Calorie Restriction as a Means to Augment Cancer Therapies

By Dr. Mercola

Calorie restriction has been scientifically proven to slow down aging, extend lifespan, and even reduce the risk of age-related chronic diseases such as cancer.

Newer research is now showing, however, that strategically restricting your calories may also be an effective form of cancer prevention and treatment. As a leading cause of death worldwide, the incidence of cancer is on the rise, despite the decades long 'war on cancer' that conventional medicine has waged against this disease.

As simple, natural methods continue to prove their merit, it's becoming clear that what are now viewed as alternative methods of cancer treatment may soon become regarded as the standard of care, and calorie restriction may be among the top go-to options.

Short-Term Calorie Restriction Improves Cancer Survival

A new animal study tested what would happen when mice with lymphoma were fed a regular diet or a calorie-restricted diet (75 percent of their normal intake) along with a targeted therapy to induce cancer cell death (known as ABT-737).¹ The idea was that the lower caloric intake might limit the expression of certain proteins associated with cancer. As explained by the American Society of Hematology:²

"When humans and animals consume calories, the body metabolizes food to produce energy and assist in the building of proteins. When fewer calories are consumed, the amount of nutrients available to the body's cells is reduced, slowing the metabolic process and limiting the function of some proteins.

These characteristics of calorie restriction have led researchers to hypothesize that reducing caloric intake could potentially help inhibit the overexpression of the protein Mcl-1, an alteration associated with several cancers."

The study showed that calorie restriction did improve survival when done along with the treatment. Specifically, median survival was 30 days in the control group that received a regular diet and no treatment, compared with:

• 33 days in mice that received a regular diet and treatment with ABT-737
• 30 days in mice that received a reduced-calorie diet without treatment
• 41 days in mice that received a reduced-calorie diet and treatment with ABT-737

Furthermore, the number of circulating lymphoma cells was reduced in the calorie-restricted/ ABT-737 mice, which suggests that the cancer cells had been sensitized to the treatment.

Is Calorie Restriction the Most Important Aspect of Cancer Prevention and Treatment?

Download Interview Transcript

Dr. Thomas Seyfried is one of the leading pioneer academic researchers in promoting how to treat cancer nutritionally, and in the video above you can hear my recent interview with him. Dr. Seyfried's work is in line with the above-mentioned study.

In fact, he believes that the most important aspect of cancer prevention and treatment is intermittent fasting, or overall calorie restriction, which includes eating less of everything, period.

That said, Dr. Seyfried's work confirms that sugar is the primary fuel for cancer, and that by restricting sugar and providing an alternate fuel, namely fat, you can dramatically reduce the rate of growth of cancer. This is because cancer cells lack the metabolic flexibility of your normal cells so when you deprive them of sugar they have no fuel, but your regular cells can thrive quite nicely on fat alone.

He explains:

"When we're dealing with glucose and [cancer] management, we know from a large number of studies that if respiration of the tumor is ineffective, in order to survive, the cells must use an alternative source of energy, which is fermentation.

We know that glucose is the primary fuel for fermentation. Fermentation becomes a primary energy-generating process in the tumor cell. By targeting the fuel for that process, we then have the capability of potentially managing the disease."

The strategy Dr. Seyfried suggests is a low-carb, low- to moderate-protein, high-fat diet, which will effectively lower your blood sugar. This is an easily measurable parameter that you can check using a diabetic blood glucose meter. This type of diet, called a ketogenic diet, will also elevate ketone bodies, as fat is metabolized to ketones that your body can burn in the absence of food. When combined with calorie restriction, the end result will put your body in a metabolic state that is inhospitable to cancer cells.

"[Ketones] is a fat breakdown product that can replace glucose as a major fuel for many of the organs and especially our brain," he says.

Carbohydrate Calorie Restriction May Be Most Important

While opinions are mixed about what ratios of protein, fats and carbs constitute the healthiest diet, most experts agree that calories from carbohydrates need to be restricted. One reason for this is a mounting body of evidence that suggests cancer is responsive to therapeutic ketosis—a natural physiologic state induced during prolonged states of decreased glucose.

Nutritional ketosis, as mentioned, involves restricting carbohydrates in order to decrease the availability of glucose. Restricting carbs also increases production of ketone bodies from your liver. Nearly all of your normal cells have the flexibility to readily adapt to using ketone bodies for fuel in lieu of glucose, but cancer cells do not have this metabolic flexibility. Hence, they effectively starve to death while all your normal cells actually operate more efficiently than before.

Additionally, when you restrict carbohydrates, you prevent spikes in blood sugar, insulin and IGF-1 from occurring. These spikes are actually very pro-inflammatory, and can activate oncogenes (genes that contribute to the conversion of a normal cell into a cancerous cell), and enhance both cancer cell proliferation and the metastatic process.

But here's a key point: While carb restriction will reduce these spikes, it will not have a major impact on baseline levels of blood glucose, unless you also restrict your calorie and protein intake. So for cancer prevention and treatment, carb restriction must be combined with calorie restriction and moderate protein restriction in order to effectively "starve" cancer cells of their preferred fuel (glucose and glutamine).

The Amount of Protein Calories You Consume Also Likely Matters

Download Interview Transcript

In order to maintain and sustain nutritional ketosis, you need to decrease both carbohydrates and protein. But how much protein is enough or too much? Dr. Seyfried is more cautious in his evaluation of reducing protein for cancer prevention, but one of my mentors, Dr. Ron Rosedale, advocates restricting protein to one gram per kilogram of lean body mass. Typically, for someone like myself, that amounts to about 50-70 grams of protein per day.

The reason he promotes this so much is because of the stimulatory effect protein (branch-chained amino acids specifically) has on mammalian target of rapamycin (mTOR)—a pathway that seems to be largely responsible for the pathology seen in cancer growth. Dr. Dominic D'Agostino, PhD, an assistant professor at the University of South Florida College of Medicine, also believes protein must be restricted for cancer prevention.

He explained in our interview (see the video above):

"The ketogenic diet is, I think, a very good strategy to make calorie restriction tolerable. Because when your brain in particular is craving glucose, and, say, for example, you go on a calorie-restricted diet, but it's a high-carbohydrate diet, you're still getting fluctuations in blood glucose. Your brain goes through these intermittent periods of glucose deprivation and you get very hungry. It's not a very comfortable feeling.

Nutritional ketosis, which occurs with carbohydrate restriction and is further enhanced with calorie restriction, forces the physiological shift from a glucose-based metabolism to a fatty acid and ketone metabolism. When your body is, shall we say, keto-adapted, your brain energy metabolism is more stable and your mood is more stable. It may take a few weeks to adapt physiologically to this. But nutritional ketosis can be maintained and sustained with carbohydrate restriction and is further enhanced with calorie restriction.

The total calories really need to be restricted, and also protein. Protein is gluconeogenic. There are gluconeogenic amino acids in protein. If protein is at, say, for example, two or three grams per kilogram per day that is probably going to feed in through the gluconeogenic pathway and contribute to glutaminolysis. It will be hard to deplete your glycogen stores, which is necessary to drive the ketogenesis in your liver."

Calorie Restriction Is Essential for Cancer Patients, But Is an Important Cancer-Preventive Strategy, Too

From my perspective, it's medically unethical to fail to integrate this safe and effective dietary strategy into a patient's cancer treatment plan (along with optimizing vitamin D). A ketogenic diet along with intermittent fasting can be easily integrated into whatever cancer treatment plan you decide to follow. Personally, I believe it's absolutely crucial, no matter what type of cancer you're trying to address.

To get more specifics about using a ketogenic diet and calorie restriction for the treatment of cancer, I highly recommend picking up Dr. Seyfried's book, Cancer as a Metabolic Disease. You can also review his papers,^{3, 4} which outline the guidelines and treatment strategies for cancer patients. If you're a cancer patient, I'd recommend printing them out for your oncologist.

That said, remember that a ketogenic diet, in which you replace carbs with low to moderate amounts of protein and high amounts of beneficial fat, like avocado, coconut oil, butter, olive oil and macadamia nuts is recommended for everyone, whether you have cancer or not. It's a diet that will help optimize your weight and health overall, as eating this way will help you convert from carb burning mode to fat burning.

Want to Try Calorie Restriction? Try Intermittent Fasting

While the research supporting calorie restriction is compelling, it's not a very popular dietary strategy for most people, for obvious reasons. Many are simply not willing to deprive themselves of calories to the extent needed to prompt the beneficial effects. An alternative that is much more acceptable is intermittent fasting, which can be as simple as restricting your daily eating to a narrower window of time of say 6-8 hours (this equates to 16-18 hours worth of fasting each and every day).

Recent research suggests that sudden and intermittent calorie restriction appears to provide many of the same health benefits as constant calorie restriction, including extending lifespan and protecting against disease.

Unless you have a very serious disease, I believe it is best for most people to implement intermittent fasting slowly over six to eight weeks. You begin by not eating for three hours before you go to bed, and then gradually extend the time you eat breakfast until you have skipped breakfast entirely and your first meal of the day is at lunch time. Of course, you are only consuming non-starchy vegetables for carbs, low to moderate protein and high-quality fats. One of the things I've noticed is that once you've made the transition from burning carbs to burning fat as your primary fuel, the desire for junk foods and sugar just disappears like magic.

It typically takes a few weeks for most to shift from burning carbs to fat-burning mode. Once you succeed and switch to fat-burning mode, you'll be easily able to fast for 18 hours and not feel hungry.