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Relationship of Plasma Polyunsaturated Fatty Acids to Circulating Inflammatory Markers

Longitudinal Studies Section (L.F.), Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 21225; Department of Clinical and Experimental Medicine (A.Ch., U.S.), Institute of Gerontology and Geriatrics, Perugia University Medical School, 06100 Perugia, Italy; Department of Geriatric Rehabilitation (S.B.), Tuscany Regional Health Agency (A.Co., F.L.), 50125 Florence, Italy; Division of Nutritional Sciences (B.B.), Cornell University, Ithaca, New York 14853; Human Nutrition Research Center on Aging (A.M.), Tufts University, Boston, Massachusetts 02111; Department of Nutrition and Food Science (C.A.-L.), CeRTA, University of Barcelona, 08028 Barcelona, Spain; and Laboratory of Epidemiology, Demography, and Biometry (J.M.G.), National Institute on Aging, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Luigi Ferrucci, M.D., Ph.D., Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, Harbor Hospital, 5th Floor, 3001 Hanover Street, Baltimore, Maryland 21225. E-mail: ferruccilu{at}grc.nia.nih.gov.

Aims: Persons with high intake of polyunsaturated fatty acids (PUFAs) have lower cardiovascular morbidity and mortality. The protective effect of PUFAs is mediated by multiple mechanisms, including their antiinflammatory properties. The association of physiological PUFA levels with pro- and antiinflammatory markers has not been established.

Methods and Results: In 1123 persons (aged 20–98 yr), we examined the relationship between relative concentration of fatty acids in fasting plasma and level of inflammatory markers. Adjusting for age, sex, and major confounders, lower arachidonic and docosahexaenoic acids were associated with significantly higher IL-6 and IL-1ra and significantly lower TGFß. Lower -linolenic acid was associated with higher C-reactive protein and IL-1ra, and lower eicosapentaenoic acid was associated with higher IL-6 and lower TGFß. Lower docosahexaenoic acid was strongly associated with lower IL-10. Total n-3 fatty acids were associated with lower IL-6 (P = 0.005), IL-1ra (P = 0.004), and TNF (P = 0.040) and higher soluble IL-6r (P < 0.001), IL-10 (P = 0.024), and TGFß (P = 0.0012). Lower n-6 fatty acid levels were significantly associated with higher IL-1ra (P = 0.026) and lower TGFß (P = 0.014). The n-6 to n-3 ratio was a strong, negative correlate of IL-10. Findings were similar in participants free of cardiovascular diseases and after excluding lipids from covariates.

Conclusions: In this community-based sample, PUFAs, and especially total n-3 fatty acids, were independently associated with lower levels of proinflammatory markers (IL-6, IL-1ra, TNF, C-reactive protein) and higher levels of antiinflammatory markers (soluble IL-6r, IL-10, TGFß) independent of confounders. Our findings support the notion that n-3 fatty acids may be beneficial in patients affected by diseases characterized by active inflammation.

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