Omega-3 fatty acids can decrease immune function

Omega-3 fatty acids from fish oil are well-known as modulators of inflammation, this being the mode of action responsible for their effectiveness against the diseases of civilization, such as heart disease or rheumatoid arthritis. But there does appear to be a downside, since inflammation is part of the immune response; fish oil appears to decrease immunity, the flip side of decreasing inflammation. For example: Fish oil-fed mice have impaired resistance to influenza infection.

Dietary fish oils, rich in (n-3) PUFA, including eicosapentaenoic acid and docosahexaenoic acid, have been shown to have antiinflammatory properties. Although the antiinflammatory properties of fish oil may be beneficial during a chronic inflammatory illness, the same antiinflammatory properties can suppress the inflammatory responses necessary to combat acute viral infection. Given that (n-3) fatty acid-rich fish oil supplementation is on the rise and with the increasing threat of an influenza pandemic, we tested the effect of fish oil feeding for 2 wk on the immune response to influenza virus infection. Male C57BL/6 mice fed either a menhaden fish oil/corn oil diet (4 g fish oil:1 g corn oil, wt:wt at 5 g/100 g diet) or a control corn oil diet were infected with influenza A/PuertoRico/8/34 and analyzed for lung pathology and immune function. Although fish oil-fed mice had lower lung inflammation compared with controls, fish oil feeding also resulted in a 40% higher mortality rate, a 70% higher lung viral load at d 7 post infection, and a prolonged recovery period following infection. Although splenic natural killer (NK) cell activity was suppressed in fish oil-fed mice, lung NK activity was not affected. Additionally, lungs of infected fish oil-fed mice had significantly fewer CD8+ T cells and decreased mRNA expression of macrophage inflammatory protein-1-alpha, tumor necrosis factor-alpha, and interleukin-6. These results suggest that the antiinflammatory properties of fish oil feeding can alter the immune response to influenza infection, resulting in increased morbidity and mortality.

Granted, the dose of fish oil fed these mice was huge, but it was for only two weeks and led to greater mortality.

A study in humans was this one: Leukocyte numbers and function in subjects eating n-3 enriched foods: selective depression of natural killer cell levels. The punchline:

…natural killer (NK) (CD3-CD16+CD56+) cell numbers were lower in n-3 supplemented subjects than in controls and were inversely related to the amount of eicosapentaenoic acid or docosahexaenoic acid in erythrocytes.

That could be either good or bad depending on the condition, but someone with an infectious illness would seem to want to go very easy on the fish oil.

For a contrary p.o.v., see Fish oil attenuates surgery-induced immunosuppression, limits post-operative metastatic dissemination and increases long-term recurrence-free survival in rodents inoculated with cancer cells.


ω-3FA feeding attenuates or even overcomes postoperative NK cell suppression, increases resistance to experimental and spontaneous metastasis, and enhances recurrence-free survival following excision of metastasizing primary tumors. These findings warrant clinical studies of ω-3FA-based nutrition in patients undergoing resection of a primary tumor.

In healthy young men, EPA does not appear to reduce immunity: Limited effect of eicosapentaenoic acid on T-lymphocyte and natural killer cell numbers and functions in healthy young males.


Greatly increasing the amount of long-chain omega-3 polyunsaturated fatty acids in the diet has been reported in some studies to decrease T-lymphocyte and natural killer functions. However, dose-response relations have not been identified. The objective of this study was to determine the effect of supplementing the diet of young male subjects with different amounts of an oil rich in eicosapentaenoic acid (EPA) on T-lymphocyte proliferation, cytokine production by T lymphocytes, and natural killer cell activity. […]

[…] Natural killer cell activity was little affected by the treatments, although there was a trend for EPA to increase activity at a low effector-to-target cell ratio.

T-lymphocyte and natural killer cell numbers and function in healthy young males are little affected by supplemental EPA intakes up to 4 g/d.

So, it appears that the jury is still out. While it has been shown that fish oil can suppress immunity at high doses in animals, it doesn’t seem to have much effect in healthy young men. However, that is precisely the group that has little need for fish oil supplementation in the first place, since presumably they will have fairly low levels of inflammation. In elderly, non-healthy people, fish oil could possible suppress immunity enough to matter. This is the population most at risk from influenza, and fish oil could affect their immunity, with perhaps severe consequences.

I take fish oil myself, but I think it’s good to keep in mind that too much of a good thing isn’t necessarily better. I do not take it daily and the dose is modest, amounting to about 3 grams omega-3 per week. That’s not to say that others could do better with more or less than that, but one should keep in mind the possible effects on immunity.


Leave a Comment:

1 comment
eah says October 9, 2012

Interesting. Thanks for posting this, Dennis.

Like many, I supplement modestly with fish oil; have been for over two years now. Cannot say I’ve noticed any difference in this regard, e.g. how often I am ill.

I wonder if vitamin D supplementation could offset some of this effect?

Vitamin D Crucial to Activating Immune Defenses

I suspect that most people who supplement with fish oil do the same with vitamin D, like I do.

Add Your Reply