(11-12-05) Relationship of Plasma Polyunsaturated Fatty Acids to Circulating Inflammatory Markers.

Ferrucci L, Cherubini A, Bandinelli S, Bartali B, Corsi A, Lauretani F, Martin A, Andres-Lacueva C, Senin U, Guralnik JM.

Longitudinal Studies Section. Clinical Research Branch. National Institute on Aging. Baltimore, MD, USA. Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, Perugia University Medical School. Perugia, Italy. Tuscany Regional Health Agency - Florence, Italy. Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA. Human Nutrition Research Center on Aging, Tufts University, Boston, USA. Department of Nutrition and Food Science - CeRTA, University of Barcelona, Spain. Laboratory of Epidemiology Demography and Biometry, National Institute on Aging, Bethesda, MD, USA.

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 anti-inflammatory properties. The association of physiological PUFAs levels with pro- and anti-inflammatory 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 (DHA) acids were associated with significantly higher IL-6 and IL-1ra and significantly lower TGF-beta. Lower alpha-linolenic acid was associated with higher CRP and IL-1ra, and lower Eicosapentaenoic acid was associated with higher IL-6 and lower TGF-beta. Lower DHA was strongly associated with lower IL-10. Total n-3 fatty acids were associated with higher IL-6 (P = 0.005), IL-1ra (P = 0.004), TNF-alpha (P = 0.040) and lower sIL-6r (P < 0.001), IL-10 (P = 0.024) and TGF-beta (P = 0.0012). Lower n-6 fatty acid levels were significantly associated with higher IL-1ra (P = 0.026) and lower TGF-beta (P = 0.014). The n-6/n-3 ration was a strong, negative correlate of IL-10. Findings were similar in participants free of cardiovascular diseases and after excluding lipids from covariates. Conclusion: In this community-based sample, polyunsaturated fatty acids, and especially total n-3 fatty acids, were independently associated with lower levels of pro-inflammatory markers (IL-6, IL-1ra, TNF-alfa, CRP) and higher levels of anti-inflammatory markers (sIL-6r, IL-10, TGF-beta) 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.

J Clin Endocrinol Metab. 2005 Oct 18; [Epub ahead of print]

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