Ketogenic diets may lead to meaningful reductions in depressive symptoms, with more mixed effects on anxiety. Digest
Depression and anxiety are leading causes of disability, yet standard treatments rarely address the metabolic disturbances that often accompany these conditions. Ketogenic diets have been suggested as one way to target this problem.
In a systematic review and meta-analysis, researchers looked at 50 human studies including 41,718 adults from psychiatric and nonpsychiatric settings in 15 countries. Interventions were ketogenic-style diets high in fat, moderate in protein, and limited to no more than 25% of calories from carbohydrate or under 50 grams per day, compared with control diets in randomized trials or with each participant's own baseline diet. Mental health outcomes were measured with validated rating scales.
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Ketogenic interventions were associated with distinct patterns of symptom change depending on study design and diet features:
- Across ten randomized clinical trials involving 631 participants, ketogenic diets produced a modest reduction in depressive symptoms compared with control diets.
- In nine randomized trials with 672 participants, ketogenic diets did not outperform control diets for anxiety.
- In nine studies where participants served as their own controls, depressive symptoms improved modestly during ketogenic interventions, and six comparable studies showed similar reductions in anxiety.
- Subgroup analyses of depression trials pointed to stronger benefits when it was confirmed that participants were actually in ketosis, when diets were very low in carbohydrate, when control groups did not follow high-carbohydrate diets, and among participants without obesity.
- Side effects were mostly mild adaptation symptoms such as constipation, tiredness, headache, nausea, and trouble sleeping.
Ketone bodies provide an alternative fuel for brain mitochondria, the energy-producing structures in cells, which may help compensate for brain glucose underuse and mitochondrial dysfunction reported in mood disorders. Beta-hydroxybutyrate, a major ketone body, also acts as a signaling molecule that can influence gene regulation, antioxidant defenses, and the behavior of microglia, the brain's immune cells. Ketogenic diets may therefore reduce oxidative and inflammatory stress, help keep the brain's quieting and activating signals in better balance, and support broader metabolic health, all of which could contribute to improvements in depressive and anxiety symptoms.
Because the studies used different diet protocols, were often short in duration, and relied mostly on self-reported outcomes, the evidence should be viewed as preliminary rather than conclusive. For now, ketogenic diets remain promising but experimental in psychiatry, and larger high-quality trials are needed to determine who benefits, how to sustain adherence, and how to manage safety. In Aliquot #88, you can learn how to master the ketogenic diet.