Proinflammatory cytokines influence the onset and course of a number of age-associated diseases. Stress and depression can substantially enhance the production of proinflammatory cytokines. Diet also influences the synthesis of these cytokines. Arachidonic acid (AA) derived (omega-6 or n-6) eicosanoids increase the production of these cytokines. In contrast, the omega-3 (n-3) polyunsaturated fatty acids (PUFAs) can curb the production of AA-derived eicosanoids. Thus, higher n-6: n-3 ratios promote proinflammatory cytokine production. Importantly, high n-6: n-3 ratios predict greater increases in cytokines during stressful periods, as well as higher levels of depressive symptoms. Furthermore, NF-*B activation is a prime pathway for up- regulating proinflammatory cytokine production;psychological stress promotes NF-/cB activation, while n-3 PUFAs can substantially decrease NF-*B activation. Accordingly, we will examine how stress and diet inter- act to influence immune function and mood in 138 adults, ages 50-80. The design will be a double-blind, placebo-controlled randomized clinical trial with supplementation over a 4-month period. Two n-3 doses will be compared to help establish the optimal intake for efficacy. Fasting blood samples to monitor changes in fatty acid levels and immunological and psychological data will be collected at baseline (0), and 1, 2, 3, and 4 months after supplementation has been initiated, providing data on the kinetics of change. To further assess the n-3 PUFA's stress-protective efficacy, mood and immunological responses to a laboratory stressor will be assessed at baseline and again at 4 months.
Specific aims : (1) to determine if n-3 supplementation will decrease NF-/fB activation, proinflammatory cytokine production and gene expression;to evaluate the time course for these changes following supplementation, and the relationship of change to dose;(2) to determine if there are reliable changes in mood (depressive and anxiety symptoms) following n-3 supplementation compared to the placebo condition, and if these differences are related to n-3 dose;(3) to assess the extent to which n-3 supplementation modulates typical stress-related increases in cytokine production following laboratory stressors;(4) to assess the influence of age on immunological and psychological responses to n-3 supplementation;and (5) to compare the utility of statistical analyses that use changes in PBMC n-3 PUFA content as continuous measures with those that simply use n-3 PUFA dose.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG029562-03
Application #
7643914
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Hannah, Judy S
Project Start
2007-07-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
3
Fiscal Year
2009
Total Cost
$574,386
Indirect Cost
Name
Ohio State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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