Exploring the Therapeutic Potential of the Ketogenic Diet on Neurological Disorders: A Comprehensive Review

Sai Krishna Vallamchetla

All India Institute of Medical Sciences, Bhopal, India

The ketogenic diet (KD) has emerged as a promising therapeutic strategy for a variety of neurological disorders, including epilepsy, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and autism spectrum disorder. The potential benefits of the KD are attributed to its capacity to modulate neurotransmission, reduce inflammation, improve mitochondrial function, and enhance synaptic plasticity. Despite the growing body of evidence supporting the KD's therapeutic potential, there remain challenges in its implementation, such as potential side effects, nutrient deficiencies, and the need for careful monitoring by healthcare professionals. Factors affecting the success of the KD include patient adherence, individual metabolic response, and appropriate diet customization. This review summarizes the current evidence supporting the KD's role in the management of neurological disorders, discusses the underlying mechanisms of action, highlights the challenges and considerations associated with its use, and addresses the factors that can influence treatment success. Further research is needed to optimize the KD for different patient populations, elucidate the specific therapeutic mechanisms, and identify potential biomarkers to predict treatment response, ultimately enhancing the quality of life and overall well-being of individuals affected by neurological disorders.


The ketogenic diet (KD), a high-fat, low-carbohydrate dietary approach, was originally developed in the 1920s to treat epilepsy1. Over the past few decades, this diet has gained considerable attention in the field of neurology for its potential role in managing various neurological disorders beyond epilepsy. The KD is known to induce a state of ketosis, where the body relies on ketone bodies produced from fat metabolism rather than glucose for energy2. This shift in energy metabolism has been suggested to exert neuroprotective effects and modulate various cellular processes, which could be beneficial for treating neurological conditions3.

Research on the KD has expanded to include its potential application in the management of Alzheimer's disease4, Parkinson's disease5, multiple sclerosis6, and autism spectrum disorder7. Studies have indicated improvements in cognitive function, motor symptoms, and overall quality of life in patients following a KD regimen7–9. The mechanisms through which the KD may exert its therapeutic effects in these disorders are not yet fully understood, but they are thought to involve reduced oxidative stress, enhanced mitochondrial function, and modulation of neurotransmitter systems10.

Despite the promising findings, implementing the KD as a therapeutic approach for neurological disorders is not without challenges. Adherence to the diet can be difficult for patients, and potential side effects, such as gastrointestinal disturbances and nutrient deficiencies, must be carefully managed11. Additionally, more large-scale, well-controlled studies are needed to determine the long-term safety and efficacy of the KD in various neurological populations. In this comprehensive review, we summarize the current knowledge on the role of the KD in various neurological disorders, discuss its potential mechanisms of action, and address the challenges faced in implementing the diet as a therapeutic strategy.


To provide a comprehensive review of the role of the ketogenic diet (KD) in the management of neurological disorders, we conducted a systematic search of the literature using the PubMed and Google Scholar from inception till 2022. The keywords and search terms used in the search strategy included "ketogenic diet," "epilepsy," "Alzheimer's disease," "Parkinson's disease," "multiple sclerosis," "autism spectrum disorder”.

Inclusion criteria for the studies were as follows: (1) original research articles (randomized controlled trials, cohort studies, case-control studies, and case reports); (2) articles investigating the effects of the KD on patients with neurological disorders; (3) articles evaluating the safety, efficacy, and mechanisms of action of the KD in neurological disorders; and (4) articles discussing challenges and strategies for implementing the KD as a therapeutic intervention. Exclusion criteria included (1) non-original research articles (e.g., reviews, editorials, and commentaries); (2) articles not focused on the KD; (3) articles not related to neurological disorders; and (4) articles with insufficient data or methodology; (5) Animal studies of neurological disorders for which sufficient clinical evidence already exists.

Ketogenic diet and Neurological Disorders

Ketogenic Diet and Epilepsy

Epilepsy is a chronic neurological disorder affecting approximately 65 million people worldwide (20), with nearly 3 million affected individuals in the United States alone21. It is characterized by recurrent, unprovoked seizures resulting from abnormal electrical activity in the brain. About 30% of epilepsy cases are considered drug-resistant, meaning that patients do not achieve seizure control with standard anti-seizure medications22. The ketogenic diet has been demonstrated as an effective treatment option for drug-resistant epilepsy, particularly in pediatric populations. Its efficacy is supported by numerous studies and long-term outcome data, showing improvements in seizure control for many patients. Some key studies are shown in Table 1.

Mechanisms Underlying the KD's Effects in Epilepsy:

The ketogenic diet (KD) has been shown to be effective in managing epilepsy, but the exact mechanisms underlying its effects are still not entirely understood. Some proposed mechanisms include:

  1. Enhanced energy metabolism: KD leads to a metabolic shift from glucose utilization to ketone bodies (such as β-hydroxybutyrate, acetoacetate, and acetone) as the primary source of energy for the brain. This shift may stabilize neuronal activity and reduce seizure susceptibility23.
  2. Reduced neuronal excitability: The KD may decrease neuronal excitability by altering neurotransmitter systems, such as increasing the brain's gamma-aminobutyric acid (GABA) levels, an inhibitory neurotransmitter, and reducing the levels of excitatory neurotransmitters like glutamate24.
  3. Modulation of ion channels: The KD may alter the function of various ion channels, such as ATP-sensitive potassium channels, voltage-gated sodium channels, and voltage-gated calcium channels, which can stabilize neuronal membrane potential and reduce seizure susceptibility25.
  4. Anti-inflammatory effects: The KD may have anti-inflammatory effects by reducing the production of pro-inflammatory cytokines, which can contribute to seizure susceptibility26.
  5. Epigenetic modifications: KD may induce changes in gene expression through histone modifications and DNA methylation, which can influence neuronal excitability and seizure susceptibility27.
Table 1: Evidence Supporting the Ketogenic Diet in Epilepsy Management


Study Design

Sample Size


Neal et al.28


145 children

38% children in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p<0.0001) after 3 months

Ye et al.29


12 studies (270 adults)

Meta-analysis of 12 studies yielded a combined efficacy rate of the KD of 42%, with significant heterogeneity.

Martin-McGill et al.30

Systematic Review

 11 studies (712 children and adolescents, 66 adults.)

After three months, reported rates of seizure freedom in a classical 4:1 KD group reached as high as 55%, while reported rates of seizure reduction reached as high as 85%.

Kossoff et al.31

Retrospective study

118 children

At 6 months, 71% children were>50% improved and 43% children were>90%improved.

Sharma et al.32


102 children

The proportion of children with >90% seizure reduction (30% vs. 7.7%, p = 0.005) and >50% seizure reduction was significantly higher in the diet group (52% vs. 11.5%, p < 0.001) in comparison with controls.

Henderson et al.33


19 studies (1084 children)

The pooled odds ratio, using a random effects model, of treatment success (> 50% seizure reduction) among patients staying on the diet relative to those discontinuing the diet was 2.25 (95% confidence interval = 1.69-2.98). 

Klein et al.34

Prospective open-label pilot study

12 adults

In all adults there was >75% seizure reduction, the full effect occurred during the first month of treatment.

Cervenka et al.12

Prospective study

24 adults

Of the 14 patients who completed KD treatment, 11 experienced resolution of super-refractory status epilepticus.

Suo et al.35

Prospective study

317 children

After 12 months, 24.3% stayed on the KD diet, 18.6% had >50% seizure reduction, and 10.7% were seizure-free.

Lambrechts et al.36

Prospective study

15 adults

5 patients who followed the diet for 1 year showed significant reduction in seizures. Of these 5 patients, 2 had a reduction between 50 and 90%.

Wirrell et al.37

Retrospective study

14 children

In 5 of 12 children (42%), the ketogenic diet succeeded, leading to either medication withdrawal (n=3) or reduction (n=2).

Carrette et al.38

Prospective study

8 adults

A comparison of seizure frequency in three patients who completed the study showed a mean reduction of 42.2% (range: 25-60%) from baseline to the final month(6th).

Mosek et al.39

Prospective study

9 adults

After 12 weeks of follow up, two patients who concluded the study had a more than 50% reduction in the frequency of the seizures.

Ketogenic Diet and Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia worldwide40. It is characterized by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau protein, leading to neuronal loss and cognitive decline41. Current treatments for AD primarily focus on symptom management, and there is no cure for the disease42. Several clinical studies have investigated the effects of the KD or ketone supplements in patients with AD as shown in Table 2. The evidence suggests that the ketogenic diet may have potential benefits in the management of Alzheimer's disease by improving cognitive function, memory, and brain energy metabolism.

Mechanisms Underlying the KD's Effects in Alzheimer's Disease:

The ketogenic diet (KD) has shown promise in Alzheimer's disease (AD) management, and several mechanisms have been proposed to explain its potential benefits:

  1. Improved brain energy metabolism: KD may help overcome the brain glucose hypometabolism commonly observed in AD by providing ketone bodies as an alternative fuel source, thereby enhancing neuronal function and resilience43.
  2. Reduction in oxidative stress: KD has been shown to upregulate antioxidant defenses and reduce the production of reactive oxygen species, which can cause oxidative damage to neurons in AD44.
  3. Modulation of amyloid-beta and tau pathology: Some studies suggest that KD may help reduce the accumulation of Aβ plaques and hyperphosphorylated tau levels, potentially slowing AD progression45.
  4. Enhancement of mitochondrial function: KD may improve mitochondrial function and biogenesis, which are often impaired in AD46.
  5. Neuroinflammation reduction: KD can modulate the immune system and reduce neuroinflammation, which is implicated in AD development and progression47.
Table 2: Evidence Supporting the Ketogenic Diet in Alzheimer's Disease







Krikorian et al.18


23 older adults with MCI

Low-carbohydrate diet

6 weeks

Improved cognitive performance

Taylor et al.48

Prospective study

15 with mild-to-moderate AD

KD intervention

12 weeks

Significant improvements in memory and cognition

Ota et al.49

Prospective study

20 with mild-to-moderate AD

Medium-chain triglyceride (MCT)-based ketogenic diet

12 weeks

Increased ketone body levels and significant cognitive improvement

Henderson et al.33


152 with mild-to-moderate AD

Medium-chain triglyceride (MCT)-based ketogenic diet

90 days

Improved cognitive performance

Fortier et al.8


83 with MCI

Medium-chain triglyceride (MCT)-based ketogenic diet

6 months

Improved cognitive function.

Newport et al.50

Case report

1 with severe AD

ketone monoester (KME)

20 months

Improved cognitive function

Phillips et al.9

RCT (cross over trail)

26 with AD

Ketogenic diet

12 weeks

Improved cognitive function, Quality of life

Ketogenic Diet and Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunction, cognitive decline, and other non-motor symptoms51. Evidence suggests that ketogenic diet has shown promise in alleviating some symptoms of Parkinson's disease, such as motor dysfunction and cognitive decline as shown in Table 3.

Mechanisms Underlying the KD's Effects in Parkinson's Disease:

  1. Enhanced mitochondrial function: The KD has been shown to improve mitochondrial function and biogenesis, which is often impaired in PD, leading to energy deficits and increased vulnerability to neurodegeneration44.
  2. Reduction of inflammation: The KD may modulate the immune system and reduce neuroinflammation, which is implicated in PD development and progression52.
  3. Promotion of neurogenesis: The KD may enhance the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), which can support the growth, survival, and differentiation of neurons and may help alleviate PD symptoms53.
  4. Antioxidant effects: The KD has been shown to upregulate antioxidant defenses and reduce the production of reactive oxygen species, which can contribute to oxidative stress and neurodegeneration in PD44.
Table 3: Evidence Supporting the Ketogenic Diet in Parkinson's Disease


Study Design

Sample Size

Follow-up Period


Vanitallie et al.5

Prospective Study

7 patients

28 days

The mean total decrease in Unified Parkinson's Disease Rating Scale (UPDRS) scores for five participants who completed the study was 43.4% (ranging from 21 to 81).

Phillips et al.54

Randomized controlled trial

47 patients

8 weeks

Both the ketogenic diet (KD) and low-fat diet groups experienced significant improvements in motor and nonmotor symptoms, with the ketogenic group demonstrating more substantial improvements in nonmotor symptoms.

Cheng et al.46

Rat Model



The KD exhibited neuroprotective effects against 6-hydroxydopamine (6-OHDA) neurotoxicity, with glutathione playing a crucial role during this period.

Kashiwaya et al.55

Rat brain mitochondria



Ketone body administration has the potential to offer symptomatic relief and neuroprotection in Parkinson's disease by circumventing the mitochondrial complex I defect.

Tieu et al.56

Rat model



Ketone bodies can safeguard against MPTP-induced neurotoxicity, indicating that the ketogenic diet may possess therapeutic potential for Parkinson's disease.

Shaafi et al.57

Rat model


4 weeks

In comparison to those on a standard diet, rats with Parkinson's disease fed a ketogenic diet exhibited significant enhancements in motor function.

Ketogenic Diet and Multiple Sclerosis

Multiple sclerosis is an autoimmune disorder characterized by the demyelination of neurons in the central nervous system58. While the KD has not been studied as extensively in multiple sclerosis as in other neurological disorders, Evidence suggests potential benefits as shown in Table 4.

Mechanisms Underlying the KD's Effects in Multiple Sclerosis:

  1. Reduction of inflammation: The KD has been shown to modulate the immune system and reduce pro-inflammatory cytokines, which may help alleviate inflammation-mediated damage in MS52.
  2. Improved energy metabolism: By promoting ketosis, the KD may provide an alternative and more efficient energy source for the CNS, which can be beneficial in MS, where energy metabolism is often impaired59.
  3. Promotion of neuroprotection and remyelination: The KD may enhance the expression of neurotrophic factors and promote oligodendrocyte differentiation, which could contribute to remyelination and neuroprotection in MS59.
  4. Reduction of oxidative stress: The KD has been shown to upregulate antioxidant defenses and reduce the production of reactive oxygen species, which can contribute to the pathogenesis of MS60.
Table 4: Evidence Supporting the Ketogenic Diet in Multiple Sclerosis


Study Design

Sample Size


Brenton et al.6

Prospective study

20 adults

A 6-month ketogenic diet intervention has been found to improve fatigue and depression scores, promote weight loss, and reduce serologic proinflammatory adipokines in participants who completed the program.

Choi et al.61

Experimental autoimmune encephalomyelitis (EAE) mice model


The fasting mimicking diet facilitated the regeneration of oligodendrocyte precursor cells and remyelination of axons in the EAE mouse model.

Kim et al.62

Experimental autoimmune encephalomyelitis (EAE) mice


The ketogenic diet (KD) has been found to ameliorate motor disability and cognitive impairment, reverse structural brain lesions, and diminish CNS inflammation and oxidative stress in EAE mice.

Ketogenic Diet and Autism Spectrum Disorder (ASD)

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by difficulties in social interaction, communication, and repetitive behaviors. Given the increasing prevalence of ASD and the limited effectiveness of current treatments, researchers have been exploring alternative therapeutic options, including the ketogenic diet63. Several preclinical and clinical studies have indicated that the KD might alleviate some ASD-related symptoms and improve cognitive and social functioning as shown in Table 5.

Mechanisms Underlying the KD's Effects in Autism Spectrum Disorder:

  1. Modulation of neurotransmission: The KD has been shown to affect the balance of excitatory and inhibitory neurotransmission, which is often altered in ASD64. By modulating the levels of neurotransmitters, the KD may help improve ASD symptoms.
  2. Improvement of mitochondrial function: Mitochondrial dysfunction has been implicated in ASD pathogenesis65. The KD has been shown to enhance mitochondrial function and biogenesis, which could help alleviate ASD-related symptoms.
  3. Reduction of inflammation: The KD has been shown to modulate the immune system and reduce neuroinflammation66, which has been implicated in the development of ASD. By reducing inflammation, the KD may help improve the symptoms of ASD.
  4. Enhancement of synaptic plasticity: The KD may help improve synaptic plasticity and neuronal connectivity, which are often impaired in individuals with ASD67.
Table 5: Evidence Supporting the Ketogenic Diet in Autism Spectrum Disorder


Study Design

Sample Size


Evangeliou et al.27

Prospective study

30 children

Improved behavior, cognition, and communication after 6 months of KD

Lee et al.7

Open-label clinical Trail

15 children

Modified ketogenic gluten-free diet with MCT supplementation led to improvements in behavior, including reduced disruptive behavior, irritability, social withdrawal, and hyperactivity in children with ASD.

El-Rashidy et al.64

Case-control study

45 children

The study compared the effects of a ketogenic diet and a gluten-free, casein-free diet on autistic children. Both diet groups showed significant improvements in autism symptoms, with the ketogenic diet group demonstrating better improvements in sociability, communication, cognitive awareness, and hyperactivity compared to the gluten-free, casein-free diet group.

Ruskin et al.68

Mouse model of ASD


KD improved sociability and decreased repetitive behaviors.

Castro et al.69

Animal model


KD was able to reverse the autism-like behavioral deficits induced by prenatal valproic acid exposure in rats, including improvements in social behavior and reduced repetitive behaviors.

Factors Affecting Ketogenic Diet Success in Neurological Disorders

  1. Adherence to the diet: Ensuring strict adherence to the ketogenic diet is crucial for its success in managing neurological disorders. Due to the diet's restrictive nature, some patients may find it challenging to maintain in the long term, which can limit its therapeutic effects12.
  2. Ketosis level: The degree of ketosis achieved can influence the efficacy of the KD in neurological disorders. Different individuals may require varying levels of ketone bodies for optimal therapeutic effect. Regular monitoring and adjusting the diet to achieve an appropriate level of ketosis is essential for success10.
  3. Individual variability: The response to the KD can vary significantly among individuals. Factors such as genetics, metabolism, and gut microbiota composition may influence an individual's response to the diet, leading to varying degrees of success13.
  4. Type and severity of the neurological disorder: The efficacy of the KD may be influenced by the specific neurological disorder being treated and its severity. Some conditions may respond better to the KD than others, and further research is needed to determine the optimal application of the diet across various neurological disorders14.
  5. Duration of the KD: The length of time an individual follows the ketogenic diet may impact its effectiveness in managing neurological disorders. Some individuals may require a longer duration on the diet to experience the full range of benefits, while others might see improvements in a shorter period15.
  6. Nutritional balance: Ensuring adequate intake of essential nutrients, such as vitamins, minerals, and protein, is important for the overall success of the KD in managing neurological disorders. Inadequate nutrient intake can potentially lead to adverse effects and may limit the diet's therapeutic potential16.
  7. Age and developmental stage: The age and developmental stage of an individual may affect their response to the ketogenic diet. For example, younger children with epilepsy may have better seizure control on the diet compared to adolescents or adults17. Moreover, adults with neurodegenerative diseases may have different metabolic requirements and comorbidities that could influence the diet's success18.
  8. Comorbid conditions: The presence of comorbid conditions, such as diabetes, gastrointestinal disorders, or cardiovascular disease, can also affect the success of the ketogenic diet in managing neurological disorders. These conditions may necessitate modifications to the diet or additional medical management to ensure its safety and effectiveness19.

Challenges and Considerations

Implementing the ketogenic diet (KD) can be challenging for individuals, especially those with neurological disorders, as it requires strict adherence to a high-fat, low-carbohydrate diet. Despite its potential therapeutic benefits, several challenges and considerations should be taken into account when implementing the KD, including potential side effects, nutrient deficiencies, and the need for careful monitoring by healthcare professionals.

Potential Side Effects: The KD may cause gastrointestinal disturbances, such as constipation, diarrhea, and vomiting, particularly during the initial adaptation period47. These symptoms usually resolve as the body adapts to the new diet. Moreover, long-term adherence to the KD has been associated with an increased risk of cardiovascular disease due to elevated levels of low-density lipoprotein (LDL) cholesterol and saturated fats70. However, recent studies suggest that the KD may have neutral or even beneficial effects on cardiovascular health when implemented properly71.

Nutrient Deficiencies: The restrictive nature of the KD can lead to nutrient deficiencies, especially in vitamins and minerals that are abundant in carbohydrate-rich foods, such as B vitamins, calcium, and potassium11. These deficiencies can potentially exacerbate neurological symptoms and impair overall health. To prevent nutrient deficiencies, healthcare professionals may recommend supplementation and regular blood tests to monitor nutrient levels in patients following the KD11.

Monitoring: Given the potential risks and challenges associated with the KD, careful monitoring by healthcare professionals is essential to ensure the safety and effectiveness of the diet in patients with neurological disorders. Regular consultations with a registered dietitian or nutritionist can help optimize the KD, ensuring adequate nutrient intake and preventing potential complications72. Furthermore, healthcare professionals may need to adjust medications or other treatments in response to the patient's progress on the KD.

By addressing these challenges and closely monitoring patients on the ketogenic diet, healthcare professionals can ensure that the diet is safe, effective, and tailored to the individual's needs. As research into the potential therapeutic effects of the KD for neurological disorders continues to evolve, a better understanding of how to optimize the diet for different patient populations will be critical in maximizing its potential benefits while minimizing risks and complications.


In conclusion, the ketogenic diet has demonstrated considerable potential in the management of a range of neurological disorders such as epilepsy, Alzheimer's disease, Parkinson's disease, multiple sclerosis and autism spectrum disorder. Although the exact mechanisms underlying these benefits remain to be fully elucidated, the diet presents a promising adjunct therapy for individuals affected by these conditions. As research continues to evolve, efforts should focus on understanding the specific therapeutic mechanisms, optimizing the implementation of the diet, and identifying potential biomarkers that may predict treatment response. By doing so, healthcare professionals can provide personalized and effective treatment strategies for patients with neurological disorders, enhancing their quality of life and overall well-being.


I would like to express my gratitude to my colleagues and peers for their valuable insights and suggestions during the development of this research article. I also acknowledge the researchers whose work has contributed to the understanding of the ketogenic diet's role in managing neurological disorders.

Conflict of Interest

The author declares that there is no conflict of interest concerning the research, authorship, or publication of this article. The author has contributed to the conception, design, and preparation of the manuscript and has approved the final version for submission. The author has no financial, personal, or professional relationships with any individuals or organizations that could potentially influence the content of this article in any way.


  1. Wheless JW. History of the ketogenic diet. Epilepsia. 2008; 49: 3-5. doi:10.1111/j.1528-1167.2008.01821.x
  2. Paoli A, Rubini A, Volek JS, et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013; 67(8): 789-796. doi:10.1038/ejcn.2013.116
  3. Rusek M, Pluta R, Ułamek-Kozioł M, et al. Ketogenic Diet in Alzheimer’s Disease. Int J Mol Sci. 2019; 20(16): 3892. doi:10.3390/ijms20163892
  4. Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimers Res Ther. 2021; 13(1): 51. doi:10.1186/s13195-021-00783-x
  5. VanItallie TB, Nonas C, Di Rocco A, et al. Treatment of Parkinson disease with diet-induced hyperketonemia: A feasibility study. Neurology. 2005; 64(4): 728-730. doi:10.1212/01.WNL.0000152046.11390.45
  6. Brenton JN, Banwell B, Bergqvist AGC, et al. Pilot study of a ketogenic diet in relapsing-remitting MS. Neurology - Neuroimmunology Neuroinflammation. 2019; 6(4): e565. doi:10.1212/NXI.0000000000000565
  7. Lee RWY, Corley MJ, Pang A, et al. A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder. Physiol Behav. 2018; 188: 205-211. doi:10.1016/j.physbeh.2018.02.006
  8. Fortier M, Castellano C, St‑Pierre V, et al. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6‑month RCT. Alzheimer’s & Dementia. 2021; 17(3): 543-552. doi:10.1002/alz.12206
  9. Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimers Res Ther. 2021; 13(1): 51. doi:10.1186/s13195-021-00783-x
  10. Gasior M, Rogawski MA, Hartman AL. Neuroprotective and disease-modifying effects of the ketogenic diet. Behavioural Pharmacology. 2006; 17(5-6): 431-439. doi:10.1097/00008877-200609000-00009
  11. Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018; 3(2): 175-192. doi:10.1002/epi4.12225
  12. Cervenka MC, Hocker S, Koenig M, et al. Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus. Neurology. 2017; 88(10): 938-943. doi:10.1212/WNL.0000000000003690
  13. Olson CA, Vuong HE, Yano JM, et al. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell. 2018; 173(7): 1728-1741.e13. doi:10.1016/j.cell.2018.04.027
  14. Włodarek D. Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer’s Disease and Parkinson’s Disease). Nutrients. 2019; 11(1): 169. doi:10.3390/nu11010169
  15. Cervenka MC, Terao NN, Bosarge JL, et al. E-mail management of the Modified Atkins Diet for adults with epilepsy is feasible and effective. Epilepsia. 2012; 53(4): 728-732. doi:10.1111/j.1528-1167.2012.03406.x
  16. van der Louw E, van den Hurk D, Neal E, et al. Ketogenic diet guidelines for infants with refractory epilepsy. European Journal of Paediatric Neurology. 2016; 20(6): 798-809. doi:10.1016/j.ejpn.2016.07.009
  17. Lambrechts DAJE, de Kinderen RJA, Vles HSH, et al. The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up. Epilepsy & Behavior. 2015; 51: 261-266. doi:10.1016/j.yebeh.2015.07.023
  18. Krikorian R, Shidler MD, Dangelo K, et al. Dietary ketosis enhances memory in mild cognitive impairment. Neurobiol Aging. 2012; 33(2): 425.e19-27. doi:10.1016/j.neurobiolaging.2010.10.006
  19. Paoli A, Rubini A, Volek JS, et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013; 67(8): 789-796. doi:10.1038/ejcn.2013.116
  20. Ngugi AK, Bottomley C, Kleinschmidt I, et al. Estimation of the burden of active and life-time epilepsy: A meta-analytic approach. Epilepsia. 2010; 51(5): 883-890. doi:10.1111/j.1528-1167.2009.02481.x
  21. Zack MM, Kobau R. National and State Estimates of the Numbers of Adults and Children with Active Epilepsy — United States, 2015. MMWR Morb Mortal Wkly Rep. 2017; 66(31): 821-825. doi:10.15585/mmwr.mm6631a1
  22. Kwan P, Brodie MJ. Early Identification of Refractory Epilepsy. New England Journal of Medicine. 2000; 342(5): 314-319. doi:10.1056/NEJM200002033420503
  23. Bough KJ, Rho JM. Anticonvulsant Mechanisms of the Ketogenic Diet. Epilepsia. 2007; 48(1): 43-58. doi:10.1111/j.1528-1167.2007.00915.x
  24. Yudkoff M, Daikhin Y, Nissim I, et al. Response of brain amino acid metabolism to ketosis. Neurochem Int. 2005; 47(1-2): 119-128. doi:10.1016/j.neuint.2005.04.014
  25. Lutas A, Yellen G. The ketogenic diet: metabolic influences on brain excitability and epilepsy. Trends Neurosci. 2013; 36(1): 32-40. doi:10.1016/j.tins.2012.11.005
  26. Dupuis N, Curatolo N, Benoist JF, et al. Ketogenic diet exhibits anti-inflammatory properties. Epilepsia. 2015; 56(7): e95-e98. doi:10.1111/epi.13038
  27. Boison D, Rho JM. Epigenetics and epilepsy prevention: The therapeutic potential of adenosine and metabolic therapies. Neuropharmacology. 2020; 167: 107741. doi:10.1016/j.neuropharm.2019.107741
  28. Neal EG, Chaffe H, Schwartz RH, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008; 7(6): 500-506. doi:10.1016/S1474-4422(08)70092-9
  29. Ye F, Li XJ, Jiang WL, et al. Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-Analysis. Journal of Clinical Neurology. 2015; 11(1): 26. doi:10.3988/jcn.2015.11.1.26
  30. Martin-McGill KJ, Jackson CF, Bresnahan R, et al. Ketogenic diets for drug-resistant epilepsy. Cochrane Database of Systematic Reviews. 2018. doi:10.1002/14651858.CD001903.pub4
  31. Kossoff EH, Laux LC, Blackford R, et al. When do seizures usually improve with the ketogenic diet? Epilepsia. 2008; 49(2): 329-333. doi:10.1111/j.1528-1167.2007.01417.x
  32. Sharma S, Sankhyan N, Gulati S, et al. Use of the modified Atkins diet for treatment of refractory childhood epilepsy: A randomized controlled trial. Epilepsia. 2013; 54(3): 481-486. doi:10.1111/epi.12069
  33. Henderson CB, Filloux FM, Alder SC, et al. Efficacy of the Ketogenic Diet as a Treatment Option for Epilepsy: Meta-analysis. J Child Neurol. 2006; 21(3): 193-198. doi:10.2310/7010.2006.00044
  34. Klein P, Janousek J, Barber A, et al. Ketogenic diet treatment in adults with refractory epilepsy. Epilepsy & Behavior. 2010; 19(4): 575-579. doi:10.1016/j.yebeh.2010.09.016
  35. Suo C, Liao J, Lu X, et al. Efficacy and safety of the ketogenic diet in Chinese children. Seizure. 2013; 22(3): 174-178. doi:10.1016/j.seizure.2012.11.014
  36. Lambrechts DAJE, Wielders LHP, Aldenkamp AP, et al. The ketogenic diet as a treatment option in adults with chronic refractory epilepsy: Efficacy and tolerability in clinical practice. Epilepsy & Behavior. 2012; 23(3): 310-314. doi:10.1016/j.yebeh.2012.01.002
  37. Wirrell EC, Darwish HZ, Williams-Dyjur C, et al. Is a Fast Necessary When Initiating the Ketogenic Diet? J Child Neurol. 2002; 17(3): 179-182. doi:10.1177/088307380201700305
  38. Carrette E, Vonck K, de Herdt V, et al. A pilot trial with modified Atkins’ diet in adult patients with refractory epilepsy. Clin Neurol Neurosurg. 2008; 110(8): 797-803. doi:10.1016/j.clineuro.2008.05.003
  39. Mosek A, Natour H, Neufeld MY, et al. Ketogenic diet treatment in adults with refractory epilepsy: A prospective pilot study. Seizure. 2009; 18(1): 30-33. doi:10.1016/j.seizure.2008.06.001
  40. Prince M, Bryce R, Albanese E, et al. The global prevalence of dementia: A systematic review and meta-analysis. Alzheimer’s & Dementia. 2013; 9(1): 63. doi:10.1016/j.jalz.2012.11.007
  41. Selkoe DJ. The molecular pathology of Alzheimer’s disease. Neuron. 1991; 6(4): 487-498. doi:10.1016/0896-6273(91)90052-2
  42. Cummings JL, Morstorf T, Zhong K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther. 2014; 6(4): 37. doi:10.1186/alzrt269
  43. Cunnane SC, Courchesne-Loyer A, St-Pierre V, et al. Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer’s disease. Ann N Y Acad Sci. 2016; 1367(1): 12-20. doi:10.1111/nyas.12999
  44. Maalouf M, Rho JM, Mattson MP. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 2009; 59(2): 293-315. doi:10.1016/j.brainresrev.2008.09.002
  45. Van der Auwera I, Wera S, Van Leuven F, et al. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab (Lond). 2005; 2(1): 28. doi:10.1186/1743-7075-2-28
  46. Cheng B, Yang X, An L, et al. Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson’s disease. Brain Res. 2009; 1286: 25-31. doi:10.1016/j.brainres.2009.06.060
  47. Koppel SJ, Swerdlow RH. Neuroketotherapeutics: A modern review of a century-old therapy. Neurochem Int. 2018; 117: 114-125. doi:10.1016/j.neuint.2017.05.019
  48. Taylor MK, Sullivan DK, Mahnken JD, et al. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. 2018; 4(1): 28-36. doi:10.1016/j.trci.2017.11.002
  49. Ota M, Matsuo J, Ishida I, et al. Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer’s disease. Neurosci Lett. 2019; 690: 232-236. doi:10.1016/j.neulet.2018.10.048
  50. Newport MT, VanItallie TB, Kashiwaya Y, et al. A new way to produce hyperketonemia: Use of ketone ester in a case of Alzheimer’s disease. Alzheimer’s & Dementia. 2015; 11(1): 99-103. doi:10.1016/j.jalz.2014.01.006
  51. Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers. 2017; 3(1): 17013. doi:10.1038/nrdp.2017.13
  52. Youm YH, Nguyen KY, Grant RW, et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nat Med. 2015; 21(3): 263-269. doi:10.1038/nm.3804
  53. Marosi K, Mattson MP. BDNF mediates adaptive brain and body responses to energetic challenges. Trends in Endocrinology & Metabolism. 2014; 25(2): 89-98. doi:10.1016/j.tem.2013.10.006
  54. Phillips MCL, Murtagh DKJ, Gilbertson LJ, et al. Low-fat versus ketogenic diet in Parkinson’s disease: A pilot randomized controlled trial. Movement Disorders. 2018; 33(8): 1306-1314. doi:10.1002/mds.27390
  55. Kashiwaya Y, Takeshima T, Mori N, et al. D-β-Hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proceedings of the National Academy of Sciences. 2000; 97(10): 5440-5444. doi:10.1073/pnas.97.10.5440
  56. Tieu K, Perier C, Caspersen C, et al. D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. Journal of Clinical Investigation. 2003; 112(6): 892-901. doi:10.1172/JCI18797
  57. Shaafi S, Najmi S, Aliasgharpour H, et al. The efficacy of the ketogenic diet on motor functions in Parkinson’s disease: A rat model. Iran J Neurol. 2016; 15(2): 63-69.
  58. Thompson AJ, Baranzini SE, Geurts J, et al. Multiple sclerosis. The Lancet. 2018; 391(10130): 1622-1636. doi:10.1016/S0140-6736(18)30481-1
  59. Storoni M, Plant GT. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis. Mult Scler Int. 2015; 2015: 1-9. doi:10.1155/2015/681289
  60. Balietti M, Giorgetti B, Di Stefano G, et al. A ketogenic diet increases succinic dehydrogenase (SDH) activity and recovers age-related decrease in numeric density of SDH-positive mitochondria in cerebellar Purkinje cells of late-adult rats. Micron. 2010; 41(2): 143-148. doi:10.1016/j.micron.2009.08.010
  61. Choi IY, Piccio L, Childress P, et al. A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms. Cell Rep. 2016; 15(10): 2136-2146. doi:10.1016/j.celrep.2016.05.009
  62. Kim DY, Hao J, Liu R, et al. Inflammation-Mediated Memory Dysfunction and Effects of a Ketogenic Diet in a Murine Model of Multiple Sclerosis. PLoS One. 2012; 7(5): e35476. doi:10.1371/journal.pone.0035476
  63. Maenner MJ, Shaw KA, Baio J, et al. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016. MMWR Surveillance Summaries. 2020; 69(4): 1-12. doi:10.15585/mmwr.ss6904a1
  64. El-Rashidy O, El-Baz F, El-Gendy Y, et al. Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study. Metab Brain Dis. 2017; 32(6): 1935-1941. doi:10.1007/s11011-017-0088-z
  65. Masino SA, Rho JM. Mechanisms of Ketogenic Diet Action. 2012.
  66. Napoli E, Dueñas N, Giulivi C. Potential Therapeutic Use of the Ketogenic Diet in Autism Spectrum Disorders. Front Pediatr. 2014; 2: 69. doi:10.3389/fped.2014.00069
  67. Boison D. New insights into the mechanisms of the ketogenic diet. Curr Opin Neurol. 2017; 30(2): 187-192. doi:10.1097/WCO.0000000000000432
  68. Ruskin DN, Svedova J, Cote JL, et al. Ketogenic Diet Improves Core Symptoms of Autism in BTBR Mice. PLoS One. 2013; 8(6): e65021. doi:10.1371/journal.pone.0065021
  69. Castro K, Baronio D, Perry IS, et al. The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid. Nutr Neurosci. 2017; 20(6): 343-350. doi:10.1080/1028415X.2015.1133029
  70. Kosinski C, Jornayvaz F. Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies. Nutrients. 2017; 9(5): 517. doi:10.3390/nu9050517
  71. Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, et al. Ketogenic Diet and Epilepsy. Nutrients. 2019; 11(10): 2510. doi:10.3390/nu11102510
  72. Martin K, Jackson CF, Levy RG, et al. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database of Systematic Reviews. 2016. doi:10.1002/14651858.CD001903.pub3

Article Info

Article Notes

  • Published on: April 13, 2023


  • Ketogenic diet
  • Epilepsy
  • Alzheimer's disease
  • Parkinson's disease
  • Multiple sclerosis
  • Autism spectrum disorder


Dr. Sai Krishna Vallamchetla, MBBS,
All India Institute of Medical Sciences, Bhopal, India.;
Email: saikrishnavallamchetla@gmail.com

Copyright: ©2023 Vallamchetla SK. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.