Reduced interleukin-2 production and increased CREMα protein expression in vegetarians and vegans due to zinc deficiency

• Vegetarians and vegans produce lower amounts of interleukin-2 • Zinc deficiency is correlated to reduced interleukin-2 production irrespective of diet • CREMalpha expression is higher in zinc deficiency • Interleukin-2 production is positive correlated to serum zinc and negative correlated to CREMalpha expression Nutrition is a key determinant of health and may be regarded as a form of preventive medicine, as an adequate supply of vitamins, fats, proteins, and trace elements is essential for proper immune function. In recent decades vegetarian and vegan diets have become increasingly popular but may increase the risk of trace element deficiencies if not carefully planned. Zinc deficiency can impair immune responses and reduce resistance to infections. While previous research has mainly focused on animal models or elderly populations, little is known about younger adults. Thus, we investigated the impact of zinc intake through different diets (omnivorous, vegetarian, and vegan) on immune function in healthy young volunteers aged 19 to 33 years. We identified zinc deficiency to be prominent in young, healthy individuals adhering to plant-based diets (vegetarian and vegan) compared with omnivorous individuals of the same age. This was associated with impaired immune function, as indicated by reduced IL-2 cytokine production, which was linked to zinc deficiency-depended overexpression of CREMα. Furthermore, we validated the applicability of our recently established food frequency questionnaire (FFQ) in this cohort. Individuals adhering to plant-based diets are at considerable risk of developing zinc deficiency. Zinc deficiency, regardless of diet, provokes immune system dysfunction by impairing IL-2 production, a consequence of zinc deficiency-dependent overexpression of CREMα. These results underscore the critical importance of ensuring adequate zinc intake among young individuals following plant-based diets to prevent severe immune dysfunction. Zinc deficiency and immune dysfunction in young adults adhering to plant-based diets Plant-based diets are associated with a higher risk of zinc deficiency through lower zinc bioavailability and uptake in healthy young adults leading to overexpression of CREMa, thereby impairing IL-2 cytokine production and immune function. Adequate zinc intake is critical for immunological health in these populations. Abbreviations for Zn: Zinc, IL-2: Interleukin-2, CREMa: cAMP response element modulator alpha. The graphical abstract was created by using FigureLabs.