribution attributable to the presence of increasing levels of linolenate in the diet. The linolenate-free diet produced high percentage of 16:1, 18:1 and, and these levels were lowered by the addition of 1% linolenate, regardless of the amounts of laurate in the diets. Consequently, the EFA index,, showed low values even in the low-growth groups receiving diets containing 1% linolenate along with 9% or 14% laurate. This suggests that it is impossible to judge from the EFA index whether or not fish are receiving a sufficient amount of EFA to maximize growth. The requirement of rainbow troutfor linolenate and .omega.3-HUFA can be postulated to be around 20% and 10% of the dietary lipids, respectively.


  225. Presence of an essential polyunsaturated fatty acid in intradigestive bacterial symbionts of a deposit-feeder echinoid (Echinodermata). Temara A, De Ridder C, Kaisin M. Comp. Biochem. Physiol., B: Comp. Biochem., V100B, N3, P503-5. 1991.
    (c) 1996 American Chemical Society. All rts. reserv.


  226. The significance of n-3 fatty acids. Tichelaar HY. SA J. Food Sci Nutr. 1993;5:67-73.
    (c) 1996 American Chemical Society. All rts. reserv.


  227. Dietary requirements and functions of alpha-linolenic acid in animals. Tinoco J. Prog Lipid Res. 1982;21:1-45.


  228. Effects of linolenic acid deficiency on the fatty acid patterns in plasma and liver cholesteryl esters, triglycerides and phospholipids in female rats. Tinoco J, Endemann G, Hincenbergs I, Medwadowski B, Miljanich P, Williams MA. J Nutr. 1980;110:1497-1505.
    These experiments were performed to measure the effects of linolenate deficiency upon neutral lipids of plasma and liver, and to search for a metabolic interaction between dietary choline and linolenic acid. Rats were fed for two generations on a linolenic acid-deficient diet containing methyl linoleate as the only source of lipid. Control rats were supplemented with methyl linolenate. Second-generation linolenate-deficient rats and control rats were fed low-methionine, choline-deficient diets for 2 weeks. Half the animals in each group were given choline-supplemented diets. Plasma and liver total cholesterol, esterified cholesterol, triglyceride and major phospholipid classes, and the fatty acids of these classes were measured. Linolenic acid deficiency reduced the concentrations of plasma triglycerides in both choline-deficient and choline-supplemented rats. Evidence for a metabolic interaction between choline and linolenic acid was not obtained because the rats responded very weakly to the choline deficiency. Linolenate deficiency reduced the proportions of n-3 fatty acids, particularly 22:6n-3, in all the lipids analyzed.


  229. Metabolic transformation of intracranially injected (1-14C)linoleic and(1-14C) alpha -linolenic acids in malnourished developing rats. Tomas MEd, Mercuri O, Serres C., Instituto de Investigaciones Bioquimicas de la Plata (INIBIOLP), Facultad de Ciencias Medicas, (1900) La Plata, Argentina. Lipids. 1991;26:891-894.
    (c) 1995 CAB International. All rts. reserv.
    Th effect of a low protein diet during pregnancy and lactation on the fatty acid composition of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) from brains of 10-day-old rats was studied. The results indicated that partial deprivation of protein during early development was associated with an increase in the fatty acids of the n-9 family in PC. The fatty acids of the linoleic acid series decreased in PE, but were not modified in PC. These minor changes did not affect the double bond index values either in PC or in PE. The effect of protein depletion on the in vivo metabolic transformation of intracranially injected (1-14C)linoleic and (1-14C) alpha -linolenic acids was also studied. The percentage distribution of the labelled precursors and their derivatives among PC and PE differed from that of the mass distribution. These results indicate that the direct uptake of polyunsaturated fatty acids from the blood and/or the low turnover rate of these acids incorporated into PC and PE might be involved in maintaining the fatty acid pattern of these brain lipids.


  230. A study of the mortality rate caused by a neurotoxicant, after a single dose IP injection, among a rat population on a linolenic acid deficient diet. Topsy K. Microbiologie, Hygiene Alimentaire. 1995;7:34-40.
    (c) 1995 INIST/CNRS. All rts. reserv.
    Les experiences entreprises sur les rats sous l'effet d'un neurotoxique et soumis respectivement au regime (i) huile de tournesol (ii) huile de soja et (iii) un melange huile de soja + huile de colza ont demontre differents degres de resistance contre les effets du toxique: minimal dans le cas huile de tournesol et maximal dans le cas du melange huile de soja + huile de colza. Ces differents degres de resistance ont ete mesures en termes de niveaux d'actetylcholineste rase sanguine et l'incidence de mortalite dans le temps parmi les differentes populations de rats (issue fatale au-dessous de 10% normal et survie au-dessus de 40% normal). Les roles differents et quantitatifs des familles n-3 et n-6 d'acides gras dans l'architecture des membranes cellulaires et leur integration dans ces structures sont demontres par et s dans une formule 6x2 SUP n SUP - SUP 1 et un graphique en se basant sur des donnees emanant des travaux de recherches (annexes 1 a 5).


  231. Importance of fats and oils for child growth and development. Uauy-Dagach R, Olivares S., Inst. de Nutr. y Tec. de los Alimentos, Univ. de Chile, Santiago, Chile . Food, Nutrition and Agriculture. 1994;11:7-14.
    (c) 1996 FSTA & VITIS IFIS Publishing. All rts. reserv. 31 ref.
    The importance of fats and oils for child growth and development is discussed. Aspects considered include: structural functions of fats and oils during early infancy (fatty acid and cholesterol components of cell membranes, and fat composition of the central nervous system and the retina); the role of essential fatty acids acquired through nutrition; fat composition of human milk (n-6 and n-3 fatty acids); effects of n-3 ALPHA-linolenic acid and docosahexaenoic acid on growth and brain development; and the relationship between fat consumption and income level in developing countries. SBI.


  232. Essential fatty acid requirements for normal eye and brain development. Uauy R, Hoffman DR., University of Texas Southwestern Medical Center, Department of Pediatrics, Dallas 75235-9063. Semin Perinatol. 1991;15:449-455.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.


  233. Safety and efficacy of omega-3 fatty acids in the nutrition of very low birth weight infants: soy oil and marine oil supplementation of formula. Uauy R, Hoffman DR, Birch EE, Birch DG, Jameson DM, Tyson J. J Pediatr. 1994;124:612-620.
    Includes references.
    Because formula-fed preterm infants may be at risk of omega 3 essential fatty acid deficiency, we tested experimental formulas supplemented with soy oil to provide alpha-linolenic acid or marine oil to provide preformed omega 3 long-chain polyunsaturated fatty acids at a level comparable to that of human milk. This report addresses the effect of feeding formula supplemented with soy oil or with soy and marine oils on growth, clinical tolerance, coagulation test results, changes in erythrocyte membrane fluidity, and plasma concentrations of vitamins A and E in very low birth weight infants from 30 to 57 weeks of postconceptional age. &quotHealthy" preterm infants were maternally selected to receive human milk or selected of random to receive commercial ready-to-feed liquid formula, which provided limited omega 3 fatty acid, or experimental formulas supplemented with soy oil or soy and marine oils. Results of this study indicate that formula enriched with soy oil or soy and marine oils containing preformed omega 3 long-chain polyunsaturated fatty acids does not induce abnormalities in growth, clotting function, erythrocyte membrane fluidity, or vitamin A or E levels in healthy very low birth weight preterm infants. Additional studies to evaluate safety in a representative preterm population are required.


  234. Role of essential fatty acids in the function of the developing nervous system. Uauy R, Peirano P, Hoffman D, Mena P, Birch D, Birch E. Lipids. 1996:31 Suppl:S167-76.
    The basis for n-3 fatty acid essentially in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by alpha-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.


  235. The essential fatty acid status of pregnant women froma community with low socio-economic status. van Jaarsveld PJ. Med Sci Res. 1994;22:719-721.
    Diets with a high n-6/n-3 fatty acid (FA) ration can be considered imbalanced and may adversely affect the long-chain polyunsaturated fatty acid (PUFA) composition of the developing central nervous system of the fetus [1]. A high dietary intake of linoleic acid (LA; C18:2n-6) has been show to impair the conversion of LA and alpha-linolenic acid (ALA; C18:3n-3) to their respective long-chain C20 and C22 metabolites [2]. The fetus requires considerable amounts of these preformed long-chain PUFAs as structural components for neural tissues. Since its potential for long-chain PUFA synthesis is limited [3], it is mainly dependent on the mother for its supply of long-chain PUFAs.
    Other factors canalso affect long-chain FA synthesis in pregnant women, viz nutritional status [4-6], smoking [7,8], alcohol consumption [6] and diet [9]. These are, however, also well-established risk factors for delivering low birth weight infants.
    The aim of this study was therefore to determine the essential FA (EFA) status of pregnant women in their third trimester and the relationship thereof, if any, to the birth weight of their infants.


  236. Essential fatty acids: the effects of dietary supplementation among children with recurrent respiratory infections. Venuta A, Spano C, Laudizi L, Bettelli F, Beverelli A, Turchetto E. J Int Med Res. 1996;24:325-330.
    The impact of dietary supplementation with essential fatty acids (EFA) on recurrent respiratory infections (RRI) in children was evaluated by means of a randomized cross-over double-blind study. Linoleic acid (596 mg/day) and alpha-linolenic acid [855 mg/day] as a commercial preparation or placebo (olive oil) were administered for two consecutive winter seasons (November to February, T0-T120) to 20 children affected by RRI, aged between 36 and 49 months. Plasma levels of n-3 and n-6 metabolites increased after the administration of EFA. The number of infective episodes, days' fever and days' absence from school were reduced significantly during the observation period (extended from T120 to T180) in children receiving EFA supplementation. Our results suggest that n-3 and n-6 polyunsaturated fatty acids may play a favourable role in the defence mechanism of these subjects.


  237. On the role of cell membrane lipids in cold hardening of winter wheatleaves and crowns. Vereshchagin AG, Trunova TI, Shayakhmetova IS, Tsydendambaev VD., V.D. Tsydendambaev, Institute of Plant Physiology, Academy of Sciences, Moscow, USSR. Plant Physiology and Biochemistry (Paris). 1990;28:623-630.
    (c) 1995 CAB International. All rts. reserv.
    At crown formation, 10-d-old wheat cv. Mironovskaya plants were cold hardened for 10 d at 2 deg C and or immersed in water or 10% sucrose solution and kept in light (10 W/m2) or darkness at 2 deg . Frost hardiness was determined by direct freezing of leaves and whole plants. In sand/soil mixtures, cold hardening of leaves and crowns was always accompanied by an increase in DM concn and by the accumulation of palmitic, linoleic and linolenic acids predominantly and of C20:2, C22:0 and C22:1 (ratio of number of carbon atoms and double bonds in a fatty acid chain) fatty acid residues (by ca. 30%) in the nonextractable fraction of leaf lipids and a sharp increase in linolenate-enriched lipids. De novo formation of these substances took place both in the light and the dark. Cold acclimatization in water culture also led to the development of frost resistance of leaves while cold hardening of the crowns took place when the plants were raised on sucrose solution and in water culture. Absolute lipid content was 3- to 5- fold lower in the crowns than in the leaves. These changes were not observed in non-hardened plants. It was concluded that the membrane hypothesis of cryoadaptation should be considered as an essential component of the hardening metabolism.


  238. Do essential fatty acids play a role in brain and behavioral development? Wainwright PE. Neurosci Biobehav Rev. 1992;16:193-205.
    The membrane phospholipids of the brain contain high levels of polyunsaturated fatty acids (PUFA), particularly arachidonic acid, 20:4n-6 and docosahexaenoic acid, 22:6n-3. These long-chain PUFA are synthesized from their respective essential fatty acid (EFA) precursors, linoleic acid, 18:2n-6 and linolenic acid, 18:3n-3. Although the necessity of n-6 fatty acids for optimum growth has been established, a similar requirement for those of the n-3 family is less clear. The rapid accumulation of the long-chain n-3 PUFA in the brain during prenatal and preweaning development suggests that the provision of n-3 fatty acids to the developing brain may be necessary for normal growth and functional development. The intent of this review is to assess the experimental work which addresses this question, most of which has been conducted on rodents. The emphasis will be on studies which measure behavioral outcomes, and particular attention will be paid to methodological issues which affect the interpretation of these data. An integration of the research findings will be presented and discussed in light of possible implications for therapeutic interventions.


  239. The role of n-3 essential fatty acids in brain and behavioral development: a cross-fostering study in the mouse. Wainwright PE, Huang YS, Bulman-Fleming B, Mills DE, Redden P, McCutcheon D. Lipids. 1991;26:37-45.
    A cross-fostering design was used to examine the effects on brain and behavioral development in mice of pre- and/or postnatal dietary supplementation with n-3 fatty acids. Pregnant mice were fed either of two liquid diets, control (con) or experimental (exp). Each diet provided 3% of the calories in the form of n-6 fatty acids; the experimental diet was supplemented with an additional 1.5% from long chain n-3 fatty acids derived from fish oil. There were four treatment groups, with all pups fostered at birth. These groups were (prenatal diet/postnatal diet): Group 1. exp/exp; Group 2, exp/con; Group 3, con/exp; Group 4, con/con; a fifth control group (unfostered) was fed lab chow (LC) throughout the study. Animals from the exp/exp and con/con groups were weaned onto lab chow for later behavioral assessment. Prenatal n-3 supplementation resulted in a small acceleration of behavioral development. The adult animals did not differ on visual discrimination learning nor did they differ in visual acuity. During development the fatty acid composition of the brain membrane phospholipids reflected closely that of the pre- and postnatal dietary conditions. Levels of 22:5n-3 and 22:6n-3 increased in the n-3 supplemented groups, accompanied by a decrease in levels of 22:4n-6 and 22:5n-6; the net effect of these changes was to increase the total levels of C22 fatty acids. While these results support considerable plasticity of the fatty acid composition of the developing brain with respect to the immediate dietary availability of n-3 compounds, they do not support long term effects on learning capacity of n-3 supplementation during the developmental period.


  240. Regulation by dietary essential fatty acid balance of tumor necrosis factor production in mouse macrophages. Watanabe S, Onozaki K, Yamamoto S, Okuyama H., Faculty of Pharmaceutical Sciences, Nagoya City University, Japan. J Leukoc Biol. 1993;53:151-156.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Increasing the dietary alpha-linolenate (18:3n - 3)/linoleate (18:2n - 6) ratio results in an increase in lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) production in mouse resident and casein-induced peritoneal macrophages [3]. We found that prostaglandin E2 (PGE2) production is inversely related to TNF production and that indomethacin abolishes the effect of changing the essential fatty acid balance in resident macrophages. The resident macrophages enriched in n - 3 did not produce a significant amount of PGE3. Accordingly, the decreased production of PGE2 appears to be a major negative regulatory factor for enhancement of TNF production in the n - 3 enriched resident macrophages. In casein-induced macrophages the situation is more complex. Indomethacin decreased PGE2 production and increased TNF production; however, the differences in TNF production between the n - 6 enriched and n - 3 enriched macrophages were not completely abolished by indomethacin treatment. Lysosomal acid phosphatase activity, a marker of activation/maturation stages, was elevated in the n - 3 enriched compared to the n - 6 enriched casein-induced macrophages but was similar in the resident macrophages of the two dietary groups. Expression of CD14, which is a receptor for LPS, was not different in casein-induced macrophages of the two dietary groups. Thus, the differences in production of TNF between the n - 3 and n - 6 enriched resident macrophages can be accounted for mostly by a difference in the production of a negative feedback effector, PGE2. However, a significant portion of the TNF production in casein-induced macrophages is regulated by a factor(s) other than PGE2 and LPS receptor; advanced activation/maturation stages induced by the diet high in alpha-linolenate may underlie the enhanced TNF production in casein-induced macrophages.


  241. Effect of dietary alpha-linolenate/linoleate balance on collagen-induced platelet aggregation and serotonin release in rats. Watanabe S, Suzuki E, Kojima N, Kojima R, Suzuki Y, Okuyama H. Chem Pharm Bull. 1989;37:1572-1575.
    Male Sprague-Dawley rats at 3 weeks of age were weaned to a diet supplemented either with perilla seed oil [alpha-linolenic acid (alpha-LnA)/linoleic acid (LA) = 3.66] or with safflower seed oil (alpha-LnA/LA less than 0.01) for 5-6 weeks. The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio in platelet phospholipids was much higher in the perilla oil group than in the safflower oil group. Platelet aggregability determined turbidometrically varied greatly among individual animals, and the difference in platelet aggregability between the two dietary groups was relatively small when higher concentrations (15 and 20 micrograms/ml) of collagen were used. However, when platelet aggregability was determined as an all-or-none phenomenon at lower concentrations (7.5 and 10 micrograms/ml) of collagen, a very distinct difference was observed between the two dietary groups; aggregability was much lower in the perilla oil group than in the safflower oil group. Collagen-induced serotonin release from platelets was significantly reduced in the perilla oil group as compared with the safflower oil group. These results emphasize the importance of estimating aggregability at threshold concentrations of collagen and confirm that dietary manipulation of the essential fatty acid balance could be useful in reducing the thrombotic tendency.


  242. Dietary manipulation of long-chain polyunsaturated fatty acids in the retina and brain of guinea pigs. Weisinger HS, Vingrys AJ, Sinclair AJ., Department of Optometry, University of Melbourne, Parkville, Victoria, Australia. Lipids. 1995;30:471-473.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    High levels of n-6 docosapentaenoic acid (22:5n-6) have been reported in the retina of guinea pigs fed commercially-prepared gain-based rations (commercial diet). In rats and monkeys, high levels of 22:5n-6 are an indicator of n-3 polyunsaturated fatty acid (PUFA) deficiency. We have examined the fatty acid composition of the retina and brain in guinea pigs fed a commercial diet or one of three semi-purified diets containing three different levels of n-3 PUFA. The diets comprised a diet deficient in n-3 PUFA (semi-purified diet containing safflower oil), two diets containing alpha-linolenic acid (standard commercial laboratory diet and semi-purified diet containing canola oil), and a diet containing alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA) (semi-purified diet containing canola oil, safflower oil, and fish oil). Two groups of guinea pigs were given the diets from day 1 to 4 wk or day 1 to 8 wk, when they were sacrificed and the retinal tissues were extracted and analyzed for PUFA content by gas-liquid chromatography. Fatty acid analyses of the retinal phospholipids of the four-week-old animals revealed that the group fed DHA (from the fish oil) had the highest level of DHA (32%), compared with values of 19 and 13% for the groups fed canola oil diet and commercial diet, respectively, and 2% for the group fed the diet deficient in n-3 PUFA.(ABSTRACT TRUNCATED AT 250 WORDS).


  243. The effect of docosahexaenoic acid on the electroretinogram of the guinea pig. Weisinger HS, Vingrys AJ, Sinclair AJ. Lipids. 1996;31:65-70.
    Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, is found in consistently high concentrations in the retinae of mammals, yet its role in vision remains unclear. In this study, a mammalian model of variable retinal DHA concentration has been developed, such that the retinal phospholipids of guinea pigs contained between 2.5 and 30.8% DHA. Visual function was assessed using full-field flash electroretinography, over a range of exposure levels spanning six log units. Trend analysis indicated that retinal function was altered by the tissue DHA level, and was described by a second-order polynomial &quotinverted U-shaped" function. The results suggested that although some amount of DHA is essential for normal retinal function, increases in the DHA level past an optimal amount, found to be 19%, provided diminishing returns. In this study, manipulation of the retinal DHA level accounted for 21-35% of the electroretinographic variability.


  244. Went NJ, Bolt AG, Whitehouse M, inventors; Anti-Inflammatory Liniment With Linolenic Acid-Containing Oils.PCT International ; WO 9007331 A1. 1990 Jul 12.
    (c) 1996 American Chemical Society. All rts. reserv.


  245. Fatty acid metabolism in normal miniature poodles and those affected with progressive rod-cone degeneration (prcd). Wetzel MG, Fahlman C, Maude MB, et al. Prog Clin Biol Res. 1989;314:427-439.
    It is possible that a genetic defect observed in the prcd poodle involves the abnormality of an enzyme which functions in phospholipid or lipoprotein metabolism. In our studies thus far, we have been unable to detect any defect in retinal phospholipid biosynthesis, but we have noted a decrease in plasma levels of 22:6w3 which may be a result of an enzyme defect in liver biosynthesis of 22:6w3 from its dietary precursor, linolenic acid, or some defect in the blood lipoprotein transport of this essential fatty acid. If 22:6w3 is essential to the normal elaboration and functioning of the photoreceptor outer segment, it is possible that decreased access to this fatty acid due to lower blood levels of 22:6w3 could cause photoreceptor abnormalities. Further studies are needed to confirm the possible defect in delta-4 desaturase activity and possible dietary modification of the course of this prcd retinal degeneration.


  246. Metabolic labeling of rod outer segment phospholipids in miniature poodles with progressive rod-cone degeneration (prcd). Wetzel MG, Fahlman C, O'Brien PJ, Aguirre GD. Exp Eye Res. 1990;50:89-97.
    The recessive genetic defect in miniature poodles which results in progressive rod-cone degeneration (prcd) has been investigated in an attempt to determine the biochemical abnormality involved. In the present study, the rod outer segments of young prcd affected miniature poodles and normal dogs have been compared with respect to the incorporation of intravitreally injected [3H]palmitic acid. [14C]linolenic acid, and [14C]docosahexaenoic acid into neutral lipids and phospholipids as well as [3H]palmitate and [14C]leucine into rhodopsin. In addition, 3 mm trephined punches of retinas were incubated with [3H]palmitic acid, [3H]arachidonic acid, [14C]linolenic acid, [3H]serine, [14C]glycerol and [14C]leucine. No difference in incorporation of labeled precursors into lipids or rhodospin was noted between prcd affected and normal retinas. Phosphatidyl choline appeared to function as a carrier of fatty acids to the rod outer segment where they were redistributed to other phospholipids. An interesting lack of conversion of the essential fatty acid linolenic acid to docosahexaenoic acid was noted in both normal and affected retinas. This conversion involves elongation and desaturation of linolenic acid and may take place primarily in extraretinal tissues such as the liver. This finding, in conjunction with a parallel study of plasma fatty acids which has shown significantly lower levels of docosahexaenoic acid in prcd affected poodles, points to a possible systemic defect in the metabolism or transport of docosahexaenoic acid, a fatty acid uniquely enriched in the photoreceptor outer segments.


  247. Linolenic acid provides a source of docosahexaenoic acid for artificially reared rat pups. Winters BL, Yeh SM, Yeh YY., Nutrition Department, Pennsylvania State University, University Park 16802. J Nutr. 1994;124:1654-1659.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The goal of the present study was to determine the effectiveness of linolenic acid for enriching docosahexaenoic acid (DHA) in infant rats. Seven-day-old rat pups were artificially reared and fed intragastrically for 8 d a milk substitute containing either 1) corn oil, high in linoleic acid (35.6 g/100 g fatty acids, 775 kJ/L); 2) menhaden oil, high in DHA (3 g/100 g, 67 kJ/L) and eicosapentaenoic acid (EPA, 6 g/100 g, 132 kJ/L); or 3) linseed oil, rich in linolenic acid (34 g/100 g, 750 kJ/L). Growth rates were comparable among the artificially fed pups and those raised by lactating dams. Feeding the DHA precursor linolenic acid enriched EPA in plasma, erythrocytes and liver, but enriched DHA only in the liver, compared with feeding corn oil. The proportion of liver DHA in the pups fed the linolenic acid-rich substitute was twice that detected in the corn oil-fed pups and 60% of the level found in the pups fed the preformed DHA. The significant elevation of hepatic DHA indicates active desaturation and elongation in the developing rat liver. The failure to enrich erythrocyte DHA suggests the need for caution in the use of erythrocytes as an index of DHA status in tissues capable of in situ synthesis. The artificial rearing of rat pups was proven suitable for studying the interaction of dietary manipulation and tissue accretion of essential fatty acids during the postnatal development.


  248. Effect of the dietary alpha-linolenate/linoleate balance on lipid compositions and learning ability of rats. II. Discrimination process, extinction process, and glycolipid compositions. Yamamoto N, Hashimoto A, Takemoto Y, et al. J Lipid Res. 1988;29:1013-1021.
    Includes references.


  249. Distribution, processing and selective esterification of essential fatty acid metabolites in the fetal brain. Yavin E, Green P. World Rev Nutr Diet. 1994;75:134-138.


  250. Nutrients, brain biochemistry, and behavior: a possible role for the neuronal membrane. Yehuda S. Int J Neurosci. 1987;35:21-36.
    Nutrients can modify brain biochemistry and behavior. Many studies indicate that one possible mode of action of nutrients is to induce alterations in the bioavailability of neurotransmitter precursors within the brain. However, a series of studies has also indicated that: (a) learning induces a decrease in the level of cholesterol in specific brain regions; (b) an iron-deficient diet induces changes in dopaminergic D receptor activity and in dopamine-associated behaviors (thermoregulation and motor activity) as well as in learning and memory capacities; and (c) dietary manipulation of a specific type of fatty acid resulted in an improved learning capacity, modification of the pain threshold level, and in thermoregulatory response. The most parsimonious explanation for these results seems to be that the treatments (learning, iron-deficient and fatty acid diets) induced changes in the lipid composition of the neuronal membrane. Such changes, in turn, resulted in changes in the membrane functions. Supportive evidence for this hypothesis is presented in this review. The neuronal membrane functional modification hypothesis should not be considered as contradictory to the accepted brain neurotransmitte¤.


  251. Essential fatty acid preparation reduces cholesterol and fatty acids in rat cortex. Yehuda S, Brandys Y, Blumenfeld A, Mostofsky DI. Int J Neurosci. 1996;86:249-256.
    Previous studies have shown that chronic administration of SR-3 (a 1:4 mixture of alpha-linolenic and linoleic acid) affects spatial learning, thermoregulation, pain threshold, and protection from seizures. The mode of action of SR-3 is unknown. One possible explanation is that SR-3 induces changes in the FA profile and in the cholesterol level in neuronal membranes. This study used 10 independent groups of rats (ni = 12) given 4 weeks of either saline, mineral oil (vehicle), alpha-tocopherol (antioxidant), alpha-linolenic acid, linoleic acid, or one of 5 different ratios of alpha-linolenic acid:linoleic acid (1:3, 1:4, 1:5, 1:6, 1:7) as free fatty acids. FA profile and cholesterol level were examined by GC method in synaptosomes obtained from the frontal cortex of the rats. The mineral oil treated group served as the control group. No difference was found in the FA profile or cholesterol level except for the SR-3 treated group. The ratio of 1:4 was found to have a significant influence on decreasing the cholesterol level and in inducing major changes in the FA profile, such as an increase in EFA. These effects of SR-3 may result in modification of the membrane fluidity, which may, in turn, enhance cognitive and neuropharmacological effects.


  252. Essential fatty acid preparation (SR-3) raises the seizure threshold in rats. Yehuda S, Carasso RL, Mostofsky DI. Eur J Pharmacol. 1994;254:193-198.
    The anticonvulsant properties of a mixture of non-esterified alpha-linolenic acid and linoleic acid with a ratio of 1:4 (SR-3) were evaluated in four rat models of epileptic seizures: (1) i.p. injection of a single convulsant dose (50 mg/kg or 100 mg/kg) of pentylenetetrazol; (2) repeated subconvulsant doses of pentylenetetrazol; (3) cortical irritation by intraventricular administration of iron chloride (FeCl3); and (4) audiogenic seizure-prone preparation created by repeated pretreatment with p-cresol. Treatment with SR-3 (about 40 mg/kg i.p.) for a period of 3 weeks prior to challenge was found effective in each of these experimental models and caused up to a 22-fold increase in latency to major motor seizures, up to 84% reduction in the number of rats with seizures, and up to a 97% reduction in the duration of seizures. It is postulated that the anticonvulsant effects of SR-3 may be related to its stabilization of neuronal membranes. SR-3 should be evaluated further as a treatment for epilepsy.


  253. Essential fatty acid preparation (sr-3) rehabilitates learning deficits induced by af64a and 5,7-dht. Yehuda S, Carraso RL, Mostofsky DI., Psychopharmacology Lab., Dep. Psychology, Bar Iian Univ., Ramat Gan 52900, Israel . Neuroreport. 1995;6:511-515.
    The purpose of this study was to examine the possible effects of a novel mixture of fatty acids, SR-3 (a specific ratio between a-linolenic and linoleic acids) on learning deficits induced by cholinergic (AF64A) and serotonergic (5,7-DHT) neurotoxins in rats. I.c.v. AF64A and 4th ventricle administration of 5,7-DHT induce severe learning deficit using the Morris Water Tank. Three weeks of treatment with SR-3 rehabilitated the learning capacity of rats. However, learning deficits induced by a lesion in area postrema was not rehabilitated by SR-3. The mode of action of SR-3 is unknown. We propose that this combination of free fatty acids modulates the composition of neuronal membrane lipids and allows better neuronal communication.


  254. Lead-catalyzed peroxidation of essential unsaturated fatty acid. Yiin SJ, Lin TH. Biol Trace Elem Res. 1995;50:167-172.
    In the present study, the reaction mixtures (lead compounds with essential unsaturated fatty acids) were preincubated at 37 degrees C for 24 h prior to the measurement of malondialdehyde (MDA) by HPLC. The metal-catalyzed reactions were also compared in the presence of butylated hydroxytoluene (BHT), a free radical scavenger. Our results showed that according to the difference in the number of double bonds of essential unsaturated fatty acids, the kinds of lead compounds, and the concentrations of lead compounds, the extent of lipid peroxidation was different. The addition of BHT to the reaction mixtures significantly reduced the production of MDA (P < 0.01). These in vitro studies support prior in vivo reports that the important mechanism of the acute toxic effects of the lead compounds is owing at least in part, to metal-catalyzed peroxidation of polyunsaturated fatty acids.


  255. Interactive effects of dietary (n-3) polyunsaturated fatty acids and chronic ethanol intoxication on synaptic membrane lipid composition and fluidity in rats. Zerouga M, Beauge F, Niel E, Durand G, Bourre JM., INSERM U 26, Hopital Fernand Widal, Paris, France. Biochim Biophys Acta. 1991;1086:295-304.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    The influence of dietary polyunsaturated fatty acids on fatty acid composition, cholesterol and phospholipid content as well as 'fluidity' (assessed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) probes) of brain synaptic plasma membranes (SPM) and their interactions with chronic ethanol effects were studied in rats fed for two generations with diets either devoid of (n-3) fatty acids (sunflower oil diet), rich in alpha-linolenic acid (soya oil diet) or in long chain (n-3) fatty acids (sunflower + cod liver oil diet). Results were compared with rats fed standard lab chow. Sunflower oil led to an increase in the (n-6)/(n-3) ratio in the membranes with an increase of the 'fluidity' at membrane apolar level; sunflower + cod liver oil decreased the (n-6)/(n-3) ratio without affecting membrane 'fluidity' while no difference was seen between the SPM of rats fed soya oil and standard diet. After 3 weeks alcohol intoxication in rat fed the standard diet: oleic alpha-linoleic acids and cholesterol levels were increased, arachidonic acid and the double bond index/saturated fatty acids were decreased and there was a decrease of 'fluidity' in the lipid core of the SPM. Soya oil almost totally abolished these usually observed changes in the SPM fatty acids composition but increased oleic acid and cholesterol without any change in fluidity. Sunflower oil led to the same general alterations of fatty acid as seen with standard diet but to a greater extent, with decrease of the 'fluidity" at the apolar level and in the region probed by TMA-DPH. When sunflower oil was supplemented with cod liver oil, oleic and alpha-linoleic acids were increased while the 'fluidity' of the apolar core of SPM was decreased. So, the small changes in fatty acid pattern seem able to modulate neural properties i.e. the responses to a neurotoxic like ethanol. A structurally specific role of PUFA is demonstrated by the pernicious effects of the alpha-linolenic acid deficient diet which are not totally prevented by the supply of long chain (n-3) PUFA.


  256. Effect of dietary n-3 fatty acid deficiency on blood-to-brain transfer of sucrose, alpha-aminoisobutyric acid and phenylalanine in the rat. Ziylan ZY, Bernard GC, Lefauconnier JM, Durand GA, Bourre JM., Department of Physiology, Istanbul Faculty of Medicine, Turkey. Neurosci Lett. 1992;137:9-13.
    (c) format only 1996 Knight-Ridder Info. All rts. reserv.
    Possible alterations in blood-to-brain unidirectional transport of sucrose (mol. wt., 342), alpha-aminoisobutyric acid (mol. wt., 104), and L-phenylalanine (mol. wt., 165) induced by a diet deficient in n-3 polyunsaturated fatty acids were studied with respect to blood-brain barrier function. Two groups of rats were for to two generations with a semisynthetic diet. One group of rats was fed a peanut oil+rapeseed oil diet which contained both essential fatty acids: linoleic acid (18:2 n-6) and alpha-linolenic acid, (18:3 n-3). Another group was fed a diet of peanut oil, this diet (containing 18:2 n-6) was deficient in alpha-linolenic acid. The experiments were performed at 6 months of age. Unidirectional transfer rate constants (Ki) of sucrose, alpha-aminoisobutyric acid and L-phenylalanine were measured. The diet based on peanut oil (deficient in n-3) caused a greater blood-to-brain transport of sucrose but not of alpha-aminoisobutyric acid or L-phenylalanine. These observations indicate that regardless of the mechanisms involved, alterations in essential fatty acids induced by diet can modulate to some extent the blood-brain transport of hydrophilic molecules without a carrier.