Zinc Supplementation as Adjunctive Therapy in Adults with Tuberculosis in Calabar, Nigeria: A Randomized Controlled Trial

Introduction: Tuberculosis (TB) still remains a leading killer from a single infectious agent worldwide, especially in Asia and Africa. Achieving the Sustainable Development Goal (SDG) 3 will be contingent on addressing ways of reducing the impact of TB to the health, socio-economic and health system of populations most at risk. Micronutrients supplementation is increasingly being recognized as having great potentials to that effect.

Objective: This study thus assessed the potential benefits or otherwise of zinc supplementation on tuberculosis treatment outcomes in Calabar, Nigeria.

Methods: Eligible patients (81) out of the 182 assessed were randomized to receive anti-TB drug regimen plus oral administration of individual zinc, 25 mg daily for 60 days (intervention group), while the control group received anti-tuberculosis drug regimen only for 60 days. Both qualitative and quantitative data were collected. Clinical examination, Karnofsky performance scale index, direct sputum examination, anthropometric measurements and blood collection for haematological and zinc assessment were carried out before and 2 months after anti-TB treatment began. Difference in treatment effects between and within groups for continuous variables was tested using t-test. Mantel-Haenszel summary estimate of the relative risk (RR) was used to test the clinical effectiveness of the intervention. The Pearson test was applied to determine the correlation between variables.

Main Results: The mean serum zinc levels at 2 months of TB treatment were significantly higher in the intervention group (14.4 ± 0.37µmol/L) in comparison with the control (12.9 ± 0.37 µmol/L); (p = 0.004). A significant difference (p = 0.010) in the serum concentrations of zinc was observed between the two groups when adjustments were made for TB-HIV co-infection. Risk reduction of about 41% for acid fast bacilli (AFB) positivity (RR: 0.59; 95% CI 0.23 to 1.46) was observed after 2 months of anti-TB treatment in favour of the intervention group. Similarly, intervention group had significantly (p = 0.005) lower proportion of patients with serum zinc levels < 10.7 µmol/L (intervention: 5; Control 10) and (p = 0.030) BMI < 18.5 kg /m2 below the lower ranges ((intervention: 9; Control 16). There was a significant improvement in the haematological parameters as evidenced by significant higher proportion of patients in the intervention group than the control group with values above the lower ranges for these parameters with risk reductions in favour of the intervention group for lower ranges as 34%, 12%, 73% and 58% respectively for haemoglobin, albumin, serum total protein and globulins.

Conclusion: Irrespective of HIV status in individuals with tuberculosis, zinc micronutrient supplementation significantly increases clinical outcomes, haematological parameters, improves nutritional status as proxied by anthropometric indices and leads to faster sputum smear conversion. The study adds to the growing body of evidence in support of the beneficial role of zinc in TB control.