Mitochondria-Targeted Nutraceuticals in Depression: Linking Energy Metabolism and Mood

Major Depressive Disorder (MDD) is a complex psychiatric illness that extends beyond monoaminergic deficits, encompassing mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired neuroplasticity. These cellular disturbances are increasingly recognized as contributing to the onset, progression, and treatment resistance seen in many patients. This review examines the potential of mitochondria-targeted nutraceuticals—such as Coenzyme Q10, Acetyl-L-carnitine (ALCAR), Alpha-lipoic acid (ALA), Nicotinamide riboside (NR), Pyrroloquinoline quinone (PQQ), and Curcumin—as adjunctive therapies in depression. These compounds enhance mitochondrial biogenesis, regulate redox balance, modulate apoptosis, and restore neurotrophic support (e.g., BDNF), while also reducing neuroinflammatory cytokines and normalizing HPA axis activity. Preclinical studies consistently show antidepressant-like effects, and early clinical trials suggest efficacy, particularly in patients with fatigue-predominant or inflammation-linked depression. However, challenges persist due to inconsistent dosing, limited bioavailability, and a lack of standardized, large-scale clinical trials. Despite these limitations, mitochondria-targeted nutraceuticals represent a promising, mechanism-based approach that complements traditional antidepressants and supports the development of personalized, integrative treatments for depression.