Nature reveals: Omega-3, vitamin D and exercise combined for better anti-aging effects

A groundbreaking study published in Nature Aging last week revealed that daily supplementation with Omega-3 and vitamin D, combined with exercise, can delay biological aging by approximately 3-4 months over three years^[1].

Led by Dr. Heike Bischoff-Ferrari from the University of Zurich and Dr. Steve Horvath of Altos Labs, the research analyzed data from the DO-HEALTH trial (2012–2014), involving 777 healthy adults aged 70+ across five European countries (Switzerland, Germany, France, Austria, and Portugal). Participants were assigned to one or more interventions:

1.Vitamin D (2000 IU/day),

2.Omega-3 (1g/day)

3.Home-based exercise (SHEP: 30 minutes, 3 times/week)

DO-HEALTH Bio-Age Trial Flowchart: Participant allocation across eight treatment groups.

Four next-generation epigenetic clocks (PhenoAge, GrimAge, GrimAge2, and DunedinPACE) were used to assess biological aging. These clocks measure DNA methylation patterns, offering a more precise evaluation of aging than chronological age.

Key findings:

• Omega-3 alone significantly slowed aging across PhenoAge, GrimAge2, and DunedinPACE, regardless of sex, age, or BMI.
• Combining Omega-3, vitamin D, and exercise amplified the anti-aging effect, reducing biological aging by 2.9–3.8 months over three years.

Impact of interventions on biological age across four epigenetic clocks.

Previous studies by the team demonstrated that this combined approach reduces frailty risk by 39%^[2] and lowers invasive cancer incidence by 61%^[3].

How Do Omega-3 and Vitamin D Combat Aging?

The research team pointed out that the anti-aging effects of Omega-3 and vitamin D are mainly related to their effects on DNA methylation patterns.

DNA methylation is an epigenetic modification that can regulate gene activity, and with age, DNA methylation patterns tend to change, thus affecting the aging process.

Omega-3, as an essential fatty acid for the human body, mainly slows down aging by reducing DNA methylation, anti-inflammatory and cardiovascular protection, while vitamin D is a well-known "sunshine vitamin" that can affect aging through immune regulation, bone health and potential epigenetic regulation. Exercise can optimize physical condition by enhancing mitochondrial function, improving metabolism and reducing inflammation.

Who Should Supplement with Omega-3?

The DO-HEALTH trial highlights Omega-3’s role in healthy aging. Though a 3–4 month delay may seem modest, sustained use could reduce chronic disease risk and improve independence in older adults. Key target groups include:

• Adults over 40 seeking to delay aging.
• Individuals with low dietary intake of fatty fish.
• Those with weakened immunity or chronic inflammation.
• People at risk of cardiovascular disease or metabolic syndrome.
• Older adults aiming to enhance muscle health and reduce frailty.

In addition to dietary supplements, supplements are a more direct and effective way to supplement Omega-3. There are many types of Omega-3 products on the market, including triglyceride type, ethyl ester type and phospholipid type, which differ in absorption rate, metabolic efficiency and bioavailability. Among them, phospholipid Omega-3 (such as Omega-3 from fish roe oil) has better effects in anti-inflammation, cardiovascular health and neuroprotection because of its stronger hydrophilicity, higher absorption rate and easier access to the brain and cell membrane. Therefore, when choosing Omega-3 supplements, phospholipid Omega-3 can be given priority.

In summary, long-term adherence to Omega-3 supplementation, vitamin D, and regular exercise may effectively slow aging and mitigate chronic disease risks.

References

[1] Bischoff-Ferrari, H.A., Gängler, S., Wieczorek, M. et al. Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial. Nat Aging (2025). https://doi.org/10.1038/s43587-024-00793-y

[2] Gagesch, M. et al. Effects of vitamin D, omega-3 fatty acids and a home exercise program on prevention of pre-frailty in older adults: the DO-HEALTH randomized clinical trial. J. Frailty Aging 12, 71–77 (2023).

[3] Bischoff-Ferrari, H. A. et al. Combined vitamin D, omega-3 fatty acids, and a simple home exercise program may reduce cancer risk among active adults aged 70 and older: a randomized clinical trial. Front. Aging 3, 852643 (2022).