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 www.flax.com.fda. 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, "People and Pet
Glow" in pet food stores and "Fortified 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Bazan NG, Murphy MG, Toffano G; Neurobiology of essential fatty acids. New York : Plenum Press; 444 p.
"Proceedings 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.
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.
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.
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.
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 "gold 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Bouziane M, Belleville J, Prost J<03 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Estimation of essential fatty acid intake in swine. Caster WO, Hill EG, Holman RT. J Animal Sc. 1963;22:389-392.
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.
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.
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<0.001) 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.
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.
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.
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.
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.
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.
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.
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.
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.
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 (>C20) 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<0.001) 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<0.05) 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.
Background to essential fatty acids and their prostanoid derivatives. Crawford MA. Br Med Bull. 1983;39:210-213.
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).
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.
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.
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.
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.
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.
A study on essential fatty acids and multiple sclerosis. Crawford MA, Stevens P. Prog Lipid Res 1981. 1981;20.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 return
