Narrative Review of n-3 Polyunsaturated Fatty Acid Supplementation upon Immune Functions, Resolution Molecules and Lipid Peroxidation (original) (raw)
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n-3 Polyunsaturated fatty acids and immune function
Proceedings of the Nutrition Society, 1998
Considerable interest in fish oil was initially generated by epidemiological studies in Eskimos showing the beneficial effect of consuming fish and fish oil in preventing IHD (Dyerberg et al. 1978; Dyerberg & Bang, 1979). In the following two decades, investigations of fish oil have been motivated by, and extended to, many different aspects of health and disease. A wide spectrum of studies has revealed the ability of fish oil to affect the course of cardiovascular disease, autoimmune and inflammatory diseases, immune function, infection, allograft rejection, and certain cancers (Fernandes & Venkatraman, 1993; Calder, 1996). The biological effects of fish oil are attributed to their n-3 polyunsaturated fatty acids (PUFA), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA can be incorporated into cell membranes where they influence membrane fluidity, receptor function, enzyme activity and production of lipid mediators. ~~ ~ ~~ Abbreviations: AA, arachidonic acid; ALA, a-linolenic acid; Con A, concanavalin A, DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid IL, interleukin; LT, leukotriene; PBMC, peripheral-blood mononuclear cells; PG, prostaglandin; PHA, phytohaemagglutinin; PUFA, polyunsaturated fatty acids; TNF, tumour necrosis factor.
The American Journal of Clinical Nutrition, 2003
Background: Greatly increasing dietary flaxseed oil [rich in the nϪ3 polyunsaturated fatty acid (PUFA) ␣-linolenic acid (ALA)] or fish oil [rich in the long-chain nϪ3 PUFAs eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids] can reduce markers of immune cell function. The effects of more modest doses are unclear, and it is not known whether ALA has the same effects as its long-chain derivatives. Objective: The objective was to determine the effects of enriching the diet with ALA or EPA+DHA on immune outcomes representing key functions of human neutrophils, monocytes, and lymphocytes. Design: In a placebo-controlled, double-blind, parallel study, 150 healthy men and women aged 25-72 y were randomly assigned to 1 of 5 interventions: placebo (no additional nϪ3 PUFAs), 4.5 or 9.5 g ALA/d, and 0.77 or 1.7 g EPA+DHA/d for 6 mo. The nϪ3 PUFAs were provided in 25 g fat spread plus 3 oil capsules. Blood samples were taken at 0, 3, and 6 mo. Results: The fatty acid composition of peripheral blood mononuclear cell phospholipids was significantly different in the groups with higher intakes of ALA or EPA+DHA. The interventions did not alter the percentages of neutrophils or monocytes engaged in phagocytosis of Escherichia coli or in phagocytic activity, the percentages of neutrophils or monocytes undergoing oxidative burst in response to E. coli or phorbol ester, the proliferation of lymphocytes in response to a T cell mitogen, the production of numerous cytokines by monocytes and lymphocytes, or the in vivo delayed-type hypersensitivity response. Conclusion: An intake of ≤ 9.5 g ALA/d or ≤ 1.7 g EPA+DHA/d does not alter the functional activity of neutrophils, monocytes, or lymphocytes, but it changes the fatty acid composition of mononuclear cells.
Unsaturated Fatty Acids and Their Immunomodulatory Properties
Biology
Oils are an essential part of the human diet and are primarily derived from plant (or sometimes fish) sources. Several of them exhibit anti-inflammatory properties. Specific diets, such as Mediterranean diet, that are high in ω-3 polyunsaturated fatty acids (PUFAs) and ω-9 monounsaturated fatty acids (MUFAs) have even been shown to exert an overall positive impact on human health. One of the most widely used supplements in the developed world is fish oil, which contains high amounts of PUFAs docosahexaenoic and eicosapentaenoic acid. This review is focused on the natural sources of various polyunsaturated and monounsaturated fatty acids in the human diet, and their role as precursor molecules in immune signaling pathways. Consideration is also given to their role in CNS immunity. Recent findings from clinical trials utilizing various fatty acids or diets high in specific fatty acids are reviewed, along with the mechanisms through which fatty acids exert their anti-inflammatory prope...
American Journal of Clinical Nutrition
Background: Supplementation of the diet with fish oil, which is rich in the long-chain nҀ3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is reported to decrease several markers of immune function. However, whether EPA, DHA, or a combination of the 2 exerts these immunomodulatory effects is unclear. Objective: The objective of the study was to determine the effects of supplementation with an EPA-rich or DHA-rich oil on a range of immune outcomes representing key functions of human neutrophils, monocytes, and lymphocytes in healthy humans. Design: In a placebo-controlled, double-blind, parallel study, 42 healthy subjects were randomly allocated to receive supplementation with either placebo (olive oil), EPA (4.7 g/d), or DHA (4.9 g/d) for 4 wk. Blood samples were taken before and after supplementation. Results: The fatty acid composition of plasma phospholipids and neutrophils was dramatically altered by supplementation with EPA or DHA, and the effects of EPA differed notably from those of DHA. DHA supplementation decreased T lymphocyte activation, as assessed by expression of CD69, whereas EPA supplementation had no significant effect. Neither the EPA-rich oil nor the DHA-rich oil had any significant effect on monocyte or neutrophil phagocytosis or on cytokine production or adhesion molecule expression by peripheral blood mononuclear cells. Conclusions: Supplementation with DHA, but not with EPA, suppresses T lymphocyte activation, as assessed by expression of CD69. EPA alone does not, therefore, influence CD69 expression. No other marker of immune function assessed in this study was significantly affected by either EPA or DHA.
Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2013
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.
Clinical Immunology and Immunopathology, 1991
We have studied the effects of dietary supplementation with fish oil on immunological parameters in a group of six normal volunteers, four of whom received a fish oil extract (total EPA dose of 2.4 g/day, which is on the lower range of clinically effective doses) for 6 weeks and two of which received a placebo (olive oil) for an identical period of time. Each volunteer was followed up for a period of 23 weeks after the dietary intervention was ended. All volunteers wei'e boosted witEtetanus toxoid (TI') at the onset of the trial. Several immune parameters were followed longitudinally, including NBT reduction and lysozyme release to test neutrophil function; lymphocyte subpopulations; mitogenic responses to phytohemagglutinin (PHA), concanavalin A (Con A) and anti-CD3; IL-2 release after PHA and pokeweed mitogen (PWM) stimulation; immunoglobulin and anti-TT antibody (ATr) synthesis by stimulated lymphocytes; and serum levels of immunoglobulins and of ATT. No consistent changes were observed in neutrophil function tests, mitogenic responses to PHA and Con A, and lymphocyte subsets. The mitogenic response to anti-CD3 and the release of IL-2 after stimulation with PHA and PWM appeared reduced as a consequence of fish oil ingestion, and levels of serum immunoglobulins decreased in three of the volunteers receiving fish oil supplementation. The systemic humoral response after the "IT booster appeared not to be influenced by the ingestion offish oil. However, in those subjects who were given fish oil supplementation, the specific in vitro response of their peripheral blood lymphocytes to TT appeared to be compromised at Week 3. This could reflect the need for progressive accumulation of EPA in lymphocyte membranes for the suppressive effect to be detectable, but it could also reflect a differential sensitivity to the effects of fish oil of circulating B lymphocytes vs. bone marrow B lymphocytes. All the parameters apparently affected by fish oil ingestion were also affected by the incubation of normal lymph_ocytes with EPA in vitro.
Effect of (n-3) polyunsaturated fatty acids on cytokine production and their biologic function
Nutrition, 1996
Cytokines are important biologic mediators with tightly regulated production. Overproduction contributes to pathogenesis of acute and chronic inflammatory, autoimmune, atherosclerotic, and neoplastic diseases. Animal and human studies have shown that production of cytokines can be reduced by long-chain (n-3) polyunsaturated fatty acids (PUFA). This, in turn, results in reduction of the severity of certain autoimmune, inflammatory, and atherosclerotic diseases and reduces cytokine-induced anorexia. Because these cytokines are also involved in control of the host defense, substantial reduction in their production could impair normal immune response. In addition, increased intake of (n-3) PUFAs without adequate antioxidant protection could result in increased free radical formation and lipid peroxidation, leading to a reduction in T cell-mediated function, natural killer cell activity, and macrophage cytotoxicity. These risks associated with the intake of (n-3) PUFAs may be minimized without compromising its beneficial effects by the intake of appropriate levels of antioxidants such as vitamin E.