The big C
There’s something special about cancer. Few, if any other diagnoses cause so much emotional distress, both for people with cancer and for their loved ones.
This is partly due to the potentially deadly nature of the condition, and partly due to the misery associated with most conventional cancer treatments—surgery, chemotherapy, and radiation. However, I’d add one more powerful emotional factor to complete the trio of terror: if you’re told you have an incomprehensibly complex genetic disease that even doctors don’t understand, you are placed in a position of powerlessness—you may feel like a helpless victim. We are fond of saying that people “fight” against cancer, and that they are brave. How exactly are you supposed to fight a disease caused by genetic mutations that have already occurred? I can completely understand why some people lose hope when they are given a diagnosis of cancer.
Standard dietary recommendations
To add to the potential for despair, there is tremendous confusion around the simple question of what people with cancer are supposed to eat. The people in my life who have cancer are told they should eat lots of cancer-fighting, antioxidant-rich vegetables, low-fat protein sources, whole grains, nuts, seeds, and colorful fresh fruits. Many people believe that a low-fat vegan diet is the healthiest diet for cancer. However, as soon as chemotherapy starts causing scary, rapid weight loss, people are told to eat whatever they can to keep to keep up their calorie intake and maintain their strength—everything from sweetened energy drinks and smoothies to carbohydrate-rich comfort foods. Some patients are even fed high-sugar solutions through I.V.’s or G-tubes. Given everything I know about nutrition and everything I have learned from Dr. Seyfried’s extensive work, nothing could be worse for you if you have cancer.
Cancer has a sweet tooth
Nearly all tumors depend heavily on glucose for survival, which is how PET scans are able to find many tumors hiding in normal tissues. PET scans follow radioactive glucose as it travels through the bloodstream. Radiolabeled glucose accumulates in tumor tissue more than in the normal tissues surrounding it, and lights up on the scan.
There is a strong connection between high blood sugar (hyperglycemia), diabetes, and cancer. It is well-documented that the growth of brain tumors is more accelerated and prognosis is worse in animals and humans with higher blood glucose levels. Hyperglycemia is directly linked with poor prognosis in humans with malignant brain cancer and is connected to the rapid growth of most malignant cancers.
High blood glucose raises insulin levels, which stimulates cancer cells to take in and use more glucose—this makes it easier for cancer cells to nourish themselves. Insulin also turns up the activity of the fermentation pathway that was described in article 2 of this series, and fermentation leads to additional cellular damage.
High blood glucose also raises levels of another circulating hormone called IGF-I (Insulin-like Growth Factor I). Cancer cells with receptors on their surfaces for this hormone grow more rapidly. IGF-I turns on a chemical pathway that drives tumor cell growth [for you cell biology buffs out there, this is the PI3K/Akt/HIF-1alpha pathway]. This pathway sets the stage for cells to multiply, escape death (“apoptosis”), and recruit their own blood supply (“angiogenesis”). Angiogenesis is required for tumors to grow beyond 2 millimeters in size (2 mm is a little less than one-tenth of an inch).
To make matters worse, the genes for this growth pathway are also turned up by the fermentation process. More glucose = more fermentation AND more insulin AND more IGF-I = more tumor growth.
In short, cancer is a disease of growth, and insulin is the mother of all growth hormones (see my carbohydrates page).
Cancer’s Achilles' heel
Regardless of which type of cancer you have, what grade or stage it might be, or which mutations (“genetic markers”) it might have, the hallmark of all cancer cells is damaged mitochondria (see article 2). According to Dr. Seyfried, cancer is not a collection of unrelated diseases that each need to be treated individually, cancer is one disease—a mitochondrial disease—and diseased mitochondria prefer glucose and glutamine for fuel. This is cancer’s Achilles’ heel. Healthy cells with healthy mitochondria are flexible and can adapt to just about any fuel source, but not cancer cells. In fact, the majority of cells in our body function best when they burn fat for energy. Cancer cells are bad at burning fat, because fat burning requires respiration, which requires healthy mitochondria. Excellent. We’ve got ‘em right where we want ‘em.
Dietary treatment of cancer: how does dietary restriction work?
If food is restricted enough to lower blood glucose, then insulin and IGF-1 levels will also be lower, quieting the tumor driving genes and pathways described above. This means that fermentation sputters, it becomes harder for tumors to recruit new blood vessels, and tumor growth slows.
Under low blood glucose conditions, insulin’s opposite hormone, glucagon, kicks in.
Glucagon stimulates fat burning, which raises ketones and fatty acids in the blood. Ketones and fatty acids are just breakdown products of fats. Ketone bodies and fatty acids cannot be fermented; therefore cancer cells cannot use them for fuel. Glucose restriction stresses cancer cells. However, most healthy cells prefer to use fatty acids and ketones for energy. Glucose restriction is good for healthy cells.
Glucagon also keeps your blood sugar from dropping too low by turning on a process in the liver called “gluconeogenesis” (making glucose from scratch). This is why we never need to eat any carbohydrates—we are always able to make all the glucose we need out of proteins and fats. The brain cannot burn fatty acids but it can burn ketones, and under low glucose conditions, the brain gradually shifts from burning mostly glucose to burning mostly ketones (to read more about why this is good for the brain, read my post: "Bipolar Disorder and Low Carb Diets"). The brain may still require a small percentage of glucose to function at its best, but there is always enough glucose in the bloodstream because of glucagon, and most other organs will pass up glucose under these conditions in order to let the brain have first dibs.
Cancer cells and healthy cells both have a molecule on their surfaces called GLUT-1. This glucose transporter ushers glucose out of the bloodstream and into cells. Interestingly, under low glucose conditions, healthy cells will create more of these transporters and display them on their surfaces so as to optimize their ability to obtain glucose. Even more fascinating is that cancer cells, which are damaged, and therefore less flexible and adaptable, are not able to do this. In fact, when glucose levels are low, cancer cells are even weaker than usual; not only can they not raise their GLUT-1 levels, their GLUT-1 levels actually drop. This is one more way that glucose restriction impairs cancer cells. Even though there is always some glucose in the bloodstream because of gluconeogenesis, cancer cells are less able to access it than healthy cells because they are damaged.
The oxidation/inflammation connection
When ketones are burned for energy instead of glucose, fewer reckless “reactive oxygen species” (ROS) are generated. These are wild free radicals that cause “oxidative damage”—a type of damage that has been associated with numerous chronic diseases. This means that shifting the body from being a carbohydrate-burning machine to becoming a fat-burning machine reduces oxidative damage, and therefore potentially reduces risk for numerous chronic diseases. Diets that raise blood levels of ketones are considered by neurologists to be “neuroprotective.” That is to say, they protect brain cells from harm. I would actually state it the other way around: glucose burning is “neurotoxic”and burning ketones instead simply restores the natural, healthy level of disease resistance we inherited from our ancestors.
One reason why “ketogenic diets” (diets that force the body to burn ketones instead of glucose) are under consideration for the treatment of so many neurological diseases—from autism to Alzheimer's to multiple sclerosis to epilepsy to Parkinson's Disease—is that the transition from glucose burning to ketone burning is powerfully anti-inflammatory. Seyfried writes:
“There is no drug therapy that I am aware of that can target as many proinflammatory mechanisms in the microenvironment as can DER (dietary energy restriction). I think real progress in tumor management will be achieved once patients and the oncology community come to recognize this fact.”
In fact, Dr. Seyfried says that it is inflammation which damages mitochondria and respiration in the first place, and therefore inflammation may be the true cause of cancer.
How to starve cancer cells
Food restriction reduces the incidence of both inherited and acquired cancers in laboratory animals.
Now, most cancer cells grow best when they have access to a combination of glucose and the amino acid glutamine (see article 2). However, there are some types of cancer cells which do just fine without any glucose as a food source, because they are especially good at burning glutamine. Dr. Seyfried argues that this is why BOTH glucose (from dietary carbohydrates) AND glutamine (from dietary protein) need to be restricted in order to best target cancer cells.
Dr. Seyfried recommends a specially-formulated low-calorie “ketogenic” diet consisting of 80% fat, with the rest (20%) being made up of protein + carbohydrate. This diet forces your cells to burn fat for energy. It contains enough protein for your cells to function properly, but no more. Excess protein means excess amino acids, and glutamine is an amino acid (cancer cells like glutamine). The ketogenic diet does not have to contain any carbohydrate (see my carbohydrates page), but, according to Seyfried, it is ok if contains significant amounts of carbohydrate, as long as calories are kept low. According to Dr. Seyfried, blood glucose levels respond more to calorie intake than to carbohydrate intake.
The goal of this diet is to shift your body from burning mostly glucose (sugar) to burning mostly ketones (fat). Fat molecules get broken down into 3 fatty acid chains plus one molecule of glycerol. The fatty acids can be turned into ketones, and the glycerol backbone can be turned into glucose. [This is why even eating too much fat can raise blood sugar a little bit in some people. Carbohydrates are best at causing high blood sugar. Proteins can raise blood sugar (although not as easily and not as steeply) because some amino acids can be turned into glucose. Dietary fat is least likely to raise blood sugar, but it is not impossible, especially if you are eating more calories than you need.] The idea behind ketogenic diets is to restrict carbohydrate and protein so much that fat from the diet (and/or from excess body fat) is broken down into ketones (instead of being stored as fat), which are burned by healthy cells for energy.
Summary of Dr. Seyfried's recommendations for cancer patients
People following strict ketogenic diets to control seizures or manage cancer need to weigh and measure everything they eat, and monitor their blood sugar and blood ketones daily. Special meters are required for home testing. The meters themselves are very inexpensive, but the test strips are very expensive. (I own a Precision Xtra blood ketone meter and the ketone strips cost about $2.00 each.) [UPDATE: Since writing this post, I have purchased a Keto-Mojo blood glucose and ketone meter. The strips are only $.99 and the meter has bluetooth capability to track your ketones. See my short review here.] Dr. Seyfried recommends that blood sugar levels be allowed to fall into the 55-65 mg/dL range, and that ketones rise to at least 4.0 mM. He refers to this combination of values as “the zone of metabolic management.” To give you an idea of the average person's values when eating a typical diet, blood sugar levels tend to be in the 80's and 90's, and ketones are usually 0.3 mM or lower.
The quickest way to get into the therapeutic zone is by fasting (water only) for 3-5 days. During the induction phase, (harmless) carbohydrate withdrawal symptoms may occur, which typically include lightheadedness, nausea, and headaches.
He offers an alternative to this fasting induction: limit carbohydrates to less than 12 grams per day and limit protein to 0.8 to 1.2 grams per kg body weight per day (0.4 to 0.6 grams per pound body weight). With this less extreme plan, he says it may take up to several weeks to reach the recommended therapeutic zone values.
Once you are in the zone, he recommends you use your daily test results to fine-tune your caloric intake—i.e. see how many calories you can get away with while staying in the zone. Everyone’s metabolism is different, so some people can get away with more calories than others without falling out of the zone. One source I read suggested an initial caloric intake of about 30% below your resting daily metabolic requirements (you can estimate your basal metabolic rate by using simple free calculators available on the internet). If you are overweight and are losing weight with this plan, he recommends eating enough so that you’re not losing more than 2 pounds per week. He also recommends supplementing your diet with a multivitamin, calcium, omega-3’s and vitamin D.
If your cancer would benefit from surgical debulking, he recommends waiting until you have been on the ketogenic diet for at least a few weeks before undergoing surgery, if you can afford to wait. This is because the diet can reduce blood vessel mass, inflammation, and tumor size, making it easier for the surgeon to remove the tumor more cleanly.
Dr. Seyfried points out that vigorous exercise can raise blood sugar levels, and therefore he advises patients to "walk, not run." Strenuous muscle activity releases lactic acid into the blood, which can be converted into glucose by the liver and released back into the bloodstream.
NOTE: Dr. Seyfried writes: "We do not believe that KD-R (restricted ketogenic dieting) alone will provide complete disease resolution for most patients." He then goes on to discuss other strategies that can be combined with dietary restriction to optimize results—these will be covered in article 4.
Some basic precautions
All of your medications must be closely monitored by your physician because this diet can significantly affect required dosages. For example, if you are taking a diuretic, you may no longer need it, since this diet has natural diuretic properties. Another example: if you are taking insulin or any blood sugar lowering medicines for diabetes, you are likely to need much lower doses rather quickly. It can be very dangerous not to pay attention to these factors. Blood tests may be needed to monitor electrolytes and other important medical values. Some people may need to begin this diet in a hospital or clinic setting for proper monitoring.
This diet will not work if you are taking steroid medications such as dexamethasone (Decadron), because steroid medications raise blood sugar. It may also not work if you are receiving intravenous medications which contain glucose.
It is very important to have the support of your household and your physician if you embark on such a plan, because it requires close monitoring, discipline, and social support (hard to keep your hand out of the cookie jar when everyone else at home is enjoying cookies).
Designing a nutritionally adequate ketogenic diet is not easy, so make sure you take advantage of the experience of others who know how to do it properly. There are a couple of good resources listed below to get you started. You may even want to hire a nutritionist with expertise in medical ketogenic diets.
Please know that I am not qualified to recommend any particular diet to anyone with cancer, and this summary of Dr. Seyfried's recommendations is not intended as medical advice. Ketogenic diets are very challenging and should not be undertaken without sufficient education, preparation, support, and medical monitoring.
So many remaining questions . . . do cancer treatment diets really need to be this strict? What is the best diet for cancer prevention?
To read the final article in this series, go to "What Causes Cancer Part IV: Got Hope."