Nutrition and Depression: A Narrative Review of Biological Mechanisms and Evidence from Observational Studies and Clinical Trials

Depression is one of the most prevalent and disabling psychiatric disorders worldwide and has a heterogeneous pathophysiology involving interacting neurobiological, neuroimmune, and metabolic processes. Alterations in neurotransmission, neuroinflammation, oxidative stress, gut–brain communication, hypothalamic–pituitary–adrenal axis dysregulation, and immunometabolic homeostasis may provide biological links between nutrition and depression. This narrative review examines current evidence linking nutrition and depression across mechanistic, observational, and clinical levels. Regarding dietary patterns, observational evidence generally associates greater adherence to the Mediterranean diet with more favorable depression-related outcomes, while evidence for the DASH diet remains more limited. In contrast, Western dietary patterns and greater consumption of ultra-processed foods are associated with higher risks of depression-related outcomes. Individual nutrients, including omega-3 polyunsaturated fatty acids, vitamin D, vitamin C, folate, vitamin B12, vitamin B6, and essential minerals, have also been investigated in relation to depression, but findings from supplementation studies vary across nutrients, study populations, and baseline nutritional status. However, much of the evidence linking nutritional factors with depression is observational and does not establish causality. Clinical trials of nutrient supplementation and dietary interventions have reported potential benefits in some populations, but findings remain heterogeneous, and large prevention trials have also reported null results. Differences in baseline nutritional status, depression phenotype, and metabolic and inflammatory profiles may partly contribute to this heterogeneity. Future well-designed clinical trials, together with advances in multi-omics and precision approaches, may help identify individuals most likely to benefit from targeted nutritional strategies.