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

Abstract

Recommendations to consume fish for cardiovascular disease (CVD) prevention and its generally recognized as safe (GRAS) status 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 for 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 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 have heightened the 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 for setting recommended dietary intake levels.

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols

“…Increased mild infections, such as upper respiratory infections, have also been reported with omega-3 fatty acid consumption. This may be related to an inhibition of inflammatory and immune responses, which could be beneficial for reducing cardiovascular risk [51]. However, the present study was not designed to evaluate such effects and this may simply be a chance finding.…”

Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance

“…43 In contrast, diets containing an excessive amount of n-3 PUFA can also exacerbate colitis, 16,20 and results in adverse outcomes in murine models of pathogen exposure (reviewed in Fenton et al). 10 It is possible that there are upper limits of dietary n-3 PUFA with excessive intake associated with pathological consequences. An optimal dose of n-3 PUFA should be determined to maintain a controlled and balanced immune response that can defend against pathogens while preventing chronic inflammatory conditions.…”

“…Most recently, in utero exposure to a "Western" diet has been shown to alter the offspring's intestinal microbes leaving a "lard legacy," 9 presumably through the alteration of maternal microbes that are passed onto offspring during delivery and lactation. However, in light of the current practice of extensive prenatal and postnatal supplementation of fish oil and/or its derivatives, 10 this study was undertaken to identify the specific in utero effects of pharmacological doses of fish oil, rich in long chain n-3 polyunsaturated fatty acids (n-3 PUFA), on the intestinal microbiota and immune cell homeostasis of the offspring.…”

“…16 In contrast, other studies in experimental mouse models have shown lower doses of fish oil to protect against colitis. 17,18 We have recently shown that post-natal fish oil supplementation (2% energy) results in dysregulated immune responses resulting in sepsis and mortality during enteric infection, 10 and increased oxidative stress in aged mice, 19 through the intestinal-microbe nexus. Additionally, our group had shown that excessive dietary n-3 PUFA (8 and 18% energy fish oil) fed to rat dams during gestation and lactation primed offspring to display impaired intestinal barrier development evident by reduced intestinal crypt length associated with altered permeability and heightened susceptibility to DNBS-colitis at 3 months of age.…”

Paying attention to the safety and efficacy of fish oil in treatment of knee osteoarthritis

“…Recent review2 states that long-chain omega-3 fatty acids (EPA+DHA) intake dampens immunity and alters pathogen clearance and can result in reduced survival in animal models of infectious disease. Recent observations that high serum long-chain omega-3 fatty acids levels are associated with higher risk of prostate cancer and atrial fibrillation raise concern for adverse outcomes 2 3.…”