Vitamin D supplementation for tuberculosis prevention

A new systematic review and meta-analysis by researchers from the Hospital of PLA Joint Logistic Support Force, China, has concluded that vitamin D supplementation does not prevent tuberculosis (TB) infection or the progression to active disease. Despite promising findings from earlier observational studies, the latest evidence from six large randomized controlled trials (RCTs) indicates no significant effect of vitamin D supplementation in preventing TB.

TB remains one of the leading infectious diseases globally, with an estimated 10.6 million people developing TB and 1.3 million dying from the disease in 2022 alone. Control efforts are challenged by issues such as transmission, drug resistance, and long treatment courses, underscoring the need for effective preventive strategies.

The Role of Vitamin D in Immune Defense

Vitamin D has long been thought to play a role in supporting the body's immune defense against infections, including TB. Experimental studies have suggested that vitamin D may enhance antimicrobial activity against Mycobacterium tuberculosis, the bacteria responsible for TB, while observational studies have highlighted a link between vitamin D deficiency and an increased risk of developing the disease. This has prompted many to explore vitamin D supplementation as a potential preventive measure.

Study Objective and Methodology

The systematic review and meta-analysis aimed to evaluate whether vitamin D supplementation could reduce the incidence of TB infection or the progression to active TB disease. The study included data from six double-blind randomized controlled trials (RCTs) involving a total of 15,677 participants from Asia and Africa, with follow-up durations ranging from 12 to 36 months.

The analysis used rigorous methods, including the Cochrane risk-of-bias tool and the GRADE framework, to assess the certainty of the evidence and identify any potential risks of bias. The trials examined varied supplementation regimens, but the findings were consistent across studies.

Key Findings

• TB Infection: Data from five trials indicated no significant reduction in TB infection rates with vitamin D supplementation (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.79–1.14).
  

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  Active TB: Four trials found no significant effect of vitamin D on the progression to active TB (OR 0.77, 95% CI 0.56–1.05).
  
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  Safety: Serious adverse events were similar between the vitamin D and placebo groups (OR 1.02, 95% CI 0.76–1.38), suggesting that vitamin D supplementation was not associated with increased harm.
  

Subgroup Analyses

The study also explored whether the results varied based on factors such as baseline vitamin D status, follow-up duration, or the diagnostic methods used to detect TB infection. However, the results showed no significant differences in outcomes across these subgroups, indicating that the lack of effect was consistent regardless of these variables.

Conclusion and Implications

Despite the promising biological rationale and earlier observational findings, the systematic review and meta-analysis provide moderate-certainty evidence that vitamin D supplementation does not reduce the risk of TB infection or progression to active TB in populations without active disease at baseline.

The authors conclude: "Our results indicate that vitamin D supplementation did not reduce the incidence of TB infection or the development of active TB."

While vitamin D remains essential for general health, particularly for bone health and immune function, the study's findings suggest it should not be considered a specific preventive strategy for TB. Public health programs should continue to prioritize established TB prevention methods, including vaccination, preventive therapy for high-risk populations, and strengthening diagnostic and treatment systems.

Next Steps for Research and Policy

The authors highlight that large trials would be needed to detect smaller effects of vitamin D on TB prevention, but such trials may not be feasible. Future research could focus on exploring other potential preventive interventions for TB, while public health efforts should continue to prioritize proven strategies that directly target TB control.

More information:

Sheng Liu et al, Vitamin D supplementation for tuberculosis prevention: A meta-analysis. Biomol Biomed [Internet]. 2025 Jul. 2 [cited 2025 Dec. 4];.

Available from: https://doi.org/10.17305/bb.2025.12527

Journal information: Biomolecules and Biomedicine

Provided by: Association of Basic Medical Sciences of FBIH

Provided by Association of Basic Medical Sciences of FBIH