Table 3.
Studies describing therapeutic effects of the ketogenic diet in bipolar disorder.
| Author(s), Year | Study Design | Number of Participants (Intervention/ Control) |
Range Age of Participants (Years) | Dietary Intervention/ Assessment of Ketosis |
Control Intervention |
Duration | Outcome Measures | Main Findings |
|---|---|---|---|---|---|---|---|---|
| Phelps et al., 2013 [114] | Two case studies | I: 2 (F) | 69 and 30 | KD, 8% carbohydrates, 22% protein, 70% fat (second case), the urine ketone strip test (first case) | none | 2 years, 3 years | Patients’ and physicians’ observations | significant subjective reduction in symptoms, ↓the amount of taken medications, ↓depressive symptoms mood stabilization, ↑calm and confidence, comfort |
| Chmiel et al., 2022 [115] | Case study | I: 1 (M) | 32 | KD; 5% carbohydrate, 15% protein, 80% fat; ≥5040 kJ, <30 g carbohydrates per day; cyclic one-day fast introduced every 7–10 days, blood concentration of β-hydroxybutyrate | none | 2 years | Body mass index (BMI), blood: CBC, lipid profile, glucose, liver tests, creatinine, uric acid | mood stabilization, elimination of anxiety, shorter and milder depressive states till complete remission, ↑mood, ↑energy, ↑cognitive functions and concentration, ↑periods of total remission of symptoms, ↓amount of taken medications, ↑HDL, ↓triglycerides |
| Needham et al., 2023 [113] | Pilot study | I: 27 | 26–54 | A modified KD, 60–75% fat, 5–7% carbohydrates, additionally calories from protein, blood ketones | none | 6–8 weeks | Medical and medication history, blood pressure and body mass index (BMI), Affective Lability Scale 18, Beck’s Depression Inventory, Young Mania Rating Scale, Within Trial Resource Use Questionnaire, EuroQol 5D quality of life instrument and the Work Productivity and Activity Impairment Questionnaire (tailored), Fasting venepuncture and MR brain scans, measurement of glucose and ketones on a KetoMojo device, daily ecological momentary assessments (EMAs) of anxiety, mood, energy, impulsivity and speed of thought, Visual Analogue Scale (VAS) | ↓body weight, normalization of total cholesterol, LDL, and triglyceride levels EQ5D-5L at baseline and follow-up, respectively, were: mobility, 90 and 85%; self-care, 90 and 85%; usual activities, 65 and 55%; pain and discomfort, 45 and 45%; and anxiety and depression, 45 and 50% The visual analogue scale (VAS) utility scores at baseline and follow up were 66.7 and 64.2, ↓mean expenditure, ↑mean productivity loss |
| Sethi et al., 2024 [62] |
Pilot study | I: 16 | 18–75 | KD, 10% carbohydrate, 30% protein, 60% fat; ≥5040 kJ, <20 g carbohydrates per day; blood ketone meter at least once a week | none | 4 months | Generalized Anxiety Disorder (GAD–7), Patient Health Questionnaire Depression Scale (PHQ–9), Pittsburgh Sleep Quality Index (PSQI), Clinical Mood Monitoring Forms (CMF), Clinical Global Impression–Schizophrenia (CGI–SCH) Scale, Global Assessment of Functioning (GAF), Manchester Short Assessment of Quality of Life (MANSA), Brief Psychiatric Rating Scale (BPRS) for Schizophrenia and screening for suicidality; HbA1c, fatty acid profile, hsCRP, HOMA-IR, HOMA2-IR, advanced lipid testing, body weight, blood pressure, HR, waist circumference, body composition analysis |
improvement in CGI scale: severity of mental illness showed improvement of >1 point in 69% of participants, ↑proportion of participants who were in the recovery state at baseline *, ↑sleep quality *, ↓anxiety *, ↓depressive symptoms, ↑life quality and satisfaction *, ↓body weight, waist and circumference and systolic blood pressure and FMI and BMI * ↓visceral adipose tissue, HbA1c, triglycerides, HOMA-IR * |
F—females; M—males; KD—ketogenic diet; HbA1c—glycosylated hemoglobin; HOMA-IR—the homeostasis model assessment-estimated insulin resistance; hs-CRP—high sensitivity C—reactive protein; HR—heart rate; FMI—fat mass index; BMI—body mass index; * all participants (patients with SZ and BD analyzed as one group); I—intervention; C—control.