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Researchers led by St Michael’s Hospital in Toronto report that ketogenic diets are associated with modest reductions in depressive symptoms in adults, while evidence for anxiety remains uncertain.
Major depressive disorder, bipolar disorder, and schizophrenia have each been linked to mitochondrial impairment, insulin resistance, cerebral glucose hypometabolism, and systemic inflammation.
Ketogenic diets, high in fat, moderate in proteins and very low in carbohydrates, entered clinical medicine a century ago as a nonpharmacologic option for refractory epilepsy.
Sustained carbohydrate restriction was discovered to shift the brain’s primary fuel source from glucose to ketone bodies such as beta-hydroxybutyrate, acetoacetate, and acetone. Switching is known to have influences on mitochondrial function, oxidative stress, and inflammatory signaling.
Previous reports have described potential effects on gamma-aminobutyric acid and glutamate signaling, gut microbiota, and neural network stability, as well as overlaps with the pharmacodynamics of mood stabilizers.
Preliminary clinical work and case reports have suggested improvements in mood, anxiety, cognition, weight, and quality of life, alongside safety concerns for specific groups such as people with mitochondrial DNA deletions or those receiving multiple medications.
In the study, “Ketogenic Diets and Depression and Anxiety,” published in JAMA Psychiatry, researchers conducted a systematic review and meta-analysis to assess the associations between ketogenic diets and mental health outcomes in adults, with a focus on depressive and anxiety symptoms.
Across 50 included studies, 41,718 participants aged 18 to 70 years contributed data from 15 countries, with 23 studies conducted in the US.
Investigators drew on both psychiatric and nonpsychiatric populations, including individuals with major depressive disorder, bipolar disorder, schizophrenia, generalized anxiety disorder, posttraumatic stress disorder, and medical conditions such as obesity. Mental health outcomes were restricted to those measured with validated psychiatric scales, including instruments such as the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7.
Study types included 14 randomized clinical trials, 17 quasi-experimental studies, five analytical cross-sectional studies, six case series, and eight case reports. Publications spanned 1965 to 2025, with a marked increase in output from 2019 and a peak in 2024. Depressive symptoms formed the most frequently evaluated domain in 41 studies, while 29 studies assessed anxiety symptoms. Twenty-two studies enrolled participants with formal psychiatric diagnoses, and 33 focused on nonpsychiatric populations in which mental health outcomes were often secondary endpoints.
Depressive symptom results
Randomized clinical trials on depressive symptoms included 10 studies with 631 participants. Pooled analysis produced a standardized mean difference of -0.48, indicating a small to medium association favoring ketogenic diets over control diets.
Studies that used biochemical ketone monitoring showed a larger association with depressive symptom improvement, with a standardized mean difference of -0.88. Trials without ketone monitoring showed a small and nonsignificant association. Subgroup comparison yielded a difference of -0.84, indicating that ketone monitoring appeared to modify the observed association.
When trials were grouped by presence of a high-carbohydrate comparator diet, studies without such comparators showed a large and significant association with depressive symptom improvement (standardized mean difference, -1.49) whereas trials with high-carbohydrate comparator diets showed no significant association. The difference in standardized mean differences between trials without and with high-carbohydrate comparators was -1.37.
Participant’s obesity status also appeared relevant. Among nonobese participants, pooled trials showed a large and statistically significant association (standardized mean difference, -0.88), while among obese participants, the association was small and nonsignificant at -0.11.
Intervention intensity mattered as well. Very low-carbohydrate diets, defined as 10% of energy from carbohydrates, formed one subgroup, while low-carbohydrate diets provided 11%-20% of energy from carbohydrates.
Very low-carbohydrate diets showed a significantly large association with depressive symptom improvement (standardized mean difference, -0.79), while low-carbohydrate diets showed a nonsignificant association of -0.05. The difference between these subgroups was -0.75. Stratification by duration into four to six weeks, eight to nine weeks, and 10 weeks or longer did not yield significant subgroup differences.
Quasi-experimental studies reinforced the depression signal. Nine such studies showed a pooled standardized mean change of -0.66, interpreted by the authors as a medium association. Studies with ketone monitoring reported an association of -0.62, while those without monitoring reported -0.88, although subgroup differences did not reach statistical significance.
Mixed picture for anxiety and other symptoms
Randomized clinical trials that focused on anxiety included nine studies and 672 participants. Pooled analysis yielded a standardized mean difference of -0.03, interpreted as no significant association between ketogenic diets and anxiety symptom change relative to comparator diets.
Subgroup analyses based on ketone monitoring, low-fat comparators, obesity status, carbohydrate restriction level, and intervention duration did not identify consistent moderators, and neither subgroup in the high-carbohydrate comparator analysis showed significant benefit.
Quasi-experimental data painted a somewhat different picture. Six studies reported anxiety outcomes, with a pooled standardized mean change of -0.58, suggesting medium within-group improvement in anxiety symptoms over time during ketogenic interventions. Subgroup analyses for anxiety did not show significant differences related to ketone monitoring, neurological disorder status, other comorbidities, or intervention length.
Study authors noted that depressive and anxiety symptoms tended to improve across diverse populations, including major depressive disorder, generalized anxiety disorder, posttraumatic stress disorder, schizophrenia, bipolar disorder, and nonpsychiatric medical groups.
Reports from case series and case reports described reductions in psychotic symptoms and mood stabilization in people with schizophrenia or bipolar spectrum disorders who followed ketogenic or closely related regimens. A feasibility trial in posttraumatic stress disorder suggested meaningful symptom reductions, although authors called for further trials in trauma-related conditions.
Cautious conclusions for clinical interpretation
Study authors conclude that ketogenic diets may confer therapeutic benefits for depressive symptoms, with results stronger when nutritional ketosis is biochemically verified, although associations for anxiety remain preliminary in randomized trials.
Improvements in quasi-experimental settings appeared larger but may reflect both closer adherence to ketogenic protocols and greater susceptibility to design-related bias.
Generalizability, in the authors’ view, is constrained by variation in diet composition, comparator regimens, adherence support, symptom measures, and trial quality, along with short follow-up in many reports. Authors caution that pooled estimates do not represent a single uniform effect or proof that ketogenic diets cause improvement, and they note that symptom change is unlikely to be consistent across all patients.
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More information:
Reinhard Janssen-Aguilar et al, Ketogenic Diets and Depression and Anxiety, JAMA Psychiatry (2025). DOI: 10.1001/jamapsychiatry.2025.3261
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Keto diet associated with reduced depressive symptoms, anxiety results remain mixed (2025, November 17)
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