Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men (original) (raw)
Related papers
British Journal of Nutrition, 2004
To determine the effects of EPA, stearidonic acid (STA) or g-linolenic acid (GLA) on immune outcomes, healthy male subjects consumed one of seven oil blends for 12 weeks. EPA consumption increased the EPA content of peripheral blood mononuclear cells (PBMC). Consumption of GLA (2·0 g/d) in the absence of STA or EPA increased di-homo-GLA content in PBMC. Neither STA nor its derivative 20 : 4n-3 appeared in PBMC when STA (, 1·0 g/d) was consumed. However, STA (1·0 g/d), in combination with GLA (0·9 g/d), increased the proportion of EPA in PBMC. None of the treatments altered neutrophil or monocyte phagocytosis or respiratory burst, production of inflammatory cytokines by monocytes, T lymphocyte proliferation or the delayed-type hypersensitivity response. Production of cytokines by T lymphocytes increased in all groups, with no differences among them. The proportion of lymphocytes that were natural killer cells decreased significantly in subjects receiving 2·0 g EPA or GLA/d. There were no other effects on lymphocyte sub-populations. Plasma IgE concentration decreased in most groups, but not in the control group. Plasma IgG 2 concentration increased in the EPA group. Thus, EPA or GLA at a dose of 2·0 g/d have little effect on key functions of neutrophils, monocytes and T lymphocytes, although at this dose these fatty acids decrease the number of natural killer cells. At this dose EPA increases IgG 2 concentrations. STA can increase immune cell EPA status, but at 1·0 g/d does not affect human immune function.
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.
Influence of very long-chain n-3 fatty acids on plasma markers of inflammation in middle-aged men
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2008
This study investigated the effects of a moderate dose of long-chain n-3 polyunsaturated fatty acids (1.8 g eicosapentaenoic acid (EPA) plus 0.3 g docosahexaenoic acid (DHA) per day) given for 8 weeks to healthy middle-aged males on cardiovascular risk factors, particularly plasma lipids and inflammatory markers. The study was double-blind and placebo-controlled. The proportion of EPA was significantly increased in plasma phosphatidylcholine (from 1.4% to 5.0% of total fatty acids; Po0.001), cholesteryl esters (from 1.2% to 4.5%; Po0.001) and triacylglycerols (from 0.3% to 1.8%; Po0.001). In contrast, the more modest increases in DHA in these lipid fractions were not significant. There was very little effect of n-3 fatty acids on the risk factors measured, apart from a reduction in plasma soluble intercellular adhesion molecule (sICAM)-1 concentration compared with placebo (P ¼ 0.05). The change in plasma sICAM-1 concentration was significantly inversely related to the change in DHA in plasma phosphatidylcholine (r ¼ À0.675; P ¼ 0.001), but less so to the change in EPA (r ¼ À0.406; P ¼ 0.076). Data from the present study suggest that marine oil providing 1.8 g of EPA plus 0.3 g DHA/day is not sufficient to demonstrate marked effects on cardiovascular risk factors (plasma lipids and inflammatory markers) in healthy middle-aged men, although there may be a slight anti-inflammatory effect as indicated by the decrease in sICAM-1. The stronger association between changes in DHA than EPA and sICAM-1 concentrations suggest that DHA may be more anti-inflammatory than EPA. Thus, one reason why only limited effects were seen here may be that the dose of DHA provided was insufficient. r
Lipids, 1998
Weanling rats were fed on high-fat (178 g/kg) diets which contained 4.4 g α-linolenic (ALA), γ-linolenic, arachidonic (ARA), eicosapentaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids. The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approximately 35 g/100 g total fatty acids) were constant, and the n-6 to n-3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Prostaglandin E 2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA-or DHA-fed rats. Replacing dietary ALA with EPA resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either γ-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.
Journal of Nutrition, 2011
Immune modulatory effects of EPA and DHA are well described. However, these fatty acids must be effectively incorporated into cell membrane phospholipids to modify cell function. To address the absence of human data regarding short-term incorporation, the present study investigated the incorporation of EPA and DHA into white blood cells (WBC) at different time points during 1 wk of supplementation with a medical food, which is high in protein and leucine and enriched with fish oil and specific oligosaccharides. Additionally, the effects on ex vivo immune function were determined. In a single-arm, open label study, 12 healthy men and women consumed 2 3 200 mL of medical food providing 2.4 g EPA, 1.2 g DHA, 39.7 g protein (including 4.4 g L-leucine), and 5.6 g oligosaccharides daily. Blood samples were taken at d 0 (baseline), 1, 2, 4, and 7. Within 1 d of nutritional intervention, the percentage of EPA in phospholipids of WBC increased from 0.5% at baseline to 1.3% (P , 0.001). After 1 wk, the percentage of EPA rose to 2.8% (P , 0.001). Additionally, the production of proinflammatory cytokines in LPS-stimulated whole blood cultures was significantly increased within 1 wk. Nutritional supplementation with a fish oilenriched medical food significantly increased the percentage of EPA in phospholipids of WBC within 1 wk. Simultaneously, ex vivo immune responsiveness to LPS increased significantly. These results hold promise for novel applications such as fastacting nutritional interventions in cancer patients, which should be investigated in future studies.
Nutrition, 2009
Objectives: We investigated whether a dietary supplement rich in eicosapentaenoic acid (EPA) increases fasting plasma ketones or postprandial ketone responses in healthy young and elderly subjects. Methods: Ten young (22 Ϯ 1 y old) and 10 elderly (75 Ϯ 1 y old) subjects were recruited and participated in two identical study days, one before and one 6 wk after providing an EPA-enriched supplement (1.4 g/d of EPA and 0.2 g/d of docosahexaenoic acid). On the study days, blood samples were collected at fasting and every hour for 6 h after giving a breakfast. Fasting and postprandial plasma -hydroxybutyrate (-OHB), free fatty acid (FFA), triacylglycerol, glucose, and insulin responses were measured. Fatty acid profiles were assessed in fasting plasma samples before and after the EPA supplement. Results: After the EPA supplement, postprandial plasma -OHB responses decreased by 44% in the young and by 24% in the elderly subjects, in addition to 20% and 34% lower FFA responses in the young and elderly adults, respectively. -OHB and FFAs were positively and significantly correlated in young but not in elderly subjects before and after the EPA supplement. In both groups, postprandial plasma triacylglycerols, glucose, and insulin were not significantly different after the intake of the EPA supplement. Before and after the EPA supplement, fasting plasma EPA was 50% higher in the elderly but increased by about five times in both groups after intake of the EPA supplement. Conclusion: Contrary to our expectations, EPA supplementation lowered postprandial -OHB response and, in the elderly subjects, the concentration of postprandial -OHB was not lowered after intake of the EPA supplement.
Lipids, 2012
Fish oils are used as therapeutic agents in chronic inflammatory diseases. The omega-3 fatty acids (FA) found in these oils are mainly eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The anti-inflammatory properties of fish oils are attributed to both omega-3 fatty acids. However, it is unknown whether such effects are due to either EPA or DHA. In this study, the effects of EPA and DHA on rat neutrophil function in vitro were compared. Both EPA and DHA increased the production of H 2 O 2 when cells were stimulated or not with lipopolysaccharides (LPS). However, EPA was more potent than DHA in triggering an increase in superoxide release by cells in the basal condition or when stimulated with phorbol myristate acetate (PMA) or zymosan. Only DHA increased the phagocytic capacity and fungicidal activity of neutrophils. Both FA increased the release of tumor necrosis factor-a (TNF-a) in nonstimulated cells, but only EPA increased the production of cytokine-inducing neutrophil chemoattractant-2 (CINC-2) in the absence or presence of LPS, whereas production of interleukin-1 beta (IL-1b) was only increased by DHA in the presence of LPS. In addition, there was no alteration in the production of nitric oxide. In conclusion, we show herein that EPA and DHA can differently modulate aspects of the neutrophil response, which may be relevant for the development of therapies rich in one or other FA depending on the effect required. Keywords n-3 Fatty acids Á Reactive oxygen species Á Cytokines Á CINC-2 Á TNF-a Á IL-1b Á Phagocytosis Á Fungicidal activity Electronic supplementary material The online version of this article (
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.
Atherosclerosis, 2007
Supplementation with fish oils, rich in n − 3 polyunsaturated fatty acids, modifies cardiovascular risk factors. However, dose-response relationships are poorly defined and whether similar effects are seen in young and older subjects is not known. This study determined the effect of supplementing the diet of young and older male subjects with different amounts of an eicosapentaenoic acid (EPA)-rich oil. Healthy young (18-42 years) and older (53-70 years) males were randomized to placebo or 1.35, 2.7 or 4.05 g EPA/day for 12 weeks. There was no effect of EPA on blood pressure or on plasma total, LDL or HDL cholesterol. EPA lowered plasma triacylglycerols, with the maximal effect at the lowest dose. Plasma lipoperoxides decreased in all groups. EPA decreased the lag time of copper-induced lipoprotein peroxidation and the ratio of reduced to total glutathione in the older subjects. The highest dose of EPA increased soluble E-selectin in young subjects, while increasing EPA tended to decrease soluble intercellular adhesion molecule 1 in young and older subjects. Young and older males will gain cardiovascular benefit from increased intake of EPA. Young males are unlikely to suffer adverse consequences from high EPA intake, whereas older males may have an increased risk of lipoprotein peroxidation.