Contemporary observational studies suggest that, on average, patients with TB, especially those with darker skin pigmentation,6
have lower serum levels of vitamin D than healthy controls despite matching on key demographic parameters such as sex, age, ethnicity, diet, and geographical location.7
The presence of vitamin D deficiency may also correlate with increased disease severity in patients with PTB8
and may be a major contributing factor to the increased burden of TB-related disease observed in patient populations with darker skin pigmentation, such as African Americans.9
Taken together, these studies provide evidence to support screening patients with TB for evidence of concomitant vitamin D deficiency.
While vitamin D deficiency is known to have detrimental effects on skeletal health, additional functions of vitamin D are currently being delineated, and these may have a significant impact on future management of infectious diseases such as TB. Vitamin D appears to modulate the innate immune response through increased expression of cathelicidin (LL-37), an antimicrobial peptide with potent activity against M tuberculosis
. Recent translational studies in healthy TB contacts found that whole blood from vitamin D–supplemented contacts restricted growth of bacillus-calmette-guerin (BCG) (an M tuberculosis
surrogate) more effectively than blood from the unsupplemented control group.10
In addition, a randomized, placebo controlled, pilot clinical trial of vitamin D supplementation as adjunctive therapy to conventional anti-TB drug therapy in 67 PTB patients in Indonesia demonstrated significantly higher sputum conversion rates at earlier time points in the vitamin D group (n = 34) compared to placebo (n = 33).11
These pre-clinical and early clinical data suggest a potential therapeutic benefit of vitamin D in TB, but more studies are needed to further evaluate the role of vitamin D as potential adjunctive therapy.
Although the consequences of uncorrected vitamin D deficiency have been well characterized,3
no universally accepted vitamin D repletion regimen has been adopted.3,12
A recent study suggests that more than 1000 IU of vitamin D daily is necessary to restore vitamin D status.13
Weekly high dose regimens have been proposed as a safe and effective method to rapidly correct vitamin D.14-16
As patients with TB are likely to have extensive derangements in vitamin D metabolism,6
our clinical experience supports the need to diagnose potential vitamin D deficiency in TB-infected patients and consider a more aggressive repletion strategy in TB patients with vitamin D deficiency.