Coronary heat diseaseHow does vitamin D work?

There are several ways that vitamin D seems to work to reduce the risk of coronary heart disease (CHD) incidence and death including reduced risk of metabolic diseases such as diabetes and hypertension, modulation of cytokine production, and, possibly, reduced risk of arterial wall thickness and calcification. The role of vitamin D in reducing the risk of diabetes and hypertension are discussed elsewhere on this website.

Anti-inflammatory cytokines, such as interleukin-10 (IL-10), reduce the risk of CHD1. Vitamin D modulates the production of IL-10. In a vitamin D supplementation study, those taking 2000 international units (IU)/day of vitamin D3 had reduced serum IL-10 levels at the end of the study2. On the other hand, treatment of Crohn’s disease with 1,25-dihydroxyvitmin D increased production of IL-103. A similar study for those with multiple sclerosis found increased production of IL-10–producing cells4.

Carotid intima-media thickness (CIMT) (thickening of the wall of the main artery leading from the heart to the head) has been identified as a risk factor for CHD5 6. However, a study in France found little benefit of CIMT in predicting CHD7. “Hypovitaminosis D is highly prevalent in type 2 diabetic adults and is strongly and independently associated with increased carotid IMT8.” A study in Morocco found an inverse correlation between low bone mineral density and CIMT9. A study in California found “geometric mean internal carotid IMT (p(trend) 0.022), but not common carotid IMT (p(trend) 0.834) decreased in a dose-dependent fashion with increasing concentration of 25(OH)D. … In subgroup analyses, 1,25(OH)(2)D was inversely associated with internal carotid IMT among those with hypertension (p for interaction 0.036). These findings from a population-based cohort of older adults suggest a potential role for vitamin D in the development of subclinical atherosclerosis10.” 

An important risk factor for CHD is coronary artery calcification (CAC)11. There is limited evidence that low serum 25(OH)D level is inversely correlated with CAC. One study found inverse correlations between serum 25(OH)D level and CAC for patients on hemodialysis12. A combined supplementation study with statins, omega-3 fatty acids, and sufficient vitamin D to raise serum 25(OH)D levels to ≥ 50 ng/mL (≥ 37 nmol/L) found a mean reduction in CAC of 15% for 20 subjects, a mean annual progression of 29% for 3 subjects, and no change for 2213. The authors pointed out that statin therapy had not been found to reduce the progression of CAC. However, there is also evidence that higher serum 1,25-dihydroxyvitamin D levels increase CAC14.

Another vitamin D mechanism may be regulation of serum cholesterol. A study found “that 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] suppressed foam cell formation by reducing acetylated low density lipoprotein and oxidized low density lipoprotein cholesterol uptake in diabetics only15.” Having diabetes is an important risk factor for CHD16.

A recent review concluded that while there is mounting evidence for a beneficial role of vitamin D in reducing the risk of atherosclerosis and CVD, the mechanisms where by vitamin D reduces risk have not been fully elucidated, and there have not been large-scale, well-conducted randomized controlled trials to test the efficacy of vitamin D supplementation17.

Page last edited: 09 May 2011


  1. Tziakas, D. N. Chalikias, G. K. Kaski, J. C. Kekes, A. Hatzinikolaou, E. I. Stakos, D. A. Tentes, I. K. Kortsaris, A. X. Hatseras, D. I. Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a factor analysis approach. Atherosclerosis. 2007 Jul; 193 (1): 196-203.
  2. Yusupov, E. Li-Ng, M. Pollack, S. Yeh, J. K. Mikhail, M. Aloia, J. F. Vitamin d and serum cytokines in a randomized clinical trial. Int J Endocrinol. 2010; 2010
  3. Bartels, L. E. Jorgensen, S. P. Agnholt, J. Kelsen, J. Hvas, C. L. Dahlerup, J. F. 1,25-dihydroxyvitamin D3 and dexamethasone increase interleukin-10 production in CD4+ T cells from patients with Crohn's disease. Int Immunopharmacol. 2007 Dec 15; 7 (13): 1755-64.
  4. Correale, J. Ysrraelit, M. C. Gaitan, M. I. Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain. 2009 May; 132 (Pt 5): 1146-60.
  5. Stein, J. H. Fraizer, M. C. Aeschlimann, S. E. Nelson-Worel, J. McBride, P. E. Douglas, P. S. Vascular age: integrating carotid intima-media thickness measurements with global coronary risk assessment. Clin Cardiol. 2004 Jul; 27 (7): 388-92.
  6. Nambi, V. Chambless, L. Folsom, A. R. He, M. Hu, Y. Mosley, T. Volcik, K. Boerwinkle, E. Ballantyne, C. M. Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk In Communities) study. J Am Coll Cardiol. 2010 Apr 13; 55 (15): 1600-7.
  7. Simon, A. Megnien, J. L. Chironi, G. The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol. 2010 Feb; 30 (2): 182-5.
  8. Targher, G. Bertolini, L. Padovani, R. Zenari, L. Scala, L. Cigolini, M. Arcaro, G. Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients. Clin Endocrinol (Oxf). 2006 Nov; 65 (5): 593-7.
  9. Hmamouchi, I. Allali, F. Khazzani, H. Bennani, L. El Mansouri, L. Ichchou, L. Cherkaoui, M. Abouqal, R. Hajjaj-Hassouni, N. Low bone mineral density is related to atherosclerosis in postmenopausal Moroccan women. BMC Public Health. 2009; 9388.
  10. Reis, J. P. von Muhlen, D. Michos, E. D. Miller, E. R., 3rd Appel, L. J. Araneta, M. R. Barrett-Connor, E. Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis. Atherosclerosis. 2009 Dec; 207 (2): 585-90.
  11. Greenland, P. LaBree, L. Azen, S. P. Doherty, T. M. Detrano, R. C. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA. 2004 Jan 14; 291 (2): 210-5.
  12. Matias, P. J. Ferreira, C. Jorge, C. Borges, M. Aires, I. Amaral, T. Gil, C. Cortez, J. Ferreira, A. 25-Hydroxyvitamin D3, arterial calcifications and cardiovascular risk markers in haemodialysis patients. Nephrol Dial Transplant. 2009 Feb; 24 (2): 611-8.
  13. Davis, W. Rockway, S. Kwasny, M. Effect of a combined therapeutic approach of intensive lipid management, omega-3 fatty acid supplementation, and increased serum 25 (OH) vitamin D on coronary calcium scores in asymptomatic adults. Am J Ther. 2009 Jul-Aug; 16 (4): 326-32.
  14. Razzaque, M. S. The dualistic role of vitamin D in vascular calcifications. Kidney Int. 2010 Oct 20;
  15. Riek, A. E. Oh, J. Bernal-Mizrachi, C. Vitamin D regulates macrophage cholesterol metabolism in diabetes. J Steroid Biochem Mol Biol. 2010 Jul; 121 (1-2): 430-3.
  16. Huxley, R. Barzi, F. Woodward, M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006 Jan 14; 332 (7533): 73-8.
  17. Brewer, L. C. Michos, E. D. Reis, J. P. Vitamin D in atherosclerosis, vascular disease, and endothelial function. Curr Drug Targets. 2011 Jan; 12 (1): 54-60.