Key Points:
Question: Do vitamin D, omega-3, and a strength-training exercise program alone or in combination prevent 6 health outcomes among relatively healthy adults aged 70 years or older?
Results: In this randomized trial that included 2157 adults aged 70 years or older, 3-year treatment with vitamin D3 (2000 IU/d), with omega-3 fatty acids (1 g/d), or with a strength-training exercise program did not result in statistically-significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rate, or cognition.
Meaning: These findings do not support the use of vitamin D, omega-3, or a strength-training exercise program for these clinical outcomes among relatively healthy older adults.
Importance: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear.
Objective: To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults.
Design, Setting, & Participants: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017.
Interventions: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270).
Main Outcomes & Measures: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and p < 0.01 was required for statistical-significance.
Results: Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically-significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both −0.8 (99% CI, −2.1 to 0.5) mm Hg, with p < 0.13 and p < 0.11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was −0.5 (99% CI, −1.2 to 0.2) mm Hg (p = 0.06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was −0.13 (99% CI, −0.23 to −0.03), with an IR ratio of 0.89 (99% CI, 0.78–1.01; p = 0.02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures. A total of 25 deaths were reported, with similar numbers in all treatment groups.
Conclusions & Relevance: Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically-significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes.
Trial Registration: ClinicalTrials.gov Identifier: NCT01745263.