EC Nutrition

Review Article Volume 18 Issue 2 - 2023

Beyond Weight Loss: A Comprehensive and Concise Review of the Ketogenic (Keto) Diet from Epilepsy Origins to Weight Management

John V Flores1,2† , Nicholas A Kerna3,4*†, Kevin D Pruitt5,6, ND Victor Carsrud7, Hilary M Holets1,2, Dabeluchi C Ngwu8,9, Sudeep Chawla10, Raymond Nomel11 and Joseph Anderson II12

1Beverly Hills Wellness Surgical Institute, USA
2Orange Partners Surgicenter, USA
3Independent Global Medical Research Consortium, USA
4First InterHealth Group, Thailand
5Kemet Medical Consultants, USA
6PBJ Medical Associates, LLC, USA
7Lakeline Wellness Center, USA
8Cardiovascular and Thoracic Surgery Unit, Department of Surgery, Federal Medical Center, Umuahia, Nigeria
9Earthwide Surgical Missions, Nigeria
10Chawla Health & Research, USA
11All Saints University, College of Medicine, St. Vincent and the Grenadines
12International Institute of Original Medicine, USA

*Corresponding Author: Nicholas A Kerna, (mailing address) POB47 Phatphong, Suriwongse Road, Bangkok, Thailand 10500. Contact:
†Indicates co-first author
Received: November 24, 2022;; Published: February 28, 2023

The ketogenic diet (KD) is a high-fat, adequate-protein, and very low-carbohydrate diet that stimulates the creation of ketones by mimicking the metabolism of the fasting state. A high level of blood ketone caused by a KD induces the state of ketosis, which has several physiological and therapeutic advantages. The KD first gained popularity as an epilepsy treatment in the 1920s and 1930s. It has rapidly attracted research interest in the last 20 years due to mounting evidence of the KD’s possible therapeutic potential for other diseases besides epilepsy, including obesity, neurodegenerative diseases, and malignancies.

The KD alters multiple cellular signaling cascades, receptors, and biomarker levels in various medical situations. KD therapy differs from the typical Western diet in that it focuses on nutritional supplements, electrolytes, and hydration in addition to the diet. If the KD is followed closely, significant dietary changes can positively affect the dieting individual. However, several treatable shortand long-term adverse effects are linked to the KD. It may be challenging to follow the KD long-term if some of the most enjoyable meals are not allowed.

Numerous physicians are considering including KD programs in the therapeutic regimen in light of the importance of lifestyle modification in managing diseases. However, before this can be advised, doctors must ensure its efficacy and safety, and further human research is necessary. Numerous economic opportunities will soon arise as a result of the potential medical benefits of the KD. These safeguards and limitations can therefore be used to develop distinctive and personalized interventional procedures replicating the effects of a KD or as potential drug development targets.

Keywords: Epilepsy Treatment; High-Fat; Low-Carbohydrate Diet; Elevated Ketone Level; Neurodegenerative Disease; Obesity

  1. Wilder RM. “The effect on ketonemia on the course of epilepsy”. Mayo Clinic Bulletin 2 (1921): 307-308.
  2. Ulamek-Koziol M., et al. “Ketogenic diet and epilepsy”. Nutrients 11 (2019): 2510.
  3. Woodyatt RT. “Objects and method of diet adjustment in diabetes”. Archives of Internal Medicine 28 (1921): 125-141.
  4. Peterman MG. “The ketogenic diet”. The Journal of the American Medical Association 90 (1928): 1427-1429.
  5. Wheless JW. “History of the ketogenic diet”. Epilepsia8 (2008): 3-5.
  6. Westman EC., et al. “The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus”. Nutrition and Metabolism 5 (2008): 36.
  7. Dowis K and Banga S. “The Potential Health Benefits of the Ketogenic Diet: A Narrative Review”. Nutrients5 (2021): 1654.
  8. Freeman JM., et al. “The efficacy of the ketogenic diet 1998: a prospective evaluation of intervention in 150 children”. Pediatrics 102 (1998): 1358-1363.
  9. Kossoff EH and McGrogan JR. “Worldwide use of the ketogenic diet”. Epilepsia 46 (2005): 280-289.
  10. Mastriani KS., et al. “Evidence-based versus reported epilepsy management practices”. Journal of Child Neurology 23 (2008): 507-514.
  11. Crosby L., et al. “Ketogenic Diets and Chronic Disease: Weighing the Benefits Against the Risks”. Frontiers in Nutrition 8 (2021): 702802.
  12. Broom GM., et al. “The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease”. Nutrition 60 (2019): 118-121.
  13. Włodarek D. “Role of ketogenic diets in neurodegenerative diseases (Alzheimer's disease and Parkinson's disease)”. Nutrients 11 (2019): E169.
  14. Taylor MK., et al. “Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease”. Alzheimer's and Dementia 4 (2017): 28-36.
  15. Krikorian R., et al. “Dietary ketosis enhances memory in mild cognitive impairment”. Neurobiology of Aging 33 (2012): 425.e19-27.
  16. Ciaffi J., et al. “The Effect of Ketogenic Diet on Inflammatory Arthritis and Cardiovascular Health in Rheumatic Conditions: A Mini Review”. Frontiers in Medicine 8 (2021): 792846.
  17. Orlando A., et al. “The Ketogenic Diet Improves Gut-Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems”. International Journal of Molecular Sciences3 (2022): 1098.
  18. Jiang Z., et al. “Effects of Ketogenic Diet on Neuroinflammation in Neurodegenerative Diseases”. Aging and Disease4 (2022): 1146-1165.
  19. Dashti HM., et al. “Beneficial effects of ketogenic diet in obese diabetic subjects”. Molecular and Cellular Biochemistry 302 (2007): 249-256.
  20. Hussain TA., et al. “Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes”. Nutrition 28 (2012): 1016-1021.
  21. Tay J., et al. “Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial”. The American Journal of Clinical Nutrition 102 (2015): 780-790.
  22. Feinman RD., et al. “Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base”. Nutrition 31 (2015): 1-13.
  23. McClean AM., et al. “Can a ketogenic diet be safely used to improve glycaemic control in a child with type 1 diabetes?” Archives of Disease in Childhood 104 (2019): 501-504.
  24. Dashti HM., et al. “Long-term effects of a ketogenic diet in obese patients”. Experimental and Clinical Cardiology 9 (2004): 200-205.
  25. Mansoor N., et al. “Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials”. British Journal of Nutrition 115 (2016): 466-479.
  26. Westerterp-Plantenga MS., et al. “Dietary protein, weight loss, and weight maintenance”. Annual Review of Nutrition 29 (2009): 21-41.
  27. Ma S., et al. “An 8-week ketogenic diet alternated interleukin-6, ketolytic and lipolytic gene expression, and enhanced exercise capacity in mice”. Nutrients 10 (2018): 1696.
  28. Paoli A., et al. “Medium term effects of a ketogenic diet and a Mediterranean diet on resting energy expenditure and respiratory ratio”. BMC Proceedings 6 (2012): P37.
  29. Feinman RD and Fine EJ. “Nonequilibrium thermodynamics and energy efficiency in weight loss diets”. Theoretical Biology and Medical Modelling 4 (2007): 27.
  30. Paneni F., et al. “Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I”. European Heart Journal31 (2013): 2436-2443.
  31. Yancy WS., et al. “A Randomized Trial of a Low-Carbohydrate Diet vs Orlistat Plus a Low-Fat Diet for Weight Loss”. Archives of Internal Medicine2 (2010): 136-145.
  32. Di Raimondo D., et al. “Ketogenic Diet, Physical Activity, and Hypertension-A Narrative Review”. Nutrients8 (2021): 2567.
  33. Kalra S., et al. “Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect”. Indian Journal of Endocrinology and Metabolism 20 (2016): 725-729.
  34. Aubert G., et al. “The failing heart relies on ketone bodies as a fuel”. Circulation 133 (2016): 698-705.
  35. Murray AJ., et al. “Novel ketone diet enhances physical and cognitive performance”. The FASEB Journal 30 (2016): 4021-4032.
  36. Dashti HM., et al. “Long term effects of ketogenic diet in obese subjects with high cholesterol level”. Molecular and Cellular Biochemistry 286 (2006): 1-9.
  37. Gupta L., et al. “Ketogenic diet in endocrine disorders: Current perspectives”. Journal of Postgraduate Medicine4 (2017): 242-251.
  38. Moran LJ., et al. “Treatment of obesity in polycystic ovary syndrome: A position statement of the androgen excess and polycystic ovary syndrome society”. Fertility and Sterility 92 (2009): 1966-1982.
  39. Newman JC., et al. “Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice”. Cell Metabolism3 (2017): 547-557.
  40. Hernandez A., et al. “Metabolic switching is impaired by aging and facilitated by ketosis independent of glycogen”. Aging9 (2020): 7963-7984.
  41. Pavlova NN and Thompson CB. “The emerging hallmarks of cancer metabolism”. Cell Metabolism 23 (2016): 27-47.
  42. Seyfried TN., et al. “Role of glucose and ketone bodies in the metabolic control of experimental brain cancer”. British Journal of Cancer 89 (2003): 1375-1382.
  43. Zahra A., et al. “Consuming a ketogenic diet while receiving radiation and chemotherapy for locally advanced lung cancer and pancreatic cancer: the University of Iowa experience of two phase 1 clinical trials”. Radiation Research 87 (2017): 743-754.
  44. Dowis K and Banga S. “The Potential Health Benefits of the Ketogenic Diet: A Narrative Review”. Nutrients5 (2021): 1654.
  45. Bistrian BR. “Clinical use of a protein-sparing modified fast”. The Journal of the American Medical Association 240 (1978): 2299-2302.
  46. Thomas DD., et al. “Protein sparing therapies in acute illness and obesity: a review of George Blackburn’s contributions to nutrition science”. Metabolism 79 (2018): 83-96.
  47. Wadden TA., et al. “Less food, less hunger: reports of appetite and symptoms in a controlled study of a protein-sparing modified fast”. International Journal of Obesity 11 (1987): 239-249.
  48. Caprio M., et al. “Very‐low‐calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE)”. Journal of Endocrinological Investigation11 (2019): 1365‐1386.
  49. Torosyan N., et al. “Changes in regional cerebral blood flow associated with a 45-day course of the ketogenic agent, caprylidene, in patients with mild to moderate Alzheimer’s disease: results of a randomized, double-blinded, pilot study”. Experimental Gerontology 111 (2018): 118-121.
  50. Paoli A., et al. “Long-term successful weight loss with a combination biphasic ketogenic Mediterranean diet and Mediterranean diet maintenance protocol”. Nutrients 5 (2013): 5205-5217.
  51. Nestler JE., et al. “Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system”. The Journal of Clinical Endocrinology and Metabolism 83 (1998): 2001-2005.
  52. Hyde PN., et al. “Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss”. JCI Insight 4 (2019): e128308.
  53. Sharma S and Jain P. “The ketogenic diet and other dietary treatments for refractory epilepsy in children”. Annals of Indian Academy of Neurology3 (2014): 253-258.
  54. Watanabe M., et al. “Scientific evidence underlying contraindications to the ketogenic diet: An update”. Obesity Reviews10 (2020): e13053.
  55. Newman JC and Verdin E. “Ketone bodies as signaling metabolites”. Trends in Endocrinology and Metabolism 25 (2014): 42-52.
  56. Murakami M and Tognini P. “Molecular Mechanisms Underlying the Bioactive Properties of a Ketogenic Diet”. Nutrients4 (2022): 782.
  57. Withrow CD. “The ketogenic diet: mechanism of anticonvulsant action”. Advanced Neurology 27 (1980): 635-642.
  58. Domouzoglou EM and Maratos-Flier E. “Fibroblast growth factor 21 is a metabolic regulator that plays a role in the adaptation to ketosis”. The American Journal of Clinical Nutrition 93 (2011): 901s-905s.
  59. Veldhorst MA., et al. “Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet”. The American Journal of Clinical Nutrition 90 (2009): 519-526.
  60. Xie G., et al. “Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy”. World Journal of Gastroenterology 23 (2017): 6164-6171.
  61. Zhu H., et al. “Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations”. Signal Transduction and Targeted Therapy1 (2022): 11.
  62. Yang X and Cheng B. “Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity”. Journal of Molecular Neuroscience 42 (2010): 145-153.
  63. Zhao Z., et al. “A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis”. BMC Neuroscience 7 (2006): 29.
  64. Kong C., et al. “Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome”. Signal Transduction and Targeted Therapy 6 (2021): 154.
  65. Chimienti G., et al. “The ketogenic diet reduces the harmful effects of stress on gut mitochondrial biogenesis in a rat model of irritable bowel syndrome”. International Journal of Molecular Sciences 22 (2021): 3498.
  66. Moriyama K., et al. “Protein-losing enteropathy as a rare complication of the ketogenic diet”. Pediatric Neurology 52 (2015): 526-528.
  67. Kanikarla-Marie P and Jain SK. “Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes”. Free Radical Biology and Medicine 95 (2016): 268-277.
  68. O'Neill B and Raggi P. “The ketogenic diet: Pros and cons”. Atherosclerosis 292 (2020): 119-126.
  69. Batch JT., et al. “Advantages and Disadvantages of the Ketogenic Diet: A Review Article”. Cureus8 (2020): e9639.
  70. Kossoff EH., et al. “Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group”. Epilepsia Open 2 (2018): 175-192. doi: 10.1002/epi4.12225. PMID: 29881797; PMCID: PMC5983110.
  71. Elisia I and Krystal G. “The Pros and Cons of Low Carbohydrate and Ketogenic Diets in the Prevention and Treatment of Cancer”. Frontiers in Nutrition 8 (2021): 634845. doi: 10.3389/fnut.2021.634845. PMID: 33718419; PMCID: PMC7946860.
  72. Ketogenic Diet Market Size, Share & Trends Analysis Report By Product (Supplements, Snacks, Beverages), By Distribution Channel (Supermarket/Hypermarket, Specialist Retailers, Online), By Region, And Segment Forecasts, 2020 – 2027.
  73. “Ketogenic Diet Therapies Market Is Dazzling Worldwide | Abbott Nutrition, Danone, Nestle, Ancient Nutrition, Zenwise Health, Ample Foods”. Digital Journal (2022).



Flores JV, Kerna NA, Pruitt KD, Carsrud NDV, Holets HM, Ngwu DC, Chawla S, Nomel R, Anderson II J. “Beyond Weight Loss: A Comprehensive and Concise Review of the Ketogenic (Keto) Diet from Epilepsy Origins to Weight Management”. EC Nutrition  18.2 (2023): 35-49.