Immunomodulation by dietary long chain omega-3 fatty acids and the potential for adverse health outcomes - PubMed (original) (raw)

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Immunomodulation by dietary long chain omega-3 fatty acids and the potential for adverse health outcomes

Jenifer I Fenton et al. Prostaglandins Leukot Essent Fatty Acids. 2013 Nov-Dec.

Abstract

Recommendations to consume fish for prevention of cardiovascular disease (CVD), along with the U.S. Food and Drug Administration-approved generally recognized as safe (GRAS) status for long chain omega-3 fatty acids, may have had the unanticipated consequence of encouraging long-chain omega-3 (ω-3) fatty acid [(eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] supplementation and fortification practices. While there is evidence supporting a protective role for EPA/DHA supplementation in reducing sudden cardiac events, the safety and efficacy of supplementation with LCω-3PUFA in the context of other disease outcomes is unclear. Recent studies of bacterial, viral, and fungal infections in animal models of infectious disease demonstrate that LCω-3PUFA intake dampens immunity and alters pathogen clearance and can result in reduced survival. The same physiological properties of EPA/DHA that are responsible for the amelioration of inflammation associated with chronic cardiovascular pathology or autoimmune states, may impair pathogen clearance during acute infections by decreasing host resistance or interfere with tumor surveillance resulting in adverse health outcomes. Recent observations that high serum LCω-3PUFA levels are associated with higher risk of prostate cancer and atrial fibrillation raise concern for adverse outcomes. Given the widespread use of supplements and fortification of common food items with LCω-3PUFA, this review focuses on the immunomodulatory effects of the dietary LCω-3PUFAs, EPA and DHA, the mechanistic basis for potential negative health outcomes, and calls for biomarker development and validation as rational first steps towards setting recommended dietary intake levels.

Keywords: B cell; CHD; Cancer; Colitis; Coronary heart disease; Fish oil; Immune function; RA; Rheumatoid arthritis; TLR; Toll-like receptor.

© 2013 Published by Elsevier Ltd.

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Figures

Figure 1

Figure 1

The model shows a proposed mechanism by which DHA acyl chains disrupt the physical clustering of lipid rafts and associated proteins. Upon LCω-3PUFA incorporation into the membrane, and possibly through changes in lipid raft organization the following could result. LCω-3PUFAs disrupt the molecular organization of the plasma membrane, which initiates changes downstream on generation of bioactive lipids, cell signaling, and gene expression. A disruption in raft domains with n-3 PUFAs will have downstream effects on immune cell function. To date, the function of several immune cells (i.e. CD4+ T, B, dendritic cells, macrophages) in addition to other cells are disrupted by incorporation of LCω-3PUFAs into the plasma membrane. Suppression of function would have utility for treatment of symptoms associated with chronic inflammation. However, a suppression of immune cell function, perhaps at high doses of LCω-3PUFAs, could have negative side effects on susceptibility to infection and targeting of cancer cells by specific immune cells. LCω-3PUFA feeding may also influence microbial community structure and risk of inflammation. It is not known whether dietary fatty acids affect microbial cell wall structure directly, whether these changes influence eukaryotic-prokaryotic signaling or whether fatty acid-induced changes in the overall balance of microbial populations contribute to increased risk of inflammation.

Figure 2

Figure 2

Observations associated with very low and high dietary intake of the LCω-3PUFA fatty acids, EPA and DHA. Deficiency of LCω-3PUFA intakes are associated with negative neurological, cardiovascular and reproductive outcomes. Excess LCω-3PUFA intakes are associated with an immune anergic phenotype in antigen-driven models of pathologies. Cell membrane phospholipid content has been proposed as a potential biomarker of dietary fatty acid intake and associated phenotypes. These require validation in support of the calls for Dietary Reference Intakes for these proposed nutrients.

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