Journal Name:
Br. J. Nutr.
Article Title:
Eicosapentaenoic and docosapentaenoic acids are the principal products of a-linolenic acid metabolism in young men.
Date Written:
2002
Volume:
88
Number:
4
Page:
355
Author(s):
Burdge, G.C.; Jones, A.E.; Wootton, S.A.
Article:
The concentration of n-3 long-chain polyunsaturated fatty acids (LCPUFA), principally eicosapentaenoic acid (20 : 5n-3; EPA) and docosahexaenoic acid (22 : 6n-3; DHA), in cell membranes is an important factor in determining cell and tissue function. Western populations generally consume diets in which the principal n-3 essential fatty acid is a-linolenic acid (18 : 3n-3; ALA), while the dietary intakes of EPA and DHA are substantially lower. Thus ability to convert ALA to n-3 LCPUFA may be an important mechanism for maintaining adequate EPA and DHA concentrations in cell membranes and thus optimal tissue function. However, the extent to which human adults satisfy their metabolic demands for DHA through either dietary intake or these synthetic processes remains unclear.
In this study, the capacity for conversion of a-linolenic acid (ALA) to n-3 long-chain polyunsaturated fatty acids was investigated in young men. Emulsified [U-13C]ALA was administered orally with a mixed meal to six subjects consuming their habitual diet. Approximately 33 % of administered [13C]ALA was recovered as 13CO2 on breath over the first 24 h. [13C]ALA was mobilised from enterocytes primarily as chylomicron triacylglycerol (TAG), while [13C]ALA incorporation into plasma phosphatidylcholine (PC) occurred later, probably by the liver. The time scale of conversion of [13C]ALA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) suggested that the liver was the principal site of ALA desaturation and elongation, although there was some indication of EPA and DPA synthesis by enterocytes. [13C]EPA and [13C]DPA concentrations were greater in plasma PC than TAG, and were present in the circulation for up to 7 and 14 d, respectively. There was no apparent 13C enrichment of docosahexaenoic acid (DHA) in plasma PC, TAG or non-esterified fatty acids at any time point measured up to 21 d. This pattern of 13C n-3 fatty acid labelling suggests inhibition or restriction of DHA synthesis downstream of DPA. [13C]ALA, [13C]EPA and [13C]DPA were incorporated into erythrocyte PC, but not phosphatidylethanolamine, suggesting uptake of intact plasma PC molecules from lipoproteins into erythrocyte membranes. Since the capacity of adult males to convert ALA to DHA was either very low or absent, uptake of pre-formed DHA from the diet may be critical for maintaining adequate membrane DHA concentrations in these individuals.
The results of the present study are in broad agreement with previous reports in human adults which show limited conversion of ALA to EPA and marginal DHA synthesis. Consistent 13C incorporation into ALA, EPA and DPA was shown here. The subjects in the present study did not consume diets enriched in fish or take fish oil supplements and so product inhibition of the ALA conversion pathway seems unlikely to explain the apparent absence of DHA synthesis. Since these subjects were essentially well-nourished it is possible that their demands for DHA were met adequately by their diet and thus there was no physiological drive for DHA synthesis leading to down regulation of conversion of DPA to DHA.
These present data are consistent with the results of studies which showed that increasing ALA intake was associated with increased EPA and/or DPA concentrations in plasma and/or membrane phospholipids. Increased plasma DHA concentration following increased ALA intakes has been reported in some studies. Together these data are consistent with the view that DHA synthesis from ALA is constrained. The few studies which report increased DHA levels following ALA supplementation suggest that the extent to which ALA is converted to DHA may differ between groups of individuals. *The principal conclusion of the present study is that these adult men possessed the capacity to synthesise EPA and DPA from ALA. However, DHA synthesis, if it occurred, was insufficient to increase enrichment above background to levels that could be detected using this methodology. These results, taken together with the findings of other isotopic studies and dietary intervention trials, would suggest that the initial conversion of ALA to EPA and DPA occurs at the levels of dietary ALA intake typically consumed by adult men, but that the conversion to DHA is severely restricted. The nutritional demands for DHA in healthy adults are likely to be modest as they reflect principally the need to supply DHA to support turnover and resynthesis of cell membranes. In these well-nourished men, metabolic demands for DHA may have been satisfied by existing pools of DHA within the body or by dietary supply of DHA so that further synthesis has been down regulated to the point where the rates of conversion were so low as to be of questionable biological importance.
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