The guest
Dr. Dom D'Agostino: Metabolic researcher at the University of South Florida who studies ketogenic diets, exogenous ketones, and beta-hydroxybutyrate for applications including Alzheimer's, cancer, seizures, and metabolic psychiatry.
What this episode covers
Tim Ferriss, who is APOE3/4 and worried about a family history of Alzheimer's, presses Dr. Dom D'Agostino on what ketogenic diets, exogenous ketones, and fasting each uniquely deliver. They cover the metabolic roots of Alzheimer's (glucose hypometabolism, neuroinflammation, possible infectious triggers), how D'Agostino fasts 'situationally' using 'sardine fasting' rather than water-only fasts, and his personal low-carb Mediterranean diet, supplements, and biomarker targets. The conversation digs into ketone measurement devices, hypercholesterol absorption and APOB management, metformin/GLP-1/SGLT2 and berberine, melatonin's safety, and NAD research. D'Agostino details his lab's work on ketones augmenting the adaptive immune system and cancer immunotherapy, plus metabolic psychiatry funded by the Bazookis (Roblox), and a large hyperbaric oxygen study at USF. He frames ketogenic therapies as pleiotropic, working through many mechanisms in synergy rather than one drug-able target.
Recommended on this episode
ProductRecommended
Keto-Mojo
Keto-Mojo
“when I recommend a meter to people, I generally recommend the Keto Mojo device”
“when I recommend a meter to people, I generally recommend the Keto Mojo device because that has the glucose ketone index in”— Dominic D'Agostino
ProductRecommended
Keto Brains MCT powder
Keto Brains
“the powder that I have is actually it's Keto Brains”
“the powder that I have is actually it's Keto Brains. It's MCT powder output GPC theanine and it has lion's mane mushroom in it.”— Dominic D'Agostino
ProductRecommended
CoQ10 / Ubiquinol
“CoQ10 is on the short list of five supplements that I would recommend to people”
“I think CoQ10 is on the short list of five supplements that I would recommend to people. Although I don't take it.”— Dominic D'Agostino
ProductRecommended
Creatine monohydrate (micronized)
“creatine monohydrate would be kind of the staple thing that I've used since I was a teenager”
“creatine monohydrate would be kind of the staple thing that I've used since I was a teenager first and foremost.”— Dominic D'Agostino
ProductRecommended
Vitamin D
“vitamin D and melatonin I think is a great neuroprotective antioxidant supplement to take”
“vitamin D and melatonin I think is a great neuroprotective antioxidant supplement to take at nighttime.”— Dominic D'Agostino
ProductRecommended
Melatonin
“I take melatonin not to sleep but as a neuroprotective agent”
“I take melatonin not to sleep but as a neuroprotective agent that has a whole host of beneficial effects for the brain”— Dominic D'Agostino
The guest's own work
ProductBy the guest
Audacious K9 supplement
Audacious Nutrition
“My wife Audacious has an Audacious K9 supplement and that's got spirulina ketones and a few other things.”— Dominic D'Agostino
ProductBy the guest
KetoStart (ketone electrolyte)
Audacious Nutrition
“also ketoart which is essentially the electro sodium, potassium, calcium, magnesium, beta hydroxybutyrate and that is will be used like two to three times per day.”— Dominic D'Agostino
Also referenced (named, not recommended)
ProductReferenced
Abbott Precision Xtra
Abbott
“For publications, we've used the Abbott precision extra because historically we've used that.”— Dominic D'Agostino
ProductReferenced
Stelo continuous glucose monitor
Dexcom
“now they have the Stella Stella device that came out. So, CGMs are over the counter now.”— Dominic D'Agostino
ProductReferenced
Levels
Levels Health
“that motivated me to be one of the first advisers for levels and I've worked with them on a research front”— Dominic D'Agostino
ProductReferenced
Ostarine (ostine SARM)
“it's ostin. Yeah. started giving it to them and it seems like yeah they are leaner, stronger.”— Dominic D'Agostino
ProductReferenced
Ezetimibe (Zetia)
Merck
“I use a zettoide monotherapy for that. So a zettoide was sold as zedia and I can get by with half of a tablet”— Dominic D'Agostino
ProductReferenced
Dry Farm Wines
Dry Farm Wines
“I typically have like every other night wine. So yeah, I do have a bit of wine, lower alcohol, non sugar, dry farm wines”— Tim Ferriss
ProductReferenced
Diphenhydramine (Benadryl)
“I took just 25 milligrams of dyen hydramine. I think that's the exact or close to the exact dose of one or two benadryil”— Dominic D'Agostino
ProductReferenced
Oura Ring
Oura
“I didn't really feel any more sleepy. I just slept like normal. My aura ring was like normal.”— Dominic D'Agostino
ProductReferenced
David Bar (David Protein Bar)
David
“Lately, I've been eating a David bar. Peter sent me some of those, and I've kind of like mixed opinions about it.”— Dominic D'Agostino
ProductReferenced
Quest MCT powder
Quest Nutrition
“Quest MCT powder. I think you can get that in like CVS and Walgreens now too.”— Dominic D'Agostino
ProductReferenced
Nutricost MCT powder / C8 powder
Nutricost
“Amazon just the Neutriost. So I bought just straight up MCT. They also have like a C8 powder and I've tested both”— Dominic D'Agostino
ProductReferenced
Metabolic Mind insulated tumbler
Metabolic Mind
“I fill this up. So, this is Metabolic Mind. So, yeah. Actually, Metabolic Mind is part of the Bazooki's group”— Dominic D'Agostino
ProductReferenced
Metformin
“Metformin I think is a very potentially effective drug for longevity. It's going to reduce blood glucose since most people are pre-diabetic”— Dominic D'Agostino
ProductReferenced
Berberine / Dihydroberberine
“I did dihydroourberine which is a more potent version of bourberine but interestingly after about a week I started to get a headache”— Dominic D'Agostino
ProductReferenced
MIB-626 (stabilized NAD)
Metro International Biotech
“if people just Google MIB626 so that's one of their drug forms of NAD that's a stabilized form of NAD”— Dominic D'Agostino
ProductReferenced
Idebenone
“idbinone is kind of a drug stabilized form of that... that was in the context of something called the Deanna protocol.”— Dominic D'Agostino
ProductReferenced
Phosphagen creatine (EAS)
EAS
“when I started using creatine in 1993, the old phosphaggen when I was in high school... EAS. I was a beta tester for that.”— Dominic D'Agostino
ProductReferenced
OmegaQuant test
OmegaQuant
“I tried the omega quant and my DHA levels and EPA levels were off the charts.”— Dominic D'Agostino
ProductReferenced
Mets-Psy (Metsy app)
Mets-Psy
“there's apps that are emerging like metsai metsai.com that's a collaboration with Dr. Alli Houston, he's at Oxford and Georgia Eid”— Dominic D'Agostino
ProductReferenced
GB Health Watch genetic testing
GB Health Watch
“I did GB health watch which looked at my genetics for dysipidemia. So GB Health Watch Dr. Spencer Nadulski reached out to me”— Dominic D'Agostino
Big reveals from this episode
- Alzheimer's is increasingly understood as a brain energy metabolism problem ('type 3 diabetes'), with glucose hypometabolism, neuroinflammation, and possibly infectious agents (herpes, Epstein-Barr, HSV) as drivers.
- D'Agostino's 'sardine fasting' (one can of sardines per day for a week, monthly) put cancer patient Dr. Fred Hatfield into rapid remission from metastatic prostate cancer despite a three-month prognosis; he died years later of something unrelated.
- HSCRP (high-sensitivity C-reactive protein) is now a better predictor of cardiovascular disease than LDL cholesterol, and a key biomarker to keep low for Alzheimer's and cancer.
- A ketogenic diet augments the adaptive immune system while a vegan diet enhances the innate immune system (published in Nature Medicine); D'Agostino's lab uses ketone metabolic therapy to boost cancer immunotherapy.
- Beta-hydroxybutyrate suppresses the NLRP3 inflammasome; a diet formulated to elevate BHB reproduced fasting's anti-inflammatory effect (Nature Medicine, 2015).
- Metabolic psychiatry is being funded largely by Jan and David Bazooki (Roblox) after Chris Palmer treated their son Matt into durable remission; they match donations dollar-for-dollar for a major Oxford study.
- D'Agostino's lab showed exogenous ketones produce an anxiolytic effect in animals comparable to a benzodiazepine, by raising the GABA-to-glutamate ratio in the brain.
- USF is running a $28 million hyperbaric oxygen study for traumatic brain injury using a true sham control (pulsed pressure to fake pressurization), the most elaborate HBOT study ever done.
Worth remembering
- D'Agostino recommends the Keto Mojo meter for consumers because it auto-calculates the glucose ketone index (GKI); meters read about 10-20% high on glucose versus lab assays.
- A glucose ketone index of 1 to 2 sustained for 3 to 5 days correlates with maximizing autophagy; normal US GKI is around 25 to 50.
- About 30% of the population are cholesterol hyperabsorbers (not 1%); D'Agostino has an NPC1L1 gain-of-function mutation and takes half a 5mg ezetimibe tablet, which halves his LDL and APOB.
- 50mg of diphenhydramine can impair memory recall acutely, but 25mg shows no such effect; D'Agostino limits it to about once a month and warns nightly use by the elderly may drive dementia.
- D'Agostino takes 5mg melatonin as a neuroprotective agent (not for sleep); he tested 20-30mg doses and confirmed no endocrine/testosterone suppression in himself, unlike in hibernating animals.
- Taking MCT with caffeine/coffee boosts ketone production by 20-30% (work by Stephen Cunnane), a 'ketogenic synergy.'
- D'Agostino is in his 50s, weighs 218-220 lbs at 9.4% body fat, eats three meals a day of mostly fish, meat, eggs, and broccoli, and drinks low-sugar dry-farm wine most evenings.
- He gives his male dogs exogenous ketones, the SARM ostarine (after injuries), creatine, and mushroom supplements; his 12-year-old Great Dane still runs 35 mph.
- Ketogenic therapies are 'pleiotropic' (many mechanisms in synergy), which frustrated pharma companies wanting a single drug-able mechanism after the NLRP3 work.
- D'Agostino's short list of supplements: creatine monohydrate (up to 20g/day split-dosed for Alzheimer's), exogenous ketones, vitamin D (target 60-80), melatonin, and CoQ10.
More from Tim Ferriss
All 35816 recommended