# Potential Role of Vitamins A, B, C, D and E in TB Treatment and Prevention: A Narrative Review
## 2 Results
### Vitamin C  
In humans, vitamin C (VC) is an essential dietary micronutrient with antioxidant and prooxidant property which is involved in a wide range of vital cellular and physiological functions [42]. In several reports, authors described an improved effect of orally administered VC in preventing and treating _M. tuberculosis_ infection in humans and animals [43; 44]; others have reported that the malnutrition and the deficiency of VC in TB patients is related to a high risk of developing the disease and also developing severe outcomes [45; 46; 47]. Different studies have focused on understanding how _M. tuberculosis_ interacts with VC, with controversial findings. Recently [PERSON] et al. discovered that VC sterilizes cultures of drug susceptible and drug resistant _M. tuberculosis_ by induced Fenton reaction [48]. In this study, authors demonstrated that the ability of VC to sterilize _M. tuberculosis_ cultures results from an increase in ferrous ion concentration leading to ROS production, lipid alterations, redox unbalance and DNA damage [48]. The sterilizing effect of VC was more substantial in Tuberculosis strains deficient for mycothiol [49; 50]. Yet, the combination of a mycothiol inhibitor and VC or other prooxidant compound could lead to more rapid _M. tuberculosis_ cell death than with most antibiotics used [48; 49]. VC has also an effect on lipid biosynthesis. In VC treated-MTB cultures the authors observed the generation of two free 2-hydroxylated long-chain fatty acids [48]. They compared their findings to those of [PERSON] e [PERSON] [51], who found that 2-hydroxylated fatty acids were more toxic to mycobacteria than the equivalent saturated fatty acids. [PERSON] and colleagues describe that the accumulation of these fatty acids could lead to a bactericidal event in tuberculosis [48]. Furthermore, the reduction in phospholipid content observed in VC-treated _M. tuberculosis_ could affect the mycobacterial cell wall structure and, as a result, _M. tuberculosis_ survival [48]. In addition, VC is believed to reduce the level of guanosine 5\({}^{\prime}\)-diphosphate 3\({}^{\prime}\)-diphosphate (ppGpp), a molecule thought to be involved in growth regulation and stress response in _M. tuberculosis_[52; 53]. The VC potentiates the Pyrazinamide (PZA) action, an essential first line TB drug because of its sterilizing activity against non-metabolizing/slowly metabolizing persistent bacilli that are resistant to other drugs, by tackling dormant organisms and inhibiting the development of rifamp-tolerant and rifamp-resistant bacilli [52]. Anyway these studies reached divergent conclusions [54; 55]. [PERSON], [PERSON] et al., demonstrated that high concentrations of VC sterilize drug-susceptible, and drug-resistant tuberculosis cultures and prevent the emergence of drug persisters, discovered in the same study, and that the combination of a sub-lethal concentration of VC with first line antitubercular drug Isoniaid (INH) resulted in sterilization of _M. tuberculosis_ cultures after 4 weeks, with no resistant mutant escape in the treatment. This suggests that the addition of a sub-inhibitory dose of VC to INH treatment could also reduce the emergence of INH-resistant mutants [48]. In another study VC alone had no activity against _M. tuberculosis_ in mice but had the potential to boost the efficacy of INH-RIF treatment, thus increasing the elimination rate of _M. tuberculosis_ in mice compared to that with INH-RIF alone [56]. Low levels of micronutrients are commonly observed among TB patients [57; 58]. Lower blood levels of vitamins A and C have been reported to be associated with higher TB incidence [59]. [PERSON] et al. observed that giving terminally ill TB patients daily high dosages (15 g/day) of VC orally for 6 to 8 months enhanced appetite and physical activity with no negative effects [60]. Although no radiological improvement in the disease was observed, the authors concluded that the addition of VC to TB treatment might improve patients' resistance to infection. As [PERSON] et al.