Nutrition & Health Info Sheets for Health Professionals - The Ketogenic Diet

Nutrition & Health Info Sheets contain up-to-date information about nutrition, health, and food. They are provided in two different formats for consumer and professional users. These resources are produced by Dr. Rachel Scherr and her research staff. Produced by Rachel Colorafi, BS, Kristen James, BS, Anna M. Jones, PhD, and Rachel E. Scherr, PhD.

What is the Ketogenic Diet?

Sometimes referred to as the “keto” diet, the ketogenic diet is a strict eating pattern that is high in fat, moderate in protein, and low in carbohydrates [1]. If the diet is followed as described, this proportion of macronutrients results in the body entering a state of ketosis. The ketogenic diet has gained popularity in recent years as a method for weight loss and other health benefits.

How did the ketogenic diet first originate?

The ketogenic diet is most notable for being used as a treatment for pediatric drug-resistant epilepsy to reduce seizure activity beginning in the 1920’s [1, 2]. The ketogenic diet is still prescribed for seizures in the United States when medications are ineffective and other treatments, such as surgery or vagus nerve stimulation, are not an option [3]. Reports of the diet’s efficacy for epilepsy treatment since the 1920’s have proven consistent across all age groups, seizure frequencies, and locations [4-7].

What are the characteristics of the ketogenic diet?

The primary focus of the ketogenic diet is not a caloric or portion restriction, but rather a restriction on certain foods so that the body will switch from glucose metabolism to fat metabolism to meet energy needs. Although there are many different forms of the ketogenic diet, clinical trials and popular versions of this diet generally restrict daily carbohydrate consumption below 50 grams, primarily from non-starchy vegetables, and emphasize protein and fat consumption [8,9]. Variations of the diet commonly consist of 70 – 80% fat, 5 – 10% carbohydrates, and 10 – 20% protein, respectively, of total daily calories [10].

Individuals following the ketogenic diet primarily consume animal products, such as meat, poultry, fish, processed meat, shellfish and eggs; salad vegetables, such as leafy greens, cucumber, and celery; and low-carbohydrate/ non-starchy vegetables, such as cauliflower, broccoli, asparagus, and squash [10].

Table 1. Examples of Foods Allowed on a Ketogenic Diet

How does the ketogenic diet work?

The general premise of the ketogenic diet is the induction of physiological ketosis (also known as nutritional ketosis) [11]. Reducing carbohydrate intake below 20 grams per day results in insufficient body glucose reserves for supplying the central nervous system with enough energy solely through glucose [11]. Glucose serves as the human brain’s primary source of energy as fatty acids are unable to pass the blood-brain barrier [12]. Due to the carbohydrate restrictions in the ketogenic diet, the liver uses body fat stores to create ketone bodies for energy metabolism. [13] These ketone bodies are able to cross the blood-brain barrier, allowing the brain to use these compounds for fuel. [12] During ketosis, the brain adapts to lower levels of available glucose by changing its fuel source to rely on ketone bodies for energy. [14] It is important to note that amino acids in protein food sources can be converted to glucose, and therefore halt physiological ketosis. This underscores a key distinction between a low-carbohydrate diet and a ketogenic diet; a low-carbohydrate diet (which is not the same as a very low carbohydrate diet), which replaces carbohydrate intake with fat and protein, will not result in physiological ketosis due to the protein content of the diet.

Figure 1. Process by which the body supports the brain's energy needs when glucose is unavailable.

Are there benefits to consuming a ketogenic diet beyond epilepsy treatment?

There has been interest in low-carbohydrate and ketogenic diets for weight loss, glycemic control in those with type 2 diabetes, cancer treatment, and other potential treatments. It is strongly advised and encouraged to receive supervision and consultation by experienced physicians and dietitians while on this diet, especially for those taking insulin or oral hypoglycemic medications for diabetes, due to a risk of serious hypoglycemia. [7, 15] This dietary pattern is not recommended for individuals with pancreatic disease, liver conditions, thyroid problems, eating disorders or a history of eating disorders, and gallbladder disease or those who have had their gallbladders removed [16].

Weight Loss

Research suggests that a ketogenic diet can be effective for weight loss. [17 20] In one randomized, controlled trail, researchers sought out to determine the effects of a very-low-carbohydrate diet (VLCD) on body composition and cardiovascular risk factors when compared to a low fat diet (LFD) – a calorie-restricted diet with 30% of calories from fat. Results showed that participants on both diets reduced calories consumption by comparable amounts at 3 to 6 months, but those on a VLCD lost more weight and more body fat than those following a LFD. Researchers concluded that VLCD diets are more effective than LFD diets in the short-term for weight loss and, after 6 months, is not associated with increased risk that would impair cardiovascular health [17]. An uncontrolled 12-week intervention with obese adults on the ketogenic diet resulted in significant weight loss in the subjects (-18 +/- 9 kg in men and -11 +/- 3 kg in women) [18]. In a meta-analysis of 13 studies that investigated whether individuals assigned to a very-low-carbohydrate ketogenic diet (VLCKD) achieved better long-term body weight management compared to individuals on a conventional low-fat diet (LFD), found that those assigned to a VLCKD achieved a greater weight loss than those assigned to a LFD in the long term, which was defined as 12 months or more post-intervention [19]. Additionally, one randomized controlled study comparing the effects of a low-carbohydrate, ketogenic diet with that of a low-fat, low-cholesterol, reduced-calorie diet showed greater weight loss in the low-carbohydrate, ketogenic diet group, even though both groups presented substantially more fat mass loss than fat-free mass loss [20].

Insulin Sensitivity and Glycemic Control

Other research has investigated the impact of the ketogenic diet on insulin sensitivity and glycemic control for diabetes management [8,15,19,21]. In one study, researchers compared the effectiveness of a VLCKD in improving glycemic control and weight loss in adults with type 2 diabetes and to an energy restricted diet with 45 - 60% of calories from carbohydrates. Results showed that the percent of participants with hemoglobin A1c (HbA1c) levels above 7% decreased from 46.7% to 12.8% in the ketogenic diet group, which was not significantly different from the energy-restricted group. However, the ketogenic diet group did experience significantly larger improvements in insulin sensitivity compared to the energy-restricted diet as measured by the Homeostasis Model Assessment for Insulin Resistance [8].

Cancer

The Warburg effect describes the tendency of cancer cells to rely on glycolysis to generate energy, which requires glucose for fuel. In contrast, healthy cells are able to adapt to alternative fuel sources, such as ketone bodies acetoacetate and beta-hydroxybutyrate; therefore, researchers have hypothesized that consuming a ketogenic diet deprives cancer cells of energy creating an anti-tumor effect [22]. This hypothesis has been tested in many animal studies and a limited number of human clinical trials. However, lack of compliance with the diet and the effect of weight loss on reducing risk makes it difficult to draw conclusions about the effect of a ketogenic diet on cancer survival [23]. Other research suggests that different types of cancer respond to a ketogenic diet with an anti-tumor effect, while others respond with no or even a pro-tumor effect [24].

Other Treatment Potential

The ketogenic diet is being investigated as a treatment for Parkinson’s disease, Alzheimer’s disease, hypercholesterolemia, autism, and depression [7]. However, to date, there are too few reported studies to enable conclusions regarding efficacy. The ketogenic diet is also being investigated as a way to promote healthy aging; many animal trials support beta-hydroxybutyrate's effect of reducing aspects of cell aging [25]. Similarly, there are too few reports in humans to enable conclusions at this time.

What are the negative aspects to consuming the ketogenic diet?

Early-onset adverse effects associated with the ketogenic diet are sometimes referred to as the “keto flu” and include acidosis (low blood pH), hypoglycemia (low blood sugar), constipation, dehydration, dizziness, and fatigue. [8, 15] Long-term harmful effects from the ketogenic diet may include dyslipidemia (abnormal amount of lipids in the blood), kidney stones, and decreased bone density. [7, 26 - 28] There is also concern that highly restrictive diets, such as the ketogenic diet , may be low in certain key nutrients. [26] For example, one intervention study observed that a ketogenic diet resulted in an average fiber intake of 6.4 grams per day, well below the recommended 28 grams per day for a 2,000 calorie diet. [29]

Dyslipidemia

Limited research suggests blood levels of cholesterol and lipids can be adversely affected when on the ketogenic diet. One study of dyslipidemia on the ketogenic diet, observed 141 children over the course of 2 years, and found an increase in very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) and a decrease in high-density lipoprotein cholesterol (HDL). Total cholesterol increased by an average of 33% in the participants of the study, resulting in 61% of participants with total cholesterol classified as “high” and another 17% who were “borderline high.” Over a 2-year follow-up period, average total cholesterol decreased, but remained above the high total cholesterol cutoff values. [26]

Kidney Stones

Kidney stones have been observed to occur more frequently in children on the ketogenic diet. [27 - 28] Kidney stones are thought to be a secondary factor associated with acidosis, urine acidification, hypercalciuria (high calcium in the urine), and hypocitraturia (low citrate in the urine) when on the ketogenic diet. [27, 9]

Bone Density

Bone density may decrease while on the ketogenic diet. There have been reports in scientific literature of a higher risk of skeletal fractures in children on the ketogenic diet. [7, 28]

How does the ketogenic diet compare to the current 2015 -2020 Dietary Guidelines for Americans?

The ketogenic diet differs from the 2015 – 2020 Dietary Guidelines for Americans (DGA) and National Academy of Medicine (NAM) recommendations for dietary proportions of protein, fat, and carbohydrates. Both the DGA and NAM recommend 20 - 35% of calories from fat per day, while the example ketogenic diet has 87% of calories from total fat. (Table 1) [30 - 31] The ketogenic diet tends to be higher in protein and fat, and lower in carbohydrates and dietary fiber than recommended by the DGA due to limited amounts of grains, refined sugars, legumes, and certain vegetables and fruits. (Table 2) [10, 31– 32].

Table 2: Comparison of Ketogenic Diet Nutrient Composition and the Dietary Guidelines for Americans

 

References

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2. Peterman MG. The ketogenic diet in epilepsy. Journal of the American Medical Association. 1925 Jun 27;84(26):1979-83.
3. Frequently Asked Questions About Epilepsy | CDC. Centers for Disease Control and Prevention. https://www.cdc.gov/epilepsy/about/faq.htm#How is epilepsy treated? Published January 4, 2019. Accessed August 19, 2019.
4. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. The Lancet Neurology. 2008 Jun 1;7(6):500-6.
5. Hartman AL, Vining EP. Clinical aspects of the ketogenic diet. Epilepsia. 2007 Jan;48(1):31-42.
6. Freeman JM, Vining EP, Pillas DJ, Pyzik PL, Casey JC. The efficacy of the ketogenic diet—1998: a prospective evaluation of intervention in 150 children. Pediatrics. 1998 Dec 1;102(6):1358-63.
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9. Groesbeck DK, Bluml RM, Kossoff EH. Long-term use of the ketogenic diet in the treatment of epilepsy. Developmental medicine and child neurology. 2006 Dec;48(12):978-81.
10. Diet Review: Ketogenic Diet For Weight Loss| Nutrition Source. Harvard T.H. Chan School of Public Health. https://www.hsph.harvard.edu/nutritionsource/healthy-weight/diet-reviews/ketogenic-diet/. Published 2019. Accessed December 5, 2019.
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12. Pardridge WM. Blood-brain barrier transport of glucose, free fatty acids, and ketone bodies. InFuel Homeostasis and the Nervous System 1991 (pp. 43-53). Springer, Boston, MA.
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18. Mohorko N, Černelič-Bizjak M, Poklar-Vatovec T, Grom G, Kenig S, Petelin A, Jenko-Pražnikar Z. Weight loss, improved physical performance, cognitive function, eating behavior, and metabolic profile in a 12-week ketogenic diet in obese adults. Nutrition research. 2019 Feb 1;62:64-77.
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20. 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 May 18;140(10):769-77.
21. Tinsley GM, Willoughby DS. Fat-free mass changes during ketogenic diets and the potential role of resistance training. International journal of sport nutrition and exercise metabolism. 2016 Feb 1;26(1):78-92.
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29. Gardner CD, Kim S, Bersamin A, Dopler-Nelson M, Otten J, Oelrich B, Cherin R. Micronutrient quality of weight-loss diets that focus on macronutrients: results from the A TO Z study. The American journal of clinical nutrition. 2010 Aug 1;92(2):304-12.
30. National Academies of Science, Engineering, and Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Published October 8, 2018. Accessed August 19, 2019.
31. Appendix 7. USDA Food Patterns: Healthy U.S.-Style Eating Pattern. Appendix 7.Nutritional Goals for Age-Sex Groups Based on Dietary Reference Intakes & Dietary Guidelines Recommendations. https://health.gov/dietaryguidelines/2015/guidelines/appendix-7/. Accessed December 5, 2019.
32. Bertoli S, Trentani C, Ferraris C, De Giorgis V, Veggiotti P, Tagliabue A. Long-term effects of a ketogenic diet on body composition and bone mineralization in GLUT-1 deficiency syndrome: a case series. Nutrition. 2014 Jun 1;30(6):726-8.

 

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