Shedding light on the vitamin D–tuberculosis–HIV connection
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The paper in PNAS by Martineau et al. (1) raises a key public health issue: how much vitamin D do you need to fight tuberculosis (TB)? Martineau et al. (1) found that there is a significant association of vitamin D deficiency with susceptibility to TB and that the impact is greater in HIV-infected than noninfected individuals. In addition, Martineau et al. (1) discover a striking temporal relationship between vitamin D deficiency and TB. The reporting of new TB cases in Cape Town, South Africa, was lowest in the months after the seasonal increase in serum 25-hydroxyvitamin D (25D) levels, whereas the reporting of new TB cases was highest in the months following the season with the lowest serum 25D levels.
The major source of vitamin D for humans derives from sun exposure; in the skin, UVB induces conversion of 7-dehydrocholesterol to previtamin D3 and then vitamin D3 (cholecalciferol). In the liver, vitamin D3 is 25-hydroxylated to form 25D. 25D is then converted in the kidney by the 1-α-hydroxylase, CYP27b1, to 1,25-dihydroxyvitamin D (1,25D), the bioactive, hormonal form of vitamin D that is bound with high affinity and specificity by the vitamin D receptor (VDR). Serum 1,25D levels are maintained in a constant range by parathyroid hormone regulation of the CYP27b1 gene. Therefore, circulating levels of 25D are the best clinical assessment of adequate vitamin D status. Some of the factors that determine 25D levels include latitude (25D levels can be maintained year round in the equatorial regions between the Tropic of Cancer and Tropic of Capricorn), skin color (10 times as much UVB is required to produce the same amount of vitamin D in dark- vs. light-skinned individuals), outdoor activity, body surface exposed, oral supplementation, and SNPs in several vitamin D metabolism genes.
Martineau et al. (1) also report that …
↵1To whom correspondence should be addressed. E-mail: rmodlin@mednet.ucla.edu.
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Biological Sciences - Medical Sciences:
Adrian R. Martineau, Shepherd Nhamoyebonde, Tolu Oni, Molebogeng X. Rangaka, Suzaan Marais, Nonzwakazi Bangani, Relebohile Tsekela, Lizl Bashe, Virginia de Azevedo, Judy Caldwell, Timothy R. Venton, Peter M. Timms, Katalin A. Wilkinson, and Robert J. Wilkinson
From the Cover: Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa PNAS 2011 108 (47) 19013-19017; published ahead of print October 24, 2011, doi:10.1073/pnas.1111825108
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Published online before print November 14, 2011, doi: 10.1073/pnas.1116513108 PNAS November 22, 2011 vol. 108 no. 47 18861-18862
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