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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
Open accessAbstract
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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In the citing paper
“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]
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In the citing paper
“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]
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Experimental — accuracy not yet measuredIn the citing paper
“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 citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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 citing paper
“83% of participants in DO-HEALTH were at least moderately physically active at baseline”
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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Cites
The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment
Nasreddine, Z. S., Phillips, N. A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J. L., & Chertkow, H. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53221.x · Cited by 25,553
EuroQol: a new facility for the measurement of health-related quality of life
(1990) · Health Policy · doi:10.1016/0168-8510(90)90421-9 · Cited by 15,736
Guralnik, J. M., Simonsick, E. M., Ferrucci, L., Glynn, R. J., Berkman, L. F., Blazer, D. G., Scherr, P. A., & Wallace, R. B. (1994) · Journal of Gerontology · doi:10.1093/geronj/49.2.m85 · Cited by 9,792
Active Ageing: A Policy Framework
Kalache, A., & Gatti, A. (2002) · The Aging Male · doi:10.1080/713604647 · Cited by 3,150
The World Report on Ageing and Health
Beard, J., Officer, A. M., & Cassels, A. (2016) · The Gerontologist · doi:10.1093/geront/gnw037 · Cited by 2,911
Sangha, O., Stucki, G., Liang, M. H., Fossel, A. H., & Katz, J. N. (2003) · Arthritis Care & Research · doi:10.1002/art.10993 · Cited by 1,799
Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease
Manson, J. E., Cook, N. R., Lee, I.-M. M., Christen, W., Bassuk, S. S., Mora, S., Luttmann‐Gibson, H., Gordon, D., Copeland, T., D’Agostino, D., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1809944 · Cited by 1,684
Self-citationWorld report on ageing and health
Dey, A. (2017) · The Indian Journal of Medical Research · doi:10.4103/0971-5916.207249 · Cited by 1,486
Pahor, M., Guralnik, J. M., Ambrosius, W. T., Blair, S., Bonds, D. E., Church, T. S., Espeland, M. A., Fielding, R. A., Gill, T. M., Groessl, E. J., et al. (2014) · JAMA · doi:10.1001/jama.2014.5616 · Cited by 1,427
Reproducibility and validity of a self-administered physical activity questionnaire
WOLF, A. M., HUNTER, D. J., COLDITZ, G. A., MANSON, J. E., STAMPFER, M. J., CORSANO, K. A., ROSNER, B., KRISKA, A., & WILLETT, W. C. (1994) · International Journal of Epidemiology · doi:10.1093/ije/23.5.991 · Cited by 1,038
Self-citationMarine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer
Manson, J. E., Cook, N. R., Lee, I.-M., Christen, W., Bassuk, S. S., Mora, S., Gibson, H., Albert, C. M., Gordon, D., Copeland, T., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1811403 · Cited by 979
Self-citationA Pooled Analysis of Vitamin D Dose Requirements for Fracture Prevention
Bischoff-Ferrari, H. A., Willett, W. C., Orav, E. J., Lips, P. T. A. M., Meunier, P. J., Lyons, R. A., Flicker, L. A., Wark, J. D., Jackson, R. D., Cauley, J. A., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1109617 · Cited by 805
Self-citationLips, P. T. A. M., Cashman, K. D., Lamberg-Allardt, C. J. E., Bischoff-Ferrari, H. A., Obermayer-Pietsch, B. M., Bianchi, M. L., Stepan, J. J., Fuleihan, G. E., & Bouillon, R. (2019) · European Journal of Endocrinology · doi:10.1530/eje-18-0736 · Cited by 696
Self-citationPfeifer, M., Begerow, B., Minne, H. W., Nachtigall, D., & Hansen, C. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.4.7393 · Cited by 645
Vitamin D: a negative endocrine regulator of the renin–angiotensin system and blood pressure
Li, Y. C., Qiao, G., Uskoković, M. R., Xiang, W., Zheng, W., & Kong, J. (2004) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2004.03.004 · Cited by 616
Ultraviolet B and blood pressure
Krause, R., Bühring, M., Hopfenmüller, W., Holick, M. F., & Sharma, A. M. (1998) · The Lancet · doi:10.1016/s0140-6736(05)60827-6 · Cited by 514
Luis, C. A., Keegan, A. P., & MULLAN, M. J. (2008) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2101 · Cited by 511
Bischoff-Ferrari, H. A., Dawson-Hughes, B., Orav, E. J., Staehelin, H. B., Meyer, O. W., Theiler, R., Dick, W., Willett, W. C., & Egli, A. (2016) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2015.7148 · Cited by 511
Self-citationKwon, S., Perera, S., Pahor, M., Katula, J. A., King, A. C., Groessl, E. J., & Studenski, S. A. (2009) · The Journal of nutrition, health and aging · doi:10.1007/s12603-009-0104-z · Cited by 494
Vitamin D and Risk of Cognitive Decline in Elderly Persons
Llewellyn, D. J. (2010) · Archives of Internal Medicine · doi:10.1001/archinternmed.2010.173 · Cited by 467
Vitamin D and disease prevention with special reference to cardiovascular disease
Zittermann, A. (2006) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2006.02.001 · Cited by 446
Del Gobbo, L. C., Imamura, F., Aslibekyan, S., Marklund, M., Virtanen, J. K., Wennberg, M., Yakoob, M. Y., Chiuve, S. E., dela Cruz, L., Frazier-Wood, A. C., et al. (2016) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2016.2925 · Cited by 404
Self-citationMiller, P. E., Elswyk, M. E. V., & Alexander, D. D. (2014) · American Journal of Hypertension · doi:10.1093/ajh/hpu024 · Cited by 354
Effect of Vitamin D Supplementation on Blood Pressure
Beveridge, L. A., Struthers, A. D., Khan, F., Jorde, R., Scragg, R. K. R., Macdonald, H. M., Alvarez, J. A., Boxer, R. S., Dalbeni, A., Gepner, A. D., et al. (2015) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2015.0237 · Cited by 315
Exercise and Vitamin D in Fall Prevention Among Older Women
Uusi‐Rasi, K., Patil, R., Karinkanta, S., Kannus, P., Tokola, K., Lamberg-Allardt, C. J. E., & Sievänen, H. T. (2015) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2015.0225 · Cited by 265
Effect of High-Dosage Cholecalciferol and Extended Physiotherapy on Complications After Hip Fracture
Bischoff-Ferrari, H. A. (2010) · Archives of Internal Medicine · doi:10.1001/archinternmed.2010.67 · Cited by 213
Self-citationBischoff-Ferrari, H. A., Dawson-Hughes, B. F., Stöcklin, E., Sidelnikov, E., Willett, W. C., Orav, E. J., Stähelin, H. B., Wolfram, S., Jetter, A., Schwager, J., et al. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.551 · Cited by 197
Self-citationGivens, D. I., & Gibbs, R. A. (2008) · Proceedings of The Nutrition Society · doi:10.1017/s0029665108007167 · Cited by 191
Mirhosseini, N. Z., Rainsbury, J., & Kimball, S. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00087 · Cited by 177
Pradelli, L., Mayer, K., Muscaritoli, M., & Heller, A. R. (2012) · Critical Care · doi:10.1186/cc11668 · Cited by 172
Changes in Montreal Cognitive Assessment Scores Over Time
Krishnan, K., Rossetti, H. C., Hynan, L. S., Carter, K., Falkowski, J., Lacritz, L., Cullum, C. M., & Weiner, M. (2016) · Assessment · doi:10.1177/1073191116654217 · Cited by 148
AbuMweis, S., Jew, S., Tayyem, R., & Agraib, L. (2018) · Journal of Human Nutrition and Dietetics · doi:10.1111/jhn.12493 · Cited by 122
Markwick, A., Zamboni, G., & de Jager, C. A. (2012) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2012.672966 · Cited by 99
Pan, C. X., Carmody, S. S., Leipzig, R. M., Granieri, E., Sullivan, A., Block, S. D., & Arnold, R. M. (2005) · Journal of the American Geriatrics Society · doi:10.1111/jgs.2005.53.issue-4 · Cited by 93
Lassere, M. N., Johnson, K. R., Schiff, M., & Rees, D. M. (2012) · BMC Medical Research Methodology · doi:10.1186/1471-2288-12-27 · Cited by 85
Swart, K. M. A., Lips, P. T. A. M., Brouwer, I. A., Jorde, R., Heymans, M. W., Grimnes, G., Grübler, M. R., Gaksch, M., Tomaschitz, A., Pilz, S., et al. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy078 · Cited by 64
Li, N., Zhou, Y., Qin, X., Chen, Y., He, D., Jin-yan, F., & Wu, X. (2013) · Clinical Nutrition · doi:10.1016/j.clnu.2013.08.013 · Cited by 59
Bischoff-Ferrari, H. A., Molino, C. D. G. R. C., Rival, S., Vellas, B. J., Rizzoli, R., Kressig, R. W., Kanis, J. А., Manson, J. E., Dawson-Hughes, B. F., Orav, E. J., et al. (2020) · Contemporary Clinical Trials · doi:10.1016/j.cct.2020.106124 · Cited by 59
Self-citationOverview of results from the Vitamin D Assessment (ViDA) study
Scragg, R. K. R. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01056-z · Cited by 46
Chonchol, M., CIGOLINI, M., & Targher, G. (2007) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfm537 · Cited by 45
Bischoff-Ferrari, H. A., Orav, E. J., Egli, A., Dawson‐Hughes, B., Fischer, K., Staehelin, H. B., Rizzoli, R., Hodler, J., von Eckardstein, A., Freystaetter, G., et al. (2018) · RMD Open · doi:10.1136/rmdopen-2018-000678 · Cited by 24
Self-citationPhysical Performance and Vitamin D in Elderly Black Women–The PODA Randomized Clinical Trial
Aloia, J. F., Mikhail, M., Fazzari, M. J., Islam, S., Ragolia, L., & Guralnik, J. M. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01418 · Cited by 17
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Reid, I. R., & Billington, E. O. (2022) · The Lancet · doi:10.1016/s0140-6736(21)02646-5 · Cited by 736
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Demay, M. B., Pittas, A. G., Bikle, D. D., Diab, D. L., Kiely, M. E., Lazaretti-Castro, M., Lips, P., Mitchell, D. M., Murad, M. H., Powers, S., et al. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae290 · Cited by 639
Jolliffe, D. A., Camargo, C. A., Sluyter, J. D., Aglipay, M., Aloia, J. F., Ganmaa, D., Bergman, P., Bischoff-Ferrari, H. A., Borzutzky, A., Damsgaard, C. T., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00051-6 · Cited by 547
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Bouillon, R., Manousaki, D., Rosen, C., Trajanoska, K., Rivadeneira, F., & Richards, J. B. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00593-z · Cited by 535
Dominguez, L. J., Veronese, N., Vernuccio, L., Catanese, G., Inzerillo, F., Salemi, G., & Barbagallo, M. (2021) · Nutrients · doi:10.3390/nu13114080 · Cited by 433
Metadata
- 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
- 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
- bronze
- doi.org
- 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 › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
- Health Sciences › Medicine › Physiology (medical) › 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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