In the 2017 SMILES randomized controlled trial, Felice Jacka and colleagues tested whether improving diet quality alone could impact major depression. Sixty-seven adults with moderate-to-severe depression and poor baseline diets were assigned to either a dietary intervention (ModiMedDiet) with structured support from a dietitian or a social support control (“befriending”) designed to control for time and attention. After 12 weeks, the dietary group showed significantly greater improvements in depression severity, with a ~7-point larger reduction in MADRS scores and higher remission rates (32% vs. 8%).

Notably, these improvements occurred without meaningful changes in weight, physical activity, or most metabolic markers, suggesting the effect was independent of those factors. Dietary adherence correlated with improvements in depression scores, supporting a potential causal role of diet quality itself. However, the trial was small and may overestimate effect size, and participants were already selected for poor diets, limiting generalizability. Overall, the findings provide early controlled evidence that improving diet quality may be a useful tool for treating depression—though larger and more rigorous trials are needed, and it remains unclear whether more metabolically impactful interventions would produce stronger or more durable effects.