May 24, 2016/ Maria Parker
I first became interested in the very low carbohydrate or Ketogenic “Keto” diet last October when I did the Rim to Rim run/hike at the Grand Canyon with Pete Quinzio. Pete is a co-founder of Notable Labs, a tech start-up with the goal of assisting patients and their doctors to find treatment for their cancers. They use an individualized approach where a patient’s cancer cells are sent to the lab to be grown and then treated with a huge list of FDA approved medicines, alone and in combination, not just the medicines that are “standard of care” for their particular cancer.
As Pete and I hiked along we talked about all the possibilities for treating cancer that are outside the current standard of care. One of those is the ketogenic, or very low carbohydrate (moderate protein, high fat) diet. Most cancer cells have defective mitochondria. Mitochondria are in every cell of the body and produce energy by breaking down carbohydrates. Because cancer cell’s mitochondria don’t work, cancer cells require lots more sugar to grow and grow very well in a high sugar environment. This was discovered by Otto Warburg and is called the Warburg effect.
Pete told me he had been on the Ketogenic diet to understand what it was like and also because it “reduced inflammation” in the body. That thought stuck with me, and when I got home, I did a lot more research, which mostly consisted of reading the book The Art and Science of Low Carbohydrate Living by Jeff Volek and Stephen Phinney, and then–because it is slightly simpler and more geared to my lifestyle–The Art and Science of Low Carbohydrate Performance, also by Volek and Phinney.
Maria, Pete Quinzio and BethAnn Telford, a brain cancer survivor, on the South Rim before the hike.
As a long-time carb addict, and I mean serious addict, I have always resisted this approach. I could imagine giving up sweets (temporarily) but bread, pasta, potatoes and rice? No way! My favorite meal would be some variation of pasta with homemade Italian bread followed by Cadbury Cream Eggs for dessert. After reading these books, Jim was completely on board to give the new diet a try, but I didn’t think I could do it.
Anyone who has read my race reports knows, nausea and vomiting are a big part of my experience as an ultra-cyclist. It has gotten worse and worse in the last few years and has seriously limited my performance. What we discovered in reading Volek and Phinney’s books is that if you can make it through the first couple of weeks on the diet, your body gets into “nutritional ketosis,” which makes you much more efficient at burning fat–both the fat you eat and body fat. We realized that if we could get into nutritional ketosis and stay there, we wouldn’t need to eat or take in any calories during our races. The thought of getting through a 12 or 24 hour race without vomiting was enough to get me to give the diet a try.
Additionally, the diet is very effective for anyone who has insulin issues including diabetics and those with prediabetes or insulin resistance. Insulin usage is decreased because you are not constantly giving your body carbohydrates to breakdown and moderate in your blood stream.
Perhaps even more importantly for overall health, a ketogenic diet has been shown to reduce inflammation. Inflammation can lead to all kinds of illnesses including cancer and heart disease.
Finally, I believed that some of the brain fog I had been experiencing over the last couple of years might be because of my high carb diet. I worried that I was on my way to early cognitive decline and even Alzheimer’s disease. Studies on the ketogenic diet show that it is good for most diseases or conditions that affect your nervous system including cognitive decline, depression, and Parkinson’s disease. Read more about that here.
So finally, I got on board and Jim and I decided to give it a try. We started in November of 2015 and planned to stick with it until February and the Sebring 12/24 races.
While the first couple of weeks were a struggle for me, Jim had just one or two days of feeling a little off. We followed the advice of Volek and Phinney and drank lots of bullion (you need more salt than usual) and took the supplements they recommended and started to feel better and better. I immediately noticed that I had many fewer episodes of the afternoon sleepies, and that I could call up nouns more quickly.
In February, I did the 12 hours of Sebring on essentially no calories. I drank water and electrolytes, and drank a couple of sips of a Starbucks drink, but otherwise nothing. I never bonked and felt physically strong.
By the time we’d been on the diet for 6 months, both Jim and I decided we were not going back. Jim has lost 25 pounds and looks great and is riding really well. I feel so much better eating very low carbohydrate that I am not even tempted by ice cream, formerly one of my favorite foods. We eat very well: a wide variety of nutritious and delicious foods with lots of fats.
Our main meals usually consist of a protein such as chicken or fish or other meat, and a bunch of vegetables (those that grow above the ground). Everything is cooked and covered in fat. It is sometimes a challenge to get all the fat you need. For snacks we eat nuts and cheese. We try to eat less than 50 grams of carbohydrates – the difference should be made up in fat, not protein, like the old Atkins diet suggested. We also take supplements such as magnesium chloride (Slow-Mag), Vitamin D3 and fish oil.
I would discourage anyone from starting this eating program without reading the science behind it. In addition to the books above, there are lots of good websites. One of the more popular ones is called Ruled.Me. Another very scientific blog on ketosis and the ketogenic diet is eating academy
Here are 3 videos explaining the program:
Much of the latest mainstream nutritional science is supporting eating less sugar and carbohydrates. The FDA just came out with their new nutritional information label requirements which now must include the number of grams of added sugar. That’s all well and good, but as my sister Anne says, “it’s easier to eat none, than a little.” This is certainly true for a carb addict like me.
On a recent trip to Taiwan I ate many more carbs than usual. I slipped out of nutritional ketosis and found that all I could think about was the next carbohydrate snack I would eat. I felt like an alcoholic falling off the wagon. I’m glad to say it was much easier to get back on the wagon at home. It just took a day or two to feel good again.
I recently learned that several Cruzbike owners have independently adopted the diet with similar positive results. I feel really enthusiastic about the power of this eating program to make people healthier. Our friends and family are sick of hearing about it–we talk about it all the time! We want to share because it has made such a positive impact on our lives and we don’t feel deprived at all. I hope this information helps you in your health and fitness goals.
Jim’s cure for cancer
One day after thinking about the ketogenic diet and studying up on it for several weeks, Jim told me, “I’ve come up with a cure for cancer.” He spent some time discussing it with our son Will and here it is:
A Proposed Method to Fight Cancer: Starve it.
The title of a 2010 documentary movie about cancer treatment, Cut Poison Burn, refers to three types of conventional treatments aimed at fighting cancer. Many cancers tend to form a mass, and surgery (cut) takes advantage of the mass-forming quality of cancers. Cancer cells also divide rapidly. Thus, chemotherapy (poison) is used to target rapidly dividing cells. Radiation (burn) also targets the mass-forming quality of cancers.
My proposal is based on targeting the unique metabolic qualities of cancer cells, thus adding “starve” to “cut, poison, and burn”. This is not a new idea, but the method we propose may be. It holds the potential to slow or cure cancer without the use of any expensive/proprietary drugs, radiation equipment, or long-term side effects. The drugs needed are inexpensive and of little or no toxicity. We present this proposal in the hope of stimulating discussion, research, and clinical trials.
The Warburg effect was first described 80 years ago, when Dr. Otto H. Warburg discovered that many cancer cells get all their energy from glycolysis–the splitting of a 6-carbon glucose molecule into two 3-carbon molecules. Healthy non-cancerous cells have other pathways to extract energy from sources other than glucose, but cancer cells are less flexible. Some research suggests that they may be able to use lactate as fuel in addition to glucose, but this remains unclear (1).
The normal range of glucose in the blood is approximately 80 to 110 mg/dl. Our bodies maintain a
constant minimum level of glucose, thus cancer cells are never without an abundant supply of glucose. Contrary to popular belief, our brains do no not have to burn glucose to stay alive and active. The brain can burn ketones. Ketones are 2-carbon molecules formed when we burn fatty acids (fats) for energy. Fatty acids cannot cross the blood-brain barrier, but ketones can. Most people are not efficient at burning fat because they don’t need to be. Most people eat a steady supply of carbohydrates which are easily converted to glucose. If people drastically cut down on their carbohydrate intake, the body will ramp up enzymes and pathways to improve fat-burning capacity. This process has been termed keto-adaptation, because the body increases its capacity to produce and burn ketones.
Here is the proposal: Selected cancer patients will be put on a very low carbohydrate diet for at least two weeks to allow for keto-adaptation. Next, in a monitored health care facility, they will undergo an infusion of insulin (and other agents to be discussed later) which will drop the blood glucose to a level that, hopefully, is deadly to cancer cells but not to healthy cells.
Supplementary methods to increase the kill rate for cancers will need to be explored. But based on existing studies (3,4), the administration of 2-DOG (2-deoxyglucose) may be useful. The analogy I like to use is the Trojan War, where the Greeks used both a siege and the Trojan Horse to bring about the fall of Troy. Cancer cells treat 2-DOG like glucose and transport it into the cell, but it cannot be metabolized by cancer cells. In the Trojan War metaphor, the 2-DOG is the Trojan Horse. The siege is the ketogenic diet and the infusion of insulin or other hypoglycemic agents (e.g. metformin) in the ketone-protected patient. We do not know what period of starvation will kill cancer cells. It could be 2 hours or 24 hours, or it might not work at all. Some cancer cells may just go dormant until the glucose returns. We don’t know how cancer cells will respond, but the hope is they will die.
Oxygen plays a central role in human metabolism. Thus, the addition of either hypoxia (low oxygen levels) via use of an altitude tent, or hyperoxia (high oxygen levels) via hyperbaric oxygen therapy (HBOT) may improve the effectiveness of my proposed treatment. Indeed, the latter therapy in combination with a ketogenic diet proved significantly beneficial in a 2013 study of metastatic cancer in mice (5).
It must be emphasized that insulin infusion into “normal” (non-keto-adapted) patients results in coma and death due to severe hypoglycemia. However, research done decades ago (2) showed that insulin infused into starving keto-adapted patients–at doses that would have killed normal people–left the patients unfazed. They remained alert and functioned normally despite rock-bottom blood glucose levels.
Here’s a sample of a protocol for this technique, for discussion only (do not try this at home). Patient A has metastatic carcinoma with less than 2-years average life-expectancy. A PET scan is
obtained prior to the procedure. Only patients with FDG (fluoro-deoxy-glucose)-avid cancers on the PET scan are eligible for this treatment. FDG is another glucose analog. The body treats it like glucose, but we can image it clearly with a PET scan, and see where and how large a cancer is inside the body.
After informed consent, the patient is brought into ketosis at a blood ketone level of approximately 5 mmol/L. This may be done with dietary restriction of carbohydrate, or infusion of ketones, or both. The patient has a PICC or other central venous access device for simple blood sampling and infusion. Next, the patient, in a fasting state, is placed comfortably in an altitude room/tent simulating 14,000 feet elevation (or perhaps in a HBOT chamber). ACLS-trained personnel and appropriate resuscitation equipment should be standing by, including IV glucose solution and an oxygen supply. The heart works well running on ketones, so the hypoglycemia should not cause any cardiac events, but better safe than sorry. Baseline glucose and ketone levels are monitored and sampled every 5 minutes. Pulse oximetry is used to chart the oxygen saturation of the blood. Insulin is infused intravenously at a slow rate, monitoring the patient’s response. The goal is a maximum reduction of blood glucose concentration with few or no symptoms in the patient. In the study mentioned above, patients reached a glucose level of less than 30 mg/dl without symptoms. The patient should be alert and oriented throughout the procedure. Ketone levels are also maintained at appropriate levels throughout the procedure.
Once maximum asymptomatic hypoglycemia is achieved, the level of hypoglycemia is maintained for X hours. Finally the insulin infusion is stopped and the patient can leave the high (or low) oxygen room. The patient has a follow-up PET scan within a week to determine the response. If the response is only partial, the treatment is repeated with longer hypoglycemia, and/or with a change of other factors, such as oxygen level or 2-DOG supplementation.
The technique will need testing and refining. It’s quite feasible that the period of treatment may need to be repeated over several weeks, or cycled over 24-hours. It may also turn out that the hypoxia is less important than the hypoglycemia, or that alternating high and low blood oxygen levels may enhance cancer apoptosis (cell death). The addition of 2-DOG may or may not improve the effectiveness of the treatment.
This idea occurred to me while sitting in a Panera Bread restaurant in Charlotte, NC on 12/5/15, after reading an excellent book by Jeff Volek and Stephen Phinney called The Art and Science of Low Carbohydrate Living. Similar proposals include a 2009 hypothesis by MW Nijsten and GM van Dam (6) and a 2014 one by Adam Kapelner and Matthew Vorsanger (7).
Jim Parker, MD
1) Goodwin ML, Gladden LB, Nijsten MWN, Jones KB. Lactate and Cancer: Revisiting the Warburg Effect in an Era of Lactate Shuttling. Frontiers in Nutrition. 2014;1:27. doi:10.3389/fnut.2014.00027.
2) Cahill GF, Jr., Aoki TT: Alternate fuel utilization by brain. In: Cerebral Metabolism and Neural Function. Passonneau, JV et al, Eds. Williams & Wilkins, Baltimore, 1980. Pp 234-42.
3) Cheong JH, Park ES, Liang J, Dennison JB, Tsavachidou D, Nguyen-Charles C, Wa Cheng K, Hall H, Zhang D, Lu Y, Ravoori M, Kundra V, Ajani J, Lee JS, Ki Hong W, Mills GB: Dual inhibition of tumor energy pathway by 2-deoxyglucose and metformin is effective against a broad spectrum of preclinical cancer models. Molecular Cancer Therapeutics. 2011 Dec;10(12):2350-62. doi: 10.1158/1535-7163.MCT-11-0497. Epub 2011 Oct 12.
4) Sahra IB, Laurent K, Giuliano S, Larbret F, Ponzio G, Gounon P, Marchand-Brustel YL, Giorgetti-Peraldi S, Cormont M, Bertolotto C, Deckert M, Auberger P, Tanti JF, Bost F: Therapeutics, Targets, and Chemical Biology:Targeting Cancer Cell Metabolism: The Combination of Metformin and 2-Deoxyglucose Induces p53-Dependent Apoptosis in Prostate Cancer Cells.
Cancer Research. March 15, 2010 70:2465-2475; Published OnlineFirst March 9, 2010;doi:10.1158/0008-5472.CAN-09-2782
5) Poff AM, Ari C, Seyfried TN, D’Agostino DP: The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer. PLoS ONE 8(6): e65522. doi: 10.1371/journal.pone.0065522
6) Nijstem MW, van Dam GM: Hypothesis: using the Warburg effect against cancer by reducing glucose and providing lactate. Med Hypotheses. 2009 Jul;73(1):48-51. doi: 10.1016/j.mehy.2009.01.041. Epub 2009 Mar 4.
7) Kapelner A, Vorsanger M: Starvation of Cancer via Induced Ketogenesis and Severe Hypoglycemia. arXiv:1407.7622v2 [q-bio.OT] 8 Dec 2014.