Randomized Clinical Trial: IS Zinc and Zinc Ionophere EGCG as Supplement Improve Outcome of Active Pulmonary Tuberculosis

1. tuberculosis -infected PMs, in vitro, elaborated IL-6 as the only major cytokine, which was significantly inhibited by anti-TB drugs. Therefore, IL-6 can be developed as a potential biomarker or biosignature to assess the success of the treatment of TB. (1) Tuberculosis is a global health problem, and there is even an increase in cases of multidrug-resistant tuberculosis in the world. Therefore, research is needed that can find new anti-tuberculosis drugs (OAT) that are more effective for tuberculosis treatment. In this study, the effect of (-)-epigallocatechin-gallate (EGCG) of tea leaves (Camellia sinensis) combined with the first-line OAT will be observed, in order to find out whether EGCG has anti-tuberculosis activity and can increase the potential of first-line OAT in-vitro. The anti-tuberculosis activity of EGCG was determined by broth dilution method using Middlebrook 7H9 media at concentration of 50, 100, 150, dan 200 ppm, then the potential of first-line OAT before and after combined with the EGCG was observed. The results showed that the activity of EGCG at concentration 50 ppm and 100 ppm could inhibit the Mycobacterium tuberculosis growth by 80%, at concentration 150 ppm by 90%, and at concentration 200 ppm by 100%. First-line OAT activity before combined with EGCG was ≥ 90% at 5 ppm rifampicin, 0.5 ppm isoniazid, 50 ppm pyrazinamide, and 5 ppm ethambutol. Whereas after combined with EGCG, the potential of each drug increased, marked by anti-tuberculosis activity achieved ≥ 90% at lower concentrations, i.e. rifampicin 0.5 ppm, isoniazid 0.25 ppm, pyrazinamide 20 ppm, and ethambutol 2 ppm. These results indicated that the potential of each first-line OAT increases after being combined with EGCG, and EGCG has potentiation effect when combined with those drugs. In conclusion, EGCG can increase the first-line OAT activity (2)

The down-regulation of TACO gene expression by epigallocatechin-3-gallate was accompanied by inhibition of mycobacterium survival within macrophages as assessed through flow cytometry and colony counts. Based on these results, the investigators propose that epigallocatechin-3-gallate may be of importance in the prevention of tuberculosis infection. (3) The effectiveness of anti-tuberculosis treatment was improved during the first two months by vitamin A and zinc supplementation," Dr. Clive E. West, a professor in the department of nutrition at Wageningen University in the Netherlands, and colleagues write in the April issue of the American Journal of Clinical Nutrition (2002;75:720-727). Previous research has shown that TB patients often suffer from malnutrition, which can weaken immune response and increase disease susceptibility. The addition of vitamin A and zinc has been observed to boost the immune response in these patients. Patients who received the supplements were twice as likely to have eliminated the TB bacteria from the mucus coughed up from their lungs by two weeks than the group receiving only standard drug treatment, and maintained that difference for seven weeks. These patients also had a greater reduction in abnormalities or lesions on their chest x-rays than those not taking the supplements. Reducing the amount of potentially contagious bacteria present in patients' sputum would cut the rate at which they spread TB to others, the researchers noted. (4) The effect of green tea extract supplementation on sputum smear conversion and weight changes in pulmonary TB patients: A randomized controlled trial (5) Zinc is an essential micronutrient (34, 40-42), and its tissue and plasma levels are influenced by dietary intake (38, 42). While severe zinc deficiency is rare in the developed world, moderate zinc deficiency is widespread, concentrated in elderly populations (42-45), and can be exacerbated in critically ill patients (33, 46-49). the investigators demonstrate that both genetic MT deficiency and dietary zinc deficiency potentiate lung injury in mechanically ventilated mice, consistent with an essential role for the zinc/MT system in protecting the lung from injurious stretch. To demonstrate clinical relevance of our findings, the investigators show that humans who go on to develop ARDS exhibit lower plasma zinc levels. Taken together, our results suggest that failure of essential stretch-adaptive responses, in this case associated with a remediable dietary deficiency among hospitalized patients, may play an important role in injury responses propagated by MV. (6)