The Ketogenic Diet

Introduction

It is self-evident that biological energy is essential for life, yet very few have a clear idea of what biological energy actually is. This post outlines the concept of human energy, focusing on the central biological energy molecule – ATP, showing how ATP couples with other molecules to produce chemical reactions that would not otherwise occur, showing how these coupled reactions drive human metabolism, and just about everything else.

This post outlines the significance of the ketogenic diet for human health and energy, showing how it removes three roadblocks to healthy weight management – fat retention, triglycerides and hunger, explaining the role of ketones as a clean superfuel which metabolises 30% more efficiently than other nutrients with far less free radical damage, finally showing the diet's role in combating several major diseases from epilepsy and Alzheimer’s to diabetes and cancer.

We show how ketosis is hard-wired into human biology, evolving over millions of years, shaping human physiology in response to scarcity and uncertainty. We then look at some compelling evidence of the value of the ketogenic diet, evidence from a recent controlled trial resulting in significantly improved biological markers for weight, BMI, cholesterol, triglycerides and blood glucose. Lastly, we look at my personal experience on the diet from December 2011 to May 2012.

Human energy

Most chemical reactions occur at very high temperatures – hundreds if not thousands of degrees. Human biology, however, constrains reaction temperatures to remain within the normal range of human body temperature (35–36 degrees Centigrade). At these temperatures, most biological reactions  simply will not occur fast enough to be useful. Biological reactions therefore require catalysts to make them react faster. One key catalyst is localised heat - kinetic energy. Human biochemistry uses localised heat to accelerate chemical reactions via coupled reactions where one part of the couple is the reaction we want to occur and the second part is a reaction that generates heat to help the first couple overcome the reaction resistance.

The second component of the couple consists of water and adenosine triphosphate or ATP. The textbooks tell us that ATP is the energy currency of human chemistry – indeed of most plant and animal life on Earth. They will also tell us that the ATP–water reaction is exothermic; a bit of jargon which simply means that when ATP and water react they give off heat. So, coupling water and ATP with slow-reacting molecules provides the heat to make them react much faster. It’s that simple. And it’s that big; the average human body turns over its own body weight in ATP every day.

So there is no mystery about where human energy comes from. It’s simply a molecule – ATP – which when reacted with water gives off heat. But where does ATP come from? There’s not much of a mystery here either, although the details can be complex. Obviously, it somehow comes from the food we eat.

It’s quite striking to see the place that food occupies in human culture: the ceremony, the significance and so on. And where would TV be today without celebrity chef? But at the end of the day, every bit of food consumed assists in producing ATP.

The Krebs Cycle and the Electron Transport Chain

Mitochondria produce ATP. There are hundreds of mitochondria in virtually every human cell. Each mitochondria consists of two microscopic capsule-like containers, one inside the other. On the walls of the inner container are hundreds of tiny processing plants called electron transport chains (ETC) which sit alongside ATP Synthase machines. Inside the inner container, a chemical process called the Kreb's Cycle (after Hans Krebs who discovered it) reduces food molecules to hydrogen atoms for transport to the electron transport chains. Hydrogen atoms each have one electron and one proton and both have a function in the ETC. Electrons power the ETC which pumps protons into the space between the two containers thereby increasing proton volume and pressure in the inter-container space. This pressure, in turn, forces protons back into the inner container via the ATP synthase machines. These are turbine like devices forced to rotate by proton pressure which, in the process, reconstitute ATP from ADP (previously spent ATP). At the end of this sequence, we have ATP and some leftovers: water and carbon dioxide; all that is left of the original food molecules.

ATP production could have been designed by Rube Goldberg; nevertheless it's effective and extensive; it is found in almost all plant and animal life on Earth, and almost half the contents of each human cell, with one or two exceptions, consists of mitochondria, and as noted, the human body will turn over amounts of ATP equivalent to its own body weight in a single day.

The actual process is much more complex than this, but despite the complexity, the essential model is correct. We now have enough to understand the significance of the ketogenic diet. But before that, two other factors need to be discussed. The first has to do with a weak spot in the electron transport chain – oxidant leakage. The ETC is made up of several stages and the earlier stages tend to leak oxidants. Oxidants are unbalanced atoms or molecules which aggressively strip electrons from nearby molecules thereby damaging them – a bit like how rust degrades (or oxidises) iron. Oxidants, unless checked, will eventually degrade mitochondria so badly that they will cease to function.

The second has to do with the relative efficiency of different types of food in generating ATP. Broadly, there are three types of food: carbohydrates (sugars from plants), proteins (amino acids from plants and animals), and fats (again from plants and animals). By the time the food has been through the digestive process, all that remains are sugars (glucose), amino acids and fats (lipids). These three nutrients comprise the food molecules referred to above. Amino acids and glucose generate, respectively, 4 calories per gram, whilst lipids generate 9 calories per gram. Lipids carry more than twice the energy of the two other nutrient types.

The differential in terms of ATPs is even higher; the numbers are: protein 15 ATPs, glucose 36 ATPs and lipids 130 ATPs. Lipids are by far the most efficient way to store energy. However, the lipid molecule is very much bigger so the comparison is not really fair.

The Ketogenic diet (KD)

The KD is often referred to as low carb, but this is ambiguous. Low carb might mean high protein or high fat, and various versions of the low carb diet do involve high protein. The KD, however, is high fat and low or zero carbs.  

The high fat character of the diet has three key characteristics:

·         Ketones are a byproduct of fat metabolism;

       ·         High fat means low fat retention;

·         High fat means absence of hunger;

We will deal with the function of ketones in a later section. High fat diets with low or zero carbs cause low fat-retention. Why? Because high fat diets significantly lower insulin and glycerol. Insulin, produced in response to carbohydrates, forces fatty acids into fat cells and keeps them there. Low insulin, on the other hand, allows fatty acids to circulate in and out of cells freely. Glycerol molecules, also derived from carbohydrates, bind themselves each to three fatty acids, forming triglycerides. Low glycerol entails low triglycerides. This is important because triglycerides are the reason why fat cells get fatter. Triglycerides once formed inside the fat cell from circulating glycerol and fatty acids are too big to escape – they are locked in. Low fat-retention therefore removes two key road blocks to healthy weight loss: insulin and glycerol.

High fat diets also involve an absence of hunger. Experiments have shown that high fat diets produce a hormone: cholecystokinin (CCK) which triggers the satiety centres of the brain. This effect is particularly pronounced with foods rich in oleic and linoleic acids such lamb and pork. Traditional dieting is predicated on the idea of ‘semi-starvation’ and most people simply cannot cope for any length of time with overwhelming hunger pangs. The absence of hunger therefore removes a third important road block.

The role of ketones

Ketones are a byproduct of fat metabolism. The liver produces ketones all the time, but on a standard diet they are almost always completely consumed. On the other hand, on a high fat diet, fat is metabolized everywhere in the body and the level of circulating ketones rises accordingly. Ketones can function anywhere in the body including the brain, and are especially preferred by the heart and the brain.   

Ketones have several important characteristics which make them extremely valuable as a source of nutrition. Firstly they are very efficient. Some estimates suggest that they have an energy advantage of almost 30% over alternative fuels. They have been referred to as superfuels:  

Recent  studies have  shown  that n-{3-hydroxybutyrate,  the  principal "ketone",  is  not just a fuel, but a "superfuel" more efficiently producing ATP energy than glucose  or  fatty acid. In a perfused rat heart preparation, it increased contractility and decreased oxygen consumption.

Ketoacids? Good Medicine? Cahill, G. F. and Veech, R. L. 2003

Given the removal of carbohydrate roadblocks , and the super efficiency of ketones as a fuel it is easy to reduce ones food intake by as much as a third without any corresponding loss of energy or hunger pangs - without, in fact, even noticing it.

But ketones are not only a more efficient fuel; they are also a cleaner one as well. In experiments conducted by Veech it was shown that not only did ATP output increase significantly, but oxygen consumption also fell sharply. Cahill and Veech go on to say:

It should also be pointed out that the altered ratio of NAD+ to NADH should reduce free radical [oxidant] formation, and, 3OHB has been shown to increase viability in neuronal cells in tissue culture exposed to the toxins associated with Alzheimer's and Parkinson's diseases (ibid, pg 157).

You will recall from above, oxidants play a key role in the creation and evolution, over time, of metabolic damage. Indeed they have been strongly implicated as some of the key players in the aging process itself.

Good Medicine?

Ketogenic diets have been successfully used to treat refractory epilepsy for nearly one hundred years. It is still today the only alternative to brain surgery in really serious cases and its success rate is better. Indeed it seems that ketogenic diets can be useful wherever there may be conditions caused by lack of oxygen (hypoxia) or by inappropriate nervous excitation of one form or another as in epilepsy or Parkinson’s. Ketogenic diets are also showing some considerable success in the treatment of Alzheimer’s disease. The areas where research and experimentation have shown significant potential for ketones include:

·         Epilepsy

·         Alzheimer’s disease

·         Parkinson’s disease

·         Cognitive disorders

·         Anti-cancer

The implications for cancer research are exciting:

Our results suggest that experimental brain cancer is manageable through principles of metabolic control where plasma glucose levels are reduced and ketone body levels are elevated. Dietary energy restriction reduces tumour growth through effects on angiogenesis, apoptosis, and inflammation. Moreover, this dietary therapy may be effective for brain cancer management in humans and can be designed according to established standards (Nebeling and Lerner, 1995; Freeman et al, 2000).

Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Seyfried et al 2003.

The ketogenic diet is similar to the calorie restricted diet which is already known to have neuroprotective properties: 

Both calorie restriction and the ketogenic diet possess broad therapeutic potential in various clinical settings and in various animal models of neurological disease. Following calorie restriction or consumption of a ketogenic diet, there is notable improvement in mitochondrial function, a decrease in the expression of apoptotic and inflammatory mediators and an increase in the activity of neurotrophic factors.

The Neuroprotective properties of calorie restriction, the ketogenic diet and ketone bodies. Maalouf, et al, 2008. 

Nor are these properties only recently discovered.

Ketones and Evolution

Current scientific thinking suggests ketosis evolved in humans because it confers a significant survival advantage. Hunter gatherers must be able to last several days without food. And then, after a big kill, they must be able to store excess food as fat to tide them through the ‘lean’ times. Clearly, this human capacity to cope with severe food uncertainty conferred significant survival value on our Palaeolithic ancestors. Ketosis has thus become hard-wired into human physiology. Under conditions of acute food shortages, without ketosis, humans would have to sacrifice lean body mass in order to survive. Such sacrifices would quickly threaten vital organs, and death would follow in a few days – hardly long enough to find the next meal. But, fortunately, human metabolism lets us save fat whenever we can and release it whenever we need. However, even under starvation conditions, we don’t consume body fat directly. More efficiently, we consume ketones instead. Scientists estimate that ketosis increases male survival time from ten up to sixty days; Female survival time up to ninety days, and an obese person could survive for up to a year.

Historically, it also conferred extremely good health. Social groups were small, so the risks of serious infections were correspondingly low, and non-infectious diseases were either very low or non-existent. This is corroborated by all the evidence we have about hunter-gatherer societies prior to their incorporation into modern ways of life. Beginning from situations where obesity, cancer, and heart disease are unknown, after a gap of about twenty years, the incidence of such diseases in hunter-gatherer societies rises to match those of their more ‘modern’ counterparts.        

The lessons for today’s society seem obvious, but the implications are enormous. All our official nutritional advice is not only wrong, but dangerously so; all of our major food and agricultural corporations have billions invested in low-fat food products and their self-interest will blinker them to any alternatives, as it did with smoking. Our academic community is unthinkingly committed to the low-fat paradigm despite there being not a shred of evidence to support their case. Our pharmaceutical industry is committed to the current low-fat way of doing things because it brings them a steadily increasing revenue stream from patients needing lifetime medical support. It is no accident that statins – the cholesterol lowering medication that started life as a rat poison – is the biggest money spinner ever for Big Pharma. And it can only grow.

The (fatty) Acid Test

In 2004 the results were published of a twenty four week study into the long-term effects of the ketogenic diet: Long-term effects of a ketogenic diet in obese patients, Dashti, HN et al, 2004. Eighty three obese patients (39M , 44F)  with a body mass index greater than 35, and high cholesterol and glucose were selected. The diet consisted of 30g carbohydrate, 1g/kg body weight of protein, and 20% saturated fat,  80% poly and monounsaturated fat.  The study found that both the weight and body mass index of the subjects decreased significantly. Additionally, total cholesterol decreased significantly with major shifts in composition from LDL to HDL - the so-called 'good' cholesterol. Furthermore, say the authors, the diet decreased the level of triglycerides and blood glucose. The charts below show the results of the study:

Weight

Body Mass Index

Cholesterol

Triglycerides

Blood Glucose

The authors conclude:

The data presented in the present study showed that a ketogenic diet acted as a natural therapy for weight reduction in obese patients. This is a unique study monitoring the effect of a ketogenic diet for 24 weeks. There was a significant decrease in the level of triglycerides, total cholesterol, LDL cholesterol and glucose, and a significant increase in the level of HDL cholesterol in the patients. The side effects of drugs commonly used for the reduction of body weight in such patients were not observed in patients who were on the ketogenic diet. Therefore, these results indicate that the administration of a ketogenic diet for a relatively long period of time is safe. Further studies elucidating the molecular mechanisms of a ketogenic diet are in progress in our laboratory. These studies will open new avenues into the potential therapeutic uses of a ketogenic diet and ketone bodies.

(ibid, Dashti, et al 2004)

It is quite extraordinary how mainstream nutritionists still insist that, in spite of all the evidence which shows that the ketogenic diet improves every vital sign, it is still somehow bad for you. This is analogous to the old joke: the operation was completely successful but the patient died. Here all the evidence about ketogenic diets is telling us the operation was successful, but mainstream nutritionists are telling us the patient died.

Well, that's how the diet performs over nearly six months on obese patients, but how about on non-obese individuals?

Personal Experience

It is not really surprising that, given my conceptual commitment to the ketogenic diet, I would have tried it to see how it performs in practice. The charts below are self-explanatory and show my results over a period of four months since December 2011. My initial BMI was 24, it's now just above 22.

The first chart speaks for itself. The second chart shows how the ketogenic diet preserves lean body mass. The fat proportion is declining sharply; but the lean body mass, muscle component is increasing. There was no change in my (low) exercise regime during this period. The diet involved a constant range of between 1500 to 1800 calories per day, mainly from fatty meats such as lamb and pork; thinly sliced cold chicken served with healthy dollops of Thomy mayonnaise is also a favorite. As is common with such diets I have felt no hunger, and indeed have often felt a mild sense of euphoria. My energy levels are high and my work output has never been higher or of better quality.