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:

• Epilepsy – Using a ketogenic diet for seizures in children is a well-established treatment. In a 2010 study done at Johns Hopkins, one-third of children with difficult-to-treat epilepsy became either seizure-free or had a greater than 90% reduction in seizure frequency, and 44% of them were free of medications.¹³ A Cochrane review found that the classic ketogenic diet led to seizure freedom in as high as 55% of participants and seizure reduction in up to 85%.¹⁴ Results are similar for adults, and one review found that 32% of patients on a ketogenic diet and 29% on a modified Atkins diet had a greater than 50% reduction in seizures with 9% and 5% experiencing a greater than 90% reduction respectively. ¹⁵ For many patients, the benefits of the diet often extend for years, even after the diet is discontinued.^{16 17}
• Weight Loss – Part of the resurgence in interest in the ketogenic diet is due to the work of Dr. Atkins and his low-carb diet for weight loss. There is strong evidence to support the use of a ketogenic diet as a weight loss therapy.^{18 19} People following a low-carb diet tend to lose more weight in the first 3-6 months than those following a more traditional diet.²⁰ Part of the benefit likely comes from the fact that ketogenic diets tend to suppress appetite and lead to a natural decrease in calorie intake.²¹ But even in studies where participants on a low carb diet ate the same number of calories per day as those on a lowfat diet, significant differences in weight loss were observed.²² This is likely due to the fact that ketosis relies on fat from the diet and body fat to produce ketones for energy.
• Metabolic Syndrome and Diabetes – Several studies have evaluated the effects of a low carbohydrate ketogenic diet on type 2 diabetes, with promising results. Among the benefits seen are improved blood glucose profiles, improved insulin sensitivity, improvements in hemoglobin A1c, decreased triglycerides, increased HDL cholesterol (commonly thought of as ‘good’ cholesterol), and an improved total cholesterol to HDL ratio.^{23 24 25 26} The aforementioned improvements not only support those with existing type 2 diabetes, but also those with metabolic syndrome.

• Neurological Function– A ketogenic diet may be neuroprotective since it increases energy production in the brain, limits the production of free radicals, limits neuronal excitability and increases production of GABA in the brain.^{27 28} Researchers have hypothesized that a ketogenic diet and, in particular, ketones might benefit neurological function in several conditions and situations, including Alzheimer’s, Parkinson’s, Friedreich’s ataxia, autism and traumatic brain injury. ^{29 30} In Alzheimer’s disease, it appears that brain cells become unable to use glucose for energy production; a ketogenic diet can provide an alternative fuel for the brain. ³¹ Several studies have found that giving patients with mild to moderate Alzheimer’s medium chain triglycerides (MCTs), a type of fat that is readily accessible for ketone formation, improves cognition, but the effects are more pronounced in those that do not carry the APOE e4 gene variant that is associated with increased risk of Alzheimer’s.^{32 33 34} Research is just beginning to explore these conditions, and a better understanding of how effective the ketogenic diet is in treating certain neurological conditions will likely be available in the near future.
• Cancer – One exciting frontier for the potential use of a ketogenic diet is as an adjunct treatment for certain types of cancers. In 1924 Otto Warburg first published his observation that, unlike healthy cells, nearly all cancer cells fuel themselves through glycolysis, a means of creating energy through the fermentation of glucose. What we now call the “Warburg Effect” has led many researchers to theorize that if cancer cells are starved of glucose, they will stop spreading, while healthy cells will continue to thrive on the alternative fuel source of ketones. In mice, a ketogenic diet is known to inhibit certain pathways and lower certain compounds involved in tumor formation.³⁵ Research thus far is very preliminary, but because a ketogenic diet appears to target major energy pathways responsible for tumor growth and survival, it may enhance the efficacy of conventional treatments and even reduce side effects in some types of cancers. ^{36 37 38}
• Cardiovascular Disease – A ketogenic diet is often feared because of its high dependence on dietary fat for energy. This misguided fear is based on the outdated notion that eating fat negatively affects cardiovascular health, in particular, blood lipids. On the contrary, a low-carbohydrate ketogenic diet may actually improve blood lipid profiles, including decreased triglycerides and total and LDL cholesterol, and increased HDL cholesterol.^{39 40 41} A ketogenic diet might also alter the size and volume of the different LDL particles in a beneficial way, shifting from small, dense particles (believed to be atherogenic) to large, fluffy particles. ⁴² (See the Natural Grocers Customer Literature File Fats— Saturated for more information)
• Polycystic Ovary Syndrome – Since PCOS shares many symptoms and underlying causes with metabolic syndrome, it has been hypothesized that women suffering from PCOS might benefit from a ketogenic diet in a similar fashion to those suffering from metabolic syndrome. One small pilot study of overweight and obese women with PCOS following a low-carbohydrate, ketogenic diet for six months saw significant improvements in many markers of the disease, such as free testosterone, and fasting insulin.⁴³

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

• Pregnant and breastfeeding women
• Children and teenagers, unless for specific therapeutic conditions under the guidance of a trained professional
• Those with impaired fat digestion or liver disease
• Those with adrenal fatigue (a.k.a. hypothalamic-pituitary-adrenal (HPA) axis dysfunction)
• Those with thyroid conditions
• People trying to gain weight or who have a hard time keeping weight on
• People with eating disorders
• Type 1 Diabetics with uncontrolled blood sugar and Type 2 diabetics on insulin
• People taking prescription medications should work with their doctor to monitor doses since the ketogenic diet can cause significant shifts in body chemistry that may impact certain medications.⁵¹

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

References Available Upon Request