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

Authors: BISCHOFF-FERRARI, HEIKE - University Hospital Zurich; VELLAS, BRUNO - Toulouse University Hospital; RIZZOLI, RENE - Geneva University Hospital; KRESSIG, RETO - University Of Basel; DA SILVA, JOSE A.P. - University Of Coimbra; BLAUTH, MICHAEL - Innsbruck Medical University; FELSON, DAVID - Boston University; MCCLOSKEY, EUGENE - University Of Sheffield; WATZL, BERNHARD - Max Rubner-Institut (MRI); HOFBAUER, LORENZ - Technical University Dresden; FELSENBERG, DIETER - Free University Of Berlin; WILLETT, WALTER - Harvard School Of Public Health; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MANSON, JOANN - Brigham & Women'S Hospital; SIEBERT, UWE - Harvard School Of Public Health; THEILER, ROBERT - University Of Zurich; STAHELIN, HANNES - University Of Basel; DEGODOIREZENDECOSTA, CAROLINE - University Hospital Zurich; CHOCANO-BEDOYA, PATRICIA - University Of Bern; ABDERHALDEN, LAUREN - University Of Zurich; EGLI, ANDREAS - University Of Zurich; KANIS, JOHN - University Of Sheffield; ORAV, JOHN ENDEL - Harvard School Of Public Health

Submitted to: Journal of the American Medical Association
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/19/2020
Publication Date: 11/10/2020
Citation: Bischoff-Ferrari, H.A., Vellas, B., Rizzoli, R., Kressig, R.W., da Silva, J., Blauth, M., Felson, D.T., McCloskey, E., Watzl, B., Hofbauer, L., Felsenberg, D., Willett, W.C., Dawson-Hughes, B., Manson, J.E., Siebert, U., Theiler, R., Stahelin, H.B., de Godoi Rezende Costa, C., Chocano-Bedoya, P.O., Abderhalden, L.A., Egli, A., Kanis, J.A., Orav, J. 2020. 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. Journal of the American Medical Association. 324(18):1855-1868. https://doi.org/10.1001/jama.2020.16909.
DOI: https://doi.org/10.1001/jama.2020.16909

Interpretive Summary: The number of older adults with age-related chronic diseases is increasing and interventions that are effective, affordable, and well-tolerated in the prevention of chronic conditions are urgently needed. The DO-HEALTH study is a multi-center clinical trial conducted in 2,157 community-dwelling men and women, age 70 and older, at 7 clinical sites in 5 European countries. The trial tested the individual and additive benefit of 3 interventions: vitamin D 2,000 IU/day, omega-3 fatty acids 1,000 mg/day and a 30-minute 3 times/week home exercise program on blood pressure, non-vertebral fractures, muscle performance, rate of infections, or cognition. The trial duration was 3 years with in-person contacts during 4 clinical visits and by quarterly phone calls. The main findings from this trial are that none of the 3 treatments resulted in statistically significant differences in improvement in systolic or diastolic blood pressure, non-vertebral fractures, physical performance, infection rate, or cognition. 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.

Technical Abstract: 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, AND PARTICIPANTS Double-blind, placebo-controlled, 2 x 2 x 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 AND 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 < .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. A total of 25 deaths were reported, with similar numbers in all treatment groups. CONCLUSIONS AND 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.