Is Vitamin D an Effective Supplementary Agent in TB?
Tuberculosis (TB) is the most common cause of infectious mortality worldwide. Use of a single agent rapidly leads to drug resistance, which is the rationale for multidrug regimen. However, multidrug resistant (MDR) TB is becoming increasingly common. Moreover, extensively drug resistant (XDR) TB which is resistant not only to primary but also secondary line drugs is also being increasingly reported and is a feared concern in medical community.
To overcome the increasing problem of resistance, scientists have attempted to develop not only secondary line drugs but also supplementary agents to reduce the duration of therapy. Among these adjuncts, vitamin D has been scrutinized for its potential role. Besides its well known role in calcium and musculo-skeletal homeostasis, vitamin D is an activator of macrophages. This is hoped to contain the tuberculous bacilli, halting the spread of infection.
Observational studies indicated that the patients with low vitamin D levels are more likely to develop the symptomatic TB infection. Hence it was hypothesized that the administration of this vitamin might be effective as a supplementary agent. To date 5 randomized controlled trials (RCT’s) on the role of vitamin D as a supplementary agent have been reported with variable results. The largest trial by Martineau et al published in Lancet showed no significant difference between the two groups. However, it showed that the receptor polymorphism of vitamin D significantly affects time to sputum culture conversion. For instance the tt genotype of taql receptor polymorphism hastens culture conversion compared with the fokl genotype.
The combined sample size of these studies is less than 1000, hence the results are underpowered. Moreover, none of these RCT’s are carried out in Indo-Pak regions which constitute the bulk of the TB patients. The genotype of vitamin D receptors and consequently the metabolism might differ in this region.
Another factor which is crucial in interpreting the results of these RCT’s is the differing doses of vitamin D used and differing end points. For instance, the 2 RCT’s of Martineaue et al are with a single dose of vitamin D (in which in-vitro immune response was used as an end-point) and with high doses of the vitamin (the primary outcome was time from initiation of antimycobacterial therapy to sputum culture conversion).
Studies with larger sample sizes, the ones in the regions with greater prevalence and with more uniform end points will enable us to understand whether the administration of this agent is effective in TB and if yes, in which target population.