Cancer Part 4: Got Hope?

clouds signifying hope using ketogenic diet for cancerThe future of cancer prevention and treatment may not be in sexy, high-tech, gene-targeting therapies, but in our own hands…or rather, on our own plates. Which diets work best for cancer treatment and prevention?

[This is the 4th in a 4-part article inspired by Dr. Thomas Seyfried’s book Cancer as a Metabolic Disease.  To begin with the first article, click HERE.]

Cancer Treatments: Standard Therapies vs. Dietary Therapies

Standard Therapies

  • Conventional treatments can help in the short-term but can cause problems in the long-term. 
  • Chemotherapy is toxic to healthy cells and can breed resistance among cancer cells, increasing the risk of more aggressive cancers if relapse occurs.
  • Radiation turns up the activity of the tumor growth pathway (PI3K/Akt/HIF), which promotes not only tumor growth, but also recruitment of new blood vessels (angiogenesis) and drug resistance.
  • Radiation increases fusion activity between cells, which means that normal and healthy cells can merge into hybrid cells and become more aggressive.
  • Radiation directly damages mitochondria, which increases risk for cancer in the future.
  • Both radiation and immunosuppression therapy (drugs that suppress the immune system) can increase the incidence of metastatic cancers (cancers that spread).
  • Steroids such as dexamethasone (Decadron), often used to reduce inflammation, raise blood sugar levels, feeding tumor cells and enhancing their survival.

Dietary Therapies

  • DER (dietary energy restriction) triggers cancer cell death via apoptosis (programmed cell suicide), which is a natural, noninflammatory process that happens from within the cell, causing no collateral damage. Conventional treatments kill cancer cells via necrosis, an inflammatory process that happens from the outside and is locally destructive. Tumor cells that are being fed glucose/glutamine are resistant to apoptosis, but under ketogenic conditions, they become better able to undergo apoptosis again.
  • DER and chemotherapy can both cause weight loss. However, the weight loss associated with DER is healthy and does not weaken people, whereas chemotherapy-induced weight loss is unhealthy and weakens people.

Dr. Seyfried wonders if some of the benefit that some people obtain from chemotherapy may be due to the calorie restriction that occurs due to loss of appetite. He notes that drug studies don’t usually take this possibility into consideration.

“DER (dietary energy restriction) can be considered a broad-spectrum, nontoxic metabolic therapy that inhibits multiple signaling pathways required for progression of malignant tumors regardless of tissue of origin. It is not clear to me why so many oncologists have difficulty appreciating this concept.

“Therapies that reduce glucose and elevate ketones can starve glucose-dependent cancer cells while protecting and fueling healthy cells. There is no other cancer therapy that can do this.”

Complementary Cancer-Fighting Strategies

Dr. Seyfried does not think that dietary restriction alone is sufficient to fight most cancers, so he proposes some additional strategies that can be used in combination with dietary measures to optimize results:

  • “Anti-glycolytic” drugs that reduce the activity of the glycolysis (fermentation) pathway, which is the primary energy pathway for most cancer cells.

“…anti-glycolytic drugs together with energy-restricted diets could act as a powerful double ‘metabolic punch’ for the rapid killing of glycolysis-dependent tumor cells.”

  • “CR-mimetic” drugs that mimic the effects of calorie restriction by lowering glucose levels. These drugs should not be used without diet, because they lower glucose without raising ketones. Without ketones, healthy cells could die of energy failure—they would have neither glucose nor ketones for fuel.
  • Hyperbaric (high pressure, 100%) oxygen. Excess oxygen reduces the activity of an enzyme called hexokinase II, which grabs onto glucose after it enters cells and traps it inside so it can be burned for energy.

But standard treatment sometimes works and diet doesn’t always work…

We all know people who have undergone successful standard treatments and who have not had a recurrence of cancer. My own mother had cancer twice, decades ago, and has had no cancer since. In both cases surgery was curative for her. If you are lucky enough to have a simple form of cancer in a body part that can be completely removed, and you catch it before it spreads, your prognosis is probably pretty good.

Chemotherapy and radiation can kill many cancer cells because (as discussed in article #1), they are more vulnerable to these agents than healthy cells, and if you have a healthy enough immune system, your own body may be able to take care of the rest. Some people never get cancer again—they may change their lifestyle after a cancer scare and start taking better care of themselves (my mother stopped smoking, for example). Some adopt a healthier diet or start exercising. Some may just be lucky. But clearly modern cancer therapies have made a difference for some people, including my own mother.

So my mom is a cancer success story, but a close family friend of ours who was diagnosed with glioblastoma multiforme (brain cancer) was not so lucky. She lived for only a few months, and those final months were of very poor quality. She had smoked for years, but had quit long before her diagnosis. She loved candy. As kids we always looked forward to her visits, because she always walked through the door with a big package of red licorice and a king-sized bag of m&m’s. And as soon as she ran out of treats, she’d say to my mother: “Ain’tcha got somethin’ sweet?”

I have no idea why she got brain cancer, of course, but modern treatments certainly were not able to help her. I do find it interesting that the second most common type of cancer among young people is brain cancer, and the brain just happens to be the organ most heavily dependent on glucose. Could it be that the brain is especially sensitive to the damaging effects of high sugar/high flour diets?

Ketogenic Diet for Cancer Case Studies

First study of ketogenic diet with human brain malignancy

Linda Nebeling, PhD, MPH, RD (now with the National Cancer Institute) authored the first-ever study of a ketogenic diet in human brain malignancy [Nebeling 1995]. This was a landmark study of two young girls with advanced-stage, inoperable brain tumors that had not responded to traditional therapies. A three-year-old girl with stage IV astrocytoma and an eight year old girl with grade III astrocytoma were treated with a ketogenic diet. Both children responded well, and experienced long-term tumor management without further chemotherapy or radiation. PET scans revealed a 22% reduction in glucose uptake by tumors in both girls.

Low-calorie/ketogenic diet with brain tumors

Giulio Zuccoli MD (Italian neuro-radiologist) and Thomas Seyfried PhD published a case report [Zuccoli 2010] of a middle-aged woman with glioblastoma (a form of brain cancer) who was treated with a 600-calorie/day ketogenic diet. Upon diagnosis, steroids (to control inflammation) and anticonvulsant medication (to control seizures) were given. She underwent surgery, fasted briefly, and then began the diet. After 14 days on the diet, steroids were stopped, and chemotherapy and radiation treatments were started. After two months, chemotherapy and radiation were discontinued. One week later, PET scan and MRI were performed and no tumor tissue or swelling was detected.The patient stopped the diet, and 10 weeks later, MRI showed evidence that the tumor had come back.

This case report demonstrated that a) the ketogenic diet was well-tolerated; b) the diet may be a useful add-on therapy, as most tumors of her type do not respond as well as hers did to standard treatments alone, and c) inflammation was well-controlled without the usual need for steroids, supporting the anti-inflammatory properties of the diet.

Very low-carb diet in ten patients with incurable cancers

Eugene Fine, MD, professor of nuclear medicine at Albert Einstein College of Medicine just published a 28-day pilot study [Fine 2012] of a very low carbohydrate diet in ten men and women ages 53-73 with incurable, advanced cancers of a variety of types (3 colon, 2 breast, 2 lung, 1 ovarian, 1 esophageal, 1 fallopian tube). Carbohydrate intake was about 9%, but protein and fat were not restricted. Interestingly, those with high ketone levels (and low insulin levels) were the only ones whose tumors either stopped growing or got smaller as evidenced by PET scan. A link to his video presentation is below in the resources section. Dr. Fine’s study is groundbreaking because it may pave the way for additional studies, which are badly needed. Here is a link to his video presentation from the 2012 Ancestral Health Symposium.

Ketogenic diet in four patients with brain cancer

Beth Zupec-Kania, RD is a nutritionist with the Charlie Foundation (an organization dedicated to raising awareness of and providing support for the use of ketogenic diets in children with epilepsy). Ten glioma (brain cancer) patients contacted her for help in using ketogenic diets in the treatment of their cancer. Four of them ultimately committed to a strictly supervised ketogenic diet. Three of the four patients had stable or atrophied (reduced) tumor size documented by MRI. Two had been on the diet for several years and were still alive despite having initially been given only a few months to live. One patient died; he had had advanced stage metastatic cancer prior to starting the ketogenic diet. He remained active and alert until the last two months of his life, and outlived his prognosis by a year.

Obstacles to Dietary Treatments

Ketogenic diets are hard to follow. They require careful monitoring, tremendous self-discipline, and essentially require that people turn their usual diet completely upside-down. You’ve got to be very motivated, and have the full support of everyone who lives with you. Even if everyone on the planet were 100% convinced that a ketogenic diet is the best diet for cancer, I would eat my hat if everyone with cancer followed it. That would be unrealistic—changing one’s diet is hard.

Ketogenic diets are, by nature, high-fat diets, and this will bother some people on a psychological level, due to (unnecessary) fear of eating fat. For more information, see my fats page and my cholesterol page.

Most physicians are taught next to nothing about nutrition during medical training, and once in practice, are too busy to learn. Nutritional treatments are not particularly sexy or high-tech and may not be of interest to some physicians. Nutritional treatments may be viewed as slower to take effect, and as time-consuming to implement.

But here is the most important obstacle: if a particular treatment is not sanctioned by the medical establishment and does not have solid studies behind it, most doctors will be afraid to recommend it or even support it, due to discomfort with uncertainty and fears of medical malpractice. Doctors take their responsibilities very seriously and want to provide the best treatment they can. In today’s world, that means applying the “standard of care.” Currently surgery, chemotherapy, and radiation are the standard of care. And what’s more, is that the standard of care is what insurance companies will pay for. They are unlikely to cover ketone meters, testing strips, special nutritional counseling, etc.

Is your doctor simply keeping up with the standard of care or is he or she interested in being on the cutting edge? Would your doctor be willing to read Dr. Seyfried’s book, or at least his journal article? [see references below]

The good news is you do not need your doctor’s permission to eat a ketogenic diet, only his or her support and willingness to monitor your progress. Open-minded, patient-centered physicians should be on board with your efforts so long as you are willing to take responsibility for your care.

Do Ketogenic Diets Really Need to Be So Strict?

If you read article 3, you may have been disheartened to see how tough Dr. Seyfried’s dietary recommendations are. Yet as draconian as his diet is, he doesn’t think it will work very well on its own without chemotherapy. While no treatments of any kind are perfect, if Dr. Seyfried’s hypothesis about mitochondria and diet are correct, shouldn’t they have the potential to work better than he thinks they will?

Having read his book and heard him speak, I believe Dr. Seyfried is a brilliant scientist and thinker. The only (gentle, constructive, but wicked important) criticism I have is the same one I have of most scientists who study diet—he thinks about diet as a simple collection of proteins, carbohydrates, and fats, and neglects the actual foods in the diet.

Dr. Seyfried compared two different types of chow in mice with cancer—one high-carb “standard” chow and one high fat “ketogenic” chow. He found that the ketogenic chow did not work against cancer if you let the mice eat as much as they wanted. Their little blood sugar levels stayed high and their cancers grew. He had to lower their calories to see benefits. He concluded that both diets worked equally well as long as you lowered calories—a lot. This made me suspicious, so I visited the chow manufacturers’ websites to see what the diets actually contained. I wonder if it will shock you as much as it shocked me.

Dr. Seyfried’s standard high-carb chow:

ProLab RMH 3000 (LabDiet)—62% carbohydrate, 22% protein, 5% fat, 5% fiber

Ingredients: ground wheat, dehulled soybean meal, wheat middlings, ground corn, fish meal, pork fat, alfalfa meal, calcium carbonate, brewer’s yeast, soybean oil, salt, vitamins, and minerals.

The first four ingredients are refined grains and legumes. Nearly 100% refined junk (including lots of refined carbohydrate) that no self-respecting mouse would naturally consume. No wonder he had to limit how much of this stuff the mice ate by 30-60% in order to lower blood glucose.

Dr. Seyfried’s ketogenic chow:

Ketocal (Nutricia)—90% fat, 1.6% carbohydrate, 8.4% protein

Ingredients: hydrogenated soybean oil, dry whole milk, refined soybean oil, soy lecithin, corn syrup solids.

Nice. Processed soy, dairy, and corn syrup. Poor little mice.

If you have read my dairy page, you will know that the whey proteins in milk raise insulin levels, which can prevent ketosis. This may have been why he had to limit how much of this stuff the mice ate to get good results.

To Dr. Seyfried’s credit, he points out in his book that other researchers have been able to achieve good results in their animal cancer experiments without having to restrict calories and he is unable to explain why. Let’s look at a mouse diet that worked without restricting calories:

Unrestricted ketogenic chow:

Ketogenic Bio-Serv F3666—8.36% protein, 0.76% carbohydrates and 78.8% fat

Ingredients: lard, butter, corn oil, casein, cellulose, mineral mix, vitamin mix, dextrose

Look, ma, no whey protein and no refined carbohydrate! The mice could eat as much of this (admittedly very weird) chow and get good results [Stafford 2010]. It makes me hopeful that even this odd diet, which is a far cry from a healthy mouse diet, delivered positive results.

Dr. Seyfried also referred to another study that used a high-protein, low-carb diet with unrestricted calories that also worked, but I could not locate the article in time to include it here. [Ho 2011]

I can’t help but wonder how these little mice would have fared had they been fed real food that mice are actually supposed to be eating.

So, do we need to restrict calories or not? It may depend on the composition of the diet… I think the jury is still out. However, people who eat well-formulated ketogenic diets report a substantial reduction in appetite and tend to naturally find themselves eating quite a bit less without having to count calories.

Metastatic Cancer Is Different

Ninety percent of all cancer deaths are due to metastatic disease (cancer that has spread to more than one organ). These are the bad boys. Once cancer is on the move it’s very hard to stop, which is why prevention is so important. But before we get to that, one of the most fascinating topics in Dr. Seyfried’s book is his theory of how and why some cancers travel through the body to distant organs. He makes a compelling argument for the role of a particular kind of immune cell called a macrophage in helping cancers to spread.

The normal role of macrophages (macs) in our immune system is a very complicated and special one. These are amazing cells, with the ability to change their personality, shape, and behavior whenever necessary, depending on the local circumstances. Every macrophage begins its little life as monocyte, a round cell that can cruise the bloodstream. When trouble is lurking anywhere in the body—if there is injury or inflammation or infection—monocytes heed the call of damaged tissues and travel to the troubled area. Once they are close enough, they squeeze themselves out of the blood vessel and into local tissue, where they magically morph into macrophages so they can to get to work.

Macrophages assess the situation and release all kinds of special chemical signals to help recruit other types of immune cells to the scene. But the coolest thing about macrophages is that they can swallow stuff whole. MAC ATTACK!! Macs engulf our own used-up, damaged, or dead cells, and devour bacteria that can do us harm.

When Macs Run Amok…

Now these cells are our best friends in infection or wound healing, but if they become cancerous, they can become our worst enemy, because they are very active, can fuse with other cells, and they are mobile. Now you’ve got macs gone amok. Metastatic tumor cells of many types have been observed to have phagocytic behavior (i.e. they eat other cells…just like macs do).  Macs are often found mixed in among tumor cells, contributing to chronic inflammation in the area by triggering local immune reactions. These macs are called TAM’s, or tumor-associated macrophages. Tumors containing TAM’s have a poorer prognosis.

Macs tend to hang out more often in their favorite organs—they are especially drawn to lung, liver, and bone. These also happen to be favorite places for cancer to migrate to, as well. Some cancers also like to spread to injured or inflamed parts of the body, just like a mac would. Plants and certain lower animals, which do not have macrophages, can also get cancer, but their cancers never metastasize. Fascinating. 

How Best to Prevent Cancer in the First Place?

Since 90% of all cancer deaths are due to metastatic cancers (cancers that have spread to more than one organ)—and this estimate has not changed in 50 years—early detection and prevention of spread plays a MAJOR role in prognosis. But the good news is that most cancer IS preventable. 

About 5% of cancers are caused by mutations that are inherited at birth. About 15% of cancers are caused by viruses. The rest—a full 80%—are associated with the following risk factors:

  • Smoking
  • Alcohol
  • Obesity
  • Age
  • Radiation exposure
  • Carcinogenic chemical exposure

This means that the vast majority of cancers are preventable using lifestyle modifications. Dr. Seyfried writes (and I have read many papers supporting this logic), that the best way to prevent cancer (and most chronic diseases, for that matter), is to avoid exposure to things that cause tissue inflammation. All of the above risk factors are directly associated with inflammation. Two of the above risk factors are dietary—alcohol and obesity, so let’s zero in on those. This is a nutrition website, after all.  For more information about how alcohol and inflammation are connected, please see my alcohol page.

What Is the Connection between Obesity and Inflammation?

The road to inflammation is paved with refined carbohydrates. To fully explain the science behind these connections here would take us too far off track, but suffice it to say for now that refined carbohydrates (such as sugar and flour) lead to high blood sugar and high insulin levels. These, in turn, increase the production of damaging free radicals within the mitochondria. They also increase the production of a molecule called NF-kappa-B, which turns on genes that promote inflammation. It would therefore make sense, whether you are overweight or not, to minimize your exposure to refined carbohydrates.

Obesity is a major risk factor for cancer, and there is no question that diet is the most powerful tool available to manage weight. If you have been paying attention to thought leaders in the field of obesity, or you are familiar with the information on this website about obesity, or you have learned through your own experiences what works best, you know that the single most effective dietary strategy for preventing and managing weight gain (as well as for preventing and managing most chronic diseases of civilization) is avoiding refined carbohydrates. Refined carbohydrates keep blood sugar and insulin levels high, promoting inflammation and oxidation throughout the body. They also encourage overeating due to loss of control over appetite, which continues the vicious cycle. 

Yet we all know people with cancer who are not overweight and who seem to take excellent care of themselves. We even know of athletes who don’t drink, don’t smoke, and are in excellent physical condition, who nevertheless have come down with cancer. Could it be that refined carbohydrate is the hidden risk factor in people like this? To learn more about the connection between carbohydrates and cancer, there is an excellent review article available free on line.

In addition to avoiding inflammation, Dr. Seyfried recommends a 7-day, water-only fast once a year. His reasoning is that a total fast forces the body to rid itself of damaged and weakened cells that may be pre-cancerous. With nothing else to eat, healthy cells turn to cannibalism, eating their vulnerable neighboring cells. How’s that for an image?

The Bottom Line

The bottom line is that diet clearly makes a huge difference, but we don’t yet know what the ideal diet for cancer treatment is. There is no question in my mind at this point that carbohydrates are bad for cancer. To what degree calories, protein and fat need to be restricted is unclear. We need more studies, and they need to be more thoughtfully designed. It seems that ketogenic diets have tremendous potential, but I don’t know if they need to be as strict as Dr. Seyfried recommends. Might people who design their ketogenic diet around healthy, whole foods and avoid dairy be able to get away with more calories?

I do think it makes sense for those of us who want to reduce our risk for cancer to minimize refined carbohydrates, minimize dairy products (particularly those with high whey content), maintain our weight in a healthy range, and choose whole foods over processed foods. Since that dietary pattern is already quite an improvement from the standard American diet, I have hope that it could make a big difference in our risk for cancer (as well as many chronic diseases).

However, if I already had cancer or were a cancer survivor, I wouldn’t touch a carbohydrate with a 10-foot pole.  Dairy, being a growth formula (for baby cows), would also be off the menu.

Taking One for the Team

Dr. Seyfried’s book, Cancer as a Metabolic Disease, inspired me to attempt a fasting jump-start to ketosis to see how long it takes to achieve his “zone of metabolic management.” To read about my 5-week experiment with Dr. Seyfried’s dietary recommendations, start with the first post: Seyfried’s Cancer Diet: My Fasting Jump-Start to Ketosis.

Resources

Cancer as a Metabolic Disease book

Seyfried, Thomas N.  Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer. Hoboken, NJ:  Wiley, 2012.

Miriam Kalamian (www.dietarytherapies.com), Hamilton, Montana.  Master’s level nutritionist who used a ketogenic diet to help her 4 year old son with brain cancer.

For those of you read German: www.umm.de/4757.0.html, a physician-run website with lots of practical advice about how to implement a ketogenic diet in the treatment of cancer.

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References

Brownlee M.  Banting Lecture 2004.  The pathology of diabetic complications: a unifying mechanism.  Diabetes 2005; 54: 1615-1625.

Fine EJ et al. Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition 28 (2012) 1028–1035.

Ho VW et al.  A Low Carbohydrate, High Protein Diet Slows Tumor Growth and Prevents Cancer Initiation.  Cancer Res 2011; 71(13); 4484–93.  MOUSE STUDY

Klement RJ and Kämmerer U.  Is there a role for carbohydrate restriction in the treatment and prevention of cancer? Nutrition and Metabolism 2011; 8:75. http://www.nutritionandmetabolism.com/content/8/1/75

Nebeling LC et al.  Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients:  two case reports.  J Am Coll Nutr 1995; 14(2): 202-8.

Seyfried, Thomas N.  Cancer as a Metabolic Disease:  On the Origin, Management, and Prevention of Cancer. Hoboken NJ: Wiley, 2012.

Seyfried TN, Shelton LM.  Cancer as a metabolic disease.  Nutr Metab 2010; 7(7).  www.nutritionandmetabolism.com/content/7/1/7

Stafford P et al.  The ketogenic diet reverses gene expression patterns and reduces oxygen species levels when used as an adjuvant therapy for glioma.  Nutr Metab 2010; 7:74.

Zuccoli G et al. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report.  Nutrition & Metabolism 2010; 7:33 http://www.nutritionandmetabolism.com/content/7/1/33

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