Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D.
Hydrochlorothiazide, an effective antihypertensive medication commonly prescribed to blacks, decreases urinary calcium excretion. Blacks have significantly higher rates of hypertension and lower levels of 25-hydroxyvitamin D. Thus, they are more likely to be exposed to vitamin D supplementation and thiazide diuretics. The risk for hypercalcemia among blacks using vitamin D and hydrochlorothiazide is undefined.
We assessed the frequency of hypercalcemia in hydrochlorothiazide users in a post hoc analysis of a randomized, double-blind, dose-finding trial of 328 blacks (median age 51 years) assigned to either placebo, or 1000, 2000, or 4000 international units of cholecalciferol (vitamin D3) daily for 3 months during the winter (2007-2010).
Of the 328 participants, 84 reported hydrochlorothiazide use and had serum calcium levels assessed. Additionally, a comparison convenience group of 44 enrolled participants who were not taking hydrochlorothiazide had serum calcium measurements at 3 months, but not at baseline. At 3 months, hydrochlorothiazide participants had higher calcium levels (0.2 mg/dL, P <.001) than nonhydrochlorothiazide participants, but only one participant in the hydrochlorothiazide group had hypercalcemia. In contrast, none of the nonhydrochlorothiazide participants had hypercalcemia. In a linear regression model adjusted for age, sex, 25-hydroxyvitamin D at 3 months, and other covariates, only hydrochlorothiazide use (Estimate [SE]: 0.05 [0.01], P = .01) predicted serum calcium at 3 months.
In summary, vitamin D3 supplementation up to 4000 IU in hydrochlorothiazide users is associated with an increase in serum calcium but a low frequency of hypercalcemia. These findings suggest that participants of this population can use hydrochlorothiazide with up to 4000 IU of vitamin D3 daily and experience a low frequency of hypercalcemia.
Chandler, PD; Scott, JB; Drake, BF; Ng, K; Forman, JP; Chan, AT; Bennett, GG; Hollis, BW; Giovannucci, EL; Emmons, KM; Fuchs, CS
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