Short-term oral zinc supplementation enhances Natural Killer cell functionality and decreases circulating Innate Lymphoid Cell counts and frequencies in healthy young adults.

BACKGROUND: Zinc is an essential trace element with high importance for immune function. Previous research has shown that vegetarians and vegans are at increased risk of zinc deficiency, due to low zinc bioavailability in plant-based food. However, its effects on immune parameters in healthy adults following these diets remain largely unexplored. Therefore, this study investigated the effects of dietary patterns, serum zinc levels, and short-term oral zinc supplementation on Natural Killer (NK) cells, circulating Innate Lymphoid Cells (cILCs), and NK cell functionality in omnivores, vegetarians, and vegans. METHODS: A total of 54 study participants, including 21 omnivores, 18 vegetarians, and 15 vegans were enrolled in our study. NK cell and cILC counts and frequencies were analyzed by flow cytometry and NK cell cytotoxicity assay was performed and compared between the three dietary cohorts as well as between zinc adequate (ZA) and zinc deficient (ZD) individuals. Based on serum zinc concentrations and/or Food Frequency Questionnaire (FFQ) scores, study participants classified as ZD were supplemented with 10 mg zinc daily for 14 days. After this period, the same experiments were performed. RESULTS: Our results show that neither dietary patterns nor baseline zinc levels significantly affect cILC or NK cell counts, frequencies, or NK cell cytotoxicity. However, short-term oral zinc supplementation significantly reduced cILC counts and frequencies, while enhancing NK cell functionality. Here, NK cell cytotoxicity is significantly positively correlated, whereas cILC counts are negatively correlated with serum zinc concentrations. Remarkably, 72% of all study participants, including 48% of omnivores, were classified as ZD. CONCLUSIONS: Since proper NK cell functionality is required for early defense against infected or malignant cells, and cILCs act as progenitors to replenish tissue resident ILCs, which are crucial for tissue homeostasis and barrier integrity, our results suggest that routine zinc supplementation might be a simple yet effective strategy to enhance immune defense and potentially prevent diseases across different dietary groups. TRIAL REGISTRATION: The study was approved and registered by the Institutional Ethics Committee of the Medical Faculty of RWTH Aachen University on the 19th of July 2023 (study numbers: EK 23-148 and EK 23-234, CTC number: 23-163).