Skip to main content


Log in

Multivitamin/mineral supplementation and the risk of cardiovascular disease: a large prospective study using UK Biobank data

European Journal of Nutrition Aims and scope Submit manuscript



Despite the widespread use of multivitamin/mineral supplements, the effects of multivitamin/mineral on cardiovascular disease (CVD) remain inconclusive. We aimed to prospectively investigate how multivitamin/mineral use is associated with CVD.


This population-based cohort study included 465,278 men and women who participated in the UK Biobank and were free from CVD at baseline. Participants were enrolled between 2006 and 2010 and followed-up until the end of 2018. Data on supplement use including multivitamin/mineral were collected using self-reported questionnaires. Cox proportional hazards models were used to estimate the hazard ratios of CVD events in relation to multivitamin/mineral use.


During the follow-up, we identified 25,772 cases of CVD events, 4754 cases of CVD mortality, 18,728 cases of coronary heart disease, 6726 cases of myocardial infarction, and 4561 cases of stroke. The multivariable-adjusted hazard ratios associated with multivitamin/mineral use were 0.96 (95% CI: 0.93, 0.99) for CVD events, 0.92 (0.86, 1.00) for CVD mortality, 0.96 (0.93, 0.99) for coronary heart disease, and 0.92 (0.86, 0.97) for myocardial infarction. Subgroup analysis suggested that multivitamin/mineral use was associated with a significantly lower risk of CVD events in participants aged < 60 years and in former and current smokers (P for interaction ≤ 0.01). Sensitivity analyses showed no substantial change in the results when we excluded participants who developed CVD events during the first 2 years of follow-up.


Multivitamin/mineral supplementation was associated with very modest reductions in CVD events. Age and smoking might modify these associations.

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

Fig. 1
Fig. 2


  1. Neuhouser ML (2003) Dietary supplement use by American women: challenges in assessing patterns of use, motives and costs. J Nutr 133(6):1992s–1996s.

    Article  PubMed  Google Scholar 

  2. Kim J, Choi J, Kwon SY, McEvoy JW, Blaha MJ, Blumenthal RS, Guallar E, Zhao D, Michos ED (2018) Association of multivitamin and mineral supplementation and risk of cardiovascular disease: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 11(7):e004224.

    Article  PubMed  Google Scholar 

  3. Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE, Gaziano JM (2012) Multivitamins in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA 308(17):1751–1760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briançon S (2004) The SUVIMAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 164(21):2335–2342.

    Article  CAS  PubMed  Google Scholar 

  5. Sherman RE, Anderson SA, Dal Pan GJ, Gray GW, Gross T, Hunter NL, LaVange L, Marinac-Dabic D, Marks PW, Robb MA, Shuren J, Temple R, Woodcock J, Yue LQ, Califf RM (2016) Real-world evidence—what is it and what can it tell us? N Engl J Med 375(23):2293–2297.

    Article  PubMed  Google Scholar 

  6. Rautiainen S, Akesson A, Levitan EB, Morgenstern R, Mittleman MA, Wolk A (2010) Multivitamin use and the risk of myocardial infarction: a population-based cohort of Swedish women. Am J Clin Nutr 92(5):1251–1256.

    Article  CAS  PubMed  Google Scholar 

  7. Dong JY, Iso H, Kitamura A, Tamakoshi A (2015) Multivitamin use and risk of stroke mortality: the Japan collaborative cohort study. Stroke 46(5):1167–1172.

    Article  PubMed  Google Scholar 

  8. Adebamowo SN, Feskanich D, Stampfer M, Rexrode K, Willett WC (2017) Multivitamin use and risk of stroke incidence and mortality amongst women. Eur J Neurol 24(10):1266–1273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rautiainen S, Lee IM, Rist PM, Gaziano JM, Manson JE, Buring JE, Sesso HD (2015) Multivitamin use and cardiovascular disease in a prospective study of women. Am J Clin Nutr 101(1):144–152.

    Article  CAS  PubMed  Google Scholar 

  10. Messerer M, Håkansson N, Wolk A, Akesson A (2008) Dietary supplement use and mortality in a cohort of Swedish men. Br J Nutr 99(3):626–631.

    Article  CAS  PubMed  Google Scholar 

  11. Rautiainen S, Rist PM, Glynn RJ, Buring JE, Gaziano JM, Sesso HD (2016) Multivitamin use and the risk of cardiovascular disease in men. J Nutr 146(6):1235–1240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li K, Kaaks R, Linseisen J, Rohrmann S (2012) Vitamin/mineral supplementation and cancer, cardiovascular, and all-cause mortality in a German prospective cohort (EPIC-Heidelberg). Eur J Nutr 51(4):407–413.

    Article  CAS  PubMed  Google Scholar 

  13. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, Downey P, Elliott P, Green J, Landray M, Liu B, Matthews P, Ong G, Pell J, Silman A, Young A, Sprosen T, Peakman T, Collins R (2015) UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 12(3):e1001779.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ma H, Li X, Sun D, Zhou T, Ley SH, Gustat J, Heianza Y, Qi L (2019) Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank. BMJ (Clin Res ed) 365:l1628.

    Article  Google Scholar 

  15. Tyrrell J, Jones SE, Beaumont R, Astley CM, Lovell R, Yaghootkar H, Tuke M, Ruth KS, Freathy RM, Hirschhorn JN, Wood AR, Murray A, Weedon MN, Frayling TM (2016) Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank. BMJ (Clin Res ed) 352:i582.

    Article  Google Scholar 

  16. Li ZH, Zhong WF, Liu S, Kraus VB, Zhang YJ, Gao X, Lv YB, Shen D, Zhang XR, Zhang PD, Huang QM, Chen Q, Wu XB, Shi XM, Wang D, Mao C (2020) Associations of habitual fish oil supplementation with cardiovascular outcomes and all cause mortality: evidence from a large population based cohort study. BMJ (Clin Res ed) 368:m456.

    Article  Google Scholar 

  17. Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, Carty C, Chaput JP, Chastin S, Chou R, Dempsey PC, DiPietro L, Ekelund U, Firth J, Friedenreich CM, Garcia L, Gichu M, Jago R, Katzmarzyk PT, Lambert E, Leitzmann M, Milton K, Ortega FB, Ranasinghe C, Stamatakis E, Tiedemann A, Troiano RP, van der Ploeg HP, Wari V, Willumsen JF (2020) World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med 54(24):1451–1462.

    Article  PubMed  Google Scholar 

  18. Holmquist C, Larsson S, Wolk A, de Faire U (2003) Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women–Stockholm Heart Epidemiology Program (SHEEP). J Nutr 133(8):2650–2654.

    Article  CAS  PubMed  Google Scholar 

  19. Bailey RL, Fakhouri TH, Park Y, Dwyer JT, Thomas PR, Gahche JJ, Miller PE, Dodd KW, Sempos CT, Murray DM (2015) Multivitamin-mineral use is associated with reduced risk of cardiovascular disease mortality among women in the United States. J Nutr 145(3):572–578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Watkins ML, Erickson JD, Thun MJ, Mulinare J, Heath CW Jr (2000) Multivitamin use and mortality in a large prospective study. Am J Epidemiol 152(2):149–162.

    Article  CAS  PubMed  Google Scholar 

  21. Jenkins DJA, Spence JD, Giovannucci EL, Kim YI, Josse RG, Vieth R, Sahye-Pudaruth S, Paquette M, Patel D, Blanco Mejia S, Viguiliouk E, Nishi SK, Kavanagh M, Tsirakis T, Kendall CWC, Pichika SC, Sievenpiper JL (2021) Supplemental vitamins and minerals for cardiovascular disease prevention and treatment: JACC focus seminar. J Am Coll Cardiol 77(4):423–436.

    Article  CAS  PubMed  Google Scholar 

  22. Salonen RM, Nyyssönen K, Kaikkonen J, Porkkala-Sarataho E, Voutilainen S, Rissanen TH, Tuomainen TP, Valkonen VP, Ristonmaa U, Lakka HM, Vanharanta M, Salonen JT, Poulsen HE (2003) Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study. Circulation 107(7):947–953.

    Article  CAS  PubMed  Google Scholar 

  23. Messner B, Bernhard D (2014) Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol 34(3):509–515.

    Article  CAS  PubMed  Google Scholar 

  24. Rautiainen S, Wang L, Lee IM, Manson JE, Gaziano JM, Buring JE, Sesso HD (2016) Multivitamin use and the risk of hypertension in a prospective cohort study of women. J Hypertens 34(8):1513–1519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Steinberg D, Witztum JL (2002) Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation 105(17):2107–2111.

    Article  PubMed  Google Scholar 

  26. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695.

    Article  CAS  PubMed  Google Scholar 

  27. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis (2002). JAMA 288(16):2015–2022. doi:

  28. McNulty H, Pentieva K, Hoey L, Ward M (2008) Homocysteine, B-vitamins and CVD. Proc Nutr Soc 67(2):232–237.

    Article  CAS  PubMed  Google Scholar 

  29. McGreevy C, Williams D (2011) New insights about vitamin D and cardiovascular disease: a narrative review. Ann Intern Med 155(12):820–826.

    Article  PubMed  Google Scholar 

  30. Rose AH, Hoffmann PR (2015) Selenoproteins and cardiovascular stress. Thromb Haemost 113(3):494–504.

    Article  PubMed  Google Scholar 

  31. Muñoz-Castañeda JR, Pendón-Ruiz de Mier MV, Rodríguez M, Rodríguez-Ortiz ME (2018) Magnesium replacement to protect cardiovascular and kidney damage? Lack of prospective clinical trials. Int J Mol Sci.

    Article  PubMed  PubMed Central  Google Scholar 

Download references


We thank UK Biobank participants. This research has been conducted using the UK Biobank Resource (application No 52632).


This study is supported by the National Natural Science Foundation of China (82173648), Innovative Talent Support Plan of the Medical and Health Technology Project in Zhejiang Province (2021422878), Internal Fund of Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences (2020YJY0212), Ningbo Clinical Research Center for Digestive System Tumors (2019A21003), and Sanming Project of Medicine in Shenzhen (SZSM201803080).

Author information

Authors and Affiliations



LH and YZ: conceptualized the manuscript; BC, CZ, and LH: contributed to the literature search and interpretation, the statistical analysis, the writing of the paper, and refining of figures and tables; RZ and MW: conducted the data collection; LH and YZ had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; and all authors: reviewed and revised the manuscript, read and approved the final manuscript.

Corresponding authors

Correspondence to Yonghong Zhang or Liyuan Han.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

This study was performed under generic ethical approval obtained by UK Biobank investigators from the National Health Service National Research Ethics Service (Ref: 11/NW/0.0382) and all participants provided written informed consent. The current analyses were carried out under application number 52632.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 31 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Che, B., Zhong, C., Zhang, R. et al. Multivitamin/mineral supplementation and the risk of cardiovascular disease: a large prospective study using UK Biobank data. Eur J Nutr 61, 2909–2917 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: