The Ketone Advantage

Finally I have the opportunity to delve into an arena I am passionate about again, after being swamped by the institution of medicine and its myopic teachings for the greater part of the year. My final year of medicine has been enlightening to say the least – as much as I have enjoyed being hands-on and part of the team, I have realised how redundant traditional medicine can be. Repeatedly seeing the same types of patients on ward rounds who land up in hospital either as a result of their environment or their own lifestyle choices has further spurred me on to pursuing an arena of medicine that is “unconventional”. I do not see myself treating symptoms, I need to treat the cause; I cannot discharge a patient because they are not acutely ill, I want them to be in optimal health. So to say this year has been frustrating is an apt description, but to say it has been uplifting is equally fitting – I now know the path I want to follow and, although the steps are not clearly demarcated, I am confident I will get to my destination. My first step is to complete my qualifications in Nutrigenomics and Functional Medicine during my internship, my next step is to specialise in Sports Performance Medicine – exciting times, which will all be documented here on my blog 🙂
But let’s get started with today’s topic: what is all this fuss about ketosis, and can it work for enhancing performance?

In order to fully understand what we are talking about, we need to delve into a bit of biochemistry, so hang in with me here… Or if you don’t care, then skip to the bottom of this section 😉 But if you really want to understand this topic, it takes some mental energy and not just reading blanket statements on web pages!

Lipids (fats) are digested by various enzymes from your salivary glands, stomach, and pancreas. After being absorbed in the intestine, they are solubilised into things called chylomicrons which then enter the lymphatic system first and then the blood. Once in the blood vessels, they are hydrolysed into their components, namely free fatty acids (FFA) and glycerol – FFA’s are absorbed primarily by adipose tissue cells (fat cells) and glycerol returns to the liver for re-use in triglyceride synthesis.

Under the action of adrenaline or glucagon, enzymes in the cell that breakdown fat (lipases), mobilise the FFA’s from adipose tissue – insulin, however, inhibits this process. Following release, the FFA’s bind to albumin (a protein made by the liver) and this complex binds to receptors on the cell. This sets up a concentration gradient causing a “flip-flop” of the membrane and then subsequent intracellular trafficking of the complex for use/storage/oxidation.

Oxidation of fatty acids occurs in little organelles within the cell called mitochondria (long chain fatty acids containing 14 or more carbon atoms actually get processed inside peroxisomes instead but that could make this discussion a bit too complicated – the relevance here, however, is that this oxidation yields significant reactive oxygen species which can damage pancreatic cells that release insulin – research this if you are interested!) The end-product of this oxidation process is acetyl-coA, which then enters a cycle called the TCA/Krebs cycle and produces energy in the form of ATP. Interestingly, the oxidation of fatty acids yields more molecules of ATP than the equivalent amount of glucose carbon atoms!!

So how is all this regulated? The pancreas is the organ responsible for sensing glucose concentration – a decrease causes glucagon release and an increase causes insulin release. In the presence of insulin, enzymes that synthesise fatty acids are stimulated whereas enzymes that cause release of fatty acids from adipose tissue are inhibited. Glucose is oxidised in a process called glycolysis into pyruvate and then into acetyl-coA. Acetyl-coA is the important one to remember here as it will come up again when we talk about ketosis. In the fed state, this acetyl-coA enters that TCA cycle we mentioned earlier to produce ATP (energy), but it also gets metabolised into another molecule (malonyl coA) which inhibits fatty acid oxidation and causes triglyceride (glycerol + fatty acids) synthesis. In the fasted state, however, glucose is spared for the brain and so glucagon causes the breakdown of fat into FFAs – with high rates of production, the TCA capacity is exceeded and so the excess acetyl-coA is metabolised into ketone bodies (namely acetoacetate, acetone and beta-hydroxybutyrate; beta-hydroxybutyrate is not technically a ketone due to its structure – something else to research if you’re interested!) Ketone bodies are used by tissues other than the liver via reactions which are a reversal of ketone body synthesis.

So in summary:

  1. When there is glucose, there is insulin
  2. Insulin causes: glucose flux into cells, glycogen accumulation in muscle and liver cells, and increased conversion of pyruvate into acetyl-coA which then enters the TCA cycle to produce ATP (energy)
  3. When glucose is low, there is glucagon
  4. Glucagon causes fat breakdown, and if the capacity of the TCA cycle is exceeded, the free fatty acids are metabolised into ketone bodies
  5. Ketone bodies are reassembled and used by tissues outside the liver
  6. And a state of ketosis gives us MORE energy: fatty acid oxidation produces more moles of ATP per carbon atom than carbohydrate oxidation (146 moles vs 114 moles)


Well Done! You made it through! But how can you use this knowledge if you’re an athlete?

The 3 primary reasons to use ketosis if you’re an athlete are:

  1. Metabolic superiority of fats as fuel: studies have shown that a ketogenic state enhances breakdown of fat, and enhances aerobic capacity and muscular endurance. Read more details here.
  2. Mental enhancement: ketones increase brain neuron regeneration and enhance focus and concentration. (Interestingly, ketosis is used for medication-resistant seizures – something else to research if you’re interested!)
  3. Health and longevity: high blood glucose levels lead to pancreatic dysfunction, diabetes, cardiovascular disease, eye and kidney problems. Read my previous post on Cholesterol too if you’re interested in how dietary fat is not linked to high cholesterol but is rather the result of carbohydrates.


So how low do you go? To be in a state of ketosis, one needs to adhere to a diet of only 5-10% carbohydrates (about 50g per day) – this is extremely difficult, and especially if you want to include vegetables in your diet which I highly recommend! In a future post, I will discuss the importance of the microbiome, but essentially my aim is to maintain a low carbohydrate diet while simultaneously supporting a good population of gut bacteria! I prefer what Ben Greenfield recommends and that is 20-30% carbohydrates, 50-60% fat, and 20-30% protein. Keeping the carbohydrates for the post-exercise window period allows for all the benefits of ketosis during the day and leading up to training, a slightly higher carb percentage to support higher intensity anaerobic training as well as immune system function, and maintenance of a good microbiome.

I hope you enjoyed this blog post – it may have been technical but I don’t believe in blindly following things that you don’t understand. Better inform yourself to make better decisions. I appreciate the feedback so leave any comments, questions and suggestions. Happy training and eating!


Soon to be published:

  1. How to use MCTs (medium chain triglycerides) to your advantage
  2. The importance of the micro biome in health and performance

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