April 30, 2010 — Low vitamin D levels are associated with a 5-fold increased risk for tuberculosis (TB) disease progression in previously healthy household contacts of patients with TB, according to the results of a 4-year cohort follow-up study in Pakistan, reported in the May issue of Emerging Infectious Diseases.
“Deficiency of vitamin D (25-hydroxycholecalciferol) has long been implicated in activation of [TB],” write Najeeha Talat from Aga Khan University in Karachi, Pakistan, and colleagues. However, disease progression in healthy patients has not been previously studied.
During 2001 to 2004, the researchers studied 109 healthy people in close contact with 20 different patients with TB and found that those with low vitamin D levels, especially women, were 5 times more likely to contract TB.
Cohort participants were in “household contact” with patients recently diagnosed with sputum-positive pulmonary TB. The researchers collected blood samples at baseline and at 6, 12, and 24 months’ follow-up. Stanford University in California analyzed vitamin D levels in the plasma samples.
Total circulating serum 25 [OH] vitamin D was measured using enzyme-linked immunosorbent assay, duplicated and reported in nanograms per milliliter.
The researchers classified vitamin D levels as low, middle, or high. Median level for the cohort participants was 9.1 ng/mL. Median level for the disease-free household contacts was 9.6 ng/mL, 7.9 ng/mL for the TB index case-patients, 4.6 ng/mL for 2 coprevalent TB case-patients who were receiving antituberculous treatment at recruitment, and 5.1 ng/mL in 6 household contacts with a history of TB treatment.
Vitamin D levels of the disease-free study participants were significantly higher than in participants with a history of TB diagnosis at baseline (P = .02). “When we stratified the cohort by vitamin D level,” the researchers write, “79% were deficient (<20 ng/mL), 14% were insufficient (20-30 ng/mL), and 7% were sufficient (>30 ng/mL). Median vitamin D levels were significantly lower in the 74 female patients than in the 54 male patients [p=0.0004].”
Progressing to Active TB
Talat and colleagues next analyzed risk for progression to active TB in relation to vitamin D levels. One hundred household contacts were disease-free at baseline; 8 (8%) progressed to active disease during the 4-year follow-up, with the following breakdown (P = .002, log rank):
- 7 (23%) of 30 patients with vitamin D levels in the lowest tertile (<7 ng/mL)
- 1 (3%) of 32 patients with vitamin D levels in the middle tertile (7 – 13 ng/mL)
- none in the highest tertile (>13 ng/mL)
“TB progression was significantly associated with relatively lower plasma vitamin D levels,” the authors write. “Our findings also suggest that vitamin D deficiency may explain the higher susceptibility of women to disease progression in our cohort.” In a separate study, researchers at Aga Khan University in Karachi reported a high prevalence of vitamin D deficiency in ambulatory women patients.
Limitations of this study include the small cohort size and lack of information about diet, body mass index, and exposure to sunlight. However, the study results are supported by a meta-analysis of 7 case-control studies of different ethnic populations that showed 70% of healthy control patients had higher vitamin D levels than did untreated patients with TB.
As the authors explain, vitamin D supplementation during TB treatment remains controversial, with mixed results from clinical trials to date of vitamin D for pulmonary TB. “Our findings,” conclude Talat and colleagues, “indicate that further studies should be conducted regarding use of vitamin D as a supplement for persons undergoing treatment for TB and those with latent TB infection.”
The study was supported by funding from the National Commission on Biotechnology, the Higher Education Commission, the International Research Support Initiative Program of the Higher Education Commission Government of Pakistan, and the Bill and Melinda Gates Foundation.