High-Dose Vitamin D3 During Tuberculosis Treatment in Mongolia: A Randomised Controlled Trial.
Am J Respir Crit Care Med
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RATIONALE: Existing trials of adjunctive vitamin D in the treatment of pulmonary tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing regimens and high baseline vitamin D status among participants. Comprehensive analyses of the effects of genetic variation in the vitamin D pathway on response to vitamin D supplementation are lacking. OBJECTIVES: To determine the effect of high-dose vitamin D3 on response to antimicrobial therapy for PTB and to evaluate the influence of single nucleotide polymorphisms (SNPs) in vitamin D pathway genes on response to adjunctive vitamin D3. METHODS: We conducted a clinical trial in 390 adults with PTB in Ulaanbaatar, Mongolia, who were randomised to receive four bi-weekly doses of 3.5 mg (140,000 IU) vitamin D3 (n=190) or placebo (n=200) during intensive-phase anti-tuberculosis treatment. MEASUREMENTS AND MAIN RESULTS: The intervention elevated 8-week serum 25-hydroxyvitamin D concentrations (154.5 nmol/L vs. 15.2 nmol/L in active vs. placebo arms, 95% CI for difference 125.9 to 154.7 nmol/L, P<0.001), but did not influence time to sputum culture conversion overall (adjusted hazard ratio [aHR] 1.09, 95% CI 0.86 to 1.36, P=0.48). Adjunctive vitamin D3 accelerated sputum culture conversion in patients with one or more minor alleles for SNPs in genes encoding the vitamin D receptor (rs4334089, rs11568820) and the 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1: rs4646536) (aHR ≥1.47, P for interaction ≤0.02). CONCLUSIONS: Vitamin D3 did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01657656.
AuthorsGanmaa, D; Munkhzul, B; Fawzi, W; Spiegelman, D; Willett, WC; Bayasgalan, P; Baasansuren, E; Buyankhishig, B; Oyun-Erdene, S; Jolliffe, DA; Xenakis, T; Bromage, S; Bloom, BR; Martineau, AR
- Population Health