Distribution, interconversion, and dose response of n−3 fatty acids in humans

Abstract

n-3 Fatty acids have important visual, mental, and cardiovascular health benefits throughout the life cycle. Biodistribution, interconversion, and dose response data are reviewed herein to provide a basis for more rational n-3 dose selections. Docosahexaenoic acid (DHA) is the principal n-3 fatty acid in tissues and is particularly abundant in neural and retinal tissue. Limited storage of the n-3 fatty acids in adipose tissue suggests that a continued dietary supply is needed. A large proportion of dietary alpha-linolenic acid (ALA) is oxidized, and because of limited interconversion of n-3 fatty acids in humans, ALA supplementation does not result in appreciable accumulation of long-chain n-3 fatty acids in plasma. Eicosapentaenoic acid (EPA) but not DHA concentrations in plasma increase in response to dietary EPA. Dietary DHA results in a dose-dependent, saturable increase in plasma DHA concentrations and modest increases in EPA concentrations. Plasma DHA concentrations equilibrate in approximately 1 mo and then remain at steady state throughout supplementation. DHA doses of approximately 2 g/d result in a near maximal plasma response. Both dietary DHA and EPA reduce plasma arachidonic acid concentrations. Tissue contents of DHA and EPA also increase in response to supplementation with these fatty acids. Human milk contents of DHA are dependent on diet, and infant DHA concentrations are determined by their dietary intake of this fatty acid. We conclude that the most predictable way to increase a specific long-chain n-3 fatty acid in plasma, tissues, or human milk is to supplement with the fatty acid of interest.

Dietary n-6- or n-3-rich vegetable fats and α-tocopheryl acetate: effects on fatty acid composition and stability of rabbit plasma, liver and meat

“…Changes in the FA composition of tissues from rabbit (Bernardini et al, 1999), other animals (Wood and Enser, 1997;Enser et al, 2000;Bou et al, 2006b) and humans (Arterburn et al, 2006) have been reported as a result of varying the FA profile of diets. In our study in rabbits, the content of trans FA in plasma and liver and the content of MUFA in liver decreased, while total PUFA in liver increased (Tables 1 and 2) as BT in feeds was replaced by increasing doses of n-6-or n-3-rich vegetable fat .…”

“…However, the effectiveness of the synthesis of DHA from linolenic acid in animals and humans is controversial, as it has been reported to be limited (Cherian and Sim, 1995;D'Arrigo et al, 2002;Hoz et al, 2003;Burdge and Calder, 2005b;Nuernberg et al, 2005). This has been related to the last step in the biosynthesis pathway of DHA, a b-oxidation of C24:6n-3 which involves translocations between the endoplasmic reticulum and peroxisomes of both DHA and its precursor (C24:6n-3) (Burdge and Calder, 2005b;Arterburn et al, 2006).…”

“…A similar effect of increasing doses of LO in feeds was found in meat FA composition ; however, due to the higher biosynthetic activity of liver, the increases in long-chain n-3 PUFA in liver were greater than in meat, as were the decreases in long-chain n-6 FA. In other animal and human studies, concomitant reductions have also been reported in the content of long-chain n-6 PUFA, as a result of increased biosynthesis of n-3 FA in several tissues due to dietary LO (Cherian et al, 1996;Bernardini et al, 1999;Nuernberg et al, 2005;Arterburn et al, 2006).…”

Dietary PUFA and cancer

“…patients without CHD of 'at least two (preferable oily) fish meals per week' or approximately 500 mg EPA + DHA/d; while for patients with CHD an EPA + DHA intake of 1 g, preferably from oily fish is recommended (52) .…”

Fish and seafood consumption and omega 3 intake in French coastal populations: CALIPSO survey

“…n-3 LC PUFA supplements might help to reduce cardiovascular risks by lowering the risk of sudden death of people with a history of cardiovascular problems (4) . Dietary n-3 LC PUFA and n-3 LC PUFA supplements have been demonstrated to be linked with n-3 LC PUFA concentrations in blood, plasma, tissues or human milk, being responsible for beneficial effects on visual and mental health and neurodevelopment (5,6) .Nevertheless, at present, the respective mechanism of action of each of EPA and DHA is debatable. As described in the Symposium 'n-3 fatty acids: recommendations for therapeutics and prevention' convened by the Institute for Human Nutrition of Columbia University on 21 May 2005 (7) , confusion exists about the recommendations and the biological link between intake and health.…”