The Complexity of Oxidative Stress, Overlapping Factors, and the Need for Collaboration in Biology

Cancer is like a computer program gone wrong, the kernel panic of the human body. Unfortunately, we have no reboot button, and so cancer is the most serious of diseases. This year, almost six hundred thousand Americans will die from cancer. Despite the fact that cancer receives more NIH funding than any other illness, the death rates remain the same as in the 1950s.

Tripping Over the Truth: The Return of the Metabolic Theory of Cancer tells the story of molecular biologist and science writer Travis Christofferson’s journey to discover why cancer has remained so elusive. The central theme of the book is that we’ve fundamentally mischaracterized the origin of cancer. Most scientists hold to the belief that cancer is a genetic disease, Travis explores the idea that cancer is, in fact, a disease of damaged metabolism.

The metabolic theory of cancer stems from Nobel laureate Otto Warburg’s observation in 1924 that cancer cells lack the ability to produce energy using anything other than an ancient and inefficient process of fermentation. Warburg’s idea failed to gain critical mass, and by the 1960s had largely faded into oblivion. In 2012, Thomas Siegfried, Ph.D., released his book Cancer as a Metabolic Disease where he expanded on Warburg’s original hypothesis. In his book, Siegfried described how all cancer cells have damaged mitochondria, the organelle responsible for creating energy with oxygen.

Inspired by The Emperor of All Maladies by Siddhartha Mukherjee, Travis has done a excellent job of telling the rich story behind the metabolic theory of cancer. In this interview, Travis and I discuss some of the potential benefits and mechanisms of a ketogenic diet, hyperbaric oxygen, gluconeogenesis inhibitors and ketone supplements as possible cancer therapy.

I would like to thank Dr. Tommy Wood for some of the questions asked in this interview, especially those about glioblastoma and women with the BRCA1 mutation and breast cancer.

Here’s the outline of this interview with Travis Christofferson:

0:00:15    Book: Tripping Over the Truth: The Return of the Metabolic Theory of Cancer Illuminates a New and Hopeful Path to a Cure

0:00:34    How Travis became in terested in biology.

0:00:54    Travis has a fundamental curiosity.

0:01:10    The best doctors are the ones that do experiments on themselves.

0:01:22    Book: Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer by Tom Siegfried.

0:01:38    Book: The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee.

0:02:16    Travis wanted to tell the rich story behind the science in Tom's book.

0:03:01    Podcast: Dominic D'Agostino on the Tim Ferriss show.

0:03:30    The Emperor is gene centric.

0:03:46    The difference between the genetic and metabolic theories of cancer.

0:04:08    Radiation, cell repair.

0:04:09    In the genetic theory, cancer arises through lesions on DNA.

0:04:43    The genetic theory is still the dominant theory.

0:04:55    In the metabolic theory, cancer is proliferated by damage to the mitochondria.

0:05:07    Cancer resorts to less efficient fermentation.

0:05:25    This less efficient metabolism sends a message to the DNA.

0:05:42    This new theory makes cancer look like a disease of order.

0:06:02    Everything that causes cancer damages mitochondria.

0:06:39    Paul Davies, cosmologist.

0:07:07    Worked with Stephen Hawking.

0:07:33    Video: Anna Barker at TEDMED 2010.

0:07:53    Cancer is incredibly complex compared to other diseases.

0:08:19    In 2008 atavistic model

0:08:48    Three million studies on cancer on PubMed.

0:09:20    In the beginning, there was single celled organisms.

0:09:26    With multicellular life, the rules changed.

0:09:43    The foetal genes are reexpressed in cancer.

0:10:03    This new understanding gives hope.

0:10:17    What can we do with this new knowledge.

0:10:28    Look after our mitochondria.

0:10:38    A ketogenic diet is a great way to achieve this.

0:10:48    Also intermittent fasting.

0:10:57    Metformin as an oncology drug.

0:11:20    Exploiting the express of early genes.

0:11:44    The Warburg Effect.

0:11:53    Hyperbaric oxygen.

0:12:01    Cancer cells decouple of the adaptive immune system.

0:12:07    Cancer patients with high fever then spontaneous remission.

0:12:25    Cancer cannot withstand infection.

0:12:56    How does the ketogenic diet work against cancer?

0:13:04    Lowering blood glucose.

0:13:11    Glucose is the preferred fuel of cancer.

0:13:25    Some cancers can utilise ketones.

0:13:45    But there's promise in all cancers.

0:14:05    There's some kind of signalling mechanism.

0:14:27    Less side-effects with chemo after fasting.

0:15:05    Dr. Tommy Wood pointed me at some studies showing that certain breast cancers can use ketones as fuel. One study of women with the BRCA1 mutation showed that those with upregulated ketone metabolism did worse, which suggests that a cancer can develop metabolic flexibility too, and would be able to avoid death on a ketogenic diet.

0:15:27    Everybody is different and your results therefore will vary.

0:15:51    The brain can obtain up to 80% of its energy requirenents from ketones.

0:16:09    Some neurons are too small to include a mitochondria.

0:16:21    There is a trial going on in Arizona with glioblastoma.

0:16:25    Dr. Adrienne C. Scheck.

0:16:29    Results by April.

0:16:41    Kid in Norway, prognosis is 8 months, that was 3 years ago.

0:17:12    Tumor has shrunk and remained stable now for 3 years.

0:17:31    Metabolic therapies are good at managing cancer, but may not be the cure.

0:17:55    The studies are all done from the same line of glioblastoma.

0:18:17    Glioblastoma is where the research started, but the principle is sound

0:18:41    Will glioblastoma be the first cancer that we see a cure for?

0:18:48    Glioblastoma is usually about a year from the time of diagnosis to death.

0:19:17    How do cancers show up in a PET scanner?

0:19:24    PET scanners detect radiolabeled glucose.

0:19:43    The tumour outcompetes normal cells for glucose and show they show up in the scanner.

0:20:25    If the tumours have been lighting up in scanners for a long time, why has it taken so long for anyone to think of this?

0:20:41    Dr. Scheck’s study is using a standard ketogenic diet.

0:20:43    In some people that doesn't drive down glucose very far.

0:21:06    You can drive blood glucose very low.

0:21:21    In extended fasts, blood glucose would go down in the 60s (mg/dL).

0:21:24    Now we have exogenous ketone supplementation.

0:21:27    And gluconeogenesis inhibitors.

0:22:50    What were gluconeogenesis inhibitors originally designed for?

0:23:05    We're only just starting to appreciate Metformin.

0:23:06    25-30% reduction in the chances of getting cancer on Metformin.

0:23:07    Nobody really knows how is works.

0:23:31    Phenylbutyrate.

0:23:55    Metformin also inhibits complex 1 of the ETC.

0:24:07    ROS are bad, but also signalling molecules.

0:24:23    Another line of research has shown that Metformin works through altering the gut microbiome.

0:24:44    Podcast: Exercise is an antioxidant.

0:25:02    Podcast: Tommy and me on the Robb Wolf podcast.

0:25:11    Podcast: Insulin resistance.

0:25:15    Podcast: Iron overload.

0:25:46    In biology, you focus on one thing. One protein, one pathway.

0:25:55    Dr. Coe? in Travis's book.

0:25:56    ATPase.

0:26:15    You need someone to do the detailed work, but then you need someone to step back.

0:26:30    Physics already has a mechanism in place to do that.

0:27:05    In physics, you can come up with an idea and there's more than enough data to test it out.

0:27:31    Worse, in nutrition the data conflicts each other.

0:27:33    The NCI said that 80% of the basic research in cancer biology were not reproducible.

0:27:56    Sorting through the studies is an art form.

0:28:08    Warren Buffett.

0:28:22    What do you think of the meta-analysis?

0:28:53    This is the Gold Standard of science!

0:29:11    Book: Good Calories, Bad Calories: Fats, Carbs, and the Controversial Science of Diet and Health by Gary Taubes

0:30:36    Ketone supplements are not currently be used in cancer therapy.

0:31:09    Dominic D'Agostino specialises in ketone supplementation.

0:31:34    Ketones are far more than a macronutrient.

0:31:49    Ketones are anti-inflammatory.

0:32:08    Seasonal ketosis.

0:32:22    Dr. Veech at the NIH: "it's not normal to have a McDonald’s on every street corner".

0:32:30    It's normal to starve periodically.

0:32:53    Alzheimer's is now being called type 3 diabetes.

0:33:41    Is it a good idea to be constantly in ketosis?

0:33:58    Dr. Peter Attia.

0:34:32    Two studies, one at the National Institute of Aging, one at the University of Wisconson

0:34:37    Caloric restriction in monkeys.

0:34:49    Caloric restriction doesn't help as much as we thought.

0:35:02    The monkeys fed a high-sugar diet did worse.

0:35:27    When is all this going to be more widely know, or even the standard of care?

0:35:40    Things move slowly, it's easy to get depressed.

0:35:57    The trial in Arizona could be groundbreaking.

0:36:34    3-Bromopyruvate (3BP) could be the final piece for the metabolic therapy.

0:37:05    Heroin as the treatment for cocaine addiction.

0:37:47    Radical mastectomy.

0:38:25    This went on for 80 years.

0:38:37    In the end, we discovered that a local lumpectomy was as effective.

0:38:58    The trials are so slow and expensive.

0:39:16    You have to eat something, why not this?.

0:39:42    Travis talked at Paleo f(x).

0:39:57    Anecdotally, word is getting out there.

0:40:24    The ketogenic diet to treat recurrence.

0:40:37    The ketogenic diet is empowering.

0:41:11    Travis wrote an article about recurrence on his website.

0:41:20    It's not about always about a single cell that got left behind.

0:41:36    20% of cases are new, i.e. the environment for cancer is still there.

0:42:09    The same is true of bacteria, if you create the environment, it will grow.

0:42:25    Nobody wants to take high-fat diets seriously for weight loss until we're talking about cancer.

0:42:48    Cachexia is the the worst case scenario.

0:43:40    Valter Longo, PhD.

0:44:21    The state of ketosis doesn't say anything about weight loss, and may even be protective against muscle wasting.

0:44:42    Travis and Dominic's articles on Robb Wolf's website.

0:45:41    The Charlie Foundation.

0:46:04    Travis's new blog with podcast, Metabolic Optimization.

0:46:43    Dominic holds the Guinness World record for the most weight squatted in 24 hours (he broke the record in six).

0:47:15    Travis is a fulltime author.