A new study of UK tuberculosis (TB) patients has shown that, for those with a certain genetic profile (genotype), supplementation of vitamin D to their standard antibiotic regimen reduces the time needed for TB bacteria to clear from sputum culture by almost a week for the population studied. The Article, published Online First in The Lancet, is by Dr Adrian R Martineau, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK, and colleagues.
Vitamin D was used to treat TB in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in cell culture (TB is caused by mycobacterium tuberculosis). While tuberculosis is still common in many developing countries, it also occurs in high-income nations such as the UK, where cases have risen by 50% since 1999 to a total of more than 9,000 in 2009. Many of these cases are in homeless people and migrants, and more than 40% are in London. UK TB patients in particular suffer deficiency of vitamin D most probably due to their lack of exposure to sunlight. This new study, which was funded by the British Lung Foundation, is the first to assess the clinical effect of vitamin D supplementation on sputum culture conversion.
In this randomised controlled trial, the authors enrolled adults with sputum smear-positive pulmonary TB in London, UK. 146 patients were allocated to receive 2•5 mg vitamin D or placebo at baseline and at 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI variants of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D.
126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). The median time to sputum culture conversion was more than a week lower in the intervention group (36 days) than the placebo group (43.5 days). TaqI genotype variation modified the effect of vitamin D supplementation on time to clear TB infection from sputum, with enhanced response seen only in patients with the tt genotype. However this genotype was only found in 8% of intervention patients (5 people) and 11% of placebo patients (7 people, proportions typical in the general population of TB patients. FokI genotype did not modify the effect of vitamin D supplementation. Mean serum 25-hydroxyvitamin D concentration at 56 days was high (101•4 nmol/L) in the intervention group and low (22•8 nmol/L) in the placebo group.
The authors say: “Administration of four oral doses of 2•5 mg vitamin D3 corrected deficiency safely and quickly in patients receiving intensive phase antimicrobial treatment for pulmonary tuberculosis, but did not significantly improve response to treatment in the study population as a whole. However, vitamin D supplementation did significantly reduce time to sputum culture conversion in patients with the tt genotype of the TaqI vitamin D receptor polymorphism suggests that this subgroup of patients with tuberculosis might derive clinical benefit from vitamin D supplementation.
Investigation of the mechanism mediating this gene-environment interaction is warranted.”
In a linked Comment, Dr Reinhold Vieth, University of Toronto, Toronto, Canada; and Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada, says that research must now explore whether vitamin D supplementation could have prevented latent TB infection in these patients in the first place. Dr Vieth adds his frustration that randomised controlled trials to test prevention in this way are unlikely to be given funding or occur.
He concludes: “Evidence-based medicine and health policy need to go beyond a fixation on randomised trials of the sort that are unlikely to happen for prevention of most diseases. Evidence-based policy needs to be realistic and to pay more than lip service the various types of evidence available.”
Ian Jarrold, Research Manager for the British Lung Foundation, said: “The findings of this study, which was funded by the British Lung Foundation, show great promise in speeding up the antibiotic treatment of TB for those patients which are receptive to vitamin D. The treatment process is currently very long and can be costly so any headway made in the medical research field for this disease is welcome to improve outcomes for patients.”
Source:The Lancet