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The ketogenic diet is a low-carbohydrate, high-fat, adequate protein diet. This dietary pattern changes the way our body produces energy – its basic principle is to get your body into a metabolic state known as ketosis where carbohydrate stores are depleted and fat becomes the main energy source. The name ketosis comes from the molecules that the liver starts to produce from fat to be used as fuel - ketone bodies or ketones.

Ketone-fuelling with BHB salts and MCT Oils has become a lifestyle approach of choice because it allows fast weight loss with no harm to physical or mental performance and resistance. In fact, an effective transition to ketosis may actually improve these outcomes.

On a regular or high-carbohydrate diet, our body is in a state optimised for the use of dietary carbohydrates. But in a continuous state of carbohydrate restriction, the body puts its plan B in motion, switching gears such as to become more efficient at using fat as the main energy source. Ketosis boosts the body's capacity to use fats as fuel.

So, instead of obtaining energy from stored carbohydrates, your body obtains energy from stored fat - you basically eat fat to lose fat. Ketogenic low-carbohydrate, high-fat diets have been shown to be highly effective in promoting weight loss, when carried out properly. 


An interesting fact about the ketogenic diet is that it was designed in the 1920s as a way to reduce the occurrence of epileptic seizures. It is still being used to this day as a non-pharmacological approach to the treatment of epilepsy, although its mechanisms of action are poorly understood.

A number of derivative diets have evolved from ketogenic dietary principles. These include the Paleo, Primal, Atkins and Bulletproof Diets. 


Ketogenic diets and the regulation of appetite 

Ketones are believed to be able to suppress appetite, often leading to better outcomes than official dietary guidelines. But how do ketone bodies regulate appetite? 

In the brain, more specifically, in the hypothalamus, incoming signals from various hormones in the blood act to regulate appetite and energy expenditure. These include hormones from the gastrointestinal tract, pancreas and adipose tissue, such as leptin, insulin, ghrelin, amylin, cholecystokinin, among others. Blood glucose and free-fatty acid levels also actively contribute to the regulation of appetite.  

A common consequence of weight loss diets is the development of a kind of compensatory mechanism that potentiates weight regain and reductions energy expenditure through the action of those hormones. However, in the context of ketosis, these changes have been shown to be suppressed, suggesting an interaction between circulating ketones and the hormonal regulators of appetite, which could explain the suppression of appetite in the ketogenic diet. Indeed, it has been shown that a ketogenic diet may have a direct effect on appetite control hormones and that ketone bodies themselves may even have a direct appetite-suppressant action. 


The biochemistry of the ketogenic diet

When regular (or high) amounts of carbohydrates are ingested, glucose is the primary source of energy.  

When blood glucose levels are low and carbohydrate stores are depleted, the liver starts to produce glucose from other sources, namely proteins and fat stores. But proteins are needed for many other functions in the body, such as building and maintaining muscles, for example. Ideally, the production of glucose from proteins during prolonged carbohydrate restriction needs to be kept to the minimum. Since the body has large amounts of stored fat, the liver uses it as a source of fuel in times of nutrient deprivation or prolonged starvation.  

However, there are some cells that can’t use fatty acids or ketones in the blood as a source of energy because they don’t have mitochondria, the factory cells needed to produce energy from these molecules. That is the case with red blood cells, which therefore depend on glucose. To keep these cells nourished, the liver uses the amino acids that make up proteins and converts them into glucose, in a process known as gluconeogenesis, allowing for a basal level of blood glucose to be maintained even during ketosis - hence the need for a regular protein intake in ketogenic diets. 

Fats stored in adipose tissue are released from the fat cells into the blood as free fatty acids and glycerol. Fatty acids are a very energetic fuel and are taken up by cells to be metabolised in a process called β-oxidation that yields acetyl-CoA, which in turn can be used to produce energy. The liver uses acetyl-Coa from fatty acid metabolism to produce ketone bodies that are then released into the blood to also be used as fuel. Fatty acids released into the blood can’t be used by cells in the central nervous system, because they can’t cross the blood-brain barrier that protects it. But ketones can cross it and act as a substitute for glucose as the fuel for the brain. In fact, some ketones may even be a more efficient energy sources than glucose. 

In case you’re wondering:The cognitive effects associated with EPA/DHA intake  is a consequence of their strong anti-inflammatory and anti-oxidative actions, and of an improvement in vascular function, which in turn improves blood flow to the brain. It's not to a direct action on the brain.

Even when you’re on a regular diet, your body can produce ketone bodies during long periods of fasting or intense exercise. In the ketogenic diet, a similar mechanism occurs. Ketone bodies in the blood become the body’s main fuel.

Humans were actually designed and optimized for periods of fasting. Throughout evolution, food wasn’t always as available as it is now and the storage of fat as a backup fuel may have kept us alive throughout times of food scarcity. By simulating our body’s response to fasting, ketogenic diets may actually meet some our body’s most efficient mechanisms.

Research has shown that intermittent fasting can improve health and even increase lifespan; it can boost the immune system, decrease inflammation and oxidation, decrease the incidence of cardiovascular and neurological diseases and improve cognitive performance. Although there is no actual fasting in ketogenic diets, the metabolic outcome is the same: we start using our backup fat reserves as our main energy source. Are the health benefits also similar?


The benefits of a ketogenic diet go way beyond simple weight loss.

First off, a ketogenic diet can decrease both plasma glucose and insulin concentrations, decreasing the likelihood of developing type 2 diabetes. Also, and as a consequence not only of weight loss, but also of the lower blood glucose levels, the ketogenic diet can have a beneficial effect in reducing complications associated with obesity and other metabolic diseases.

Weight loss can improve insulin sensitivity, decreasing the amount of insulin needed to lower blood glucose. In the context of ketogenic diets, despite the lower levels of circulating insulin, studies have shown contradictory results regarding its effect in insulin sensitivity. There is a considerable amount of evidence showing that a ketogenic diet can improve insulin sensitivity, but an increased insulin resistance (a decreased ability of insulin in lowering blood glucose) has also been described in the context of a high-fat, low-carbohydrate diet. However, insulin resistance was reversed when carbohydrate intake was restored. Overall, individuals with metabolic syndrome, insulin resistance and type II diabetes will most likely benefit from a ketogenic diet.

These metabolic benefits can lead to many other health benefits, namely in cardiovascular health. Ketosis can significantly reduce the levels of blood triglycerides, reduce LDL and increase HDL cholesterol, decreasing the risk of cardiovascular diseases.

As seen previously (link to chronic low-grade inflammation article), high blood glucose levels can contribute to the development of chronic low-grade inflammation and oxidative stress, which in turn can drive a number of pathologies. Fat-storing cells can also release inflammatory molecules that further contribute to chronic low-grade inflammation. Although high fat diets cause inflammation, this is due to the increased fat storage in adipose tissue. In the ketogenic diet, despite its high fat content, the net result is a decrease in adipose tissue, which in turn will lead to a decrease in systemic inflammation. By decreasing the levels of blood glucose, and by burning fat, the ketogenic diet can actively contribute to a decrease in chronic low-grade inflammation and its associated disorders.

A number of neurological benefits have also been described. Besides their anti-epileptic activity, ketogenic diets are regarded as beneficial in multiple neurological disorders, including cognitive impairment, migraine, Alzheimer’s and Parkinson’s disease, sleep disorders, autism and multiple sclerosis. It is speculated that this effect may be due to a neuroprotective action of ketone bodies. Although the mechanisms are still poorly understood, this neuroprotective effect may be due to an an increase in the activity of antioxidant molecules induced by ketones.

This antioxidant action can also have a beneficial effect on mental skills. Indeed, many people on ketogenic diets describe an improvement in cognitive performance. Interestingly, research has also shown that a ketogenic diet may actually increase the number of mitochondria in brain cells, particularly in areas of the brain associated with learning and memory. This is a rather important effect – an increase in the number of energy-producing mitochondria may enhance these cognitive skills and decrease mental fatigue, which stands in line with the reports of improved mental abilities associated with this diet.


Ketogenic diets and sports performance

When thinking of low blood glucose levels one wonders how it can affect physical performance. Glucose is the main fuel for our muscles, but that doesn’t mean they can’t be just as effective running on ketone bodies. 

There are a few studies on the effect of a ketogenic diet in sports performance. A couple of studies with Taekwondo athletes, for example, showed that the ketogenic diet allowed fast weight loss, while also improving aerobic capacity and fatigue resistance. It was also shown that it could decrease inflammatory and oxidative responses that are associated with muscle pain. These results showed that the ketogenic diet allows fats to be used efficiently as an energy source during high energy expenditure, maybe even contributing to a better performance. 

Likewise, a study with off-road cyclists also showed that ketogenic diets may actually favour endurance athletes by increasing fat metabolism during exercise, decreasing body mass and fat content, and reducing muscle damage. A study in elite artistic gymnasts showed that there was no loss of lean body mass, muscle and percentage of muscle during the ketogenic diet, with an actual improvement of body composition being reported. The generation of ketone bodies prevents the loss of muscle by preventing the use of proteins for the generation of energy; muscles could otherwise be broken down to obtain amino acids for the synthesis of glucose in low carbohydrate conditions. 

An increasing number of athletes have adopted a low-carbohydrate, high-fat ketogenic diet. The list includes NBA superstar LeBron James. A couple of years ago he reported that he had lost a high amount of weight on a low-carb ketogenic diet. Endurance athletes seem to be particularly fond of the physical benefits of this diet, particularly the increased physical resistance and faster recovery time. 

There are a multitude of benefits to be obtained from a ketogenic diet. The biggest challenge is to stay away from carbohydrates - sugars naturally found in vegetables and fruit will be enough, so skipping all the refined carbohydrates (bread, rice etc) is an easy starting point. 


Tips for Getting Started on a Ketogenic Diet and avoiding common pitfalls that will make you want to quit:

Start slow. Adaptation to a new fuel source takes time. 

Watch out for keto-flu.

Recognise what nutrients you are removing from your diet. When you for example, cut out bread, you need to replace the fibre and other nutrients.

Understand that your kidneys tend to excrete salt, so you need to replace this with a higher intake. This is why electrolyte supplements have become a staple supplement for keto dieters. You’re likely cutting out processed foods from your diet too. That in itself dramatically reduces your sodium intake.

Try Bulletproof Coffee. This offers a first step into the world of ketone fuelling where you add some MCT oil and Grass Fed Butter or Ghee to your morning coffee.



Sara Adaes is a biochemist with a PhD in neuroscience and with a keen enthusiasm for science communication.


References and further reading

Bueno NB, et al (2013). Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr, 110(7):1178-87. doi: 10.1017/S0007114513000548

Davidson TL, et al (2013). Inter-relationships among diet, obesity and hippocampal-dependent cognitive function. Neuroscience, 253:110-22. doi: 10.1016/j.neuroscience.2013.08.044

Gano LB, et al (2014). Ketogenic diets, mitochondria, and neurological diseases. J Lipid Res, 55(11):2211-28. doi: 10.1194/jlr.R048975

Gibson AA, et al (2015). Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes Rev, 16(1):64-76. doi: 10.1111/obr.12230

Kinzig KP, et al (2010). Insulin sensitivity and glucose tolerance are altered by maintenance on a ketogenic diet. Endocrinology, 151(7):3105-14. doi: 10.1210/en.2010-0175

Klein P, et al (2014). Dietary treatment in adults with refractory epilepsy: a review. Neurology, 18;83(21):1978-85. doi: 10.1212/WNL.0000000000001004

Noh HS, et al (2004). A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet. Brain Res Mol Brain Res, 129(1-2):80-7. doi: 10.1016/j.molbrainres.2004.06.020

Paoli A, et al (2012). Ketogenic diet does not affect strength performance in elite artistic gymnasts. J Int Soc Sports Nutr, 26;9(1):34. doi: 10.1186/1550-2783-9-34

Paoli A, et al (2013). Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr, 67(8):789-96. doi: 10.1038/ejcn.2013.116

Partsalaki I, et al (2012). Metabolic impact of a ketogenic diet compared to a hypocaloric diet in obese children and adolescents. J Pediatr Endocrinol Metab, 25(7-8):697-704. doi: 10.1515/jpem-2012-0131

Rhyu HS & Cho SY2 (2014). The effect of weight loss by ketogenic diet on the body composition, performance-related physical fitness factors and cytokines of Taekwondo athletes. J Exerc Rehabil, 10(5):326-31. doi: 10.12965/jer.140160

Rhyu HS, et al (2014). The effects of ketogenic diet on oxidative stress and antioxidative capacity markers of Taekwondo athletes. J Exerc Rehabil, 10(6):362-6. doi: 10.12965/jer.140178

Sumithran P, et al (2013). Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur J Clin Nutr, 67(7):759-64. doi: 10.1038/ejcn.2013.90

Zajac A, et al (2014). The effects of a ketogenic diet on exercise metabolism and physical performance in off-road cyclists. Nutrients, 6(7):2493-508. doi: 10.3390/nu6072493

Conor McGregor's diet guru states that you've probably been fueling workouts all wrong. https://www.joe.co.uk/fitness-health/conor-mcgregors-diet-guru-reveals-youve-probably-been-fueling-workouts-all-wrong-49603

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