Vitamin D Boosts Immunity Against Tuberculosis

LONDON, May 18 -- A single oral dose of vitamin D may give the immune system enough ammunition to fight off tuberculosis for six weeks after exposure, according to researchers here.

The findings suggest that exposed persons should receive vitamin D supplements, said Adrian R. Martineau, M.R.C.P., of Barts and The London, Queen Mary's School of Medicine and Dentistry and Imperial College here, and colleagues.

A single dose of vitamin D could serve "as a safe, effective and cheap (.20) public health intervention," the researchers concluded online in the American Journal of Respiratory and Critical Care Medicine.

They noted that vitamin D was used to treat tuberculosis in the pre-antibiotic era. At that time, sunlight, a healthy diet, and rest were the optimal treatments at sanatoria.

With the discovery of antibiotics, though, vitamin D was neglected, they added, and no prospective studies were done on its effect on immunity to mycobacteria-like tuberculosis.

So Dr. Martineau and colleagues conducted a double-blind randomized controlled trial that included 131 healthy adults who had been exposed to a patient with active tuberculosis and were attending a tuberculosis contact clinic in London.

Those with symptoms or radiographic evidence of active tuberculosis were excluded, as were those already taking supplementary vitamin D. Both groups had similar baseline characteristics.

Although most of those approached for the study refused to enroll and quite a few were lost to follow-up, those lost participants were similar to the 131 who completed the study.

After the participants' blood was drawn for an assay, they were randomized to receive a single oral dose of 2.5 mg of vitamin D or placebo. At six weeks they returned to the clinic and had their blood drawn again.

The assay consisted of mixing their whole blood with recombinant luminescent mycobacteria.

Efficacy of vitamin D was determined by comparing luminescence of samples before and after the dose because a stronger immune response would suppress growth of the bacteria and thus luminescence.

The researchers found that vitamin D supplementation significantly improved innate immune response to tuberculosis. The mean luminescence ratio at 24 hours after "infection" was 20.4% lower for the vitamin D group (0.57 versus 0.71, P=0.03).

Vitamin D did not appear to affect acquired immune response to the bacteria, as measured by the mean luminescence ratio at 96 hours after "infection" (1.34 versus 1.30 placebo, 95% CI for difference -0.27 to 0.25; P=0.94).

"Given that innate immune responses are mobilized more rapidly than acquired immune responses, 24-hour and 96-hour outcomes may be interpreted as indicators of innate and acquired responses, respectively," the researchers wrote.

If the findings are real, they reflect "a clinically meaningful enhancement" of immune response to tuberculosis, they added.

There was no significant effect on antigen-stimulated interferon-gamma secretion, which was used as a secondary measure of immune response to M. tuberculosis (P=0.13 and P=0.23 for two assays).

The researchers noted that the population of patients exposed to tuberculosis might particularly benefit from vitamin D supplementation.

Of 202 exposed patients tested, 41.6% were profoundly vitamin D deficient, with serum levels below 20 nmol/l. Almost all the patients (93.6%) were vitamin D-insufficient with serum levels below 75 nmol/l at baseline.

Significant risk factors for vitamin D deficiency in the study on a multivariate analysis were black or Asian ethnicity (P=0.01 and P=0.02, respectively) as well as lack of fish in the diet and enrolment in winter or spring months (both P=0.01).

Further study is needed to see whether the vitamin could prevent reactivation of latent tuberculosis infection, they said.