Alpha-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

There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n-3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n-3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n -3 tissue fatty acid   content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes beta-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n-3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n-3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n- 3 levels. (Author's abstract)
In this extensive review, the authors present an overview of the metabolism of alpha -linolenic acid (ALA, 18:3n-3), the essential precursor of the longer chain n-3 PUFA. Evidence from several studies in vivo and in vitro, indicate that the n-6 and n-3 fatty acid families compete for the same enzymes to convert these fatty acids into longer chain fatty acids. There are two basic metabolic fates for ALA. First, it is subjected to beta oxidation and extensive carbon recycling. Second, it is converted into longer fatty acids via elongation and desaturation. The scientific evidence obtained in a variety of models has confirmed that ALA is significantly accumulated and converted to longer n-3 fatty acids. In addition, these studies provide evidence indicating that the fatty acid accumulation is tissue-dependent, suggesting that the metabolism is based upon a tissue-selective need for longer n-3 fatty acids, such as DHA. In this review, these two metabolic fates of ALA are discussed in detail as well as the downstream impact of n-3 fatty acids on health and disease. The authors demonstrate significant evidence that dietary ALA is rapidly accumulated in different compartments despite the fact that a certain percentage is subjected to beta-oxidation. Based upon kinetic evidence, dietary studies with ALA, and human studies, the conversion of ALA to DHA by the liver and other specific DHA requiring tissues such as the brain, will provide ample DHA when sufficient ALA (>1200 mg) is consumed. (Editor's comments)