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Am Fam Physician. 2010 Sep 15;82(6):577-583.
Vitamin D Supplementation in Patients with Tuberculosis
Original Article: Recognition and Management of Vitamin D Deficiency
Issue Date: October 15, 2009
Available at: http://www.aafp.org/afp/2009/1015/p841.html
to the editor: Dr. Bordelon and colleagues provide a timely and useful summary of the management of vitamin D deficiency. However, they cite tuberculosis as a contraindication to vitamin D supplementation, which is not the case. Activated macrophages produce elevated amounts of 1-α-hydroxylase, which can potentially produce toxic levels of 1,25-dihydroxyvitamin D if adequate substrate 25-hydroxyvitamin D is available; therefore, there are concerns about the risk of hypercalcemia in patients with tuberculosis or other granulomatous diseases.
In 1984, Narang and colleagues reported high rates of hypercalcemia in patients with or without tuberculosis receiving vitamin D supplementation,1 forming the basis of these concerns. However, these results have not been reproduced and are speculated to have stemmed from underestimating the actual amount of vitamin D administered in the study.2
More recent data show that vitamin D supplementation in patients with tuberculosis does not appear to be associated with hypercalcemia. In preliminary safety data from one study, 11 patients with tuberculosis were administered a single dose of 100,000 IU ergocalciferol (vitamin D2).3 At eight weeks, there was a significant rise in serum vitamin D2 levels and no episodes of hypercalcemia. In a randomized trial of 100,000 IU cholecalciferol (vitamin D3) in patients with tuberculosis in Guinea-Bissau,4 t here was no difference in hypercalcemia symptoms or detection of biochemical hypercalcemia in those randomized to the treatment arm; however, patients in the treatment arm did not attain higher serum vitamin D levels than those randomized to placebo, suggesting that the vitamin D formulation used (an injectable preparation given orally) may have been poorly absorbed. Other studies, summarized elsewhere,5,6 have also reported safe administration of vitamin D in patients with tuberculosis.
Given the evidence of the potential benefits of vitamin D3 in the immune response to Mycobacterium tuberculosis, 6 optimizing vitamin D levels (while monitoring calcium levels) should not be considered contraindicated in patients with tuberculosis. Results from trials of vitamin D adjunctive therapy that are currently underway will provide further clarification of the benefit, if any, of vitamin D supplementation in patients with tuberculosis.
1. Narang NK, Gupta RC, Jain MK. Role of vitamin D in pulmonary tuberculosis. J Assoc Physicians India. 1984;32(2):185–188.
2. Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001;73(2):288–294.
3. Martineau AR, Nanzer AM, Satkunam KR, et al. Influence of a single oral dose of vitamin D(2) on serum 25-hydroxyvitamin D concentrations in tuberculosis patients. Int J Tuberc Lung Dis. 2009;13(1):119–125.
4. Wejse C, Gomes VF, Rabna P, et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2009;179(9):843–850.
5. Martineau AR, Honecker FU, Wilkinson RJ, Griffiths CJ. Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol. 2007;103(3–5):793–798.
6. Ralph AP, Kelly PM, Anstey NM. L-arginine and vitamin D: novel adjunctive immunotherapies in tuberculosis. Trends Microbiol. 2008;16(7):336–344.
editor's note: This letter was sent to the authors of "Recognition and Management of Vitamin D Deficiency," who declined to reply.
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