Medicine from the sun: Vitamin D and the body’s natural TB drug

Dr. Anh Innes is the Chief of Party of the CAP-TB Project.

 
Decades before the discovery of modern anti-tuberculosis drugs, there were just two recommended treatments for patients suffering from tuberculosis:  Sunlight and clean, dry air.  Sanitoria, facilities where patients rested amid the sunny weather and dry air, were found throughout Switzerland and Scandinavia, as well as in the Southwestern United States.  During that era, the body’s own immune system was the only arsenal to fight the disease. Without anti-tuberculosis drugs, the only hope for treating TB was for the infection to be “walled off”, with the infected tissue eventually scarring down to kill the organisms (which need oxygen to survive) and thus mitigate spread.

These tuberculosis sanitoria began to close after the discovery of the first anti-TB drug, streptomycin, in 1947. But the valid scientific basis underlying that pre-drug treatment for TB -- sunlight -- was largely silent in the literature until recent years. In 1986, one of the first articles was published showing an immunologic effect of Vitamin D -- which is produced in the skin when exposed to sun -- on monocytes and macrophages, which are the primary cells that fight TB infection in the body. And within the past decade, there has been a resurgence of interest in Vitamin D and its important role in the body’s immune system. Notably, infections in the lung, including tuberculosis, have been associated with low levels of Vitamin D, and presumably a weakened immune defense. The Institute of Medicine released a report on Vitamin D in 2010 that studied the North American population needs for Vitamin D. The evaluators could not state conclusively that low levels of Vitamin D increased the risk for infections but recommended rigorously conducted studies to answer the question. The data in the literature are not 100% conclusive, but there appears to be increasing evidence to support the role of Vitamin D in its role to strengthen the body’s response to tuberculosis. The potential mechanism is as follows: Vitamin D triggers macrophages, which are a key line of defense against microbial pathogens, to produce a molecule called “cathelicidin”. Cathelicidin kills bacteria, viruses, and fungi, and it is thus one of the body’s natural defense mechanisms against microbes. Essentially, Vitamin D triggers a natural “anti-bacterial response” by this action within macrophages. It is hard not to be enthusiastic at the possibility of such a built-in mechanism against infectious diseases like TB.

There are two main ways that the body obtains Vitamin D: through sunlight, which activates the production of Vitamin D in the skin, and through one’s diet, either in natural sources such as fish oil, or fortified in dairy products, as is practiced in many countries. Interestingly, people who have darkly pigmented skin have been found to be susceptible to Vitamin D deficiency due to melanin inhibition of vitamin D production in the skin. This means that on the African continent, where sunlight is strong without much seasonal variation -- particularly in equatorial Africa -- the protective mechanism of skin pigmentation against sun damage can hinder Vitamin D production and render people Vitamin D deficient. In other parts of the world such as China, Thailand, and other countries in Asia (Chailurkit et al, Shin et al), the population has also been found to be Vitamin D deficient, likely for other reasons, including cultural variables such as clothing styles or decreased time spent outdoors. Some literature has also shown that women have lower Vitamin D levels compared to men, particularly in the Middle East, Africa, and Asia Pacific Regions (Hilger et al, Dogar et al, Salahuddin et al).

Specific population groups may be particularly susceptible to the effects of Vitamin D deficiency and its impact on infectious disease. HIV patients who are deficient in Vitamin D have a higher risk of developing pulmonary tuberculosis, as demonstrated by data from Tanzania (Sudfeld et al). Studies from Pakistan have shown higher prevalence of TB among women than men. Why does Pakistan show a gender finding for TB prevalence that is in remarkable contrast to most countries in the world? One hypothesis is that women in these regions are often home-bound, caring for children and the elderly, and when leaving the house, they are fully covered from the sun by their clothing. This minimizes their exposure to sunlight and renders them deficient in Vitamin D.

Other recent studies have demonstrated the importance of Vitamin D in tuberculosis. One study found that in patients with pulmonary tuberculosis, supplementing Vitamin D accelerates clinical and radiographic recovery (Salahuddin et al), and that it hastened the resolution of the inflammatory response during TB treatment (Coussens et al). It’s easy to see a pattern. Vitamin D deficiency may place people at risk for developing pulmonary TB, while treatment with Vitamin D in patients with pulmonary TB can hasten clinical resolution. Vitamin D is a compound that deserves attention moving forward.

What’s the take-home message? The scientific rationale behind age-old therapies can enlighten us -- even today, in the age of elucidation at the molecular level for disease pathogenesis and treatment. For Vitamin D and its role in tuberculosis, the final verdict is not yet in. But it may very well be that for certain populations and among certain risk groups, supplementing diets with Vitamin D may decrease the risk for developing pulmonary TB. And among those who have active TB disease, supplementation may augment the activity of anti-tuberculosis drugs and hasten clinical recovery. Of course, many questions remain, including the ideal dose of Vitamin D and the recommended range of blood serum levels. Both of these would impact public health policy if Vitamin D supplementation is eventually recommended in high TB-prevalent areas.

 

Sources:

Chailurkit et al, Regional variation and determinants of vitamin D status in sunshine-abundant Thailand

Coussens et al, Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment

Dogar et al, Gender disparity in tuberculosis cases in eastern and western provinces of Pakistan

Gunville et al, The Role of Vitamin D in Prevention and Treatment of Infection

Hilger et al, A systematic review of vitamin D status in populations worldwide

Ross et al, The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know

Salahuddin et al, Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study

Shin et al, High prevalence of vitamin D insufficiency or deficiency in young adolescents in Korea

Sudfeld et al, Vitamin D Status and Incidence of Pulmonary Tuberculosis, Opportunistic Infections, and Wasting Among HIV-Infected Tanzanian Adults Initiating Antiretroviral Therapy

 

Photo:  Abergele Chest Hospital Sanitorium, Abergele, Wales, United Kingdom. Credit: abergelepost.com

Posted by: Dr. Anh Innes