Vitamin D boosts anti-TB immunity, now being tested as add-on to TB therapy

Sunlight was considered an essential element of tuberculosis (TB) control in the pre-antibiotic era because ultraviolet light and heat kill mycobacteria. TB sanatoria were designed to let in light, and even today TB wards are recommended to have large external windows for good ventilation and sunlight exposure.

Nevertheless, direct sunlight was thought to exacerbate TB in the lungs, and so was not recommended as a component of TB treatment for people with pulmonary TB.

However, British researchers have now found that the effects of sunlight on the human body are likely to be beneficial for TB patients and people at risk of TB.

They conducted a randomised controlled trial amongst 202 contacts of people diagnosed with TB in east London, in which people were assigned either to receive a single dose of vitamin D (2.5mg) or a placebo. Although this dose considerably exceeds the daily recommended dose, investigator Adrian Martineau of the Institute of Community Health Sciences at Bart's and Royal London Hospitals Medical School told aidsmap: "No subject suffered symptoms or hypercalcaemia. This dose, and indeed higher doses, have been widely used as single doses without adverse effect."

Blood levels of 25-hydroxy-vitamin D were measured at baseline, day 7 and day 49, and the study also assessed anti-mycobacterial immunity by means of an assay that measured mycobacteria levels by attaching a luminous probe to mycobacteria.

Mycobacterial immunity was 20% stronger in vitamin D recipients after six weeks, but among those who were vitamin D deficient at baseline the difference was greater. Vitamin D recipients in this subset had mycobacterial levels 49% below those of the vitamin D-deficient placebo recipients (p<0.0001).

Vitamin D has no direct antimycobacterial effect, but it modulates the immune response by inducing secretion of interleukin-10, even though it reduced the secretion of interferon gamma, TNF-alpha and IL-12, all type 1 cytokines that are down-regulated in tuberculosis and in HIV infection.

Further research on the therapeutic value of vitamin D in TB patients is already underway. Adrian Martineau told aidsmap: "We have just been funded to conduct a randomised controlled trial of high-dose vitamin D as an adjunct to standard therapy in smear positive pulmonary TB cases in east London in the UK."

"There are no plans to do an intervention study in HIV-positive people at present, but I am involved with an ongoing observational study of micronutrient status and anti-mycobacterial immune response in HIV-positive children in collaboration with University of Cape Town."

The same research group also found that vitamin D deficiency was more common among TB patients (N=49) than blood donors (N=53) in the Samara region of Russia (odds ratio 3.8, 95% confidence interval 1.56-9.42, p<0.01). However, due to its cross-sectional design the study could not establish whether vitamin D deficiency predisposed individuals to TB, or whether it was a consequence of mycobacterial infection or TB treatment.

Both rifampicin and isoniazid have been shown to reduce vitamin D levels, and the ability of some HIV protease inhibitors to impair vitamin D metabolism has been proposed as one of the causes of the reduced bone mineral density seen in some people receiving long-term antiretroviral treatment (vitamin D is critical for the formation and maintenance of healthy bones).

Lack of sunshine during the winter months in northern latitudes reduces vitamin D levels markedly, but darker skin pigmentation reduces vitamin D synthesis as a result of exposure to sunlight among people of African and Asian origin wherever they live.