Omega-3 supplementation reduces perceived social isolation in a sex-dependent manner: Secondary analysis of an RCT

Loneliness and chronic inflammation create a vicious cycle, and females may be especially vulnerable. In these secondary analyses of an RCT, we investigated whether omega-3 (n-3) supplementation decreased loneliness and perceived social isolation in a sex-dependent manner, and whether changes in n-3 in peripheral blood mononuclear cell (PBMC) membranes or inflammatory biomarkers predicted changes in social perception.

Healthy medical students (n = 38 males, n = 30 females) were randomized to 2.5 g/day of n-3 supplementation or placebo for 12 weeks. Perceived social isolation (Trier Inventory of Chronic Stressors), loneliness (UCLA Loneliness Scale), PBMC n-3 percentage, and serum and LPS-stimulated interleukin-6 and tumor necrosis factor-α were assessed multiple times throughout the trial.

PBMC n-3 percentage increased in the supplementation group (p < .001), with supplemented females showing higher levels than males at weeks 6 (95% CI [0.51, 5.17], p = .019) and 9 (95% CI [0.30, 5.40], p = .030). There were no sex-dependent supplementation effects on inflammatory markers (ps > .14). Sex moderated supplementation's effect on perceived social isolation over time (95% CI [-7.46, -0.36], p = .031) but not loneliness (95% CI [-3.79, 8.65], p = .44). Specifically, n-3 marginally reduced perceived social isolation among females (95% CI [-3.63, 0.05], p = .056), but not males (95% CI [-1.19, 2.21], p = .55). Similarly, PBMC n-3 change had a marginal sex-dependent effect on perceived social isolation (95% CI [-0.86, 0.02], p = .063) but not loneliness (95% CI [-0.59, 1.24], p = .48).

n-3 supplementation may reduce perceived social isolation particularly among females, possibly due to sex differences in absorption or sensitivity to its effect on social perception; replication is needed.