The ketogenic diet (KD) is unique in improving symptoms for many conditions, from epilepsy to addiction, according to a recent JAMA Psychiatry article. It’s a high-fat, very-low-carbohydrate nutritional therapy that shifts the body’s from glucose dependence to ketone production as the primary fuel source. Increasing evidence implicates metabolic dysfunction, neuroinflammation, and neurotransmitter imbalance in psychiatric and addictive disorders—domains directly influenced by ketosis.
Formulated in the 1920s by Dr. Russell Wilder at the Mayo Clinic to mimic the effects of fasting as a treatment for epilepsy, the ketogenic diet replicates the biochemical effects of fasting through carbohydrate restriction. Such restriction creates a metabolic state called ketosis that helps control seizures. Wilder’s KD provided a 4:1 ratio of fat to carbohydrate and protein (80% fat, 15% protein, 5% carbohydrates).
Inducing ketosis through diet improved anticonvulsant outcomes while allowing adequate nutrition. The approach declined after effective anti-seizure drugs were developed, but it resurged in the 1990s for intractable pediatric epilepsy. Today, KD is an established therapy for drug-resistant epilepsy, with seizure reduction rates exceeding 50% in many patients.
The diet also helps people with alcohol use disorder (AUD). Acute alcohol intake shifts brain energetics from glucose to acetate, an alcohol metabolite. In individuals with AUD, low brain glucose and high acetate metabolism persist beyond acute intoxication. This nutritional state may contribute to alcohol withdrawal signs and symptoms, as well as to alcohol craving, and relapses. The KD reduces neural hyperexcitability and oxidative stress, abetting detoxification.
Interest in KD extends to psychiatry, where metabolic dysfunction increasingly appears central to mental illness. Conditions such as schizophrenia, bipolar disorder, major depression, and AUD share features with epilepsy, including disrupted neural networks, impaired mitochondrial function, glucose hypometabolism, and chronic low-grade inflammation.
The KD restores metabolic flexibility and reduces neuroinflammation, correcting some underlying biology of multiple disorders. Ketones act as signaling agents, modulating gene expression, oxidative stress responses, and neurotransmitter balance.
Schizophrenia
Mitochondrial dysfunction and abnormal glucose metabolism are well-documented in schizophrenia. KD may normalize brain energy metabolism, reducing inflammatory cytokine activity that worsens psychotic symptoms.
Functional imaging studies show reduced cerebral glucose utilization, particularly in prefrontal regions, along with oxidative stress and impaired GABA–glutamate balance. Early clinical reports suggest KD may alleviate metabolic and psychiatric symptoms. In a trial of individuals with schizophrenia or bipolar disorder and metabolic syndrome, a four-month ketogenic intervention led to significant improvements in metabolic markers and symptom severity. Case reports described improved mood, reduced psychosis, and better cognitive clarity—though sample sizes were small.
Depression
KD may also have antidepressant properties. A recent meta-analysis of 10 randomized controlled trials found a moderate reduction in depressive symptoms among KD participants versus controls. Proposed mechanisms include reduced neuroinflammation, improved mitochondrial efficiency, stabilization of neurotransmitter synthesis (notably serotonin and GABA), and normalization of hypothalamic–pituitary–adrenal axis activity.
Addiction
Addiction medicine is one of the most promising fields for KD application. SUDs—whether related to alcohol, opioids, or stimulants—are disorders of brain reward circuitry and metabolic regulation. Chronic substance use disrupts glucose metabolism, promotes oxidative stress, depletes micronutrients, and alters neurotransmitters. Preclinical models have demonstrated that the ketogenic diet by itself can reduce alcohol self-administration and alcohol withdrawal. The changes persist into early recovery, decreasing withdrawal severity, mood instability, and relapse risk.
Ketogenic Diet Essential Reads
AUD impairs brain glucose metabolism, damages hepatic mitochondria, and triggers systemic inflammation. Chronic alcohol consumption leads to thiamine, folate, and zinc deficiencies, worsening neuronal energy deficits. Davis et al. (2021) reported that KD significantly reduced AUD withdrawal symptoms during detoxification. Patients with AUD on KD reported lower alcohol craving. In human studies, researchers showed that the diet led to a significant decrease in the need for benzodiazepines to manage acute alcohol withdrawal, as well as to reduced alcohol craving when exposed to alcohol cues.
Opioid use disorder (OUD) suppresses appetite, slows gastrointestinal motility, and causes marked micronutrient depletion (B-vitamins, zinc, iron, selenium). The deficiencies exacerbate fatigue, anemia, and immune dysfunction. Pilot studies in OUD indicate that KD may attenuate cravings, enhance cognitive flexibility, and stabilize mood during detoxification. Likely mechanisms include modulation of dopamine and glutamate signaling and anti-inflammatory neuroprotection. Case-based reports describe sustained abstinence when KD is combined with pharmacotherapy (buprenorphine) and micronutrient repletion.
Stimulant abuse (cocaine, methamphetamine) induces severe appetite suppression and depletes antioxidant stores of vitamin C and B-complex vitamins. Individuals entering recovery often present with significant metabolic instability and malnutrition, which can perpetuate cravings, hindering recovery. Addressing the nutrient deficits through nutritional rehabilitation may improve outcomes during withdrawal and recovery.
Case reports describe reduced stimulant craving and improved mood stability in individuals adopting KD. The proposed mechanisms include stabilization of blood glucose, reduced neuroinflammatory signaling, and improved mitochondrial efficiency.
Nutritional Rehabilitation and Relapse Prevention
People with SUDs have vitamin, mineral, and other nutritional deficiencies, including deficiencies of A, B, C, D, and E vitamins, as well as of minerals such as zinc, magnesium, potassium, selenium; and iron, often leading to iron-deficiency anemia. Nutrition is typically an afterthought in addiction treatment, despite strong evidence that substance use causes serious deficiencies. This must change.
AUD damages hepatic and intestinal absorption of fat-soluble vitamins (A, D, E, K) and impairs amino acid metabolism. OUD patients commonly show deficiencies in B vitamins, zinc, and selenium, while stimulant users may be profoundly thin and deficient in many vitamins. The nutrient deficits compromise overall recovery potential.
A structured diet, such as KD, can provide a metabolic scaffold during early recovery. By maintaining stable glucose and insulin levels and providing an alternative fuel source to the brain, KD may blunt cravings and mood instability. Ketone bodies may also reduce post-acute withdrawal symptoms (PAWS), a period marked by anxiety, irritability, and dysphoria, often triggering relapse.
Clinical Challenges
Despite the promise, KD poses practical challenges. Adherence to the diet can be challenging due to its restrictiveness, and it requires medical supervision. Many with SUD experience social instability and erratic eating patterns, complicating long-term adherence. Modified or cyclical ketogenic plans, or hybrid diets combining low-glycemic principles with partial ketosis, may improve feasibility in clinical settings.
Conclusion
Nutritional assessment and therapies are essential to consider in SUDs. Integrating nutritional rehabilitation early in recovery could transform substance use disorder treatment. In addition, utilizing KD can improve detoxification and long-term outcomes.
KD is an underutilized tool bridging neurology, psychiatry, and addiction medicine. Increasing evidence suggests that a ketogenic diet reduces alcohol withdrawal severity and craving in individuals with AUD by shifting brain energetics from glucose to ketones.
While more rigorous clinical trials are needed—especially in addiction medicine—existing evidence supports KD as a promising adjunct in treatment.