Keto Diet Fundamentals

A ketogenic diet, or “keto diet,” refers to an extremely “low-carbohydrate, high-fat” pattern of eating. This article explains the basics elements of a ketogenic diet, some of the keto diet’s benefits, the science behind ketogenic diets, some sample keto diet menus, and goes over the types of keto diet foods that you may want to incorporate into your recipe list. 

Ketogenic Diet Principles 

A ketogenic diet reduces intake of carbohydrates (approx < 5% calories) and protein (approx < 15%) of total calories and increases the amount of fat (approx > 80% calories). Importantly, restricting proteins as well as carbohydrates limits the amount of substrate available for gluconeogenesis. This is the process of making glucose from non-glucose molecules such as lactate, glycerol or protein. It can take several days of the ketogenic eating pattern before the body starts to produce ketones (become ketogenic)  from fat1. When blood ketone levels exceed 0.5 mM, this is called 'ketosis.' The time taken to get into ketosis varies between individuals. 

A ketogenic diet is, by nature, a low carbohydrate diet, but not all low carbohydrate diets are ‘ketogenic.’ Despite this, people often group the different types of ‘low carbohydrate’ or ‘ketogenic’ diet together, this ultimately results in some confusion. Subtle differences in the macronutrients provided in the diet determine if the diet is ‘ketogenic.’ A macronutrient is something that humans consume in large quantities to provides the bulk of the energy to the body.  The primary macronutrients are carbohydrates, fats, and proteins. For a diet to be ketogenic, it must be high in fat, low-moderate in protein and very low in carbohydrate.   

Here are some helpful definitions of diets that have an element of  reduced carbohydrate intake:

  • Ketogenic diet: The aim is to trigger the production of ketones in the body. The diet is best described as high fat, low/moderate protein, and low carbohydrate. 
  • Low-calorie ketogenic diet: The aim is to severely restrict calories to a level below the basic metabolic needs (i.e., <800 kCal). Even if this diet is relatively high in carbohydrate, the calorie deficit created can still lead to a state of ketosis. However, this is not sustainable long term. 
  • Low carbohydrate: In the medical literature a “low carbohydrate diet” is a diet with < 30% energy from carbohydrate2. This diet may not lead to ketosis as carbohydrate and protein intake may still be too high.
  • Atkin’s diet: This diet has several phases. Initially, the aim is to restrict carbohydrate intake below 20g per day.  This degree of restriction is likely to lead to ketosis, although this is not an explicit aim. Subsequently, the diet reintroduces carbohydrates to a level that ‘the body can tolerate’3. In the Atkin’s diet, there is less restriction on protein compared to a ‘true ‘ketogenic diet.' It is high fat, moderate protein, low carbohydrate. 
  • Paleo diet: The Paleo diet aims to limit the diet to foods that would have been available to Paleolithic man4. There is wide variability in the way people interpret the diet. Foods allowed typically include vegetables, fruits, nuts, roots, and meat. Foods excluded include dairy, grains, sugar, legumes, processed oils, alcohol and coffee. There is no structured macronutrient target, however following a Paleo diet results in higher protein and fat consumption than an average diet.

It is important to note that every individual has differences in their metabolic responses and requirements. For example, caloric requirements are higher for men than women and increase with activity level. Also, insulin sensitivity can vary depending on a person's normal diet; therefore calorie intake and exact macronutrient composition of a diet that is ‘ketogenic’ varies from person to person. Some individuals can eat 50-100g of carbohydrate per day and maintain elevated ketone levels, where others must keep carbohydrate levels much more restricted to stay in ketosis. Furthermore, metabolism of ketones themselves changes as the body becomes adapted to the ketogenic diet. For example, more ketones are used as a fuel, and lower amounts are excreted in the urine5. To optimise the ketogenic diet protocol, ketone levels should be measured to quantify if the body is in ketosis. 

Keto Diet for Weight Loss

The ketogenic diet can be used to help with weight loss and also to treat some diseases (discussed in detail elsewhere). Recently, the number of positive keto diet reviews has increased. The increased popularity of the diet has led to a  demand for further randomised control trials to study its long-term efficacy.  A key reason that the ketogenic diet helps weight loss is that it decreases hunger. This makes it easier to maintain a calorie deficit. It is important to stress that overconsumption of calories will prevent weight loss, regardless of macronutrient composition. 

Macronutrients Composition of a Keto Diet

Macronutrients are food groups that humans consume in large quantities. They provide the bulk of the energy to the body. The primary macronutrients are carbohydrates, fats, and proteins. The macronutrient composition of a diet can be described using the mass of each macronutrient, the ratio of macronutrients in the diet or the percentage of each macronutrient in the diet. The variety of descriptions can make things a little confusing! 

For example:

  • A ketogenic diet contains about 5% of energy as carbohydrate. 
  • A ketogenic diet has a ratio of 2-4g of fat to every 1g of carbohydrate plus protein.
  • A classical ketogenic diet contains 20-30 g of carbohydrate per day

When starting off on the ketogenic diet, these are good target macronutrient ratios:

Examples of food rich in:

  1. Carbohydrate: bread, pasta, potatoes, cereals, sugary food (sweets). 
  2. Fat: oils (olive oil, coconut oil),  butter, fatty cuts of meat, brazil nuts, macademia nuts, avocado.  
  3. Protein: beef, chicken, pork, fish, milk, cheese, yogurt, eggs.

Carbohydrates

The main function of dietary carbohydrates (‘carbs’),  is to be a source of energy. Some say that dietary carbohydrate is not ‘essential’ as it can be made from dietary protein and fat6

Carbohydrates are biological molecules that contain carbon, hydrogen, and oxygen, usually with a 2:1 ratio of hydrogen: oxygen. Carbohydrates occur as a collection of single units (monosaccharides, e.g., glucose), two molecules joined (disaccharides, e.g., sucrose) and chains of molecules (oligosaccharides and polysaccharides). 

When following a ketogenic diet, carbohydrate intake should be very low. This contrasts to the modern western diet, where most dietary calories come from carbohydrate. Consuming carbohydrate causes insulin release, which inhibits ketone production in the liver. This kicks you out of ketosis. Therefore, monitoring and modulating carbohydrate intake is an important part of following the ketogenic diet. 

Dietary carbohydrate replenishes the stores in muscle and liver (glycogen). It also maintains blood glucose concentrations to provide fuel for the whole body, but most importantly for the brain. Blood glucose is easy to measure using a handheld blood glucose monitor.  Normal blood glucose levels fluctuate throughout the day and vary between individuals. Therefore, it is useful to track over the long term and in response to different ‘challenges’ such as a meal or exercise. Ranges for clinical diagnosis are as follows:

Blood glucose (mM / mgDl)

Fasting: healthy =                              4-6 mM / 70-110 mgDl

Fasting: diabetic =                             ~ 7 mM / 125 mgDl

90 minutes post-meal: healthy =      < 8 mM / 140 mgDl

90 minutes post-meal: diabetics =   > 11 mM/ 200 mgDl

(Source: Diabetes UK7)

When following the ketogenic diet, key concepts are the total amount of carbohydrate, the ‘net’ amount of carbohydrate (accounting for the accompanying fiber) and the speed with which carbohydrate raises blood glucose (glycemic index).

With a standard ketogenic diet, it’s recommended to keep the total amount of carbohydrate to less than 5% of energy intake8. See Table 1 for a calculation of the advised carbohydrate intake grams for a 2000 cKal per day 4:1 ketogenic diet.

Dietary fiber is carbohydrate-based material from plants that is not entirely broken down by the small intestine. Instead, it passes to the large intestine, and either undergoes fermentation (which supports the growth of beneficial bacteria9), or excretion. 

Fibre is a significant part of a well-formulated ketogenic diet. It helps to maintain gut health, and also increases food bulk and helps with the feeling of ‘fullness.' Green and cruciferous vegetables are rich in fiber and are helpful to include in a ketogenic diet. 

Depending on how ‘complex’ the source of fiber is, it has different assumed caloric values. One approach is to treat fiber as having the same amount of calories per gram as carbohydrate: 4 kCal/gram. However, as a proportion of fibre is not digested others approaches use a lower value of 2 kCal/g. Digestion resistant fiber does not contribute to calorie intake, as it is not broken down.  

Net carbohydrate refers to the mass of total carbohydrate, minus the total fiber. Net could be a better metric to judge carbohydrate intake than total because:

  • Fiber is mostly digestion resistant and so should not increase blood glucose9
  • Studies have shown an increase in fiber does not affect blood ketone levels10.  

The  ‘glycemic index' is a scale that ranges between 1-100, and it indicates how quickly food raises blood glucose after consumption. Pure glucose is the reference and is set at 100, (i.e., raises blood glucose quickly). Other foods have a comparatively lower value as they raise blood glucose more slowly. Example values for the glycemic index of food are white potato: ~80, white bread: ~75, apple: ~35, peanuts: ~15. 

‘Glycemic load’  accounts for both the speed of carbohydrate release and the TOTAL amount of carbohydrate in food.

Glycemic load = (total carbohydrate (g) x glycemic index) / 1000. 

Food can have a relatively high glycemic index (i.e. carrot = 47) but, because the total carbohydrate amount is low (carrot = 5g per serving), the glycemic load of one serving is very low. 

Proteins 

Proteins are large biological molecules made up of chains of amino acids. The functions of dietary protein are: 

  • Building structural and functional components of cells. 
  • Conversion to glucose via gluconeogenesis 
  • Used to top up intermediates in other metabolic pathways, such as the Krebs Cycle. 

While it is possible for protein to be used as a fuel, this is not its primary function. 

When following a ketogenic diet, protein must be sufficient to maintain muscle mass but not too high. This is because if dietary protein exceeds 20-25% of calories, gluconeogenesis from protein can stop ketone production. Initially, target a protein intake of 0.8-1.2g per kilogram of body weight. This target balances the need for protein against the chance of excess gluconeogenesis11.

Some individuals (such as strength or endurance athletes) may have higher protein requirements. In these individuals a ‘modified ketogenic macronutrient ratio’ of 2:1 fat: non-fat (where 65% energy is fat, 30% is protein and 5% carbohydrate can still be effective for therapeutic ketosis.   

Fats

In nutrition, 'fat' refers to the dietary macronutrient made up of ‘triglyceride’ molecules. The main functions of fats in the diet are to provide energy and also to make up key functional and structural parts of the human system. The term ‘fat’ is often misused: proper terms exist to differentiate between ‘fat’ in cells vs.  different types of ‘fat’ molecules:

  • Adipose tissue: The tissue that stores energy as fats/lipid droplets inside adipocytes (fat cells). ‘Body fat.' 
  • Adipocytes:  Individual cells that store fats/lipids.
  • Lipid: The most general term for insoluble and polar biological 'fat' molecules. The lipid class of molecules includes mono-, di- and tri- glycerols, cholesterols, and phospholipids.  
  • Triglyceride: A lipid molecule made up of glycerol (that acts as a backbone) joined to three fatty acid molecules.
  • Fatty acids: A molecule that is made up of a chain of carbon atoms bonded to one another with a carboxylic acid at one end. 

To use the correct terms, our diet includes many sources of ‘lipid.’ Lipid is digested and travels in the blood as ‘triglyceride’ and ‘fatty acids,' before being used as a fuel or stored by ‘adipocytes’ in ‘adipose tissue.' Dietary lipid undergoes many tightly regulated metabolic steps before storage in adipose tissue. Fat in the diet does not equal instant stored ‘body fat.’

Fat (triglycerides) are the most important source of energy in a ketogenic diet. It accounts for >70% of dietary calories.  For people following a ketogenic diet, it is helpful to understand how the lipid source in the diet is processed in the body:

Fatty acids can be saturated (no double bonds between carbons), or unsaturated (one or more double bonds between carbons). Unsaturated fatty acids can be further divided into monounsaturated fats (only one double bond between carbons), and polyunsaturated fats (multiple double bonds between carbons). The number of double bonds is important as it determines how the fatty acid behaves both inside and outside of the body. 

Saturated fats are relatively stable and tend to be solid at room temperature (i.e., lard, butter, coconut oil). Historical guidelines recommended that people limit the intake of dietary saturated fats. This is because fat consumption was thought to be associated with heart disease.  However, emerging research has shown that saturated fat can have beneficial effects on blood biomarkers (i.e., increase ‘healthy’ HDL levels)12. Furthermore, increased fat consumption is NOT associated with cardiovascular disease13. Moderate saturated fat consumption is unlikely to be as harmful as previously believed, and saturated fat consumption as part of a ketogenic diet is unlikely to increase the risk of cardiovascular disease.   

Unsaturated fats tend to be liquid at room temperature (i.e vegetable-based fats such as olive oil). Unsaturated fats are thought of as ‘healthier’ than saturated. Increased consumption of mono- and polyunsaturated fats has been linked to improved blood biomarkers (i.e lower blood triglycerides)14. Eating enough unsaturated fats is important when following a ketogenic diet.   

Trans-fats are produced artificially when hydrogen is added to unsaturated fatty acids in order to solidify it and make them last longer. Because of associations with poor health outcomes, these artificial fats had their ‘generally regarded as safe’ status removed in 201515. Avoid high levels of trans-fat consumption by eating a diet based around whole foods. 

Essential fatty acids are important to include in the diet because the body cannot make them itself. This group includes poly-unsaturated omega 3, omega 6 and omega 9 fatty acids. It is believed that the anti inflammatory effects of essential fatty acids may have broad benefits for health and performance. Oily fish, such as sardines and mackerel, and seeds (i.e flax)  are good dietary sources of essential fatty acids. 

The number of carbons in the fatty acid chain also has an important effect on its metabolism. The carbon chain of fatty acids can be up to 28 carbons atoms long. If there are >13 carbons in the fatty acid, it is called a “long chain fatty acid,” between 8-12 is a “medium chain fatty acid” and under 5 carbons is a “short chain fatty acid.” 

The body metabolizes fats differently according to their chain length. Long chain fatty acids are absorbed and go from the gut into the lymphatic drainage system and from there are released directly into the blood. By comparison, medium and short chain fatty acids do not go into the lymphatic system. They travel in the blood from the gut directly to the liver (Bhavsar2016). If a large amount of these short and medium chain fats are delivered to the liver at once, this can trigger the liver to convert them into ketones, even without dietary carbohydrate restriction. Medium chain fatty acids are highly ketogenic. They can be found in natural sources such as coconut oil or an artificially purified form. However, for many people, consuming a high amount of medium chain fatty acids can cause an upset stomach. This limits their use to raise ketones artificially.    

When integrating these concepts into a ketogenic diet, the message is to target the majority of dietary calories as fat. Aim to include a variety of fats from different animal and plant sources (i.e red meat, poultry, fish, dairy, olive oil, coconut oil, nuts and avocados).

Micronutrients in a Ketogenic Diet

Micronutrients are nutrients that must be obtained in the diet in small quantities but are essential to health. Vitamins and minerals are examples of micronutrients.  When following a ketogenic diet, it is important to be mindful of micronutrient intake because:

  • Reducing carbohydrate intake can lower consumption of micronutrient-rich foods (i.e. fruits and vegetable).
  • In the initial 28 days of following a ketogenic diet, the balance of some micronutrients (such as sodium, potassium, magnesium, and calcium) can become disturbed due to an increase in their excretion5. This issue tends to resolve naturally as the body adapts to the diet.  

Sodium is the principal cation in the extracellular fluid.  Its principal functions are related to blood volume maintenance, water balance, and cell membrane potential.  Sodium is also essential for acid-base balance and nerve conduction. Level of sodiums can fall at the start of a ketogenic diet. Adding extra sodium into meals (i.e., adding salt or consuming bouillon/ bone broth) can reduce the chance of side effects of low sodium (i.e. cramp). 

Potassium is the principal cation in the intracellular fluid. It;s primary functions are related to maintaining cell membrane potential and for electrical activity in cells such as neurons and cardiomyocytes. As with sodium, levels of potassium fall at the initiation of a ketogenic diet due to increased excretion.  Sources of potassium to include at the onset of a ketogenic diet include nuts, dark green vegetables, and avocados. 

Magnesium is an essential element in biological systems, especially for nerve, muscle and immune function. Levels of magnesium also fall at the initiation of a ketogenic diet due to increased excretion. Sources of magnesium to include in a ketogenic diet include oily fish, dark green vegetables, and seeds. 

Calcium has a role in muscle contraction and is important for cardiovascular and bone health.  Calcium deficiency is less common in a ketogenic diet, as staples of the diet such as fish, cheese, and greens are rich sources of the mineral.   

How to Start a Ketogenic Diet

It is advisable not to try and ‘gradually’ start the diet. This is because if carbohydrate intake is moderate-low, blood sugar levels may not be enough to fuel the brain, but carbohydrate in the diet might still be enough to stop the body making ketones.  

The main objectives when starting the ketogenic diet are to:

  • Restrict carbohydrates to 20 digestible grams per day or less – a strict low-carb diet. 
  • Consume plenty of fiber.
  • Restrict protein to moderate levels. If possible stay at or below 0.45 gram of protein per day, per lb of body weight (1g/kg). So about 70 grams of protein per day if you weigh ~155 lbs (~70kg). If your goal is to lose weight, aim for 1 gram of protein per kg of your target weight. 
  • Consume fat until you are satiated. 

Useful  Tips for Starting the Ketogenic Diet

  • Make a keto diet menu. It is a good idea to plan your meals before you start and make a shopping trip and stock up on a range of foods that are low in carbohydrate and high in fat. 
  • Use an app to track your macronutrient intake.  Apps such as “MyFitnessPal” are great to use to get an idea of the macronutrients in common foods. There is also a range of specialist online keto diet calculators.
  • Search for a few keto diet recipes to adapt your cooking methods. Due to the high-fat consumption required to get into ketosis, you may want to change your daily staples or cooking methods. Keep an eye out for coconut oil, heavy cream, and lots of cheese. 
  • Make a keto diet food list and get rid of carbohydrate-rich foods. It will be easier to follow the diet if you first throw out any foods in your house that you should avoid on a ketogenic diet. It is recommended to check the labels for hidden added sugars. 
  • Consider starting your ketogenic diet with a short period (16-36 hours) of fasting, which means no caloric intake. Fasting depletes your carbohydrate stores and can accelerate ketone production. Follow the link to read more about fasting protocols.
  • Gentle cardio exercise (~30 minutes) or some short high-intensity intervals (10-second sprints) can deplete carbohydrate stores and speed up ketone production.

Cyclical Ketogenic Dieting and ‘Cheating’

At the moment, there is not a clear answer as to if the benefits of the ketogenic diet can be achieved by taking an approach that cycles on and off the diet. It is advisable to stick to the diet for 1-2 months minimum to see benefits. This is because it can take several days to get into ketosis (Cahill1966) and 3 - 6 weeks to become ‘fat adapted,”11

That said, some research indicates that  ~40 days on the ketogenic diet interspersed with periods of healthy eating with higher carbohydrate  (Mediterranean diet) could maintain weight loss16.

‘Cheating’ and consuming high carbohydrate food quickly stops ketone production by the liver. It can then take a considerable amount of time to get back into ketosis. Time taken to get back into ketosis will depend on many factors. These include the amount of carbohydrate consumed, how adapted the body is to produce ketones and activity level, etc. 

That said, cyclical ketogenic diets are a promising area of scientific investigation.  Recently, scientists studied the effect of long-term cycling of the ketogenic diet (one week on, one week off the diet) compared to normal diet in mice.  Cyclical keto dieting reduced mid-life mortality and increased healthspan17

Optimal Range of Ketosis

As with all processes in metabolism, the state of ketosis is a spectrum. Past a threshold (which varies from person to person), even a small increase in dietary carbohydrate intake can trigger enough insulin release to take the body out of ketosis.

Guidelines for target levels for blood ketones are:  

  • No ketosis:   under 0.5 mM BHB in blood
  • Low ketosis:   0.5 - 1.5 mM BHB in blood
  • Moderate ketosis:  1.5 - 3 mM BHB in blood
  • High ketosis:   over 3 mM BHB in blood
  • Pathological ketosis: over 15 mM BHB in blood

The level of ketosis required for different physiological benefits is unknown. For endurance sports, a higher level of ketosis (~4 mM) appears to be superior to lower levels18,19. This is possibly because a benefit of ketones to athletes is that ketones are a fuel. However, some other benefits of ketosis, such as reduced appetite may be seen at much lower levels (0.5 mM)20

The best way to know if you are in ketosis is to measure the levels of ketones (BHB) in your blood. You can also estimate blood levels by measuring ketones in your breath or urine.  

Physiological Ketosis

The typical methods used to generate a ‘physiological’ level of ketosis are fasting, the ketogenic diet and consuming exogenous ketones. 

After an overnight fast, a low amount of ketones (0.1-  0.2 mM) can often be detected in the blood. As the time spent fasting increases, blood ketone levels slowly rise until a plateau at 8 - 10 mM of BHB is reached after many days. The scientist, Hans Krebs, described this plateau as ‘physiological ketosis.’21 

As fasting long term is unsustainable, following a strict ketogenic diet can be used to maintain a low level of continuous ketosis. Research suggests that blood BHB levels between 0.4 - 1mM can be achieved while following a ketogenic diet11. Anecdotal evidence suggests that it is sometimes possible to reach higher levels. 

Using exogenous ketones can raise blood ketones to a ‘physiological’ level without the ketogenic diet or fasting. The level of ketosis reached depends on the exogenous ketone supplement used. Reported levels range from 0.6 mM with a ketone salt or a medium chain triglyceride supplement18,22 up to  6 mM with a ketone ester drink19.   

Pathological Ketosis

Sometimes the body starts producing ketones as a result of a disease (pathology).  This can lead to dangerous levels of ketones in the body.  These high levels are very uncommon in healthy people following the ketogenic diet. 

Alcoholic ketoacidosis (AKA) is a result of chronic alcohol consumption usually accompanied by malnutrition. AKA is characterized by increased ketone production (levels > 15 mM) via liver alcohol metabolism, in conjunction with a mild elevation in blood glucose levels. Symptoms include nausea and vomiting, fatigue, altered breathing and abdominal pain23

Diabetic ketoacidosis (DKA) occurs most frequently in patients with Type I diabetes. DKA is characterized by the simultaneous occurrence of high blood ketones (> 20 mM), high blood glucose and acidification of the blood23. It develops when insulin is absent, or insulin signaling is no longer functional. This means the physiological state of starvation is triggered, even in the presence of high blood glucose. As during starvation, lipolysis (fat release) increases. This causes the liver to produce a high amount of ketones, and blood pH to fall (as ketones are an organic acid). As glucose levels are very high, the excess is excreted in the urine. This draws water and electrolytes out of the body causing dangerous dehydration. Symptoms of DKA include nausea, vomiting, altered breathing, abdominal pain, and unconsciousness. The rapid onset and alarming nature of DKA is a reason why ketosis has a bad stigma in the medical community. 

Who Should Avoid a Ketogenic Diet?

Following a ketogenic diet may not be advisable for people with the following medical considerations:

  • Pregnancy
  • Kidney failure
  • Impaired liver function
  • Impaired fat digestion (gall bladder disease, gastric bypass, pancreatitis)
  • Genetic defects in metabolism (CPTI/II deficiency, beta oxidation defects, fatty acyl dehydrogenase deficiency)

Potential side effects of the ketogenic diet

When starting a ketogenic diet there can be a period of 2-3 days where blood glucose levels are low, but ketone production has not reached a sufficient rate to provide enough fuel for the brain. This can result in a series of symptoms, known as the ‘keto- flu,” which include:

  • Headache
  • Muscle cramp 
  • Fatigue 
  • Nausea
  • Dizziness

Exogenous ketone supplements such as esters, salts, and medium chain triglycerides can be used to reduce  symptoms of ‘keto- flu.” They provide the brain with a source of energy without carbohydrate consumption. These supplements increase the levels of ketones in the blood artificially. Exogenous ketones do not increase endogenous ketone production and actually INHIBIT24 the release of fatty acids from adipocytes. 

It can be initially tricky to adjust food intake to ensure adequate nutrition when following a ketogenic diet. Also, some people find the diet is not sustainable because of individual differences in metabolism or lifestyle. If the diet does not provide the correct balance of macro and micronutrients,  some individuals develop other symptoms beyond the ‘keto-flu' after the adaptation period.  These include:

  • Constipation
  • Bad breath
  • Difficulty in maintaining physical performance
  • Hair loss
  • Gallstones
  • Elevated blood triglycerides or cholesterol

To treat these symptoms, check that the diet provides enough calories and enough micronutrients. Many people reduce fruit and vegetable consumption on a ketogenic diet (due to carbohydrate content). This means it is easy to become deficient in vitamins and to under-consume fiber. The ketogenic diet can alter the way that the kidneys excrete electrolytes (such as sodium). Electrolyte supplementation can reduce side effects of an electrolyte imbalance. 

Possible clinical applications of the ketogenic diet and ketosis:

Some of the earliest reports of the ketogenic diet describe its use in a clinical setting. In the early-20th century, ketogenic diets helped treat drug-resistant epilepsy in the early 20th century. Doctors also prescribed ketogenic diets to treat Type I diabetes before the invention of insulin. As analytical techniques progressed, scientists learned that ketones themselves might be a crucial part of the success of the ketogenic diet to treat disease. This finding stemmed a field of research to examine the potential benefits of ketosis in a range of disease states:

  • Weight loss
  • Diabetes and metabolic syndrome
  • Neurological disease: epilepsy, Alzheimer's disease, Parkinson's disease, migraine, concussive disease and traumatic brain injury.
  • Cancer
  • Inflammatory diseases

While the ketogenic diet is not yet first-line treatment recommended by doctors for any of these diseases, it is a relatively easy and tolerable way that patients with these conditions can take steps that could improve their health. Emerging research suggests there may be beneficial effects of ketosis for some people, and further studies are required to confirm how best to use the diet in these clinical settings. 

The History of the Ketogenic Diet

Fasting and early pioneers of the ketogenic diet

The concept of fasting (taking in no calories) predates the ‘ketogenic diet’ as we now understand it. That said, many of the benefits of fasting are likely due to the presence of ketones in the body. 

Fasting has been used as a tool to physically and spiritually cleanse oneself since the earliest days of man. The Bible describes fasting as a treatment for convulsions in the bible. The Ancient Greek philosopher Hippocrates said: ‘to eat when you are sick is to fuel your sickness.’ 

The early advocates of therapeutic fasting were unaware that ketosis is a crucial factor in the anticonvulsant effect of fasting. In the early 1900s, physicians at the Mayo Clinic observed a link between low carb diet and fasting. They discovered that severely restricting dietary carbohydrates and increasing fat could decrease seizures in the same way as fasting25. It was not until the mid-1900s when scientists could measure ketones that we understood that fasting led to the presence of ketones in the body. 

Epilepsy was not the only disease historically treated with a low carbohydrate, high-fat diet. Low carbohydrate diets were also advocated for patients with diabetes and obesity. Before the discovery of insulin in 1921 , diabetes was usually managed through carbohydrate restriction. William Banting, an obese British mortician,  popularized the weight-loss benefits of a diet ‘striped of starchy foods’ in a pamphlet "Letter on Corpulence, Addressed to the Public".

The dark ages for the ketogenic diet

To many, a low carbohydrate and high-fat diet is a counter-intuitive approach to support health. There is a widespread fear of dietary fat and its link to obesity and its associated health complications. 

In 1953 Ancel Keys, an American biochemist published an epidemiological study that introduced the "diet-heart" hypothesis. The study claimed that dietary fat was a key risk factor in the development of heart disease. The "diet-heart" hypothesis proposed that blood LDL and cholesterol derived from dietary fat accelerates the development of atherosclerotic plaques26

His work came at the time that the president of the USA, Dwight Eisenhower, suffered a heart attack. Following the advice of his physician, the then president publicly cut back his fat intake. Nutrition was in the spotlight and Keys was able to push his hypothesis forward. This led to radical changes in global food policy and public practice. The USDA 1977 Dietary Goals for Americans recommended a decrease in dietary fat intake, and a diet based on grains and cereals27

No clinical evidence supported Keys' "diet-heart" hypothesis. Subsequent large trials including the Framingham Study and Women's Health Initiative Randomized Controlled Dietary Modification Trial failed to show that decreasing dietary fat lowered the risk of heart disease28,29

The incidence of obesity rose following the adoption of the USDA guidelines. Some investigators hypothesized that increased dietary carbohydrates were responsible for the developing health crisis. Most famously, John Yudkin describes this phenomenon in his book "Pure White and Deadly"30. The widespread fear of dietary fats has caused scientists and nutritionists to overlook the role of sugar and starch. 

Resurgence of ‘low carbohydrate’ diets

'Low fat' dieting was widespread in the late 1900s. During this time, Dr. Robert Atkins became an infamous spokesperson for the keto diet. Dr. Atkins brought his version of the ketogenic diet to the masses in his 1972 book: “Dr. Atkins' Diet Revolution”3. In his 40 years of practice, Dr. Atkins treated an estimated 60,000 patients for obesity and related conditions. At that time, there were no clinical studies to validate the benefits of the diet. Many patients reported side effects while starting the diet, including fatigue, weakness, dizziness, headache, and nausea. This uncomfortable induction phase labeled the "Atkins Flu".

After Atkins' death in 2003, others started to promote the ketogenic diet for health. The Atkins Foundation recently funded a group of scientists to study the effects of the Atkins diet formally. This group of scientists includes Jeff Volek, Stephen Phinney, and Dr. Eric Westman. They discovered that the Atkins diet outperformed a diet based on the 1977 USDA guidelines with respect to measured coronary risk factors including decreased low-density lipoprotein-cholesterol and total blood saturated FFA alongside increased high-density lipoprotein cholesterol31. This outcome may be due to the decrease in carbohydrate and concomitant changes in the hormonal milieu, or due to effects of ketone bodies on substrate metabolism. 

The pendulum of public perception begun to swing in favor of diets higher in fat, thanks to the emergence of influential writers and speakers such as Gary Taubes, Robert Lustig, and Nina Teicholtz and clinicians and scientists such as Professor Tim Noakes, Dr. Jason Fung, and Professor Thomas Seyfried. The work of these individuals exposed flaws in the "diet-heart hypothesis." 

These influencers helped expose corruption in the political decisions that resulted in the last decades of vilification of dietary fat. Evidence illustrating the role of high dietary carbohydrate in the development of obesity and diabetes has started to grow. Much of the recent research suggests that low-fat diets may be harmful to health. This culminated with a recent meta-analysis of data from 18 countries, which linked increases in carbohydrate intake with increases in mortality12

The fear of fat has continued to reverse. Over the last few years, the ketogenic diet has grown in popularity. Popular culture is starting to recognize and adopt the keto diet, and online searches have grown. More and more doctors now encourage and prescribe the ketogenic diet to treat metabolic disorders and obesity. Large online commmunities bring thousands of people together to discuss research, share keto diet before and after photos, and encourage each other. 

  1. Cahill, G.F., Jr. (2006). Fuel metabolism in starvation. Annu Rev Nutr 26, 1-22.

  2. Arora, S.K., and McFarlane, S.I. (2005). The case for low carbohydrate diets in diabetes management. Nutr Metab (Lond) 2.

  3. Atkins, R.C., Mandell, F.G., and Monica, H. (1972). Dr. Atkins' diet revolution: The high calorie way to stay thin forever. (D. McKay Company).

  4. Loren Cordain: The Paleo Diet: Lose Weight and Get Healthy by Eating the Food You Were Designed to Eat

  5. Rabast, U., Vornberger, K.H., and Ehl, M. (1981). Loss of weight, sodium and water in obese persons consuming a high- or low-carbohydrate diet. Ann. Nutr. Metab. 25, 341-349.

  6. Westman, E.C., Yancy, W.S., Edman, J.S., Tomlin, K.F., and Perkins, C.E. (2002). Effect of six-month adherence to a very-low-carbohydrate diet program. Am J Med 113.

  7. Diabetes UK Website: Blood Sugar Level Ranges

  8. Kossoff, E.H., and Rho, J.M. (2009). Ketogenic Diets: Evidence for Short- and Long-term Efficacy. Neurotherapeutics 6, 406-414.

  9. Slavin, J. (2013). Fiber and Prebiotics: Mechanisms and Health Benefits. Nutrients 5, 1417-1435.

  10. Pfeifer, H.H., and Thiele, E.A. (2005). Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology 65, 1810-1812.

  11. Volek, J.S., and Phinney, S.D. (2012). The Art and Science of Low Carbohydrate Performance. (Beyond Obesity LLC ).

  12. Mente, A., Dehghan, M., Rangarajan, S., McQueen, M., Dagenais, G., Wielgosz, A., Lear, S., Li, W., Chen, H., Yi, S., Wang, Y., Diaz, R., Avezum, A., Lopez-Jaramillo, P., Seron, P., Kumar, R., Gupta, R., Mohan, V., Swaminathan, S., Kutty, R., Zatonska, K., Iqbal, R., Yusuf, R., Mohammadifard, N., Khatib, R., Nasir, N.M., Ismail, N., Oguz, A., Rosengren, A., Yusufali, A., Wentzel-Viljoen, E., Puoane, T., Chifamba, J., Teo, K., Anand, S.S., and Yusuf, S. (2017). Association of dietary nutrients,with blood lipids and blood pressure in 18 countries: a cross-sectional analysis from the PURE study. The lancet. Diabetes & endocrinology 5, 774-787.

  13. Dehghan, M., Mente, A., Zhang, X., Swaminathan, S., Li, W., Mohan, V., Iqbal, R., Kumar, R., Wentzel-Viljoen, E., Rosengren, A., Amma, L.I., Avezum, A., Chifamba, J., Diaz, R., Khatib, R., Lear, S., Lopez-Jaramillo, P., Liu, X., Gupta, R., Mohammadifard, N., Gao, N., Oguz, A., Ramli, A.S., Seron, P., Sun, Y., Szuba, A., Tsolekile, L., Wielgosz, A., Yusuf, R., Hussein Yusufali, A., Teo, K.K., Rangarajan, S., Dagenais, G., Bangdiwala, S.I., Islam, S., Anand, S.S., and Yusuf, S. (2017).,Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet.

  14. Volek, J.S., Gomez, A.L., and Kraemer, W.J. (2000). Fasting lipoprotein and postprandial triacylglycerol responses to a low-carbohydrate diet supplemented with n-3 fatty acids. J. Am. Coll. Nutr. 19, 383-391.

  15. FDA Website: Final Determination Regarding Partially Hydrogenated Oils (Removing Trans Fat)

  16. Paoli, A., Bianco, A., Grimaldi, K.A., Lodi, A., and Bosco, G. (2013). Long term successful weight loss with a combination biphasic ketogenic Mediterranean diet and Mediterranean diet maintenance protocol. Nutrients 5, 5205-17.

  17. Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice Newman, John C. et al. Cell Metabolism , Volume 26 , Issue 3 , 547 - 557.e8

  18. Rodger, S., Plews, D., Laursen, P., and Driller, M. (2017). The effects of an oral β-hydroxybutyrate supplement on exercise metabolism and cycling performance.

  19. Cox, P.J., Kirk, T., Ashmore, T., Willerton, K., Evans, R., Smith, A., Murray, Andrew J., Stubbs, B., West, J., McLure, Stewart W., et al. (2016). Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metabolism 24, 1-13.

  20. Gibson, A.A., Seimon, R.V., Lee, C.M., Ayre, J., Franklin, J., Markovic, T.P., Caterson, I.D., and Sainsbury, A. (2015). Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes. Rev. 16, 64-76.

  21. Krebs, H.A. (1966). The regulation of the release of ketone bodies by the liver. Adv. Enzyme Regul. 4, 339-354.

  22. Vandenberghe, C., St-Pierre, V., Pierotti, T., Fortier, M., Castellano, C.-A., and Cunnane, S.C. (2017). Tricaprylin Alone Increases Plasma Ketone Response More Than Coconut Oil or Other Medium-Chain Triglycerides: An Acute Crossover Study in Healthy Adults. Current Developments in Nutrition 1.

  23. Laffel, L. (1999). Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab. Res. Rev. 15, 412-426.

  24. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. Taggart et al J Biol Chem. 2005 Jul 22;280(29):26649-52.

  25. Wheless, J.W. (2004). Chapter 2- History and Origin of the Ketogenic Diet. (Humana Press Inc).

  26. Keys, A. (1953). ATHEROSCLEROSIS: A PROBLEM IN NEWER PUBLIC HEALTH*‘. Atherosclerosis 1, 19.

  27. McGovern, S.G. (1977). Dietary Goals for The United States. (U.S Government Prniting Office).

  28. Anderson, K.M., Castelli, W.P., and Levy, D. (1987). Cholesterol and mortality. 30 years of follow-up from the Framingham study. JAMA 257, 2176-2180.

  29. Howard, B.V., Van Horn, L., Hsia, J., Manson, J.E., Stefanick, M.L., Wassertheil-Smoller, S., Kuller, L.H., LaCroix, A.Z., Langer, R.D., Lasser, N.L., et al. (2006). Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295, 655-666.

  30. Yudkin, J., and Lustig, R.H. (2013). Pure, White, and Deadly: How Sugar Is Killing Us and What We Can Do to Stop It. (Penguin Group USA).

  31. Forsythe, C.E., Phinney, S.D., Fernandez, M.L., Quann, E.E., Wood, R.J., Bibus, D.M., Kraemer, W.J., Feinman, R.D., and Volek, J.S. (2008). Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation. Lipids 43, 65-77.

Emails worth reading.

Once a week, we'll send you the most compelling research, stories and updates from the world of human enhancement.

HVMN Co-founders Michael Brandt and Geoffrey Woo