Ketogenic diet for depression: A potential dietary regimen to maintain euthymia?

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jul 13:109:110257. doi: 10.1016/j.pnpbp.2021.110257. Epub 2021 Jan 23.


Approximately 30% of patients with major depressive disorder (MDD) present resistance to current pharmacological therapies. There is the possibility that an appropriate nutritional regimen can maintain euthymia. Poor dietary pattern and lack of nutritional knowledge are common among today's population; nutrient-rich foods are being replaced by highly processed foods that lead to a higher risk of developing chronic diseases such as metabolic syndrome, hypercholesterolemia, and diabetes. There is growing evidence of the beneficial role of vitamins and dietary supplements for improving symptoms in a range of affective disorders by regulating the gut microbiome, gut-brain axis, and neurotransmitter levels. Reduced GABA neurotransmission is regularly observed in MDD. Moreover, positive allosteric GABA modulators (i.e benzodiazepines) are widely prescribed to alleviate depression symptoms, but their use needs to be limited, as it can lead to addiction. An alternative option may be the adherence to a ketogenic diet, which consists of low-carbohydrate, moderate-protein, and high-fat intake. It is mainly known for its beneficial role in weight-loss, refractory epilepsy treatment, and balancing glucose levels. A ketogenic diet can also increase GABA levels to aid the mechanism of action of monoaminergic drugs. Thus, it could potentially be used in the treatment for affective disorders due to its potential role in GABA/glutamate balance. While more research is needed before this regimen can be regularly recommended to patients, here we discuss evidence that may encourage physicians to prescribe ketogenic diet as an adjuvant for patients receiving psychotherapy and pharmacology.

Keywords: GABA; Gut microbiome; Gut-brain axis; Ketosis; Major depressive disorder; Neurotransmission.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain-Gut Axis / physiology*
  • Depressive Disorder / diet therapy*
  • Diet, Ketogenic*
  • Gastrointestinal Microbiome / physiology
  • Humans