Vitamin Deficiency and Tuberculosis : Need for Urgent Clinical Trial for Managment of Tuberculosis

Surajit Chakraborty1, Kirtiman Syal2, Rajasri Bhattacharyya3 and Dibyajyoti Banerjee1* 1Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh-160012, India 2Department of Biophysics, Indian Institute of Science, Bangalore, India 3Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala, India Journal of Nutritional Health & Food Science Open Access Review Article


Introduction
Tuberculosis is one of the deadliest bacterial killers affecting almost all corners of the globe.In-spite of the discovery of antitubercular antibiotics and an available vaccine (BCG vaccine) against Mycobacterium tuberculosis we are unable to tackle the occurrence of tuberculosis.Moreover the increasing prevalence of HIV-AIDS and diabetes mellitus is being proved to be providing predisposition to tuberculosis (Global tuberculosis controlsurveillance, planning, financing [1][2][3][4][5].As witnessed by the WHO, which has estimated that, in the year 2012, 8.6 million people have developed tuberculosis and 1.3 million have died of the disease, including 320000 deaths of HIV-TB co-infected people [6].Long term multiple antibiotic therapy, which is associated with many adverse drug related events have diminished patient compliance with the anti-tubercular chemotherapy.This fact, in turn, has raised the new, deadlier MDR-TB and XDR-TB strains [7][8][9].The whole scenario of current day tuberculosis is a matter of panic.It questions the effectiveness of anti-tubercular antibiotics, immunologic efficacy of century old BCG vaccine and all other medical advents present at the moment to combat tuberculosis.
Malnutrition has always been recognized to be a very important predisposing factor for all infectious diseases including is believed to be very essential for the mycobacterial entry and successful intra-phagosomal survival in the macrophages as it inhibits the phagosome maturation i.e., the phagosome-lysosome fusion and acidification and thus contribute in the pathogenecity and virulence of Mycobacterium tuberculosis [67,68].Vitamin A helps in the normal function of immune cells and also enhances the synthesis of iNOS and other essential cytokines with antitubercular activity [69][70][71][72][73][74][75][76][77].Moreover, oral administration of retinoic acid can reduce mycobacterial growth in vivo and physiological and pharmacological doses of retinoic acid in pre and post infectious conditions show preventive and therapeutic effects respectively [74,78].So, deficiency in dietary vitamin-A can hamper the activity of both innate and adaptive immunity while supplementation can boost the body's fight against Mycobacterium tuberculosis along with the administration of anti-tubercular drug regimens.

Vitamin-B
Though the direct association between tuberculosis and vitamin-B deficiency is not known, but vitamin-B supplementation is well recommended in order to avert several neurological complications in tuberculosis patients.Administration of pyrazinamide, isoniazid while treating tuberculosis commonly causes vitamin-B 6 deficiency in the body which in turn gives rise to different peripheral neuropathies [79,80].It is also reported that vitamin-B 12 deficiency is a cause of neuropathy in patients with ileal tuberculosis [81].

Vitamin-C
Vitamin-C is well known for its anti-oxidant and prooxidant actions [82][83].As an immunological maintenance measure vitamin-C can enhance the function of the immune system in different ways like T-lymphocyte proliferation etc. and thus strengthens the cell mediated immunity [84][85][86][87][88].Both lower dietary intake and lower blood concentration of vitamin-C are considered to be associated with the higher incidence of tuberculosis [89,90].In patients with active cavitary tuberculosis, the anti-oxidant vitamin-C level gets substantially decreased with an increase in lipid peroxides [91][92][93].Vitamin-C can halt spreading of infections including tuberculosis.It also accelerates recovery from tuberculosis by healing decay cavity and turns sputum acid fast bacillus (AFB) negative [94].Most interestingly in a recent study, vitamin-C has been shown to have an extraordinary capability of killing of drug susceptible, multi-drug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis, which strongly suggest and support the incorporation of vitamin-C and iron (needed for its strong mycobactericidal action) supplementation along with the antitubercular antibiotic therapy [95].Paradoxically, it is believed that the blind exogenous administration of antioxidants may augment the mycobacterial antioxidant system to protect itself in patient suffering from tuberculosis, but experimental supports are there which show that an adequate dietary supplementation of vitamin-C contributes protection against tuberculosis and lowers the incidents [94,[96][97][98].Adequate anti-oxidant vitamin supplementation along with standard anti-tubercular antibiotic regimen has been demonstrated to accelerate healing of tuberculosis [94].

Vitamin-D
Vitamin D is well known for its pivotal role in bone mineral density (BMD) and calcium homeostasis in the body [99].Vitamin D deficiency and its association with tuberculosis is very well known from the pre-antibiotic era as in those days exposure to sunlight and vitamin D supplementation (cod liver oil) were the most reliable treatment choice for treating tuberculosis [100][101].
It is believed that vitamin-D deficiency is associated with increased infection of the upper respiratory tract [99].Till date, a large number of studies have proven the association between vitamin D deficiency and the occurrence of tuberculosis [102][103][104][105][106][107].Vitamin D receptors (VDR) are found to be present on different immune cell surfaces including T and B cells suggest that, they need vitamin-D for performing the cellular functions [99].Vitamin D has been shown to increase the phagocytic activity of macrophages.Monocytes incubated with cholecalciferol (vitamin-D 3 ) metabolites have been shown to induce antitubercular activity [108].Moreover, it enhances the production of the body's antimicrobial/antimycobacterial peptide LL-37, a member of the cathelicidin peptide family [109][110][111].Vitamin-D also enhances the fusion of phagosome and lysosome, a very significant step towards the elimination of intra-phagosomal Mycobacterium tuberculosis from the human body [110,112].Vitamin-D deficiency has been recognized as a major risk factor for tuberculosis as low serum vitamin-D found to be associated with the development of active tuberculosis.Hypovitaminosis D is also found as a common feature in HIV positive patients and maybe that's why the most common opportunistic infection in these people is tuberculosis [113,114].Vitamin-D supplementation in this HIV-TB co-infected patient population has shown some amazing hope with sputum clearance and radiological improvement which in turn caused an appreciable reduction in mortality [115].

Vitamin-E
Several studies have reported substantial reduction of antioxidant vitamin-E in patients suffering from tuberculosis.Alpha tocopherol (vitamin-E) is as capable as ascorbic acid (Vitamin-C) in cavity healing in active cavitary tuberculosis and thus having an accelerating role in healing tuberculosis [94,116].

Vitamin-K
Vitamin-K has vital functions in the formation of coagulation factors by the liver.Hepatotoxic anti-tubercular drug (e.g.; Pyrazinamide, Isoniazid, Rifampicin) induced hepatotoxicity may hamper the blood coagulation physiology e.g., cerebral hemorrhage is reported due to vitamin-K deficiency in patients suffering from congenital tuberculosis [117].
Pre-infective routine dietary nutrition with essential vitamins and minerals has effective preventive capability against the occurrence of disease tuberculosis.Multivitamin

Vitamin Deficiency and Tuberculosis: Need for Urgent Clinical Trial for Managment of Tuberculosis
Copyright: © 2014 Banerjee et al.
supplementation along with anti-tubercular antibiotic therapy is very much needful as it provides anti-tubercular capability to the body, accelerates healing of Mycobacterium tuberculosis caused cavity and ulcer, reduces anti-tubercular drug induced adverse effects and helps the body reclaiming normal physiological function of affected organs.Dietary vitamin supplementation as a measure of nutritional up gradation will definitely help in effective tuberculosis treatment and also low down the prevalence of tuberculosis especially in the countries with higher disease burden.However, blind supply of antioxidant vitamins may also be harmful.Therefore, we feel systematic clinical trials should be conducted focusing on the above area to construct a combination regime of vitamin supplementation that can combat tuberculosis.