title: Immunomodulation by dietary long chain omega-3 fatty acids and the potential for adverse health outcomes.
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.
authors.affiliation: Department of Food Science and Human, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI, United States; College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, United States. Electronic address: imigjeni@msu.edu.
authors.forename: Jenifer I
authors.initials: JI
authors.lastname: Fenton
authors.forename: Norman G
authors.initials: NG
authors.lastname: Hord
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Ghosh
authors.forename: Eric A
authors.initials: EA
authors.lastname: Gurzell
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases; D004041:Dietary Fats / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000009:adverse effects / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000009:adverse effects / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects* / Q000494:pharmacology*; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D007239:Infections; D007249:Inflammation; D009369:Neoplasms; D018673:Nutrition Policy; D012307:Risk Factors
chemical_list: D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D007155:Immunologic Factors; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: B cell; CHD; Cancer; Colitis; Coronary heart disease; Fish oil; Immune function; RA; Rheumatoid arthritis; TLR; Toll-like receptor