Sarah Rice BSc. (Hons), MCOptom (UK), MHP, NNP

Introduction

Ketogenic diets for neurological conditions have been extensively researched since the 1920s, when they were first used in the treatment of epilepsy (1). Ketogenic metabolism alters brain energy metabolism to favour ketones over glucose, which drives other beneficial neurometabolic pathways that promote (1, 2):

• Reduced inflammation and inflammatory signalling
• Reduced oxidative stress
• Epigenetic regulation by reducing DNA methylation status
• Altered microbiome and gut-brain signalling
• Neurotransmitter regulation

Recent studies have highlighted the potential role of ketogenic metabolic therapies in neonatal and paediatric neurological conditions, which provide a framework for further research.

Neonatal brain injury: Hypoxic–Ischaemic Encephalopathy

Neonatal Hypoxic-Ischaemic Encephalopathy (HIE) is a significant cause of neonatal mortality and neurodevelopmental disability worldwide. A recent review examined the potential of ketogenic strategies to mitigate key features of HIE, which include excitotoxicity, neuroinflammation, oxidative stress, and bioenergetic crisis (3). In particular, 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 posits that a ketogenic intervention for neonates with HIE could be safe and feasible, though currently the available evidence does not support its use for this condition (3). Studies do demonstrate the benefits of ketogenic therapies in infants with refractory epilepsies, including those with hypoxic–ischaemic injury, so there may be a role for the intervention in this setting in specialised centres. Although preclinical work indicates the potential of ketogenic therapies for neurotrauma, there is an urgent need for further human studies (4, 5).

A ketogenic diet in the neonatal ICU

A case study by D’Amato et al. (2026) describes using a ketogenic diet in the neonatal intensive care unit for a preterm baby (31 weeks) with mitochondrial DNA depletion syndrome Type 13 (MTDPS13) (6). This syndrome causes severe lactic acidosis and a ketogenic diet may 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 the ketogenic intervention rapidly reduced lactate, corrected acidosis, allowed discontinuation of bicarbonate, and supported growth and haemodynamic stability. The study reports that the diet was feasible in preterm NICU patients with suspected mitochondrial disease but requires close metabolic, nutritional, and organ monitoring (6).

Epilepsy and Autism Spectrum Disorder

Research shows that ketogenic therapies used for epilepsy and mitochondrial disorders may also be relevant for autism spectrum disorders (ASD) because of the shared mechanistic factors between these conditions. ASD and epilepsy share common causes that lead to both conditions occurring together, including genetic factors (like 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). Core processes affected by these coexisting conditions include (7):

• Neurotransmitter excitatory/inhibitory imbalance (GABAergic and glutamatergic systems)
• Brain network abnormalities (particularly involving glia cells and astrocytes)
• Immune dysregulation (may include 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 a PTEN mutation-associated autism spectrum disorder (8). PTEN mutations lead to abnormal signalling in the PI3K/AKT/mTOR pathway, impact synaptic plasticity, and have a strong correlation with ASD. A ketogenic metabolism may modulate this pathway and reduce neuroinflammation, offering a nutritional approach in 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% carbohydrates) with diet adjustments targeting glucose (target 3.9–5 mmol/L) and ketone (target 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 without adverse events, and biomarkers remained in the normal range. By day 6, there were improvements in emotional stability and other stereotypical behaviours (e.g., vocal tics), as well as better sleep. At 11 days, there was improved attention and task completion. Improvements were ongoing and included fine motor skills, novel gross motor skills (rope-jumping), puzzle completion, expanded verbal communication, eye contact, and ability to follow instructions. Other improvements included metabolic (decreased inflammatory markers), stool, and electroencephalographic normalisation (from borderline to typical patterns). A combined ketogenic diet and repetitive transcranial magnetic stimulation (rTMS) reduced hyperexcitable behaviour compared to rTMS monotherapy (8).

Nutritional sufficiency

Ketogenic diets sometimes attract concerns regarding nutritional sufficiency. In general, care should be taken to ensure any dietary intervention is well formulated while seeking to deliver 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 supplements can be considered. At the same time, different dietary protocols within the ketogenic spectrum can offer greater diet flexibility while maintaining therapeutic effect, such as the modified Atkins diet, which allows for a higher carbohydrate intake while still achieving ketosis and providing essential nutrients. 

A recent study examined the nutritional sufficiency of a ketogenic diet for paediatric epilepsy (9). They found that a well-formulated modified Atkins diet (carbohydrate 2–5% of total energy intake, fat 65–75%, protein 20–25%) improved the diet compared to baseline by increasing fibre, mono- and polyunsaturated fat, and omega-3 essential fatty acid intake while maintaining ketosis at the therapeutic level (2.5–5.5 mmol/L). They recommend a ‘food first’ ketogenic approach and the following foods feature heavily in their table of nutrient-dense suggestions (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 classic ketogenic diet. They found no evidence of negative effects on nutritional status (10).

It should be noted that the ketogenic diet for neurological conditions (this often includes psychiatric conditions) is distinct from the ketogenic, or carbohydrate-reduced, dietary interventions for children with metabolic conditions like obesity and type 2 diabetes (11, 12). For metabolic conditions, a more flexible reduced-carbohydrate approach may be sufficient; the removal of ultraprocessed foods and a focus on nutrient-dense whole foods can be sufficient to meet therapeutic goals.

Conclusion

Ketogenic metabolic therapy for paediatric neurological, neurodevelopmental, and neuropsychiatric conditions is promising but remains understudied at present. Nutritional ketosis and its associated metabolic effects have a robust base in preclinical and early human studies. Combined with over 100 years of research on the ketogenic diet for epilepsy, these findings should urgently promote research into ketogenic metabolic therapies for children with neurological and neuropsychiatric conditions. 

References

1. 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.
2. Wang, Y. et al. (2025) ‘Ketogenic diet and neurological diseases’, Precision Nutrition, 4(2), p. e00109. Available at: https://doi.org/10.1097/PN9.0000000000000109.
3. 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.
4. Lin, C. et al. (2023) ‘Ketogenic diet and β-Hydroxybutyrate alleviate ischemic brain injury in mice via an IRAKM-dependent pathway’, European Journal of Pharmacology, 955, p. 175933. Available at: https://doi.org/10.1016/j.ejphar.2023.175933.
5. Rauk, Z. et al. (2026) ‘β-hydroxybutyrate Modulates Neuroinflammatory Responses and Astrocyte Reactivity in an In Vitro Model of Traumatic Brain Injury’, Molecular Neurobiology, 63(1), p. 490. Available at: https://doi.org/10.1007/s12035-026-05759-2.
6. 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, p. 6492770. Available at: https://doi.org/10.1155/crig/6492770.
7. Shan, M. et al. (2026) ‘Autism spectrum disorder comorbid with epilepsy: Etiology, mechanism, and therapy’, Neural Regeneration Research [Preprint]. Available at: https://doi.org/10.4103/NRR.NRR-D-25-00734.
8. 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.
9. Tsang, E. et al. (2025) ‘The nutritional adequacy of the ketogenic diet in paediatric epilepsy: detailed nutrient analysis and dietary recommendations’, Clinical nutrition ESPEN, pp. S2405-4577(25)01775–9. Available at: https://doi.org/10.1016/j.clnesp.2025.07.023.
10. De Amicis, R. et al. (2023) ‘Long-term follow-up of nutritional status in children with GLUT1 Deficiency Syndrome treated with classic ketogenic diet: a 5-year prospective study’, Frontiers in Nutrition, 10, p. 1148960. Available at: https://doi.org/10.3389/fnut.2023.1148960.
11. Calkins, M. et al. (2024) ‘Carbohydrate reduction for metabolic disease is distinct from the ketogenic diet for epilepsy’, Journal of Metabolic Health, 7(1), p. 4. Available at: https://doi.org/10.4102/jmh.v7i1.95.
12. Cucuzzella, M. et al. (2024) ‘Beyond Obesity and Overweight: the Clinical Assessment and Treatment of Excess Body Fat In Children : Part 2 – the Prescription of Low-Carbohydrate Eating as the First Approach’, Current Obesity Reports [Preprint]. Available at: https://doi.org/10.1007/s13679-024-00564-1.