Please get pleasure from this transcript of my interview with Dr. Dominic D’Agostino (@DominicDAgosti2), a tenured affiliate professor within the Division of Molecular Pharmacology and Physiology on the College of South Florida Morsani School of Medication and a Visiting Senior Analysis Scientist on the Institute for Human and Machine Cognition. His analysis focuses on the event and testing of dietary methods and metabolic-based therapies for neurological issues, most cancers, and human efficiency optimization.
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Learn how to Use Ketosis for Enhanced Temper, Cognition, and Lengthy-Time period Mind Safety — A Sensible and Tactical Information with Dr. Dominic D’Agostino (Plus: Deconstructing Tim’s Newest Keto Experiment)
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Tim Ferriss: Dom, glad holidays. Good to see you.
Dominic D’Agostino: Nice to see you, Tim. Thanks for connecting.
Tim Ferriss: So I urged — positively — I urged we hop on the telephone as a result of I’ve been harassing the dwelling hell out of you with so many questions by way of textual content message. And I believed, this have to be fairly annoying. So fairly than reply me as soon as, why don’t we hop on and report a bunch of the small print as a result of the small print are so fascinating. And for people who find themselves simply tuning in who won’t know the nice physician, D’Agostino, “Dom” Dominic, we must always set up some fundamentals. And I at this level have been quote-unquote in ketosis for 18 days now.
And we’ll dig into loads of questions round that, tactical sensible questions. However earlier than we do, why would somebody — and we will discuss what it’s and so forth, however first let’s simply give among the — let’s name it established advantages ideally in human research, however might lengthen to animal fashions. After which, if there’s something on the horizon, say within the subsequent few years, since you’re on the leading edge, should you assume there’s something that may plausibly be established as a profit, what might that be?
So what would you placed on the bullet listing of advantages of intermittently or for prolonged durations of time, being in ketosis?
Dominic D’Agostino: Yeah, there are a lot of advantages to being in ketosis and a ketogenic food regimen, if we’re going to go there, form of has the advantages of fasting. And for millennia, we all know the advantages of fasting, with out the bags, with out the metabolic baggage. The muscle loss, the fatigue, clearly, you’ll be able to’t reside in that stage of caloric deficit. However regarding the sensible purposes of it, we all know that being in a state of ketosis actually quiets the thoughts. And I feel that has main implications. And this was from centuries we knew this. And now over the previous many years, this has been like a time period form of used.
And it’s backed up by experimental information to point out that there’s an elevation of GABA. Clearly, it’s silencing a broad array of seizures unbiased of the etiology, temporal lobe seizures. Lennox-Gastaut syndrome, Dravet syndrome, uncommon types of epilepsy. The ketogenic food regimen simply quiets the mind, lowers glutamate, and elevates GABA, a mind stabilizing, calming neurotransmitter. And that’s why individuals gravitate in the direction of alcohol, proper? The GABA-ergic results of alcohol and benzodiazepines.
So you’ll be able to type of, in a really light means, transition your physiology to a state of ketosis, which modifications the neuropharmacology of your mind to type of quiet it down. And that, I feel, actually echoes its broad software for metabolic psychiatry, which is all the things from main melancholy to bipolar, to schizophrenia, to nervousness issues, to anorexia nervosa. In order that’s a really attention-grabbing and quickly increasing software of ketosis that’s being funded largely by the Baszucki Group.
Tim Ferriss: Yeah. Had David on. And on the bodily facet, some people, in the event that they’re sufficiently old, might bear in mind the Atkins food regimen. Not saying that’s what we must always maintain up because the essentially the tip all be all of any sense, however why would somebody go on this for advantages outdoors of the cognitive psychiatric? Are there every other advantages that you would listing off?
Dominic D’Agostino: Yeah, I feel at first, it’s weight reduction. So it’s very satisfying to enter a state of ketosis since you do see the dimensions change fairly dramatically, and that’s due partly to some fluid loss related to a discount of fluid quantity. So it does have a diuretic impact. Ketosis does, ketogenic diets and clearly fasting, and in addition a natriuretic impact the place you dump out some sodium. Your plasma quantity, your blood quantity will contract slightly bit.
So if in case you have hypertension, that may probably go down. So should you’re on blood stress medicine, you must take into consideration that. However at first, it’s an efficient technique to get your physique to decrease the hormone insulin, if in case you have insulin resistance, and shift your metabolism to burning fat. And as we burn an increasing number of fats, that stimulates the manufacturing of ketones, ketogenesis. And ketones have a broad array of purposes, metabolic signaling epigenetic which have actual world purposes.
And that’s why the entire subject of exogenous ketones has developed and there’s 160 or extra registered medical trials on exogenous ketones, on clinicaltrials.gov. So yeah. And I might go into every of the purposes individually if we wish to go there.
Tim Ferriss: Properly, as we talked about earlier than recording, and I’ll should act as a little bit of a referee for my viewers as a result of I do know you’ll be able to go as deep as we wish down the rabbit gap into the 17 dimensions of biochemistry. So should you get possessed by the natural chemistry demons and begin talking in tongues, I’ll reign you in slightly bit. Nonetheless, let me maybe present a private instance first for people as a result of a few of this might be acquainted to individuals who’ve listened for a very long time, perhaps to different episodes of the 2 of us.
However loads of it’s going to be new. However I wish to set up some priors simply so persons are conscious of what this would possibly appear like in apply. So I’ve experimented with the ketogenic food regimen, additionally prolonged fasting, and you’ll arrive at some comparable locations, however such as you stated, Dom, there could be some fairly heavy taxes to pay with prolonged fasting. The ketogenic food regimen, I’ve experimented with all the best way again to the ’90s. A few of you weren’t even born in all probability who’re listening, however a few of you’ll bear in mind the ’90s.
And I used to be utilizing it particularly for temper stabilizing. This was in the direction of the tip of school, but in addition to lean out whereas constructing muscle on one thing referred to as the cyclical ketogenic or ketogenic food regimen. So we’re going to get to that later within the dialog, however it was successfully, let’s name it six days of specializing in a ketogenic food regimen with someday or a half to 3 quarters of a day of glycogen depletion after which, loading with extra carbohydrates, decrease fats, et cetera.
The rationale that the ketogenic food regimen turned doubly attention-grabbing to me is that once I had Lyme illness the second time, which got here with all types of co-infections like babesiosis and so forth. And this isn’t power fatigue or melancholy trying to find a prognosis that’s exterior. I really feel like typically the cottage trade of diagnosing and treating individuals for quote-unquote Lyme illness could be shady at finest. However on this case, I’m coming from Lengthy Island. All people in my household has had tickborne illness and was credibly recognized.
So the second time I had Lyme, I acquired to a degree — as a result of I didn’t see the bullseye rash, assumed I didn’t have it, which is a mistake as a result of typically you don’t see the dermatological response and also you nonetheless have contracted one thing like Lyme illness. I ended up weeks later slurring my speech, took me minutes to get off the bed as a result of my joints damage a lot, forgetting buddies’ names. And my assistant stated, “Tim, you actually need to see somebody. This isn’t fatigue. I’ve seen you sick. I’ve seen you drained. That is one thing else.”
And suffice to say, that become a number of months, even put up antibiotic therapy, which I do assume is essential, of we might name it pseudo dementia. I imply, I actually felt like I used to be working at 10 p.c cognitive capability. And principally at my wit’s finish, I stated, “Properly, what can I management? As a result of loads has not achieved the job.” And I went into strict ketosis. What does that imply? That implies that I’m consuming average protein, in all probability getting not less than 50 p.c of my energy from fats and holding my carbohydrates to lower than 20 grams a day in all probability at that time.
And inside three or 4 days, I’d in all probability say round day three or 4, as a result of I wasn’t very fats tailored on the time. My physique wasn’t well-trained to make use of fats as a result of I wasn’t doing intermittent fasting, which we’ll come again to. And inside three or 4 days, successfully, all of my cognitive signs disappeared. And I stayed in that state by way of dietary ketosis for a number of weeks, had full remission of any of the cognitive signs plus the joint ache signs, and people by no means got here again.
And I really helpful that, and this isn’t a randomized managed trial, however through the years, as as a result of varied components, we’ve had ticks rising in inhabitants, additionally increasing to the coasts and on the West Coast that’s, and elsewhere, had three buddies replicate this with ketosis after struggling varied signs from tickborne illness. And we have been texting, perhaps even speaking about this, however I by no means had an important rationalization for why it labored.
I stated, “I don’t know the precise mechanism. Possibly I’ve defective glucose metabolism that was one way or the other — perhaps one thing was impaired by the ticks and subsequently I’m giving my mind this alternate gasoline that it actually likes ketones,” however it didn’t clarify, essentially, the sturdiness of the modifications. In short, do you will have a principle or an evidence for why that might work?
Dominic D’Agostino: Yeah. I’m glad you introduced that up as a result of shortly dozens, if not lots of of individuals with tickborne illnesses, together with Lyme illness and all of the tickborne illnesses have communicated with me. And one of many sufferers is definitely Deanna Tedone, who was recognized with ALS previous to 2010, and has principally been stabilized given three years to reside. So I spotted that it’s underdiagnosed, the assessments to do this are form of controversial with the CDC testing, the two-tiered testing, and IGeneX.
So I do know I’m going off monitor slightly bit right here, however sure, I feel it’s essential to say that the spirochete, Borrelia, that spirochete is basically 100% glycolytic. And while you restrict glucose availability and glycolysis, you’re focusing on the vitality methods of that microbe. In order that’s one factor to consider. And it’s effectively established now. It wasn’t three years in the past, however a ketogenic food regimen specifically, beta-hydroxybutyrate elevated within the blood, stimulates the adaptive immune response.
And that’s basically your physique’s capability to focus on international invaders and neutralize them. And that has change into a quickly rising space of curiosity. College of Pennsylvania, simply — they’re doing CAR-T remedy and checkpoint inhibitors due to the ketogenic enhancement of the adaptive immune response. So I feel that performs a task. And situationally, I’ve noticed that you just go into ketosis if in case you have an inflammatory course of and Lyme illness is inflammatory.
However individuals who have shingles and herpes simplex and issues like that, I’ve an inbox filled with those that try this. And I want to experimentally go down that path to know why. However I feel there’s two causes you’re focusing on the vitality methods and also you’re augmenting the immune response to maintain the spirochete in a dormant stage or perhaps eradicating it in some context.
PREROLL?
Tim Ferriss: It’s actually unbelievable on a complete lot of ranges. And I’m simply fortunate that I had the prior expertise with the ketogenic food regimen to even have it happen to me as a final ditch effort. And for individuals simply to — if it wasn’t clear, I imply, you defined it clearly, however glycolytic, I’m simplifying right here, however it implies that one thing must eat sugar or metabolize carbohydrates to outlive, proper? And there are additionally, Dom, right me if I’m unsuitable, however explicit cancers which can be very delicate to being starved of glucose as effectively.
And for individuals who need extra on type of fasting ketosis because it pertains to most cancers, we might come again to it additionally, however we’ve had prior conversations about this and the advantages, among the unbelievable results of fasting previous to most cancers therapies of varied sorts.
PREROLL
So is it truthful to say, do you assume many of the advantages that somebody would derive from fasting previous to most cancers therapies, they might additionally get from ketosis or is it dialed again to a smaller proportion of impact?
Dominic D’Agostino: Yeah, that’s a very good query. I feel it requires a nuanced reply that we in all probability don’t have time for. However in case you are chubby and your BMI, for instance, is like — as many most cancers sufferers are usually like 28, 30, 32, a fasting or a calorically restricted ketogenic food regimen is the best way to go. If a affected person is trending in the direction of being lighter, like a BMI, 20, 22, one thing like that, a eucaloric, that means like holding steady caloric stage to keep up your weight goes to be essential.
After which elevating beta-hydroxybutyrate might be essential to get among the anti-inflammatory results and in addition the immune boosting results and the neuroprotective results going into most cancers remedy as a result of there’s individuals learning ketosis for chemo mind, like reversing chemo mind and like managing that. So it has a broad array of purposes, not simply focusing on — it’s focusing on the tumor development and placing a break on it.
It’s not a remedy for most cancers, and I cringe when individuals discuss that like on-line, the ketogenic food regimen curing most cancers, it does gradual it down, particularly if it’s extremely glycolytic, which 80 p.c of cancers are. And it enhances and augments the response to the usual of care that’s radiation, chemo and immune-based therapies. So we all know that now.
Tim Ferriss: All proper. Why have I been in ketosis for 18 days and why am I doing it a number of occasions a 12 months? Properly, a part of how I implement this does hinge and can proceed to hinge on among the solutions on this dialog, as a result of that is very self-interested. However what I’ve discovered is that for temper stabilization, and also you talked about metabolic psychiatry, and also you made the introduction, I imagine, Chris Palmer out of Harvard on the podcast to debate this.
However there’s sure circumstances, whether or not it’s melancholy, however much more squirrelly while you’re coping with one thing like schizophrenia, as an illustration, or various kinds of bipolar, individuals who’ve been on dozens of medicines who go into, let’s name it remission, or they not meet the factors for the prognosis of a few of these issues after being handled on a ketogenic food regimen, of 1 sort or one other.
It’s astonishing. And so for my very own psychological well being, I’ve observed full stabilization and with out subduing the highs, proper? I’ve by no means had mania essentially, I’m not speaking about that, however I’m not muted. I really feel simply calm, steady, sharp and that’s one motive in and of itself to do it for durations of time, however I appear to really feel a carryover impact, even have Alzheimer’s and different neurodegenerative illnesses in my household.
I’ve three kin with quickly advancing Alzheimer’s in the meanwhile. So perhaps we might discuss additionally to how this stuff would possibly intersect. However my feeling is probably, and I’d love your enter right here, if I comply with a ketogenic food regimen for a lot of weeks or perhaps a month and a half or one thing like that, I’d like to know the timing you would possibly suggest. Let’s say I try this two or thrice a 12 months, that there might be enduring results which have type of a protecting carryover, proper?
And I additionally discover it a lot simpler now that I began doing intermittent — I’ve been in intermittent fasting just about every single day for the final six months, which suggests I’m consuming between sometimes 2:00 p.m. and like 8:00 or 9:00 p.m. and having two meals a day, that’s it. Not hungry in any respect. I haven’t eaten at the moment, it’s 12:30 my time, I can’t be hungry for an additional two, two and a half hours. That by itself utterly revolutionized. I imply, that’s an overused phrase, however utterly polished my insulin sensitivity and metabolic well being on a bunch of ranges.
My labs have by no means been higher. My oral glucose tolerance take a look at has by no means been higher. And one query I’ve for you, which is only for Timmy, Tim, Tim, however will apply to different individuals is, is there an argument to be made, and perhaps I’m completely off base, however that should you comply with a ketogenic food regimen and make it work for a multi-week time period, that you just’re altering your metabolic equipment or simply your physique ultimately that has carryover results, even after you cease the food regimen, or is that me simply performing some hand wavy fancy footwork as a muggle? I don’t know if there’s a there, there, however what are your ideas?
Dominic D’Agostino: Yeah, I might say completely. I feel the science remains to be working to make clear that and make it much less ambiguous, the advantages that we’re deriving from that. However that’s form of like one of many pitches for the fasting mimicking food regimen by Dr. Valter Longo, who was certainly one of our keynote audio system at Metabolic Well being Summit, and he’s introduced some actually compelling analysis on that, that opened my eyes to that 5 days of fasting can have — I feel he introduced a time, even three months of results on type of cardiometabolic biomarkers.
Tim Ferriss: And in his case, this may be the quick mimicking food regimen, so a number of hundred energy a food regimen, of — yeah.
Dominic D’Agostino: Yeah, like 600, utilizing his protocol of varied meals, form of gravitating in the direction of extra of a plant-based decrease protein technique. And I feel that it’s selling metabolic flexibility and ramping up fatty acid oxidation enzymes. And very like muscle reminiscence, I feel there’s a metabolic reminiscence. So the extra you keep in ketosis, the better it will get and the extra advantages you derive from it and the extra that you just shift your physique to being extra fats tailored, similar to you’ll be able to construct your VO2.
While you construct your VO2 max otherwise you construct as much as like a 400-pound bench press and you’re taking like months off and also you return and you’ll solely do like 225 for a pair reps, it solely takes like two or three months to get again, however it took you 10 years to get there. That muscle reminiscence snaps again fast and all people agrees that there’s this metabolic reminiscence and I feel there’s loads of issues at play, together with gene packages, epigenetic regulation that involves play.
So at first is altering our mitochondrial perform and mitochondrial capability. So the variety of mitochondria enhance, after which while you take a break after which stimulate, get that stimulation once more, that mitochondria is form of there and it responds very quickly.
Tim Ferriss: Yeah, thanks for that. And I imply, I need a bookmark, perhaps we come again to this, but when persons are attempting to consider this, understanding that the science proper now could be perhaps provisional or there’s slightly bit, speculation price disproving at this level, however that it appears to make sense from an evolutionary perspective that each muscle reminiscence and metabolic reminiscence can be a factor. In any other case, it is smart your physique would wish to adapt to be ready for the subsequent famine or no matter it may be, proper? If there’s a —
Dominic D’Agostino: I simply wish to say muscle reminiscence is metabolic reminiscence. So somebody — I gave the analogy of like lifting weights, however somebody who runs marathons, it’s the identical situation. They take day off after which that VO2 max shortly establishes once more and it’s muscle, however it’s metabolic. So I like to make use of the time period metabolic reminiscence.
Tim Ferriss: Metabolic reminiscence. Okay. Yeah, metabolic reminiscence. So simply so individuals know the place I’m in the meanwhile and really, yeah, I’ll simply inform individuals what I’m doing as a result of I do know they’re in all probability getting itchy for some similar to, what does this appear like in apply? After which, I wish to discuss a bit about how ketosis or the ketogenic food regimen might or might not be useful for perhaps not treating, perhaps treating. I’ve definitely seen some attention-grabbing results in a few of my kin once I give them exogenous ketones the place all of the sudden their sentences are three or 4 occasions longer, half-hour later, which is wild to see.
However by way of prevention or staving off the onset of a few of these illnesses, I’d love to listen to your perspective. However let me inform individuals what I’ve been doing for the previous couple of months, and particularly within the final 18 days. So for the final no matter it’s, I feel I discussed six months, I’ve been doing intermittent fasting. And that was after listening to a dialog between Dr. Rhonda Patrick, who I’m a giant fan of, and Mark Mattson, M-A-T-T-S-O-N, who’s achieved loads of analysis associated to intermittent fasting.
And the important thing piece for me, since you see all of those various kinds of intermittent fasting, all of those other ways to do time restricted feeding, and I’m going to paraphrase right here. So Mark, I apologize if I’m getting this unsuitable or oversimplifying, however in impact, it’s essential that you just quick, this implies no energy, or we might discuss pure fats, however let’s simply assume you’re not consuming any energy for 16 hours since you wish to deplete your liver of glycogen. And when you deplete your liver of glycogen, your physique experiences this metabolic switching.
And I’ve definitely felt this simply doing intermittent fasting the place my meals include carbohydrates later, that across the finish of that fasting interval, growth, one thing switches and my thoughts is sharper, proper? After which once I acquired to the purpose of going into the ketogenic food regimen this time and in addition a number of months in the past, as a result of I used to be doing the intermittent fasting, and it took me a couple of week and a half for my physique to get comfy with that, at which level it was no downside.
However I used to be slightly pissy, slightly irritable for a short while, slightly foggy. After which once I went into the ketogenic food regimen this time, it was the simplest transition I’ve ever had. I didn’t have any fogginess, I didn’t have low vitality, I didn’t have what some individuals would possibly name the form of keto flu adaptive interval, which appears to be fairly remediated or addressed with electrolytes for lots of people, however it was extremely simple.
Simply straight into the ketogenic food regimen with no downside as a result of I used to be already doing the intermittent fasting.
After which for 18 days, I’ve been having two meals a day and also you’ve really helpful a number of that sound frankly fairly disgusting, however which can be truly very easy, like two cans of canned mackerel with about two tablespoons, 30 milliliters of MCT oil plus apple cider vinegar with some salt and pepper. It’s truly scrumptious. I simply love mackerel.
There it’s. Yeah, you’ve acquired your apple cider vinegar proper there.
Dominic D’Agostino: Low cost stuff you will get on Amazon. Yeah.
Tim Ferriss: Yeah. For individuals who would possibly assume, “Oh, wow, that is what for fancy individuals who can do all types of high-priced issues of their food regimen,” we’re speaking about like, how a lot does that meal value, three bucks?
Dominic D’Agostino: Yeah, a greenback a can for that Rooster of the Sea. And actually you get nearly a pound of mackerel, and that is like third-party examined very low chub mackerel, the little mackerel, much less —
Tim Ferriss: Yeah.
Dominic D’Agostino: So yeah, you bought like a $1.50 for nearly a pound of mackerel you could get that for. And the omega-3s are off the charts, the heavy metals are low. I devour kilos of these items and I’ve gotten my blood and my hair heavy metals examined and it’s like tremendous low, like non-detected. So I wouldn’t fear about that. Individuals have questions on value and heavy metals and that’s a non-issue for me.
Tim Ferriss: Yeah. And perhaps you would point out, I’ll put hyperlinks within the present notes as effectively, however since we’re on the subject, any manufacturers that you just default to, that you just like. And that chub mackerel piece for people, that element is essential as a result of they’re a mackerel of many various sizes.
Dominic D’Agostino: Yeah. King mackerel is form of excessive. That is Rooster of the Sea. So if you wish to do the finances, you purchase the case, the extra you purchase after which Amazon subscription after which, it goes on sale. You may truly get it for like lower than a greenback a can. And I do the identical with Rooster of the Sea jack mackerel or yeah, simply chub mackerel or jack mackerel. So that they’re each small fish. And I form of just like the King Oscar model too.
Tim Ferriss: Yeah.
Dominic D’Agostino: That’s slightly bit extra dear and Seasons model is fairly good too, however I imply, it’s like as low cost as pet food. I imply, we purchase some fairly fancy like freeze dry, we don’t purchase the kibble stuff, however while you run the numbers and we purchase —
Tim Ferriss: It’s very cheap.
Dominic D’Agostino: Circumstances of eggs for like 120 per — should you do like eggs, fish, beef and in addition turkey, you will get turkeys for below a greenback a pound, the entire turkey.
Tim Ferriss: Yeah, and only for people who find themselves like, “Oh, my God, I can’t imagine you guys are consuming mackerel combined with oil and vinegar in a canine bowl.” That’s not all you’ll be able to eat. There’s extra you could eat. You may have, like, rooster with cheese on it. You may have greens. There are specific issues you must be careful for, so that you’re not whacking your self out of ketosis. However in my explicit case, I don’t thoughts — and the very fact of the matter is once I wrote The 4-Hour Physique, individuals have been like, “Oh, my God, you need us to repeat the identical meals again and again?”
I’m like, “What did you will have for breakfast the final 5 days?” They usually ate the identical factor. You’re simply swapping out to fall meals. So my first meal is one thing sometimes fairly small, just like the macro I defined, after which I’ve a giant meal. I may need some extra protein in between, however it’s like yesterday I had lamb chops that have been scrumptious with some greens made in an air fryer, no downside. And in a while, I may need a rib eye on a giant — chopped up on a giant gigantic salad with another stuff added to it.
However that’s about it. You must watch out with the macadamia nuts. These issues will creep up on you. However that’s in impact the food regimen, proper? And I’m doing my coaching, I’m doing my rehab, I’m doing my zone two. I do discover them slightly, let’s say decrease efficiency once I’m in ketosis, however what I needed to speak about is perhaps a false damaging that I’ve skilled and I’ll clarify what that’s. So how have you learnt should you’re — and I hold placing this in citation marks like quote unquote in ketosis, proper?
As a result of most individuals are, or perhaps all persons are producing some stage of ketones. So there are completely different concentrations you could measure with a finger prick similar to you’d have a look at glucose. And not less than with the finger prick, I feel that’s measuring what you talked about earlier as being so helpful in loads of research, the beta-hydroxybutyrate, BHB. I even have — as a result of I needed to run this monitoring, a G7 Dexcom steady glucose monitor on one arm after which a SiBio.
Apologies if I’m not announcing that appropriately, steady ketone monitor on the opposite arm, and I’m sporting an Oura ring once I sleep to see how all of this impacts my sleep structure and all the things else.
So I’m gathering all of this, however then I observed one thing actually bizarre, which I’ve texted you about as a result of I hold feeling like I’m failing at keto. I really feel nice. I really feel sharp. And but once I have a look at not simply the continual glucose monitor, however even with the finger prick, since you do should usually calibrate this stuff, proper? Don’t assume that your steady displays are correct. You wish to calibrate them.
However I’m wanting on the numbers. And as an illustration, my girlfriend freaked out the opposite evening as a result of my telephone began screaming. I had earplugs in as a result of I didn’t hear it. And it was essential medical alert or regardless of the code crimson was as a result of my glucose was 69, I suppose.
It’s gotten fairly a bit decrease on ketosis, however often hovers someplace between 65 and 80. And my ketones have been 0.2 millimolars. Now, once we’ve talked in prior conversations about what sort of goal you would possibly purpose for, it looks like between 1.2 and two millimolars is anxiolytic, lowers nervousness and you then’re on the lookout for this ratio.
You would discuss this, however the GKI, there’s a ratio of glucose to ketones. And I have a look at these numbers and I’m like, “This is senseless to me as a result of I’m not getting sufficient glucose to perform effectively.
And if I’m basing it off of the Keto-Mojo finger prick, even the Precision Xtra from Abbott or my steady ketone monitor, I’m not getting any ketones both should you’re taking it at face worth. So how am I functioning?
How would you reply that? As a result of I don’t assume I’d be the one one that looks like they’re doing one thing unsuitable in the event that they run into this, however how would you interpret this?
Dominic D’Agostino: Yeah, I might positively say you’re operating lean. And I feel what you’ve achieved in your OGTT take a look at is absolutely good. I feel you had messaged that.
Tim Ferriss: Yeah, and the OGTT for people is simply that oral glucose tolerance take a look at the place you drink a bunch of dextrose water after which they take your blood each half-hour for 2 hours to see the way you’re responding to it.
Dominic D’Agostino: Yeah. The most important metabolic lever can be you will have enhanced insulin sensitivity. And I feel that has been the main focus. For instance, Ben Bikman wrote a e book on this and doing lots of of podcasts on insulin resistance, reversing insulin resistance and low carb ketogenic being efficient for that.
In order that, at first, your insulin sensitivity could be very excessive. Your fats oxidation is absolutely excessive and your glucose disposal is excessive. And should you’re in a caloric deficit, your ketone uptake could be very excessive. We see this fairly convincingly.
In older rats the place we gavage, the place we tube feed the rats and so they’re older, the ketones get to poisonous ranges. Whereas a youthful metabolically match rodent will get rid of it in a short time. Similar with a sofa potato human, identical with an elite stage athlete. So you will have very speedy —
So while you measure ketones within the blood, that’s a perform of ketone manufacturing and ketone utilization. And you would have two to 5 occasions greater ketone utilization with excessive metabolic health. And that’s due partly to ketolytic enzymes, you up-regulate the MCT transporters, that might be two, or in rodents, two or thrice greater.
I haven’t achieved that personally and we now have some information in people we haven’t printed but, however that could be a actual factor and I feel that you just’re experiencing. Additionally, should you’re in a caloric deficit, there’s much less spillover.
I simply purchased an vintage bike and it’s acquired a carburetor and the float sticks slightly bit and it all the time drips out the carburetor once I’m operating it. And once I cease and it’s pouring out the carburetor. So there’s spillover of gasoline, proper? However once I’m operating it’s operating lean as a result of I’m utilizing the gasoline that’s going to the carburetor.
And the identical analogy right here is that if, for instance, it may be good to only sit in a single spot and chill out and perhaps eat slightly little bit of surplus energy and even eat slightly little bit of carbs. And what you’ll see usually is your ketones spike up.
So I bear in mind a few of my highest ketone ranges ever is once I consumed carbohydrates after I used to be fasting or in a state of ketone. It jumped as much as 5, six, seven, and I used to be like, “What’s going on right here?” However the glucose in that context is ketone sparing, however the glucose may even shut off ketogenesis so it’ll tank afterwards.
Tim Ferriss: Yeah, afterwards. Yeah, okay. So it feels like then due to in all probability the intermittent fasting largely, I might assume, if my insulin sensitivity is excessive sufficient, that may be paired with greater ketone utilization.
So if on the meeting line of my physique, proper, they’re producing 10 models of ketones. If I didn’t have good ketone utilization and it was my first rodeo with ketosis, let’s simply say, or a ketogenic food regimen, the finger prick would possibly decide up all 10 of these models.
I’m simplifying right here, proper? But when I’ve excessive ketone utilization and my physique’s shortly utilizing eight of these, particularly in a caloric deficit, then it’s solely measuring two and I’m getting the false damaging that I’m not truly producing ketones within the first place.
Is {that a} truthful, very, very simplified description?
Dominic D’Agostino: Yeah. And also you’re not measuring tissue ranges of ketones, which we now have achieved too, even within the mind, and that may shoot up actually excessive.
In order that’s additionally, and I’ve achieved this with Peter Attia too, we have been measuring blood after which breath, and it looks like once we have been in a caloric deficit fasting, our ketones have been actually low within the blood.
Low is one to 2, however we have been actually deep into fasting, whereas our breath ketones have been maxing out the meters. So the breath ketones on this — we concluded that after loads of testing that the breath ketones have been nearly a greater indicator of ketosis, a extra correct, I assume you would say, in a caloric deficit.
As a result of while you’re in a caloric deficit, you simply have very excessive ketone disposal uptake into the tissues.
Tim Ferriss: It seems like a breathalyzer, proper? So is that measuring, what’s it, acetoacetate? No, I’m simply attempting to repeat phrases that I’ve heard a few times, however it’s not BHB.
Dominic D’Agostino: Acetone.
Tim Ferriss: Acetone. God dammit. All proper. I do know I used to be shut. It was a 50/50.
Dominic D’Agostino: It comes from the spontaneous decarboxylation of acetoacetate. We’ll spit out about 20 p.c of the acetoacetate will kick off to acetone after which you’ll be able to measure it.
Tim Ferriss: I acquired it.
Dominic D’Agostino: We’ve measured blood ranges of every, and it’s very difficult to do this, however we’ve achieved it within the lab.
Tim Ferriss: All proper. Right here’s one other sensible, tactical query for you as a result of I’ve gone backwards and forwards on this and Uncle ChatGPT has confused the shit out of me so perhaps you’ll be able to assist resolve it. Gluconeogenesis and protein consumption, proper? So that you devour, what’s it, between 240 grams of protein a day, one thing like that? Is that roughly?
Dominic D’Agostino: Yeah, on lively days. On much less lively days, if I’m simply behind my pc all day, perhaps nearer to 180, 200, however yeah.
Tim Ferriss: And folks may need picked up when Dom was casually throwing round like, “While you’ve been squatting 400 and you’re taking a break and you then return and also you solely can squat 300 kilos.” Dom’s a reasonably large man who’s additionally deadlifted 500 kilos for 10 reps earlier than, after fasting for every week.
So he and I aren’t the identical measurement, however nonetheless, I’m attempting to determine on one hand how a lot protein I can eat with out my liver taking extra protein amino acids and turning it into glucose, proper?
And relying on what I have a look at, and I’ve checked out sources outdoors of ChatGPT, on one hand, there are people who say, “Don’t fear about it. Should you’re consuming sufficient fats, you actually don’t have to fret about it.”
After which there are folks who’re like, “Be careful, be careful. Should you devour greater than X variety of grams at a given meal, you’ll be able to very simply knock your self out of ketosis,” which might, if that’s true, be perhaps an alternate rationalization for why I’m getting these low readings, if I’m having a small meal round 3:00 after which a big meal in a while.
How ought to I and the way ought to listeners take into consideration this?
Dominic D’Agostino: Yeah. So should you have been to devour protein within the type of liquid, for instance, like whey or one thing like that, then the speedy entry of amino acids into your bloodstream out of your small gut will shut off ketosis.
So fats and fiber and salt, as a result of your pyloric sphincter will principally be fairly tight till your —
Tim Ferriss: Speaking soiled, Dom.
Dominic D’Agostino: Pyloric sphincter is the place your abdomen connects to your small gut, if in case you have a really fatty, salty, excessive fiber meal, that entryway, we name that the sphincter, it’s the pyloric sphincter, will stay shut till the contents of your abdomen change into isotonic.
Which implies that your physique has to surrender water and it’s acquired to churn it and break it down. So you would delay gastric absorption merely with fats, fiber, and salt is fairly good too. You would do ketone salts or simply salt electrolytes.
So that may delay the entry of amino acids or protein into the small gut and thus amino acids into the bloodstream. And that’s the key regulator of ketosis having an influence on insulin and in addition having influence on gluconeogenesis to that fee of entry. And should you can gradual that down, you see nothing on the CGM and your ketosis ranges can principally keep.
You would additional increase that through the use of MCT oil with the protein and the fiber. And so if in case you have lengthy chain fat from a fatty steak and MCT oil after which fiber. And that might be insoluble fiber is fairly good to soluble and insoluble, that may gradual the entry of amino acids and basically buffer the gluconeogenic response.
Tim Ferriss: So let’s say I used to be caught in San Francisco late. I’m simply taking a uncommon journey over right here, which is a fairly thrilling time to be right here with all the mania with AI happening. However I imply, everybody’s form of drunk on the Kool-Support, however that’s a separate story.
I acquired trapped downtown as a result of didn’t wish to cope with visitors and blah, blah, blah, blah, blah. So I ended up having an enormous bunless double cheeseburger. Gigantic, this factor, I didn’t count on it to be as large because it was, proper?
And so I’m going on-line to attempt to determine what the protein content material of this factor may be. And it’s 80 grams of protein, proper? However loads of fats, definitely. Tons of fats, salty AF, loads of salt, proper? Not loads of fiber, we’ll give that one a go. Ought to I be anxious about one thing like that knocking me out of ketosis?
Dominic D’Agostino: I feel that you must measure. So I’m default again to all people’s a novel metabolic entity, however should you eat that and your exercise stage is excessive and also you’re in a little bit of a caloric deficit and also you have been to have that and never overdo it on the full energy.
I do know my physique. I do know my physique, I might keep in ketosis, however if in case you have that oversatiated feeling — so we now have neurons, we now have neuronal pathways to and from the liver and to and from the intestine. We name that afferent and efferent signaling within the enteric nervous system.
And a giant meal will principally inform your mind that you just had a giant meal. And unbiased, I talked concerning the amino acids going into the bloodstream kicking you out of ketosis. However there’s additionally this, when you will have stretch receptors and you’ve got the massive full meal in your intestine, then that might truly inform your mind to activate the sympathetic nervous system.
After which that, by advantage of spilling out catecholamines can principally, we’re speaking adrenaline, epinephrine, issues like that, that may additional increase and improve gluconeogenesis.
Tim Ferriss: Okay. Let me simply translate that for a second. So individuals get up. Cortisol has developed this dangerous popularity amongst loads of on-line influencers, however you actually need cortisol, proper? So while you get up within the morning and also you see a little bit of a glucose spike, it’s truly essential to get your ass up and shifting.
Should you’re in ketosis, it’s a special factor, proper? So if I’m listening to you appropriately, outdoors of how individuals take into consideration digestion, blood sugar, insulin, et cetera, that simply based mostly on stretching your abdomen, et cetera, with these mechanoreceptors, taking the inputs, that that indicators to the mind, it’s go time.
So let’s principally get issues shifting with these hormones and that might in and of itself then set off the liver to provide extra glucose or liberate extra glycogen, I assume.
Dominic D’Agostino: Yeah. It will possibly. It’s above and past what you usually eat. Should you prepare your physique to that measurement meal, however it additionally prompts different intestine hormones like cholecystokinin, that’s referred to as CCK, and different issues that may then activate the parasympathetic nervous system that is available in slightly bit after.
On the identical time, it bifurcates, however then the parasympathetic nervous system is chill out, digest, relaxation and chill out, digest. In order that is available in after. So that you would possibly see a blip and make you are feeling stimulated.
Additionally, all of the salt, if it’s a salty meal, it’s going to develop your plasma quantity. Your blood quantity will enhance and that may enhance your blood stress slightly bit and that may activate your sympathetic nervous system.
So it’s all the time good to go take a stroll after a giant meal.
Tim Ferriss: Yeah. I try this.
Dominic D’Agostino: Not like a strenuous — not like go squat and deadlift, however simply yeah. Even a ten, 15, ideally a 20-minute brisk stroll is absolutely good after a giant meal.
Tim Ferriss: Yep. Now let me ask you this on the stroll timing. So when I’ve a giant meal, and I’ll say, I feel I’ve educated my physique to have large meals. What the precise response is, I can solely provide you with subjectively what I really feel and I may give you what the displays present, proper? However I sometimes really feel fairly good.
Nonetheless, if I’ve a giant meal, whether or not that is in ketosis or in any other case, I don’t see the most important spike till one thing like, relies on the meal, proper? However 60 to 90 minutes later, that’s once I see the spike. So ought to I do the stroll at 60 to 90 minutes, or ought to I do the stroll proper after the meal? When ought to I truly time the stroll?
Dominic D’Agostino: So that you eat a meal, you go stroll, and you then see the rise 60 to 90 minutes after, or is that unbiased of the stroll?
Tim Ferriss: Unbiased of the stroll. Yeah.
Dominic D’Agostino: Okay. So that you’re not strolling, however you see the rise 60 to 90 minutes later. So I’m saying that you just won’t see that rise 60 or 90 minutes later as a result of —
Tim Ferriss: Should you did it proper after the meal?
Dominic D’Agostino: Yeah, simply because slightly bit goes a great distance. So similar to strolling, truly performing some stretching and strolling too, it prompts the glucose 4, the GLUT4 transporters. In order that’s an insulin unbiased. So much less insulin is dumped, larger glucose uptake.
And also you’re additionally utilizing the sympathetic nervous system mobilization of glucose by way of gluconeogenesis throughout that stroll. So it then attenuates the buffering of ketogenesis, and a really quick stroll can go a great distance.
Tim Ferriss: Yeah. Okay, cool. Is it GLUT4? GLUT4? How do you pronounce that? I don’t know. How do individuals say that?
Dominic D’Agostino: I say GLUT. I say GLUT4.
Tim Ferriss: Okay. All proper, GLUT4.
Dominic D’Agostino: Individuals say GLUT. Yeah, yeah.
Tim Ferriss: Yeah. For the OGs within the viewers, return and search for GLUT4 in The 4-Hour Physique. It’s in there.
So the opposite measurement query I wish to ask you about, which is these steady glucose and ketone displays aren’t designed for somebody like me, proper? They’re developed presumably, I don’t know concerning the keto monitor, however within the case of glucose to assist individuals with severe circumstances not find yourself in very severe conditions, proper?
So when I’m taking a look at my ketone ranges, like proper now I really feel very sharp. I had some KetoStart, you recognize this effectively. Exogenous ketone salt-based product not too way back, simply in scorching water with slightly little bit of MCT oil. This was, I assume, an hour, hour and a half in the past, however I’m at 0.4 millimolars.
And I assume what I’m saying is whether or not I’ve an enormous meal or I’m fasting as I’m proper now, my vary is principally 0.1 to 0.4 95 p.c of the time. There are a number of outlier circumstances. If I’m simply doing a YOLO, as many grams as attainable exogenous ketone occasion, then perhaps I can goose it, however we will discuss this.
As soon as it will get previous a sure level, then I would spike insulin and have a subsequent crash. However I assume what I’m attempting to say in short is my vary for essentially the most half is 0.1 to 0.4, no matter whether or not I’m fasting or consuming a big double cheeseburger. So I’m probably not certain how one can decide what impact it’s having.
I can watch the glucose, however proper now I’m 0.4 millimolars of focus on the SciBio. And as we’ve talked about, perhaps the Precision Xtra would give me an additional 0.1 or 0.2, however they’ve been fairly shut up to now.
After which ever since my cheat meal, we had this experiment, proper? I needed to see if I did a exercise after which had one or two cheat meals final Saturday. It’s now Thursday, however my glucose proper now could be 103, proper, which is greater than the week prior, however it goes round. It strikes round, proper? Final evening it was in all probability 70 one thing.
Do you will have any solutions for how one can learn the tea leaves or is it principally simply subjective really feel? I imply, nonetheless occupied with the scale of the meal, proper? However I assume what I’m saying is, if my system is telling me as it’s proper now, 0.4, fats not burning. You’re nearly not burning fats in the meanwhile, not in ketone. It’s very chastising.
So if I’m to imagine this by the letter of the regulation on the display, I’m failing at ketosis, proper? Any ideas on how one can learn the tea leaves right here?
Dominic D’Agostino: Properly, I might ignore that. I feel that’s an app within the technique of being developed, the fats —
Tim Ferriss: Yeah.
Dominic D’Agostino: You would want entire physique metabolomics to actually reply that query should you’re in fats burning or do metabolic cart and have a look at respiratory quotient or no matter. However subjectively, should you really feel good —
We’ve got seen an athlete, particularly extra superior athletes that, and we do a really strict, strict keto macros and all the things that principally with a bunch of athletes with 0.8 is about as excessive as we get, and that’s the typical throughout.
Generally you get guys 2.5, 2.6 every single day. And the identical man with the identical basically metabolic phenotype might be operating 0.4 or 0.3. He might probably simply have larger ketone utilization. So I feel it will be essential to measure your blood. So a steady ketone monitor measures interstitial — that may be completely different. The SciBio, I feel it’s an important system. It’s very versatile. I can soar out and in of salt water. The factor stays on me. It’s nearly extra dependable than a CGM. However I did discover, and I’ve in all probability used about 50 of those units that the primary week, is fairly correct after which it tapers off, the sensitivity.
And it is a identified limitation of the know-how is that basically the enzyme-based sensor system tends to only — and you would get round that conceivably simply by being able within the app to calibrate it.
So should you have been to measure it and the continual ketone monitor is measuring 1.0, however your blood ketones is 2.0 that it is best to be capable of calibrate it like you’ll be able to with a Dexcom. So that they acknowledged that on the firm and so they stated, “Sure, we understand that that might repair the issue,” however that’s not a characteristic of the app but.
Tim Ferriss: They do have in occasions, they’ve blood ketone on the underside proper. I simply don’t know if it truly calibrates it. It could simply report the blood ketone at this level.
Dominic D’Agostino: It doesn’t have the power to calibrate it to my data.
Tim Ferriss: I inputted one measurement on the Keto-Mojo and it didn’t appear to vary it, proper? The quantity stayed the identical. So I feel it’s simply logging it as a result of you are able to do that with a glucometer.
Dominic D’Agostino: Properly, you are able to do it with Dexcom, however not Abbott.
Tim Ferriss: Dexcom. Okay.
Dominic D’Agostino: That’s an issue with the Abbott FreeStyle too. And that’s the suggestions I gave them as a result of I put these units on, it’s studying me 130, however I measure I’m like 80, actually 50. As a result of —
Tim Ferriss: Wow.
Dominic D’Agostino: — in case you are lean and it’s caught in your muscle as a substitute of your adipose tissue, the glucose ranges are going to be greater, particularly when —
Tim Ferriss: Wow.
Dominic D’Agostino: — you’re employed out and stuff. So I’ve observed this and that’s for me, in order that’s why the Dexcom could be very good as a result of I can calibrate it too, and I persistently present that. And that was a serious problem I had.
Tim Ferriss: Let me hop in additionally and simply inform people this isn’t going to be very quantifiable, however for what it’s price. A part of my motive I averted intermittent fasting for therefore lengthy is that I believed I might not be capable of get ample protein or caloric consumption and that I might lose a bunch of muscle mass.
I used to be useless unsuitable about that. I used to be very, very unsuitable. If something, it appears to have enhanced my capability to placed on muscle per calorie or per gram of protein ingested. And so I admit I used to be completely unsuitable about that.
Moreover, on this ketogenic food regimen the place I’ve traditionally discovered it fairly exhausting to placed on muscle or — I imply, I shouldn’t say hold muscle as a result of I’m solely doing it for a number of weeks, however I’ve been astonished by having one small meal. I’ll have some oxtail soup after this with some veggies and clearly oxtail. It’s a complete separate story.
After which I’ll exit and have one other meal in all probability in three or 4 hours, which might be a a lot larger meal. And simply with that, and I’m watching among the grams of protein consumption and so forth, however I’ve not, wanting within the mirror and looking out on the weights that I’m placing up within the gymnasium, I don’t really feel like I’ve misplaced any muscle and I really feel like I’ve leaned out.
A few of that’s dropping fluid, however I’ve been actually impressed with how little relative to what I used to do in school, taking weight gainers and simply all this rubbish, how little it truly takes to not less than keep muscle mass.
However I do have a query for you, which I’ve by no means actually been in a position to reply to my satisfaction, and it pertains to rabbit hunger. So for individuals who don’t know what that’s, you would in all probability give a greater description, however should you’ve ever watched the present Alone, Alone might be the one actuality TV present that I like to look at.
seasons six and 7 specifically are excellent for people. However what you’ll discover is that if persons are attempting to outlive within the wilderness to outlast everybody else, that’s what the present is. You get to choose a handful of things, you get dropped off, you don’t get to decide on the place you’re dropped, and you then simply must survive for so long as attainable.
Generally it’s 100 days, typically it’s final man or lady standing. If any person is simply consuming lean protein like rabbits, they may waste away. They won’t final. They should get yanked out for medical causes, and that may appear unusual to individuals.
My query although is on a ketogenic food regimen particularly, are you able to simply devour leaner protein after which depend on physique fats for the fats? And a few persons are like, “Yeah, all people is aware of that doesn’t work.” However I actually wish to perceive why that’s the case, proper?
As a result of I perceive dietary fats dampens insulin response, proper? Or not less than that’s my understanding. Possibly there’s a fee limiting step in how a lot physique fats you’ll be able to break down and use, proper? And who is aware of if that’s mediated by the kidneys or who the hell, liver, I don’t know, proper?
I assume it will in all probability be liver, however I’d love to listen to your tackle it, proper? As a result of definitely previously, I and plenty of individuals studying The 4-Hour Physique have been in a position to lose extra physique fats than they’re advised they’re able to dropping, as measured by way of DEXA scans and different issues.
Are you able to do a average fats or low fats protein-based keto food regimen in case your aim partly is to lose physique fats, or does that backfire?
Dominic D’Agostino: Yeah, simply not indefinitely. So once I did the ketogenic food regimen for a 12 months, I used to be cruising at about 300 to 320 grams of fats, typically 350 grams of fats per day. After which simply experimenting, I might throw in a two days per week of protein veggies with about 50 to 100 grams of fats.
And in these days of dropping to 300 plus grams of fats to 50 to 100 grams of fats, after two days, I swore I misplaced two p.c physique fats and I might simply transition again. So I might simply periodically throw in protein veggie days. I might cruise on keto after which periodically titrate within the protein veggie days to help physique composition alterations.
So if I stored that going, I might get fairly dramatic, nearly scary lean to the place it occurred very quick. It’s nearly keto trains your fats metabolism after which should you simply begin titrating in, it’s simply pulling fats out.
And I feel my physique actually appreciated throwing within the veggies with the fiber appeared to assist with the intestine well being and I might try this twice every week and it’s fairly dramatic.
Tim Ferriss: Why not do it seven days every week? What occurs while you attempt to do it for extra?
Dominic D’Agostino: If the concept is to remain in ketosis, it was actually exhausting for me to remain in ketosis if I do protein veggies. After two days, I might be out, however my metabolism can be cranking.
Tim Ferriss: Mechanistically, why is that the case? Why doesn’t your physique simply break down extra physique fats?
Dominic D’Agostino: Yeah, as a result of, effectively, it’s taking physique fats exogenously and endogenously and I feel the extra fats going to the liver and the extra fats that’s in circulation, it will get shuttled to the liver after which that’s stimulating beta oxidation within the liver. You simply have a larger fats pool.
However truly, I feel, the day that I might do protein veggie days after which the day I might soar again into ketosis, I might see this large ramp up in ketones that day. Whereas if I did like a cheat day and simply ate loads of carbohydrates, it took me two or three days to get again into ketosis.
But when I simply did like protein and veggies and cruised again into ketosis, then I might quickly get again into ketosis and simply give my physique a break from the fats. However I feel simply that quick period of time actually stimulates mobilization of fats out of your physique as a result of your physique is used to getting it exogenously, and you then’re pulling extra fats off.
However yeah, I feel on the protein veggie days, I’m getting greater quantities of energy from protein. In order that has a little bit of an anti-ketogenic impact. After which shifting again into ketosis on that third day, I all the time had in all probability the very best ketone numbers for the week.
Tim Ferriss: Yeah. I don’t wish to beat this useless horse too lengthy, however I’d love to only hear you riff on this slightly bit extra as a result of I assume in my thoughts I’m considering, effectively, in your protein veggie-only days, should you’re getting sufficient protein, not sufficient protein to fulfill all your resting metabolic fee, such as you’re hypocaloric, however you’re getting sufficient protein to not lose muscle, why wouldn’t the physique simply break down the fats that it must proceed producing ketones, proper?
So I’m attempting to keep away from the gluconeogenesis downside the place you’re having like 200 grams at a meal with no fats to offset it, however should you’re having smaller quantities which can be slowly digested, however it’s simply sufficient to maintain you from dropping muscle mass, perhaps you’re performing some weight coaching to assist with that or no matter, then I assume what I’m attempting to determine is why the dietary fats is so essential? As a result of I consider the physique, proper? It’s like every pound of saved physique fats is what?
Dominic D’Agostino: 3,600.
Tim Ferriss: All proper. So 3,600 energy, that’s an honest quantity of energy, proper? And for any person who’s, let’s simply say you’re 150 kilos, 10 p.c physique fats, okay, you bought 15 occasions 3,600, you bought loads of physique fats to go round.
So it will appear to be sufficient to do a number of weeks of ketosis that’s low fats, greater protein, however not sufficient protein to essentially be hammering your liver with gluconeogenesis should you’re dividing it up, slowly digested protein. Some persons are going to be actually irritated with me dragging this out so lengthy, however why is dietary fats so essential?
Dominic D’Agostino: As a result of I imply, that’s the gasoline that you’re utilizing, you coax your physique into utilizing. And I ought to in all probability add slightly little bit of context to my protein veggie days. So I might go from like 125 grams of protein to love 300 grams of protein.
Tim Ferriss: Proper, proper.
Dominic D’Agostino: That’s a reasonably large bolus of protein.
Tim Ferriss: That’s loads, yeah.
Dominic D’Agostino: And if one was to go 100 grams of protein or no matter, after which bump it as much as like 170 or 200 or one thing, they could not kick out of ketosis. However I bear in mind simply decrease ketones, however not out of — I used to be nonetheless in ketosis, however sometimes how I feel I did it like my protein veggie days have been following like a heavy deadlift or squat exercise.
So the considering was that I’m recovering for these two days and the additional amino acids and proteins and mTOR activation is type of helping in restoration and regeneration and skeletal muscle protein synthesis. After which I might form of return. I calculated it in that means. So yeah, I like double the protein on the protein veggie days, however my energy have been about the identical or perhaps slightly bit decrease.
Tim Ferriss: Yeah. I would like a SiBio should you’re listening, please permit me to calibrate this with a finger prick as a result of I would like slightly extra vary. I would like slightly extra vary than 0.01 to 0.04 for me to have the ability to learn one of these factor successfully, proper? As a result of technically, if I’m studying this as it’s, I’m by no means in ketosis. I shouldn’t say by no means, that’s not true. However in any case, it will not be good to have the ability to calibrate.
Let’s come again to one thing I promised that I might ask about, which is neurodegenerative illness, Alzheimer’s, et cetera. May the ketogenic food regimen profit individuals with these circumstances? And simply as essential, definitely for me personally, might this, is it believable that there’s a mechanism by which the ketogenic food regimen usually achieved might assist delay the onset of any of those illnesses? Or am I simply Pollyanna hoping for a pie within the sky?
Dominic D’Agostino: Yeah. I feel that’s a query we don’t have an unambiguous reply to, however I feel all of the science factors into the path that should you enhance upon and optimize your cardiometabolic — I wish to say cardioimmunometabolic biomarkers, as a substitute of cardiometabolic biomarkers as a result of should you can decrease, for instance, your insulin and hold that between two to 6, and should you decrease your hsCRP beneath 0.6 after which optimize your hemoglobin A1C or glucose. And I feel additionally, and I’ve talked about this with Rhonda Patrick and different individuals, too, that should you measure your omega-3 fatty acids and have a look at your omega-3 to six ratio, I feel that’s going to be a biomarker that’s in all probability going to finish up in commonplace blood work as a result of it’s so compelling, the info behind it.
And also you additionally measure your B12, too. I feel that’s essential. Individuals coming into the Alzheimer’s middle that may current as flat-out Alzheimer’s illness and you then right their B12, a B12 deficiency will trigger mind atrophy, and that might be reverse with B12.
So the issues that should you’re following ketone metabolic remedy, it’s impacting the issues that we all know are driving age-related power illnesses, after which clearly certainly one of them is Alzheimer’s. So the extent of irritation, hsCRP now might be extra atherogenic than LDL. There’s in all probability individuals promoting statins that don’t wish to hear that, however we all know that the info is rising on that now. So decrease insulin, decrease irritation —
Tim Ferriss: And that’s an inflammatory marker, proper? The C-reactive protein. What does the HS stand for or what’s that?
Dominic D’Agostino: Excessive-sensitivity C-reactive protein.
Tim Ferriss: Excessive-sensitivity.
Dominic D’Agostino: Yeah. So it measures in that decrease vary. And I used to development to love two to 2 to 3, like my early CRP, hsCRP once I was like on a excessive carb, I solely had it measured twice once I was on like a high-carb food regimen, however since I’ve been keto, it’s like both non-detectable or like 0.2. Or once I did excessive setting analysis on myself, then I might bump it up slightly bit. And once I had a bacterial or viral gastroenteritis, it shot by way of the roof as a result of it activated your immune system. However usually that hsCRP is a giant driver.
I used to snort at it and be like, “Ah, it’s this nonsensitive factor.” However now like all the info is pointing to the path that we have to add that to that.
And your omega-3 standing, your B12, ensure you don’t have any deficiencies as a result of that might result in type of speedy development to Alzheimer’s illness, your magnesium ranges.
But additionally simply normally like train, the most important metabolic lever and your physique weight, physique composition.
Get DEXA scans. I do know it may be good so that you can do a DEXA scan together with your keto experiments, too. So I used to be doing yearly, however now I find yourself doing like three or 4 occasions a 12 months as a result of I do these mini experiments to see how acutely among the issues are impacting my physique composition as a result of I simply get antsy for like a solution to that.
However it’s a long-winded rationalization to only principally say that your metabolic well being is tightly linked to your mind well being and may dramatically delay the onset of Alzheimer’s illness. Not that you just’re going to get it or reverse it altogether earlier than one thing else will get you ultimately. Yep.
Tim Ferriss: Properly, I imply, the metabolic well being piece, simply to underscore that, I imply, certainly one of my kin in query, APOE 3/3, I perceive that’s not the one threat issue, however there’s one thing simply appeared to be lacking as a result of the decline was so precipitous. It didn’t map to any affected person information or medical information that a lot of docs, who’re additionally researchers I used to be working with, had seen. Additionally as a result of this individual, this relative had been assessed 4 or 5 years prior and didn’t present any indication of predisposition to a speedy decline.
And I’m APOE 3/4, once more, recognizing there are different components at play, however when she simply form of disintegrated, there are some things that got here to gentle. Primary is her native GP had principally missed extreme metabolic dysfunction for years. And I can’t bear in mind the reference vary, however like insulin, let’s name it higher sure of 12. I’m making this up, however you’ll get the concept. And she or he was like 43, proper? It was simply completely atrocious.
Dominic D’Agostino: And her physique weight and simply common composition?
Tim Ferriss: I imply, poor physique composition. Yeah. Poor physique composition, little or no train regardless of my finest efforts, misbehaves horribly, dietarily, not morbidly overweight, however definitely —
Dominic D’Agostino: Smoking, alcohol, different medication?
Tim Ferriss: No smoking or alcohol.
However right here’s the opposite piece that, so she had been recognized with stage one breast most cancers, had a lumpectomy, was eliminated, late 70s was placed on an estrogen, I feel it’s an estrogen blocker referred to as letrozole.
And I checked out this and I spoke to a good friend of mine who was a radio-oncologist and he or she stated it is vitally poorly tolerated by most ladies from a cognitive perspective, like they get smashed by and huge.
Dominic D’Agostino: Guys, too, by the best way. Guys who take —
Tim Ferriss: Okay. Yeah, guys do.
Dominic D’Agostino: — aromatase inhibitors, yeah, for like TRT and issues like that. It’s not a very good factor to do.
Tim Ferriss: Yep, yeah. So I used to be taking a look at it and I imply, it’s upsetting that I’m the one who has to form of discover this stuff, however it’s like, okay, effectively, we take into consideration the oncologist’s position. It’s to stop my mother from dying of most cancers. That’s the directive, proper? But when she have been 30 and had later stage most cancers that was actually aggressive, it’s one factor, however she’s late 70s, stage one, all most cancers eliminated, and so acquired her off of the letrozole with the cooperation and after discussions with docs and nearly noticed an instantaneous turnaround inside a handful of weeks after the washout interval and all the things.
However it appears to, I imply, look, I’m not an MD. I don’t play one on the web, however it appears to have achieved some actual harm. I imply, there’s the metabolic piece that could be very non-trivial, however the acceleration of decline was simply so absurd over the course of a handful of months, terrifying to see.
However I assume I’m laying this all in, not essentially to discover this explicit case as a result of I’ve acquired lots of people on it for all of my kin, however it’s simply to say that my — like I’m not going quietly into the evening with one thing like Alzheimer’s, proper? And so what I’m attempting to determine for myself, I’d be curious to listen to your perspective.
I might be trustworthy, I discover keto fairly goddamn boring. I don’t discover it to be essentially the most numerous food regimen on the earth. I don’t actually wish to do all of it 12 months spherical. I even have some perhaps compromising cardiac parts. I’m a ldl cholesterol hyper-absorber, so I do use — once more, guys, discuss to your doc. Don’t simply copy me, however it’s like I’m utilizing Repatha, taking ezetimibe. I’ve been additionally taking Nexlizet, however that may find yourself being redundant, the bempedoic acid with the Repatha.
That may be a great distance of claiming I’ve acquired to control the center stuff as a result of neurodegenerative illness and heart problems is what kills all people in my household. So for lots of causes, I don’t wish to do keto all 12 months, however I’m attempting to determine what’s the type of minimal efficient dose that — and I do know we’re going to should in all probability take a few speculative leaps right here, however simply as a working speculation, what does a minimal efficient dose of following a strict ketogenic food regimen appear like for me?
Assuming the remainder of the time I’m nonetheless doing intermittent fasting, I’m not consuming loads of refined carbohydrates, however how would possibly you recommend that I take into consideration that? As a result of I don’t know what the sturdiness of form of keto reminiscence, like metabolic reminiscence is. So I’m attempting to determine like can I get away with two, three to four-week durations a 12 months the place there’s some carryover of like cancer-protective — our final dialog we form of talked about occupied with ketones as hormones, however by way of neuroprotective, anti-inflammatory, yada, yada, yada, what are your ideas?
Dominic D’Agostino: Yeah. Properly, I feel in your context it’s exhausting to say, like to present absolutes, however I might say you will get 80 p.c of the advantages with a low-carb food regimen. Low-carb that means 100 grams a day, simply fibrous, non-starch, non-sugar carbs, low-carb Mediterranean, if you wish to name it that.
After which periodically, perhaps one week out of a month, get right into a deeper state of ketosis and at greater shouldn’t be higher. We all know that from the analysis. When ketones get into that two, three, 4, 5 millimolar vary, that creates vitality toxicity and one thing we name reductive stress, and that’s not good.
I didn’t know this earlier than stepping into this sort of analysis, however the candy spot appears to be between one and two for therapeutic ketosis, until you’re metabolically managing a dysfunction that’s extremely attentive to a ketogenic food regimen like neurometabolic illnesses.
And among the issues that we truly examine should be within the two to 3 millimolar. And oxygen toxicity must be like 4 to 5 as a result of it’s a — very highly effective seizures. However one to 2 appears to be the candy spots for metabolic administration of many various issues and in addition simply common metabolic well being.
And I feel what you’d be doing, simply doing low-carb and periodic ketosis is simply enhancing your metabolic flexibility and perhaps rising the variety of meals that you just’re consuming to stop micronutrient deficiencies, too.
I’m of the opinion that crops are good so that you can eat broccoli, asparagus, salads, colourful greens, issues like that, that form of match right into a sample of consuming that we’ve identified. Even issues like lentils are in all probability good. Lentils even have like zero CGM response to me, however I —
Tim Ferriss: Actually?
Dominic D’Agostino: Yeah, lentils appears to love, skyrocket different those that I do know. I’m like utterly flat.
Tim Ferriss: I’m like someplace in between. Yeah, I’m someplace in between.
Dominic D’Agostino: Okay. Like utterly flat. I don’t know. Possibly it’s the time of day that I’ve them at dinner, then I all the time go take a stroll, however it’s like no bump in any respect in my CGM.
And I feel that’s the place CGM comes into play and we will do a private precision engineered food regimen, if you’ll, and it offers us perception into the kinds of meals and the quantity of meals that we will eat. And I feel that’s going to be actually essential info.
And I do know there’s lots of people harping on, as a result of one other examine got here out on CGMs present no profit in any respect to the non-diabetic. And I’ve had this dialog with individuals truly at a giant occasion and those that have been sort 2 diabetics and I requested them simply flat-out, I simply went across the desk and simply saying, “Should you’re sort 2 diabetic, while you have been recognized like three years in the past, should you have been to be giving a CGM 5 years earlier than that, and even one 12 months earlier than that, do you assume you’d’ve been recognized with sort 2 diabetes?” They usually stated no.
They stated as soon as they acquired sort 2 diabetes and acquired a CGM, it gave them the attention. I imply, you’ll be able to ask anybody who has flat-out over sort 2 diabetes and simply ask them the query, “Hey, if you got a CGM a 12 months or two prematurely and also you understood the influence of meals.” So I feel a CGM goes to be essential for delaying that Alzheimer’s illness. And if in case you have family members, Tim and your loved ones, that I feel you’d encourage them to slap on a CGM and get some perception into what they’re consuming.
However it’s additionally forcing them to train as a result of we’re speaking about food regimen right here, however simply getting out and doing a brisk stroll 20, half-hour a day can go a great distance. Resistance train, I’m slightly biased in the direction of that, however muscle is like an endocrine organ that produces hormones and varied molecules which can be neuroprotective and muscle is tightly linked to mind measurement and, in fact, your waist and your visceral fats.
I might additionally encourage them to get a DEXA scan and gamify it and say, yearly I’m going to get a DEXA scan and yearly like I do, I simply form of create loads of stress for myself to beat my DEXA scan yearly and get their buddies concerned, make it like a social occasion. All people goes and will get their DEXA after which yearly you return and simply attempt to beat your scores. However I imply, these are low-hanging fruit form of issues individuals must be doing.
Tim Ferriss: Yeah. Let me, I feel in all probability truthful to say, ensure you persistently hydrate for any of this stuff like a DEXA scan.
I do have a follow-up query. So additionally on the train piece, individuals can lookup one thing referred to as klotho, Okay-L-O-T-H-O. There’s much more that comes of train like BDNF and all these varied issues. There’s a e book referred to as Spark that covers a few of it, however it’s very outdated, however take a look at klotho. There are loads of good causes to train. Pondering of muscle like an endocrine organ, that’s a very good technique to put it.
My query to you was, you talked about, say, one week per thirty days going to extra of a decrease carb or ketotic state. How would you concentrate on the advantages of 1 week per thirty days? Assuming that the remainder of the time I’m behaving, more often than not with a decrease carbohydrate Mediterranean food regimen, let’s simply say, okay, one week per thirty days, each three months or three weeks, like contiguous weeks as soon as 1 / 4. Do you are feeling like a kind of is superior to the opposite?
Dominic D’Agostino: Not likely. I feel no matter sample works finest, I feel you’d achieve advantages for each. That may be an attention-grabbing experiment to do.
Tim Ferriss: I’m simply occupied with the lead time to get right into a correctly ketogenic state. If I’m going from some carbohydrate to ketosis, I’m simply — we might discuss issues that may speed up it, but when it takes me two days to get there or three days after which I solely have form of 4 days within the candy spot, these are issues operating by way of my thoughts. I’m simply curious to get your take.
Dominic D’Agostino: Yeah. The one-week intervention for the month, my form of opinion is that it might be fairly aggressive. Such as you minimize energy 50 p.c the primary two days after which cruise into it, so that you’re actually cranking ketones by the tip of the week. And you then’re additionally cruising into it from what must be like a low-carb food regimen. So it is best to have that metabolic flexibility to form of seamlessly transition into that ketosis state. And you would do intermittent fasting with delicate caloric restriction for the primary two days to ramp up ketones.
Alternatively, in case your schedule permits and like your work schedule, you will have like three weeks the place that you must actually dig deep right into a analysis undertaking or one thing and ketosis appears to present you that cognitive circulate or increase, then that may situationally match into your schedule. And I positively have durations of time the place I try this, particularly like if my spouse is touring or one thing like that, or on a analysis undertaking or one thing, I similar to, okay, I clear the home of sure meals after which I simply put together.
I imply, easy issues like that, too, I do know simply from the medical ketogenic world is that if in case you have a member of the family that shares the cabinets with sure meals that may set off and trigger meals noise, then that might actually hamper your compliance to that. However you wish to put together the home, or should you’re going right into a one week otherwise you’re going into a 3 week, put together the home and simply just remember to might do. After all, you would simply name Uber Eats and get something delivered, however you wish to form of have the home ready for that and mentally put together for it.
Tim Ferriss: So for you, personally, should you had some hereditary gnarliness, should you look again at your loved ones tree and also you’re like, ooh, whether or not it’s a bunch of most cancers or a bunch of neurodegenerative stuff, perhaps little bit of each, who is aware of, would you be extra inclined to do the one week per thirty days, only for you personally or yeah, one week per thirty days?
Dominic D’Agostino: Yeah. And I might shoot to get a glucose ketone index of like one to 2 for not less than three days out of that week. So actually do a reasonably aggressive ketone metabolic remedy intervention, form of even give it some thought as like a prescription intervention, similar to Valter Longo’s food regimen is a prescription medical remedy, proper?
So I might shoot to realize a glucose ketone index of 1 to 2 for 3 days. And all the things that we’ve seen within the lab that I’ve seen type of on paper, in fact, individuals aren’t on the market measuring the autophagosome like P62 and different issues, however that you’re reaching a stage of autophagy and that’s additionally stimulating lots of the advantages of ketosis, not simply ketones as an vitality supply, however you’re getting lots of the sturdy signaling results and actually adapting your metabolism to fats and ketone type of oxidation that has long-term advantages that may go not less than three weeks.
So I’m satisfied of that. So that you get advantages for 3 weeks, reset one week, advantages for 3 weeks, reset one week so that you’re all the time form of getting — whereas should you do three weeks after which take a time period off, I’m not completely satisfied that these advantages are going to span that quantity of timeframe. That’s my considering.
Tim Ferriss: And also you talked about individuals can discover calculators on the market and really loads of the units will attempt to present this to you. Really, is that true? I assume they must have each information streams, so in all probability not, however the GKI.
So the glucose ketone index, you will discover calculators for this, however fact-check this, since that is AI overview from Google, I needed to only check out it. Divide your blood glucose stage by your ketone stage. In case your glucose is milligrams per deciliter, frequent within the US, you first divide it by 18, this is a vital step, to transform it to millimolars per liter, matching the ketone models, then carry out the division. So you’ll be able to determine this out very simply. And that’s the GKI that you just have been mentioning of a one to 2.
What would possibly that appear like simply offhand? I’m very not identified for my fast psychological arithmetic on the podcast, however what would a GKI of, say, one or two appear like by way of the readout on the glucose, on the glucometer and the readout on the finger prick for the millimolars for ketones? What can be an instance?
Dominic D’Agostino: If persons are like don’t wish to do the millimolar focus of glucose, in case your glucose is 80 after which your ketones are two millimolar, that might be, you’re proper into that one to 2 form of the glucose ketone index of 1 to 2, you’ll be between that stage.
Should you might convey your glucose down to love 18, so like 68, 70 and get your ketones as much as three, so that might be a GKI of 1. In order that’s fairly exhausting to realize, however comparatively positively doable with exogenous ketones and MCT and issues like that. I feel what’s completely possible is getting your glucose down to love 80, 80 to 85 in that vary and getting your ketones on the finish of the one-week quick as much as two and sustaining that. So that might be form of reaching that GKI of two.
Tim Ferriss: I feel I’m in all probability saying what I want to be true, which is that my insulin sensitivity has improved loads within the final definitely 12 months specifically, and that’s to clarify partly, or perhaps wholly, the decrease readout on the ketone meters.
However a part of the rationale I’ve confidence in that’s that I’m utilizing the identical units that I used to make use of. And again within the day, I might have a lot greater millimolar readouts.
After all, I’ve new strips. I did, not less than to the extent that I can, for the continual displays, I’ve achieved calibration for the CGM not less than, the glucose monitor, however that presents an issue. Even when that’s, “Excellent news, Tim Ferriss, you’re not failing at keto. You’ve truly simply made your self loads more healthy with intermittent fasting and different issues,” it nonetheless presents an issue for me to determine if I’m in that GKI candy spot.
So how would you recommend I attempt to determine that out? Is there a technique to measure my ketone uptake and, subsequently, modify the equation such that I issue that in one way or the other? Like there’s a multiplier of the readout on the finger prick or one thing like that? How would you deal with that?
Dominic D’Agostino: Yeah. Let me look actual fast.
Tim Ferriss: Dom is wanting into his Santa’s workshop of varied metabolic units.
Dominic D’Agostino: Yeah. So I’ve loads of completely different units. So one is the Keto-Mojo system right here.
Tim Ferriss: Yep, that’s the one I’ve. Yeah, I’ve acquired the Keto-Mojo.
Dominic D’Agostino: Okay. In order that, I imply, you would simply calibrate it such that it reads in millimolar focus in glucose and ketones, and it truly offers you, that is the GKI model. It’ll simply spit out the GKI.
Tim Ferriss: Oh, you recognize what? I do have the GKI since you’re proper, the Keto-Mojo additionally measures glucose.
I assume what I’m asking for myself is since my readouts are so low, presumably as a placeholder as a result of improved insulin sensitivity and ketone utilization, I’m going to fail if I’m simply utilizing the glucose and the ketone strips for the Keto-Mojo. As a result of proper now, if it’s telling me that I’m at 0.4 millimolars, and I can inform you subjectively, I don’t really feel like I’m at 0.4. I really feel like I’ve acquired much more juice and much more gasoline within the tank.
Is there a technique to, whether or not it’s on paper or in any other case, account for the elevated ketone utilization? I imply, it’d be nice for me simply to confirm that one way or the other, however then whether or not I can confirm it or not, if I needed to attempt to decide throughout that week, like if I’m hitting my goal GKI, how would you recommend that somebody like me try this if I’m simply not getting the numbers essential to make the common math work?
Dominic D’Agostino: So one to 2 is a excessive bar, I assume, a GKI of 1 to 2. And I feel we’ve had this dialog backwards and forwards with this group that we’re working with within the most cancers group.
The Society for Integrative Metabolic Oncology is a bunch that we’re discussing the GKI, and Thomas Seyfried could be very adamant about, like, getting to 1 to 2. However I give pushback and say one to 4 is should you have a look at the printed literature, one to 4 is completely 100% therapeutic throughout not solely most cancers, but in addition like seizures and all the things. So I’m going to develop that vary to a one to 4.
So what does that imply? That may imply that your glucose stage could be upwards of 80. And so you would have a glucose stage of 75 to 80, after which get your ketone ranges to 1, and that might be a GKI of 1 basically should you don’t have the glucose calibration for that. Or that might be a GKI of 4, fairly. And it will be actually uncommon, if not inconceivable, for anybody within the common inhabitants consuming to even obtain a GKI of like 5 to 10. In order that’s indicative of excessive fats oxidation, ketone manufacturing, and I feel that you just’re getting loads of therapeutic advantages. Additionally, a millimolar focus of 1 in your blood represents a ten p.c obtainable vitality on your mind. And in addition the Keto-Mojo units measuring D-beta-hydroxybutyrate. And should you’re doing supplementation with racemic D and L, you then’re not choosing up the L. In order that might be an element too should you’re utilizing racemic ketone salts.
And there’s a lot of publications which have already occurred and a few within the pipeline principally displaying that elevate hydroxybutyrate takes about 4 to five occasions longer to metabolize. In order that’s in circulation extra. And in addition like, should you’re on a ketogenic food regimen for causes we don’t absolutely perceive and we’re to tear out the center, about 34 to 40 p.c of the ketone within the coronary heart is elevate hydroxybutyrate. And we don’t know why it converts the D to the L, however it serves a perform that — the teams which have achieved the analysis are satisfied it’s not an lively, however it’s truly impacting cardiac output and decreasing peripheral vascular resistance, perhaps on the glycocalyx. So I don’t wish to go down that rabbit gap. However principally, it’s like in case your coronary heart is pumping towards stress and consider it as like a backyard hose and you’re taking the kink out of the backyard hose, the elevate hydroxybutyrate is taking the kink out of the backyard hose of your vascular endothelium after which that’s additionally in your mind. So you will have higher blood circulate to your mind.
I imply, there’s tons of information on the market displaying a rise in mind blood circulate with beta-hydroxybutyrate and the L developments higher to rising that blood circulate. We do a Doppler blood circulate measurement on varied wound therapeutic issues that we’ve achieved within the lab. I imply, lots of people have vascular dementia, proper?
Tim Ferriss: Yep.
Dominic D’Agostino: So there’s various kinds of dementia, and it may be not like utterly one or the opposite. And the metabolic phenotype of dementia might be vascular. You get a restriction of oxygen and vitality to the mind. My level is that one millimolar of beta-hydroxybutyrate in circulation has an lively impact and it additionally has a pronounced impact on the vascular endothelium to extend blood circulate and circulation. So you’re getting a profit.
Tim Ferriss: I’ve by no means had this expertise in ketosis earlier than the place these ranges have been this low. It’s so weird. And but, let’s say, again within the day earlier than the intermittent fasting, and it’s just about the lever that I pulled that I feel modified issues. Previous to that, I might inform you in all probability inside 60 minutes of hitting 0.7 millimolars on the precision additional. Like I knew when my mind clicked previous that time. And I did years and years and years of these items. I feel as a lot as I wish to measure issues, I ought to simply assume, proper? If I’m having a bowl of mackerel pet food with MCT oil and apple cider vinegar and salt and pepper, then having a meal later that successfully has near zero carbohydrates, if I’m doing that for nearly three weeks, there doesn’t appear to be a physiological possibility C for failure, proper?
It’s like, what’s my physique going to do? It needs to be doing one thing as a result of I’m not getting the dietary carbohydrate, and I’m not simply mainlining whey protein isolate all day. So, I feel I’ll in all probability simply should belief within the course of as a result of if I do have the elevated ketone utilization and I’m simply someplace between 0.2 and 0.4 millimolars, for essentially the most level, or for essentially the most half, I simply don’t assume that the maths may be actually exhausting even to hit the GKI of 4. However it’s like, should you’re following the method, I assume you’re following the method, proper?
Dominic D’Agostino: I say belief the method and in addition take into consideration — I’m speaking about like blood biomarkers, however let’s discuss bodily metrics that might be thought-about biomarkers, proper?
So for me, it’s all concerning the numbers. Like my lab books and stuff like which have numbers within the lab, but in addition coaching. It’s like, I do know precisely what I’m going to do going into the subsequent exercise and it’s all about X quantity of weight for X quantity of reps. So it’s also possible to try this with varied mind coaching apps the place you are able to do response time. So for our NASA NEEMO experiments the place we’re in an excessive setting and we’re working with astronauts, we’re assessing response time, determination making, threat taking, the place like this balloon blows up and also you don’t know when it’s going to explode, however you must cease. It’s like a bizarre threat sport.
So we now have this entire metric of testing cognitive perform, response time and issues like that. So there are issues that you would do even with an app-based factor to evaluate that, and I feel that might be a very good factor. We’ve got an enormous NIH grant at College of South Florida on mind coaching video games and assessing efficiency on that. Alzheimer’s was in my household, I might principally be doing all the things attainable, bodily coaching, dietary metabolic coaching with diet, supplementation, and in addition mind coaching.
And mind coaching video games, and we use Joggle, the NIH Toolbox, I imply, we now have like about six or eight various kinds of assessments that we do to get a really goal measure of cognitive perform. And I feel it will be good to determine that at times get your baseline similar to we’re doing a DEXA for physique composition, after which take a look at that each six months. After which do it within the absence and presence of being in ketosis. So I might recommend one thing like that.
Tim Ferriss: Yeah. I’ve time blocked out in my calendar this Friday to do a complete battery of cognitive testing. And once more, this isn’t tremendous exact, however having tracked myself for therefore lengthy and developed a water gasoline for sure kinds of efficiency, zone two feels loads simpler proper now, loads simpler than normal. And coming again to your prior feedback. After which, I might say, I’m utilizing software program proper now. In some unspecified time in the future I’ll be capable of discuss extra about this, however to principally prepare my visible processing to compensate for presbyopia, it’s loopy, among the results that these items has. However it additionally could be very a lot not directly a measure of response velocity, and so they see some actually cool carryover results. And my velocity by way of time to completion for 4 bouts, like modules of duties has simply gone up and up and up since I’ve type of been in prolonged ketosis. Once more, that’s very simple for me to see. So people who’re listening, I’ll have extra to share on that later, however it’s fairly mind-blowing stuff.
So Dom, a number of issues have come up that I might love to talk about as a result of I get these questions on a regular basis, which relate to exogenous ketones. And folks have heard this time period, exogenous, endogenous. It’s very fancy discuss and a tuxedo for outdoor the physique, within the physique, proper? I’m simplifying right here, however the simple technique to bear in mind exogenous is exoskeleton, proper? It’s like a skeleton on the surface of your physique. Exogenous ketones, ketones that you just’re taking from outdoors and placing inside. Individuals all the time ask, and I do know you will have a canine within the battle right here, so I wish to acknowledge that too. However how ought to individuals take into consideration supplemental ketones? And are there any warnings or disclaimers that you just wish to add to that, proper?
As a result of it is a subject du jour. I feel there’s in all probability no organic free lunch if persons are going to be mainlining fruity pebbles and consuming tons of carbohydrates, perhaps not an important concept to eat tons of exogenous ketones. I don’t know, I’d be curious to get your tackle that. However what’s the nice, the dangerous, and the ugly of exogenous ketones? The place ought to individuals go? How ought to they give it some thought?
Dominic D’Agostino: The issues to contemplate can be while you’re occupied with a ketone complement to consider palatability. If it doesn’t style okay, you’re not going to devour it. I might, however most individuals gained’t. Palatability, tolerability, if it offers you catastrophe pants or it makes you nauseous or one thing. So palatability, tolerability, after which the subsequent one, the third one can be the pharmacokinetics. So that you need one thing that while you devour it, that it has an excellent pharmacokinetics, that means it’s not going to spike up in half-hour and be out of your system in like an hour or two.
Tim Ferriss: Yeah. Pharmacokinetics is just like the inventory chart for one thing you set in your physique, proper? On this case, proper?
Dominic D’Agostino: Yeah, yeah. And that’s essential as a result of if in case you have a really speedy fee of rise of ketones, that may set off an insulin response. And what I’ve noticed, if I’m cruising in ketosis and I take a big dose of a ketone ester, it shoots my ketones up actual excessive and it’s again down inside like two hours, however it additionally kicks out insulin and that shuts off my very own ketone manufacturing. Then I’m hypoketotic and hypoglycemic from the insulin. And that may create an vitality deficit within the mind.
Tim Ferriss: How lengthy does that final for you?
Dominic D’Agostino: And it lasts within the context of consuming, for instance, a ketone ester by itself. However should you devour the ketone ester with MCT, should you might tolerate that, you would buffer that response to some extent, otherwise you take it with meals or one thing, or you would avert that by completely different ketone formulations and we might discuss that. However I simply wish to transfer down, so you bought palatability, tolerability, pharmacokinetic properties, and also you even have toxicity. So that might be the 4 issues that that you must take into account when type of deciding on an exogenous ketone. And people issues differ relying upon should you’re utilizing it acutely, like in a medical scenario, or it’s like a each day factor that you just wish to take every single day for prevention, proper?
Tim Ferriss: Yeah, let’s discuss toxicity first.
Dominic D’Agostino: Toxicity might be an important too.
Tim Ferriss: Yeah. Let’s, in the interim, not discuss concerning the acute medical supply. Let’s discuss leisure/higher stated layperson use, proper? That is as a dietary complement. So might you communicate to the toxicity piece?
Dominic D’Agostino: Yeah. Properly, what we noticed about 10 years in the past was that formulations that contained 1,3-Butanediol, that features an ester. I’ve loads of patents on and I’ve truly ongoing experiments with 1,3-Butanediol by itself is a ketogenic agent and that may have toxicity when used chronically. 1,3-Butanediol is an alcohol dimer and it will get metabolized by way of alcohol dehydrogenase and aldehyde dehydrogenase. Aldehyde dehydrogenase kicks out a beta-hydroxybutyrate aldehyde that may be poisonous.
Tim Ferriss: How is it poisonous? What are its poisonous results?
Dominic D’Agostino: Yeah. So alcohol dehydrogenase makes use of NAD, consumes NAD as its perform, proper? So it will possibly principally deplete the liver of NAD. And aldehyde dehydrogenase additionally consumes up NAD and it quickly depletes, for instance, the liver, the hepatocytes of ATP. So we all know that there’s a paper popping out that’ll present that in our lab we’ve seen therapeutic results in sure contexts, however when delivered acutely. However when consumed chronically, once we transcend our experimental window and provides this stuff chronically as like a way of life, exogenous ketone. After which we sacrifice the animals after which we do blood work and we have a look at the liver, we see indicators which can be scary, proper? And this might be irritation within the liver, TNF-α, sinusoidal dilation, type of like gaps within the liver, fatty liver, a lot of various things begin to floor. And that’s just about simply as a result of metabolizing one thing that’s thought-about a toxin to the physique, 1,3-Butanediol.
It’s a really versatile drug. 1,3-Butanediol by itself is extra poisonous than 1,3-Butanediol based mostly ketone esters. So you will have the ketone monoester, which is technically the millimolar focus. You’ve 51 p.c of a ketone monoester is 1,3-Butanediol. So it hydrolyzed within the liver, will get into circulation. Nonetheless over 50 p.c of that’s 1,3-Butanediol. That form of must be detoxified, however 1,3-Butanediol does get damaged all the way down to beta-hydroxybutyrate. The diester is about 35 p.c 1,3-Butanediol. So, I see these as probably problematic.
Tim Ferriss: The diester is what proportion?
Dominic D’Agostino: A ketone diester, which might be 11,3-Butanediol with two ketones on it. We use acetyl acetate on every, that’s 35 p.c of that molecule is 1,3-Butanediol in circulation.
Tim Ferriss: I acquired it.
Dominic D’Agostino: After which the beta-hydroxybutyrate monoester is 51 p.c 1,3-Butanediol in circulation. So this could change into problematic when it’s used as like a complement and a way of life factor like day in and day trip.
Tim Ferriss: Are you able to translate from the animal fashions to people, do you assume, proper? As a result of everyone knows, people aren’t simply large furry mice, proper? Do you assume it interprets, proper? And this may be similar to a precautionary measure the place it’s like, “Properly…” Like pending further research, let’s hit pause in a way. But when it have been to translate, do you will have any concept what sort of dosing per day or per week with which we would see this toxicity in people, proper?
Dominic D’Agostino: Yeah. So there’s a paucity of information, and there’s a deficiency of information on the usage of these brokers 1,3-Butanediol which can be long-term research. The one examine that I’m conscious of is a case report with Dr. Mary Newport’s husband, Steve, after which there’s a 28-day examine that used 25 grams.
Tim Ferriss: 25 grams.
Dominic D’Agostino: 25 grams per day, yeah.
Tim Ferriss: Oh, shit.
Dominic D’Agostino: And that produces like 0.1 to 1 millimolar. However what I’ve achieved is I took the R-1,3-Butanediol after which the racemic 1,3-Butanediol at completely different time factors. And I principally dosed it for 2 weeks to maintain my ketone ranges at two millimolar, which might be like a therapeutic. And while you try this, what you will notice, and I — effectively, I used to be going to say, I inform those that go forward and do it, however perhaps don’t do that. However while you take one thing like 1,3-Butanediol at a dose, which for me requires 30 milliliters thrice per day to maintain at two millimolar all through the course of the day. Should you try this for 2 weeks and you then take a look at your transaminases, so that might be AST, ALT, and GGT, they may go up, in order that’s a transparent indication that — so we’ve achieved this in animals and fed it at a fairly excessive stage, and we didn’t see transaminases going up.
Tim Ferriss: So transaminases are what individuals might consider as liver enzymes on their blood panels, proper? ALT. Is GGT sometimes examined?
Dominic D’Agostino: GGT is just like the wild carb, however what’s good about GGT is it’s the canary within the coal mine. It is going to go up earlier than ALT and AST. Should you count on somebody has an issue with alcohol and so they say they’re not consuming and also you wish to work out in the event that they’re consuming or not, say, “Hey, can I see your blood work and ensure the physician provides GGT simply to get a greater,” and that’s elevated and your AST aren’t. The one issues that’ll actually shoot up GGT is like alcohol. And in addition the scale of the crimson blood cell too could be in the event that they’re like bigger, that’s a sign like somebody’s consuming an excessive amount of alcohol. And it might be similar to two or three glasses a day, however that may elevate GGT. So we noticed that transaminases truly didn’t go up in our animals fed. The ketone esters or 1,3-Butanediol chronically, however once we pulled the livers out after which regarded on the livers, then we noticed issues that involved us. And we printed this not too long ago.
And it’s good to know when somebody has non-alcoholic fatty liver illness, they’ll have regular transaminases however have a necrotic liver.
Tim Ferriss: Yuck. I didn’t know that. It’s terrifying.
Dominic D’Agostino: Yeah, yeah. I imply, you look very intently at ALT longitudinally and that creeps up, however you principally should do like a CT scan or a excessive decision ultrasound of the liver. And principally, you would simply take a subset of the American inhabitants that developments to be chubby and also you do some liver scans and you discover that they’ll have overt fatty liver illness and have utterly regular transaminases are simply trending up, proper?
Tim Ferriss: Mm-hmm.
Dominic D’Agostino: So my liver enzymes are inclined to development slightly bit greater simply because I eat loads of protein. So with 1,3-Butanediol and 1,3-Butanediol based mostly ketone esters, you will have an issue with tolerability, palatability, probably possible pharmacokinetics and in addition toxicity. So it nearly like checks all of the bins in a damaging means. So the sphere is trending in the direction of non 1,3-Butanediol based mostly exogenous ketones, and that might be free acids, it might be a triester with glycerol and in addition the ketone electrolyte salts, however you would additionally avert a part of this simply by formulation. The problem is that corporations have one molecule after which they take a look at that one molecule, however you would — I feel formulation is the best way to go. And corporations don’t wish to hear that as a result of they’ve all their IP in a single molecule. However we’ve all the time been a formulation form of based mostly lab, and all the time noticed that this stuff all the time have drawbacks when used as a monotherapy, however while you begin combining them collectively, that’s while you get higher therapeutic results.
Tim Ferriss: Obtained the hounds on the market. Hopefully, not subsequent to the gators. We gained’t spend any time on this, however I simply needed to inform those that earlier than we begin recording, you’re telling me that you just caught a 10-foot alligator that was attempting to eat your canines and you then pinned it down and taped its mouth after which measured its glucose and ketones. Seems that alligator had a fairly good GKI, however that’s a narrative for an additional time. So solely within the issues that Dom would do class that stand out, however we’re speaking about loads of phrases which can be probably unfamiliar to people. I don’t wish to throw anyone below the bus right here, however individuals ought to do their homework. 1,3-Butanediol could be very, very, quite common. It’s very cheap, or comparatively cheap to provide. So simply hold an eye fixed out for 1,3-Butanediol. If that is of curiosity to you, I’ve no funding in any ketone complement firm or something.
I should not have a stake on this, however I want to ask a few issues. So I’ve experimented, as you recognize, with ketone monoester, diester, ketone salts, I’ve performed with all the things, and I’ve discovered the diester to trigger fairly a little bit of intestinal discomfort, to place it mildly, not less than the primary one or two occasions. I’ll say for people, if at first you don’t succeed, that means you must run to the bathroom. You could acclimate to it, which I did in that case, however I felt subjectively much less and fewer impact. I appear to develop tolerance in a short time. I don’t know why that might be the case, however I appear to expertise it. The ketone monoester, which is the 1,3-Butanediol sure to BHB, if I perceive it appropriately, proper? I do like that. I just like the subjective feeling of it, but when that’s solely at about 11 milliliters.
If I take 25 plus, chatting with your pharmacokinetics, proper? Just like the inventory pops after which it drops after which I really feel very drained and sometimes really feel extra nervousness. It appears to immediate in me extra nervousness. I imply, look, we acquired to speak about this. Not that it invalidates what you’re saying in any means, however your spouse runs an organization that sells ketone salts, which I additionally I’ve been utilizing most persistently. Keto’s Remedy, individuals can test it out. However on the ketone monoester, what I’m questioning is that if I’m solely taking, let’s say, 11 milliliters a few times a day, and I’m taking it alongside MCT oil, the place would you set the danger evaluation on one thing like that?
Dominic D’Agostino: I might say, the danger could be very minimal for a wholesome individual. So I’ve a brilliant wholesome liver. I even take N-acetylcysteine, alpha-lipoic acid, all this stuff. So I used to be stunned to see type of liver climbing. What we see in our older animals is that they’re selectively weak to 1,3-Butanediol toxicity from acutely and in addition chronically. So for a traditional wholesome individual, particularly somebody that’s type of actually good metabolic well being and liver perform and so they don’t drink or medication that compromise the liver, I might say upwards of 1,3-Butanediol 20 to twenty milliliters a day might be the place you wish to cap it and perhaps not do it every single day. 1,3-Butanediol based mostly ketone ester would try this, however it’s also possible to in all probability obtain and keep the identical stage of ketosis with a ketone salt, a beta-hydroxybutyrate salt.
And I do like the concept of a D and the L, the 2 enantiomers, which is a dialog that you could be or might not wish to have. So the L is principally like, it’s packaged beta-hydroxybutyrate within the time launch kind and it has some signaling results. After which you will have free acids too which can be developing available on the market, and varied liposomal formulations. I’m undecided in the event that they’re commercially obtainable but, however these are some issues within the pipeline. However yeah, 1,3-Butanediol based mostly monoester, I feel there’s good information behind it. I feel the science that’s printed is biased below the path as a result of that was the molecule that loads of corporations affiliate with, after which they take a look at that molecule in and of itself as a monotherapy. And I’m of the opinion that issues are positively optimized. You would avert loads of the issues simply by formulation.
Tim Ferriss: How does the MCT oil assist? I assume principally it makes the ramp up extra gradual. Is that the impact that the type of co-consumption of the MCT oil has?
Dominic D’Agostino: Yeah. It delays gastric absorption for one factor, however it’s additionally stimulating your endogenous manufacturing. So the MCT goes to the liver, not by way of like chylomicrons, it goes proper to the liver and stimulates your physique’s ketone manufacturing. And I feel that’s essential. It’s nearly like coaching your liver to ramp up fats oxidation, and it’s nearly like exercising your liver to stimulate it. What we’ve additionally noticed, and we printed on that, like a big dose of MCT, while you take the liver out and have a look at it, there’s globules of fats all within the liver.
Tim Ferriss: Oh, that sounds dangerous.
Dominic D’Agostino: Properly, we see a fatty liver, however we didn’t see proof of necrosis, however we did see some inflammatory markers.
Tim Ferriss: Necrosis is useless tissue, useless cells.
Dominic D’Agostino: Yeah. Yeah, we didn’t see that, however we noticed indicators. We noticed sinusoidal dilation and TNF-α was elevated and another issues to recommend that enormous doses of MCT. And should you do the human equivalence, it will be like me taking upwards of like 80 to 100 milliliters per day. In order that’s loads.
Tim Ferriss: Though, it’s not that a lot although, proper? I imply, as a result of 30 milliliters is like two tablespoons, is that roughly, proper? So it’s like six tablespoons. Should you’re simply squirting it into your espresso, it’s not exhausting to essentially get above 100. It’s truly fairly simple. So the place would you suggest capping MCT consumption? I’ll eliminate my camel again with the MCT oil in it, however the place would you suggest capping the MCT consumption?
Dominic D’Agostino: The research that have been achieved displaying advantages is like 20 milliliters per day, however they solely did a single dose, which is bizarre, however that was the outdated Axona research. And like 80 p.c of individuals tolerated that, 20 p.c didn’t. However I’m of the opinion that 20 milliliters twice per day can be completely positive for basically most individuals that may tolerate that. And also you’re going to have in all probability about 30 p.c or extra that may, however MCT is way more tolerable while you take it with a meal. So should you take MCT on empty abdomen, put together to be nearer to a toilet, proper? So yeah.
Tim Ferriss: Yeah. Of all of the disgusting issues that I’ve consumed in my life, and I’ve had loads, proper? I imply, I’ve tried early prototypes of among the esters and all types of stuff. I’m not going to say it was a Piña Colada, however I used to be positive with it. MCT oil to this present day, I simply discover so completely revolting. I don’t know if it’s the neutrality and the mouth really feel, however combined with the mackerel and that apple cider vinegar, it sounds so disgusting. My good friend nearly puked in his mouth yesterday once I was describing it. It’s truly actually good. I’m only a sucker for mackerel. I’ll take mackerel over sardines all day lengthy, however — let’s see right here… So I feel we’ve coated loads of the exogenous ketones. I’ll simply pull this from our textual content thread as a result of I feel it may be a query on some individuals’s minds.
As I used to be attempting to troubleshoot my obvious failure mode with ketosis due to my low numbers, I requested you, is there any argument to be made that I ought to have a ketogenic breakfast as a substitute of intermittent fasting? May it’s that I’m inflicting issues with exogenous ketones, proper? Am I delaying probably the onset of my very own ketosis? Is it like TRT, proper? Should you’re taking exogenous, keep in mind that phrase, should you’re injecting or rubbing on or swallowing testosterone, it’s like your Leydig cells are fairly good. That’s the rationale your balls flip into Raisinets is as a result of it’s like, “Cool, we don’t should make that anymore.” So I believed, am I capturing myself within the foot by taking exogenous ketones? And it feels like slightly bit goes a great distance, however like most issues, in extra, it turns into its reverse, proper? It turns into a hindrance and makes it problematic. Is that truthful to say?
Dominic D’Agostino: Yeah. We’ve solely seen the anti-endogenous ketosis impact with 1,3-Butanediol or 1,3-Butanediol-based ketone esters, and that’s due partly to their efficiency and in addition the speedy elevation of ketones appear to have an insulin impact that may double or triple insulin. And even when we elevate ketones to the identical stage with a salt, we don’t see that spike up in insulin. In order that might be coming into play together with your low ketones in case you are consuming the monoester.
Tim Ferriss: Not a lot. Each on occasion, like earlier than train, as a result of I won’t thoughts the spike, however I’m not consuming a ton. Yeah.
Dominic D’Agostino: However the breakfast, I’m of the opinion that protein loading within the morning, truly while you first get up, and I feel Donald Layman and perhaps Stu Phillips would additionally agree with this, and perhaps Layne Norton too, the protein guys within the camp, is that protein within the morning form of amps up your metabolism all through the remainder of the day. And I feel should you abstain from consuming throughout the day, you are inclined to get the munchies later within the day and also you are inclined to overeat, whereas if in case you have a protein-heavy meal within the morning with excessive fats, then that may type of rev up your metabolism for a very good a part of the day. However then once more, some individuals, me included, my thoughts shouldn’t be as sharp when I’ve —
Tim Ferriss: Properly, that’s the factor. That’s the factor, proper?
Dominic D’Agostino: Yeah.
Tim Ferriss: Yeah, I might say that, I imply, for 15 years, the type of 30 grams inside half-hour of waking up has been this type of simple to recollect heuristic that I’ve really helpful for people and that, if I’m not intermittent fasting, that’s additionally what I do, however I’ve change into so hooked on the psychological sharpness that it’s similar to, man, I do know that if, as an illustration, if I wish to do three hours of writing, I don’t wish to have meals instantly previous to that.
Dominic D’Agostino: Yeah.
Tim Ferriss: However I might say, I’m additionally at some extent, I feel, the place throwing up actually heavy weight for me and getting as large and powerful as attainable is simply not — it’s much less of a precedence than it as soon as was, after shoulder surgical procedures and elbow surgical procedures and varied issues. Not that I wish to be the skinniest man within the room, however —
Okay. It sounds just like the pharmacokinetics are perhaps accountable with the related spike in insulin for among the points you would possibly run into should you’re taking the 1,3-Butanediol-based merchandise.
Dominic D’Agostino: It may be, and I believe it’s, and I’ve form of confirmed with myself that’s the case, however it additionally could be mitigated partly by mixing, taking it with a meal or taking it with MCT. However you then get the — it’s metabolized, like 30 milliliters of 1,3-Butanediol is form of like 30 milliliters of ethanol.
Tim Ferriss: Yeah.
Dominic D’Agostino: After which 1,3-Butanediol can create dependence and it can also create — you get withdrawal. So it’s establishing literature. There’s a number of publications simply displaying that with 1,3-Butanediol will produce dependency, and while you abruptly cease 1,3-Butanediol after consuming it for a time period, there’s basically alcohol withdrawal from that.
Tim Ferriss: What are the signs of that? I imply, think about you don’t get DT, proper? You’re not getting shakes or something, are you? However, I imply, what occurs?
Dominic D’Agostino: Yeah, it’s, I imply, it’s like classical form of ethanol withdrawal, perhaps not fairly as dramatic, however the glycols or diol alcohols do have a GABAergic impact, so that you’re doing that. And yeah, I imply, it’s effectively established it has narcotic-like properties and that form of stymied its use as an artificial meals for area flight. Properly, I feel that the palatability additionally factored into that, but in addition within the literature, it notes a narcotic impact of this after which the animal research and actually confirmed dependency and withdrawal.
Tim Ferriss: Simply to present a reiteration of that, I imply, the 1,3-Butanediol-based stuff can be bought as an alcohol substitute. So in fact, being the fool that I’m, not fool, similar to I’m desirous to experiment right here and there if it’s not going to kill me, and so I believed, “ what? I don’t wish to drink tonight.” I bear in mind the place I used to be. I used to be in Upstate New York, about to go to a restaurant with a good friend. I knew he would wish to drink, after which I needed to have the ability to say, “Hey, I already had this forward of time. Don’t fear. We’re on the identical stage.”
And I chugged a small can. It wasn’t, by way of liquid quantity, loads, proper? I don’t know, six ounces, eight ounces. And I felt like I might barely stroll to the lavatory. I used to be smashed. It was, like nearly knocked a glass off the desk. I used to be like, “Holy shit, I didn’t do that threat evaluation correctly. Thank God I’m not about to get right into a automobile,” as a result of it took a short while to put on off. In order that narcotic impact is absolutely, it’s not all the time delicate.
Dominic D’Agostino: I made jello pictures. I made 1,3-Butanediol jello pictures. And earlier than we made the ketone esters in 2009, Patrick Arnold and I form of formulated this.
Tim Ferriss: Patrick Arnold. So individuals who don’t acknowledge Patrick, take heed to my dialog with him from years in the past, but when you recognize BALCO or bear in mind when Barry Bonds grew a number of head sizes or any of that stuff, anyway, Patrick’s acquired some tales.
Dominic D’Agostino: Yeah.
Tim Ferriss: So the jello pictures, so what occurred with the jello pictures?
Dominic D’Agostino: Yeah. Properly, that was the best way to get it down as a result of 1,3-Butanediol is so nasty, proper? So you would principally simply heat up pure 1,3-Butanediol in a pot after which add cherry-flavored sugar-free jello after which stir it up after which pour it into like a cookie pan after which minimize it into cubes, which you get 20 milliliters per jello shot, and make it fairly sturdy so it’s like agency jello, and I might simply hit like two or three of them and simply be buzzing. And I discuss it, like 1,3-Butanediol could be enjoyable and it’s a lesser of two evils once we’re speaking about ethanol. So I truly tried to file a patent for the usage of 1,3-Butanediol for alcohol withdrawal and issues like that. However truly, there was some prior artwork on that, and that is a few years in the past, however I truly do assume it might be half utilized by individuals if they might transition off of ethanol, probably use that, however there are different methods to get off alcohol. I’m not advocating for that.
However my concern, is why I’m speaking about it now too, is that I do know there’s older individuals on the market with dementia, maybe Alzheimer’s illness, that in the event that they’re consuming 1,3-Butanediol as a ketogenic complement, it’s going to make you dizzy. It’s going to lower your stability, prefer it’s going to make you probably fall, break your hip. After which while you’re older, your liver, your capability to detoxify alcohol, an 80-year-old solely has like 20 or 30 p.c of the capability to do this. So the identical quantity of 1,3-Butanediol for a 20-year-old goes to be like three to 5 occasions more durable in your liver as we age, proper? And folks word that, like as you age, you simply can’t tolerate the identical quantity of alcohol.
Tim Ferriss: Yeah.
Dominic D’Agostino: So I feel this stuff, the 1,3-Butanediol-based dietary supplements, the straight up 1,3-Butanediol and 1,3-Butanediol-based ketone esters are problematic for the age inhabitants that I feel a few of these merchandise or corporations are focusing on. And I say that not solely as a scientist, however due to the amount of emails that I get on that. Individuals have been like, “I acquired tremendous buzzed. I didn’t know what occurred.” And a few persons are very delicate to it, like I gave my spouse — she will be able to’t tolerate alcohol in any respect and he or she took a shot glass of the stuff and he or she couldn’t imagine that it was a authorized complement to promote.
And now this can in all probability curiosity lots of people, so that they’ll in all probability exit and purchase it, however I’m simply saying like should you’re delicate to alcohol, you’re going to get overly buzzed, and my concern is that, hey, if you wish to use it for leisure, that’s your factor and perhaps it’s higher than alcohol, however for older individuals, a big dose of 1,3-Butanediol is problematic from a narcotic, from simply the potential for simply getting drunk, simply straight up drunk. And Dr. Veech advised me that a very long time in the past, I used to be like, as a result of I used to be attempting to get the ester from him and I used to be like, “What if I simply use 1,3-Butanediol?” It’s like, “You’ll get drunk.” So it’s like he instilled that, that, “Don’t try this.” That’s what he stated.
Tim Ferriss: And Veech was the co-inventor, is that truthful to say, of the bonded monoester that was funded partly by, was it the DOD or DARPA?
Dominic D’Agostino: DARPA.
Tim Ferriss: DARPA after which patented at Oxford. Is that proper? Am I getting my details straight or am I getting issues combined up?
Dominic D’Agostino: Yeah. Properly, Oxford type of acquired the IP and made an organization out of it, however we now have to credit score Dr. Richard Veech, who handed away a number of years in the past, for the conception of a ketone ester for simply — Dr. Veech was the coed of Hans Kreb.
Tim Ferriss: Kreb of Krebs cycle?
Dominic D’Agostino: Krebs cycle, sure.
Tim Ferriss: That’s wild. Wow.
Dominic D’Agostino: Yeah.
I went to Dr. Veech’s lab on the NIH. I noticed the entire ketone course of, I examined various things. We have been in communication, and I feel he was a really colourful character and he had an incredible thoughts. We disagreed, we agreed to disagree on some issues, however I take into account him a mentor of mine, and I feel all of us owe loads. I don’t assume exogenous ketones might even not exist. Properly, Henri Brunengraber and another individuals, Sami Hashim developed the triester. So there was different individuals on this area, however he actually superior the science and in the end the applying of exogenous ketones and I feel has written extensively about it. I imply, this stuff have been round for a very long time, and I feel as science advances, we now have extra info after which we will — I’ve pivoted away from this stuff, though we nonetheless use them in some experiments. I printed some very nice information on 1,3-Butanediol, truly even in most cancers research too, however on the identical time, I spotted that the damaging results, I can pivot away from that. We’ve got different molecules in growth now.
Tim Ferriss: So I do know as I’m watching issues get darkish on the East Coast for you that we’ll wrap up in only a few minutes. However in short, you talked about fats, salt, fiber as issues that may be useful for slowing, I assume, gastric emptying of those meals that I’m having. And I’m curious for you, on a ketogenic food regimen, what are your favourite sources of fiber, supplemental or in entire meals kind?
Dominic D’Agostino: Complete meals kind. I like broccoli, and I purchase broccoli florets, after which I minimize the tip of the floret off, and I’ve a bowl of that and I give the stalk and stuff to my canines and I chop it up for his or her fiber. In order that’s one thing that I do, I don’t know, simply to get the next dose of broccoli. However broccoli, after which wild blueberries that has about half of the sugar and extra fiber. They’re a couple of quarter of the scale of like the large blueberries you purchase at, like, Walmart. However so wild blueberries, I like apples as a result of they’ve a sure fiber referred to as pectin in it. Some those that have an issue with fiber can’t digest pectin or they get gassy, so it’s on the FODMAP listing or no matter. However wild blueberries, simply inexperienced greens normally, however I like broccoli, and apples are just about one thing I’ve every single day.
Tim Ferriss: Now, the wild blueberries, I simply wish to actually underline wild for individuals as a result of that’s not what you’re essentially going to get at your native grocery retailer that’s been optimized to be as candy as —
Dominic D’Agostino: No. They’re in Publix. So I can get them in Publix down right here. And I feel, I don’t know, truly I feel they’re in Walmart too. I feel you’ll be able to go to Walmart, and I feel you may need to sneak round for them, however there’s like a model, they’ve wild raspberries and blueberries and blackberries collectively. I overlook the identify of the model, however they arrive in like large two or three-pound luggage too.
Tim Ferriss: How a lot are you able to eat of apples or berries earlier than undoing all the nice metabolic work that you just’re doing in ketosis, proper? As a result of even, as an illustration, we’ve talked about how simple it’s, and it actually is straightforward so long as you’re fairly easy to please dietarily, to, say, journey for keto, proper? So that you simply pack a bunch of canned sardines, mackerel, perhaps some oysters, and macadamia nuts, and also you’re form of good to go, like this stuff are fairly calorically dense. However the macadamia nuts, I used to be wanting on the bag the opposite day as a result of it’s one of many few form of crunchy issues that I really feel like I can eat other than a few of these greens, and I used to be like, “Wow, should you go entire hog within the macadamia nuts, you’ll be able to rack up the carbs after some time.” What about apples and berries? The place’s your cutoff level for your self?
Dominic D’Agostino: Properly, macadamia nuts even have that three-to-one to four-to-one ratio of fats to — so they’re fairly excessive in fats, however like cashews after which like almonds and different nuts. I like walnuts too, I forgot to say. So I’ve walnuts, a small natural apples we purchase, wild blueberries, and broccoli just about every single day, and all that collectively finally ends up being about 60 to 70 grams of carbs, however one third of the carbs is fiber, so it’s basically non-glycemic. I haven’t had any of that at the moment, however I are inclined to have that at dinner after which my snack at nighttime. So all the things that I simply talked about, the carbs. However I don’t give it some thought as undoing like ketosis, and I do assume my glucose tank is all the time like perhaps 10 or 20 p.c full, so I’m all the time operating form of low on glucose, and on some days I’m extra lively.
Tim Ferriss: What’s your peak and weight, Dom, in the meanwhile?
Dominic D’Agostino: Six foot, 220, and I’ve been, give or take, 5 kilos for years now, yeah. So simply all the time cruise at like 220. Yeah.
Tim Ferriss: Yeah. I imply —
Dominic D’Agostino: 100 kilograms.
Tim Ferriss: Yeah, good physique composition. That’s loads of muscle for people who find themselves not watching the video. I’m simply attempting to set the perhaps context for what your tolerance may be for grams of carbohydrates.
Dominic D’Agostino: I’ve fairly good tolerance for carbs now, however I feel I’ve good tolerance extra now as a result of I’ve titrated some carbs again in, as a result of I did go in all probability not less than 5 years on like very low, like medical ketogenic. And I did find yourself dropping like nearly like 18 kilos of like lean physique mass, after which I took a 12 months off in 2018, once we purchased our farm. I used to be very busy on the farm. Then I purchased weights and simply have it on the farm. After which I’ve been doing DEXA. My final DEXA, it was 218, however below — I used to be like 9.8 p.c physique fats, like nonetheless below 10 p.c. However I gained muscle once I acquired again into lifting and simply did the heavy compound actions once more. I don’t go tremendous loopy on the burden, however I do prepare exhausting. However —
Tim Ferriss: You discovered the addition of the carbohydrates to be helpful, that barely greater amount of carbohydrates?
Dominic D’Agostino: Yeah. I’ve added extra carbs again in through the years, and that has helped me keep my physique weight. And I like consuming these meals. I get pleasure from these meals. I feel they’ve helpful fiber, phytonutrients, different micronutrients that I feel are helpful. And I can keep a stage of ketosis about 0.5 to 1.5 day in and day trip consuming these meals every single day. And I do titrate in just like the MCTs and I get like one or two packets of KetoStart of day, perhaps as much as three if I’m touring, however that’s my regular protocol and that has optimized all my biomarkers. I truly acquired full blood work at the moment. Sort of ready for that to come back again to see. It must be attention-grabbing. I used to be inadvertently took one thing that I believed was laced with one thing, some gummies I advised you about, however —
Tim Ferriss: Persons are going to imagine. When individuals hear gummies, they assume it’s THC, however this was what, theanine and magnesium? It ought to have been actually innocuous, proper? Is that proper?
Dominic D’Agostino: Yeah. Theanine and magnesium, my spouse purchased it at Marshalls. We each took two. We awoke within the morning and he or she says,” I’m dizzy.” She’s asking me, “What did you give me final evening?” I used to be like, “I didn’t provide you with something.” As a result of typically I give her stuff. I attempted to rise up, fell flat on the ground. Each of us couldn’t stroll. We have been each utterly incapacitated. I referred to as the Poison Management Middle. And yeah, so principally I’ve been operating round to completely different labs, and now I’m doing forensics, so do one thing. I’m nonetheless buzzed —
Tim Ferriss: Wow. Actually?
Dominic D’Agostino: — so if I don’t seem to be myself, as a result of I’m nonetheless buzzed 48 hours later. So we took one thing —
Tim Ferriss: That’s wild.
Dominic D’Agostino: We had the spinnies, and even this morning I awoke, I had the spinnies strolling to — so no matter it was, it was fairly highly effective. And I’ve slightly little bit of a again damage from a couple of week in the past, and I don’t have any ache from that. So I feel no matter it’s, I’m considering probably a fentanyl spinoff or one thing, however —
Tim Ferriss: Yikes, that’s terrifying.
Dominic D’Agostino: My spouse doesn’t drink, she doesn’t use any medication, so she was just about actually floored by this.
Tim Ferriss: Wow. Did you return and purchase some extra of them to ship off to get analyzed?
Dominic D’Agostino: Properly, I’ve it. Yeah. So I collected my urine, my spouse collected her urine, after which I’m doing the required blood work, and I’ve contacted a forensic lab, and we now have docs concerned in all this now.
Tim Ferriss: Wow. Dosed the unsuitable man. Or the fitting man, since you think about like what if that had been a 80-year-old lady sleeping on the second flooring. I imply, that’s harmful.
Dominic D’Agostino: Completely. Yep, completely. I simply took two and I’m a reasonably large man and all the things, but when slightly child took two or 4 or 5 — so clearly, I don’t know, the corporate, and the corporate you will discover it on Amazon, combined it up and it’s laced with one thing or they only put excessive focus THC and I form of know what, however that is, we’re speaking 48 hours later and I’m nonetheless feeling it.
Tim Ferriss: That’s wild.
Dominic D’Agostino: I’m tremendous curious with my blood work, so I’m ready for that to come back in. Watch out, individuals on the market as a result of —
Tim Ferriss: Watch out of these gummies, people.
Dominic D’Agostino: Yeah. Not regulated.
Tim Ferriss: Yeah. Dom, is there the rest you want to point out or wherever you’d wish to level individuals earlier than we wind this to an in depth?
Dominic D’Agostino: I don’t assume so. I imply, we talked loads about like sardine fasting and all the things, I feel, earlier than.
Tim Ferriss: Within the prior dialog, yeah.
Dominic D’Agostino: Yeah, yeah. I’d wish to credit score to Dr. Annette Bosworth, Dr. Boz, as a result of, I imply, I’ve form of got here up with this concept, however it acquired traction, and I feel she has — lots of people that electronic mail me about sardine fasting heard it from Dr. Boz, and he or she’s amplified the message with thousands and thousands of YouTube followers. However she form of took an concept and really put it into apply and amplified it by way of lots of people, after which these individuals emailed me about it, in order that amplified and secured my data. “Sure, okay, these advantages are…” And now she’s been on like Diary of a CEO podcast, I feel, and another podcasts.
So I’d additionally like to say, I’m testing at the moment even, there’s an organization popping out, I don’t know if I can point out or not, however I’ll, Medifoodz. And for years, there’s no entire food-based ketogenic food regimen prescription meals. So I’ve no affiliation with the corporate, I’m simply testing their product, however they’re referred to as Medifoodz. And
Tim Ferriss: How do you spell that? M-E-T-I? M-E-T —
Dominic D’Agostino: M-E-D-I-F-O-O-
Tim Ferriss: Oh, Medi. I acquired it. Medifoodz.
Dominic D’Agostino: Yeah, Medifoodz. With a Z. And I acquired to inform you, these are like gourmand meals, after which they hit the macros of a modified ketogenic food regimen. And we talked about if somebody says the ketogenic food regimen shouldn’t be palatable, they should see these meals. They’re prescription entire meals. There’s different corporations that attempted to do that, and so they even acquired just like the packaging is like compostable, prefer it seems like plastic, however I might throw it in my backyard and it breaks down. I’m very impressed with this. I simply talked about that as a result of I simply acquired these meals yesterday and I used to be actually impressed, however different corporations haven’t been so spectacular. So Medifoodz is fairly spectacular. And Quest Diet tried to do that some time again and I feel their meals have been good, however they acquired a brand new CEO and simply phased it out.
However I like the concept of a prescription, entire meals, ketogenic food regimen that probably a health care provider might write a prescription. And every week of meals might be despatched to the sufferers. I’ve been questioning why somebody has not achieved this, however I do know the margins are very small within the meals world, so it’s exhausting to form of get that up and operating.
Tim Ferriss: I imply, they might take the strategy that loads of corporations take, loads of tech startups take, like Uber, Tesla, et cetera, you promote at first for a lot greater value to people who find themselves keen to pay that. You utilize that to subsidize the R&D or the dimensions essential to then supply, proper? As a substitute of Uber Black, you will have UberX, and equally for lots of corporations. I imply, I might pay for this, proper? And yeah, I wouldn’t say completely price-insensitive, however I’m keen to pay for comfort as a result of there does come some extent the place I’ve had sufficient canned mackerel and salads with rib eye that I might like to have one thing else in any case. So I’ll take a look at Medifoodz.
Let’s see. Dom, are you lively on social wherever? Ought to individuals discover you wherever on-line?
Dominic D’Agostino: Yeah, I’m not too lively, however I attempt to soar on about a few times every week, and I cap my social to perhaps an hour every week.
Tim Ferriss: Yep. Good man.
Dominic D’Agostino: I attempt to reply again to issues, yeah. Sort of delete the apps from my telephone or a few of them, however I repost issues and attempt to acknowledge some questions and stuff individuals have on this, after which I gather questions after which — we now have our personal podcast, the Metabolic Hyperlink Podcast. And we now have a Metabolic Initiative Platform which has ACCME accreditation, so it’s like you will get CME credit from it. In order that has been a undertaking that we’re engaged on and attempting to advance all the things we’re speaking about into human software by way of that.
Tim Ferriss: Yeah. Stunning. Properly, I’m attempting to consider every other hyperlinks. Are there every other hyperlinks that you just wish to point out? And we’ll stick these all within the present notes as effectively for individuals.
Dominic D’Agostino: Yeah. Ketonutrition.org. No merchandise. I don’t promote something. So ketonutrition.org info web site, the Metabolic Hyperlink Podcast, and the Metabolic Well being Initiative Training Platform are just like the three biggies, I feel.
Tim Ferriss: Stunning. We’ll hyperlink to all these issues for individuals listening in addition to — God save — Individuals who assist me do the present notes, they’re going to have loads to dig by way of, however we are going to hyperlink to all the things that we will discover a hyperlink for at tim.weblog/podcast. Simply search Dominic, and this would be the most up-to-date episode. I imply, we might have some sooner or later, so that you’ll discover it.
And Dom, thanks a lot for taking the time, man. At all times nice to see you.
Dominic D’Agostino: My pleasure. Thanks, Tim, for having me. Recognize it. Good seeing you.Tim Ferriss: Yeah. And all people, as per all the time, thanks for tuning in, and till subsequent time, be only a bit kinder to others and in addition to your self, particularly should you may be self-flagellating your self over not hitting your GKIs, like yours actually. All proper. Take care, all people.
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