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Omega-3 supplementation and stress reactivity of cellular aging biomarkers: an ancillary substudy of a randomized, controlled trial in midlife adults


Higher levels of omega-3 track with longer telomeres, lower inflammation, and blunted sympathetic and cardiovascular stress reactivity. Whether omega-3 supplementation alters the stress responsivity of telomerase, cortisol, and inflammation is unknown. This randomized, controlled trial examined the impact of omega-3 supplementation on cellular aging-related biomarkers following a laboratory speech stressor. In total, 138 sedentary, overweight, middle-aged participants (n = 93 women, n = 45 men) received either 2.5 g/d of omega-3, 1.25 g/d of omega-3, or a placebo for 4 months. Before and after the trial, participants underwent the Trier Social Stress Test. Saliva and blood samples were collected once before and repeatedly after the stressor to measure salivary cortisol, telomerase in peripheral blood lymphocytes, and serum anti-inflammatory (interleukin-10; IL-10) and pro-inflammatory (interleukin-6; IL-6, interleukin-12, tumor necrosis factor-alpha) cytokines. Adjusting for pre-supplementation reactivity, age, sagittal abdominal diameter, and sex, omega-3 supplementation altered telomerase (p = 0.05) and IL-10 (p = 0.05) stress reactivity; both supplementation groups were protected from the placebo group’s 24% and 26% post-stress declines in the geometric means of telomerase and IL-10, respectively. Omega-3 also reduced overall cortisol (p = 0.03) and IL-6 (p = 0.03) throughout the stressor; the 2.5 g/d group had 19% and 33% lower overall cortisol levels and IL-6 geometric mean levels, respectively, compared to the placebo group. By lowering overall inflammation and cortisol levels during stress and boosting repair mechanisms during recovery, omega-3 may slow accelerated aging and reduce depression risk. identifier: NCT00385723.

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Fig. 1: Omega-3 supplementation impacted telomerase reactivity to an acute stressor (p = 0.05).
Fig. 2: Omega-3 supplementation lowered total salivary cortisol output throughout an acute stressor (p = 0.04).
Fig. 3: Omega-3 supplementation influenced IL-10 stress reactivity (p = 0.05).
Fig. 4: Omega-3 supplementation lowered overall IL-6 release throughout an acute stressor (p = 0.03).


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This study was supported in part by NIH grants AG029562, AG038621, UL1RR025755, TL1TR002735, and CA16058. OmegaBrite (Waltham, MA) supplied the omega-3 PUFA supplement and placebo without charge and without restrictions; OmegaBrite did not influence the design, funding, implementation, interpretation, or publication of the data.

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Correspondence to Janice K. Kiecolt-Glaser.

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ESE and JL are co-founders of Telome Health, Inc., a telomere measurement company. All other authors report no competing interests.

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Madison, A.A., Belury, M.A., Andridge, R. et al. Omega-3 supplementation and stress reactivity of cellular aging biomarkers: an ancillary substudy of a randomized, controlled trial in midlife adults. Mol Psychiatry 26, 3034–3042 (2021).

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