Table Info

Table 2.

Role of the ketogenic diets therapy in several mental disorders

Authors/Country	Intervention characteristics	Instruments	Outcomes
Calabrese et al. [62]/USA	Depression: N = 3 adults (32–36 years old) with MDD and GAD. Treatment with KD for 12–16 weeks.	GAD-7, PHQ-9.	Two from three patients achieved remission in MDD and GAD within 12 weeks of KD treatment.
Danan et al. [97]/France	Depression, bipolar disorder, and schizophrenia: N = 31 adults. Treatment with KD for 248 days.	HDRS, MADRS, PANSS.	The KD treatment for patients with refractory mental illness was feasible, well-tolerated, and associated with significant improvements in depression and psychosis symptoms.
Adams et al. [98]/USA	Depression: N = 262 adults (21–65 years old) with diabetes type 2. Treatment with carbohydrate restriction diet for 2 years.	CESD	Subclinical depressive symptoms decreased over the first 10 weeks and reductions were maintained out to 2 years with the tested diet.
Garner et al. [99]/United Kingdom	Mood: N = 147 patients (> 18 years old). Treatment with KD for 8 months. Depression and anxiety: N = 276 (> 18 years old). Treatment with KD for 6 months.	BL-VAS, DASS-21.	KD was associated with higher self-reported mental and emotional well-being behaviors, including calmness, alertness and contentedness (improved mood). In addition, individuals who consumed a KD were less anxious and depressed.
Iacovides et al. [100]/South Africa	Mood: N = 11 healthy subjects (mean age 30 years old). Treatment with KD and an isocaloric diet (HCLF) for 3 weeks.	Cogstate, PSQI.	The results suggest that 3 weeks of sustained nutritional ketosis had no effect on cognitive performance, mood, or subjective sleep quality.
Needham et al. [103]/United Kingdom	Bipolar disorder: N = 20 euthymic individuals with bipolar disorder (18–70 years old). Treatment with KD for 6 weeks.	BDI, YMRS, ALS, WTRUQ.	The adverse events in the majority of participants were generally mild and modifiable.
Sethi et al. [104]/USA	Bipolar disorder and schizophrenia: N = 23 (18–75 years old). Treatment with KD for 4 months.	BPRSS, CGI.	Participants with schizophrenia showed a reduction in BPRSS, and the severity of CGI improved.
Longhitano et al. [107]/Australia	Bipolar disorder, schizoaffective disorder, and schizophrenia: N = 100 (> 18 years old). Treatment with modified KD for 14 weeks.	PANSS, BDI, YMRS, ALS, CCB.	The modified KD therapy was well tolerated and improved psychiatric and metabolic outcomes. The authors suggested a correlation between the levels of ketones and metabolic, cognitive and psychiatric improvements.
Palmer et al. [108]/USA	Schizophrenia: N = 2 adults (39 and 82 years old). Treatment with KD for 2 weeks.	PANSS	The cases suggest that KD may be an effective treatment for schizophrenia and for restoring function in life.
Lee et al. [111]/USA	Autism: N = 15 children with ASD (2–17 years old). Treatment with a modified KD (gluten free) supplemented with MCT for 3 months.	ADOS-2, CARS.	The modified diet is a potentially beneficial treatment tool to improve the features of ASD.
Żarnowska et al. [112]/Poland	Autism: N = 1 child (6 years old). Treatment with KD for 16 months.	WISC-R, CARS.	KD improved the behavior and intellect of the subject.
Tidman et al. [113]/USA	Parkinson: N = 1 PD patient (53 years old). Treatment with KD for 24 weeks.	CESDR, PAS, UPDRS.	KD results in the elevation of blood ketones that provide an enhanced mood, motivation and sleep quality, reduced levels of anxiety, and improved cognitive functions while reducing PD symptoms.
Phillips et al. [114]/New Zealand	Parkinson: N = 38 PD patients (40–75 years old). Treatment with KD or low-fat KD for 8 weeks.	UPDRS, MoCA.	Both diet groups significantly improved motor and non-motor symptoms; however, the KD group showed greater improvements in non-motor symptoms.
Neth et al. [115]/USA	Alzheimer: N = 20 AD patients (11 with subjective memory complaints and 9 with mild cognitive impairment). Treatment with modified Mediterranean-KD (MMKD) for 6 weeks.	SMC, MRI.	All participants improved metabolic indices following MMKD. This diet has been associated with decreased tau and it is adequate in the prevention of cognitive decline.
Ota et al. [116]/Japan	Alzheimer: N = 20 AD patients (mean age 73.4 years). Treatment with MCT for 12 weeks.	MMSE, ADAS-Cog.	Diet produced significant improvement in verbal memory and processing speed in AD patients.
Phillips et al. [117]/New Zealand	Alzheimer: N = 21 hospitalized patients with AD (mean age 73.4 years old). Treatment with modified KD or low-fat KD for 10 weeks.	ACE, QoL-AD, ADCS-ADL.	AD patients who consumed modified KD increased ADCS-AD and QoL-AD scores.
Brandt et al. [118]/USA	Alzheimer: N = 9 patients with AD. Treatment with MAD for 12 weeks.	MCS	MAD participants increased MCS scores, enhanced episodic memory, and patient-reported vitality in very early AD.
Henderson et al. [119]/USA	Alzheimer: N = 413 mild-to-moderate AD patients. Treatment with AC-1204 (caprylic triglyceride) for 24 weeks.	ADAS-Cog, ADCS-ADL.	The formulation AC-1204 (caprylic triglyceride) failed to improve cognition or functional ability in AD patients.

KD: ketogenic diet; MCT: medium-chain triglyceride; MAD: modified Atkins diet; MDD: major depression disorder; GAD: generalized anxiety disorder; ASD: autism spectrum disorder; PD: Parkinson’s disease; AD: Alzheimer’s disease; ACE: Addenbrookes Cognitive Examination; ADAS-Cog: Alzheimer’s disease Assessment Scale-Cognitive Subscale; ADCS-ADL: Alzheimer’s disease Cooperative Study-Activities of Daily Living Inventory; ADOS-2: Austism Diagnostic Observation Schedule-2; ALS: Affective Lability Scale; BDI: Beck’s Depression Inventory; BL-VAS: Bond-Lader Visual Analog Scales; BPRSS: Brief Psychiatric Rating Scale Scores; CARS: Childhood Autism Rating Scale; CCB: Cambridge Cognitive Battery; CESD: Center for Epidemiologic Studies Depression Scale; CESDR: Center for Epidemiologic Studies Depression Scale-Revised; CGI: Overall Clinical Global Impression; Cogstate: Psychological Computer-based Test Battery; DASS-21: Depressive Anxiety Stress Scale-21; GAD-7: Generalized Anxiety Disorder Scale-7; HDRS: Hamilton Depression Rating Scale; MADRS: Montgomery-Asberg Depression Rating Scale; MCS: Memory Composite Score; MMSE: Mini-Mental State Examination; MoCA: Montreal Cognitive Assessment; MRI: magnetic resonance imaging; PANSS: Positive and Negative Syndrome Scale; PAS: Parkinson’s Anxiety Scale; PHQ-9: Patient Health Questionnaire-9; PSQI: Pittsburg Sleep Quality Index; QoL-AD: Quality of Life in Alzheimer’s disease; SMC: Cognitive Change Index; UPRS: United Parkinson’s Disease Rating Scale; WISC-R: Wechsler Intelligence Scale for Children-Revised; WTRUQ: Within Trial Resource Use Questionnaire; YMRS: Young Mania Rating Scale

Declarations

Author contributions

ABR: Conceptualization, Writing—original draft, Writing—review & editing, Supervision. JJB: Conceptualization, Investigation, Writing—original draft. Both authors read and approved the submitted version.

Conflicts of interest

Both authors declare that they have no conflicts of interest.

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