Update: Ketogenic diets may not offer the solution that scientists hoped for, but looking at how cancer cells burn fuel for energy is for sure generating insight into how cancer grows and spread. Since this article was published, some scientists have found that cancers can switch to feeding on ketones, which are generated by fat. They’ve also added some fatty acids to the list of nutrients that cancer cells may feed on. Palmitic acid, which is in coconut, may feed cancer, especially in people with certain genetic profiles. The good news is that scientists have also identified phytonutrients that keep cancer cells from using fatty acids as fuels. Among them, luteolin–present in radicchio, thyme, sage, parsley, celery flakes and seeds–is key.
Is the war on cancer now witnessing its own D-Day, a turning point in the anti-cancer fight that will change the world for good?
With the recent settlement of a major lawsuit among scientists over who owns the rights to new revolutionary approaches to managing cancer, all the experts in the field are presumably now free to talk openly—and what they’re talking about is a radical new view of the disease.
Cancer is caused by faulty metabolism within the cancer cell, they say, and we can control it by restricting the fuels that cancer cells use to generate energy—glucose and glutamine, a common amino acid . Rather than eating carbohydrates and even protein, people with advanced, metastatic cancers should turn to low calorie, high fat diets instead. This will force the body to produce compounds called ketones that regular cells can use for energy but that–and here’s the clencher–tumor cells cannot metabolize for fuel.
That’s the view proposed by Boston College biology professor Dr. Thomas N. Seyfried in his new book “Cancer as a Metabolic Disease” and landmark article as well as by other eminent scientists, including those from Memorial Sloan- Kettering and Harvard.
(Truth be told, some of these scientists have been working to develop methods of gauging cancer cell metabolism and drugs that target glucose and glutamine, and the current president of Sloan-Kettering along with his private company, Agios Pharmaceuticals, recently settled a lawsuit in which his former employer, the University of Pennsylvania, claimed he absconded with this important line of research.)
Ketogenic diets, pioneered by a team at Johns Hopkins, have been used for years to manage epilepsy in some people. Seyfried takes the approach one big step further: The diet for managing cancer also requires fasting. Some patients with advanced, metastatic disease have to stop eating for several days to get their blood sugar very low and ketones elevated, and that’s a stumbling block, he admits.
(If you want to go directly to the sources, check out this interview with Seyfried at a conference funded by the National Cancer Institute and this interview and this presentation, which you must watch til the end! Professor of cell biology Dr. Richard David Feinman also hosts a fascinating discussion that starts here and continues here. )
So what does fasting do? And why is this approach so revolutionary?
For years, scientists have viewed cancer as a disease caused by damage to the nucleus of cells –the part containing most of its genetic material. Thousands of genetic mutations have been implicated, and countless research dollars have been spent trying to figure out how to personalize cancer therapy according to an individual’s genetic blueprint.
Seyfried and company kibosh that theory and propose that cancer is caused by damage to the cell’s mitochondria instead—the part that generates energy, its metaphorical power plant.
Normally, mitochondria turn glucose into energy in a process called oxidative phosphorylation (OxPhos), which requires oxygen as its name suggests. But when carcinogens impact cells, the damage causes chronic inflammation and respiratory insufficiency. Deprived of oxygen, some cells simply die. Others, however, adopt an alternative way to keep on breathing. Like yeast growing in bread, cancer cells turn to fermenting glucose instead, inefficiently transforming it into a limited amount of energy that produces carbon dioxide and lactic acid as waste.This faulty method of generating energy from glucose, which Seyfried calls compensatory fermentation, drives the cancer process, he says.
Back in the early 1930s, German scientist Otto H. Warburg (MD, PhD) won a Nobel Prize when he described this process, also known as anaerobic glycolysis, and identified cancer as a sugar feeder. But Warburg soon fell out of favor, perhaps due to his reputation as a Nazi sympathizer, which he was not. (The son of a physicist whose own father had converted from Judaism to Christianity, Otto was granted privileged status as an “honorary Aryan” and allowed to continue working during the war.)
More recently, many studies have shown that obesity and high insulin concentrations in the blood, both linked to diets high in carbohydrates (hence high in glucose), are associated with an increased risk for a variety of cancers.
Seyfried’s work goes even further: In addition to fermenting glucose for fuel, Seyfried says that some cancer cells can also ferment glutamine–an amino acid naturally present in a host of foods. (For a discussion of cancers that use glutamine, see the chapter in this recent review from China. Better yet, have the discussion with your own oncologist.)
Seyfried’s version of the ketogenic diet minimizes both glucose and glutamine:
● 70 percent of calories come from fat (Omega 3 fats from fish oil are good, he says, as is coconut oil, which contains medium chain triglycerides, a type of fat that promotes the production of ketones.)
● 12 to 15 percent of calories from protein (Another study suggests that less than 10 percent protein may be necessary. Glutamate is an amino acid, used to build proteins, and the body can make glucose from protein.)
● and the rest from carbohydrates. How low carb is that? The typical US diet provides 250 to 400 grams of carbohydrates daily. According to Dr. Eugene Fine, who recently did a small human trial on low-carb diets for cancer, you need to eat 50 grams or less a day to put your body into a state of ketosis, where it produces ketones as a result of utilizing fat as its main energy source. The fewer carbs, the better.
Seyfried’s approach also involves giving drugs that restrict the supply of glucose to tumor cells and lower circulating levels of glutamate.
Most brain cancer patients are actually dying because of the standard treatment, Seyfried claims. Radiation creates inflammatory chemicals in the brain, which facilitate survival of the cancer cells that weren’t destroyed by the treatment. To counter the swelling, doctors then give patients steroids, which sends blood glucose soaring.
Instead, Seyfried proposes that patients start by fasting in order to bring their blood sugar levels down. As those levels decline, tumors will shrink. There’s nothing more powerful than calorie restriction in reducing the tumor’s ability to grow blood vessels and spread, he says. In fact, fasting shuts down the entire inflammatory process that drives cancer, forcing the body to eliminate damaged mitochondria and enhancing the efficiency of surviving mitochondrial cells, he says.
But how can you ask a patient to fast if s/he’s already losing weight because of the cancer? The patient is losing weight because the tumor cells are mobilizing glucose from stores of fat and protein in a process known as cachexia, Seyfried explains. When you lower glucose, you kill tumor cells that are causing the problem in the first place by depriving them of fuel. At the beginning, the patient will lose weight but the body will ultimately regain weight and become much healthier. Then, once the cancer is managed, you can increase caloric consumption to gain weight back.
(Fasting in fact is so powerful in rejeuvenating mitochondria that Seyfried recommends we all go on a water-only fast for a week every year.)
Will this revolutionary approach work for all cancers? Will the sneaky cells one day figure out a way to live on ketones instead?
For sure, all cancers don’t respond to dietary restriction, Fine says. Take prostate cancer, for example. The common slow-growing forms metabolize fat as an energy source (although some very aggressive forms, he points out, feed on glucose.) “Even within a single individual with a primary cancer and metastases, the cancer’s behavior…can vary from one cell to the next,” he adds.
That’s probably why so much was at stake in that lawsuit. If scientists can figure out a way to measure a cancer cell’s metabolism, to understand what nutrients fuel it and what nutrients don’t, that could be worth the $1 billion plus in damages the plaintiffs sought.