In 1924, Dr. Otto Warburg, a Nobel Prize winning biochemist noticed that the cancer cells he studied exhibited bizarre metabolic behavior. These cells seemed to prefer using sugar to fuel themselves even when the oxygen that normal cells use for energy creation was available.
After studying the phenomenon for several years, he concluded that: “…the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.”1
In fact, cancer cells are so reliant on glucose that physicians use a radioactive glucose analog (a drug that acts like sugar) to locate cancer in the body. The cancer cells take up the drug in great amounts and the radioactive tracer can then be seen on a PET (positron emission tomography) scan.2
Dr. Warburg’s hypothesis became known as the Warburg Effect and although additional research over the past 40 years has confirmed that all cancer cells do indeed exhibit signs of metabolic impairment, the modern oncology industry has continued to stubbornly focus on the idea that cancer is instead a disease caused by genetic mutations.
However, this genetic defect idea has started to lose its luster in the past several years, presumably because the Human Genome Project failed to reveal a definitive genetic cause for cancer3. To the oncology world’s chagrin, all 30,000 or so genes in the human genome were mapped, and not one was identified as a definitive cause of any of the major forms of cancer. And today, despite the billions of dollars spent on cancer research and treatment, we are no closer to a cure than we were 50 years ago.
But there is hope. In his book, Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer4, Dr. Thomas Seyfried provides some solid evidence that Dr. Warburg was on the right path and that cancer starts with metabolic damage brought on by various factors such as inflammation or viral infection. And in fact, it’s actually the metabolically deranged behavior of cancer cells that leads to the downstream genetic damage on which research has been so focused.5,6
Metabolic derangement stems from conditions in which a cell’s metabolism or energy pathways are broken or abnormal in some way. Normal body cells can create energy by breaking down food stuffs and the oxygen we breath in to make ATP (adenosine triphosphate), our main cellular energy source. Most of this energy production happens in the mitochondria, tiny organelles known as the “powerhouses” of the cell. There are several metabolic pathways involved in cellular energy production:
- One cellular fuel pathway involves glucose, which is commonly known as blood sugar. Glucose is a product of the starches and sugars (carbohydrates) in our diet, and it is converted into energy in our cells via a process called glycolysis. In normal cells, glycolysis is an initial metabolic reaction which feeds into the Krebs or TCA cycle pathway where normal “oxygen dependent” cellular respiration occurs. The amounts of ATP created from glycolysis is small, so lots of glucose is needed to fuel any cell relying on this process.
- The second cellular fuel pathway uses the products of fat metabolism. When blood glucose is low, the liver breaks down stored or dietary fat into products called ketone bodies or ketones. These ketones can then flow into the Krebs/TCA cycle to provide energy substrate for cellular respiration. Since the breakdown of ketones provides greater amounts of energy substrate, a cell can make a lot more ATP from ketones than it can from glucose.
Our cells choose their primary metabolic pathway on the fly based on the foods we choose. For example, if we eat large amounts of carbohydrate containing foods, blood sugar levels surge. In response to elevated blood sugar, our pancreas increases the output of insulin, a hormone which helps move glucose out of the bloodstream and into our cells. More insulin in the bloodstream means that more glucose will get pushed into cells to be used as fuel. Eating a high carb diet every day guarantees that the body will be forced to rely mostly on carbohydrate as the main body fuel.
But if we restrict carbohydrate intake and instead eat more protein and fat, then cells have less glucose to burn, insulin levels drop and the body begins to rely more on the ketones produced from dietary fats and stored body fat to fuel cellular energy needs.
This is where the ketogenic diet comes into play. Ketogenic diets restrict carbohydrate intake to about 5% of calories and promote more fat and protein consumption. The body responds by reducing blood sugar and insulin and increasing the breakdown of fats into ketones. This process is called ketogenesis, and it results in elevated amounts of blood ketones while blood sugar and insulin levels fall, a metabolic state called nutritional ketosis.
Getting into and staying in nutritional ketosis is an effective, nontoxic method for creating an inhospitable metabolic environment for cancer cells while at the same time, nourishing and protecting normal tissues.
Normal cells are metabolically flexible. When blood sugar falls (as when you skip a meal or restrict carbohydrate intake) normal cell mitochondria will easily switch to using ketone bodies as an alternative fuel. Even brain and nerve cells, which ultimately must have some glucose can utilize ketone bodies for the majority of their fuel needs if there are enough of them floating around in the blood stream7. In fact, studies have shown that heart, brain and muscle cells perform better when they rely on fats or ketones as a fuel source.8
This ability of the mitochondria in most normal cells to use ketones when glucose is unavailable gives them an metabolic edge that cancer cells don’t have. As Dr. Warburg explained, most cancer cells are limited to using glycolysis to fuel themselves. They can’t metabolize ketones because their mitochondria are broken, so they have no fuel switch to flip when glucose levels drop. Creating and maintaining a metabolic environment in which blood sugar levels are low and ketone levels are high hampers cancer’s ability to thrive. In fact, cancer’s metabolic inflexibility is why ketogenic diets are so effective against it. In a nutshell, by lowering glucose and increasing ketone levels in the blood, the ketogenic diet becomes an effective weapon for starving cancer cells.
In addition, elevated insulin levels also set the stage for the elevation of other hormones which support cancer growth. The ketogenic diet’s inhibition of insulin also inhibits hormones such as insulin-like growth factor 1 (IGF-1) and other metabolic pathways which promote cancer progression.
And that’s not all. One of the functions of cell mitochondria is to repair damage caused by the free radicals which constantly bombard all cells. Free radical damage can be equated to metal damage caused by rusting. Because cancer cells have defective mitochondria, low blood sugar levels cause shortages of energy needed to repair this rust-like oxidative stress. Hence they are more likely to sustain fatal injuries from interactions with oxidizing free radicals. Since radiation therapy works by increasing free radical activity around cancer tissue, it’s no surprise that studies have shown that nutritional ketosis seems to enhance this destructive free radical effect.
In short, the ketogenic diet has a domino effect on cancer. It lowers blood sugar which starves cancer and reduces serum insulin. Reducing insulin effectively inhibits the production of other cancer supporting hormones such as IGF-1. In turn, low insulin and low IGF-1 levels inhibit other hormonal drivers of cancer like TAF (tumor angiogenesis factor), a substance that cancer cells secrete in order to build a blood supply network for themselves. And to top it all off, low glucose supplies leave cancer cells without a way to repair free radical damage. All in all, a ketogenic diet acts like a metabolic bomb dropped on the supply convoy for cancer cells.
This is all rather technical, so I’ll end this with the short summary. To fight cancer, it is crucial to achieve lower blood glucose and insulin levels and increase circulating ketone bodies. This is exactly what a ketogenic diet does. You can learn more on my website and from my book Fight Cancer with a Ketogenic Diet.
1 Warburg O. The chemical constitution of respiration ferment. Science. 1928;68:437–443.
2 Fludeoxyglucose (18F). Wikipedia website. Available at http://en.wikipedia.org/wiki/Fludeoxyglucose_(18F) Accessed June 27, 2014.
3 Single Cause, Single Cure website. Available at http://www.singlecausesinglecure.org/metabolic-theory-of-cancer/ Accessed June 27, 2014.
4 Seyfried T. Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer. New York: Wiley, 2012.
5 Seyfried TN, Flores RE, Poff AM, D’Agostino DP. Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis. 2014 Mar;35(3):515-27.
6 Seyfried TN, Shelton LM. Cancer as a metabolic disease. Nutr Metab (Lond). 2010 Jan 27;7:7.
7 Cahill GF Jr. Fuel metabolism in starvation. Annu Rev Nutr. 2006;26:1-22. Review.
8 Cahill GF Jr, Veech RL. Ketoacids? Good medicine? Trans Am Clin Climatol Assoc. 2003;114:149-61; discussion 162-3. Review.