Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older adults

Abstract

Objective: To address how interactions between polyunsaturated fatty acid (PUFA) levels and depressive symptoms were related to proinflammatory cytokine synthesis. Depression and stress promote proinflammatory cytokine production. Dietary intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs also influence inflammation; high n-6:n-3 ratios enhance proinflammatory cytokine production, although n-3 has anti-inflammatory properties.

Methods: Blood samples from 43 older adults (mean age = 66.67 years, SD = 10.09) provided data on PUFAs and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-6 soluble receptor (sIL-6r). Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale.

Results: Depressive symptoms and n-6:n-3 ratios worked together to enhance proinflammatory cytokines beyond the contribution provided by either variable alone, with substantial variance explained by their interaction: 13% for IL-6 and 31% for TNF-alpha, whereas full models accounted for 18% and 40%, respectively. Although predicted cytokine levels were consistent across n-6:n-3 ratios with low depressive symptoms, higher n-6:n-3 ratios were associated with progressively elevated TNF-alpha and IL-6 levels as depressive symptoms increased. Higher levels of sIL-6r were associated with higher n-6:n-3 ratios. Six individuals who met the criteria for major depressive disorder had higher n-6:n-3 ratios and TNF-alpha, IL-6, and sIL-6r levels than those who did not meet the criteria; excluding these six individuals reduced the variance explained by the depressive symptoms and n-6:n-3 ratio interaction.

Conclusions: Diets with high n-6:n-3 PUFA ratios may enhance the risk for both depression and inflammatory diseases.

Figure 1

a–c. IL-6 (1a) and TNF-α (1b) plots showing the predicted cytokine response by n-6:n-3 ratio separately for different CES-D depressive symptom levels. Although the analyses used continuous variables, predicted cytokine values are plotted for the midpoint of each depressive symptom quartile (2, 4, 9, 18) to illustrate the effect of depression on the cytokine n-6:n-3 ratio relationship. The predicted values for IL-6 and TNF-α are non-linear because the model was on the log scale and then the predicted values were transformed back to the original scale. In the IL-6sr model (1c) the n-6:n-3 ratio main effect was significant, and the ratio did not differ significantly by depression. Therefore only one response curve is on the plot, at the mean depression level of 7.4. Responses at other depression levels would yield parallel curves.