Vitamin D as an Adjunctive Treatment to Standard Drugs in Pulmonary Tuberculosis Patients: An Evidence-Based Case Report

Table 4

Summary of included randomized controlled trials.

Author	Study population	Vitamin D (method of administration, dose)	Outcome measure	Results
Afzal et al. (2018)	Adult newly diagnosed TB patients with vitamin D deficiency in Lahore, Pakistan (n = 120)	Intramuscular injection of vitamin D (four doses of 100,000 IU) after 14 days during the intensive-phase	Sputum examination repeated at 2nd, 4th, 6th, 8th, 10th, and 12th weeks. Early SCR shown by the conversion of AFB to negative four weeks after treatment initiation	The intervention group who received vitamin D was 1.11 times as likely to have earlier SCR during the 12-week examination; significant results of positive SCR seen in control vs vitamin D (11.7% vs 1.7%, p = 0.028)
Daley et al. (2015)^+∗	Adult TB patients in Tamil Nadu, India (n = 247)	Four doses of adjunctive 2.5 mg oral vitamin D3 oil (100,000 IU) at weeks 0, 2, 4, and 6	Sputum culture conversion (time to first negative smear), estimate in median time to culture conversion	No significant difference of the median time to culture conversion between vitamin D and the placebo group (RR = 1.02)
Ganmaa et al. (2017)^∗	Adult TB patients in Ulaanbaatar, Mongolia (n = 390)	Four oral doses of 3.5 mg (140,000 IU) vitamin D3 (each dose is 4 tablets containing 875 μg)	The proportion of participants with negative sputum culture at week 8	The administration of vitamin D versus the placebo did not influence the proportion of participants with sputum culture conversion at week 8 (Adjusted OR = 1.47, 95% CI = 0.88–2.45, p = 0.14)
Martineau et al. (2011	Adult TB patients in London, UK (n = 126)	Adjunctive oral vigantol oil (2.5 mg)	Proportion of TB patients with a negative sputum culture at 56 days as the secondary outcome	Vit D3 group is 0.98 times as likely to achieve the negative sputum culture result at 56 days than the placebo group (p = 0.85)
Mily et al. (2015)^∗	Adult TB patients in Dhaka, Bangladesh (n = 288)sd	Adjunctive oral vigantol oil (5000 IU vitamin D3) once daily	Proportion of TB patients became culture negative and major clinical endpoints at weeks 4 and 8 as primary outcomes	Odds of sputum culture being negative at week 4 are 2.20 times higher in vit D3 group (95% CI = 1.07–4.51, p = 0.032), and 7.26 higher at week 8 (95% CI = 0.90–25.50, p = 0.062)
Nursyam EW (2006	Adult TB patients visiting the Pulmonary Clinic of RSCM from Jan 1st to Aug 31st in 2001 (n = 67)	Oral Vitamin D tablets (0.25 mg/day) given in initial 6 weeks of Anti-TB drugs therapy (2RHZE/4H)	Negative AFB at the beginning of trial, on the 6th and 8th week; If AFB (+) test, another AFB test on 12th week	Significant differences in the proportion of negative SCR observed between vitamin D and the placebo group (100% vs 76.7%, p = 0.002) at 6th week; however, at the 8th week the differences of SCR versus the placebo were 100% vs 96.9% (p = 0.99)
Ralph et al. (2013	Adult newly diagnosed PTB patients in Timika, Southern Papua, Indonesia (n = 79)	Oral adjunctive active cholecalciferol (vitamin D3, “Calciferol Strong®”) 50,000 IU (1250 mcg, 1 tablet) 4 times a week	Negative sputum culture on liquid medium at week 4 and a composite clinical severity score at week 8 (including presence/absence of sputum and sputum smear conversion time)	Risk difference of vitamin D versus vitamin D-Placebo: 7%, 95% CI [−9, 22].; Vit D did not, at dose administered and with the power attained, affect the outcomes of TB
Tukvadze et al. (2015	Adult TB patients in Tbilisi, Georgia (n = 199)	Adjunctive oral 1.25 mg vitamin D3 (50,000 IU) 3 times weekly for 8 consecutive weeks, and 50,000 IU oral vitamin D3 every 2 weeks for an additional 8 weeks	Sputum culture conversion at 8th week as the secondary clinical outcome	No significant difference between the high dose vitamin D3 and the placebo groups in achieving a negative sputum culture (HR = 1.20, 95% CI = 0.80−1.88, p = 0.004)

in Wallis et al.,  included in Wang et al., ^∗ included in Wu et al.;
PTB: Pulmonary Tuberculosis; TB: Tuberculosis; SCR: Sputum Conversion Rate.