No causal relation between vitamin D supplementation and changes in blood pressure

Vitamin D Therapy in Individuals with Pre-Hypertension or Hypertension: The DAYLIGHT Trial

Literature - Arora P et al., Circulation Oct. 30 2014

Arora P, Song Y, Dusek J, et al.
Circulation Oct. 30 2014. Published online before print. Doi: 10.1161/CIRCULATIONAHA.114.011732


Vitamin D deficiency has been associated with a higher risk of cardiovascular disorders, including hypertension [1,2]. Throughout the cardiovascular system vitamin D receptors have been identified, for instance in vascular smooth muscle, endothelium and cardiomyocytes [3,4]. Animal studies have linked receptor disruption to increased levels of blood pressure, which can be normalised by the administration of vitamin D [5].
Since adequately designed studies to investigate the link between vitamin D and blood pressure are limited, the investigators conducted the DAYLIGHT study. This a double-blind, 6-month, controlled, randomised trial. High-dose vitamin D3 supplementation (liquid formulation; 4,000 IU/day) was compared with a low-dose (400 IU/day) in a racially diverse population (aged 18-50 years old) with prehypertension and untreated stage 1 hypertension (120-159 mm Hg) and vitamin D deficiency (25-hydroxyvitamin D levels ≤ 25 ng/ml). The primary endpoint was the change in mean 24-hour ambulatory systolic blood pressure.

Main results

  • After 6 months, the change in 24-hour systolic blood pressure from baseline was not significantly different  between the high-dose and low-dose groups (-0.8 mm Hg vs -1.6 mm Hg, respectively, P=0.71).
  • At the 6-month follow-up, the mean 24-hour systolic blood pressure was 126.5 ± 10 mm Hg in the high-dose arm and 125.7 ± 9 mm Hg in the low-dose arm (P=0.58).
  • In the high-dose group, vitamin D status improved within 2 months (median vitamin D levels at 2-month visit: 33 ng/ml (IQR: 26 to 40) in the high-dose arm versus 20 ng/ml (IQR: 15 to 25) in the low-dose arm (P<0.001), after which it remained stable. At the final visit, 21% of individuals in the high-dose and 48% in the low-dose arm had 25-hydroxyvitamin D < 20 ng/ml.
  • The association between change in 25-hydroxyvitamin D and change in 24-hour blood pressure was non-significant (Spearman coefficient: -0.05, P=0.34), not even in individuals showing the largest increases in 25-hydroxyvitamine D.
  • Pre-specified subgroup analyses did not reveal evidence of heterogeneity in the results.


The present study found that vitamin D supplementation is not related to lower blood pressure in individuals with vitamin D deficiency and untreated pre- or stage 1 hypertension. Furthermore, it suggests that the association between vitamin D status and hypertension that has been described in previous observational studies is not causal. The ongoing VITAL study [6] may clarify whether vitamin D supplementation may be beneficial for other cardiovascular risk factors.

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1. Forman JP, Giovannucci E, Holmes MD et al. Plasma 25-hydroxyvitamin d levels and risk of incident hypertension. Hypertension. 2007;49:1063-1069.
2. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin d deficiency and risk of cardiovascular disease. Circulation. 2008;117:503-511.
3. Somjen D, Weisman Y, Kohen F, et al.25-hydroxyvitamin d3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds. Circulation. 2005;111:1666-1671.
4. Merke J, Milde P, Lewicka S et al. Identification and regulation of 1,25-dihydroxyvitamin d3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin d3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries. J Clin Invest. 1989;83:1903-1915.
5. Li YC, Kong J, Wei M, et al. 1,25-dihydroxyvitamin d(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110:229-238.
6. Giovannucci E. Cholecalciferol treatment in older patients with isolated systolic hypertension. JAMA Intern Med. 2013;173:1680-1681.

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