Eicosapentaenoic and docosapentaenoic acids are the principal products of a-linolenic acid metabolism in young men

The capacity for conversion of alpha-linolenic acid (ALNA) to n-3 long-chain polyunsaturated fatty acids was investigated in young men. Emulsified [U- 13C]ALNA was administered orally with a mixed meal to six subjects consuming their habitual diet. Approximately 33% of administered [13C]ALNA was recovered as 13CO 2 on breath over the first 24h. [13C]ALNA was mobilised from enterocytes primarily as chylomicron triacylglycerol (TAG), while [13C]ALNA incorporation into plasma phosphatidylcholine (PC) occurred later, probably by the liver. The time scale of conversion of [13C]ALNA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) suggested that the liver was the principal site of ALNA 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 14d, 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 21d. This pattern of 13C n-3 fatty acid labelling suggests inhibition or restriction of DHA synthesis downstream of DPA. [13C]ALNA, [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 ALNA 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. (Author's abstract)
The ability to convert ALNA 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 the present study, the fate of [U-13C]ALNA administered in the context of a mixed meal, designed such that the lipid component reflected the n-3 fatty acid content of the UK diet to men consuming their habitual omnivorous diet, was assessed. The results describe incorporation of 13C into n-3 LCPUFA in plasma,  incorporation of 13C-labelled fatty acids into erythrocyte membrane phospholipids and the extent of partitioning of [13C]ALNA towards beta-oxidation. The principal products of desaturation and elongation of ALNA were EPA and DPA. There was no evidence for increased 13C enrichment in DHA. The extent to which ALNA is used as an energy source may be driven by the precise metabolic requirements or dietary intake of the organism. Incorporation of labelled ALNA into plasma PC was primarily the result of hepatic PC biosynthesis and mobilisation from the liver by VLDL. These present data are consistent with the results of studies which showed that increasing ALNA intake was associated with increased EPA and/or DPA concentrations in plasma and/or membrane phospholipids. Increased plasma DHA concentration following increased ALNA intakes has been reported in some studies. In this study, 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. In other individuals with different metabolic demands for DHA and under different experimental conditions, these demands may not be met, necessitating an increase in DHA synthesis to rates greater than that observed here. According to the authors, if for any reason, the ability to increase DHA synthesis was constrained to levels seen in the present study, these demands could only be met by an increased intake and assimilation of pre-formed DHA from the diet. (Editor's comments)