Journal Name:
J. Clin. Endocrinol. Metab.
Article Title:
Relationship of Plasma Polyunsaturated Fatty Acids to Circulating Inflammatory Markers
Date Written:
2006
Volume:
91
Number:
0
Page:
439
Author(s):
Ferrucci, L.; Cherubini, A.; Bandinelli, S.; Bartali, B.; Corsi, A.; Lauretani, F.; Martin, A.; Andres-Lacueva, C.; Senin, U.; Guralnik, J.
Article:
There is evidence that a diet rich in polyunsaturated fatty acids (PUFAs) and, in particular, the omega-3 family (n-3), is associated with lower cardiovascular morbidity and mortality and reduced risk of sudden death, independent of other known cardiovascular risk factors. Studies have suggested that the protective effects of n-3 PUFA are mediated by multiple mechanisms, including their antiinflammatory properties. Using data from a representative sample of the general population, the objective of this study was to assess the association of physiological PUFA levels with pro- and antiinflammatory markers.
In 1123 persons (aged 20–98 yr), the relationship between relative concentration of fatty acids in fasting plasma and level of inflammatory markers was examined in this study. Adjusting for age, sex, and major confounders, lower arachidonic (AA) and docosahexaenoic (DHA) levels were associated with significantly higher I L-6 and IL-1ra and significantly lower TNFƁ. Lower alpha-linolenic acid was associated with higher C-reactive protein and IL-1ra, and lower eicosapentaenoic acid were associated with significantly higher IL-6 and lower TNFƁ. Lower DHA was strongly associated with lower IL-10. Total n-3 were associated with lower IL-6, IL-1ra and TNFa and higher soluble IL-6r, IL-10, and TNFƁ. Lower n-6 fatty acid levels were significantly associated with higher IL-1ra and lower TNFƁ. 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.
This is one of the first investigations of the relationship between plasma concentrations of fatty acids and multiple proinflammatory and antiinflammatory cytokines based on a representative sample of the general population. Different fatty acids were directly measured in plasma and not estimated from dietary reports. Because no participants were using dietary supplements, the findings are based on physiological plasma concentrations; this information is more precise and provides a more objective measure of fatty acid exposure, which depends on both intake and metabolism. Information on multiple potential confounders, including dietary intake, was available for all participants.
In this community-based sample, total n-3 fatty acids were independently associated with lower levels of proinflammatory markers (IL-6, IL-1ra, TNF-alpha, C-reactive protein) and higher levels of antiinflammatory markers (soluble IL-6r, IL-10, TNFƁ). These results were independent of confounders. This data supports the hypothesis that n-3 fatty acids may be beneficial in patients affected by diseases characterized by active inflammation.
The data suggest that the immunomodulatory effect of PUFAs may be influenced by the n-6 to n-3 ratio, which in this study was the strongest negative correlate of IL-10 and TGF-alpha, two powerful antiinflammatory cytokines. Further, the findings show that plasma levels of AA and omega-3 PUFAs, which probably reflect higher dietary intake, are associated with lower serum concentrations of certain proinflammatory cytokines and lower concentrations of certain anti-inflammatory cytokines. Therefore, these findings support the view that AA and n-3 PUFAs may modulate the inflammatory response by acting both on the proinflammatory and anti-inflammatory arms of the cytokine network. Such a modulatory effect on multiple signaling pathways suggests a direct regulatory effect on gene expression.
In summary, because serum levels of specific fatty acids can be easily modified by a different selection of foods in the diet or dietary supplementation, the authors advise that physicians should consider dietary interventions to suppress production of proinflammatory compounds as part of the prevention and treatment of diseases in which inflammation exerts adverse effects on clinical progression.
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