Sarah Rice BSc. (Hons), MCOptom (UK), MHP, NNP
Ketogenic diets for neurological conditions have been extensively researched since the 1920s, when they were first used to treat epilepsy (1). Ketogenic metabolism alters the brain’s energy metabolism to favor ketones over glucose, which drives other beneficial neurometabolic pathways that promote (1, 2):
- Reduced inflammation and inflammatory signaling
- Reduced oxidative stress
- Epigenetic regulation by reducing DNA methylation status
- Altered microbiome and gut-brain signaling
- Regulation of neurotransmitters
Recent studies have highlighted the potential role of ketogenic metabolic therapies in neonatal and pediatric neurological conditions, which provide a framework for further research.
Neonatal hypoxic-ischemic encephalopathy (HE) is a major cause of neonatal mortality and neurodevelopmental disability worldwide. A recent revision examined the potential of ketogenic strategies to mitigate key features of HIE, which include excitotoxicity, neuroinflammation, oxidative stress, and bioenergetic crisis (3). Specifically, ketogenic therapy may be beneficial by increasing the efficiency of ATP production, reducing oxidative damage and reactive oxygen species (ROS) production, reducing glutamate (excitotoxicity), reducing neuroinflammation, and promoting epigenetic modulation. These features combine to improve network stability and may be neuroprotective. Based on data from neonates receiving ketogenic therapy for epilepsy, this review argues that a ketogenic intervention for neonates with HIE could be safe and feasible, although currently available evidence does not support its use for this condition (3). Studies demonstrate the benefits of ketogenic therapies in infants with refractory epilepsies, including those with hypoxic-ischemic injury, so there may be a role for intervention in this setting in specialized centers. Although preclinical work suggests the potential of ketogenic therapies for neurotrauma, further human studies are urgently needed (4, 5).
A case study from D’Amato et al. (2026) describes the use of a ketogenic diet in the neonatal intensive care unit for a premature baby (31 weeks) with mitochondrial DNA depletion syndrome Type 13 (MTDPS13) (6). This syndrome causes severe lactic acidosis, and a ketogenic diet can improve mitochondrial bioenergetics and reduce lactate. The ketogenic diet was administered gradually (initial ratio 0.9–1:1 to 1:1) via parenteral and nasogastric routes plus high-dose vitamins. In this case study, ketogenic intervention rapidly reduced lactate, corrected acidosis, allowed bicarbonate discontinuation, and supported growth and hemodynamic stability. The study reports that the diet was feasible in preterm ICU patients with suspected mitochondrial disease, but requires close monitoring of metabolism, nutrition, and organs (6).
Research suggests that ketogenic therapies used for epilepsy and mitochondrial disorders may also be relevant to autism spectrum disorders (ASD) due to shared mechanistic factors between these conditions. ASD and epilepsy they share common causes that lead to the occurrence of both conditions together, including genetic factors (such as gene mutations and variations in chromosome numbers) and environmental influences (such as exposure to sodium valproate during pregnancy, diet and the mother’s immune response). Key processes affected by these co-occurring conditions include (7):
- Excitatory/inhibitory neurotransmitter imbalance (GABAergic and glutamatergic systems)
- Abnormalities of the brain network (especially involving glial cells and astrocytes)
- Immune dysregulation (may involve the gut-brain axis)
In a recent case study Wang et al. (2026) evaluated the efficacy and safety of a ketogenic diet in a young boy with autism spectrum disorder associated with a PTEN mutation (8). PTEN mutations lead to aberrant signaling in the PI3K/AKT/mTOR pathway, affect synaptic plasticity, and have a strong association with ASD. A ketogenic metabolism can modify this pathway and reduce neuroinflammation, offering a nutritional approach to a treatment-resistant phenotype. In the case documented, a 7-year-old male received a modified Atkins ketogenic diet (60% fat, 30% protein, and 10% carbohydrate) with dietary adjustments targeting glucose (goal 3.9–5 mmol/L) and ketone (goal 2–5 mmol/L) measurements in the desired range (8). Stable readings (mean glucose: 4.4 mmol/L, ketones: 2.4 mmol/L) were achieved with no adverse effects and biomarkers remained in the normal range. By day 6, there were improvements in emotional stability and other stereotyped behaviors (eg, vocal tics), as well as better sleep. At 11 days, there was improved attention and task completion. Improvements were continuous and included fine motor skills, new gross motor skills (rope), puzzle completion, expanded verbal communication, eye contact, and ability to follow directions. Other improvements included metabolic (reduced markers of inflammation), stool, and EEG normalization (from borderline to typical standards). A combined ketogenic diet and repetitive transcranial magnetic stimulation (rTMS) reduced hyperarousal behavior compared to rTMS monotherapy (8).
Ketogenic diets sometimes raise concerns about nutritional adequacy. In general, care should be taken to ensure that any nutritional intervention is well designed while seeking to provide a therapeutic effect. In some cases, particularly when protein intake needs to be managed to promote higher levels of ketosis, increased vigilance may be required and supplementation may be considered. At the same time, different nutritional protocols within the ketogenic spectrum can offer greater dietary flexibility while maintaining therapeutic effect, such as the modified Atkins diet, which allows for higher carbohydrate intake while achieving ketosis and providing essential nutrients.
A recent study examined the nutritional adequacy of a ketogenic diet for pediatric epilepsy (9). They found that a well-designed modified Atkins diet (carbohydrates 2-5% of total energy intake, fat 65-75%, protein 20-25%) improved the diet compared to baseline, increasing intake of fiber, monounsaturated fat, and omega-3 essential fatty acids while maintaining ketosis at a therapeutic level (5mmol/5). They recommend a “foods first” ketogenic approach, and the following foods feature heavily in their nutrient recommendations table (9):
- Eggs
- Meat
- Fish/oily fish/shellfish
- Green leafy vegetables
- Nuts/seeds
- Avocado
- Cruciferous vegetables
- Tofu (a good option for vegetarians)
- Berries
These findings are supported by long-term data (5 years) studying the nutritional status of children with GLUT1 deficiency treated with a classical ketogenic diet. They found no evidence of negative effects on nutritional status (10).
It should be noted that the ketogenic diet for neurological conditions (often including psychiatric conditions) differs from ketogenic or low-carb dietary interventions for children with metabolic conditions such as obesity and type 2 diabetes (11, 12). For metabolic conditions, a more flexible reduced-carb approach may be sufficient. Removing highly processed foods and focusing on nutrient-dense whole foods may be sufficient to achieve therapeutic goals.
Ketogenic metabolic therapy for pediatric neurological, neurodevelopmental, and neuropsychiatric conditions is promising but remains poorly studied at present. Nutritional ketosis and its associated metabolic effects have a strong basis in preclinical and early human studies. Combined with over 100 years of ketogenic diet research for epilepsy, these findings should urgently advance research into ketogenic metabolic therapies for children with neurological and neuropsychiatric conditions.
- Lin, K.-L., Lin, J.-J. and Wang, H.-S. (2020) ‘Application of ketogenic diets for pediatric neurocritical care’, Biomedical Journal, 43(3), p 218. Available at: https://doi.org/10.1016/j.bj.2020.02.002.
- Wang, Y. et al. (2025) ‘Ketogenic diet and neurological diseases’, Precision Nutrition, 4(2), pp. e00109. Available in: https://doi.org/10.1097/PN9.0000000000000109.
- Falsaperla, R. et al. (2026) ‘Ketogenic Strategies in Neonatal Hypoxic–Ischemic Encephalopathy—The Road to Opening Up: A Scoping Review’, Neurology International, 18(2), p 24. Available at: https://doi.org/10.3390/neurolint18020024.
- Lin, C. et al. (2023) ‘Ketogenic diet and β-hydroxybutyrate alleviate ischemic brain injury in mice through an IRAKM-dependent pathway’, European Journal of Pharmacology, 955, pp. 175933. Available at: https://doi.org/10.1016/j.ejphar.2023.175933.
- Rauk, Z. et al. (2026) ‘β-Hydroxybutyrate Modulates Neuroinflammatory Responses and Astrocyte Reactivity in an In Vitro Traumatic Brain Model’, Molecular Neurobiology, 63(1), p 490. Available at: https://doi.org/10.1007/s12035-026-05759-2.
- D’Amato, G. et al. (2026) ‘The Ketogenic Diet in the Neonatal Intensive Care Setting: The Case of a Preterm Newborn With Mitochondrial DNA Depletion Syndrome Type 13 (MTDPS13)’, Case Reports in Genetics, 2026, pp. 6492770. Available at: https://doi.org/10.1155/crig/6492770.
- Shan, M. et al. (2026) ‘Autism Spectrum Disorder Comorbidity with Epilepsy: Etiology, Mechanism and Treatment’, Neuroregeneration Research [Preprint]. Available in: https://doi.org/10.4103/NRR.NRR-D-25-00734.
- Wang, Y. et al. (2026) ‘A Case Report: Effects of a ketogenic diet on PTEN mutation-associated autism spectrum disorder’, Frontiers in Nutrition, 13. Available at: https://doi.org/10.3389/fnut.2026.1721018.
- Tsang, E. et al. (2025) ‘The nutritional adequacy of the ketogenic diet in pediatric epilepsy: detailed nutrient analysis and dietary recommendations’, Clinical nutrition ESPEN, pp. S2405-4577(25)01775–9. Available in: https://doi.org/10.1016/j.clnesp.2025.07.023.
- De Amicis, R. et al. (2023) ‘Long-term follow-up of nutritional status in children with GLUT1 deficiency syndrome treated with a classical ketogenic diet: a 5-year prospective study’, Frontiers in Nutrition, 10, pp. 1148960. Available at: https://doi.org/10.3389/fnut.2023.1148960.
- Calkins, M. et al. (2024) ‘Carbohydrate reduction for metabolic disease differs from the ketogenic diet for epilepsy’, Journal of Metabolic Health, 7(1), p 4. Available at: https://doi.org/10.4102/jmh.v7i1.95.
- Cucuzzella, M. et al. (2024) ‘Beyond obesity and overweight: the clinical assessment and treatment of excess body fat in children: Part 2 – the low-carbohydrate diet prescription as a first approach’, Current Obesity Reports [Preprint]. Available in: https://doi.org/10.1007/s13679-024-00564-1.
