Daily omega-3 supplementation can slow biological aging, research shows

Taking one gram of omega-3 daily over three years slows biological aging by an average of 2.9–3.8 months, according to a statistical analysis of 777 Swiss participants in a clinical trial. The researchers used DNA methylation clocks to measure the effects. Combining omega-3 with vitamin D (2,000 international units daily) and home exercise had additional benefits, according to one of these clocks. 

These latest findings add to existing health aging benefits identified in the DO-HEALTH study. This randomized, double-blind, placebo-controlled trial enrolled 2,157 healthy and active men and women aged 70 or older from five European countries. 

The DO-HEALTH study, led by the Swiss University of Zurich, aims to establish whether vitamin D, omega-3s, and a home exercise program prevent disease at older ages. It considers bone health, functional muscle decline, cardiovascular health risk, cognitive decline, and immunity. 

The DNA methylation analysis aims to assess the effects of these interventions at a molecular level. 

Nutrition Insight discusses the findings with co-authors Heike Bischoff-Ferrari, professor at the Swiss University of Basel and University of Zurich’s Department of Geriatrics and Aging Research, and Steve Horvath, Ph.D. from Altos Labs, a US biotechnology company. 

“Our results in DO-HEALTH for preventing infections, falls, cancer, and pre-frailty translated to slowing biological aging in the same trial. This supports these three public health strategies as a combined solution at the public health level to extend the health span in older adults. Further, these strategies are affordable and safe as shown in DO-HEALTH over a three-year follow-up,” say the authors. 

“The effects documented may appear small, with three to four months of biological age rejuvenation in three years. If sustained, it may have relevant effects on population health.”

Combining interventions

The researchers randomized the trial participants into one of eight treatment arms in the DO-HEALTH trial. Individuals either took a placebo, a vitamin D supplement, or an omega-3 supplement, followed a simple 30-minute home exercise program three times a week, or combined two or all three interventions. 

For the biological age trial subset, published in Nature Aging, each group had between 92 and 104 participants. 

“All three strategies have documented health benefits for multiple organ functions, and their synergistic benefit is best explained by the fact that they address different mechanistic pathways,” highlight Bischoff-Ferrari and Horvath. 

DO-HEALTH aims to assess interventions’ impact on fractures, functional decline, blood pressure increase, cognitive decline, and infection.“For example, when we think about cancer prevention, omega-3 has an anti-inflammatory effect to fight cancer, vitamin D prevents uncontrolled cell proliferation, and exercise induces apoptosis (cell death) of cancer cells.” 

In earlier analyses, DO-HEALTH demonstrated that omega-3 reduced falls by 11% and infections by 13%. Combined with vitamin D and exercise, it reduced cancer risk by 61% and incident pre-frailty by 39%. 

The authors note: “Our results are encouraging that omega-3 has geroprotective benefits, which may be enhanced in combination with vitamin D and exercise.”

They say that prior observational studies and small pilot trials of 20 to 100 participants suggest that each intervention tested in DO-HEALTH may slow biological aging based on epigenetic clock measures. 

“Proving these benefits in the largest clinical trial to date with over 700 participants is very encouraging,” say Bischoff-Ferrari and Horvath. “Additionally, these findings were seen in a conservative sub-population of DO-HEALTH, the Swiss participants, who were already at baseline ‘Healthy Agers’ in over 50% of cases.” 

The team followed participants for an intervention period of three years with yearly examinations and in-person phone calls every three months. The researchers collected blood samples at baseline and each follow-up year and extracted and biobanked DNA. 

DNA methylation clocks

The co-authors stress that one of the most critical questions in rejuvenation is if a treatment can benefit humans, not just mice. 

The researchers used epigenetic aging clocks to measure chemical modifications in DNA.“Given the well-documented health benefits of omega-3, we explored whether it also influences the most reliable molecular markers of biological age: epigenetic clocks. To answer this fundamental question, we conducted a rigorous clinical trial using the latest and most validated epigenetic clocks.”

The experts explain that epigenetic aging clocks measure chemical modifications in the DNA molecule, known as methylation. Quantifying these modifications explains biological versus chronological aging. 

“At this time, several epigenetic clocks have been developed to measure biological aging. We focus on methylation-based estimators of mortality risk (PhenoAge, GrimAge1, GrimAge2) and the pace of aging (DunedinPACE).” 

Bischoff-Ferrari and Horvath say that prior observational and small clinical studies have linked each of the treatments tested in DO-HEALTH with slowing the rate of biological aging. 

“However, these clocks have not yet been translated to clinical care as validation in large clinical trials is largely missing. DO-HEALTH is the largest clinical trial that tested the responsiveness of the clocks to treatment. Thus, it is very encouraging to see the consistency of how omega-3 supplementation slowed biological aging in three of four clocks.”

These clocks showed the clearest signal for omega-3, while the fourth, PhenoAge, indicates additional benefits of combining the fatty acid with vitamin D and exercise. 

Next steps

Bischoff-Ferrari and Horvath highlight that a recent biomarker on aging meeting at Harvard University, US, evaluated epigenetic clocks as “the most validated and robust molecular measure of pan-tissue biological aging.” 

Epigenetic clocks test the difference between biological and chronological aging.Due to continuous advancements, scientists have developed first-, second-, and third-generation clocks. As no gold standard for measuring biological age exists, the team used the best currently validated clocks from the second and third generations. 

However, the experts caution that there is a lack of studies that test these clocks in their response to interventions expected to slow biological aging. They point to DO-HEALTH and the CALERIE trial, which showed that caloric restriction slowed the pace of aging, as the most significant trials to date to test the responsiveness of epigenetic clocks to interventions over time. 

“To further advance clinical application of biological aging clocks, we plan to use DO-HEALTH as a validation platform for novel biomarkers aging such as protein-based biomarkers that reflect the biological age of individual organs in still healthy adults.”

Moreover, the team hopes to extend its analyses on biological aging to all 2,157 trial participants, including those from Germany, France, Austria, and Portugal.