Vitamin D as Adjunctive Host-Directed Therapy in Tuberculosis: A Systematic Review

Abstract

Vitamin D plays an important role in innate defenses against intracellular pathogens. Seasonal vitamin D insufficiency (VDI) due to reduced sun exposure far from the equator increases tuberculosis risk. Eight randomized controlled trials examined vitamin D as adjunctive therapy during tuberculosis treatment. The studies varied substantially regarding patient genetic backgrounds, the extent of baseline VDI, the administered dose, the study endpoints, and the quality of the reported data. One carefully performed study in which moderately large vitamin D doses were given to markedly VDI patients found a benefit sufficient to support shortening treatment from 6 to 4 months, although other similar studies did not. Vitamin D is thought to have anti-inflammatory effects. However, 2 studies reported 3 vitamin D recipients with severe paradoxical inflammatory reactions. Future studies of vitamin D in tuberculosis in patients with specific genetic backgrounds must monitor these events closely to determine their risks and underlying mechanisms.

Autophagy: A new strategy for host-directed therapy of tuberculosis

“…In addition, highdose vitamin D3 regimens safely correct vitamin D3 deficiency without improving the rate of sputum Mtb clearance [89]. Inconsistent results regarding vitamin D-based HDT-TB may be due to the basal levels of vitamin D in the patient population, VDR polymorphisms, and geographic and/or ethnic variation associated with TB susceptibility [78,97,98]. In addition, it is difficult to show the comparative effects of randomized clinical trials in which standard TB drugs are given together with the adjuvant drug (e.g., vitamin D) or placebo.…”

Host-Directed Therapy as a Novel Treatment Strategy to Overcome Tuberculosis: Targeting Immune Modulation

“…VitD 3 as adjunct therapy in TB treatment has been utilized in several clinical trials, and the primary clinical outcomes are not always in line with the expected protective effects. A recent systematic review by Wallis et al has discussed eight clinical studies where vitD 3 was used as adjunctive therapy in TB treatment [152]. Among these eight studies only two of them showed significant microbiologically positive effects of vitD 3 .…”

“…The authors acknowledge that it is difficult to compare the studies because they are different in relation to patients' genetic backgrounds, baseline vitD 3 , administered dose, dosing schedule, study endpoints, and the quality of the reported results [152]. Another recent randomized and placebo-controlled trial with a high dose of vitD 3 (four biweekly doses of 3.5 mg) during TB treatment has been conducted in Mongolia [153].…”

Improving treatment outcomes for MDR-TB — Novel host-directed therapies and personalised medicine of the future

“…Vitamin D has also been tested in many clinical trials involving large patient cohorts although there still appears to be no decisive effect on the clinical outcome of TB in treated individuals (reviewed by Wallis and Zumla, 2016). However, further clinical trials are warranted due to a clinical benefit observed in some of the studies described in the review.…”