Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.

To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.

Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.

Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).

These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.

Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date.

To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.

Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198.

Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication).

The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

Members of online bipolar disorder forums often report experiences of mood-stabilisation on the ketogenic diet, which has traditionally been used in the treatment of epilepsy. We examined the nature and extent of such reports.

To investigate associations between a ketogenic diet and mood stabilisation among individuals with bipolar disorder.

We undertook an observational analytic study of free-text comments in online forums about mood effects of dietary interventions (ketogenic, omega-3 enriched or vegetarian) classified by a priori categories of change in mood stabilisation in 274 people with bipolar disorder.

There were 141 (85.5%) free-text comments on ketogenic diets that reported a positive impact on mood stabilisation. Reports of significant mood stabilisation or remission of symptoms over a period were substantially higher for a ketogenic diet than for other diets (93/165, 56.4%, 95% CI 48.4–64.1) v. 14/94, 14.9%, 95% CI 8.4–23.7), odds ratio 7.4, 95% CI 3.8–14.1, P < 0.0001), many with detailed reports of the improvements experienced and several lasting for extended periods (months to years). Other reported associations included fewer episodes of depression (in 41.2%, 95% CI 30.6–52.4 of individuals); improved clarity of thought and speech (28.2%, 95% CI 19.0–39.0); increased energy (25.9, 95% CI 17.0–36.5); and weight loss (25.9%, 95% CI 17.0–36.5).

Despite the inherent limitations of the observational data based on self-reports posted online, the association strength and reports of sustained benefit support a hypothesis of a ketogenic diet being associated with beneficial effects on mood stabilisation. Caution should be exercised in interpreting this data until a controlled trial can be carried out to examine this hypothesis. These preliminary observations are generally consistent with a mitochondrial dysfunction component to bipolar disorder aetiology with ketones bypassing a block between glycolysis and the tricarboxylic acid cycle.

None.