Skip to main content
Log in

Overview of results from the Vitamin D Assessment (ViDA) study

  • Short Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background

The Vitamin D Assessment (ViDA) study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy of monthly vitamin D supplementation in reducing the incidence of a range of acute and chronic diseases and intermediate outcomes.

Methods

The study was carried out in Auckland, New Zealand, among 5110 adults, aged 50–84 years, who were followed for a median 3.3 years. The intervention was vitamin D3 (2.5 mg or 100,000 IU) or placebo softgel oral capsules, mailed monthly to participants’ homes, with two capsules sent in the first mail-out post-randomisation (i.e. 200,000 IU bolus, or placebo), followed 1 month later (and thereafter monthly) with 100,000 IU vitamin D3 or placebo capsules. Outcomes were monitored through routinely collected health data and self-completed questionnaires.

Results

The results showed no beneficial effect of vitamin D supplementation on incidence of cardiovascular disease, falls, non-vertebral fractures and all cancer. However, beneficial effects from vitamin D supplementation were seen: for persistence with taking statins in participants on long-term statin therapy; and also in bone mineral density and arterial function in participants with low 25-hydroxyvitamin D levels, and in lung function among ever smokers (especially if vitamin D deficient). The latter findings are consistent with several previous studies,

Conclusion

Monthly high-dose vitamin D supplementation does not prevent a range of diseases, but may be beneficial for some intermediate outcomes in people who are vitamin D deficient.

Trial registration

Australian New Zealand Clinical Trials Registry identifier: ACTRN12611000402943.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, Vasan RS (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117(4):503–511

    Article  CAS  PubMed  Google Scholar 

  2. Melamed ML, Michos ED, Post W, Astor B (2008) 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 168(15):1629–1637. https://doi.org/10.1001/archinte.168.15.1629

    Article  PubMed  PubMed Central  Google Scholar 

  3. Scragg R, Sowers M, Bell C (2004) Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 27(12):2813–2818

    Article  CAS  PubMed  Google Scholar 

  4. Scragg R, Sowers M, Bell C (2007) Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am J Hypertens 20(7):713–719

    Article  CAS  PubMed  Google Scholar 

  5. Black PN, Scragg R (2005) Relationship between serum 25-hydroxyvitamin D and pulmonary function in the Third National Health and Nutrition Examination Survey. Chest 128(6):3792–3798

    Article  CAS  PubMed  Google Scholar 

  6. Ginde AA, Mansbach JM, Camargo CA Jr (2009) Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med 169(4):384–390. https://doi.org/10.1001/archinternmed.2008.560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Autier P, Gandini S (2007) Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 167(16):1730–1737

    Article  CAS  PubMed  Google Scholar 

  8. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL, Robbins J, Rohan TE, Sarto GE, Sharma S, Stefanick ML, Van Horn L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR, Bonds DE, Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C, Gass M, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Judd H, Kooperberg CL, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Lewis CE, Limacher MC, Manson JE (2006) Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 354(7):684–696

    Article  CAS  PubMed  Google Scholar 

  9. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O’Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354(7):669–683

    Article  CAS  PubMed  Google Scholar 

  10. Newmark HL, Heaney RP (2006) Calcium, vitamin D, and risk reduction of colorectal cancer. Nutr Cancer 56(1):1–2

    Article  CAS  PubMed  Google Scholar 

  11. Scragg R (2018) Limitations of vitamin D supplementation trials: why observational studies will continue to help determine the role of vitamin D in health. J Steroid Biochem Mol Biol 177:6–9. https://doi.org/10.1016/j.jsbmb.2017.06.006

    Article  CAS  PubMed  Google Scholar 

  12. Heaney RP (2008) Vitamin D in health and disease. Clin J Am Soc Nephrol 3(5):1535–1541. https://doi.org/10.2215/cjn.01160308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Meyer HE, Holvik K, Lips P (2015) Should vitamin D supplements be recommended to prevent chronic diseases? BMJ 350:h321. https://doi.org/10.1136/bmj.h321

    Article  PubMed  Google Scholar 

  14. Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, Zaharris E, Macfadyen JG, Danielson E, Lin J, Zhang SM, Buring JE (2012) The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials 33(1):159–171. https://doi.org/10.1016/j.cct.2011.09.009

    Article  CAS  PubMed  Google Scholar 

  15. Scragg R, Waayer D, Stewart AW, Lawes CM, Toop L, Murphy J, Khaw KT, Camargo CA Jr (2016) The Vitamin D Assessment (ViDA) Study: design of a randomized controlled trial of vitamin D supplementation for the prevention of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. J Steroid Biochem Mol Biol 164:318–325. https://doi.org/10.1016/j.jsbmb.2015.09.010

    Article  CAS  PubMed  Google Scholar 

  16. Reid IR, Bolland MJ, Grey A (2010) Does calcium supplementation increase cardiovascular risk? Clin Endocrinol (Oxf) 73(6):689–695. https://doi.org/10.1111/j.1365-2265.20

    Article  CAS  Google Scholar 

  17. Scragg R, Stewart AW, Waayer D, Lawes CMM, Toop L, Sluyter J, Murphy J, Khaw KT, Camargo CA Jr (2017) Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the vitamin D assessment study: a randomized clinical trial. JAMA Cardiol 2(6):608–616. https://doi.org/10.1001/jamacardio.2017.0175

    Article  PubMed  PubMed Central  Google Scholar 

  18. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Gordon D, Copeland T, D’Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE, Group VR (2019) Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 380(1):33–44. https://doi.org/10.1056/nejmoa1809944

    Article  CAS  PubMed  Google Scholar 

  19. Lamb SE, Jorstad-Stein EC, Hauer K, Becker C, Prevention of Falls Network E, Outcomes Consensus G (2005) Development of a common outcome data set for fall injury prevention trials: the Prevention of Falls Network Europe consensus. J Am Geriatr Soc 53(9):1618–1622. https://doi.org/10.1111/j.1532-5415.2005.53455.x

    Article  PubMed  Google Scholar 

  20. Khaw KT, Stewart AW, Waayer D, Lawes CMM, Toop L, Camargo CA Jr, Scragg R (2017) Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial. Lancet Diabetes Endocrinol 5(6):438–447. https://doi.org/10.1016/s2213-8587(17)30103-1

    Article  CAS  PubMed  Google Scholar 

  21. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL (2017) Effect of vitamin D and calcium supplementation on cancer incidence in older women: a randomized clinical trial. JAMA 317(12):1234–1243. https://doi.org/10.1001/jama.2017.2115

    Article  CAS  PubMed  Google Scholar 

  22. Scragg R, Khaw KT, Toop L, Sluyter J, Lawes CMM, Waayer D, Giovannucci E, Camargo CA Jr (2018) Monthly high-dose vitamin d supplementation and cancer risk: a post hoc analysis of the vitamin D assessment randomized clinical trial. JAMA Oncol 4(11):e182178. https://doi.org/10.1001/jamaoncol.2018.2178

    Article  PubMed  PubMed Central  Google Scholar 

  23. Reid IR, Horne AM, Mihov B, Gamble GD, Al-Abuwsi F, Singh M, Taylor L, Fenwick S, Camargo CA, Stewart AW, Scragg R (2017) Effect of monthly high-dose vitamin D on bone density in community-dwelling older adults substudy of a randomized controlled trial. J Intern Med 282(5):452–460. https://doi.org/10.1111/joim.12651

    Article  CAS  PubMed  Google Scholar 

  24. Macdonald HM, Reid IR, Gamble GD, Fraser WD, Tang JC, Wood AD (2018) 25-Hydroxyvitamin D threshold for the effects of vitamin d supplements on bone density: secondary analysis of a randomized controlled trial. J Bone Miner Res 33(8):1464–1469. https://doi.org/10.1002/jbmr.3442

    Article  CAS  PubMed  Google Scholar 

  25. Sluyter JD, Camargo CA, Waayer D, Lawes CMM, Toop L, Khaw KT, Scragg R (2017) Effect of monthly, high-dose, long-term vitamin d on lung function: a randomized controlled trial. Nutrients. https://doi.org/10.3390/nu9121353

    Article  PubMed  PubMed Central  Google Scholar 

  26. Cazzola M, MacNee W, Martinez FJ, Rabe KF, Franciosi LG, Barnes PJ, Brusasco V, Burge PS, Calverley PM, Celli BR, Jones PW, Mahler DA, Make B, Miravitlles M, Page CP, Palange P, Parr D, Pistolesi M, Rennard SI, Rutten-van Molken MP, Stockley R, Sullivan SD, Wedzicha JA, Wouters EF, American Thoracic S, European Respiratory Society Task Force on outcomes of C (2008) Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J 31(2):416–469. https://doi.org/10.1183/09031936.00099306

    Article  CAS  PubMed  Google Scholar 

  27. Sluyter JD, Camargo CA Jr, Stewart AW, Waayer D, Lawes CMM, Toop L, Khaw KT, Thom SAM, Hametner B, Wassertheurer S, Parker KH, Hughes AD, Scragg R (2017) Effect of monthly, high-dose, long-term vitamin D supplementation on central blood pressure parameters: a randomized controlled trial substudy. J Am Heart Assoc. https://doi.org/10.1161/jaha.117.006802

    Article  PubMed  PubMed Central  Google Scholar 

  28. Raed A, Bhagatwala J, Zhu H, Pollock NK, Parikh SJ, Huang Y, Havens R, Kotak I, Guo DH, Dong Y (2017) Dose responses of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency: a placebo controlled randomized trial. PLoS One 12(12):e0188424. https://doi.org/10.1371/journal.pone.0188424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kumar V, Yadav AK, Lal A, Kumar V, Singhal M, Billot L, Gupta KL, Banerjee D, Jha V (2017) A randomized trial of vitamin D supplementation on vascular function in CKD. J Am Soc Nephrol 28(10):3100–3108. https://doi.org/10.1681/asn.2017010003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, Roden M, Stein E, Tokgozoglu L, Nordestgaard BG, Bruckert E, De Backer G, Krauss RM, Laufs U, Santos RD, Hegele RA, Hovingh GK, Leiter LA, Mach F, Marz W, Newman CB, Wiklund O, Jacobson TA, Catapano AL, Chapman MJ, Ginsberg HN, European Atherosclerosis Society Consensus P (2015) Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 36(17):1012–1022. https://doi.org/10.1093/eurheartj/ehv043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Michalska-Kasiczak M, Sahebkar A, Mikhailidis DP, Rysz J, Muntner P, Toth PP, Jones SR, Rizzo M, Kees Hovingh G, Farnier M, Moriarty PM, Bittner VA, Lip GY, Banach M, Lipid Blood Pressure, Meta-analysis Collaboration G (2015) Analysis of vitamin D levels in patients with and without statin-associated myalgia—a systematic review and meta-analysis of 7 studies with 2420 patients. Int J Cardiol 178:111–116. https://doi.org/10.1016/j.ijcard.2014.10.118

    Article  PubMed  Google Scholar 

  32. Khayznikov M, Hemachrandra K, Pandit R, Kumar A, Wang P, Glueck CJ (2015) Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci 7(3):86–93. https://doi.org/10.4103/1947-2714.153919

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wu Z, Camargo CA Jr, Khaw KT, Waayer D, Lawes CMM, Toop L, Scragg R (2018) Effects of vitamin D supplementation on adherence to and persistence with long-term statin therapy: secondary analysis from the randomized, double-blind, placebo-controlled ViDA study. Atherosclerosis 273:59–66. https://doi.org/10.1016/j.atherosclerosis.2018.04.009

    Article  CAS  PubMed  Google Scholar 

  34. Wu Z, Malihi Z, Stewart AW, Lawes CM, Scragg R (2016) Effect of vitamin D supplementation on pain: a systematic review and meta-analysis. Pain Physician 19(7):415–427

    PubMed  Google Scholar 

  35. Wu Z, Camargo CA Jr, Malihi Z, Bartley J, Waayer D, Lawes CMM, Toop L, Khaw KT, Scragg R (2018) Monthly vitamin D supplementation, pain, and pattern of analgesic prescription: secondary analysis from the randomized, double-blind, placebo-controlled vitamin D assessment study. Pain 159(6):1074–1082. https://doi.org/10.1097/j.pain.0000000000001189

    Article  CAS  PubMed  Google Scholar 

  36. Malihi Z, Wu Z, Stewart AW, Lawes CM, Scragg R (2016) Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis. Am J Clin Nutr 104(4):1039–1051. https://doi.org/10.3945/ajcn.116.134981

    Article  CAS  PubMed  Google Scholar 

  37. Malihi Z, Lawes CMM, Wu Z, Huang Y, Waayer D, Toop L, Khaw KT, Camargo CA, Scragg R (2019) Monthly high-dose vitamin D supplementation does not increase kidney stone risk or serum calcium: results from a randomized controlled trial. Am J Clin Nutr. https://doi.org/10.1093/ajcn/nqy378

    Article  PubMed  Google Scholar 

  38. Malihi Z, Lawes CMM, Wu Z, Huang Y, Waayer D, Toop L, Khaw KT, Camargo CA Jr, Scragg R (2018) Monthly high-dose vitamin D3 supplementation and self-reported adverse events in a 4-year randomized controlled trial. Clin Nutr. https://doi.org/10.1016/j.clnu.2018.07.034

    Article  PubMed  Google Scholar 

  39. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC (2010) Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 303(18):1815–1822. https://doi.org/10.1001/jama.20

    Article  CAS  PubMed  Google Scholar 

  40. Hollis BW, Wagner CL (2013) Clinical review: the role of the parent compound vitamin D with respect to metabolism and function: why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab 98(12):4619–4628. https://doi.org/10.1210/jc.2013-2653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Heaney RP, Armas LA (2015) Quantifying the vitamin D economy. Nutr Rev 73(1):51–67. https://doi.org/10.1093/nutrit/nuu004

    Article  PubMed  Google Scholar 

  42. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr (2017) Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 356:i6583. https://doi.org/10.1136/bmj.i6583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jolliffe DA, Greenberg L, Hooper RL, Griffiths CJ, Camargo CA Jr, Kerley CP, Jensen ME, Mauger D, Stelmach I, Urashima M, Martineau AR (2017) Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. Lancet Respir Med 5(11):881–890. https://doi.org/10.1016/s2213-2600(17)30306-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Jolliffe DA, Greenberg L, Hooper RL, Mathyssen C, Rafiq R, de Jongh RT, Camargo CA, Griffiths CJ, Janssens W, Martineau AR (2019) Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax. https://doi.org/10.1136/thoraxjnl-2018-212092

    Article  PubMed  Google Scholar 

  45. Scragg R (2018) Emerging evidence of thresholds for beneficial effects from vitamin D supplementation. Nutrients 1:1. https://doi.org/10.3390/nu10050561

    Article  CAS  Google Scholar 

  46. Rose G (1985) Sick individuals and sick populations. Int J Epidemiol 14(1):32–38

    Article  CAS  PubMed  Google Scholar 

  47. Minisola S, Colangelo L, Cipriani C, Pepe J, Cook DP, Mathieu C (2019) Screening for hypovitaminosis D: cost-effective or not? Eur J Endocrinol Eur Fed Endocr Soc 180(3):D1–D7. https://doi.org/10.1530/eje-18-0977

    Article  CAS  Google Scholar 

Download references

Funding

The ViDA study was funded by the Health Research Council of New Zealand (Grant 10/400) and the Accident Compensation Corporation of New Zealand.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. K. R. Scragg.

Ethics declarations

Conflict of interest

The author declares no conflict of interest.

Ethical approval

This was granted for the ViDA study by the Multiregion Ethics Committee, Wellington (MEC/09/08/082). All procedurers in this study on human participants were in accordance with the ethical standards of the aforementioned committee, and with the 1964 Helsinki declaration and its later ammendments.

Informed consent

All participants in the ViDA study gave written informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scragg, R.K.R. Overview of results from the Vitamin D Assessment (ViDA) study. J Endocrinol Invest 42, 1391–1399 (2019). https://doi.org/10.1007/s40618-019-01056-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-019-01056-z

Keywords

Navigation