Medical Advisory Board: Dr. Ram Dandillaya, Clinical Chief, Cardiology, Cedars-Sinai; Dr. Antonio J. Forte, Faculty, Mayo Clinic; Dr. Rinn Song, Fmr. Faculty, Harvard Medical School; Dr. Daniel Kahneman, Nobel Prize Laureate. OpenEvidence is a Mayo Clinic Platform Accelerate Company.
What Does the Science Say About a Ketogenic Diet?
Medically Reviewed By: Dr. Ram Dandillaya, MD FACC, Clinical Chief, Department of Cardiology Cedars-Sinai Medical Center, and Fernanda Ferreira, PhD (Harvard) and Methodologically Reviewed By: Daniel Nadler, PhD (Harvard)
Updated: Feb. 4, 2023
More Like This
Open Evidence Search and Ranking
OpenEvidence has screened and evaluated the published universe of 34,000,000+ peer-reviewed medical studies and identified and analyzed 154 robust clinical trials that tested the Ketogenic diet; of those, here are the most frequently-cited findings in leading medical journals:
Keto & Healthy Adults I
Findings: A study in the journal Nutrients assessed two popular diets–a cyclical ketogenic reduction diet (focused on limiting carbohydrate intake in order to encourage the body to enter a state of ketosis), and a nutritionally-balanced reduction diet (which provided a more traditional balance of nutrients)–for their ability to improve body composition, muscle strength, and endurance performance in 25 healthy young males. Participants also regularly practiced resistance and aerobic training. The results revealed that a cyclical ketogenic diet resulted in weight loss but had no effect on muscle strength and actually decreased lean body mass marginally. Conversely, the nutritionally-balanced diet improved both muscle strength while preserving lean body mass levels across all test subjects; the study also examined the diets' impact on endurance. The nutritionally-balanced diet had a positive effect, while the cyclical ketogenic diet had no effect. The findings suggest that in healthy adult males, a nutritionally-balanced diet may be the better choice for improving muscle strength and endurance performance. [1]
Keto & Healthy Adults II
Findings: A study published in Nutrients examined the effects of a low-carb, high fat (keto) diet on muscle fatigue among 24 young and healthy women. The results showed that while grip strength was unaffected during handgrip tests, time to cycling fatigue decreased for those adhering to the keto lifestyle by almost two minutes compared with other diets. Furthermore, higher ratings of perceived exertion were reported when performing daily activities as well as exercising - indicating an unfavorable effect on muscle exhaustion levels due to the keto dietary approach. [2]
Keto & Cognitive Function
Findings: A Japanese research study published in Neuroscience Letters concluded that a ketogenic formula containing medium-chain triglycerides (MCTs) like coconut oil may potentially improve cognitive abilities among individuals suffering from mild-to-moderate Alzheimer's disease. Among the 20 study participants, there was no noteworthy difference after a single administration of the formulation; however, participants who consumed the formula for 12 weeks saw considerable gains on memory and cognition related tests when analyzed against their original test results. These findings suggest that the chronic consumption of a ketogenic formula containing MCTs may have positive effects on cognitive function in Alzheimer's disease patients. [3]
Findings: A study published in The Journal Of Clinical Endocrinology And Metabolism found that a very-low-calorie ketogenic diet (VLCK) may be an effective way to reduce fat mass while preserving muscle strength. 20 patients with obesity who consumed the VLCK for four months saw significant weight loss, which was primarily the result of reductions of fat mass as measured by three techniques that analyze body composition. Though there was a mild decrease in fat free mass during the period – primarily due to changes in total body water - it partially recovered after completion of the diet. [4]
Low-Carb Beats Low-Fat?
Findings: A study published in Annals of Internal Medicine suggests that a low-carbohydrate, ketogenic diet may be more effective for weight loss and improving lipid levels than a traditional reduced-calorie, low-fat diet. After 24 weeks observing 120 overweight individuals with hyperlipidemia who followed either type of diet, those on the low-carbohydrate regime experienced greater overall weight loss along with lower serum triglyceride concentrations and higher high density lipoprotein cholesterol readings compared to those following the low-fat diet. 30% of participants in the low-carbohydrates group experienced a greater than 10% increase in low density lipoprotein cholesterol levels after 24-weeks, suggesting that monitoring serum lipid profiles is important for individuals following this diet. [5]
Type of Protein & Obesity
Findings: In a study published in The Journal Of Clinical Endocrinology And Metabolism, researchers found that very-low-calorie ketogenic diets (VLCKDs) containing whey or vegetable protein may be safer and result in a healthier microbiota composition (i.e., a “healthier gut”) than those containing animal proteins. The study, which compared the efficacy and safety of 45-day isocaloric VLCKDs incorporating different types of protein in patients with obesity and insulin resistance, found that VLCKDs led to significant weight loss and a marked improvement in metabolic parameters over a 45-day period. Patients consuming VLCKDs based on whey protein also experienced a more pronounced improvement in muscle strength. However, markers of renal function worsened slightly in the group consuming animal protein. The findings suggest that protein source may play a role in modulating the gut microbiota’s response to VLCKD interventions and highlight the potential benefits of using plant or whey protein in these diets. [6]
Epilepsy in Children
Findings: A randomized controlled trial published in Lancet Neurology found that the ketogenic diet is a viable treatment option for children with epilepsy. Of 145 study participants between 2 and 16 years of age who had not responded to two antiepileptic drugs, 38% experienced more than 50% reduction in seizures after three months on the diet - compared to only 6% of those assigned to a control group. This effective approach was seen across generalized and focal syndromes alike. [7]
Type 2 Diabetes
Findings: A study published in the journal Nutrition of 363 overweight and obese individuals, 102 of whom had type 2 diabetes, compared the effects of a low-carbohydrate ketogenic diet (LCKD) with a low-calorie diet (LCD) on various health parameters. While both diets showed improvements in body weight, body mass index, waist circumference, blood glucose level, glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, urea, and creatinine, these changes being more pronounced in the LCKD group. Initial doses of some antidiabetic medications were decreased or discontinued in the LCKD group, and dietary counseling and medication adjustments were made on a biweekly basis. The LCKD appears to have beneficial effects on glycemic control, but should be used with caution as it can significantly lower blood glucose levels. [8]
Ketogenic Diet versus Mediterranean Diet
Findings: A study published in The American Journal of Clinical Nutrition compared the effects of a ketogenic diet and a Mediterranean diet on glucose control and cardiometabolic risk factors in individuals with prediabetes and type 2 diabetes mellitus. The study, called the Keto-Med trial, involved 40 participants who followed both diets for 12 weeks in random order. The primary outcome was the percentage change in glycated hemoglobin after 12 weeks on each diet. The results showed that glycated hemoglobin values did not differ between the two diets after 12 weeks, but both diets led to improvements from baseline. Triglycerides decreased more on the ketogenic diet, but LDL cholesterol was also higher on this diet. Follow-up data looking at diet adherence suggested that the Mediterranean diet was more sustainable, while the ketogenic diet was harder to maintain. The study suggests that both diets improve glycated hemoglobin levels, and in a clinical setting individuals with prediabetes and type 2 diabetes mellitus should choose the diet that best supports their needs. [9]
Ketogenic Diet versus Non-Ketogenic Low-Carbohydrate Diets
Findings: The American Journal of Clinical Nutrition published the results of a study that compared ketogenic and non-ketogenic low-carbohydrate diets. After six weeks, both groups experienced similar weight loss and improvements in biomarkers – insulin sensitivity, fat mass reduction, resting energy expenditure– but those on the keto diet were negatively impacted with respect to inflammatory risk factors as well as vigor levels. These data indicate that using a “keto” approach may not be advisable when attempting to achieve meaningful health benefits through dietary change. [10]
Ketogenic Diet Overview
The ketogenic diet is a high-fat, low-carbohydrate dietary therapy that has been traditionally used to treat epilepsy, particularly in children. The diet works by forcing the body to burn fats instead of carbohydrates, leading to the production of ketone bodies in the blood. These ketone bodies can then partially replace glucose as an energy source in the brain, potentially reducing the frequency of seizures; the mechanism by which the ketogenic diet works is still unknown. Given this diet’s effects on epilepsy, it may also be effective in treating other neurological disorders, such as Alzheimer's disease and Parkinson's disease, but human studies are needed to confirm this hypothesis. However, the diet can have side effects, including constipation, high cholesterol, slower growth, acidosis, and kidney stones.
The original version of the ketogenic diet, known as the classic ketogenic diet, usually contains a 3:1 or 4:1 ratio of fat to combined protein and carbohydrates. A variant of the diet, called the MCT ketogenic diet, uses an oil that is rich in medium-chain triglycerides, generally coconut oil, to provide around half of the calories. This variant allows for a greater variety of food choices, as it requires a smaller amount of fat and allows for the consumption of more protein and carbohydrates.
Was this page informative?
2. Sjödin A, Hellström F, Sehlstedt E, Svensson M, Burén J. Effects of a Ketogenic Diet on Muscle Fatigue in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial. Nutrients. 2020;12(4):E955. doi:10.3390/nu12040955.
3. 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. Neuroscience Letters. 2019;690:232-236. doi:10.1016/j.neulet.2018.10.048.
4. Gomez-Arbelaez D, Bellido D, Castro AI, et al. Body Composition Changes After Very-Low-Calorie Ketogenic Diet in Obesity Evaluated by 3 Standardized Methods. The Journal of Clinical Endocrinology and Metabolism. 2017;102(2):488-498. doi:10.1210/jc.2016-2385.
5. Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. A Low-Carbohydrate, Ketogenic Diet Versus a Low-Fat Diet to Treat Obesity and Hyperlipidemia: A Randomized, Controlled Trial. Annals of Internal Medicine. 2004;140(10):769-77. doi:10.7326/0003-4819-140-10-200405180-00006.
6. Basciani S, Camajani E, Contini S, et al. Very-Low-Calorie Ketogenic Diets With Whey, Vegetable, or Animal Protein in Patients With Obesity: A Randomized Pilot Study. The Journal of Clinical Endocrinology and Metabolism. 2020;105(9):dgaa336. doi:10.1210/clinem/dgaa336.
7. Neal EG, Chaffe H, Schwartz RH, et al. The Ketogenic Diet for the Treatment of Childhood Epilepsy: A Randomised Controlled Trial. The Lancet. Neurology. 2008;7(6):500-6. doi:10.1016/S1474-4422(08)70092-9.
8. Hussain TA, Mathew TC, Dashti AA, et al. Effect of Low-Calorie Versus Low-Carbohydrate Ketogenic Diet in Type 2 Diabetes. Nutrition (Burbank, Los Angeles County, Calif.). 2012;28(10):1016-21. doi:10.1016/j.nut.2012.01.016.
9. Gardner CD, Landry MJ, Perelman D, et al. Effect of a Ketogenic Diet Versus Mediterranean Diet on Glycated Hemoglobin in Individuals With Prediabetes and Type 2 Diabetes Mellitus: The Interventional Keto-Med Randomized Crossover Trial. The American Journal of Clinical Nutrition. 2022;116(3):640-652. doi:10.1093/ajcn/nqac154.
10. Johnston CS, Tjonn SL, Swan PD, et al. Ketogenic Low-Carbohydrate Diets Have No Metabolic Advantage Over Nonketogenic Low-Carbohydrate Diets. The American Journal of Clinical Nutrition. 2006;83(5):1055-61. doi:10.1093/ajcn/83.5.1055.