Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men

Kelley, Darshan S.; Taylor, Peter; Nelson, Gary J.; Schmidt, Patrick; Ferretti, Aldo; Erickson, Kent L.; Yu, Rina; Chandra, Ranjit Kumar; Mackey, Bruce E.

doi:10.1007/s11745-999-0369-5

Cited by 222 publications

(158 citation statements)

References 41 publications

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“…Most of these studies, however, were small and used fish oil, with little attention given to specific DHA effects. Our findings do agree with data from in vitro studies, particularly from cultured cells, including monocytes and endothelial cells 77, 78, 79, 80. We thus conclude that the atheroprotective effect of DHA is transduced by alterations in flow leading to an arterial environment in which levels of these plasma chemoattractants are reduced.…”

Section: Discussionsupporting

confidence: 90%

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

Alfaidi

Chamberlain

Rothman

et al. 2018

JAHA

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BackgroundHypertension is a complex condition and a common cardiovascular risk factor. Dietary docosahexaenoic acid (DHA) modulates atherosclerosis and hypertension, possibly via an inflammatory mechanism. IL‐1 (interleukin 1) has an established role in atherosclerosis and inflammation, although whether IL‐1 inhibition modulates blood pressure is unclear.Methods and ResultsMale apoE−/− (apolipoprotein E–null) mice were fed either a high fat diet or a high fat diet plus DHA (300 mg/kg per day) for 12 weeks. Blood pressure and cardiac function were assessed, and effects of DHA on wall shear stress and atherosclerosis were determined. DHA supplementation improved left ventricular function, reduced wall shear stress and oscillatory shear at ostia in the descending aorta, and significantly lowered blood pressure compared with controls (119.5±7 versus 159.7±3 mm Hg, P<0.001, n=4 per group). Analysis of atheroma following DHA feeding in mice demonstrated a 4‐fold reduction in lesion burden in distal aortas and in brachiocephalic arteries (P<0.001, n=12 per group). In addition, DHA treatment selectively decreased plaque endothelial IL‐1β (P<0.01).ConclusionsOur findings revealed that raised blood pressure can be reduced by inhibiting IL‐1 indirectly by administration of DHA in the diet through a mechanism that involves a reduction in wall shear stress and local expression of the proinflammatory cytokine IL‐1β.

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Section: Discussionsupporting

confidence: 90%

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

Alfaidi

Chamberlain

Rothman

et al. 2018

JAHA

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“…The relative resistance of immune cells to change in DHA content is reported by others [23][24][25] . The FA composition of immune cell phospholipids may not alter as much as blood lipid pools because these cells exert a significant level of control over their plasma membrane composition 26 .…”

Section: Discussionsupporting

confidence: 57%

“…It is for this reason that we were interested in the time course of FA composition changes, because it may be desirable in some clinical settings to provide n-3 FAs quickly. The main clinical outcomes from this trial have been published recently 24 .…”

Section: Introductionmentioning

confidence: 99%

The impact of an omega-3 fatty acid rich lipid emulsion on fatty acid profiles in critically ill septic patients

Hall

Bilku

Neal

et al. 2016

Prostaglandins, Leukotrienes and Essential Fatty Acids

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SummaryDeath from sepsis in the intensive therapy unit (ITU) is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with omega-3 fatty acids (FAs) has been demonstrated to attenuate the effects of uncontrolled inflammation. A study investigating the effects of parenteral nutrition providing fish oil (FO) was conducted. Septic ITU patients were randomised to receive either parenteral FO and standard medical care or standard medical care only.FA composition of plasma phosphatidylcholine (PC), plasma non-esterified FAs (NEFAs) and peripheral blood mononuclear cells (PBMCs) was determined by gas chromatography. EPA and DHA were rapidly incorporated.There was a reduction in the arachidonic acid (AA) to EPA+DHA ratio in plasma PC and NEFAs. Fewer patients died in the FO group compared with the control group although this was not statistically significant. A reduction in the AA/(EPA+DHA) ratio in PBMCs and plasma PC was associated with improved survival.

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“…Taken together, the effects of long-chain n-3 PUFA on NK cell activity remain unclear and the inconsistency has only increased with this recent report. Previous suggestions that 'high' but not 'low' doses of DHA can decrease NK cell activity (Kelley et al 1999;Thies et al 2001b) and that cells from older subjects might be more susceptible to the effects of EPA and DHA than those of young subjects (Calder, 2001a) are not rejected by the recent data. Again, it would be useful to conduct a well-powered study comparing the effects of long-chain n-3 PUFA on NK cell activity in young and older subjects.…”

Section: Effects Of Epa and Dha On Natural Killer Cell Activitymentioning

confidence: 78%

“…7 g DHA/d in elderly subjects. Kelley et al (1999) have reported inhibition of NK cell activity following 6 g DHA/d in young males. In contrast, Yaqoob et al (2000) have found no effect of 3 .…”

Section: Effects Of Epa and Dha On Natural Killer Cell Activitymentioning

confidence: 99%

Differential immunomodulation with long-chainn-3 PUFA in health and chronic disease

Sijben¹,

2007

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The balance of intake of n-6 and n-3 PUFA, and consequently their relative incorporation into immune cells, is important in determining the development and severity of immune and inflammatory responses. Some disorders characterised by exaggerated inflammation and excessive formation of inflammatory markers have become among the most important causes of death and disability in man in modern societies. The recognition that long-chain n-3 PUFA have the potential to inhibit (excessive) inflammatory responses has led to a large number of clinical investigations with these fatty acids in inflammatory conditions as well as in healthy subjects. The present review explores the presence of dose-related effects of long-chain n-3 PUFA supplementation on immune markers and differences between healthy subjects and those with inflammatory conditions, because of the important implications for the transfer of information gained from studies with healthy subjects to patient populations, e.g. for establishing dose levels for specific applications. The effects of long-chain n-3 PUFA supplementation on ex vivo lymphocyte proliferation and cytokine production by lymphocytes and monocytes in healthy subjects have been studied in twenty-seven, twenty-five and forty-six treatment cohorts respectively, at intake levels ranging from 0 . 2 g EPA + DHA/d to 7 . 0 g EPA + DHA/d. Most studies, particularly those with the highest quality study design, have found no effects on these immune markers. Significant effects on lymphocyte proliferation are decreased responses in seven of eight cohorts, particularly in older subjects. The direction of the significant changes in cytokine production by lymphocytes is inconsistent and only found at supplementation levels ‡ 2 . 0 g EPA + DHA/d. Significant changes in inflammatory cytokine production by monocytes are decreases in their production in all instances. Overall, these studies fail to reveal strong dose-response effects of EPA + DHA on the outcomes measured and suggest that healthy subjects are relatively insensitive to immunomodulation with longchain n-3 PUFA, even at intake levels that substantially raise their concentrations in phospholipids of immune cells. In patients with inflammatory conditions cytokine concentrations or production are influenced by EPA + DHA supplementation in a relatively large number of studies. Some of these studies suggest that local effects at the site of inflammation might be more pronounced than systemic effects and disease-related markers are more sensitive to the immunomodulatory effects, indicating that the presence of inflamed tissue or 'sensitised' immune cells in inflammatory disorders might increase sensitivity to the immunomodulatory effects of long-chain n-3 PUFA. In a substantial number of these studies clinical benefits related to the inflammatory state of the condition have been observed in the absence of significant effects on immune markers of inflammation. This finding suggests that conditionspecific clinical end points might be more sensitive markers...

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Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men

Cited by 222 publications

References 41 publications

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

The impact of an omega-3 fatty acid rich lipid emulsion on fatty acid profiles in critically ill septic patients

Differential immunomodulation with long-chainn-3 PUFA in health and chronic disease

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