INT J TUBERC LUNG DIS 14(9):1147–1152 © 2010 The Union Serum 25-hydroxy-vitamin D 3 concentrations increase during tuberculosis treatment in Tanzania A. Tostmann,* † J. P. M. Wielders, ‡ G. S. Kibiki, § H. Verhoef, ¶ M. J. Boeree,* † A. J. A. M. van der Ven # * Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, † University Centre for Chronic Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, ‡ Department of Clinical Chemistry, Meander Medical Centre, Amersfoort, The Netherlands; § Kilimanjaro Clinical Research Centre, Kilimanjaro Christian Medical Centre, Moshi, Tanzania; ¶ Nutrition and Public Health Intervention Research Unit, London School of Hygiene and Tropical Medicine, London, UK; # Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Correspondence to: Alma Tostmann, Department of Pulmonary Diseases (454), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel: (+31) 24 36 10325. Fax: (+31) 24 36 10324. e-mail: almatostmann@yahoo.com Article submitted 3 September 2009. Final version accepted 9 March 2010. SETTING: Vitamin D deiciency is associated with sus- ceptibility to active tuberculosis (TB) in many settings. In vitro studies and studies on human volunteers showed that two of the irst-line anti-tuberculosis drugs, isoniazid and rifampicin, reduce 25-hydroxy vitamin D (25[OH]D) concentrations. OBJECTIVE: To study changes in vitamin D status dur- ing treatment of Tanzanian hospitalised patients with pulmonary TB (PTB). DESIGN: We compared serum 25[OH]D concentrations in 81 Tanzanian PTB patients before and after 2 months of treatment. RESULTS: Median serum 25[OH]D concentrations in- creased from 91 nmol/l at baseline to 101 nmol/l after 2 months of TB treatment (median increase 6.0 nmol/l, IQR −0.7–25.0, P = 0.001). Median serum parathyroid hormone concentrations increased from 1.6 to 2.0 pmol/l (median increase 0.46, IQR −0.2–1.1, P < 0.001). CONCLUSION: 25[OH]D serum concentrations in- creased during the irst 2 months of TB treatment in 81 PTB patients in northern Tanzania. Improved dietary intake and increased sunlight exposure may have con- tributed to the increased 25[OH]D concentrations. KEY WORDS: anti-tuberculosis treatment; Mycobacte- rium tuberculosis; nutrition; rifampicin; isoniazid IN THE PRE-ANTIBIOTIC ERA, Vitamin D from cod liver oil and from sun exposure (in sanatoria) was used for treating tuberculosis (TB). 1,2 Several ob- servational studies indicate that vitamin D deiciency plays a role in susceptibility to TB. 3,4 Polymorphisms in the vitamin D receptor gene have been associated with delayed treatment response. 5,6 Vitamin D is metabolised by several cytochrome P450 (CYP450) enzymes. Vitamin D 3 is synthesised in the skin during exposure to sunlight and is also avail- able in the diet, mainly from oily ish or fortiied foods (Figure). Vitamin D 3 is hydroxylated in the liver to 25-hydroxy-vitamin D 3 (25[OH]D), the accepted in- dicator of vitamin D status, which is further hydrox- ylated to 1,25-dihydroxy-vitamin D (1,25[OH] 2 D), under the regulation of the parathyroid hormone. The kidneys play a major role in this hydroxylation step. Neither vitamin D 3 nor its biologically active me- tabolite 1,25[OH] 2 D have direct antimycobacterial ac- tion, but 1,25[OH] 2 D induces in vitro anti-tuberculosis activity in both monocytes 10 and macrophages. 11 Activated macrophages can convert 25[OH]D to 1,25[OH] 2 D. 1,12 Several CYP450 are involved in vi- tamin D metabolism: vitamin D 3 25-hydroxylase (CYP27A1), 25-hydroxyvitamin D 3 1-alpha-hydrox- ylase (CYP27B1) and 1,25-dihydroxyvitamin D 3 24- hydroxylase (CYP24A1) are key enzymes in vitamin D metabolism. 7,8 Two of the standard irst-line anti-tuberculosis drugs, isoniazid (INH) and rifampicin (RMP), are known for inhibiting and inducing CYP450 activity, respectively, and can affect vitamin D metabolism. INH reduces 25[OH]D and 1,25[OH] 2 D concentra- tions by the inhibition of 25-hydroxylase, as has been shown in in vitro studies, animal studies and hu- man volunteers. 7,9,13,14 RMP is a strong inducer of CYP3A4, 15 which is a vitamin D 24- and 25- hydrox- ylase. 8 Induction of these enzymes increases the enzy- matic conversion of 25[OH]D to the inactive metab- olite 24,25[OH] 2 D and results in decreased 25[OH]D and 1,25[OH] 2 D concentrations, as shown in studies in human volunteers. 14,16 Combined use of INH and RMP reduces 25[OH]D and 1,25[OH] 2 D concentra- tions in both human volunteers and TB patients. 14 SUMMARY