Dietary Alpha-linolenic Acid Research Articles

Dose effect of alpha-linolenic acid on PUFA conversion, bioavailability, and storage in the hamster.

If an increased consumption of alpha-linolenic acid (ALA) is to be promoted in parallel with that of n-3 long-chain-rich food, it is necessary to consider to what extent dietary ALA can be absorbed, transported, stored, and converted into long-chain derivatives. We investigated these processes in male hamsters, over a broad range of supply as linseed oil (0.37, 3.5, 6.9, and 14.6% energy). Linoleic acid (LA) was kept constant (8.5% energy), and the LA/ALA ratio was varied from 22.5 to 0.6. The apparent absorption of individual FA was very high (>96%), and that of ALA remained almost maximum even at the largest supply (99.5%). The capacity for ALA transport and storage had no limitation over the chosen range of dietary intake. Indeed, ALA intake was significantly correlated with ALA level not only in cholesteryl esters (from 0.3 to 9.7% of total FA) but also in plasma phospholipids and red blood cells (RBC), which makes blood components extremely reliable as biomarkers of ALA consumption. Similarly, ALA storage in adipose tissue increased from 0.85 to 14% of total FA and was highly correlated with ALA intake. As for bioconversion, dietary ALA failed to increase 22:6n-3, decreased 20:4n-6, and efficiently increased 20:5n-3 (EPA) in RBC and cardiomyocytes. EPA accumulation did not tend to plateau, in accordance with identical activities of delta5- and delta6-desaturases in all groups. Dietary supply of ALA was therefore a very efficient means of improving the 20:4n-6 to 20:5n-3 balance.

Alpha-linolenic acid metabolism in men and women: nutritional and biological implications.

This review critically evaluates current knowledge of alpha-linolenic acid metabolism in adult humans based on the findings of studies using stable isotope tracers and on increased dietary alpha-linolenic acid intake. The relative roles of alpha-linolenic acid and of longer-chain polyunsaturated fatty acids in cell structure and function are discussed together with an overview of the major metabolic fates of alpha-linolenic acid. The extent of partitioning towards beta-oxidation and carbon recycling in humans is described. The use and limitations of stable isotope tracers to estimate alpha-linolenic acid desaturation and elongation are discussed. A consensus view of the extent of alpha-linolenic acid conversion to longer-chain fatty acids in humans is presented. The extent to which increasing dietary alpha-linolenic acid intake alters the concentrations of longer-chain n-3 fatty acids is described. The biological and nutritional implications of these findings are discussed. Conversion of alpha-linolenic acid to eicosapentaenoic acid is limited in men and further transformation to docosahexaenoic acid is very low. A lower proportion of alpha-linolenic acid is used as a substrate for beta-oxidation in women compared with men, while the fractional conversion to longer-chain fatty acids is greater, possibly due to the regulatory effects of oestrogen. Overall, alpha-linolenic acid appears to be a limited source of longer-chain n-3 fatty acids in man and so adequate intakes of preformed n-3 polyunsaturated fatty acids, in particular docosahexaenoic acid, may be important for maintaining optimal tissue function. Capacity to upregulate alpha-linolenic acid transformation in women may be important for meeting the demands of the fetus and neonate for docosahexaenoic acid.

Effects of dietary alpha linolenic acid on cholesterol metabolism in male and female hamsters of the LPN strain

N-3 polyunsaturated fatty acids and estrogens are recognized as protective factors of atherosclerosis, however their interactions on cholesterol metabolism remain unclear. Male and female hamsters were fed for 9 weeks diets containing 12.5% lipids and rich in either α-linolenic acid (“linseed” diet) or saturated fatty acids (“butter” diet). Hamsters fed the “linseed” diet exhibited lower plasma concentrations of cholesterol (-29%), total LDL (-35%) and HDL (-17%), glucose (-20%), insulin (-40%) and of the LDL-cholesterol/HDL-cholesterol ratio (-27%) than those fed the “butter” diet. In the liver, cholesterol content was 2.7-fold lower in response to the “linseed” diet, whereas the concentration of HDL receptor (SR-BI) and the activities of HMGCoA reductase and cholesterol 7α-hydroxylase were 30 to 50% higher than with the “butter” diet. By contrast, the LDL receptor concentration did not vary with the diet. Females exhibited higher concentration of LDL (+24%), lower concentration of plasma triglycerides (-34%), total VLDL (-46%) and VLDL-cholesterol (-37%) and of biliary phospholipids (-19%). Besides, there was also an interaction between gender and diet: in males fed the “butter” diet, plasma triglycerides and VLDL concentration, were 2 to 4 fold higher than in the other groups. These data suggest that gene and/or metabolic regulations by fatty acids could interact with that of sex hormones and explain why males are more sensitive to dietary fatty acids. Key words: α-linolenic acid; Gender; Hamster; Cholesterol; Dietary lipids

Dietary alpha-linolenic acid suppresses the formation of lysophosphatidic acid, a lipid mediator, in rat platelets compared with linoleic acid

Rats fed a high linoleic acid (LA, 18:2n-6) diet or a high α-linolenic acid (ALA, 18:3n-3) diet for 4 months after weaning. Platelets from the high-LA group contained more arachidonic acid (AA, 20:4n-6) and less eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) compared with those from the high-ALA group. Incorporation of [ 32P]orthophosphate into platelet phospholipids was increased by thrombin-treatment, and was greater by ca. 30% in the high-LA group than in the high-ALA group both in the presence and absence of thrombin. The formation of [ 32P]lysophosphatidic acid (LPA), a lipid messenger, in [ 32P]orthophosphate-labeled platelets was increased 6.6-fold in the high-LA group and 4.1-fold in the high-ALA-group by thrombin-treatment. The formation of [ 32P] LPA in activated platelets was reduced by 35% in the high-ALA group.

Research Communication: Plant and Marine Derived (n-3) Polyunsaturated Fatty Acids Do Not Affect Blood Coagulation and Fibrinolytic Factors in Moderately Hyperlipidemic Humans

Dietary alpha-linolenic acid (ALA) can be converted to long-chain (n-3) PUFA in humans and may potentially reproduce the beneficial effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on risk factors for coronary heart disease (CHD). This study compared the effects of increased intakes of ALA with those of dietary EPA and DHA on blood coagulation and fibrinolytic factors in fasting subjects. A placebo-controlled, parallel study was conducted in 150 moderately hyperlipidemic subjects, age 25-72 y. Subjects were randomly assigned to one of five interventions and consumed a total intake of 0.8 or 1.7g/d EPA+DHA, 4.5 or 9.5g/d ALA or control (linoleic acid; LA) for 6 mo. Fatty acids were incorporated into 25 g of fat spread, which replaced the subject's normal spread and three capsules. Long-term supplementation with either dietary EPA+DHA or estimated biologically equivalent amounts of ALA did not affect factors VIIa, VIIc, VIIag, XIIa, XIIag, fibrinogen concentrations, plasminogen activator inhibitor-1 or tissue plasminogen activator activity compared with the control. (n-3) PUFA of plant or marine origin do not differ from one another or from LA in their effect on a range of blood coagulation and fibrinolytic factors.

Plant- and marine-derived n−3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects

Dietary alpha-linolenic acid (ALA) can be converted to long-chain n-3 polyunsaturated fatty acids (PUFAs) in humans and may reproduce some of the beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease risk factors. This study aimed to compare the effects of increased dietary intakes of ALA and EPA+DHA on a range of atherogenic risk factors. This was a placebo-controlled, parallel study involving 150 moderately hyperlipidemic subjects randomly assigned to 1 of 5 interventions: 0.8 or 1.7 g EPA+DHA/d, 4.5 or 9.5 g ALA/d, or an n-6 PUFA control for 6 mo. Fatty acids were incorporated into 25 g of fat spread and 3 capsules to be consumed daily. The change in fasting or postprandial lipid, glucose, or insulin concentrations or in blood pressure was not significantly different after any of the n-3 PUFA interventions compared with the n-6 PUFA control. The mean (+/- SEM) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention (-7.7 +/- 4.99%) was significantly (P < 0.05) different from the change after the 9.5-g/d ALA intervention (10.9 +/- 4.5%). The ex vivo susceptibility of LDL to oxidation was higher after the 1.7-g/d EPA+DHA intervention than after the control and ALA interventions (P < 0.05). There was no significant change in plasma alpha-tocopherol concentrations or in whole plasma antioxidant status in any of the groups. At estimated biologically equivalent intakes, dietary ALA and EPA+DHA have different physiologic effects.

Dietary alpha-linolenic acid lowers postprandial lipid levels with increase of eicosapentaenoic and docosahexaenoic acid contents in rat hepatic membrane.

This study was designed to examine the effects of dietary n-3 and n-6 polyunsaturated fatty acids (PUFA) on postprandial lipid levels and fatty acid composition of hepatic membranes. Male Sprague-Dawley rats were trained for a 3-h feeding protocol and fed one of five semipurified diets: one fat-free diet or one of four diets supplemented with 10% (by weight) each of corn oil, beef tallow, perilla oil, and fish oil. Two separate experiments were performed, 4-wk long-term and 4-d short-term feeding models, to compare the effects of feeding periods. Postprandial plasma lipid was affected by dietary fats. Triacylglycerol (TG) and total cholesterol levels were decreased in rats fed perilla oil and fish oil diets compared with corn oil and beef tallow diets. Hepatic TG and total cholesterol levels were also reduced by fish oil and perilla oil diets. Fatty acid composition of hepatic microsomal fraction reflected dietary fatty acids and their metabolic conversion. The major fatty acids of rats fed the beef tallow diet were palmitic, stearic, and oleic. Similarly, linoleic acid (LA) and arachidonic acid in the corn oil group, alpha-linolenic acid (ALA) and eicosapentaenoic acid (EPA) in the perilla oil group, and palmitic acid and docosahexaenoic acid (DHA) in the fish oil group were detected in high proportions. Both long- and short-term feeding experiments showed similar results. In addition, microsomal DHA content was negatively correlated with plasma lipid levels. Hepatic lipid levels were also negatively correlated with EPA and DHA contents. These results suggest that n-3 ALA has more of a hypolipidemic effect than n-6 LA and that the hypolipidemic effect of n-3 PUFA may be partly related to the increase of EPA and DHA in hepatic membrane.

α-Linolenic acid intake is not beneficially associated with 10-y risk of coronary artery disease incidence: the Zutphen Elderly Study

Data on the relation between alpha-linolenic acid intake and coronary artery disease (CAD) are limited. Other dietary components appear to modify the reported relation between alpha-linolenic acid intake and CAD. We examined whether dietary alpha-linolenic acid intake was inversely associated with risk of CAD. We prospectively studied 667 men aged 64-84 y from the Zutphen Elderly Study who were free of CAD at baseline. Dietary intake was assessed by using a cross-check dietary history method. During the 10-y follow-up, we documented 98 cases of CAD. After adjustment for age, standard coronary risk factors, and intake of trans fatty acids and other nutrients, alpha-linolenic acid intake was not significantly associated with CAD risk. The relative risk of CAD for the highest compared with the lowest tertile of alpha-linolenic acid intake was 1.68 (95% CI: 0.86, 3.29). alpha-Linolenic acid intake from sources containing trans fatty acids was also nonsignificantly, yet positively, associated with CAD risk. alpha-Linolenic acid intake from foods that did not contain trans fatty acids was not associated with CAD risk, the relative risk of CAD for the highest compared with the lowest tertile was 1.15 (95% CI: 0.63, 2.11). We did not observe a beneficial effect of dietary alpha-linolenic acid intake on the risk of 10-y CAD incidence. Investigating this hypothesis was complicated by the association between intakes of alpha-linolenic acid and trans fatty acids. Given the results of current prospective studies, a protective cardiac effect of alpha-linolenic acid is questionable.

Maternal Dietary α-Linolenic Acid (18:3n-3) Alters n-3 Polyunsaturated Fatty Acid Metabolism and Liver Enzyme Activity in Hatched Chicks

We investigated the effects of dietary alpha-linolenic acid (LNA; 18:3n-3) of laying hens on the fatty acid composition of liver microsomes and activity of Δ-6 desaturase in hatched chicks. Laying hens were fed wheat-soybean meal-based diets with (Flax) or without ground flax (control). At Day 21 of feeding, fertile eggs were collected and incubated. On the day of hatching, chicks (n = 6) were killed, and liver microsomes were isolated and assayed for Δ-6 desaturase enzyme activity. The total n-3 fatty acids in the Flax eggs was 13.0% compared with 2.3% (P < 0.001) in the control group. LNA was the major n-3 fatty acid in the Flax eggs and constituted 10%. The long-chain n-3 polyunsaturated fatty acids (PUFA) (20:5n-3, 22:5n-3, and 22:6n-3) constituted 3.1% in Flax eggs compared with 1.5% in control eggs. Docosahexaenoic acid (22:6n-3) composed 2.1 and 1.2% in Flax and control eggs (P < 0.05), respectively. The liver microsomes of Flax chicks incorporated higher 18:3n-3, 20:5n-3, and 22:5n-3 (P < 0.05) with a concomitant reduction in 20:4n-6, 22:4n-6, and 22:5n-6 compared with control chicks (P < 0.05). The Δ-6 desaturase activities in Flax and control groups were 49.4 and 82.8 pmol/min per mg of protein, respectively (P < 0.05). These results demonstrate the role of maternal and yolk n-3 fatty acids in modulating the activity of rate-limiting enzymes for PUFA synthesis in hatched chicks.

1-14C-linoleic acid distribution in various tissue lipids of guinea pigs following an oral dose.

A recent study on the metabolism of 1-14C-alpha-linolenic acid in the guinea pig revealed that the fur had the highest specific activity of all tissues examined, 48 h after dosing. The present study investigated the pattern of tissue lipid labeling following an oral dose of 1-14C-linoleic acid after the animals had been dosed for the same time as above. Guinea pigs were fed one of two diets with a constant linoleic acid content (18% total fatty acids) and a different content of alpha-linolenic acid (0.3 or 17.3%) from weaning for 3 wk and 1-14C-linoleic acid was given orally to each animal for 48 h prior to sacrifice. The most highly labeled tissues (dpm/mg of linoleic acid) were liver, followed by brain, lung and spleen, heart, kidney and adrenal and intestines, in both diet groups. The liver had almost a three-fold higher specific activity than skin and fur which was more extensively labeled than the adipose and carcass. Approximately two-thirds of the label in skin plus fur was found in the fur which, because of a low lipid mass, would indicate that the fur was highly labeled. All tissues derived from animals on the diet with the low alpha-linolenic acid level were significantly more labeled than the tissues from the animals on the high alpha-linolenic acid diet, by a factor of 1.5 to 3. The phospholipid fraction was the most highly labeled fraction in the liver, free fatty acids were the most labeled fraction in skin & fur, while triacyglycerols were the most labeled in the carcass and adipose tissue. In these tissues, more than 90% of the radioactivity was found in fatty acids with 2-double bonds in the tissue lipids. These data indicate that the majority of label found in guinea pig tissues 48 h after dosing was still associated with a fatty acid fraction with 2-double bonds, which suggests there was little metabolism of linoleic acid to more highly unsaturated fatty acids in this time frame. In this study, the labeling of guinea pig tissues with linoleic acid, 48 h after dosing, was quite different from the labeling with alpha-linolenic acid reported previously. The retention of the administered radioactivity from 14C-linoleic acid in the whole body lipids was 1.6 times higher in the group fed the low alpha-linolenic acid diet (diet contained a total of 1.8 g PUFA/100 g diet) compared with the group fed the high alpha-linolenic acid diet (diet contained 3.6 g PUFA/100 g diet). The lack of retention of 14C-labeled lipids in the whole body would be consistent with an increased rate of beta-oxidation of the labeled fatty acid on the diet rich in PUFA, a result supported by other studies using direct measurement of labeled carbon dioxide.

The Significance of Alpha-Linolenic Acid for Humans.

The omega 3 polyunsaturated fatty acids have had a major impact on thinking in medicine in the last twenty-five years. The parent fatty acid in the omega 3 fatty acid family is alpha-linolenic acid (ALA) which is an essential fatty acid found in high concentrations in certain plant oils, such as flaxseed oil, walnut oil and canola oil. Several longer chain or derived omega 3 fatty acids are formed in the body from ALA, including eicosapentaenoic acid, EPA, decosapentaenoic acid and docosahexaenoic acid, DHA. Dietary sources of these longer-chain fatty acids are fish, fish oils and from other marine organisms. DHA is specifically localised in the retina and the brain in humans and other mammals where it has a primary role via effects on membrane order (fluidity), the activity of membrane-bound enzymes, ion channels and signal transduction. For many years, ALA has been considered to be important only as a precursor of these longer chain compounds, however it is now recognaised that ALA is metabolished by other pathways which may be quantiatively more important than the formation of DHA. For example, ALA is extensively β-oxidised in mammals including humans, especially on diets rich in polyunsaturated fatty acids. ALA appears to play an important role in the nervous system (carbon recycling) for the synthesis of saturated and monounsaturated fatty acids and cholesterol, with estimates of the proportion of ALA being matabolised via this pathway being several fold greater than that to DHA. Furthermore, recent studies have indicated that ALA is deposited in the skin of small mammals and may also play a role in fur. Since ALA is extensively metabolised via these pathways (β-oxidation, carbon recycling and deposition in skin/fur) and is subject to competitive inhibition from linoleic acid in metabolism via the delta-6 desaturase, it is not surprising tha dietary DHA is substantially more effctive than an equivalent dose of dietary ALA in maintaining neural DHA levels. Despite the limited efficiency of DHA formation from ALA, it is clear that certain tissues possess the capacity to synthesise DHA at rates greater than other tissues. The brain, retina and reproductive tissue may be able to synthesis sufficient DHA to meet the DHA demands of these tissues, although in infants at the peak of brain growth and DHA deposition, a dietary supply of DHA (as in milk) may be important to maintain the brain DHA level. In plants, ALA is a substrate for lipoxygenase enzymes leading to the poduction of bioactive hydroxy compounds. This information might provide a clue to other routes of ALA metabolism in mammals. It is concluded that it may no longer be appropriate to consider the function for ALA to be solely a precursor of EPA and DHA.

Increased alpha-linolenic acid intake increases tissue alpha-linolenic acid content and apparent oxidation with little effect on tissue docosahexaenoic acid in the guinea pig.

The essential fatty acids do not have identical roles in nutrition. Linoleic acid (LA) accumulates throughout the body of most mammals, whereas alpha-linolenic acid (ALA) is rarely found in tissue lipids to the same extent as LA. It has been argued that this is the result of metabolism of ALA to docosahexaenoic acid (DHA) or that ALA is rapidly beta-oxidized to acetyl CoA and CO2. In this study, we consider the effect of high and low ALA levels on the tissue distribution of ALA and other n-3 polyunsaturated fatty acids (PUFA) in all tissues. Guinea pigs were fed one of two defined diets for 3 wk from weaning with both diets containing 1.8% (by weight) of LA and either 1.7% ALA or 0.03% ALA. The high ALA diet was associated with significantly increased ALA levels in all tissues except the brain and significantly increased levels of long-chain n-3 PUFA in all tissues except intestines, brain, carcass, and skin. The long-chain n-3 PUFA content of the whole body was less than 5% of that of the ALA content in both diet groups, and the major long-chain n-3 PUFA (>66% of total) in the body was 22:5n-3. The brain was the only tissue where the DHA content exceeded that of 22:5n-3. On the low ALA diet, there appeared to be conservation of ALA based on a comparison of the ratio of LA to ALA in the tissues compared with that in the diet. On the high ALA diet there was a loss of ALA relative to LA in the tissues compared with the diet. These studies suggest that the low levels of tissue ALA in the guinea pig are likely the result of beta-oxidation or excretion via the skin and fur rather than metabolism to DHA.

Low alpha-linolenic acid content of adipose breast tissue is associated with an increased risk of breast cancer

Data derived from experimental studies suggest that alpha-linolenic acid may have a protective effect in breast cancer. Observations obtained from epidemiological studies have not allowed conclusions to be drawn about a potential protective effect of dietary alpha-linolenic acid on breast cancer, possibly because of methodological issues. This case–control study conducted in an homogeneous population from a central area in France was designed to explore the hypothesis that alpha-linolenic acid inhibits breast cancer, using fatty acid levels in adipose breast tissue as a biomarker of past qualitative dietary intake of fatty acids. Biopsies of adipose breast tissue at the time of diagnosis were obtained from 123 women with invasive non-metastatic breast carcinoma. 59 women with benign breast disease served as controls. Individual fatty acids were analysed by capillary gas chromatography. An unconditional logistic regression model was used to obtain odds ratio estimates whilst adjusting for age, menopausal status and body mass index (BMI). No association was found between fatty acids (saturates, monounsaturates, long-chain polyunsaturates n-6 or n-3) and the disease, except for alpha-linolenic acid which showed an inverse association with the risk of breast cancer. The relative risk of breast cancer for women in the highest quartile of adipose breast tissue alpha-linolenic acid level was 0.36 (95% confidence interval=0.12–1.02) compared with those in the lowest quartile ( P trend=0.026), suggesting a protective effect of alpha-linolenic acid in the risk of breast cancer. The effects of dietary alpha-linolenic on the risk of breast cancer warrant further study.

Effect of dietary α-linolenic acid on thrombotic risk factors in vegetarian men

Vegetarians have lower platelet and plasma concentrations of n-3 polyunsaturated fatty acids (PUFAs) than do omnivores. We recently showed that male vegetarians have higher platelet aggregability than do omnivores. We investigated whether male vegetarians (n = 17) who consumed an increased amount of dietary alpha-linolenic acid (ALA) showed any changes in their tissue profile of PUFAs, plasma thromboxane concentrations, platelet aggregability, or hemostatic factors. During the study, all subjects maintained their habitual vegetarian diets except that a proportion of dietary fat was replaced with vegetable oils and margarines that were provided. Initially, all subjects consumed a low-ALA diet (containing safflower oil and safflower oil-based margarine) for 14 d; they then consumed either a moderate-ALA diet (containing canola oil and canola oil-based margarine) or a high-ALA diet (containing linseed oil and linseed oil-based margarine) for 28 d. Blood samples were collected at day 0 (baseline), day 14, and day 42. Eicosapentaenoic acid, docosapentaenoic acid, total n-3 PUFAs, and the ratio of n-3 to n-6 PUFAs were significantly increased (P < 0.05), whereas the ratio of arachidonic acid to eicosapentaenoic acid was decreased (P < 0.05), in platelet phospholipids, plasma phospholipids, and triacylglycerols after either the moderate-ALA or high-ALA diet compared with the low-ALA diet. No significant differences were observed in thrombotic risk factors. ALA from vegetable oils (canola and linseed) has a beneficial effect on n-3 PUFA concentrations of platelet phospholipids and plasma lipids in vegetarian males.

Long-term effects of dietary alpha-linolenic acid from perilla oil on serum fatty acids composition and on the risk factors of coronary heart disease in Japanese elderly subjects.

Although important roles of dietary n-3 fatty acids in the prevention of coronary heart disease (CHD) have been suggested, long-term effects of dietary alpha-linolenic acid (ALA, 18:3n-3) have not yet been established under controlled conditions. We tested whether a moderate increase of dietary ALA affects fatty acids composition in serum and the risk factors of CHD. Oxidized LDL (OxLDL) was directly measured by ELISA using antibody specific to OxLDL. By merely replacing soybean cooking oil (SO) with perilla oil (PO) (i.e., increasing 3 g/d of ALA), the n-6/n-3 ratio in the diet was changed from 4:1 to 1:1. Twenty Japanese elderly subjects were initially given a SO diet for at least 6 mo (baseline period), a PO diet for 10 mo (intervention period), and then returned to the previous SO diet (washout period). ALA in the total serum lipid increased from 0.8 to 1.6% after 3 mo on the PO diet, but EPA and DHA increased in a later time, at 10 mo after the PO diet, from 2.5 to 3.6% and 5.3 to 6.4%, respectively (p<0.05), and then returned to baseline in the washout period. In spite of increases of serum n-3 fatty acids, the OxLDL concentration did not change significantly when given the PO diet. Body weight, total serum cholesterol, triacylglycerol, glucose, insulin and HbA1c concentrations, platelet count and aggregation function, prothrombin time, partial thromboplastin time, fibrinogen and PAI-1 concentration, and other routine blood analysis did not change significantly when given the PO diet. These data indicate that, even in elderly subjects, a 3 g/d increase of dietary ALA could increase serum EPA and DHA in 10 mo without any major adverse effects.

Dietary alpha-linolenic acid increases the biosynthesis of the choline glycerophospholipids from [14C]CDPcholine in rat liver and kidney but not in brain.

The effect of feeding rats for 30 days with diets containing high levels of linoleic acid (sunflower oil, SO) or alpha-linolenic acid (perilla oil, PO) was studied in the liver, kidney and brain. The PO group showed a higher labeling of choline glycerophospholipids (CGP) in liver and kidney but no difference with the SO group in ethanolamine glycerophospholipids (EGP) labeling. The brain displayed the lowest incorporation of both precursors and no difference between the two diets. Analyses of brain CGP and EGP fatty acid composition showed that in the PO group the ratio n-6/n-3 was lower than in the SO group, mainly as a consequence of lower levels of n-6 fatty acids. The mole % of docosahexaenoate (DHA) in these lipids was the same for both groups and only triacylglycerols (TAG) displayed a higher DHA. Therefore, at least in the brain, the magnitude of fatty acid changes observed in CGP and EGP for the PO group does not affect the uptake/incorporation of the precursors into phospholipids.

The ratio of n-6 to n-3 polyunsaturated fatty acids in the rat diet alters serum lipid levels and lymphocyte functions.

Previous studies have reported that feeding rats diets rich in fish oils, which contain high proportions of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic and docosahexaenoic acids, results in lowering of blood lipid levels and suppression of lymphocyte functions tested ex vivo and in vivo. The effects of other n-3 PUFA, such as alpha-linolenic acid, which is found in high proportions in linseed oil, are not as well documented. Therefore, in the present study, weanling male rats were fed for six weeks on one of five high-fat (20% by weight) diets made by mixing together sunflower and linseed oils; the resulting blends had n-6/n-3 PUFA ratios of 112.5:1 (pure sunflower oil), 14.8:1, 6.5:1, 0.81:1, and 0.33:1 (pure linseed oil); the levels of all other components in the diet were identical. The final body weight and total dissectable fat were lowest in rats fed the pure linseed oil diet. Serum cholesterol, triacylglycerol and nonesterified fatty acid concentrations decreased as the n-6/n-3 PUFA ratio of the diet decreased. The fatty acid composition of the serum and of spleen lymphocytes was influenced by the diet fed-there was a progressive decrease in the proportions of linoleic and arachidonic acids and a progressive increase in the proportion of alpha-linolenic acid as the n-6/n-3 PUFA ratio of the diet decreased. Eicosapentaenoic and docosahexaenoic acids were detected in the serum but not in spleen lymphocytes. Inclusion of alpha-linolenic acid in the diet resulted in significant suppression of spleen lymphocyte proliferation in response to the T-cell mitogen concanavalin A and in spleen lymphocyte natural killer cell activity, both measured ex vivo. The localized graft vs. host response, a measure of cell-mediated immunity in vivo, progressively decreased as the n-6/n-3 PUFA ratio of the diet decreased. Thus, this study shows that dietary alpha-linolenic acid results in lowered blood lipid levels and suppressed lymphocyte functions ex vivo and in vivo. With respect to these effects, alpha-linolenic acid is as potent as dietary fish oil.

Antithromboxane activity of dietary alpha-linolenic acid: a pilot study

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

α‐Linolenic Acid Dietary Deficiency Alters Age‐Related Changes of Dopaminergic and Serotoninergic Neurotransmission in the Rat Frontal Cortex

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.

Immunologic effects of marine- and plant-derived n-3 polyunsaturated fatty acids in nonhuman primates

The effect of marine- and plant-derived n-3 polyunsaturated fatty acids (PUFAs) on T cell-mediated immune response was studied in cynomolgus monkeys. Animals were first fed a 14-wk baseline diet; 10 animals were then fed diets containing 1.3% or 3.3% of energy as eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) which the other 10 were fed diets containing 3.5% or 5.3% of energy as alpha-linolenic acid (ALA) for two consecutive 14-wk periods. Both diets significantly decreased the percentage of T cells (except 1.3% EPA + DHA), T helper cells (except 1.3% EPA + DHA and 3.5% ALA), and T suppressor cells. Proliferative response of lymphocytes to T cell mitogens significantly increased after the diet containing 3.3% EPA + DHA. Interleukin 2 production significantly increased after the diets containing 1.3% and 3.3% EPA + DHA. No significant changes in mitogenic response or interleukin 2 production were found after ALA diets. Feeding 1.3% or 3.3% EPA + DHA or 5.3% ALA significantly suppressed prostaglandin E2 production in response to T cell mitogens. Plasma tocopherol concentrations were decreased significantly only in monkeys fed ALA diets. We conclude that after adjustment for the tocopherol concentration, marine-derived n-3 PUFAs but not plant-derived n-3 PUFAs increased T cell-mediated mitogenic response and interleukin 2 production. This is most likely due to diet-induced quantitative differences in cellular fatty acid composition and, thus, in prostaglandin E2 production and tocopherol status.