Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements

There is considerable interest in the potential impact of several polyunsaturated fatty acids (PUFAs) in mitigating the significant morbidity and mortality caused by degenerative diseases of the cardiovascular system and brain. Despite this interest, confusion surrounds the extent of conversion in humans of the parent PUFA, linoleic acid or alpha-linolenic acid (ALA), to their respective long-chain PUFA products. As a result, there is uncertainty about the potential benefits of ALA versus eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Some of the confusion arises because although mammals have the necessary enzymes to make the long-chain PUFA from the parent PUFA, in vivo studies in humans show that <5% of ALA is converted to EPA and <0.5% of ALA is converted to DHA. Because the capacity of this pathway is very low in healthy, non-vegetarian humans, even large amounts of dietary ALA have a negligible effect on plasma DHA, an effect paralleled in the n-6 PUFA by a negligible effect of dietary linoleic acid on plasma arachidonic acid. Despite this inefficient conversion, there are potential roles in human health for ALA and EPA that could be independent of their metabolism to DHA through the desaturation � chain elongation pathway. (Author's abstract)
This review focuses on two questions with regard to the nutritional importance of n-6 and n-3 PUFA in adult humans: (i) estimating the percentage conversion through the desaturation � chain elongation pathway of the shorter chain PUFA to their principal respective long chain PUFA, i.e., metabolism of LA to AA or ALA to DHA, and (ii) the implications of inefficient conversion of parent to long-chain PUFA in humans for the nutritional or potentially health protective roles of individual PUFA. The context that the authors base their review is that limited conversion of short chain to long-chain PUFA in humans exists (although this assumption is flawed in itself). The data presented does indicate that human infants need preformed dietary DHA.  Adult humans cannot normally synthesis a lot of DHA, but it is still uncertain which conditions lead to clear and specific symptoms of DHA deficiency in adults. The authors present a compelling case for the need to define and agree on the conditions of dietary essentiality of LA, AA, ALA, EPA, and DHA. The review provides data to suggest that most adult humans are virtually unable to convert ALA (or EPA which is often overlooked) to DHA. People not eating foods or supplements containing DHA have lower plasma and tissue DHA and have a higher risk of declining mental and cardiovascular function. The clinical impact of supplemental EPA and DHA is lower in those who, for other reasons (such as having a healthier diet), are already at lower risk of declining mental or cardiovascular function. ALA has protective effects but probably more so in those at lower risk. It has been argued that the low capacity of the human desaturation � chain elongation system is a result of humans evolving on diets that contained fish and shellfish, resulting in a continuous consumption of preformed AA, EPA, and DHA. The authors call for additional research as well as promotion of diets with higher n-3 and lower n-6 PUFA intake, especially as related to mental and cardiovascular health. (Editor�s comments)