Zinc Deficiency and Cyclic Feeding Behavior—From Animal Models to Potential Human Implications

Abstract This narrative review synthesizes 5 decades of evidence on zinc deficiency–induced cyclic feeding in animal models, examines the underlying neurobiological mechanisms—with emphasis on recent advances in gut–brain axis signaling—and critically evaluates whether analogous periodic appetite fluctuations may occur in zinc-deficient humans. Zinc deficiency induces a distinctive cyclic feeding pattern in rodents, with food intake oscillating at an approximately 3.5-day period, as demonstrated by cosinor analysis, yet the mechanistic basis and potential human relevance of this phenomenon remain incompletely understood. PubMed was searched (through March 2026, with no date restrictions) using terms related to zinc, appetite-regulating neuropeptides and hormones, neuropsychiatric outcomes, and zinc-sensing receptors/transporters. A total of 41 references were selected on the basis of topical relevance, supplemented by citation chaining. The approximately 3.5-day cyclic feeding pattern has been reproducibly observed in several rat studies under controlled laboratory conditions, persisting at the individual-animal level and across dietary carbohydrate sources, though the evidence base is limited to predominantly male rats from a small number of research groups. Mechanistically, this periodicity involves paradoxical neuropeptide Y elevation with putatively impaired release, hypothalamic–pituitary–adrenocortical axis dysregulation, vagal zinc sensing, enteroendocrine cholecystokinin signaling, and intestinal and salivary functions mediated by the zinc-sensing receptor ZnR/GPR39. Clinical data—including zinc deficiency in anorexia nervosa and avoidant/restrictive food intake disorder patients, refeeding hypozincemia, and population-specific effects of zinc supplementation on body weight—provide circumstantial but not direct support for a human correlate. No direct evidence for cyclic feeding in zinc-deficient humans currently exists; however, conserved neurobiological substrates and emerging clinical findings warrant prospective studies employing continuous dietary monitoring and serial zinc assessment to test this hypothesis.