# Potential Role of Vitamins A, B, C, D and E in TB Treatment and Prevention: A Narrative Review
## 2 Results  
### Vitamin A  
Vitamin A (VA) is a lipid-soluble molecule that belongs to the retinoic acid family. It is made up of four isoprenoid units linked head to tail. Provitamin A carotenoids (beta-carotene, alpha-carotene, and beta-cryptoxanthin) and preformed vitamin A are the two major forms of vitamin A [4]. Table 1 summerize main findings on VA and Tuberculosis infection. Various studies found association between VA deficiency and a variety of infectious diseases, including diarrheal and respiratory diseases, schistosomiasis, malaria, tuberculosis, leprosy, rheumatic fever, and otitis media [6; 7]. Vitamin A is involved in both T- and B-lymphocyte function, the generation of antibody responses, and macrophage activity [8]. Several studies demonstrated that VA and its metabolites play a role in the pathogenesis of TB. While low levels of the circulating form of VA, retinol, correlate with susceptibility to disease with a 10-fold increased risk of TB [9; 10], high levels of the bioactive hormonal form of vitamin A, all-trans retinoic acid (ATRA), induces antimicrobial activity in \(M\). _tuberculosis_-infected macrophages, as it has been shown in laboratory studies [11]. Many researchers have looked at the effects of VA supplementation in patients with pulmonary tuberculosis, and many of them have looked at vitamin A and zinc co-administration. [PERSON] et al. [12] found that vitamin A and zinc supplementation improves the impact of tuberculosis medicine after two months of antituberculosis treatment and resulted in earlier sputum smear conversion in a double-blind, placebo-controlled study [12]. On the other hand, a randomized controlled trial demonstrated that supplementation with vitamin A and zinc did not affect treatment outcomes at eight weeks [13]. Another study found no improvement in sputum smear conversion with zinc and vitamin A supplementation [14]; [PERSON] et al. [15] did not observe any effect of high dose vitamin A therapy on disease outcomes in South African children with TB [15]; a Tanzanian trial reported no effect of vitamin A and other vitamin and mineral supplementation on sputum culture conversion and overall survival in patients with pulmonary TB [16; 17]. In a review of vitamin A and zinc [PERSON] and [PERSON] [18] concluded that zinc deficiency could cause a secondary VA deficiency in protein-energy deficient populations and disease states with severely compromised liver function. Zinc is in fact required for the mobilization of VA from the liver, making it a key component in vitamin A metabolism [18]. This may be the explanation for a strong association between vitamin A deficiency and wasting observed in patients with TB [19; 20]. Therefore, supplementation with VA may not be beneficial in TB without correction of the zinc deficiency. In a small study, [PERSON] showed better sputum conversion with antituberculosis treatment (ATT) supplemented with multivitamin-trace elements [21]. [PERSON] et al. [16; 17] in their clinical study, as already mentioned, tested the supplementation of multiple micronutrients, including vitamin A but not zinc, without positive results on the rate of sputum culture conversion. A Peruvian study found that VA deficiency strongly predicted risk of incident TB disease among household contacts of TB patients. These data suggest that vitamin A supplementation among individuals at high risk of TB may provide an effective means of preventing TB disease [9]. Furthermore, low VA levels are common not only in patients with active tuberculosis but also in HIV patients, and are even more severe among patients with HIV/TB coinfection [20; 22]. [PERSON] et al. [22] observed a highly significant improvement in levels of vitamin A in HIV-negative tuberculosis patients at two months from treatment [22]. Few studies have shown that low vitamin A levels return to normal after ATT even in the absence of vitamin A supplementation [10; 22; 23]. Specifically, it is difficult to know whether the vitamin A deficiency led to TB, or whether TB led to the vitamin A deficiency.