DOMINIC D’AGOSTINO

Dr. Dominic “Dom” D’Agostino (TW: @DOMINICDAGOSTI2, KETONUTRITION.ORG), PhD, is an associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine, and a senior research scientist at the Institute for Human and Machine Cognition (IHMC). He has also deadlifted 500 pounds for 10 reps after a 7-day fast.

He’s a beast and—no big surprise—he’s a good buddy of Dr. Peter Attia, my MD friend (here) who consumed “jet fuel” in search of optimal athletic performance. The primary focus of Dom’s laboratory is developing and testing metabolic therapies, including ketogenic diets, ketone esters, and ketone supplements to induce nutritional/therapeutic ketosis, and low-toxicity metabolic-based drugs. Much of his work is related to metabolic therapies and nutritional strategies for peak performance and resilience in extreme environments. His research is supported by the Office of Naval Research, Department of Defense, private organizations, and foundations.

Spirit animal: Beaver

LITTLE-KNOWN FACTS

PREFACE

This profile is one of several that might save your life, and it has certainly changed mine. As such, it deviates from the usual format to act as more of a mini-primer on all things ketosis. There is a lot of diet talk, but the supplements and fasting can be treated as separate tools—no bacon or heavy cream required. For ease of reading, some of the concepts are slightly simplified for a lay audience. My current personal regimen is included.

FIRST, SOME BASICS

“I like to promote mild to moderate ketosis for health and longevity, which is between 1 to 3 mmol.”

TF: These levels help protect DNA from damage, among other benefits.

WHY CONSIDER KETOSIS OR SUPPLEMENTAL KETONES?

WHY CONSIDER FASTING?

Dom has discussed the idea of a therapeutic “purge fast” with his colleague Dr. Thomas Seyfried of Boston College. Per Dom: “If you don’t have cancer and you do a therapeutic fast 1 to 3 times per year, you could purge any precancerous cells that may be living in your body.”

If you’re over the age of 40, cancer is one of the four types of diseases (see Dr. Peter Attia here) that will kill you with 80% certainty, so this seems like smart insurance.

There is also evidence to suggest—skipping the scientific detail—that fasts of 3 days or longer can effectively “reboot” your immune system via stem cell–based regeneration. Dom suggests a 5-day fast 2 to 3 times per year.

Dom has done 7-day fasts before, while lecturing at the University of South Florida. On day 7, he went into class with his glucose between 35 and 45 mg/dL, and his ketones around 5 mmol. Then, before breaking the fast, he went to the gym and deadlifted 500 pounds for 10 reps, followed by 1 rep of 585 pounds. Dom was inspired to do his first 7-day fast by George Cahill, a researcher at Harvard Medical School, who’d conducted a fascinating study published in 1970fn1 wherein he fasted people for 40 days.

Fasting doesn’t need to make you miserable and weak. In fact, it can have quite the opposite effect. But let’s start with how not to do it….

SOME PERSONAL BACKGROUND

I did my first extended fast as a last resort. Lyme disease had decimated me and put me at 10% capacity for nearly 9 months. My joints hurt so much that it took 5 to 10 minutes to get out of bed, and my short-term memory worsened to the point that I began to forget good friends’ names. Adding inputs (e.g., drugs, IV treatments, etc.) didn’t seem to help, so I decided to try removing all inputs, including food. I did my homework, found the best-reviewed fasting clinics in the U.S., and headed off.

My first 7-day fast was excruciating. It was medically supervised at a clinic, where we also had room and board. Patients were permitted to consume nothing but distilled water. Tap water, toothpaste, and even bathing were advised against. No exercise or leaving the facility were permitted for liability reasons. From days 3 to 4, my lower back pain was so extreme that I remained on my bed in the fetal position. The doctors told me this was “toxins” being released, which I didn’t accept. I insisted on blood testing instead, and the explanation for the lower-back pain was simple: My kidneys were getting hammered by sky-high uric acid levels. I wasn’t allowed to exercise (not even brisk walking), so it was taking forever to get into ketosis. My body was breaking down muscle tissue so the liver could convert it into glucose, and uric acid was a by-product. On top of this, since patients were limited to distilled water, nearly all the fasters (about 40 in total) couldn’t sleep due to electrolyte depletion and subsequent cholinergic responses (e.g., rapid heart rate when trying to sleep). Nonetheless, I noticed benefits: Long-standing skin issues disappeared after a few days, as did chronic joint pain.

On the morning of day 7, I woke up to blood spilling out of my mouthguard. I had been dreaming of strawberry shortcake (seriously) and chewed the fucker so hard that my gums split open. Basta.

I broke my fast with stewed pork—against doctor’s orders—and decided two things: Fasting was very interesting, but this wasn’t how I would do it.

WAIT … SO WHAT’S THE FASTING YOU PRACTICE?

In the last 2 years, I’ve done a lot of fasting experiments, focusing on real science instead of old wives’ tales (e.g., you must break your fast with shredded cabbage and beets). I now aim for a 3-day fast once per month and a 5- to 7-day fast once per quarter. I would like to do one 14- to 30-day fast per year, but the logistics have proven too inconvenient.

The longest fast I’ve done to date was 10 days. During that fast, I added vitamin C IVs and hyperbaric oxygen (2.4 ATA x 60 minutes) 3 times per week. I did DEXA body scans every 2 to 3 days for tracking and also consumed roughly 1.5 g of BCAAs upon waking and roughly 3 g of BCAAs intra-workout. After a 10-day fast, I had lost zero muscle mass. In contrast, I lost nearly 12 pounds of muscle in that first 7-day fast.

How and why the difference?

First, I allowed trace amounts of BCAAs and 300 to 500 calories of pure fat per day on my “fast.”

Second, I got into ketosis as quickly as possible to skip muscle wasting. I can now do this in under 24 hours instead of 3 to 4 days. The more often you enter keto, the faster the transition takes place. There appears to be a biological “muscle memory” related to monocarboxylate transporters and other things beyond my pay grade. Fasting is key, which is why the keto protocol used at Johns Hopkins for children with drug-resistant seizures begins with fasting.

Here’s my protocol for my usual monthly 3-day fast from Thursday dinner to Sunday dinner:

ONCE YOU’RE IN KETO, HOW CAN YOU KEEP IT GOING WITHOUT FASTING?

The short answer is: Eat a boatload of fat (~1.5 to 2.5 g per kilogram of body weight), next-to-no carbs, and moderate protein (1 to 1.5 g per kilogram of body weight) each day. We’ll look at Dom’s typical meals and day in a minute, but a few critical notes first:

All that preamble out of way, here’s what Big Dom eats. Keep in mind that he weighs roughly 100 kg (220 lbs), so scale as needed:

Breakfast

4 eggs (cooked in a combo of butter and coconut oil)

1 can of sardines packed in olive oil (such as Wild Planet brand)

½ can oysters (Crown Prince brand. Note: Carbs on the label are from non-glycemic phytoplankton)

Some asparagus or other vegetable

TF: Both Dom and I travel with boxes of sardines, oysters, and bulk macadamia nuts.

“Lunch”

Instead of lunch, Dom will consume a lot of MCT throughout the day via Quest Nutrition MCT Oil Power. He will also make a Thermos of coffee with a half stick of butter and 1 to 2 scoops of MCT powder, which he sips throughout the day, totaling about 3 cups of coffee.

Dinner

“One trick I’ve learned is that before dinner, which is my main meal of the day, I’ll have a bowl of soup, usually broccoli cream soup or cream of mushroom soup. I use concentrated coconut milk in place of the dairy cream. I thin it out [with a bit of water] so it’s not super dense in calories. After eating that, the amount of food that I want to consume is cut in half.”

Dom’s dinner is always some kind of large salad, typically made up of:

Mixed greens and spinach together

Extra-virgin olive oil

Artichokes

Avocado

MCT oil

A little bit of Parmesan or feta cheese

A moderate amount—about 50 g—of chicken, beef, or fish. He uses the fattiest versions he can get and increases the protein in the salad to 70 to 80 g if he had a workout that day.

In addition to the salad, Dom will make some other vegetable like Brussels sprouts, asparagus, collard greens, etc., cooked in butter and coconut oil. He views vegetables as “fat delivery systems.”

Dom’s Recipe for Keto Ice Cream

Dom’s “ice cream” recipe contains roughly 100 g of fat, or 900 kcal of keto goodness. It can save the day if your dinner is lacking fat (remember to hit 70 to 85% of total calories from fat!):

2 cups sour cream (I like Straus Creamery brand) or unsweetened coconut cream (not coconut water)

1 tablespoon dark chocolate baking cocoa

1–2 pinches of sea salt (my favorite is flaky Maldon)

1–2 pinches of cinnamon

A small dash of stevia (Dom buys NOW Foods organic stevia in bulk)

Optional: 1/3–½ cup blueberries, if Dom hasn’t had carbs all day, or if he has worked out

Stir that all into a thick mousse and stick it in the freezer until it takes on an ice cream–like consistency. Once you’ve removed it and are ready to dig in, you can eat it straight or add toppings:

The keto diet calls for around 300 g of fat per day at Dom’s body weight of 100 kg (220 lbs). This dessert helps up the ante dramatically. It’s also delicious. Dom’s wife does not follow a ketogenic diet, but even she loves this dessert.

Dom’s Tip for Vegetarians

“MRM Veggie Elite Performance Protein—the chocolate mocha is very good. If you take roughly one scoop and mix it with coconut milk, throw in a half an avocado, pour in some MCT oil—the C8 oil—the [shake] that I made up has 70% of the calories from fat and 20% of the calories from protein, 10% of the calories from carbohydrates.”

DOM’S GO-TO SUPPLEMENTS

Both Prüvit and Kegenix are based on a BHB + MCT patent Dom’s lab developed, which is owned by his university.

MORE ON FASTING AND CANCER TREATMENT

“Fasting before chemotherapy is definitely something that should be implemented in our oncology wards,” says Dom. He adds, “Fasting essentially slows (sometimes stops) rapidly dividing cells and triggers an ‘energetic crisis’ that makes cancer cells selectively vulnerable to chemo and radiation.” There are good studies to support this.fn2

One of my friends is in full remission from advanced testicular cancer. Others in his chemo cohort were laid out for 2 to 3 days in bed after chemo sessions, but he fasted for 3 days before sessions and was running 10 miles the next morning. Fasting sensitizes cancer cells to chemo, as mentioned, but it also helps normal cells resist the toxicity. This isn’t appropriate for all patients, especially those with extreme cachexia (muscle wasting), but it is applicable to many.

In cases of cachexia, some selective androgen receptor modulators (SARMs), which are designed to have the anabolic tissue-building potency of testosterone (and other anabolic steroids) without the androgenic (i.e., secondary hormonal) effects, could be helpful. Dom is also researching the use of BCAAs. He has had ~50% increase in survival in cancerous rats by adding the branched-chain amino acids to a ketogenic diet. Just as promising, the animals maintained their body weight.

In one study, treating mice with aggressive metastatic brain cancer using keto and hyperbaric oxygen treatment (HBOT), Dom, Dr. Seyfried, and other scientists were able to increase the average survival time from 31.2 days (standard diet) to 55.5 days. For the HBOT protocol, Dom used 2.5 Atmospheres (2.5 ATA) for 60 minutes on Monday, Wednesday, and Friday. Including pressurization and depressurization, each session lasted about 90 minutes.

Even in a worst-case scenario—if a patient is intubated and on their last legs—one could potentially add exogenous ketones to an IV alongside (or in place of) glucose, as exogenous ketones have been demonstrated to have a significant tumor-suppressing or -shrinking effect, even in the presence of dietary carbohydrates. To me, the last italicized part is the most remarkable.

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.

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:

  1. No radiation
  2. *Calorie-restricted keto diet with support from exogenous BHB
  3. *Metformin at 2 or 2.5 g/day
  4. DCA
  5. *Hyperbaric oxygen
  6. Rapamycin in modest, intermittent doses
  7. 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.