As far back as the 5th century, Hippocrates noted that fasting reduced seizures, and in the 1920s a diet was developed to mimic changes brought on by fasting that could be maintained long-term, specifically to treat seizures, and thus the ketogenic diet was born.1 This original ketogenic diet was very low in carbohydrates and protein and supplied 80-90% of the calories as fat.2 3 While the original ketogenic diet was successful in treating intractable childhood epilepsy, it fell out of favor when the modern antiepileptic drugs became available. In the 1990s the diet began to see a resurgence as people once again turned to it for difficult-to-treat cases of childhood epilepsy, such as those that do not respond to medication, and as a weight loss tool. The most recent research on the benefits of the ketogenic diet and ketones, in particular, have expanded to examine its possible therapeutic effects on other neurological diseases, cardiovascular disease, diabetes and even cancer.
When ketones are present in the body fluids at elevated concentrations, a person is said to be in ketosis. Dietary ketosis is a normal physiological response to sustained low carbohydrate intake that results in lowered blood glucose and insulin levels and stimulates the production of something known as ketone bodies. During ketosis, fats, either from the diet or from body stores, become the obligatory source of cellular energy for most body tissues while ketone bodies are produced in the liver to supply the rest of the body’s energy needs.4 Dietary ketosis should not be confused with diabetic ketoacidosis, a pathological condition that occurs mainly in type I diabetics due to an acute severe insulin deficiency (usually due to missing insulin injections) and a resulting inability to use glucose, though it is abundant. During diabetic ketoacidosis, blood ketone levels can be as high as 10-15 mM/l (significantly higher than what can be achieved in dietary ketosis). As ketone production exceeds the tissues’ ability to use them, the ketones build up and the blood pH is lowered.5 Immediate medical attention is required to prevent serious complications. This document deals with dietary ketosis only.
When there is ample glucose available (derived from dietary carbohydrates), the body will use that glucose as its main fuel source for producing ATP (the body’s main energy currency). Small amounts of glucose can be stored, but once incoming glucose has been used up and those stores run out, the body shifts gears and increases the use of fatty acids (derived from body fat stores or dietary fats) to produce energy. While most cells can directly use free fatty acids in order to produce sufficient energy, fats cannot cross the blood-brain barrier making them inaccessible to the brain as a fuel source. To overcome this, the liver converts fat into acetoacetate, acetone and beta-hydroxybutyrate (a.k.a. ketone bodies or ketones) which can be used by red blood cells and cells of the central nervous system (including the brain) as an alternative energy source when glucose levels are low. Importantly, the vast majority of other bodily tissues can also use ketones to produce energy. In fact, ketone production is a normal part of healthy metabolism and small amounts of ketones are produced regularly—such as during extended exercise or during an overnight fast. If glucose supplies continue to remain low, the body will increase its production of ketones. Using ketones as an alternative energy source reduces muscle protein breakdown, when carbohydrate is low. In addition to being used for energy, ketones have signaling functions that positively regulate genes related to aging, oxidative stress and healthy sympathetic nervous system activity. 6 7
The precise mechanisms behind the physiological effects of the ketogenic diet and ketones are not fully understood. It is believed that the ketogenic diet is anti-inflammatory, that it decreases free radical production while enhancing production of the body’s own natural anti-oxidants, and it improves metabolic efficiency.8 9 10 11 12 Specific conditions a ketogenic diet may benefit include:
Ketone production is the body’s natural response to very low or no carbohydrate availability. The ketogenic diet was developed to mimic the effects of fasting while still supplying adequate nutrition to maintain health. The classic ketogenic diet, developed in the early 1900s for children with epilepsy, consisted of a 3 or 4:1 ratio of fats to protein and carbohydrates combined, supplying up to 90% of the daily calories from fats.44 More recently, modified versions have emerged with similar rates of efficacy, and the wider variety of food and flexibility make the diet less arduous. Two such possible modifications are: a 1:1 and 2:1 ratios of fats to combined protein and carbohydrates and/or the addition of medium chain triglyceride (MCT) oil supplements. The medium chain fats that makeup MCTs more readily produce ketones than the long chain fats commonly found in the diet, allowing for a lower amount of total fat intake, and therefore increasing the amount of carbohydrate and protein that can be included in the diet.45
In practice, a ketogenic diet is one that keeps net carbohydrates below 50 grams per day, although the absolute number necessary to achieve ketosis will vary from individual to individual and may be as high as 100 grams/day for some. 46 (Because fiber is indigestible when eaten, it is usually not included in the carbohydrate count on a ketogenic diet, therefore net carbohydrates equals the total amount of carbohydrate minus the fiber.) Including some protein and carbohydrate on a ketogenic diet is important too since it supplies the needed substrate for the body to produce ketones, but too much can interfere with ketosis.47 48 A ketogenic diet usually includes low-moderate amounts of meat, fish, poultry, and eggs, moderate amounts of low-carb vegetables such as leafy greens and broccoli, and lots of healthy fats like avocados, nuts, and seeds, coconut oil, olive oil, etc. For those intent on ensuring they are in ketosis, home devices for testing ketone levels are available.
When a person first starts onto a low-carbohydrate ketogenic diet, it takes the body several days to a few weeks to shift from relying on glucose to instead rely on fat. During this transition, people may experience what is sometimes referred to as the “keto-flu”—muscle cramps, headaches, fatigue, dizziness, nausea, and sugar and carbohydrate cravings.49 There may also be increased urination which can result in a loss of minerals, such as sodium and potassium. To counter these effects one should strive to get more minerals and in particular, more sodium and potassium, drink plenty of water, get some exercise and ensure adequate caloric intake. Once the body becomes keto-adapted, these symptoms largely resolve, and many people report increased energy, decreased cravings and weight loss.
Once the body is adapted to ketosis, constipation and/or diarrhea are the most commonly reported side effects along with increased urination. Continuing to keep your mineral intake high and ensuring adequate water and fiber intake will help to counter these effects. People in ketosis may also notice a sweet or fruity odor on their breath, which is the result of increased production of the ketone acetone, which is a very volatile compound that is eliminated mainly through respiration in the lungs. 50
Although the ketogenic diet has been around for a long time and may be efficacious in many medical conditions, there is a surprising dearth of long-term studies on its safety. The bulk of the information comes from children using a ketogenic diet for epilepsy. Negative effects seen in children on a ketogenic diet long-term (≥2 years) are poor growth (while on the diet), kidney stones, and dyslipidemia (elevated cholesterol and/or triglycerides). Many of these effects can be overcome with careful attention to mineral intake while on the diet and/or termination of the diet.52 Most long-term studies evaluating adults using a ketogenic diet for weight loss have found very few serious adverse effects.53 54 55 56 However it should be noted that these studies only looked at one year duration on the diet, and poor adherence to the diet was frequently noted as a problem.
Some practitioners have raised the concern that long-term adherence to a ketogenic diet may shift the composition of the microbiota (the beneficial microbes that live in our bodies) in an undesirable direction and may even encourage the overgrowth of ‘bad’ bacteria. These beneficial bacteria feed on prebiotics (such as fiber and resistant starch), both of which are likely to be low in a low-carbohydrate ketogenic diet. Without prebiotics, beneficial bacteria are not able to produce substances like butyrate and other short chain fatty acids that keep the intestinal cells healthy, and long-term disruption of the microbiota can lead to a host of health problems throughout the body. 57 58
Another possible concern with long term adherence to a ketogenic diet is that some people are ‘hyper-responders’ to high fat intake. In these people, (estimated to be around 25-30% of the population) a high fat intake may lead to increased cholesterol and triglyceride levels. While this may be cause for concern in some people, in others this increase might be temporary, and still others may find, after considering things such as inflammation levels, total cholesterol:HDL ratio, and triglyceride:HDL ratio, the increase is not cause for concern.
Other concerns that may arise from remaining on a ketogenic diet long term include mineral deficiencies, decreased bone mass, decreased thyroid function, thinning hair and/or hair loss, heart problems, and menstrual irregularities.59 While it is possible that some of these problems can be mitigated with appropriate supplementation (e.g. fiber, adaptogenic herbs and minerals), ensuring regular adequate caloric intake, and adjusting carbohydrate intake to meet personal needs, not all people will thrive on a ketogenic diet. It is wise to work with an experienced practitioner who can help monitor blood work and symptoms for unwanted changes if you plan to stay on a ketogenic diet long-term.
The Coconut Ketogenic Diet by Bruce Fife
Fat for Fuel by Joseph Mercola
Primal Fat Burner by Nora T. Gedgaudas
Keto Cookery by Bruce Fife
Ketogenic Cookbook by Jimmy Moore and Maria Emmerich