Monday, October 15, 2018

Book Review: Tripping Over the Truth

Summary


Tripping Over the Truth is a book about one of the most dreaded words in the world. Cancer. Because we have all known and loved people affected by cancer, it’s not a topic to be brought up in polite conversation. And because we have all known and loved people affected by cancer, it is a critically important topic. Throughout his book, author Travis Christofferson weaves together history, science, personal drama, and level-headed criticisms of the status quo in cancer research. This attention-demanding book is likely to make any reader take a step back and consider viewing the disease differently.



Christofferson suggests that the last several decades of cancer research have approached cancer from the wrong angle. Viewing cancer as a genetic disease has led to billions of dollars (and thousands of research careers) being spent on relatively uninspiring results. Despite many claims of breakthroughs, statistically, cancer rates have barely budged since the 1950s. A gripping anecdote: Senator Ted Kennedy signed the National Cancer Act in 1971, and the nation was optimistic that cancer would soon be overcome. Nearly 40 years later in 2009, despite having access to world-class oncologists, Kennedy died from brain cancer. His treatment induced toxic side effects and provided no life extension.

For the last several decades, cancer research has been conducted under the dominant paradigm of the somatic mutation theory (SMT). The SMT postulates that cancer is caused by DNA mutations. However, in practice, cancer is proving to be more complex than the SMT predicted. Some cancers have no driver gene mutations, whereas the SMT predicted that all tumors require sequential genetic alterations. Beyond that, mutations between different tumors and even within tumors are usually too variable to treat. Targeting specific mutations via pharmaceuticals ends up being like playing “Whac-a-Mole”; as soon as one mutation is targeted and destroyed, another mutation pops up. During this time, toxic side effects accumulate for the patient. With all of these moving pieces and parts, it is no wonder prominent oncologist Bert Vogelstein questioned, “Is it possible to make sense out of this complexity?”

The book is certainly critical of the dominant cancer research paradigm, but it does more than simply criticize the SMT. It provides another view for what causes cancer; in this view, DNA mutations are side effects rather than causes. A small group of scientists have been approaching cancer from this other perspective, based on the research of the late Otto Warburg. Warburg said “the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.” His theory states that cancer is a problem related to cellular energy production (metabolism). Cancer cells producing energy via sugar fermentation rather than via aerobic respiration is now known as the Warburg Effect.

After Otto Warburg’s 1970 death, Pete Pederson may have been the only researcher still approaching cancer from this metabolic perspective. Pederson made discoveries and published work consistent with Warburg’s theory. He discovered that tumors form when mitochondria (cellular energy producers) become so damaged that they cannot provide enough energy via aerobic respiration, so they send out a distress signal. This distress signal leads to a retrograde response which tells cells to start fermenting sugar for energy.

Decades into his research career, Tom Seyfried (who holds a master’s degree in genetics and a PhD in classical genetics) discovered that caloric reduction could have antitumor effects. Intrigued by this idea, Seyfried then discovered some of Pederson’s research. He also discovered research from Jerry Shay and Warren Schaeffer. Shay and Schaeffer, completely independently, found that inserting malignant cytoplasms (i.e. damaged mitochondria) into healthy cells led to tumor formation. And inserting a healthy cytoplasm into mutated cells led to mainly tumor-free results (only 1 in 68 mice developed tumors in this scenario). Looking at this research, despite never having heard of the metabolic theory of cancer until the 2000s, Seyfried became convinced that cancer is not genetic, but that it is a metabolic disease. He has since become an outspoken advocate of that view, and he published the 2010 paper Cancer as a metabolic disease and the 2012 book of the same name.

Once the metabolic theory of cancer is accepted, ketosis becomes a potentially therapeutic cancer treatment. If you fast, or if you have a very low intake of carbohydrates, your liver will produce ketones. Your normal cells with healthy mitochondria are fueled by these ketones in the absence of glucose. Cancer cells cannot utilize ketones for fuel, so a ketogenic diet can work to “starve” the cancer cells. At the same time, the ketones help the healthy cells deal with the stresses of radiation. So ketosis has a double benefit in cancer treatment. Because of this, Seyfried (building off the work of many other researchers) has become a major proponent of the restricted ketogenic diet for cancer patients. So far, the ketogenic diet’s success in cancer therapy is relatively small in scope: preclinical experiments, case studies, some trials, and many anecdotes. Many more clinical trials are needed. However, in the meantime, it shows tremendous potential as a non-toxic adjunct therapy. And the ketogenic diet’s early success could help reframe how cancer is viewed. Perhaps cancer could be more effectively battled if viewed as a single metabolic disease and not as one of thousands of indecipherably complex mutations. Nothing is certain; like the book says, “only time will tell.”

The Book's Afterword


This book was initially published in 2014. The version I read is the revised version published in 2017, and with it comes a very enlightening Afterword section. In this section, he provides some tidbits showing that the metabolic view of cancer continues gaining momentum and that the ketogenic diet is currently being used successfully as part of a cancer treatment strategy. But the most interesting part of the Afterword is the story how the author’s mother was diagnosed with endometrial cancer in July 2015, just nine months after the book’s publishing. It is a true “skin in the game” moment: how would his mother choose approach her own cancer treatment? At the age of 73, she underwent surgery to remove her tumor, followed by localized radiation treatment, the adoption of a ketogenic diet, and twice-weekly sessions of hyperbaric oxygen treatment. Christofferson’s mother “felt good and recovered remarkably fast from the radiation.” Actions speak loudly.

Other Topics Covered by Tripping


  • The FDA approving drugs based on tumor shrinkage despite that not being correlated with prolonged survival
  • History of how cancer came to be known as a genetic disease
  • Short history of chemotherapy and details of how controversial it has been to essentially poison cancerous and healthy cells indiscriminately
  • The struggle of Pederson’s lab partner Young Hee Ko to bring potential breakthrough cancer drug 3BP to human clinical trials
  • The success of chronic myeloid leukemia drug imatinib (Gleevec)
    • What it means in the big picture of cancer research
    • Whether it truly supports the somatic mutation or metabolic theory of cancer
  • The difficulty in getting funding for research of ketosis as a cancer treatment
  • The regulatory difficulties impeding the testing of cancer drugs in combination
  • The building momentum for metabolic approach to cancer research and treatment even from luminaries like DNA structure discoverer James Watson
  • Press-pulse strategy: constant stress on cancer cells (press) via ketosis, periodic acute cancer stress (pulse) via hyperbaric oxygen treatment
  • Notes about scientific consensus being overturned including the story of how Barry Marshall went from “quack” to Nobel Laureate by drinking bacteria juice and giving himself an ulcer


My Thoughts


Two concepts were constantly flowing through my mind while reading this book.
  1. Baseline beliefs and assumptions matter.
  2. The Pareto Principle is important.
Baseline beliefs and assumptions matter. I believe that, like other wild animals, humans evolved to be naturally healthy and largely free of chronic disease. The “primitive” populations studied by Weston A. Price did not eat white flour, sweetened goods, or vegetable oils. Those same populations had nearly nonexistent incidence of cancer. (For what it’s worth, other studies of traditionally-living hunter-gatherers also show the same low incidence of cancer.) This makes me skeptical of approaching cancer research in a gene-centric way*. The metabolic theory of cancer just explains the sudden increase in cancer rates upon Westernization better than the somatic mutation theory.

The Pareto Principle is important. The Pareto Principle states that the 80% of benefits come from 20% of causes. Lots of brilliant, caring researchers have dedicated their entire careers to studying cancer. But Tripping causes me to wonder whether many of these researchers are simply looking at the wrong cause. Perhaps DNA mutations are not the cause (as suggested by Somatic Mutation Theory), but the effect of mitochondrial damage (Metabolic Theory). Perhaps focusing more on mitochondrial damage and reversal of the Warburg Effect would be the “20%” that provides “80%” of cancer research benefit. 80/20 probably actually undersells the Pareto distribution in this case, as 95% of cancers are PET-positive. PET-positive cancers are cancers that feed off of sugar, making cancer cell sugar starvation (reversal of the Warburg Effect) a potentially fruitful approach.

All of that being said, I think the ketogenic diet is likely to be a very important non-toxic approach for cancer treatment. It’s a simple idea: cancer cells feed off of glucose, so don’t ingest glucose. Starve the cancer cells while your healthy cells can still feed off of ketone bodies. Your body being in a ketogenic state (via fasting, a ketogenic diet, or a combination thereof) will help mitigate the nausea and weakness brought about by other cancer treatments such radiation and/or chemotherapy. Periodic hyperbaric oxygen treatments could be beneficial as well. Doing this could lead to a more effective and less toxic cancer treatment than standard of care**.

Cancer is often seen as something that just randomly happens to people, based on genetics. I do not share this view***. Seeing how much impact lack of nutrition had in previously healthy peoples in a single generation in Weston A. Price’s studies makes me a firm believer that what we eat is far, far more of a driver of cancer than genetics. (In other words, the people studied by Price were genetically healthy but their diets changed and they became afflicted by chronic diseases. Similarly, every single day I see anecdotal reports online of modern people making radical health improvements via diet. These observations significantly impact my view here.) Diet is not the only environmental factor that can cause cancer, but I find it likely to be the most prevalent one. I also find diet likely to play an important role in treating the disease.


*I am not saying there is nothing about cancer that is related to genetics. As the book says, about 5-7% of cancers are related to germline mutations (passed from parent to offspring). But even those inherited mutations interfere with mitochondrial function, consistent with the metabolic theory of cancer.


**I am not claiming that ketosis will cure cancer, nor that there are no possible negative side effects. Ketogenic diet cancer researchers at the OSU Low Carb conference in August mentioned the existence of a reverse Warburg effect in some types of cancer cells (where cancer is fueled by ketones), so ketosis is not a panacea. But ketosis has a lot of potential for improving cancer treatment in a large percentage of cancer cases.

***I also do not mean to blame anyone suffering from cancer. But I do want to provide the perspective that you don’t need to resolve yourself to the idea that “maybe I’ll get it, maybe I won’t, not much I can do”-- there may be steps you can take to lower your risk (steps mentioned in How to Improve Your Insulin Sensitivity here would be among steps that deserve consideration). And if you do suffer from cancer, perhaps you could find therapeutic benefits from fasting, ketosis, or other treatments targeting cancer metabolism (certainly, there are no guarantees, but it might be worth researching further).

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