Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial.
Level 2 - randomized trial
Individual double-blind, placebo-controlled factorial randomized trial
PubMed 33170239 · doi:10.1001/jama.2020.16909
What was done
A 3-year, double-blind, placebo-controlled 2x2x2 factorial randomized clinical trial (DO-HEALTH) evaluated the individual and combined effects of vitamin D3 (2000 IU/d), omega-3 fatty acids (1 g/d), and a strength-training exercise program. The study randomized 2,157 community-dwelling adults aged 70 years or older (mean age 74.9 years; 61.7% women) with good cognitive status, sufficient mobility, and no major health events in the 5 years prior to enrollment. Participants were assigned to 1 of 8 treatment groups. The 6 primary outcomes evaluated over 3 years (median follow-up 2.99 years) were changes in systolic and diastolic blood pressure, Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates of nonvertebral fractures and infections. Statistical significance was set at P < .01 (99% CIs reported) to adjust for multiple primary end points.
What was found
A total of 1,900 participants (88%) completed the study. There were no statistically significant benefits of any intervention, individually or combined, for the 6 primary end points. Differences in mean change in systolic blood pressure were -0.8 mm Hg (99% CI, -2.1 to 0.5; P = .13) for vitamin D vs no vitamin D and -0.8 mm Hg (99% CI, -2.1 to 0.5; P = .11) for omega-3s vs no omega-3s. For diastolic blood pressure, the difference for omega-3s vs no omega-3s was -0.5 mm Hg (99% CI, -1.2 to 0.2; P = .06). The difference in mean change in infection incidence rate with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03; incidence rate ratio 0.89 [99% CI, 0.78-1.01]; P = .02, exceeding the P < .01 threshold). No effects were observed for SPPB, MoCA, or nonvertebral fractures. A total of 25 deaths occurred, with similar distribution across groups.
Why it matters
This large trial demonstrates that routine supplementation with vitamin D3, omega-3s, or a strength-training program does not meaningfully prevent functional decline, cognitive worsening, fractures, or infections in relatively healthy, active older adults.
Limits
The study was restricted to older adults without major comorbidities, intact cognitive status, and sufficient mobility, limiting generalizability to frail, institutionalized, or deficient populations. Baseline 25-hydroxyvitamin D levels, omega-3 index, and exercise compliance metrics are not reported in the abstract.
Cited by
- context In the DO-HEALTH trial, omega-3 supplementation alone reduced infections by 13% and decreased falls by 13%.