Ketogenic Diet May Improve Symptoms of Depression, But Not Anxiety

Depressive symptoms among adults may modestly improve with a ketogenic diet, but there is inconclusive evidence about its effect on anxiety, according to study results published in JAMA Psychiatry.

Investigators evaluated the potential association between ketogenic diets (<26% energy from carbohydrates or <50 g/day) and psychiatric symptom severity, including those from anxiety and depression.

Through a systematic review and meta-analysis, the investigators searched medical databases for peer-reviewed studies in English that were randomized clinical trials (RCTs), quasi-experimental (QSE) studies, cohort studies, cross-sectional studies, and case reports.

Participants were adults aged at least 18 years using a ketogenic diet (high in fat, low in carbohydrates, moderate in protein; modified Atkins diet), evaluated with validated psychiatric scales.

No significant associations were found for anxiety in randomized clinical trials.

Overall, 50 studies (n=41,718 participants; 54.3% women) were identified, with 18 studies enrolling 100% women participants; 22 enrolling participants with formal psychiatric diagnoses; and 33 focusing on nonpsychiatric populations, A total of 15 countries (primarily the United States) were included in analysis.

A significant association was found between ketogenic diet for depressive symptoms and control diets in 10 RCTs (n=631; standardized mean difference [SMD], -0.48; 95% CI, -0.87 to -0.10), during comparisons between ketone monitoring vs without ketone monitoring (SMD, -0.88 vs -0.04, respectively). Investigators noted that there was a significant difference between ketone monitoring and without ketone monitoring (-0.84; 95%; CI, -1.50 to -0.18; P =.01) and stronger associations in studies using nonhigh-carbohydrate comparators, very low-carbohydrate interventions, and among participants without obesity.

No significant association was found with anxiety in 9 RCTs (n=672; SMD, -0.03; 95% CI, -0.18 to 0.12). A consistent association was noted in 9 QSE studies on depressive symptoms (standardized mean change using change scores [SMCCs], -0.66; 95% CI, -0.83 to -0.50), with similar results in 6 QSE studies on anxiety (SMCC, -0.58; 95% CI, -0.81 to -0.36). A consistent medium association was noted in studies with ketone monitoring (SMCC, -0.62; 95% CI, -0.80 to -0.43), and a larger association in studies without ketone monitoring (SMCC, -0.88; 95% CI, -1.51 to -0.25).

Study limitations include significant heterogeneity in sample size, intervention length, and design quality. Additionally, most studies were small with dropout and adverse event reporting inconsistency, as well as the study design failing to establish causality. 

“… K[etogenic diet]s were associated with small to moderate improvements in depressive symptoms in randomized clinical trials and with larger improvements in quasi-experimental studies,” the investigators concluded. “No significant associations were found for anxiety in randomized clinical trials.”

Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.