ReviewAlpha-linolenic acid and its conversion to longer chain n−3 fatty acids: Benefits for human health and a role in maintaining tissue n−3 fatty acid levels
Section snippets
Introduction to n−3 fatty acids and their metabolism
All-cis-9,12,15-octadecatrienoic acid or α-linolenic acid (ALA, 18:3n−3), is a polyunsaturated fatty acid (PUFA) abundant in some vegetable oils (Table 1). In the early 1930s, the essentially of ALA and linoleic acid (18:2n−6; LNA) in rat diets was identified [1], but in humans the first demonstration of this was reported only in the early 1980s [2], [3]. Hence, ALA is referred to as the essential precursor of the longer chain n−3 PUFA (commonly known as omega−3 fatty acids) because it is the
Conversion of ALA into long chain n−3 PUFA
Because ALA is the precursor for DHA, it is considered as an adequate dietary source to provide and maintain the required levels of DHA in mammals. This statement is based upon several important points, yet is fraught with controversy. First, the minimal ALA requirement for developing rats is 2.4 g/kg diet (0.4% of energy), while for adult rats to maintain the maximal DHA level the requirement for ALA is 1.3 g/kg diet (0.26% of dietary energy) [52], [53]. Similar values were obtained using [U-13
A kinetic perspective on ALA conversion to DHA
The most elusive, yet perhaps the most important concept, in the field of n−3 fatty acid metabolism is whether ALA is efficiently converted to DHA and in which tissue(s) does this occur in mammals. In previous sections, we examined several key points. First, that if ALA is converted, it is done in a tissue-selective manner. This is based upon our own studies as well as those by others, demonstrating an accretion of DHA in brains in ALA-fed rats combined with studies showing a tissue-selective
ALA health benefits
Chronologically, the studies on the health benefits of DHA alone or together with EPA preceded the interest in the potential beneficial effects of ALA. Recently, there has been an increased interest in this topic as we expand our understanding of ALA metabolism. As is the case of DHA and EPA, it is still not clear the mechanism by which ALA may exert its beneficial effects. First, ALA could be beneficial by simply acting as the precursor of EPA and DHA. As demonstrated in previous sections, an
ALA sources
One major contributor to reduced ALA consumption was increased consumption of high LNA containing grains, such as corn, in the Western diet. In Western Europe and North America, this has dramatically shifted the ratio n−6 to n−3 fatty acids from 8:1 to as high as 20:1 [66], [263], [264], [265]. This very high ratio is far from what is considered optimal, that is, a ratio LNA to ALA of 4:1 [23], [67]. This led to an ever increasing awareness on the part of governments to educate the public as
Conclusion
Thus, in this review we demonstrate significant evidence to conclude that dietary ALA is rapidly accumulated in different compartments despite the fact that a certain percentage of this fatty acid, as is the case of many fatty acids, is subjected to β-oxidation. Upon entering tissues, ALA is the substrate of the elongation and desaturation enzymatic machinery in a tissue-dependent manner, leading to the synthesis of longer chain fatty acids as EPA, DPA and, in certain tissues, of DHA. Taking
Acknowledgements
This work was supported by the Ministerio de Ciencia e Innovación providing a contract “Juan de la Cierva” to G.B.-C. and by a grant from the NIH R21 NS060141 to E.J.M. We thank our colleagues from around the world who have supported our work in the field over the years and who have provided thought provoking conversations.
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