L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial

Abstract

BackgroundVitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB).MethodsIn a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339.Results200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference −3%, 95% CI −19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI −9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes.ConclusionNeither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes.Registry ClinicalTrials.gov. Registry number: NCT00677339

A study of vitamin D supplementation with directly observed treatment short course for Pulmonary Tuberculosis

“…This study also did not observe any significant change in the above mentioned clinical score with vitamin D in PTB patients. 18 The similar non-significant findings were also reported by Salahuddin et al inTB score, with Vitamin D supplemented and placebo groups at 4 weeks (p-value 0.16), 8 weeks (p-value 0.89) and 12 weeks (p-value 0.16). 14 Farazi et al found an association between TB severity score with lower levels of serum calcidiol (p-value = 0.043) in Vitamin D (single dose of 450,000 IU) supplemented and placebo groups over 3 months.…”

“…15 A similar clinical outcome score was designed in a randomized, double-blind, placebo-controlled study conducted by Ralph et al (2013) where change in body weight, %FEV1 change, cough, sputum, hemoptysis was included. This study also did not observe any significant change in the above mentioned clinical score with vitamin D in PTB patients.…”

Differential Requirements for l-Citrulline and l-Arginine during Antimycobacterial Macrophage Activity

“…Schö n et al (44) treated TB patients with oral L-arginine and observed subtle benefits, including increased sputum conversion and reduced cough and chest pain in HIV 2 patients. Yet a more recent study found no clinical benefit in supplementing L-arginine to M. tuberculosis-infected patients (45). The metabolic consequences of oral L-arginine supplementation may be responsible for these results.…”

Correlation Between the Vitamin D Intake with Clinical Symptoms of Patients Pulmonary Tuberculosis

“…Determinant of vitamin D status consists of; exposure to UVB radiation, clothing, nutrition, BMI, serum cholesterol, and genetic factors like skin pigmentation and enzymes in the metabolism of vitamin D [16]. Exposure to UV radiation is the most determinant factor [17].…”