Cancer & Ketosis

I wanted to thank reader Sully for sending a link to the Time Online article on the use of ketogenic diets and cancer treatment. The article is surprisingly well written and informative…I wonder if the author has a personal interest in the topic as the usual counter point, mainstream prattle was refreshingly absent. I guess that exposes a bias on my part…I’ll flesh out from where that bias arises on both an emotional and logical level later, but right now I want to point out a few nuggets in the paper. Before I do that, lets quickly review what ketosis is.

Ketosis In 100K Words Or Less
I could just say ketosis is a metabolic state the 99.9% of doctors and registered dieticians CAN NOT ACCURATELY DEFINE OR DESCRIBE, but that does not help much as to details and mechanisms now does it? Ketosis is the state in which glucose is relatively limited or lacking as a fuel and cells begin to use fat as a primary fuel source. Not dissimilar to the formation of lactate from glucose, ketone bodies are the incompletely metabolized remnants of fatty acids. Ketones have the interesting characteristic of being water-soluble and thus are capable of passing through cell membranes, including the blood brain barrier. This is handy since the brain does need SOMETHING to run on and if glucose is in short supply, ketones work remarkably well, in fact better than glucose in nearly every conceivable way. That is a brief run down on ketones, if you want to geek out on the topic you need to read Dr. Eade’s post on ketones. I really want to emphasize the point that ketosis is a normal metabolic state. I’ wager THE DEFAULT metabolic state in humans but this is going to be a long enough post without that side diversion. So, back to that link to the Time article! Here is the main point I want to make from that paper:

“…we are only allowed to enroll patients who have completely run out of all other therapeutic options.” That means that most people in the study are faring very badly to begin with. All have exhausted traditional treatments, such as surgery, radiation and chemo, and even some alternative ones…”

 
I guess my point is actually a question. WHY? Why are the sickest people, who have exhausted every conventional option, many of which are VERY dangerous, why is a safe nutritional intervention handled like it is an atomic bomb? Theories concerning the potential of a limited carbohydrate diet as a cancer treatment have existed since the 1960’s. A few animal studies exist on the topic and a one or two human trials…but this potential therapeutic intervention has been avoided like the plague. This is just baffling, especially when we look at the “safety” of modern chemotherapeutics.

Chemotherapeutics: Toxic is better!
To understand what scientists are looking for with regards to chemotherapeutics you need to understand a few of the mechanisms underlying cancer. Very generally cancer has an initiation phase, typified by damage or changes to the DNA, a growth phase in which otherwise well-behaved cells begin to push out against other tissues, and finally spreading or metastasis in which cancer can disseminate throughout the body. Keep in mind this is a generalization and does not describe all cancers or scenarios.

Many chemotherapies target the DNA of cancer, either preventing the replication or actually attempting to damage the DNA to such a degree that apoptosis (programmed cell death) occurs. In one case specific enzymes involved in the DNA replication process are the targets for chemotherapeutics. The premise being: stop all cellular replication and you stop cancer. This works…kind of. Unfortunately cancer is enough like us that drugs that stop “IT” from replicating also stops stuff like our gut lining, hair and other goodies from replicating. This is where folks loose their hair and shed their intestinal and mouth linings after the use of folate blockers like Methotrexate. Did I mention that folate (folic acid) is a potent up-stream PREVENTION of DNA damage and CANCER formation? Yep, one of the mainline defenses AGAINST cancer is a drug that not only causes you to shed your GI lining, but it also disables one of your primary systems for preventing FUTURE cancer.

A second class of drugs goes right to the heart of the matter. Drugs like Cisplatin actually DAMAGE DNA! These substances rate remarkably high on the AMES test. The AMES test, developed by Bruce Ames, is a measure of the mutigenicity of a given substance. In simple terms is how much DNA damage a substance can be expected to exert in a living system. If you recall from above, rapidly growing things require loads of DNA synthesis. If you want to kill something, why not destroy the DNA? It’s a great idea, but then again you are subjecting people to a substance that is KNOWN to promote cancer formation. Mutagens are typically CARCINOGENS.

A third class of drugs attempts to stimulate apoptosis of cancer by disrupting cellular stability. Paclitaxel (Taxol) is perhaps the best known of these drugs and acts on the microtubules. The theory again, is that rapidly dividing cells will be preferentially targeted in this process.

The real problem with all these approaches, and in fact the major thrust of cancer research is that cancer is US. It is not a foreign invader; it is a modified version of us. How do you kill just a little bit of yourself? This is one element of the problem facing cancer research and this may be born of our success with antibiotics. Prior to penicillin, death from pneumonia and simple infections was horribly high. Folks just do not remember this and few people appreciate how powerfully this affected the collective psyche of medicine. People who otherwise would have died are now saved with a pill. Unfortunately the magic bullet has never materialized in the case of cancer.

By now you may be thinking: “OK, Robb needs to cut back on the Americanos and chill out! I mean this is SCINECE and MEDICINE! This stuff must be helpful to someone despite the ominous spin Robb is putting on this…” Well…despite the fact that the “War On Cancer” was declared in the 1960’s things have not improved…at all. Don’t believe me? We will look at some statements from the medical establishment itself. In a few instances some cancers are much more effectively treated than they were 30 years ago. Unfortunately this is the exception, not the rule and all this while cancer rates in total have increased. Much of the supposed success trumpeted by researchers and drug companies is an outgrowth of improved imaging and diagnostic techniques. This has simply shifted the time people know they have cancer forward but it has done little to improve actual survival. People are also being diagnosed with “cancer” when it is pre-cancerous tissue that may or may not ever advance into full-blown cancer. It does wonders for survival statistics to diagnose and subsequently “cure” folks of a disease they would never have died from.

From JAMA
Are Increasing 5-Year Survival Rates Evidence of Success Against Cancer?

H. Gilbert Welch, MD, MPH; Lisa M. Schwartz, MD, MS; Steven Woloshin, MD, MS JAMA. 2000;283:2975-2978.

You can read the abstract here but I’ve pulled out the results and conclusion for a closer look:

Results  From 1950 to 1995, there was an increase in 5-year survival for each of the 20 tumor types. The absolute increase in 5-year survival ranged from 3% (pancreatic cancer) to 50% (prostate cancer). During the same period, mortality rates declined for 12 types of cancer and increased for the remaining 8 types. There was little correlation between the change in 5-year survival for a specific tumor and the change in tumor-related mortality (Pearson r=.00; Spearman r=-.07). On the other hand, the change in 5-year survival was positively correlated with the change in the tumor incidence rate (Pearson r=+.49; Spearman r=+.37).

Conclusion  Although 5-year survival is a valid measure for comparing cancer therapies in a randomized trial, our analysis shows that changes in 5-year survival over time bear little relationship to changes in cancer mortality. Instead, they appear primarily related to changing patterns of diagnosis.  Emphasis mine.

Like I said above, all that is happening here is folks find out they have cancer sooner and begin treatments that appear to do nothing. The high carb, low fat diet is perhaps the only instance I can think of that has this type of society wide paralysis or selective memory occurring. Imagine a sports team or legitimate non-governmental business trying to run for 30 years with nothing to show for it’s efforts but failure. Amazing.

There IS awareness within the medical establishment that our present course is not working, it just continues to be ignored. This piece from the Journal of The Royal Society of Medicine came out in 1991 and has it mostly right. Even these folks were duped by the colon cancer/fiber shtick. The whole text is available and the paper is actually quite good. The authors make the point that our understanding of the molecular underpinning of cancer has exploded; yet this has translated into few advances in treatment or survivability. The authors also make the point we have plenty of information to make lifestyle and environmental changes that will dramatically reduce the OCCURANCE of cancers. Aside from smoking little effort has been placed in the prevention category. The author makes the telling prediction that if we attack the “Western Diseases” we will see a dramatic improvement in health and consequent reduction in cancers…I suspect however the solution would be a low fat, heart healthy diet! The low carb solution is ignored again and the researchers fumble about for another 20 years looking for the solution that is sitting in their laps. Oy vey!

I want to briefly look at the therapeutic potential of a ketogenic diet, possibly with adjunctive techniques such as caloric restriction and intermittent fasting. My interview with Dr. Thomas N. Seyfried of Boston College on the topic of cancer, ketosis and metabolic control analysis is a good place to start. A google or pubmed search for ketosis or ketogenic diet will generate some interesting returns.

I want to make the point that I do not think ketosis is the cure for all cancers…but it might be for some, for others it may dramatically slow progression and all without the dangers inherent in modern chemotherapeutics. The point must be made however that preventing a disease is much easier than treating a disease…what if periodic bouts of ketosis/fasting or caloric restriction could dramatically reduce the occurrence of cancers? There is much to be learned here but no one is much interested due to the lack of money to be made from a low carb diet vs. drugs.

Personal bias
Now, it may be obvious that I have a pretty strong bias on this topic. Some of this I’d like to think is the result of being a critical thinker, looking at the data and empirical evidence and drawing sound conclusions. I worked in and around cancer research for quite some time and I have my leanings towards evolutionary medicine and the notion that an ancestral diet is likely the best one for optimum health. That’s all the intellectual bias I bring to this topic. My emotional bias started on January 4^th, 1988 when my girlfriend, then 16 years old, died from complications due to an astrocyte brain tumor. Her name was Stacy Barnett, she was class president, a cheerleader, 4.0 student…and a pretty damn cool chic. She was first diagnosed with a brain tumor at the end of 8^th grade and was not expected to make it to the 9^th grade. Her cancer went through 3 different remissions before the final growth that started in Oct, ’87. Astrocyte brain tumors are thought to be particularly responsive to ketosis. 15 years later I can only wonder if a ketogenic diet might have saved her life. I’d like this information to be more available and better researched…I’d like simple, safe interventions to be considered in preference to approaches that are known to be both dangerous and ineffective. I don’t think that’s an un-reasonable desire.

In the photo (scanned, sorry for the quality) you see Stacy at Children’s Hospital at UCSF. She has her trademark scarf that covered the bald spot where the first surgery removed the tumor. In the other photo we are headed to the movies. Stacy was on high dose prednizone in an attempt to reduce the swelling caused by the re-growing cancer. She HATED how the prednizone made her cheeks puffy.