Review Article | Published:

Vitamin D and cardiovascular disease prevention

Nature Reviews Cardiology volume 13, pages 404417 (2016) | Download Citation

Abstract

Vitamin D is a precursor of the steroid hormone calcitriol that is crucial for bone and mineral metabolism. Both the high prevalence of vitamin D deficiency in the general population and the identification of the vitamin D receptor in the heart and blood vessels raised interest in the potential cardiovascular effects of vitamin D. Experimental studies have demonstrated various cardiovascular protective actions of vitamin D, but vitamin D intoxication in animals is known to induce vascular calcification. In meta-analyses of epidemiological studies, vitamin D deficiency is associated with an increased cardiovascular risk. Findings from Mendelian randomization studies and randomized, controlled trials (RCTs) do not indicate significant effects of a general vitamin D supplementation on cardiovascular outcomes. Previous RCTs, however, were not adequately designed to address extraskeletal events, and did not focus on vitamin D-deficient individuals. Therefore, currently available evidence does not support cardiovascular benefits or harms of vitamin D supplementation with the commonly used doses, and whether vitamin D has cardiovascular effects in individuals with overt vitamin D deficiency remains to be evaluated. Here, we provide an update on clinical studies on vitamin D and cardiovascular risk, discuss ongoing vitamin D research, and consider the management of vitamin D deficiency from a cardiovascular health perspective.

Key points

  • The vitamin D receptor (VDR) and enzymes for vitamin D metabolism are expressed throughout the cardiovascular system

  • VDR and 1α-hydroxylase knockout mice have hypertension with myocardial hypertrophy and increased activity of the renin–angiotensin–aldosterone system

  • The molecular effects of VDR activation indicate various antiatherosclerotic and protective effects on the heart and on common cardiovascular risk factors

  • Observational studies have shown that low 25-hydroxyvitamin D levels are associated with an adverse cardiovascular risk profile and significantly increased risk of cardiovascular events

  • Mendelian randomization studies and randomized clinical trials have not shown significant effects of vitamin D on cardiovascular events, but these trials were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals

  • Vitamin D supplementation is currently not indicated for the purpose of cardiovascular disease prevention, but treatment of vitamin D deficiency is critical for skeletal health

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Author information

Author notes

    • Stefan Pilz
    •  & Nicolas Verheyen

    These authors contributed equally as first authors.

Affiliations

  1. Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

    • Stefan Pilz
    •  & Martin R. Grübler
  2. Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, Netherlands.

    • Stefan Pilz
  3. Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

    • Nicolas Verheyen
    •  & Andreas Tomaschitz
  4. Swiss Cardiovascular Center Bern, Department of Cardiology, Bern University Hospital, Freiburgstrasse 8, 3010 Bern, Switzerland.

    • Martin R. Grübler
  5. Specialist Clinic of Rehabilitation PV Bad Aussee, Braungasse 354, 8990 Bad Aussee, Austria.

    • Andreas Tomaschitz
  6. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

    • Winfried März
  7. Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Mannheim Medical Faculty, University of Heidelberg, Theodor Kutzer-Ufer 1–3, 68167 Mannheim, Germany.

    • Winfried März
  8. Synlab Academy, Synlab Holding Deutschland GmbH Augsburg, Gottlieb Daimler Strasse 25, 68165 Mannheim, Germany.

    • Winfried März

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Contributions

All the authors contributed to researching data, discussions of content, writing the article, and to reviewing and editing of the manuscript before submission.

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The authors declare no competing financial interests.

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Correspondence to Stefan Pilz.

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DOI

https://doi.org/10.1038/nrcardio.2016.73

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