Every paper and discussion of the metabolic theory of cancer begins with a description of what is referred to as the Warburg effect. Since this is key to understanding the science behind the ketogenic diet, let’s look at the origins of this observation. On some level, we’re all familiar with how fermentation works. That’s the process responsible for turning cabbage and milk, for example, into more gut-friendly foods such as sauerkraut and yogurt. It’s relatively simple to bring about. You introduce a bacterial starter culture to a food, cover it to prevent contamination, keep it warm, and voilà. You’ve just fed the bacteria with the sugar in that food, which allows the bacteria to multiply. As the bacterial colony grows, the available sugars are rapidly fermented.
Fermentation is a primitive process that meets a bacterium’s simple needs for energy. But in humans, fermentation by itself usually contributes relatively little to overall energy production. Yet as Warburg observed, cancer cells behave differently than normal cells: They become increasingly dependent on the fermentation of glucose within the cytoplasm of the cell for cellular energy. This differs from normal cells, which produce the majority of cellular energy within highly specialized organelles known as mitochondria. This switch in the fate of glucose within a cell may be the first indication that something has gone terribly wrong with cell function. If that cell survives and multiplies into a group of dysfunctional cells that are able to bypass immune system surveillance, we now have a malignant tumor.
As the tumor grows, it restricts the flow of blood containing oxygen and other vital nutrients. A cancer cell’s ability to ferment glucose allows it to survive and thrive in a hypoxic (low oxygen) environment. This oxygen-starved state reprograms cell metabolism, promotes cell survival and proliferation, increases cancer’s invasiveness, and stimulates the development of new blood vessel networks (referred to as angiogenesis) that serve to feed the tumor. A prime waste product of fermentation is lactic acid. This acidic waste is toxic, so it is quickly shunted to the microenvironment, the area immediately adjacent to the cell. Cancer thrives in this acid-inflamed environment, which leads to faster proliferation of cancer cells and acceleration of disease progression.
This reliance on a more primitive way to fuel the cell’s needs wouldn’t make sense if I didn’t mention that cancer cells ferment a lot of glucose, much more than what a normal cell would use. In fact, the rate of glycolysis in cancer cells is typically 10 to 15 times the rate in a normal cell. For that to occur, cancer cells need a way to allow more transport of glucose into the cell. They do this by increasing the number of glucose transporters and insulin receptors on the cell’s surface.
Recall that Warburg identified this process back in the first quarter of the twentieth century. In essence, his observation was the birthplace of the metabolic theory of cancer, and for a time, researchers worked to further explore this theory. But in the 1950s the discovery by James Watson and Francis Crick of the double helix structure of DNA derailed those explorations. Then, in the 1970s, the discovery of genetic mutations in the nuclear genome of cancer cells caused the pendulum to swing toward almost universal acceptance of the belief that cancer was a genetic disease.
With this shift in thinking, research efforts turned to identifying genetic mutations in DNA that could be linked to cancer initiation and progression. And, as is so clear from modern press releases, the medical and scientific community is still enamored with developing drugs that target these specific genetic mutations. So is the public. After all, who doesn’t want to see a cure for cancer in a pill? In reality, though, decades of research and billions of dollars invested in this concept have produced little improvement in cancer outcomes. In other words, real people with real cancers are still dying from this disease.
Cancer Thrives on Glucose and Glutamine
Cancer thrives on fermentable fuels. Study after study has confirmed this. A well-planned ketogenic diet (low-carb, high-fat) restricts cancer’s access to its preferred fuel sources, glucose and to a lesser degree glutamine, while providing abundant energy to healthy cells. That makes evolutionary sense given that early humans wouldn’t have survived unless they had a backup system for those times when food was in short supply. Your body will respond to carbohydrate restriction similarly to how it responds to fasting or starvation: by flipping a metabolic switch that allows stored fat to be used as fuel.
The body’s ability to switch fuels also explains why a well-planned ketogenic diet is uniquely positioned to interrupt not only the flow of glucose but also the supply of other cancer-promoting fuels, including glutamine. Furthermore, a ketogenic diet and other strategies that mimic starvation can compromise the very existence of diseased cells, which helps restore the normal cellular signaling that is responsible for putting the brakes on cancer. While this nutritional strategy is an extremely powerful tool, it is not a cure for cancer. Instead it can be used as a long-term management strategy with the added benefit of other improvements in health.
Introducing Ketogenic Metabolic Therapy
A new term—“ketogenic metabolic therapy”—has recently been proposed by a group of researchers and clinicians who want to emphasize the use of a ketogenic nutritional intervention as an antineoplastic (anticancer) strategy (Winter et. al. 2017 Crit Rev Oncol Hematol). This new paradigm exploits cancer’s metabolic cravings for glucose and other fermentable fuels.
One of the most damaging nutrition myths of our time is that our bodies need a continuous supply of carbohydrates supplied by the foods we eat—45 to 65 percent of our total calories. That is simply not true! Most of the people who regurgitate this “conventional wisdom” don’t understand that this is only an opinion that has been repeated so often that it is accepted as the truth. In fact, even the very mainstream manual Dietary Reference Intakes, published by the Food and Nutrition Board of the Institute of Medicine (The National Academies Press, 2005), acknowledges that a combination of gluconeogenesis and ketone bodies is sufficient to meet the brain’s energy needs even in the total absence of dietary carbohydrates.
This excerpt is from Miriam Kalamian’s book Keto for Cancer: Ketogenic Metabolic Therapy as a Targeted Nutritional Strategy (Chelsea Green Publishing, October 2017) and is reprinted with permission from the publisher.
Miriam Kalamian is a board-certified nutrition consultant, educator, and author specializing in the implementation of ketogenic therapies. In her book Keto for Cancer: Ketogenic Metabolic Therapy as a Targeted Nutritional Strategy (Chelsea Green Publishing, October 2017) she draws on a decade of experience to provide comprehensive guidelines that specifically address the many diet and lifestyle challenges associated with a cancer diagnosis.