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Study Identifies Link Between Vitamin A Levels and Tuberculosis

Vitamin A has long been linked with eye and skin health. Now, the results of a new study suggest it may play an important role in tuberculosis (TB) risk as well.
Indeed, in a study published on May 20, 2017 in the journal Clinical Infectious Diseases, researchers from Harvard Medical School, along with colleagues from Partners in Health, the University of Massachusetts, the University of Texas Health Sciences Center, and the Warren Alpert School of Medicine at Brown University, found a “dose-dependent” relationship between the vitamin and TB, with vitamin A deficiency associated with a 10-fold increase in risk for infectious disease. The team reached their conclusions after conducting a “case-control study nested within a longitudinal cohort of household contacts of pulmonary TB cases in Lima, Peru” between September 2009 and August 2012. Ultimately, the study enrolled 6751 HIV-negative household contacts of index patients 15 years of age and older who tested positive for pulmonary TB.
“We initially were interested in vitamin D and drew and stored blood to evaluate [the link between it and TB], but [we] added vitamin A based on a previous study we had done suggesting that fruits and vegetables were protective against TB in kids,” senior author Megan Murray, DPH, MD, Ronda Stryker and William Johnston Professor of Global Health at Harvard Medical School told Contagion®. “We were really surprised to find the strong connection as it was very much unsuspected.”
In fact, the work of Dr. Murray et al is arguably the first modern study to identify a link between vitamin A and TB, which, according to World Health Organization (WHO) data, remains a troubling disease, with more than 10.4 million new cases and 1.8 million deaths in 2015 (the most recent year for which data are available). According to Dr. Murray, she and her coauthors only learned of a 1940s study—conducted in Philadelphia, Pennsylvania, which linked the disease with vitamin A and C deficiency—as they were writing up their own findings.
For the more recent research, the team identified all (HIV-negative) household contacts for each case of confirmed pulmonary TB (the index patient). For those household contacts who tested positive for TB within 15 days of identification of the index patient in their respective cases, the authors randomly selected 4 controls for each household contact from among contacts who did not develop pulmonary TB, matching them according to gender and age. Among their sample, 192 of the 6751 household contacts developed secondary TB (with an additional 66 coprevalent cases), and the authors analyzed 180 of these cases against 709 matched controls.
After dividing the study subjects into quartiles based on levels of vitamin A in their blood samples, they found that the 76 household contacts with the lowest levels of vitamin A in their blood had 6 times the risk for TB compared to the 18 contacts with the highest levels. Further analysis revealed that vitamin A deficiency (with a univariate odds ratio of 7.65 and a multivariate odds ratio of 10.53) was a more significant risk factor for TB than even low socioeconomic status (1.69/1.61) and prior history of TB (2.89/2.11).
Based on their findings, the authors believe vitamin A deficiency has a potential role in identifying individuals at risk for TB, and that vitamin A supplementation may be an effective—and cost-effective—method for preventing new infections. On the latter point, Dr. Murray and her team are in the process of applying for a National Institutes of Health (NIH) grant to fund a study assessing the possible benefits of vitamin A supplementation in this setting.
“This is one of the strongest risk factors reported in a large epidemiological study in years,” Dr. Murray said in a statement released by Harvard Medical School in conjunction with the study’s publication. “If the link is affirmed in a clinical trial of vitamin A supplementation, it would make a powerful case for using this approach to prevent TB in people at high risk of disease. It’s exciting to think that something as simple and inexpensive as supplementing people’s diets with vitamin A may be a powerful tool for preventing TB.”
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition. 
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