How Fasting Can Starve Cancer Cells, While Leaving Normal Cells Unharmed

People use the "curing cancer" as a metaphor for a giant achievement. There is no question that literally curing cancer would indeed be a giant achievement. Cancer is not only the second biggest cause of death, it can often be agonizingly painful. Moreover, the common cancer treatments of radiation and chemotherapy are awful experiences that can themselves cause lasting damage even if the cancer itself is defeated. So I was fascinated to read Thomas Seyfried's argument for another way to attack cancer in his book Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer.

Cancer as a Metabolic Disease is not a well-written book. But it has an important set of ideas that are more mainstream than Thomas Seyfried lets on: 

  • A majority of cancer cells have damaged metabolisms, often because delicate structures in their mitochondria—the folds called cristae—are damaged.

  • Metabolically damaged cancer cells can't produce as many handy ATP energy packets from each molecule of glucose (blood sugar). They can still produce ATP from the initial splitting of of a glucose molecule into two molecules of called glycolysis, which does not use oxygen. But they are not good at producing ATP from combining oxygen with the products of glycolysis to produce additional ATP.

  • This means that metabolically damaged cancer cells need to take in more glucose than normal cells to produce a given amount of ATP energy packets. They are more glucose-hungry than normal cells. So it helps cancer cells if glucose is abundant.

  • As an alternative to splitting glucose, cancer cells with damaged metabolisms can make ATP by using the energy in glutamine--an amino acid human bodies can make from many other amino acids.

Two key messages are that anything that boosts glucose or glutamine availability leads to better-fed cancer cells:

  • Eating sugar or other easily-digested carbohydrates is a good way to boost glucose levels in the bloodstream. Indeed, this is exactly what the glycemic index for different foods is designed to measure.

  • Eating high-protein foods is a good way to make amino-acids that can be turned into glutamine highly abundant. (It would be great to have measurements of a "glutamine index" for the effect of different foods on glutamine availability, parallel to the glycemic index.)

I am intrigued by cancer cells' ability to burn glutamine for energy in conjunction with the evidence for an association between protein intake and cancer that T. Colin Campbell and Thomas M. Campbell emphasize in "The China Study: Revised and Expanded Edition: The Most Comprehensive Study of Nutrition Ever Conducted and the Startling Implications for Diet, Weight Loss, and Long-Term Health." I wrote about that in "Meat Is Amazingly Nutritious—But Is It Amazingly Nutritious for Cancer Cells, Too?" At the time I wrote that post, I thought complete protein might be helpful as a raw material for the growth of cancer cells, which still might be true; but in addition, any kind of protein is likely to increase the availability of glutamine for cancer cells to burn. 

The third key message is that fasting—a period of time without eating (while still drinking water)—will be harder on cancer cells than normal cells:

  • Fasting lowers glucose levels in the bloodstream. Normal cells can get a lot more ATP energy packets out of scarce glucose.

  • Fasting is likely to reduce glutamine availability.

  • Normal cells can burn fat during fasting. Cancer cells have a really tough time metabolizing fat. (During fasting, stored fat is often broken down to produce ketone bodies that circulate in the bloodstream to provide energy.)

If you actually get diagnosed with cancer, the current status of medical knowledge and the rules of medical ethics will mean your doctor will recommend that you try fasting only in conjunction with the usual treatments: surgery, radiation and chemotherapy according to standard protocols. But if you periodically fast as a preventative measure, you may starve cancerous or precancerous cells before you ever get diagnosable cancer. Fasting is relatively easy when you are eating foods low on the insulin index in any case. (See Forget Calorie Counting; It's the Insulin Index, Stupid.) And fasting is one of the best ways to lose weight, with all of the benefits from losing weight in reducing the risk of other diseases besides cancer. (See "Stop Counting Calories; It's the Clock that Counts" and "Obesity Is Always and Everywhere an Insulin Phenomenon.")

When I googled Thomas Seyfried, I found Orac's Respectful Insolence blog post "More hype than science: Ketogenic diets for cancer." Orac has two main points:

  • Thomas Seyfried is premature in recommending that people with diagnosed cancer depend on fasting and dietary changes to fight their cancer instead of surgery, radiation and chemotherapy. Much research should be done before that.

  • The idea of attacking cancer cells by their metabolic Achilles heel is now a mainstream idea, as I previewed above.

Consider these quotations from Orac's post, which is billed as critical of Thomas Seyfried:

Dr. Seyfried is a professor of biology at Boston College, who’s pretty well published. He’s also working in a field that has gained new respectability over the last five to ten years, namely cancer metabolism, mainly thanks to a rediscovery of what Otto Warburg discovered over 80 years ago. What Warburg discovered was that many tumors rely on glycolysis for their energy even in environments with adequate oxygen for oxidative phosphorylation, which generates the bulk of the chemical energy used by cells. ...

If you do a Pubmed search on “targeting cancer metabolism,” which is what Dr. Seyfried is talking about, you’ll find over 22,000 articles, with over 3,000 in 2013 alone, with a sharply increasing curve since 2000 that only now appears to be leveling off. A search on “cancer metabolism” brings up 369,000 references, with 28,000 in 2013 alone. Cancer metabolism is an incredibly important topic in cancer research and has been for several years now, and finding means of targeting the common metabolic abnormalities exhibited by cancer cells is currently a hot area of research. From my perspective, Dr. Seyfried is exaggerating how hostile the cancer research community is towards metabolism as an important, possibly critical, driver of cancer, although, to be fair, one prominent cancer researcher, Robert Weinberg, has been very skeptical. 

After pointing out that, given current knowledge, human subjects review boards would insist on trying metabolic therapies on top of the standard approaches of surgery, radiation and chemotherapy, Orac writes:

... you might as well do a proper phase I/II clinical trial, which is what is happening. For instance:

In other words, clinical data should be rolling in fairly soon, and that’s a good thing.

Along the way, Orac points out that "only approximately 60-90% of cancers demonstrate the Warburg effect." To me, 60-90% sounds like a large fraction! What is more, in his book, Thomas Seyfried has what seem to me plausible criticisms of the experimental procedures used to conclude that some types of cancers can effectively oxidize the products of glycolysis. The basic problem, according to Thomas, is that to the unwary experimenter, metabolizing glutamine can generate indicators that create the illusion that a cancer cell is producing ATP by the oxidation of the products of glycolysis. 

Orac's link above on the phrase "60-90% of cancers demonstrate the Warburg effect" is to the Science article "Energy Deregulation: Licensing Tumors to Grow" by Ken Garber. The claim 60-90% of cancers demonstrate the Warburg effect itself is attributed by Ken Garber to cancer biologist Craig Thompson.

In his article, Ken gives this useful background on metabolism in cancer cells:

[Eyal] Gottlieb, a biologist at the Beatson Institute for Cancer Research in Glasgow, U.K., notes that tumor cells need an unusual amount of energy to survive and grow. "The overall metabolic demand on these cells is significantly higher than [on] most other tissues," he says.

Tumors often cope by ramping up an alternative energy production strategy. For most of their energy needs, normal cells rely on a process called respiration, which consumes oxygen and glucose to make energy-storing molecules of adenosine triphosphate (ATP). But cancer cells typically depend more on glycolysis, the anaerobic breakdown of glucose into ATP. This increased glycolysis, even in the presence of oxygen, is known as the Warburg effect, after German biochemist Otto Warburg, who first described the phenomenon 80 years ago. Warburg thought this "aerobic glycolysis" was a universal property of cancer, and even its main cause.

Otto Warburg won a Nobel Prize for his work on respiration, but his claim that messed-up metabolism was a central cause of cancer fell out of favor. In Cancer as a Metabolic Disease, Thomas Seyfried provides strongly-argued modern rehabilitation of Warburg's theory of the origin of cancer. Thomas argues in detail that the oxidation of the products of glycolysis in "respiration" is crucial for maintaining the genetic stability and polite behavior of a cell: if cellular respiration fails, a cell usually dies, but sometimes manages to survive and go wild.

A key part of Thomas Seyfried's rehabilitation of Otto Warburg's claim about cancer origins is modifying Otto Warburg's idea that cancer cells derive their energy from splitting glucose to the idea that cancer cells derive their energy from splitting glucose and metabolizing glutamine. The mid-20th century criticisms of Otto Warburg's idea focused on his hypothesis that cancer derived their energy almost entirely from splitting glucose alone. These criticisms that, in Ken Garber's word, "discredited" Otto Warburg's ideas about the origins of cancer have much less bite against Thomas Seyfried's version in which cancer cells get energy from glutamine as well as glucose. Accounting fully for glutamine metabolism by cancer cells might raise the estimated percentage from Craig Thompson's "60-90% of cancers demonstrate the Warburg effect."

Regardless of whether damaged metabolism is important in the origins of cancer or not, the much less controversial proposition that cancer cells often have damaged metabolism means that fasting can stress out cancer cells a lot more than it stresses out normal cells.

I first learned about Thomas Seyfried in Jason Fung's book The Obesity Code. (See Five Books That Have Changed My Life.) Jason retails Thomas's advice to do a 7 to 10 day fast once a year in order to try to kill any cancerous or precancerous cells one may be hosting. I did that toward the end of 2017 and plan to do it again this year. I am a lot more scared of cancer than I am of fasting. 

If I were ever diagnosed with cancer, the first thing I would do would be to begin fasting immediately; my hope would be to slow down the progress of the cancer during the time it took to develop a more conventional treatment strategy for my cancer. I would also do my best to try to convince my cancer doctor to read Thomas Seyfried's book in the hope my cancer doctor might get some good ideas for improving the treatment strategy.   

I hope research on metabolic approaches to cancer treatment and cancer prevention continues at a brisk pace. Those outside the usual cancer research guild may well be able to think of ways to help the progress of this research. 

 

For annotated links to other posts on diet and health, see:

For example, here is what the first section looks like:

I. The Basics