Dietary ALA,EPA and DHA have distinct effects on oxylipin profiles in female and male rat kidney,liver and serum

There is much data on the effects of dietary n-3 fatty acids on tissue fatty acid compositions, but comparable comprehensive data on their oxygenated metabolites (oxylipins) is limited. The effects of providing female and male rats with diets high in α-linolenic acid (ALA), EPA or DHA for 6 weeks on oxylipins and fatty acids in kidney, liver and serum were therefore examined. The oxylipin profile generally reflected fatty acids, but it also revealed unique effects of individual n-3 fatty acids that were not apparent from fatty acid data alone. Dietary ALA increased renal and serum DHA oxylipins even though DHA itself did not increase, while dietary EPA did not increase DHA oxylipins in kidney or liver, suggesting that high EPA may inhibit this conversion. Oxylipin data generally corroborated fatty acid data that indicated that DHA can be retroconverted to EPA and that further retroconversion to ALA is limited. Dietary n-3 fatty acids decreased n-6 fatty acids and their oxylipins (except linoleic acid and its oxylipins), in order of effectiveness of DHA > EPA > ALA, with some exceptions: several arachidonic acid oxylipins modified at carbon 15 were not lower in all three sites, and EPA had a greater effect on 12-hydroxy-eicosatetraenoic acid and its metabolites in the liver. Oxylipins were predominantly higher in males, which was not reflective of fatty acids. Tissue-specific oxylipin profiles, therefore, provide further information on individual dietary n-3 fatty acid and sex effects that may help explain their unique physiological effects and have implications for dietary recommendations.     

Comparative anti-inflammatory effects of plant- and marine-derived omega-3 fatty acids explored in an endothelial cell line

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower risk of cardiovascular disease. The primary source of EPA and DHA is fatty fish. Plant-derived alpha linolenic acid (ALA) and stearidonic acid (SDA) could provide sustainable land-based alternatives, but their functionality is underexplored. Omega-3 fatty acids (n-3 FAs) may influence atherogenic processes through changing endothelial cell (EC) function and lowering inflammation. This study compared effects of marine- and plant-derived n-3 FAs on EC inflammatory responses. EA.hy926 cells were exposed to ALA, SDA, EPA or DHA prior to stimulation with tumor necrosis factor (TNF)-α. All FAs were shown to be incorporated into ECs in a dose-dependent manner. SDA (50 μM) decreased both production and cell-surface expression of intercellular adhesion molecule (ICAM)-1; however EPA and DHA resulted in greater reduction of ICAM-1 production and expression. EPA and DHA also significantly lowered production of monocyte chemoattractant protein 1, interleukin (IL)-6 and IL-8. ALA, SDA and DHA (50 μM) all reduced adhesion of THP-1 monocytes to EA.hy926 cells. DHA significantly decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)p105 gene expression and phosphorylated NFκBp65 protein. Both EPA and DHA (50 μM) significantly decreased cyclooxygenase (COX)-2 protein. Thus, both marine-derived n-3 FAs, particularly DHA, had potent anti-inflammatory effects in this EC model. Of the plant-derived n-3 FAs, SDA showed the greatest inhibition of inflammation. Although neither ALA nor SDA reproduced the anti-inflammatory effects of EPA and DHA in this model, there is some potential for SDA to be a sustainable anti-inflammatory alternative to the marine n-3 FAs.     

Omega-3 fatty acids, energy substrates, and brain function during aging

The maintenance of optimal cognitive function is a central feature of healthy aging. Impairment in brain glucose uptake is common in aging associated cognitive deterioration, but little is known of how this problem arises or whether it can be corrected or bypassed. Several aspects of the challenge to providing the brain with an adequate supply of fuel during aging seem to relate to omega-3 fatty acids. For instance, low intake of omega-3 fatty acids, especially docosahexaenoic acid (DHA), is becoming increasingly associated with several forms of cognitive decline in the elderly, particularly Alzheimer's disease. Brain DHA level seems to be an important regulator of brain glucose uptake, possibly by affecting the activity of some but not all the glucose transporters. DHA synthesis from either alpha-linolenic acid (ALA) or eicosapentaenoic acid (EPA) is very low in humans begging the question of whether these DHA precursors are likely to be helpful in maintaining cognition during aging. We speculate that ALA and EPA may well have useful supporting roles in maintaining brain function during aging but not by their conversion to DHA. ALA is an efficient ketogenic fatty acid, while EPA promotes fatty acid oxidation. By helping to produce ketone bodies, the effects of ALA and EPA could well be useful in strategies intended to use ketones to bypass problems of impaired glucose access to the brain during aging. Hence, it may be time to consider whether the main omega-3 fatty acids have distinct but complementary roles in brain function.     

Elongase reactions as control points in long-chain polyunsaturated fatty acid synthesis

Background

Δ6-Desaturase (Fads2) is widely regarded as rate-limiting in the conversion of dietary α-linolenic acid (18:3n-3; ALA) to the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (22:6n-3; DHA). However, increasing dietary ALA or the direct Fads2 product, stearidonic acid (18:4n-3; SDA), increases tissue levels of eicosapentaenoic acid (20:5n-3; EPA) and docosapentaenoic acid (22:5n-3; DPA), but not DHA. These observations suggest that one or more control points must exist beyond ALA metabolism by Fads2. One possible control point is a second reaction involving Fads2 itself, since this enzyme catalyses desaturation of 24:5n-3 to 24:6n-3, as well as ALA to SDA. However, metabolism of EPA and DPA both require elongation reactions. This study examined the activities of two elongase enzymes as well as the second reaction of Fads2 in order to concentrate on the metabolism of EPA to DHA.

Methodology/Principal Findings

The substrate selectivities, competitive substrate interactions and dose response curves of the rat elongases, Elovl2 and Elovl5 were determined after expression of the enzymes in yeast. The competitive substrate interactions for rat Fads2 were also examined. Rat Elovl2 was active with C₂₀ and C₂₂ polyunsaturated fatty acids and this single enzyme catalysed the sequential elongation reactions of EPA→DPA→24:5n-3. The second reaction DPA→24:5n-3 appeared to be saturated at substrate concentrations not saturating for the first reaction EPA→DPA. ALA dose-dependently inhibited Fads2 conversion of 24:5n-3 to 24:6n-3.

Conclusions

The competition between ALA and 24:5n-3 for Fads2 may explain the decrease in DHA levels observed after certain intakes of dietary ALA have been exceeded. In addition, the apparent saturation of the second Elovl2 reaction, DPA→24:5n-3, provides further explanations for the accumulation of DPA when ALA, SDA or EPA is provided in the diet. This study suggests that Elovl2 will be critical in understanding if DHA synthesis can be increased by dietary means.     

Methodologic challenges in designing clinical studies to measure differences in the bioequivalence of n-3 fatty acids

Although epidemiologic studies suggest a role for alpha-linolenic acid (ALA) in the prevention of coronary heart disease and certain types of cancer, the findings of clinical studies suggest that ALA is inferior biologically to the n-3 long-chain fatty acids because its bioconversion to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is limited in humans and because the magnitude of its biologic effects is smaller than that of EPA and DHA. This paper reviews several methodologic issues that may confound the findings of clinical studies and complicate our interpretations of them: the ALA and EPA + DHA dietary enrichment levels; the choice of tissue; the choice of lipid species; and the method of reporting fatty acid composition. Although the ALA enrichment levels used in most clinical studies can be achieved by consuming ground flaxseed, flaxseed oil, canola oil and other ALA-rich plants as part of a typical dietary pattern, the EPA + DHA enrichment levels are not practical and can only be obtained from fish oil supplements. The lack of consistency in the choice of lipids species and the reporting of data makes it difficult to compare outcomes across studies. The choice of tissue (blood) for analysis is a limitation that probably cannot be overcome. The use of practical ALA and EPA+ DHA dietary enrichment levels and some standardization of clinical study design would allow for greater comparisons of outcomes across studies and ensure a more realistic analysis of how individual n-3 fatty acids differ in their biologic effects in humans.     

Compartmental modeling to quantify alpha-linolenic acid conversion after longer term intake of multiple tracer boluses

To estimate in vivo alpha-linolenic acid (ALA; C18:3n-3) conversion, 29 healthy subjects consumed for 28 days a diet providing 7% of energy from linoleic acid (C18:2n-6) and 0.4% from ALA. On day 19, subjects received a single bolus of 30 mg of uniformly labeled [(13)C]ALA and for the next 8 days 10 mg twice daily. Fasting plasma phospholipid concentrations of (12)C- and (13)C-labeled ALA, eicosapentaenoic acid (EPA; C20:5n-3), docosapentaenoic acid (DPA; C22:5n-3), and docosahexaenoic acid (DHA; C22:6n-3) were determined on days 19, 21, 23, 26, 27, and 28. To estimate hepatic conversion of n-3 fatty acids, a tracer model was developed based on the averaged (13)C data of the participants. A similar tracee model was solved using the averaged (12)C values, the kinetic parameters derived from the tracer model, and mean ALA consumption. ALA incorporation into plasma phospholipids was estimated by solving both models simultaneously. It was found that nearly 7% of dietary ALA was incorporated into plasma phospholipids. From this pool, 99.8% was converted into EPA and 1% was converted into DPA and subsequently into DHA. The limited incorporation of dietary ALA into the hepatic phospholipid pool contributes to the low hepatic conversion of ALA into EPA. A low conversion of ALA-derived EPA into DPA might be an additional obstacle for DHA synthesis.     

Omega-3 fatty acids and metabolic syndrome: Effects and emerging mechanisms of action

Epidemiological, human, animal, and cell culture studies show that n−3 fatty acids, especially α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), reduce the risk factors of cardiovascular diseases. EPA and DHA, rather than ALA, have been the focus of research on the n−3 fatty acids, probably due to the relatively inefficient conversion of ALA to EPA and DHA in rodents and humans. This review will assess our current understanding of the effects and potential mechanisms of actions of individual n−3 fatty acids on multiple risk factors of metabolic syndrome. Evidence for pharmacological responses and the mechanism of action of each of the n−3 fatty acid trio will be discussed for the major risk factors of metabolic syndrome, especially adiposity, dyslipidemia, insulin resistance and diabetes, hypertension, oxidative stress, and inflammation. Metabolism of n−3 and n−6 fatty acids as well as the interactions of n−3 fatty acids with nutrients, gene expression, and disease states will be addressed to provide a rationale for the use of n−3 fatty acids to reduce the risk factors of metabolic syndrome.     

Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids

The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07–17.1 en%) and ALA (0.02–12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1–3 en% ALA and 1–2 en% LA but was suppressed to basal levels (～2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).     

Failure of conjugated linoleic acid supplementation to enhance biosynthesis of docosahexaenoic acid from alpha-linolenic acid in healthy human volunteers

A rate-limiting step in docosahexaenoic acid (DHA) formation from alpha-linolenic acid (ALA) involves peroxisomal oxidation of 24:6n-3 to DHA. The aim of the study was to determine whether conjugated linoleic acid (CLA) would enhance conversion of ALA to DHA in humans on an ALA-supplemented diet. The subjects (n=8 per group) received daily supplementation of ALA (11g) and either CLA (3.2g) or placebo for 8 weeks. At baseline, 4 and 8 weeks, blood was collected for plasma fatty acid analysis and a number of physiological measures were examined. The ALA-supplemented diet increased plasma levels of ALA and eicosapentaenoic acid (EPA). The addition of CLA to the ALA diet resulted in increased plasma levels of CLA, as well as ALA and EPA. Plasma level of DHA was not increased with either the ALA alone or ALA plus CLA supplementation. The results demonstrated that CLA was not effective in enhancing DHA levels in plasma in healthy volunteers.     

Effects of ALA,EPA and DHA in high-carbohydrate,high-fat diet-induced metabolic syndrome in rats

We compared the cardiovascular, hepatic and metabolic responses to individual dietary n-3 fatty acids (α-linolenic acid, ALA; eicosapentaenoic acid, EPA; and docosahexaenoic acid, DHA) in a high-carbohydrate, high-fat diet-induced model of metabolic syndrome in rats. Additionally, we measured fatty acid composition of plasma, adipose tissue, liver, heart and skeletal muscle in these rats. The same dosages of ALA and EPA/DHA produced different physiological responses to decrease the risk factors for metabolic syndrome. ALA did not reduce total body fat but induced lipid redistribution away from the abdominal area and favorably improved glucose tolerance, insulin sensitivity, dyslipidemia, hypertension and left ventricular dimensions, contractility, volumes and stiffness. EPA and DHA increased sympathetic activation, reduced the abdominal adiposity and total body fat and attenuated insulin sensitivity, dyslipidemia, hypertension and left ventricular stiffness but not glucose tolerance. However, ALA, EPA and DHA all reduced inflammation in both the heart and the liver, cardiac fibrosis and hepatic steatosis. These effects were associated with complete suppression of stearoyl-CoA desaturase 1 activity. Since the physiological responses to EPA and DHA were similar, it is likely that the effects are mediated by DHA with EPA serving as a precursor. Also, ALA supplementation increased DHA concentrations but induced different physiological responses to EPA and DHA. This result strongly suggests that ALA has independent effects in metabolic syndrome, not relying on its metabolism to DHA.     

Long-chain conversion of [13C]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men

We studied the long-chain conversion of [U-13C]alpha-linolenic acid (ALA) and linoleic acid (LA) and responses of erythrocyte phospholipid composition to variation in the dietary ratios of 18:3n-3 (ALA) and 18:2n-6 (LA) for 12 weeks in 38 moderately hyperlipidemic men. Diets were enriched with either flaxseed oil (FXO; 17 g/day ALA, n=21) or sunflower oil (SO; 17 g/day LA, n=17). The FXO diet induced increases in phospholipid ALA (>3-fold), 20:5n-3 [eicosapentaenoic acid (EPA), >2-fold], and 22:5n-3 [docosapentaenoic acid (DPA), 50%] but no change in 22:6n-3 [docosahexanoic acid (DHA)], LA, or 20:4n-6 [arachidonic acid (AA)]. The increases in EPA and DPA but not DHA were similar to those in subjects given the SO diet enriched with 3 g of EPA plus DHA from fish oil (n=19). The SO diet induced a small increase in LA but no change in AA. Long-chain conversion of [U-13C]ALA and [U-13C]LA, calculated from peak plasma 13C concentrations after simple modeling for tracer dilution in subsets from the FXO (n=6) and SO (n=5) diets, was similar but low for the two tracers (i.e., AA, 0.2%; EPA, 0.3%; and DPA, 0.02%) and varied directly with precursor concentrations and inversely with concentrations of fatty acids of the alternative series. [13C]DHA formation was very low (<0.01%) with no dietary influences.     

Paradigm shift – Metabolic transformation of docosahexaenoic and eicosapentaenoic acids to bioactives exemplify the promise of fatty acid drug discovery

Fatty acid drug discovery (FADD) is defined as the identification of novel, specialized bioactive mediators that are derived from fatty acids and have precise pharmacological/therapeutic potential. A number of reports indicate that dietary intake of omega-3 fatty acids and limited intake of omega-6 promotes overall health benefits. In 1929, Burr and Burr indicated the significant role of essential fatty acids for survival and functional health of many organs. In reference to specific dietary benefits of differential omega-3 fatty acids, docosahexaenoic and eicosapentaenoic acids (DHA and EPA) are transformed to monohydroxy, dihydroxy, trihydroxy, and other complex mediators during infection, injury, and exercise to resolve inflammation. The presented FADD approach describes the metabolic transformation of DHA and EPA in response to injury, infection, and exercise to govern uncontrolled inflammation. Metabolic transformation of DHA and EPA into a number of pro-resolving molecules exemplifies a novel, inexpensive approach compared to traditional, expensive drug discovery. DHA and EPA have been recommended for prevention of cardiovascular disease since 1970. Therefore, the FADD approach is relevant to cardiovascular disease and resolution of inflammation in many injury models. Future research demands identification of novel action targets, receptors for biomolecules, mechanism(s), and drug-interactions with resolvins in order to maintain homeostasis.     

α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans

Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors.     

Enhancement of EPA and DHA biosynthesis by over-expression of masu salmon Δ6-desaturase-like gene in zebrafish

The n – 3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have important nutritional benefits in humans. Farmed fish could serve as promising sources of EPA/DHA, but they need these fatty acids or their precursors in their diets. Here we transferred masu salmon 6-desaturase-like gene in zebrafish to increase its ability for synthesizing EPA and DHA. Expression of this gene in transgenic fish elevated their EPA content by 1.4-fold and DHA by 2.1-fold. On the other hand, the -linolenic acid (ALA) content decreased, it being a substrate of 6-desaturase, while the total lipid remained constant. This achievement demonstrates that fatty acid metabolic pathway in fish can be modified by the transgenic technique, and perhaps this could be applied to tailor farmed fish as even better sources of valuable human food.     

Metabolism of linoleic and α-linolenic acids in cultured cardiomyocytes: Effect of different N-6 and N-3 fatty acid supplementation

The metabolites of linoleic (LA) and -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 could cause undesirable effects. Since they appear to have different and synergistic roles, only combined treatment with both n-6 and n-3 metabolites is likely to achieve optimum results.     

Linoleic and α-linolenic acid as precursor and inhibitor for the synthesis of long-chain polyunsaturated fatty acids in liver and brain of growing pigs

Studies suggested that in human adults, linoleic acid (LA) inhibits the biosynthesis of n-3 long-chain polyunsaturated fatty acids (LC-PUFA), but their effects in growing subjects are largely unknown. We used growing pigs as a model to investigate whether high LA intake affects the conversion of n-3 LC-PUFA by determining fatty acid composition and mRNA levels of Δ5- and Δ6 desaturase and elongase 2 and -5 in liver and brain. In a 2 × 2 factorial arrangement, 32 gilts from eight litters were assigned to one of the four dietary treatments, varying in LA and α-linolenic acid (ALA) intakes. Low ALA and LA intakes were 0.15 and 1.31, and high ALA and LA intakes were 1.48 and 2.65 g/kg BW0.75 per day, respectively. LA intake increased arachidonic acid (ARA) in liver. ALA intake increased eicosapentaenoic acid (EPA) concentrations, but decreased docosahexaenoic acid (DHA) (all P < 0.01) in liver. Competition between the n-3 and n-6 LC-PUFA biosynthetic pathways was evidenced by reductions of ARA (>40%) at high ALA intakes. Concentration of EPA (>35%) and DHA (>20%) was decreased by high LA intake (all P < 0.001). Liver mRNA levels of Δ5- and Δ6 desaturase were increased by LA, and that of elongase 2 by both ALA and LA intakes. In contrast, brain DHA was virtually unaffected by dietary LA and ALA. Generally, dietary LA inhibited the biosynthesis of n-3 LC-PUFA in liver. ALA strongly affects the conversion of both hepatic n-3 and n-6 LC-PUFA. DHA levels in brain were irresponsive to these diets. Apart from Δ6 desaturase, elongase 2 may be a rate-limiting enzyme in the formation of DHA.     

Preferential accumulation of fatty acids in the testis and ovary of cultured and wild sweet smelt Plecoglossus altivelis

The effect of dietary lipid on the fatty acid composition of muscle, testis and ovary of cultured sweet smelt, Plecoglossus altivelis, was investigated and compared with that of wild sweet smelt. Cultured fish were fed three different diets for 12 weeks: a control diet rich in docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) (CO group); a diet deficient in DHA and EPA (DP group); and a diet rich in alpha-linolenic acid (ALA, 18:3n-3), but deficient in DHA and EPA (LP group). The fatty acid composition of muscle and gonad lipids was related with dietary fatty acids. Despite the difference in DHA and EPA content in the diets, muscles and gonads, respectively, contained almost equal levels of DHA and EPA in each CO and DP group. However, the muscle and gonad of the LP group showed a lower level of DHA than other groups, due to having the highest level of ALA. In the wild fish muscle, the DHA content was similar to that of CO and DP groups, but the EPA content showed the highest level in all groups. There was no difference in the muscle fatty acid proportions between male and female. On the other hand, the testes of cultured and wild fish were rich in DHA, EPA, docosapentaenoic acid and arachidonic acid, while ovaries were rich in oleic, palmitoleic, linoleic acids and ALA. Moreover, of all the groups, the fish fatty acid composition of the LP group was closest to that of wild fish. These results indicate that in the sweet smelt, tissue n-3 polyunsaturated fatty acids (PUFAs) greater than C20 can be synthesized from dietary precursors and special fatty acids are preferentially accumulated to the testis or ovary, respectively, to play different physiological functions.     

Effect of increasing the omega-3 fatty acid in the diets of animals on the animal products consumed by humans

As shown by huge amount of assays in human as well as in animal models, w-3 polyunsaturated fatty acids play important role in the development and maintenance of different organs, primarily the brain, and could be useful in the prevention of different pathologies, mainly the cardiovascular diseases, and, as proposed recently, some psychiatric, dermatological or rheumatological disorders. For ALA, the major and cheapest source for human is rapeseed oil (canola oil), and walnut "noix de Grenoble" oil). The actual goal is first to identify which foods are naturally rich in w-3 fatty acids, and, second, to determine the true impact of the formulations (enriched in w-3 fatty acids) in chows used on farms and breeding centres on the nutritional value of the products and thus their effect on the health of consumers, thanks to quantities of either ALA, or EPA or DHA or both. This concern fish (in proportion of their lipid content, mainly mackerel, salmon, sardine and herring), eggs (wildly naturally rich in w-3 fatty acids, both ALA and DHA, or from laying hen fed ALA from linseed or rapeseed), meat from birds, mammals (from the highest concentration : rabbit, then pig and monogastrics, then polygastrics such as beef, mutton and goat) \; in butter, milk, dairy products, cheese (all naturally poor in w-3 fatty acids)... Indeed, the nature of fatty acids of reserve triglycerides (found in more or less large amounts depending on the anatomical localisation, that is to say the butcher's cuts) can vary mainly as a function of the food received by the animal. EPA and DHA are mainly present in animal's products. The impact (qualitative and quantitative) of alterations in the lipid composition of animal foods on the nutritional value of derived products (in terms of EPA and DHA content) eaten by humans are more important in single-stomach animals than multi-stomach animals (due to their hydrogenating intestinal bacteria). The intestinal physiology of birds results in the relatively good preservation of their dietary w-3 fatty acids. The enrichment in eggs is proportional to the amount of w-3 fatty acids in the hen's diet and can be extremely important. Including ALA in fish feeds is effective only if they are, like carp, vegetarians, as they have the enzymes required to transform ALA into EPA and DHA \; in contrast, it is probably less effective for carnivorous fish (75 % of the fish used for human), which have little of these enzymes : their feed must contain marine animals, mainly fish or fish oil. Analysis of the published results shows that, under the best conditions, feeding animals with extracts of linseed and rapeseed grains, for example, increases the level of ALA acid by 20 to 40-fold in eggs (according to the low or high level of ALA in commercial eggs), 10-fold in chicken, 6-fold in pork and less than 2-fold in beef. By feeding animals with fish extracts or algae (oils), the level of DHA is increased by 20-fold in fish, 7-fold in chicken, 3 to 6-fold in eggs, less than 2-fold in beef. In practise, the effect is considerable for fish and egg, interesting for poultry and rabbit, extremely low for beef, mutton and sheep. The effect on the price paid by the consumer is very low compared to the considerable gain in nutritional value.     

Eicosapentaenoic acid and arachidonic acid: collaboration and not antagonism is the key to biological understanding

Much of the literature on omega-3 and omega-6 fatty acids suggests that desirable effects of omega-3 fatty acids are in part related to depletion of arachidonic acid (AA). However, in rats and humans, we have found that low doses of EPA actually elevate membrane AA phospholipid concentrations. In patients with schizophrenia, treatment with eicosapentaenoic acid (EPA) produced clinical improvement, but that improvement was greater at a dose of 2 g/day than at 4 g/day. The improvement was not significantly correlated with changes in either EPA or docosahexaenoic acid (DHA) but was highly significantly positively correlated with rises in red cell membrane AA. We suggest that elevation of concentrations of both AA and EPA in cell membranes may be important for health.     

Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent

Vegans do not consume meat and fish and have therefore low intakes of long chain polyunsaturated fatty acids (LCP). They may consequently have little negative feedback inhibition from dietary LCP on conversion of alpha -linolenic acid (ALA) to the LCP omega 3 eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. We investigated whether supplementation of nine apparently healthy vegans with 2.01 g ALA (4 ml linseed oil), 1.17 g gamma-linolenic acid (GLA) (6 ml borage oil) or their combination increases the LCP omega 3 contents of erythrocytes (RBC) and platelets (PLT), and of plasma phospholipids (PL), cholesterol esters (CE) and triglycerides (TG). The supplements changed the dietary LA/ALA ratio (in g/g) from about 13.7 (baseline) to 6.8 (linseed oil), 14.3 (borage oil) and 6.4 (linseed + borage oil), respectively. ALA or GLA given as single supplements did not increase LCP omega 3 status, but their combination augmented LCP omega 3 (in CE) and EPA (in fasting TG) to a statistically significant, but nevertheless negligible, extent. We conclude that negative feedback inhibition by dietary LCP, if any, does not play an important role in the inability to augment notably DHA status by dietary ALA. The reach of a DHA plateau already at low dietary ALA intakes suggests that dietary DHA causes a non-functional DHA surplus, or is, alternatively, important for maintaining DHA status at a functionally relevant level.