Compare The Standard Western Diet With The KMP

Let’s compare the ketogenic diet with the Standard Western diet in terms of macro-nutrients: - Carbohydrate intake averages about half of calorie intake in most Western diets - Fat and protein intake varies but combined they make up the other half of calorie intake When looking at the Standard Western diet, carbs make up about 45-65% of calorie intake, protein about 10-35% and Fat is 20-35%.

Digestion of carbohydrates on a Standard Western diet usually leads to a rise in blood glucose. All carbohydrates, whether unrefined or refined, will eventually lead to increased blood sugars- at different rates, of course. Once blood glucose goes above a certain threshold and can become dangerous for the body, the pancreas starts to produce a hormone called insulin. Insulin has a lot of different roles in the body. One of them is to move glucose from the blood stream into the cells. There are glucose receptors on every cell membrane and they allow the transfer of glucose from the blood into cells where it is used for energy generation.

Insulin is also our “fat storing” hormone, i.e. turns glucose into fat when we can’t use it all up- which is often the case. Insulin also has an important role to play when it comes to regulation of sodium in kidneys, for instance. This is why initially, when somebody goes on a ketogenic diet, dehydration can become an issue when insulin drops. The membranes of cancer cells typically contain more glucose and insulin receptors than normal cells and we will see later why this is so important. So, this ready supply of glucose allows to “fuel” cancer cells, allowing them to survive and thrive. Fat intake on a ketogenic diet for cancer is at least 70% of total calorie intake but ideally much higher and for most people it is more around 85%. For children and in the case of epilepsy especially, it can be over 90% even. Protein intake is 12-20% of total calorie intake or about 1-1.5g per ideal body weight.

There are important considerations to make when it comes to protein: People who are going through treatment, are scheduled for surgery or need to support their immune system need a higher intake. We will look into this in further detail. Carbohydrate consumption is minimal at around 3-5% of total calorie intake, according to Professor Tomas Seyfried, author of the book “Cancer as a metabolic disease”. He recommends net carb intake of 12 gram per day.

Is Cancer Really a Genetic Disease?

Recently, more and more researchers have started to question whether it’s a good idea to pour a lot of money into genome projects. Hundreds and thousands of gene mutations in different cancers have been identified and have certainly led to advances in the field of molecular biology, but have they done much to defeat cancer?

Gene-based targeted therapies show a lot of promise against those few cancers that are inherited (5-10%) but what about the rest of them that aren’t? Dr Thomas Seyfried provides plenty of evidence that cancer is a metabolic rather than a genetic disease. Source: “Cancer as a Metabolic Disease”,  Thomas Seyfried.

You see on the left that a healthy cell begets two healthy cells and a cancer cell begets two cancer cells. But what is responsible for the unregulated cell growth in the tumour cell? Is it the mutations in the nucleus as mainstream medicine views it or is there a possible connection with abnormalities in the mitochondria? Mitochondria are small organelles sitting in the cytoplasm, the area surrounding the nucleus, and generate the energy in a cell.

We know that they’re also abnormal in the tumour cell because energy metabolism is disrupted. In experiments, when the nucleus of a tumour cell is moved into a healthy cytoplasm, the result is normal cells and sometimes even normal tissue. Although the nucleus is supposed to contain the mutations that drive cancer, we don’t see this happening in these experiments. When the nucleus is taken out of a normal cell and put into a cancer cell cytoplasm, the result is dead or cancerous cells. Could it be that normal mitochondria suppress the formation of tumours? Could this indicate that the gene mutations in the nucleus are NOT the drivers of this disease? Does it make sense to focus the majority of research on finding all the possible mutations?

Mechanisms of the KMP Framework

So why exactly is it that a ketogenic diet compromises cancer cell metabolism - in other words how a cancer cell produces energy? How can a simple reduction of carbohydrates  and an increase fat intake make such a difference? So the first thing we need to know is that: - Tumour tissue relies heavily on glucose as a fuel. In cancer diagnostics this has been taken advantage of for quite a good while now with the PET scan. With the help of a PET scan, oncologists aim to detect cells that take up glucose at a much higher rate, i.e. cells that are metabolically more active and “gobble up” glucose. Before the scan, radioactive glucose is injected into the veins. Once the glucose starts to spread, the metabolically active areas light up more than others.

We also know that when insulin levels are low because the glucose is at a consistently low level, there’s a decrease amount of glucose that can reach cancer cells. And this has several consequences: less insulin means that fewer insulin receptors are activated and we know cancer cells have up to 10 times the number of receptors as normal cells both for glucose and insulin. If fewer receptors are present, less glucose is moved across the cell membrane.

As a result, glucose is becoming scarce for healthy cells but they just switch to burning fat as a fuel. The graphic below hopefully helps to illustrate this whole process: On the left side, you see differentiated tissue- which are the healthy cells- and what happens if oxygen is present so (+O2). Glucose enters the cell, it is split into two molecules (by glycolysis) and turned into pyruvate. Pyruvate then enters the so-called mitochondria, small organelles that are the powerhouse of cells. Through oxidative phosphorylation, 36  molecules of ATP are produced. ATP is the energy currency of the cell.

As a by-product, there’s some CO2 and also a little bit of lactate. If no oxygen is present (-O2), for instance when we exercise heavily and go into an anaerobic state as a sprinter, then glucose enters the cell, it is split and we end up with pyruvate again. Also as a by-product, a large amount of lactate is produced. It’s what causes that burning sensation in our muscles.

As you can see, this process is a lot less efficient in terms of energy generation. Through anaerobic glycolysis, we generate 2 molecules of ATP as opposed to 36 when oxidative phosphorylation is used. On the right side, we have proliferative tissue or a tumour cell. It doesn’t matter whether oxygen is present or not - the process of energy generation in a cancer cell is usually the same.

So glucose enters the cell, then glycolysis breaks down glucose and forms pyruvate. Some pyruvate then can go into the mitochondria as well but that’s very much dependent on how damaged the mitochondria are- usually they are severely compromised in cancer cells or even lack completely. The majority of the pyruvate is converted into lactate. Lactate has a few major roles in cancer cells: it makes sure that the immune system has a hard time recognizing that tumour tissue is present and it also makes it easy for a cell to metastasize.

In case anybody is wondering what happens to the 10% here because we have 5% going into the mitochondria and 85% converted into lactate. About 10% of glucose is diverted into so-called bio-synthetic pathways upstream of pyruvate production. These pathways are very necessary for producing new cells for instance and but also just to maintain a certain balance of the cancer cell (called redox balance).

This whole process of energy generation in a cancer cell here is called “aerobic glycolysis” and it’s also called the Warburg effect. Otto Warburg was a Germany scientist carrying out lots of research in the 1920’s 1930’s. He showed that whether oxygen is present or not, cancer cells prefer to use glycolysis (the splitting of glucose) for energy generation. The whole process or effect is also referred to as “fermentation”.

As we have seen, in comparison to oxidative phosphorylation, this process is a lot less effective because it only generates 4 molecules of ATP. You will probably come across the term “Warburg effect” quite a lot when researching the ketogenic diet and I hope you have a clearer idea now what it is.

Did you know… … that Otto Warburg won the Nobel Prize for his research into metabolism of tumours and respiration of cells in 1931?

So is cancer as a metabolic disease really a new discovery? As a summary of what we looked at earlier, cancer cells are “glucose-avid”- this is the scientific terms for cells that require unusually large amounts of glucose. When an oncologist gets the result of the PET scan, he will also know what the rate of glucose efficiency is. By lowering glucose levels and interfering with glucose and insulin transport, cancer cells are deprived of their preferred fuel.