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Hypertension is quickly increasing in prevalence worldwide and is particularly common in African-Americans in the United States. Clinical studies suggest that vitamin D insufficiency contributes to the development of hypertension. We sought to evaluate the effect of vitamin D on blood pressure and proteinuria in a single-blinded study of five hypertensive African-American adult females. Subjects were randomized to either calcitriol (1,25-dihydroxycholecalciferol), which is the active form of vitamin D3 , or placebo. Therapies were administered for a one week period. An ambulatory blood pressure (ABP) monitor was used to collect 24-hour blood pressure data. Blood samples and 24-hour urine samples were also collected. Mean systolic blood pressure (SBP), mean arterial pressure (MAP), percent dip, and heart rate decreased significantly in the calcitriol group as compared to the placebo group. No subjects showed signs or symptoms of hypercalcemia; therefore safety was also demonstrated in the use of calcitriol. Vitamin D shows potential for use as a safe and effective therapy for the reduction of blood pressure in hypertensive adults.
In the year 2000, 26.4% of the world’s adult population was found to be afflicted by hypertension. That number is expected to increase by 60% by the year 2025 (1).
Hypertension has become widespread in the U.S., affecting 72 million adults over the age of 20. Only about 34% of hypertensive adults have been able to successfully control their hypertension (2).
Recent evidence from clinical trials suggests that vitamin D insufficiency may be closely related to hypertension.
Calcium supplementation has been shown to lower blood pressure and was found to be more effective when paired with vitamin D3 (3).
Calcitriol, the active form of vitamin D, increases calcium absorption and suppresses renin gene expression. Thus, calcitriol may lower blood pressure by inhibiting signaling of the renin-angiotensin II system (4).
HYPOTHESIS
In the hypertensive adult, calcitriol supplementation lowers blood pressure by lowering plasma renin levels.
Subjects were recruited from Atlanta Veterans’ Affairs Medical Center (VAMC) outpatient clinic in Decatur, Georgia. Subjects were screened and, if they met criteria, were randomized to calcitriol or placebo therapy. Blood pressure was measured using an ambulatory blood pressure (ABP) monitor manufactured by SpaceLabs, which measured blood pressure every fifteen minutes for a 24-hour period. Urine was collected over a 24-hour period to measure albumin, calcium, and creatinine excretion. Urine calcium excretion levels were analyzed to ensure that the subjects did not develop hypercalcemia (based on calcium/creatinine ratio; Table 1).
Serum samples were collected and sent to a commercial laboratory to determine plasma renin activity (Quest Diagnostics, San Juan Capistrano, CA). The Atlanta VAMC laboratory analyzed urine albumin, calcium, and creatinine excretion levels and serum calcium levels. Vitamin D levels were assessed in our laboratory using IDS ELISA kit for vitamin D3. Blood, urine, and ABP data were collected twice during the study: at baseline (week 0) and follow-up (week 1). Mean arterial pressure was calculated by SpaceLabs computer software. Percent dip was calculated as a percent difference between the last systolic blood pressure (SBP) reading while sleeping and the first SBP reading upon wakening.
We studied two women randomized to calcitriol therapy and three women randomized to placebo. Mean systolic blood pressure (SBP) significantly decreased in subjects randomized to calcitriol (p<0.001) (Figure 2).
In contrast, there was no significant change in SBP in subjects randomized to placebo. Mean arterial pressure (MAP) significantly decreased in subjects randomized to calcitriol but not in those randomized to placebo (data not shown). Mean heart rate significantly decreased in subjects randomized to calcitriol but not in those randomized to placebo (Figure 3). There was a significant decrease in percent dip in subjects randomized to calcitriol as compared to those randomized to placebo (Figure 4). Serum vitamin D levels increased moderately in subjects randomized to calcitriol but not in subjects randomized to placebo. Mean plasma renin levels and urine protein excretion remained unchanged for both study groups. No subjects developed calcium-creatinine excretion ratios characteristic of hypercalcemia, though calcium-creatinine excretion ratios nearly doubled in subjects randomized to calcitriol.
1. Our study demonstrates that calcitriol, the active form of vitamin D, significantly lowers both blood pressure and heart rate. This finding supports our hypothesis that vitamin D may decrease blood pressure.
2. Vitamin D therapy further lowered blood pressure in those taking anti-hypertensive medications, suggesting that vitamin D may be a potential complimentary therapy for adults with high blood pressure.
3. Our study also demonstrates that short-term vitamin D usage is safe, as no subjects developed signs or symptoms of hypercalcemia.
FUTURE DIRECTIONS
Vitamin D may be useful in correcting high blood pressure in patients who have a vitamin D insufficiency. The only known side effect of vitamin D is hypercalcemia, a relatively rare condition.
Larger studies to investigate the role of vitamin D in hypertension and the mechanism of vitamin D on blood pressure reduction should be conducted.
This material is based upon work supported by the Howard Hughes Medical Institute under Grant No. 52005873, a fellowship award by the Atlanta Clinical and Translational Science Institute to Sara Raiser, and a grant by the Atlanta Veterans’ Affairs Medical Center Atlanta Research and Education Foundation.
-Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217-223.
-Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252.
-Pfeifer M, Begerow B, Minne HW, et al. Effects of a short-term vitamin D3 and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab. 2001;86:1633-7.
- Li YC, Qiao, G, Uskokovic M, et al. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. J Ster Biochem Molec Bio. 2004;89-90;387-92.
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