Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys.

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

Depletion of docosahexaenoic acid in retinal lipids of rats fed a linolenic acid-deficient, linoleic acid-containing diet.

Rats were raised for 2 generations on a diet in which 1.25% methyl linoleate was the only source of fat. Control rats were given 1.0% methyl linoleate plus 0.25% methyl linolenate. Lipids were extracted from retinas and their fatty acids were analyzed by gas-liquid chromatography. Docosahexaenoic acid accounted for 33.8% of total fatty acids in control retinas, for 13% of fatty acids in first-generation deficient retinas, and for 2.7% of fatty acids in second-generation deficient retinas.

Dietary alpha-linolenic acid deficiency in adult rats for 7 months does not alter brain docosahexaenoic acid content, in contrast to liver, heart and testes.

In adult rats, 22:6(n - 3) dietary deficiency does not affect brain membranes, but has a significant effect on some other visceral organs. 60-day-old male rats fed a diet containing sufficient amounts of both linoleic and alpha-linolenic acid were divided into three groups. One group continued the same diet; the second was fed a diet containing 2% sunflower oil, the third was fed 10% sunflower oil (sunflower oil contains linoleic acid, but trace amount of alpha-linolenic acid). Animals were killed different times after receiving the new diets (1 to 31 weeks). For animals fed the diets containing only sunflower oil, deficiency in cervonic acid content (DHA, docosahexaenoic acid, 22:6(n - 3)) was not detected in whole brain, myelin or nerve endings within 31 weeks. In contrast, this acid progressively declined in liver, heart and testes up to 3 weeks and remained nearly stable thereafter. In parallel to the reduction of cervonic acid content, 22:5(n - 6) content increased in liver and heart, but not in testes. It also increased in brain, nerve endings and myelin from week 3, 6 and, 9 respectively. These results suggest that brain cervonic acid is highly preserved or is maintained at the expense of other organs.

Effect of dietary alpha-linolenic acid on functional characteristic of Na+/K(+)-ATPase isoenzymes in whole brain membranes of weaned rats.

The influence of dietary fatty acids on Na+ sensitivity and ouabain affinity of Na+/K(+)-ATPase isoenzymes of whole brain membranes were studied in weaned rats fed for two generations with diets either devoid of alpha-linolenic acid (sunflower oil diet) or rich in alpha-linolenic acid (soya oil diet). The (n--3) deficiency induced by the sunflower oil diet led to an increase in the (n--6)/(n--3) molar ratio in whole brain membranes. Na+/K(+)-ATPase isoenzymes were discriminated on the basis of their differential affinities for ouabain. In rats fed sunflower oil diet, the ouabain titration displayed three inhibitory processes with markedly different affinities: low affinity (alpha 1); high affinity (alpha 2); and very high affinity (alpha 3). Membranes of rats fed soya oil diet exhibited only two inhibitory processes, i.e., low affinity (likely alpha 1+ alpha 2) and high affinity (likely alpha 2+ alpha 3) with the low affinity form intermediate between the sunflower alpha 1 and alpha 2 forms, and the high affinity form intermediate between the sunflower alpha 2 and alpha 3 forms. In fact, the Na+ response shows that the three isoenzymes have different Na+ sensitivities. Regardless of the diet, alpha 1 has a similar Na+ sensitivity (less than 1 mM), whilst alpha 2 and alpha 3 are more sensitive in soya oil membranes compared to sunflower oil membranes (5.1 vs. 7.2 mM and about 11 vs. 22.5 mM, respectively). Thus, sodium appears to be a better criterion of heterogeneity than ouabain.

A case of human linolenic acid deficiency involving neurological abnormalities.

A 6-yr-old girl who lost 300 cm of intestine was maintained by total parenteral nutrition. After 5 months on a preparation rich in linoleic acid but low in linolenic acid she experienced episodes of numbness, paresthesia, weakness, inability to walk, pain in the legs, and blurring of vision. Diagnostic analysis of fatty acids of serum lipids revealed marginal linoleate deficiency and significant deficiency of linolenate. When the regimen was changed to emulsion containing linolenic acid neurological symptoms disappeared. Analysis indicated that linoleate deficiency had worsened but linolenate deficiency had been corrected. The requirement for linolenic acid is estimated to be about 0.54% of calories.

Alpha-linolenic acid deficiency in patients on long-term gastric-tube feeding: estimation of linolenic acid and long-chain unsaturated n-3 fatty acid requirement in man.

Alpha-linolenic acid deficiency is described in four adults fed by gastric tube. In plasma and erythrocytes, total lipid 20:3n-9 was slightly increased but total n-6 fatty acids, arachidonic acid, and dihomo-gamma-linolenic acid were normal. Total n-3 fatty acids, 18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3 were decreased in both plasma and erythrocytes. Patients had a slight but definite scaly dermatitis, which disappeared with essential fatty acids supplementation. Simultaneously, levels of 18:3n-3, 20:5n-3, 22:5n-3, 22:6n-3, 20:3n-9, and total n-3 fatty acids became normal while 18:2n-6, 20:3n-6, 20:4n-6, and total n-6 acids were unchanged or slightly lowered. Estimated minimal daily requirement of linolenic acid and of long-chain unsaturated n-3 acids in adults is approximately 0.2-0.3% and 0.1-0.2%, respectively, of total energy intake. Results suggest that conversion of linolenic acid to 22:6n-3 is increased in linolenic acid deficiency.

alpha-Linolenic acid and long-chain omega-3 fatty acid supplementation in three patients with omega-3 fatty acid deficiency: effect on lymphocyte function, plasma and red cell lipids, and prostanoid formation.

alpha-Linolenic acid deficiency is described in three patients. Observed clinical symptoms were hemorrhagic dermatitis, hemorrhagic folliculitis, skin atrophy, and scaly dermatitis. Supplementation with ethyl alpha-linolenate followed by a purified fish oil (EPA-oil) began to normalize symptoms within 10 d. The mitogenic response in isolated lymphocytes was reduced whereas the number of T lymphocytes increased significantly. Serum thromboxanes, urinary excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (PGI2-M), and bleeding time were unaffected. The results indicate that omega-3 fatty acids are essential for normal accumulation of erythrocyte omega-6 acids. The dietary intake of long-chain omega-3 acids required to obtain midnormal concentrations of omega-3 acids in plasma and erythrocyte lipids was estimated to be 350-400 mg/d (0.4% of calories), whereas the corresponding mean intake of alpha-linolenic acid was 990 mg/d (1.0% of calories). It is suggested that essential fatty acid requirement should be stated as grams or milligrams per day, similarly to other essential nutrients.

Effect of age and alpha-linolenic acid deficiency on delta 6 desaturase activity and liver lipids in rats.

The combined effects of age and of diet deficient in n-3 fatty acids on delta 6 desaturation of linoleic acid and on lipid fatty acid composition were studied in the liver of the rat at 2, 6, 12, 18 and 24 mon of age. The profiles of delta 6 desaturase activity and fatty acid composition were studied in the deficient rats refed, at these different ages, either with 18:3n-3 (mixture of peanut and rapeseed oils) or with 20:5n-3 + 22:6n-3 (fish oil) diets for 2, 4, 8 or 12 wk. Results showed that the liver delta 6 desaturation activity in the control rats remained high at 2 and 6 mon, decreased by 30% from 6 to 12 mon, and then remained stable from 12 to 24 mon. In the deficient rats, this activity remained high during the entire period studied. Thus, the profile of liver delta 6 desaturase activity after puberty was not related to age only; it also depended on the polyunsaturated fatty acid (PUFA) n-6 and n-3 balance in the diet. In the controls, in parallel with the delta 6 desaturase activity, PUFA metabolism could be divided into three periods: a "young" period, and "old age" period, separated by a period of transition between 6 and 12 mon. Recovery from PUFA n-3 deficiency occurred at all ages but in a different manner depending on whether the rats were "young" or "old". Recovery was faster if long-chain n-3 PUFA rather than alpha-linolenic acid were supplied in the diet.

Linolenic acid deficiency.

Linolenic acid deficiency has not been demonstrated clearly in warm blooded animals, yet circumstantial evidence suggests that n-3 fatty acids may have functions in these animals. The fact that several species of fish definitely require dietary n-3 fatty acids indicates that n-3 fatty acids have important and specific functions in these animals and suggests that such functions may also be present in warm blooded animals. It is also true that n-3 fatty acid distribution in tissues of birds and mammals appears to be under strict metabolic control, and that this complex metabolic control mechanism apparently has survived evolutionary pressure for a very long time. So far, attempts to produce linolenic acid deficiency in mammals have not revealed an absolute requirement for n-3 fatty acids. If functions for n-3 fatty acids do exist in warm blooded animals, it seems probable that they may be located in the cerebral cortex or in the retina, because these tissues normally contain high concentrations of n-3 fatty acids.

A deficiency in dietary gamma-linolenic and/or eicosapentaenoic acids may determine individual susceptibility to AIDS.

We hypothesize that a relative deficiency in gamma-linolenic and eicosapentaenoic acids and in their derivatives may contribute to the development of AIDS. These polyunsaturated fatty acids (PUFAs) may be the source of natural endogenous agents against AIDS by preventing the spread of viral infection due to their ability to destroy enveloped viruses, by controlling cancer development either directly due to their cytostatic and cytotoxic effects on cancer cells or indirectly by modulating the immune response and by protecting from genetic damage. Supplementation of these dietary PUFAs in the prevention, and possibly in the treatment of AIDS, is considered.

Chronic arachidonic acid eicosanoid imbalance: a common feature in coronary artery disease, hypercholesterolemia, cancer and other important diseases. Significance of desaturase enzyme inhibition and of the arachidonic acid desaturase-independent pathway.

A chronic imbalance between the essential fatty acid metabolites arachidonic acid, gamma-linolenic acid and eicosapentaenoic acid and of their respective eicosanoid derivatives appears to be implicated in the etiology of many intractable disease. Most notable among these are coronary artery disease, cancer and chronic inflammation. The factors leading to such an imbalance and their relatively simple prophylactic and therapeutic circumvention are discussed briefly.

Essential fatty acid status in southern Thai preschool children.

Essential fatty acid (EFA) status was assessed in 15 Southern Thai preschool children. The mean (+/- SD) serum linoleate (18:2 n-6), arachidonate (20:4 n-6), linolenate (18:3 n-3), eicosapentaenoate (20:5 n-3), and docosahexaenoate (22:6 n-3) percentages in the preschool children were 21.7 +/- 4.0, 6.0 +/- 1.2, 0.4 +/- 0.1, 1.2 +/- 0.8, and 4.4 +/- 1.3, respectively. Since EFA composition of total serum lipids in healthy children are not available and age and sex do not largely influence these parameters, the results of the preschool children were compared with those of 10 healthy Bangkok adults. The corresponding figures of the aforementioned fatty acids in adults were 34.9 +/- 8.5, 4.6 +/- 1.5, 0.8 +/- 0.4, 0.5 +/- 0.4, and 1.6 +/- 0.8, respectively. The data indicate linoleate and linolenate depletion in the preschool children. This was due to their low fat intake and lack of consumption of vegetable oil rich in linoleic and linolenic acids. Their high serum arachidonate percentage was probably due to the increased conversion of 18:2 n-6 to 20:4 n-6 in the presence of linolenate depletion. The significantly higher serum 20:5 n-3 and 22:6 n-3 percentages in the preschool children should be due to direct consumption of these two n-3 fatty acids from fish intake.

The nutritional contribution to bovine spongiform encephalopathy.

Evidence that changes in feeding style alter the membrane fatty acid composition of ruminant tissue is presented here by comparing zoo giraffe with the same species from their natural habitat. The membrane changes seen are similar to those used experimentally to make animals susceptible to basic brain protein and encephalomalacia. Similar membrane responses have been noted in cattle. Use of animal protein and increased nitrogen in cattle feeds would lead to a relative deficiency of essential fatty acids in the cell membranes and hence reduced membrane stability. By analogy with crazy chick disease (nutritional encephalomalacia) and experimental encephalomyelitis in rats, the possibility that the changes in animals feeds would have depleted cattle tissue membranes and made them susceptible to BSE is discussed. The assumption being made is that the principle of a requirement of essential fatty acids for neural integrity and immune system function would apply to cattle as well as to other species.

[Essential fatty acids: its transformations and functions]. / Los ácidos grasos esenciales: sus transformaciones y funciones.

Essential fatty acids, in animals, pertain to two different fatty acid families: the linoleic and the linolenic. These, and the non-essential families of oleic and palmitoleic are produced by action of the enzymes proper. The lack of essential fatty acids produces typical symptoms that are accompanied by fatty acid compositions, also typical, utilized with diagnostic value. The biological effects of essential fatty acids can be specific and nonspecific. The latter manifest themselves particularly in the phospholipid composition and, therefore, in the structure and fluency of the membranes. In contrast, specific essential fatty acids act in the formation of prostaglandins, prostacyclins, tromboxans and leucotriens. Each essential fatty acid produces specific effects, depending on the prostanoids formed and the tissue in question.