High Grade Non-Hodgkin Lymphoma (NHL) is a malignancy with limited therapeutic alternatives and poor prognosis. Zinc is a known micronutrient that is involved in immune response expression. It was hypothesized that zinc therapy can modulate the immune system following chemotherapy in patients with high grade NHL. This study aimed to explore the effect of zinc supplementation on serum zinc levels and inflammatory profile (NF-κB and Interleukin-12). In a randomized, double-blind, placebo-controlled trial, 34 patients with high-grade NHL undergoing R-CHOP chemotherapy were equally divided into control and intervention groups. The intervention group received oral zinc therapy for six chemotherapy cycles, while the control griouo recived a placebo. All patients received similar overall management. Serum zinc levels and inflammatory profiles were analyzed using the ELISA. Various statistical methods were utilized to evaluate comparative pre-post results compared between the intervention and control groups. Zinc levels decreased in both groups, with a more significant reduction in the intervention, although not statistically significant (2 ± 0.9 vs. -3.4 ± 1.6; p = 0.13). NF- κB parameters showed a decrease within the intervention group (281 (31 - 1131) to 140 (19 - 347), p = 0.004) and an increase within the control group (179 (0 - 5868) to 387 (7 - 2345)). However, the primary analysis (Mixed ANOVA) showed no statistically significant interaction effect of the intervention on NF-κB levels over time (p = 0.865). The IL-12 parameter showed no significant change or between-group difference. In this pilot study, adjuvant oral zinc supplementation did not demonstrate a statistically significant modulating effect on systemic NF-κB or IL-12 levels over six cycles of chemotherapy compared to placebo, as assessed by the primary statistical model. More research is encouraged to explore whether different dosing regimens, patient populations, or inflammatory markers might reveal a significant regulatory pathway from zinc to immune response.
