Purpose of Review
The objective of this study is to explore the current literature supporting the use oral multivitamins and multi/minerals (OMVMs) for cardiovascular diseases (CVD) treatment and prevention.
Data on multivitamins, vitamin C and D, coenzyme Q, calcium, and selenium, has showed no consistent benefit for the prevention of CVD, myocardial infarction, or stroke, nor was there a benefit for all-cause mortality to support their routine supplementation. Folic acid alone and B vitamins with folic acid, B6 and B12, reduce stroke, whereas niacin and antioxidants are associated with an increased risk of all-cause mortality. Iron deficiency should be avoided and treated if found, but routine supplementation to those without deficiency is not evidence based.
Despite the high supplement use by the general public, there is no evidence to support the routine supplementation of oral multivitamins and multi/minerals (OVMN) for CVD prevention or treatment.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1736–88.
Kantor ED, Rehm CD, Du M, White E, Giovannucci EL. Trends in dietary supplement use among US adults from 1999-2012. Jama. 2016;316(14):1464–74.
2018 CRN consumer survey on dietary supplements: https://www.crnusa.org/sites/default/files/images/2018-survey/CRN-ConsumerSurvey-Infographic-2019f.pdf). Accessed October 28, 2019.
Skeie G, Braaten T, Hjartåker A, Lentjes M, Amiano P, Jakszyn P, et al. Use of dietary supplements in the European prospective investigation into cancer and nutrition calibration study. Eur J Clin Nutr. 2009;63(S4):S226.
• Jenkins DJ, Spence JD, Giovannucci EL, Kim YI, Josse R, Vieth R, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol. 2018;71(22):2570–84 Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated.
NIH State-of-the Science Panel. National Institutes of Health state-of-the-science conference statement: multivitamin/mineral supplements and chronic disease prevention. Am J Clin Nutr. 2007;85(1):257S–64S. https://doi.org/10.7326/0003-4819-145-5-200609050-00136.
Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2013;159(12):824–34. https://doi.org/10.7326/0003-4819-159-12-201312170-00729.
Steinberg D, Witztum JL. Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation. 2002;105:2107–11.
Stephens NG, Parsons A, Brown MJ, Schofield PM, Kelly F, Cheeseman K, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347(9004):781–6.
Moyer VA. Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160(8):558–64.
Ruiz-León AM, Lapuente M, Estruch R, Casas R. Clinical advances in immunonutrition and atherosclerosis: a review. Front Immunol. 2019;10:837. https://doi.org/10.3389/fimmu.2019.00837.
Csepanyi E, Czompa A, Haines D, Lekli I, Bakondi E, Balla G, et al. Cardiovascular effects of low versus high-dose beta-carotene in a rat model. Pharmacol Res. 2015;100:148–56.
Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, et al. Multivitamins in the prevention of cardiovascular disease in men: the physicians’ health study II randomized controlled trial. JAMA. 2012;308(17):1751–60. https://doi.org/10.1001/jama.2012.14805.
Myung S-K, Ju W, Cho B, Oh S-W, Park SM, Koo B-K, et al. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials. BMJ. 2013;346:f10. https://doi.org/10.1136/bmj.f10.
Ye Y, Li J, Yuan Z. Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials. PLoS One. 2013;8:e56803. https://doi.org/10.1371/journal.pone.0056803.
Schwingshackl L, Boeing H, Stelmach-Mardas M, Gottschald M, Dietrich S, Hoffmann G, et al. Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials. Adv Nutr. 2017;8(1):27–39.
Zhao LG, Zhang QL, Zheng JL, Li HL, Zhang W, Tang WG, et al. Dietary, circulating beta-carotene and risk of all-cause mortality: a meta-analysis from prospective studies. Sci Rep. 2016;6:26983.
Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996;334(18):1150–5.
• María R-LA, María L, Ramon E, Rosa C. Clinical advances in immunonutrition and atherosclerosis: a review. Front Immunol. 2019. https://doi.org/10.3389/fimmu.2019.00837This review also analyzes the possible molecular mechanisms underlying the protective action of supplements.
Bleys J, Miller ER III, Pastor-Barriuso R, Appel LJ, Guallar E. Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2006;84(4):880–7.
• Christen WG, Cook NR, Van Denburgh M, Zaharris E, Albert CM, Manson JE. Effect of combined treatment with folic acid, vitamin B6, and vitamin B12 on plasma biomarkers of inflammation and endothelial dysfunction in women. J Am Heart Assoc. 2018;7(11):e008517. https://doi.org/10.1161/JAHA.117.008517Long-term, combined treatment with folic acid, vitamin B6, and vitamin B12 lowers homocysteine concentrations, but does not alter major biomarkers of vascular inflammation, consistent with the lack of clinical cardiovascular disease benefit in the trial.
Hosseini B, Saedisomeolia A, Skilton MR. Association between micronutrients intake/status and carotid intima media thickness: a systematic review. J Acad Nutr Diet. 2017;117(1):69–82. https://doi.org/10.1016/j.jand.2016.09.031.
Bønaa KH, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354(15):1578–88.
Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354(15):1567–77.
Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA. 2015;313:1325–35.
Spence JD. Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke. Nutr Res. 2016;36:109–16.
Garg A, Sharma A, Krishnamoorthy P, Garg J, Virmani D, Sharma T, et al. Role of niacin in current clinical practice: a systematic review. Am J Med. 2017;130(2):173–87.
HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high risk patients. N Engl J Med. 2014;371:203–12.
Anderson TJ, Boden WE, Desvigne-Nickens P, Fleg JL, Kashyap ML, McBride R, et al. Safety profile of extended-release niacin in the AIM-HIGH trial. N Engl J Med. 2014;371:288–90.
Lee D, Folsom A, Harnack L, Halliwell B, Jacobs D. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am Am J Clin Nutr. 2004;80:1194–200.
Martín-Calvo N, Martínez-González M. Vitamin C intake is inversely associated with cardiovascular mortality in a cohort of Spanish graduates: the SUN project. Nutrients. 2017;9(9):954.
Ashor AW, Lara J, Mathers JC, Siervo M. Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials. Atherosclerosis. 2014;235(1):9–20.
Juraschek S, Guallar E, Appel L, Miller E. Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012;95:1079–88.
Al-Khudairy L, Flowers N, Wheelhouse R, Ghannam O, Hartley L, Stranges S, et al. Vitamin C supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2017;3.
Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168:1629–37.
Al Mheid I, Patel RS, Tangpricha V, Quyyumi AA. Vitamin D and cardiovascular disease: is the evidence solid? Eur Heart J. 2013;34(48):3691–8.
Beveridge LA, Khan F, Struthers AD, Armitage J, Barchetta I, Bressendorff I, et al. Effect of vitamin D supplementation on markers of vascular function: a systematic review and individual participant meta-analysis. J Am Heart Assoc. 2018;7(11):e008273.
Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115(7):846–54.
Zittermann A, Ernst JB, Prokop S, Fuchs U, Gruszka A, Dreier J, et al. Vitamin D supplementation of 4000 IU daily and cardiac function in patients with advanced heart failure: the EVITA trial. Int J Cardiol. 2019;280:117–23.
Zhang R, Li B, Gao X, Tian R, Pan Y, Jiang Y, et al. Serum 25-hydroxyvitamin D and the risk of cardiovascular disease: dose-response meta-analysis of prospective studies. Am J Clin Nutr. 2017;105(4):810–9.
Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33–44.
Zittermann A, Pilz S. Vitamin D and cardiovascular disease: an update. Anticancer Res. 2019;39(9):4627–35.
Chin K, Appel LJ, Michos ED. Vitamin D, calcium, and cardiovascular disease: a “D” vantageous or “D” etrimental? An era of uncertainty. Curr Atheroscler Rep. 2017;19(1):5.
Singh U, Devaraj S, Jialal I. Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr. 2005;25:151–74. https://doi.org/10.1146/annurev.nutr.24.012003.132446.
Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet. 2000;356(9237):1213–8. https://doi.org/10.1016/S0140-6736(00)02783-5.
Rapola JM, Virtamo J, Ripatti S, Huttunen JK, Albanes D, Taylor PR, et al. Randomised trial of α-tocopherol and β-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet. 1997;349(9067):1715–20.
Cordero Z, Drogan D, Weikert C, Boeing H. Vitamin E and risk of cardiovascular diseases: a review of epidemiologic and clinical trial studies. Crit Rev Food Sci Nutr. 2010;50:420–40. https://doi.org/10.1080/10408390802304230.
Shekelle PG, Morton SC, Jungvig LK, Udani J, Spar M, Tu W, et al. Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. J Gen Intern Med. 2004;19:380–9. https://doi.org/10.1111/j.1525-1497.2004.30090.x.
Stonehouse W, et al. Short term effects of palm-tocotrienol and palm-carotenes on vascular function and cardiovascular disease risk: a randomised controlled trial. Atherosclerosis. 2016;254:205–14.
Curtis AJ, Bullen M, Piccenna L, McNeil JJ. Vitamin E supplementation and mortality in healthy people: a meta-analysis of randomised controlled trials. Cardiovasc Drugs Ther. 2014;28:563–73. https://doi.org/10.1007/s10557-014-6560-7.
Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37–46. https://doi.org/10.7326/0003-4819-142-1-200501040-00110.
Mathur P, Ding Z, Saldeen T, Mehta JL. Tocopherols in the prevention and treatment of atherosclerosis and related cardiovascular disease. Clin Cardiol. 2015;38:570–6. https://doi.org/10.1002/clc.22422.
Ohsaki Y, Shirakawa H, Miura A, Giriwono PE, Sato S, Ohashi A, et al. Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor κB through the repression of IKKα/β phosphorylation. J Nutr Biochem. 2010;21:1120–6. https://doi.org/10.1016/j.jnutbio.2009.09.011.
van Ballegooijen AJ, Beulens JW. The role of vitamin K status in cardiovascular health: evidence from observational and clinical studies. Curr Nutr Rep. 2017;6:197–205. https://doi.org/10.1007/s13668-017-0208-8.
Shea MK, Booth SL, Massaro JM, Jacques PF, D'Agostino RB, Dawson-Hughes B, et al. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol. 2008;167:313–20. https://doi.org/10.1093/aje/kwm306.
Madhavan MV, Tarigopula M, Mintz GS, Maehara A, Stone GW, Généreux P. Coronary artery calcification: pathogenesis and prognostic implications. J Am Coll Cardiol. 2014;63:1703–14.
Knapen MHJ, Braam LAJLM, Drummen NE, Bekers O, Hoeks APG, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015;113:1135–44. https://doi.org/10.1160/TH14-08-0675.
Dalmeijer GW, van der Schouw YT, Magdeleyns E, Ahmed N, Vermeer C, Beulens JWJ. The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein. Atherosclerosis. 2012;225:397–402.
Chen HG, Sheng LT, Zhang YB, Cao AL, Lai YW, Kunutsor SK, et al. Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis. Euro J Nutri. 2019;58:1–15. https://doi.org/10.1007/s00394-019-01998-3.
Vossen L, Schurgers L, van Varik B, Kietselaer B, Vermeer C, Meeder J, et al. Menaquinone-7 supplementation to reduce vascular calcification in patients with coronary artery disease: rationale and study protocol (VitaK-CAC Trial). Nutrients. 2015;7(11):8905–15. https://doi.org/10.3390/nu7115443.
Reid IR, Mason B, Horne A, Ames R, Clearwater J, Bava U, et al. Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial. Am J Med. 2002;112:343–7.
Reid IR, Horne A, Mason B, Ames R, Bava U, Gamble GD. Effects of calcium supplementation on body weight and blood pressure in normal older women: a randomized controlled trial. J Clin Endocrinol Metab. 2005;90:3824–9.
Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000;342:1478–83.
Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008;336:262–6.
Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. Bmj. 2011;342:d2040.
Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. Bmj. 2010;341:c3691.
Xiao Q, Murphy RA, Houston DK, et al. Dietary and supplemental calcium intake and cardiovascular disease mortality. The National Institute of Health-AARP Diet and Health Study. JAMA. 2013;173(8):639–46.
Bullón P, Román-Malo L, Marín-Aguilar F, Alvarez-Suarez JM, Giampieri F, Battino M, et al. Lipophilic antioxidants prevent lipopolysaccharide-induced mitochondrial dysfunction through mitochondrial biogenesis improvement. Pharmacol Res. 2015;91:1–8. https://doi.org/10.1016/j.phrs.2014.10.007.
Flowers N, Hartley L, Todkill D, Stranges S, Rees K. Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2014;12. https://doi.org/10.1002/14651858.CD010405.pub2.
Jorat MV, Tabrizi R, Mirhosseini N, Lankarani KB, Akbari M, Heydari ST, et al. The effects of coenzyme Q10 supplementation on lipid profiles among patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials. Lipids Health Dis. 2018;17(1):230. https://doi.org/10.1186/s12944-018-0876-4.
Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. Am J Clin Nutr. 2012;97(2):268–75. https://doi.org/10.3945/ajcn.112.040741.
Madmani ME, Solaiman AY, Agha KT, Madmani Y, Shahrour Y, Essali A, et al. Coenzyme Q10 for heart failure. Cochrane Database Syst Rev. 2014;52:1435–41. https://doi.org/10.1002/14651858.CD008684.pub2.
Alehagen U, Aaseth J, Alexander J, Johansson P. Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: a validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly. PLoS One. 2018;13(4):e0193120.
Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999;341(26):1986–95.
Von Haehling S, Jankowska EA, Van Veldhuisen DJ, Ponikowski P, Anker SD. Iron deficiency and cardiovascular disease. Nat Rev Cardiol. 2015;12(11):659.
Ponikowski P, Van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2014;36(11):657–68.
Danesh J, Appleby P. Coronary heart disease and iron status: meta-analyses of prospective studies. Circulation. 1999;99:852–4.
Lapice E, Masulli M, Vaccaro O. Iron deficiency and cardiovascular disease: an updated review of the evidence. Curr Atheroscler Rep. 2013;15(10):358.
Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Marine n−3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med. 2019;380(1):23–32.
Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA. 2006;296:1885–99.
Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58:2047–67.
Bowman L, Mafham M, Wallendszus K, et al. Effects of n−3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018;379:1540–50.
Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308:1024–33.
Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77 917 individuals. JAMA Cardiol. 2018;3:225–34.
Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;7:CD003177–7.
Benstoem C, Goetzenich A, Kraemer S, Borosch S, Manzanares W, Hardy G, et al. Selenium and its supplementation in cardiovascular disease—what do we know? Nutrients. 2015;7(5):3094–118.
Xu GL, Wang SC, Gu BQ, Yang YX, Song HB, Xue WL, et al. Further investigation on the role of selenium deficiency in the aetiology and pathogenesis of Keshan disease. Biomed Environ Sci. 1997;10:316–26.
Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, Guallar E. Selenium and coronary heart disease: a meta-analysis. Am J Clin Nutr. 2006;84:762–73.
Loscalzo J. Keshan disease, selenium deficiency, and the selenoproteome. N Engl J Med. 2014;370(18):1756–60.
Padayatty SJ, Levine M. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer. Ann Intern Med. 2014;160:654. https://doi.org/10.7326/L14-5009.
Mattila C, Knekt P, Männistö S, Rissanen H, Laaksonen MA, Montonen J, et al. Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care. 2007;30:2569–70.
Bonithon-Kopp C, Kronborg O, Giacosa A, Räth U, Faivre J, European Cancer Prevention Organisation Study Group. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. Lancet. 2000;356:1300–6.
Conflict of Interest
David Perez Ingles, Jose B. Cruz Rodriguez, and Hernando Garcia declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Ischemic Heart Disease
About this article
Cite this article
Ingles, D.P., Cruz Rodriguez, J.B. & Garcia, H. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment. Curr Cardiol Rep 22, 22 (2020). https://doi.org/10.1007/s11886-020-1270-1
- Cardiovascular disease