Dr. Thomas Seyfried is one of the leading pioneer academic researchers in promoting how to treat cancer nutritionally. He’s been teaching neurogenetics and neurochemistry as it relates to cancer treatment at Yale University and Boston College for the past 25 years.He’s written over 150 peer-reviewed scientific articles and book chapters, and has also published a book, Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer.
The ketogenic diet has actually been used for managing seizures in children for quite some time. While Dr. Seyfried and his team worked on brain cancer and epilepsy in mice, one of his students suggested investigating whether or not a ketogenic diet might also be effective against tumors.
So, in the late ’90s, they began dovetailing their work on ketogenic diets and epilepsy and cancer together, eventually bringing them to a better understanding of how changing your whole-body metabolic state can be effective in targeting and eliminating tumor cells.
Interestingly, clinical medicine has recognized the ketogenic diet as a valuable option in the treatment of epilepsy since the late 90’s.
“I served as the organizer for the Ketogenic Diet Special Interest Group at the American Epilepsy Society,” Dr. Seyfried says.
“We initially started as a small focus group with the folks from Johns Hopkins Medical School, where the diet has had its greatest use and impact. And then we started to grow and substantially increase interest mainly through the efforts of Jim Abrahams.
Jim started the Charlie Foundation for his son Charlie, who went through a near-death experience from seizures and was rescued using ketogenic diets. His colleague, Meryl Streep, the famous movie actress, became very involved in this.
Now the ketogenic diet is receiving considerable attention in the epilepsy community as a first line of approach. Although this is still not widely accepted, I have to admit that the ketogenic diet is now recognized as an important component for the management of refractory seizures in children.”
According to Dr. Seyfried, the mechanism by which the ketogenic diet manages seizures is not nearly as clear as the way the ketogenic diet manages cancer. This is ironic considering that it’s barely known, let alone applied, within oncology circles, while it’s already a first line of treatment for epilepsy. In the case of cancer, it’s well-established that it’s the glucose reduction that kills the cancer cells.
Dr. Seyfried has developed a process called metabolic control analysis, which essentially analyzes the metabolic flux through different pathways that occurs when you transition your body from one major fuel source to another major fuel source, to maintain energy homeostasis in your body. Many believe or are under the impression that cancer is primarily a genetic disease, but Dr. Seyfried dispels such notions.
“We’re not going to make major advances in the management of cancer until it becomes recognized as a metabolic disease. But in order to do that, you have to present a massive counterargument against the gene theory of cancer,” he says.
“One of the key issues here is that if you transplant the nucleus of a cancer cell into a normal cell, you don’t get cancer cells. You can actually get normal tissues and sometimes a whole normal organism from the nucleus of a cancer cell. Now, if the tumors are being driven by driver genes – all these kinds of mutations and things that we hear about – how is it possible that all of this is changed when you place this cancer nucleus into the cytoplasm of a cell with normal mitochondria?
The gene theory cannot address this. It clearly argues strongly against the concept that genes are driving this process. Actually, a very few people inherit genes that predispose them to cancer. Most people inherit genes that prevent cancer. And those few genes that are inherited – the germ line like the BRCA1 mutations, B53, and a few other very rare cancers – these inherited mutations appear to disrupt the function of the mitochondria.”
According to Dr. Seyfried, the mitochondria—the main power generators in your cells—are the central point in the origin of most cancers. Your mitochondria can be damaged not only by inherited mutations, thereby increasing your risk for a particular type of cancer, such as the BRCA1 and BRCA2 mutations that increase your risk of breast and ovarian cancer. They can also be damaged by environmental factors, such as toxins and radiation, both ionizing and non-ionizing. Over time, damage to your mitochondria can lead to dysfunction and tumor formation.
“It’s ultimately a disease of the mitochondrial energy metabolism, which is the origin of the disease,” Dr. Seyfried says. “[O]nce the mitochondria become dysfunctional or insufficient in ability, mutations will occur. The drugs that have been developed based on the genome projects have been largely ineffective in providing long-term care and are associated with toxic effects. As long as the field continues to focus on that part of the disease, which is a downstream epiphenomenon, there will be no major advances in the field simply because that’s not the relevant aspect of the disease.”
Controlling your blood-glucose leptin and insulin levels through diet, exercise and emotional stress relief can be one of the most crucial components to a cancer recovery program. These factors are also crucial in order to prevent cancer in the first place.In 1931, the Nobel Prize was awarded to German researcher Dr. Otto Warburg, who discovered that cancer cells have a fundamentally different energy metabolism compared to healthy cells, and that malignant tumors tend to feed on sugar. More recently, researchers discovered that while cancer cells feed on both glucose and fructose, pancreatic tumor cells use fructose specifically to divide and proliferate.
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. 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.
Tumor cells, however, cannot use ketone bodies because of their respiratory insufficiency. So the ketogenic diet represents an elegant, non-toxic way to target and marginalize tumor cells. It also allows you to dramatically lower your glucose levels, as the ketones will protect your body against any hypoglycemia that might otherwise be induced by carb restriction.
“All of the newer cells in your body will be transitioned to these effective ketones, thereby preventing them from damage from hypoglycemia. At the same time, the tumor cells are now marginalized and under tremendous metabolic stress. It’s a whole body therapy—you need to bring the whole body into this metabolic state,” he explains.
“We like to call it a new state of metabolic homeostasis: a state where ketones have reached the steady state level in your blood and glucose has reached a steady lower level in your blood… If it’s done right and implemented right, it has powerful therapeutic benefits on the majority of people who suffer from various kinds of cancers. Because all cancers have primarily the same metabolic defect.”
Dr. Seyfried uses ketones and glucose as the measures of this new metabolic state. The parameters associated with an ideal state are ketone levels equal to or higher than the glucose level in your blood.
“There’s a high ratio of glucose to ketones. But in a fasted or therapeutic state, this ratio is actually reversed. Ketones can actually become higher than glucose,” he says. “What they can do is they can get their blood sugars down to 2.5 to 3 millimolar [equivalent to about 55-65 mg/dl], and then their ketones to up to 3 or 4 millimolar, where the ratio is now reversed. It’s this state that now brings the body into this new physiology.”
You can easily check your glucose levels at home, you’d need to work with a doctor to measure ketone levels in your blood. Generally speaking, a fasting glucose under 100 mg/dl suggests that you’re not insulin resistant, while a level between 100-125 suggests you’re either mildly insulin resistant or pre-diabetic. Here, Dr. Seyfried recommends getting your glucose down to a steady level of about 55-65 mg/dl, which is about HALF of what’s conventionally considered “good” or “normal.”
Blood ketones can be easily measured using the Medisense Precision Xtra blood glucose and ketone monitor from Abbot Laboratory. As many pharmacies might not stock the meter (bar code #, 93815 80347), it might be necessary to call Abbott directly (1-800-527 3339) to obtain the meter. According to Dr. Seyfried, the Precision Xtra seems the most accurate of all the ones he’s used.
It is important to mention, however, that the blood ketone strips are more expensive than the blood glucose strips. Dr. Seyfried therefore recommends measuring your blood ketones every few days rather than 3x/day for blood glucose. Although urine ketone measurement is a cheap way to assess ketones, urine ketone levels are not always indicative of blood ketone levels. It is best if you can measure ketones from both blood and urine.
“I work with nutritionists and physicians,” Dr. Seyfried says. “The problem with cancer patients is that many of the practitioners are unfamiliar with this whole approach, so there’s this tremendous gap. We have knowledge of how to do this. We have patients willing to do it. But we lack professionals that are trained or even understand the concepts of how to implement these kinds of approaches.”
All of the guidelines are included in Dr. Seyfried’s book, Cancer as Metabolic Disease, which is available on Amazon. He’s also published a couple of papers 1,2 that outline the guidelines and treatment strategies for cancer patients. One caveat to consider is your use of medications, as you need to know what the adverse effects might be if you use a medication at a particular dosage along with this kind of metabolic therapy.
In my experience, the vast majority of people are adapted to burning carbs as their primary fuel, as opposed to burning fat. One of the most effective strategies I know of to become a fat burner is to restrict your eating to within a six- to eight-hour window, which means you’re fasting for about 16-18 hours each day. This upregulates the enzymes that are designed to burn fat as a fuel, and downregulates the glucose enzymes. This kind of intermittent fasting plan can be a useful modality to help you make the transition to a ketogenic diet.
“That’s the way it started in the clinic for children with epilepsy. Basically, the child is given a 24-hour and sometimes 48-hour fast – water only. And then the ketogenic diet is introduced in relatively measured and small amounts,” Dr. Seyfried says.
“Your body transitions naturally that way. Intermittent fasting is actually a very strong component of the approach. A three-day fast is uncomfortable, but it’s certainly doable. It gets your body into a new metabolic state, and then you can apply these therapies. The hardest part, I think, of this fasting is the first three to four days, depending on the individual and how many times they’ve done this.
That’s basically trying to break your addiction to glucose. The removal of glucose from the brain elicits the same kind of problems or events as you would if you were addicted to drugs, alcohol, or something like this. You get malaise, headaches, nausea, lightheadedness. You get all the kinds of physiological effects that you would get from withdrawal of any addicting substance. I look at glucose as an addictive substance. It’s an addictive metabolite. Your brain is comforted by having glucose; your body is comforted. And when you break that glucose addiction, you have these particular feelings.
… Fasting certainly has remarkable health benefits to the body: strengthening the mitochondria network system within the cells of your body. As long as the mitochondria of your cells remain healthy and functional, it’s very unlikely that cancer can develop under these particular states.”
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 rather than a three-day complete fast. 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.
Glutamine–one of the most common amino acids found in proteins—is another interesting aspect of cancer that Dr. Seyfried is still investigating. In his opinion, most oncologists who do cancer metabolism recognize that sugar (both glucose and fructose) is the prime fuel for driving tumor growth. However, mounting research also indicates that glucose and glutamine together act powerfully and synergistically on the growth of tumor cells.
“These two fuels work together in concert to provide a continual growth,” he says.
One of my early mentors was Dr. Ron Rosedale. He taught me, about 20 years ago, about the importance of insulin control and then, more recently, about the importance of reducing protein intake, for this very reason. Most Americans likely eat far more protein than they really need, and this excess could be a factor in cancer. The Paleo approach makes sense on many levels, especially with regards to intermittent fasting and lowering your glucose levels. The Paleo approach is very clear about reducing grains and any food that raises your blood sugar. But there are, of course, two other macronutrients left: fat and protein.
Many Paleo followers are overly concerned about getting high amounts of protein, which could increase your glutamine and branched chained amino acid levels, which in turn tend to activate mTOR. In some, that could be problematic. According to Dr. Rosedale’s research, the pathway known as the mammalian target of rapamycin (mTOR), is controlled by lowering your protein intake. This pathway may be another metabolic pathway that helps control and prevent cancer growth.
Dr. Seyfried, however, is more cautious in his evaluation of mTOR and reducing protein for cancer prevention. In his view, the most important aspect of cancer prevention and treatment is the intermittent fasting, or overall calorie restriction, which includes eating less of everything, period. But while calories from carbohydrates should be virtually eliminated, calories from protein just need to be reduced, while most need to increase their intake of healthful fats to get a more ideal ratio of fat to protein. As far as the specific types of fats recommended, Dr. Seyfried uses medium-chain triglycerides, i.e. coconut oil, butter, macadamia nuts, and other types of saturated fats, which is what I’ve long recommended as well. “The saturated fats are converted to ketones much more readily than polyunsaturated fats,” he explains.
So, keep in mind that for cancer prevention and treatment, the actual calorie restriction is an important part of the equation:
“We did some studies on this with our model of glioma… The mTOR in our model was not dramatically changed by these metabolic therapies. But I know others have reported it, and this could be an important component for certain other kinds of cancers. But my limited work with this did not demonstrate this to be a major issue, at least in the glioma model that we looked at. We showed that you could give animals a high-fat, low-protein diet, as much as they want (zero carbs in this diet), and their blood glucose was just as high or higher than the mice that were eating the protein-carb diet.
It was more or less related to the total consumption of calories. Most calories boil down to glucose. Proteins will be metabolized to glucose. Carbs are metabolized to glucose; fats are not… We don’t get any therapeutic benefit either in epilepsy or cancer when we allow the animals or people to eat as much of these high-fat diets as they want. We get no therapeutic benefit.
Therapeutic benefit comes from the restriction of the calories in the diet. The ketogenic diet or a low-carb, low-protein diet is simply a way to take the sting out of a therapeutic fast. Because as long as the glucose and ketones can get into the metabolic range (and you can do it with eating small amounts of a high-fat diet rather than therapeutic fasting), then that just makes people feel a little better about how they’re doing this rather than feeling that I’m starving to death.”
I recently interviewed Dr. D’Agostino who is another cancer as a metabolic disease researcher. He published a recent paper3 that shows a phenomenal synergy with a ketogenic diet and the use of hyperbaric oxygen for cancers that have metastasized. These types of cancers are notoriously difficult to treat. I would strongly encourage anyone struggling with this challenge to consider this type of therapy.
From my perspective, it’s nothing short of medical malpractice and negligence to fail to integrate this type of 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.
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.
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,4,5 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.