If you think the ketogenic diet is for lunatics, exogenous ketones only require mixing a scoop in water and swigging it down.
5 THINGS in Case of Late-Stage Emergency
Here are the 5 things Dom would do if he were diagnosed with one of the worst-case scenarios—late-stage glioblastoma (GBM), an aggressive brain cancer.
Some of Dom’s colleagues are opposed to the “standard of care” protocols, like chemotherapy. Based on the literature, Dom feels these are warranted in situations involving testicular cancer, leukemia, lymphoma, and stage 1 and 2 breast cancer. Outside of those examples, “it makes little sense to treat cancer with something we know is a powerful carcinogen (chemotherapy).”
Dom’s 5 picks all appear to work through overlapping mechanisms. This means that there is a synergy in using them together. The whole is greater than the sum of its parts. 1 + 1 + 1 + 1 + 1 = 10, let’s say, not 5. I’ve starred those on the following list that I’ve experimented with myself.
*Ketogenic diet as base therapy. This is the foundation.
*Intermittent fasting: 1 meal per day within a daily 4-hour window
*Ketone supplementation 2 to 4 times per day: His objective would be to elevate his BHB levels 1 to 2 mmol above his baseline, achieved by the aforementioned two. In other words, if he were running at ~1.5 mmol using a 1-meal-per-day modified Atkins diet, he would take enough supplemental ketones to consistently achieve 2.5 to 3.5 mmol. The easiest options are KetoCaNa and/or Quest Nutrition MCT Oil Powder. Combining them, you’re “approaching the potency of a ketone ester developed for military applications.” The powdered MCT increases gut tolerability 2 to 3 times versus oil, so you can consume more of it.
*Metformin: He would titrate the daily dosage (i.e., start low and gradually increase) until he reached GI distress (diarrhea or reflux), then dial it back slightly. This would give him his upper tolerable limit, which ranges from 1500 to 3000 mg/day for most people.
DCA (dichloroacetic acid): For reasons not completely understood, and under some circumstances, DCA can kill cancer cells at dosages relatively non-toxic to normal cells. Dom would start with 10 mg per kilogram of body weight (he weighs ~100 kilograms) and titrate up, not exceeding 50 mg per kilogram, as you can start to experience peripheral neuropathy at that level (thiamine [B1] can reduce neuropathy). Clinical trials use around 20 mg per kilogram. DCA appears to work well on all diets, including high-carbohydrate.
I asked another MD I trust the same question (“What would you do if you had late-stage GBM?”), without sharing Dom’s answers. His anonymized answer is below. I’ve again starred those I’m experimenting with.
“If I (meaning [name omitted], freak of all time) had GBM I would do the following:
No radiation
*Calorie-restricted keto diet with support from exogenous BHB
*Metformin at 2 or 2.5 g/day
DCA
*Hyperbaric oxygen
Rapamycin in modest, intermittent doses
Sequence the tumor to see if a checkpoint inhibitor (a type of immunotherapy) could be effective
“Not sure I could recommend this to anyone, though.”
✸ Dom’s most-gifted or recommended books
Cancer as a Metabolic Disease by Thomas Seyfried: required reading for all of Dom’s students
Tripping Over the Truth by Travis Christofferson: Dom has gifted this to seven or eight people over the last year
The Language of God: A Scientist Presents Evidence for Belief by Francis Collins
✸ Recommended to watch
“The Gut Is Not Like Las Vegas: What Happens in the Gut Does Not Stay in the Gut,” presentation by Alessio Fasano
✸ A fantastic idea I wish would expand nationwide
KetoPet Sanctuary (KPS): Funded by the Epigenix Foundation, KPS goes out of its way to rescue dogs with incurable, terminal cancer. Their goal isn’t to provide hospice-like treatment for terminal dogs. Of course, they care for and love the animals, but instead of writing off the canine companions to their fate, KPS provides groundbreaking human-grade metabolic-based cancer therapy for dogs.
* * *
* Cahill, George F. “Starvation in Man.” New England Journal of Medicine 282 (1970): 668–675.
** Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, Cohen P, Longo VD. “Fasting and cancer treatment in humans: A case series report.” Aging (Albany NY) 1.12 (2009): 988–1007. Dorff TB, Groshen S, Garcia A, Shah M, Tsao-Wei D, Pham H, Cheng CW, Brandhorst S, Cohen P, Wei M, Longo V, Quinn DI. “Safety and feasibility of fasting in combination with platinum-based chemotherapy.” BMC Cancer, 16.360 (2016). Bianchi G, Martella R, Ravera S, Marini C, Capitanio S, Orengo A, Emionite L, Lavarello C, Amaro A, Petretto A, Pfeffer U, Sambuceti G, Pistoia V, Raffaghello L, Longo VD. “Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models.” Oncotarget 6.14 (2015): 11806–19. Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, Pistoia V, Wei M, Hwang S, Merlino A, Emionite L, de Cabo R, Longo VD. “Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy.” Science Translational Medicine 4.124 (2012): 124ra27.
* * *
Patrick Arnold
Patrick Arnold (FB: @prototypenutrition, prototypenutrition.com), widely considered the “father of prohormones,” is the organic chemist who introduced androstenedione (remember Mark McGwire?) and other compounds into the dietary supplement world. He also created the designer steroid known as THG, or “The Clear.” THG and two other anabolic steroids that Patrick manufactured (best known: norboletone) weren’t banned at the time of their creation. These hard-to-detect drugs were at the heart of the BALCO doping scandal involving Barry Bonds and others. These days, Patrick is innovating in the legal world of ketone supplementation, including breakthroughs for military and commercial applications.
The New Performance Enhancers
No big surprise, I’m fascinated by all performance-enhancing drugs, which have been used since before the first Olympiad. On the legal side, here are two of Patrick’s creations that I’ve found useful:
“Ur Spray” Ursolic Acid
Ursolic acid helps with body recomposition. The benefits are summarized nicely in the title of one study: “Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease.”* It can’t be ingested in pill form, as it will be destroyed by first-pass (liver) metabolism; nor can be it be injected, as it doesn’t mix with oil. This led Patrick to create a topical alcohol suspension, as ursolic acid is neither hydrophilic nor hydrophobic. Tricky stuff. Ur Spray is sold on his Prototype Nutrition site.
Funny side note: The dose is 50 sprays for approximately 249 mg of active ursolic acid. That’s a lot of pumping. Some other guests’ wives have complained about late-night bathroom Pssshhh! Pssshhhh! Pssshhh! sessions that seem to go on forever.
Patrick Arnold’s Pre-Workout “Shake”
If you are in ketosis, drinking exogenous ketones pre- and intra-workout can substitute for carbs. As Patrick elaborates: “It’s pretty amazing. I’ve given it to people who tell me, ‘I’m on the ketogenic diet, and I work out and I feel like crap.’ I say, ‘Try this,’ and they say, ‘Wow! I didn’t get tired. My body had all the fuel it needed.’
“My friend Ian Danney’s company, Optimum EFX, has a product called Amino Matrix. It’s very expensive but since I’ve worked with him—we make some of his products—I get it for free. It’s basically a full spectrum of essential amino acids, branched-chain amino acids with some other things thrown in there: lipoic acid, citrulline malate, and a few other things.
“I mix that with about 45 ml of KetoForce, which is the [liquid exogenous ketones] you’re not supposed to drink straight (see the “jet fuel” story on page 60). If you mix it
with the Amino Matrix, which is very tart, it buffers the alkalinity of the KetoForce and it ends up tasting quite good.”
TF: A tablespoon of lemon juice (in the water you use to dilute KetoForce) will also work for buffering. If KetoForce is too odd for your stomach, try the powdered KetoCaNa, also developed by Patrick, which I often use before aerobic exercise.
Metformin for Life Extension
Both Patrick Arnold and his frequent collaborator, Dominic D’Agostino, PhD (page 21), are interested in metformin, which is not their creation. Dom considers it the most promising of the anti-aging drugs from a scientific standpoint, and I would estimate that a dozen of the people in this book use it.
In type 2 diabetics (to whom it’s prescribed), metformin decreases the liver’s ability to make and deposit glucose into the bloodstream. Metformin also dampens the signaling pathways associated with cancer growth proliferation. Rats with metastatic cancer in Dom’s studies have increased survival rates by 40 to 50%. It mimics calorie restriction and fasting in many respects. Some researchers believe it could damage mitochondria, but nonetheless, many MDs and technologists are taking metformin prophylactically to prevent cancer.
Dom did a test where he took 1 g of metformin daily for 12 weeks, and had blood work done throughout. His diet and exercise didn’t change. In his “post” test, his triglycerides were the lowest they had ever been, his HDL was around 98 (bumping up from 80), and his C-reactive protein wasn’t even measurable. The only side effect he saw was that his testosterone was lower, and that came back into normal range once he stopped taking metformin.
* * *
* Kunkel SD, Elmore CJ, Bongers KS, Ebert SM, Fox DK, Dyle MC, et al. “Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.” PLoS ONE 7(6) (2012): e39332 doi:10.1371/journal.pone.0039332.
Spirit animal: Wolf
* * *
Joe De Sena
Joe De Sena (TW/FB/IG: @SpartanRace, Spartan.com) is the co-founder of the Death Race, Spartan Race (more than 1 million competitors), and more. He has completed the famously grueling Iditarod dogsledding race . . . by foot. He also finished the Badwater Ultramarathon (135 miles at over 120°F/49°C), Vermont 100, and Lake Placid Ironman—all in the same week. The man is a maniac, and he’s a very strategic businessman. I first met him through Summit Series (summit.co). He keeps inviting me to visit him in Vermont, and I refuse because I’m afraid.
Why He Started Tackling Insane Events While Working on Wall Street
“You make and lose $30K, $40K in minutes screwing up an order or having customers tell you that they are no longer going to deal with you. It was very stressful business. [I wanted] to get back to the core of life. . . . [A friend] said, ‘Well, you could die. There is this one—the Iditarod in Alaska. They do it in the middle of the winter, it is by foot, and it is 30 below. But, you have to —’ ‘Sign me up. I have to do it.’ I had to get back to this place where you just want water, food, and shelter. All the craziness of my life—this Wall Street life I had taken on—would go away, would melt away.”
On the Origins of the Death Race
“And what if I created—with a buddy of mine—this race that purposely broke these people? Not the way the races I had done or a marathon does, but where I would actually drive the participants crazy? Not tell them when it is starting, not tell them when it is ending, not giving them water, giving them buses during the middle of the race and saying, ‘You could quit here. Just get on the bus. This is not for you. You are too weak,’ . . . and that was the beginning of my race business.”
TIM: “How do you break people?”
JOE: “Well, I don’t think they knew what they were getting into, because we had never done it before. One guy—I remember specifically—started crying and he was like, ‘I am a really good runner. I just do not know how to chop wood.’ Broken. Because no one knew. We did not tell them. So, Doug Lewis, who is an Olympic-level downhill skier, is 15, 18 hours into this thing and he is cracking. He is broken and he turns to me and says, ‘I made the Olympics. I trained my whole life. I am a pretty tough guy.’ He goes, ‘This is fucking crazy.’ That moment, we knew we had a winner.”
Funny Anecdote from Amelia Boone
Amelia Boone (page 2) has finished the Death Race three times and sent this to me:
“Hurricane Irene washed out a bridge on his property. A 1-ton metal I-beam had been stuck in the water for a few years, and the state was going to fine him some obscene amount if he didn’t remove it. It would have cost him tens of thousands of dollars to have it removed, so instead, he had his winter Death Racers get in the river in January and remove it for him. It took us probably 8 hours. I came away with second-degree frostbite in most of my toes, as did many others. And the hilarious part? People paid HIM to experience that (the race entrance fee) AND he avoided fines and the cost of removal. Fucking genius.”
Random Tidbits from Follow-Up Conversations
Joe, like Jocko [Willink, page 412], believes that you shouldn’t need caffeine or alcohol. He also thinks, “You should sweat like you’re being chased by the police daily.”
When people tell Joe to stop and smell the roses, his first response is, “Who is maintaining the roses?”
✸ Do you have any quotes you live your life by or think of often?
“It could always be worse.”
“Breathe, motherfucker! ”
—Wim’s answer to “What would you put on a billboard?”
* * *
Wim “The Iceman” Hof
Wim Hof (TW/IG: @Iceman_Hof, icemanwimhof.com) is a Dutch world record holder nicknamed “The Iceman.” He is the creator of the Wim Hof Method and holds more than 20 world records. Wim is an outlier of daredevils, as he routinely asks scientists to measure and validate his feats. Here are just a few examples:
In 2007, he climbed past the “death zone” altitude on Mount Everest (~7,500 meters) wearing nothing but shorts and shoes.
In 2009, Wim completed a full marathon above the Arctic Circle in Finland, once again only in shorts, despite temperatures close to −20°C (−4°F).
Wim has set multiple records for ice bath endurance, with his best time at nearly 2 hours.
In 2011, he ran a full marathon in the Namib Desert without water. He can also run at altitude without suffering altitude sickness.
WARNING: NEVER DO BREATHING EXERCISES IN WATER OR BEFORE TRAINING IN WATER. SHALLOW-WATER BLACKOUTS CAN BE FATAL, AND YOU WILL NOT FEEL THE ONSET UNTIL IT’S TOO LATE.
Wim Hof breathing should never be done near water. Joshua Waitzkin (page 577), another podcast guest with decades of free-diving experience, suffered a shallow-water blackout at a public pool in New York City and was underwater for an additional 3 minutes before being pulled out by a lifeguard. He remained unconscious for an additional 20 minutes, and was then hospitalized for 3 days and subjected to a barrage of tests to assess the damage, including potential brain damage. He could have died extremely easily. So, to reiterate: Do not practice this type of breath work in combination with water immersion. There will be no warning sign before you lose consciousness. M’kay?
A Mind-Blowing Experiment
Before I describe the exercise, I shall repeat my usual refrain: Don’t be stupid and hurt yourself, please. Use a very soft surface in case you face plant.
Do a set of push-ups and end a few repetitions short of failure. Record the number.
Rest at least 30 minutes.
Do ~40 repetitions of the following breathing exercise: Max inhale (raise chest) and “let go” exhale (drop chest sharply). The let-go exhale can be thought of as a short “hah.” If you’re doing this correctly, after 20 to 30 reps you might feel loose, mild lightheadedness, and a little bit of tingling. The tingling is often felt in the hands first.
On the last breathing cycle, breat
he in completely, exhale completely, then do another set of push-ups. More often than not, people will experience a sharp increase in the max number of push-ups, even though their lungs are empty.
Cold Is a Great Purifying Force
Wim, surfing king Laird Hamilton (page 92), and Tony Robbins (page 210) all use cold exposure as a tool. It can improve immune function, increase fat loss (partially by increasing levels of the hormone adiponectin), and dramatically elevate mood. In fact, Van Gogh was prescribed cold baths twice daily in a psychiatric ward after severing his own ear.
“All the problems I have in the daily world subside when I do [cold exposure]. Exposing myself to the worthy cold . . . it is a great cleaning purifying force.”
Wim takes cold to terrifying extremes (his retinas froze once while swimming in a lake under sheets of ice), but you can start with a cold water “finish” to showers. Simply make the last 30 to 60 seconds of your shower pure cold. Among others in this book, Naval Ravikant (page 546), Joshua Waitzkin (page 577), and I now do this. Josh does it with his tiny son, Jack, who he’s trained to say “It’s so good!” when it feels unbearable.
Below is my current cold regimen, often alternated with heat, which we covered on page 7. My full “workout” process then, is 1) pre-workout BCAA, 2) workout, 3) post-exercise whey protein, 4) immediate heat (~20 minutes) followed by 5) cold (5 to 10 minutes). I repeat the hot-cold cycle 2 to 4 times.
Tools of Titans Page 6