A post hoc analysis of a randomized clinical trial of 777 older adults found that omega-3 fatty acid supplementation may slow biological aging, with enhanced effects when combined with vitamin D and exercise, according to research.
In the DO-HEALTH Bio-Age trial, published in in Nature Aging and conducted from December 2012 to November 2017, researchers analyzed DNA methylation markers in generally healthy participants aged 70 and older from Switzerland who received daily supplements of vitamin D (2,000 IU), omega-3 (1 g), and/or participated in a home exercise program for over 3 years. The DNA methylation analysis, funded by the Swiss National Foundation, was conducted only on the Swiss subset of the larger DO-HEALTH trial participants.
"Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2, and DunedinPACE, and all three treatments had additive benefits on PhenoAge," reported lead study author Heike A. Bischoff-Ferrari, MD, DrPH, of the University of Zurich.
The study population was well-characterized: mean age 75 years, 60% female, mean body mass index 25.72 kg/m², with 52% meeting the Nurses' Health Study definition for healthy aging. At baseline, 30% had 25-hydroxyvitamin D levels below 20 ng/mL, and mean omega-3 (DHA + EPA) blood levels were 94.32 ng/mL. The cohort was notably active, with 29% exercising one to three times per week and 59% exercising more than three times per week.
Study adherence was high, with 86% of the participants completing at least 80% of prescribed supplements. Exercise compliance showed 70% performing activities at least two times per week and 62% meeting the target of three times per week.
The standardized effects ranged from 0.16 to 0.32 units, equivalent to approximately 2.9 to 3.8 months of reduced biological aging over the 3-year study period. Subgroup analyses revealed stronger omega-3 effects on PhenoAge in participants with baseline vitamin D levels ≥ 20 ng/mL. Women and those with lower baseline blood DHA and EPA levels showed enhanced benefits from combined treatments.
Using the Infinium Methylation EPIC array analyzing 866,238 CpGs, the researchers measured DNA methylation at baseline and 36 months. All aging clocks showed correlation with chronological age: GrimAge (r = 0.92), GrimAge2 (r = 0.71), PhenoAge (r = 0.60), and DunedinPACE (r = 0.19).
The findings built on previous DO-HEALTH trial results showing that omega-3 alone reduced infection rates by 13% and fell by 10%, while the combination of all three interventions reduced prefrailty by 39% and incident invasive cancer by 61%.
When examining specific biomarkers, omega-3 supplementation modified three out of seven DNA methylation–based plasma protein markers: plasminogen activation inhibitor 1 (PAI-1), leptin, and tissue inhibitor metalloproteinase 1 (TIMP-1). Additionally, the combination of treatments showed additive benefits on four proteins: PAI-1, beta-2 microglobulin (B2M), TIMP-1, and growth differentiation factor 15 (GDF-15).
The researchers acknowledged study limitations, including analysis of only two time points and the lack of a gold standard measure of biological aging. The Swiss cohort represented a healthier subgroup of the total DO-HEALTH population.
Full disclosures can be found in the study.
