Broad-spectrum therapeutic potential of the combination of zinc and L-carnosine in psychiatry

抄録

Zinc and L-carnosine are biologically active agents of increasing clinical importance in psychiatry. Zinc is essential for enzymatic catalysis, maintenance of protein structural integrity, regulation of cellular signaling, neurotransmission, synaptic plasticity, neurogenesis, and antioxidant defense. Disturbances in zinc homeostasis are associated with depression, schizophrenia, attention deficit/hyperactivity disorder, and Alzheimer’s disease. Meanwhile, L-carnosine, a dipeptide abundant in the nervous tissue, has antioxidant, anti-inflammatory, anti-glutamatergic, histamine-enhancing, metal-chelating, and neuroprotective properties. It also enhances zinc bioavailability by promoting intestinal absorption and acting as a zinc ionophore to facilitate cellular uptake. The zinc–L-carnosine complex (polaprezinc) is a drug used to treat gastric ulcers. This combination provides mechanistic benefits that extend beyond gastrointestinal indications, offering synergistic and multifaceted effects. It mitigates oxidative stress and neuroinflammation, modulates the transmission of glutamate, γ-aminobutyric acid, and serotonin, enhances histamine production, and increases neurotrophic factor levels. It may also regulate synaptic zinc homeostasis and protect neurons from excess zinc-induced neurotoxicity. Emerging clinical evidence suggests that zinc–L-carnosine combination therapy can treat various psychiatric disorders plausibly related to zinc deficiency, including binge eating disorder, bulimia nervosa, dissociative identity disorder, and burning mouth syndrome. Symptoms such as flashbacks, self-harm, and hypersomnia may also respond to treatment. This review summarizes the molecular mechanisms and clinical findings for zinc, L-carnosine, and their combinations in the treatment of psychiatric conditions. While the current evidence is preliminary, the natural origin, favorable safety profile, and clinical feasibility of this combination therapy support further controlled investigations as an integrative nutritional-neuropsychiatric strategy for these difficult-to-treat conditions.