Vitamin D status and risk of incident tuberculosis disease: a systematic review and individual participant data meta-analysis

Abstract

Background: Few studies have evaluated the association between pre-existing vitamin D deficiency (VDD) and incident TB. We assessed the impact of baseline vitamin D on TB risk. Methods:We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6751 household contacts of TB patients in Peru. We also conducted a one-stage individual participant data meta-analysis searching PubMed and Embase for studies of vitamin D and TB until December 31, 2017. We included studies that assessed vitamin D before TB diagnosis. We defined VDD as 25-(OH)D <50 nmol/L, insufficiency as 50-75 nmol/L and sufficiency as >75nmol/L. We estimated the association between vitamin D and incident TB using conditional logistic regression in the Peru cohort and generalized linear mixed models in the meta-analysis. Findings:In Peru, baseline VDD was associated with a statistically insignificant increase in incident TB (aOR 1·70, 95% CI 0·84-3·46; p=0·14). We identified seven studies for the meta-analysis and analyzed 3544 participants. Individuals with VDD and very low vitamin D (<25nmol/L) had increased TB risk (aOR 1·48, 95% CI 1·04-2·10; p=0·03 and aOR 2·08, 95% CI 0·88-4·92; p trend=0·02 respectively). Among HIV-positive patients, VDD and very low vitamin D conferred a 2-fold (aOR 2.18, 95% CI 1·22-3·90; p=0·01) and 4-fold (aOR 4·28, 95% CI 0·85-21·44; p trend=0·01) increased risk of TB respectively.Interpretation: Our findings suggest vitamin D predicts TB risk in a dose-dependent manner and vitamin D supplementation may play a role in TB prevention. Evidence before this studyNumerous studies have found lower serum vitamin D levels among patients with active TB disease compared to healthy controls. However, research has not clarified whether low vitamin D increases TB risk or whether TB disease leads to decreased vitamin D levels. We conducted PubMed and Medline searches for all studies available through December 31, 2017 on the association between vitamin D status and TB disease. We included the following keywords: "vitamin D," "vitamin D deficiency," "hypovitaminosis D," "25-hydroxyvitamin D," "1,25-dihydroxyvitamin D," "vitamin D2," "vitamin D3," "ergocalciferol," "cholecalciferol," and "tuberculosis." We found only seven studies had prospectively evaluated the impact of baseline vitamin D levels on risk of progression to TB disease.We report here the results of a case control study nested within a large prospective longitudinal cohort study of household contacts of TB cases and the results of an individual participant data (IPD) metaanalysis of available evidence on the association between vitamin D levels and incident TB disease. Added value of this studyWe demonstrated that low vitamin D levels predicts risk of future progression to TB disease in a dosedependent manner. Implications of all the available evidenceThese findings suggest the possibility that vitamin D supplementation among individuals at high risk for developing TB disease might play a role in TB prevention efforts.

Vitamin D In Gambian Children With Discordant Tuberculosis Infection Status Despite Matched TB Exposure: A Case Control Study

“…While the trend between elevated vitamin D and absence of TB infection despite high TB-exposure reported here is consistent with results from existing literature 1,10 , a study in Gambian adults reporting higher serum vitamin D levels in adults with TB disease compared to household contacts 5 points towards variation in associations even within the same country.…”

“…A meta-analysis of 3,544 participants included in prospective trials investigating vitamin D and TB risk found a median vitamin D level of 26 ng/mL ( 65.0 nmol/L; IQR 19.5-33.4 ng/mL) and a dose-dependent relationship between de ciency of vitamin D (<10ng/mL) and increased risk of incident TB, a nding which was signi cantly exacerbated by HIV 1 . The applicability of these ndings to the Gambian population being studied here is not clear.…”

“…Vitamin D de ciency has been associated with increased risk of tuberculosis (TB) disease 1 , and infection 2 . Host vitamin D Receptor (VDR) genetic variants are also associated with risk of TB disease 3 .…”

Systems Nutrology of Persons with Tuberculosis Identifies Specific Dietary Profiles Associated with Dysglycemia

“…In addition, other studies have reported the variation of the body mass index (BMI) among TB patients, before, during and at the end of TB treatment [10] and the underweight as a high risk factor for TB-speci c and non-TB-speci c mortality during anti-TB treatment [11]. There is also evidence that vitamin D [12] and vitamin A [13] concentrations in peripheral blood could affect the incidence and progression of TB. However, there is a gap in the literature about the evaluation of dietary patterns in the comorbid condition of TB and DM, and on whether such information may be useful to guide optimization of clinical management.…”