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Cited by 353Vitamin D Research StudiesNutrition and Health in AgingBone health and osteoporosis research

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

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Bischoff-Ferrari, Heike A., Vellas, Bruno, Rizzoli, René, Kressig, Reto W., da Silva, José A. P., Blauth, Michael, Felson, David T., McCloskey, Eugene V. +16 more·2020·JAMA
DOI 10.1001/jama.2020.16909PMC PMC7656284
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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 × 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 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. 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 < .13 and P < .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 = .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 = .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 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. Trial Registration: ClinicalTrials.gov Identifier: NCT01745263.

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  • Strength training is recommended in older adults to improve physical function.

    “Strength training is recommended in older adults to improve physical function.7,8,9,10”

    From Comparison of Power Training vs Traditional Strength Training on Physical Function in Older Adults: A Systematic Review and Meta-analysis (2022) · cites this paper as [8]

    The Discussion (p. 1863) reports that the strength-training program did not improve lower-extremity function in adults aged 70 or older without major comorbidities. The paper acknowledges other benefits of exercise, but its finding on physical function runs contrary to the rationale attributed to it here. (LLM, conf=0.82)

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  • Micronutrient optimization, especially with ≥800 IU/day of vitamin D and adequate calcium, is important for muscle function and fall prevention.

    “Micronutrient optimization, especially with ≥ 800 IU/day of vitamin D and adequate calcium, is important for muscle function and fall prevention [119].”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [119]

    The Conclusions report that 2000 IU/day of vitamin D did not significantly improve physical performance in adults aged 70 or older without major comorbidities, contrary to the claimed muscle-function benefit in this trial population. The paper does not establish that vitamin D plus adequate calcium prevents falls: calcium was not a randomized intervention, and falls were not among the reported primary outcomes (Study Participants; Primary End Points). (LLM, conf=0.78)

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  • 83% of participants in DO-HEALTH were at least moderately physically active at baseline, yet were prescribed exercise that did not challenge their capacities sufficiently to induce adaptation.

    “83% of participants in DO-HEALTH were at least moderately physically active at baseline, yet were prescribed exercise that did not challenge their capacities sufficiently to induce adaptation [312].”

    From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [312]

  • In the DO-HEALTH trial, a simple low intensity, home-based, body weight/elastic band exercise program in 2157 generally healthy and active adults age 70 and older compared with a control exercise of seated stretching found no benefit on fracture reduction or BMD over a 3-year follow-up.

    “in a 5-country European healthy longevity trial, DO-HEALTH, testing a simple low intensity, home-based, body weight/elastic band exercise program in 2157 generally healthy and active adults age 70 and older compared with a control exercise of seated stretching, found no benefit of the exercise program on fracture reduction [312] or BMD [313] over a 3-year follow-up.”

    From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [312]

  • The DO-HEALTH study of low intensity exercises had no benefit for bone health or other clinical outcomes and was also ineffective for falls prevention.

    “Similarly the DO-HEALTH study [312] of low intensity exercises, which had no benefit for bone health or other clinical outcomes, was also ineffective for falls prevention.”

    From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [312]

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Authors
Bischoff-Ferrari, H. A., Vellas, B., Rizzoli, R., Kressig, R. W., da Silva, J. A. P., Blauth, M., Felson, D. T., McCloskey, E. V., Watzl, B., Hofbauer, L. C., Felsenberg, D., Willett, W. C., Dawson-Hughes, B., Manson, J. E., Siebert, U., Theiler, R., Staehelin, H. B., de Godoi Rezende Costa Molino, C., Chocano-Bedoya, P. O., Abderhalden, L. A., Egli, A., Kanis, J. A., Orav, E. J., & DO-HEALTH Research Group
Affiliations
  • University of Zurich (CH)
  • Université Toulouse III - Paul Sabatier (FR)
  • University of Geneva (CH)
  • University of Basel (CH)
  • Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
  • Innsbruck Medical University (AT)
  • Boston University (US)
  • University of Sheffield (GB)
  • Max Rubner Institut (DE)
  • Center for Regenerative Therapies Dresden (DE)
  • Charité – Universitätsmedizin Berlin (DE)
  • Harvard University (US)
  • Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
  • Brigham and Women's Hospital (US)
  • Center on Aging and Mobility, University Hospital Zurich, City Hospital Waid & Triemli and University of Zurich, Zurich, Switzerland
  • Australian Catholic University (AU)
Corresponding author
Bischoff-Ferrari, Heike A.
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2020-11-10
Volume
324
Issue
18
Pages
1855
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2020.16909
PMC
PMC7656284
OpenAlex
W3099091911
Cited by
353
References
45
Citations by year
2026: 43 · 2025: 65 · 2024: 70 · 2023: 65 · 2022: 61 · 2021: 45 · 2020: 4
FWCI
28.77
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
  • OpenAgrar (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Funders
  • Pfizer
  • Nestec
  • Medical Research Council (MR/P020941/1)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR072571)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords
vitamin D supplementation, omega-3 fatty acids, resistance training, older adults, blood pressure, physical function, cognitive function, non-vertebral fractures, infection, disease prevention, combination supplementation, exercise intervention, frailty, sarcopenia, quality of life, health-related quality of life, anxiety, social isolation
MeSH terms
Aged, Aged, 80 and over, Cholecalciferol, Cognition Disorders, Double-Blind Method, Female, Follow-Up Studies, Health Status, Humans, Hypertension, Immunity, Male, Physical Fitness, Vitamins, Fatty Acids, Omega-3, Treatment Outcome, Dietary Supplements, Fractures, Bone, Resistance Training

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