Study shows synergistic effects of vitamin D3, omega-3s and exercise on pre-frailty prevention

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Supplementation with vitamin D3 and omega-3 fatty acids may not reduce the risk of pre-frailty on their own but have a synergistic effect when combined with home exercise, according to a recent study published in The Journal of Frailty & Aging.

The research evaluated a subset of participants from the wider DO-Health healthy aging study – a multi-center clinical trial carried out in a generally healthy population of community-dwelling European adults aged 70 and over in Switzerland, Germany, France, Austria and Portugal. 

“In this three-year, double-blind, randomized controlled trial among 1,137 older adults who were robust at baseline, the combined interventions of daily supplemental 2,000 IU vitamin D3 plus daily 1g marine omega-3 plus a simple home exercise program (SHEP) had significant benefits with regard to the prevention of pre-frailty,” the team of international researchers wrote. 

“However, this benefit was not significant for the three treatments individually, highlighting the importance of the additive effect of all three preventive strategies.”

The study was funded by the Seventh Framework Program of the European Commission, the University of Zurich (Chair for Geriatric Medicine and Aging Research), DSM Nutritional Products, Roche, NESTEC, Pfizer and Streuli. 

The additive effect

The study divided the subset of 1,137 robust older adults (mean age 74.3 years, 56.5% women, mean gait speed 1.18 m/s) into eight groups to evaluate the effect of daily vitamin D3, omega-3s and SHEP, alone and in combination, as compared to a placebo control. Frailty status was assessed at baseline and annually over three years of follow-up.

“Odds ratios for becoming pre-frail were not significantly lower for vitamin D3, or omega 3s or SHEP, individually, compared to control (placebo for the supplements and control exercise),” the researchers concluded. “However, the three treatments combined showed significantly decreased odds (OR 0.61 [95% CI 0.38–0.98; p=0.04) of becoming pre-frail compared to control.”

None of the individual treatments or their combination significantly reduced the odds of becoming frail.

The study suggests that effects might be explained by the complementary influences of the three interventions on the “complex pathophysiological pathways that are linked to the development of frailty, including muscle function, chronic inflammation, cardiovascular health and immune system regulations.”

In commenting on the additive effect, Luke Huber, vice president of scientific and regulatory affairs at the Council for Responsible Nutrition (CRN) called the significant reduction in pre-frailty impressive.  

“CRN continues to encourage consumers to follow a range of healthy lifestyle choices, including a proper diet, supplementation and exercise for healthy aging, as this study reinforces,” he added.

‘No magic pill to prevent frailty’

The results of the DO-Health study echo findings from an ancillary study of another multi-year, large cohort trial carried out in the U.S. population (the VITAL trial), which found that vitamin D3 or omega-3 fatty acid supplementation did not affect the rate of frailty change or incidence over time in older adults. 

In an accompanying editorial published in the same issue of the JAMA Network OPEN medical journal entitled “There Is No Magic Pill to Prevent Frailty—You Still Have to Eat Your Vegetables”, Elizabeth Eckstrom and Bryanna De Lima of the Department of Medicine at Oregon Health & Science University noted:

“It is tempting to think one could take supplements, such as omega-3 fatty acid and vitamin D3 and receive similar benefits [as the Mediterranean Diet] for frailty prevention, but studies to date assessing the effect of dietary supplements on frailty have shown no benefit.”

The researchers on the DO-Health study suggest further investigation into the underlying mechanisms behind the additive effect and whether it is superior to a healthy and active lifestyle that includes comparative amount of dietary omega-3s and regular physical exercise.

Source: The Journal of Frailty & Aging, 12, 71–77 (2023)

doi: dx.doi.org/10.14283/jfa.2022.48

“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”

Authors: Michael Gagesch, et al.