Please take pleasure in 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 Faculty of Medication and a Visiting Senior Analysis Scientist on the Institute for Human and Machine Cognition.
He teaches medical neuroscience, physiology, diet, and neuropharmacology, and his analysis focuses on the event and testing of dietary methods and metabolic-based therapies for neurological issues, most cancers, and human efficiency optimization. His work spans each primary science and human scientific trials.
He has a powerful private curiosity in environmental medication and enhancing the protection and resilience of navy personnel and astronauts. On this capability, he served as a analysis investigator and crew member on NASA’s Excessive Surroundings Mission Operations. His analysis has been supported by the Workplace of Naval Analysis, the Division of Protection, the Nationwide Institutes of Well being, personal organizations, and nonprofit foundations.
He earned his B.S. in Dietary Science and Organic Sciences from Rutgers College in 1998, adopted by a predoctoral fellowship in Neuroscience and Physiology at Rutgers and the College of Medication and Dentistry of New Jersey. He then accomplished postdoctoral coaching in Neuroscience at Wright State College’s Boonshoft Faculty of Medication in 2004 and at College of South Florida Morsani Faculty of Medication in 2006.
Transcripts could include just a few typos. With many episodes lasting 2+ hours, it may be tough to catch minor errors. Take pleasure in!
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Dr. Dominic D’Agostino — All Issues Ketones, Learn how to Shield the Mind and Enhance Cognition, Sardine Fasting, Weight loss program Guidelines, Revisiting Metformin and Melatonin, and Extra
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Tim Ferriss: Dom, good to see you once more. It’s been just a few years. Thanks for making the time.
Dr. Dominic D’Agostino: Yeah, it’s nice to see you, Tim. Yeah, we’ve stayed involved right here and there with texting, however yeah.
Tim Ferriss: Numerous texts. And why not? This is among the textual content threads I might in all probability really make public in my life with out some sort of mutually assured destruction with a lot of my buddies.
I’ve been revisiting the whole lot ketogenic and positively taking a look at exogenous ketones for a variety of causes.
And one in all which we had been chatting somewhat bit earlier than recording, is that I’ve a variety of relations who’re deteriorating from neurodegenerative illness, together with Alzheimer’s. And one in all them is APOE33, and my siblings and I are APOE34, which would appear to point we might have probably a, let’s simply name it two and a half X, greater likelihood of creating one thing like Alzheimer’s, regardless that information may change. Who is aware of?
Nonetheless, I’m trying to throw as a lot potential at this from a preventative perspective. What information do we have now, and if there’s somewhat little bit of hypothesis of all them, superb with that too by way of future instructions for analysis and what may come up for functions of, say, the ketogenic weight loss plan and, or exogenous ketones to one thing like Alzheimer’s, whether or not it’s from a preventative perspective, a mitigation of, or slowing of, development of signs or anything.
Dr. Dominic D’Agostino: Yeah, that’s a quickly rising space of analysis, and I believe you’re conscious, we talked beforehand of the case reviews which are on the market that acquired put this on everyone’s radar. I might say the early adopters of this concept had been the individuals who understood that mind power metabolism was fairly central to Alzheimer’s illness.
Tim Ferriss: Generally referred to as sort 3 diabetes, if I’m getting that proper.
Dr. Dominic D’Agostino: Yeah. That was coined again in 2005 or ‘6, I believe, and that was dropped at my consideration really by Dr. Mary Newport and her husband, Steve Newport, was the topic really within the case report for the usage of the beta-hydroxybutyrate monoester for that. Dr. Richard Veech of the NIH was additionally on that. And Mary was close to and expensive to my coronary heart. I really coincidentally hosted her for dinner final evening on the home and had her over right here. And he or she’s an in depth good friend of mine. We co-teach collectively at USF. She’s a visitor trainer.
Apparently, I noticed Steve Newport in 2008 or ’09, and I witnessed the statement. He’s a 3/4. He has Alzheimer’s. He was 3/4 for APOE4. And he additionally had, he had Lewy physique dementia, however confirmed Alzheimer’s illness too once they appeared on the mind. And I noticed — I used to be nonetheless fairly — I used to be questioning this concept of ketones rescuing the mind within the context of Alzheimer’s illness.
Symptomatically, there was little question in my thoughts that it did, as a result of I witnessed him. He wasn’t utilizing the ketone ester on the time, however we shortly transitioned to that after assembly, however he was taking coconut oil and MCT oil. And he would convey these little shot glasses. Mary taught my class. We went out to dinner. He did the shot glasses. His tremors stopped. He turned animated, and he talked. And after about 4 hours, he began to say no and began getting superb tremors once more. After which he would grow to be reanimated upon growing his ketones to about one to 2, which we’d give him a 30 milliliter shot of MCT plus coconut oil that was combined in there. So she was actually — and doing that three to 4 occasions a day with meals.
In order that was my first statement. And it was clear to me that there was no less than a metabolic — throughout the Alzheimer’s spectrum, I identical to to — Alzheimer’s is form of a fuzzy prognosis and —
Tim Ferriss: Positive. Very fuzzy.
Dr. Dominic D’Agostino: Yeah. And I identical to to name it dementia, cognitive dementia. There’s vascular dementia and there’s Aβ and tau. And my spouse was engaged on tau on the Alzheimer’s middle once we met. She was working beneath a man who studied tau. Then there was folks there who studied amyloid beta, and there was the tauists and the beta. And there was an argument as to what was extra profound.
However a common function of Alzheimer’s is amyloid plaque accumulation. But additionally now we all know that glucose hypometabolism is central to that. And as we age, our skill to make use of glucose as an power supply decreases over time on account of they thought possibly vascular causes. However come to seek out out, it’s actually, it’s a constellation of issues, together with the glucose transporter, the GLUT3 is on neurons. Pyruvate dehydrogenase advanced, which is absolutely the governor or the speed limiter of glucose metabolism in neurons. That’s PDH, pyruvate dehydrogenase advanced.
And the manufacturing of — should you have a look at that protein for that decreases over time, as does the catalytic exercise of that enzyme over time. So we all know that. After which there’s neuroinflammation, there’s a vascular element. So all this stuff form of contribute to metabolic dysregulation, but additionally a giant driver is neuroinflammation.
And I do imagine, as does Dr. Mary Newport, who’s the creator of that paper with a case report and a variety of different leaders within the discipline, together with, I’m blanking on his title, the chair of neurology at Harvard simply gave an NIH seminar on an infection as an etiological agent for Alzheimer’s illness. So Epstein-Barr virus, cytomegalovirus, herpes simplex virus. We do know — yeah, HPV — know can contribute to issues like —
Tim Ferriss: So we’re in all probability speaking about —
Dr. Dominic D’Agostino: — most cancers.
Tim Ferriss: — if, I imply, 50, 60 % of the inhabitants having one in all this stuff.
Dr. Dominic D’Agostino: Positive, yeah. Effectively, Steve Newport, the topic in that case report, had bouts of herpes, HSV, across the eyes and acquired hit fairly onerous with that. But additionally individuals who have shingles that I believe they’re in danger too. We all know Epstein-Barr virus, you’re 4 or 5 occasions extra danger for issues like MS. It’s triggering the immune system.
So I believe there’s a renewed curiosity in taking a look at Alzheimer’s illness, wanting on the root trigger. And I believe metabolism is central, however the metabolic hit that could be contributing to dysregulated metabolism and neuroinflammation may very well be an an infection. And I believe there’s accumulating proof for that. I used to be skeptical 10 years in the past, in all probability, once we talked. Nevertheless, this saved placing on my radar. After which I used to be in an NIH sponsored workshop on this taking a look at numerous elements, and the information offered by a variety of completely different labs was very compelling for this.
So what does that imply? Our immune system is — there’s the 4 horsemen that our good friend Dr. Peter Attia talks about. I believe the fifth horseman is absolutely the immune system. I like so as to add a sixth horsemen as our bodily type, our skeletal construction, so our bones, and that can give over time too. However the immune system is absolutely central to longevity. And the metabolic management of epigenetic regulation and metabolic management of immune system operate is of very excessive curiosity. I do know the Buck Institute has refocused on that, and lots of longevity clinics are actually taking a look at that.
Tim Ferriss: What’s your most popular system for measuring ketones lately?
Dr. Dominic D’Agostino: For publications, we’ve used the Abbott Precision Xtra as a result of traditionally we’ve used that. Nevertheless, after I advocate a meter to folks, I usually advocate the Keto-Mojo system as a result of that —
Tim Ferriss: Keto-Mojo.
Dr. Dominic D’Agostino: — has the glucose ketone index. And so the glucose ketone index is the millimolar focus of over ketones, and the strips are about, these days, nonetheless much less — I used to be going to say, I don’t know, just a few years in the past, they had been about half the value. And we’ve examined the Keto-Mojo. We’ve a human scientific trial the place we did breath, we did urine, and we did Precision Xtra and Keto-Mojo all collectively. Then topics go into the chamber and we did metabolomics and the whole lot else. However the Keto-Mojo persistently offers us numbers which are extra in step with our organic assays that we run within the lab.
Tim Ferriss: Okay, attention-grabbing.
Dr. Dominic D’Agostino: Just like the [inaudible] on that.
Tim Ferriss: Yeah, yeah. Let me simply let you know what I’m as much as and you may inform me how ridiculous I’m in off base or fact-check as wanted. Are you able to remind me of the way to pronounce this Dr. Thomas? Is it Seyfried? Am I getting that proper?
Dr. Dominic D’Agostino: Yeah. He’s good friend and colleague. Dr. Tom Seyfried.
Tim Ferriss: Tom Seyfried. All proper. So by way of fasting, we’ve talked fairly a bit about fasting. It nonetheless may be very attention-grabbing to me. And I’m questioning simply briefly, should you might, with out getting an excessive amount of within the weeds, however I’m questioning what the ketogenic weight loss plan does that exogenous ketones don’t obtain? After which I’m questioning what fasting does that the ketogenic weight loss plan doesn’t do.
However the way in which I need to get to that’s to ask you, as a result of for a very long time I used to be doing a one week, we might name it a water-only quick, however let’s name it a calorie-free quick, proper? Black espresso and black tea and stuff I used to be consuming, however a week-long, water lengthy quick a 12 months, and I used to be doing possibly a three-day quick each quarter. I didn’t actually need to do three to 4 week-long fasts a 12 months, simply didn’t need to do it. However by way of probably purging precancerous cells and so forth, I used to be like, you recognize what? I just like the aesthetic observe — looks as if a little bit of autophagy and mobile cleanup is an efficient factor. Why don’t I try this?
Do you do any fasting anymore or is that one thing that you’ve omitted from the present model of Dom’s schedule?
Dr. Dominic D’Agostino: Yeah, I do it situationally and I believe there’s conditions the place I believe I’ll profit from fasting or from simply inducing a state of an power deficit. So you could possibly do caloric restriction, time restricted feeding, dietary restriction. You possibly can do a restricted ketogenic weight loss plan, a cyclic ketogenic weight loss plan, modified, a modified supplemented ketogenic weight loss plan, which is what I do. I love to do what I name, I imply I coined it. It’s like sardine fasting. And I had a most cancers affected person a very long time. One of many first that I kind of engaged with, really his title was Dr. Fred Hatfield. So he was form of a well-known —
Tim Ferriss: That is Dr. Squat?
Dr. Dominic D’Agostino: Yeah, yeah, Dr. Squat.
Tim Ferriss: Again within the day. Wow.
Dr. Dominic D’Agostino: Yeah, we had been good buddies. He was a mentor to me in some ways. However he had superior metastatic prostate most cancers, and it went to the bones the place they did a PET. And I used to be simply entering into this space of analysis and I used to be like, “Right here’s what I might do.” And I might go to his home and I’d convey him issues, and he was testing issues. And he cherished sardines. So I believe he steered me onto sardines in possibly 2007 or oh eight or one thing like that. In order that was my love for sardines was in all probability from him.
However he would do low-carb. He referred to as it ketogenic, however I believe it was simply extra of a low-carb weight loss plan. After which he would do 5 days, he would do a fasting mimicking weight loss plan that Valter Longo has superior, however he has extra of a plant-based method. However Dr. Hatfield would do, Fred would do one or two cans of sardines, possibly one can of sardine per day for every week. So we referred to as it sardine fasting. And that was simply as I used to be entering into this. And primarily what occurred is that he went into fast remission and the medical doctors didn’t actually know. Fred ended up passing away possibly eight years later of one thing fully unrelated to his most cancers.
Tim Ferriss: As a non-oncologist, I’ve to pause and simply say, I imply, it looks as if prostate, for lots of people, they hear that, they assume “Loss of life sentence.” Metastasized prostate most cancers, they assume, “No manner, you’re completed.” Am I exaggerating? I imply, how frequent is it that folks have full remission of one thing like that? Possibly I’m exaggerating issues.
Dr. Dominic D’Agostino: Yeah, there’s a whole lot of components just like the Gleason rating and his was not good in a variety of components. So he was given, I believe he informed me three months to stay, however he went years and years —
Tim Ferriss: Wow.
Dr. Dominic D’Agostino: — after that. And he was like, no proof of illness.
Tim Ferriss: How typically was he doing the sardine fasting? Was that after each month? What did his cadence seem like?
Dr. Dominic D’Agostino: Yeah, he stayed ketogenic, after which I might go over there and encourage him to try this, and he cherished to do it. He was like, “Okay, I do that and now I really feel higher after I’m doing it.” Fred additionally surprisingly, would smoke somewhat bit, and I acquired him to possibly cease that too. So we acquired him to dial again on another behaviors and possibly he would drink somewhat bit too, however not that a lot. However his well being improved dramatically when he adopted a low-carb after which ketogenic weight loss plan. After which for years, he did the sardine fasting and we communicated and I simply inspired, “Hey, preserve sending me your medical reviews.”
And I used to be like, “Possibly there’s something to this.” So that really steered me into identical to the Alzheimer’s, we did began Alzheimer’s analysis due to Dr. Mary Newport. I studied seizures due to Mike Dancer. Simply Google Mike Dancer, epilepsy, and also you’ll discover some exceptional tales. I steered him to the ketogenic weight loss plan and it was a exceptional. He acquired off all meds and it labored manner higher than the meds. So Fred, however that was prostate most cancers. However then I began participating with different sufferers after which related with Thomas Seyfried quickly after that.
Tim Ferriss: How continuously was Fred doing the week-long sardine fasts, should you needed to guess?
Dr. Dominic D’Agostino: As soon as a month. Sorry. Yeah, I meant to —
Tim Ferriss: As soon as a month.
Dr. Dominic D’Agostino: Yeah, it’s analogous to the fasting mimicking weight loss plan. I believe Valter Longo can try this. He advises sufferers primarily based on, situationally, their scenario. However I encourage Fred to do it each month. And his suggestions to me was that he would do it as soon as each month to 2 months. He loved doing it, so it was one thing that he form of appeared ahead to doing.
Tim Ferriss: Sardine quick. I can’t anticipate that to grow to be a factor. That’s going to unfold. I don’t need to gloss over what you personally do. So for you, as an example, I discovered lately — and everyone get your checkups. Don’t skip colonoscopies. Don’t skip. In my case, I acquired an endoscopy as a result of I used to be having some bother swallowing each now and again. I assumed it was like, ah, possibly it’s identical to I’m consuming too shortly with dried hen or one thing. And suffice to say, placing that apart, that was kind of the symptom that catalyzed it.
However I ended up having very unexpectedly a hiatal hernia. Hiatal, I believe additionally associated to the phrase hiatus etymologically. I’m going to get the definition incorrect, I’m positive. However principally out of your esophagus to your abdomen, usually there’s a pleasant form of sphincter or ring, and principally the abdomen is form of pushed out of that ring. And there’s really a whole lot of scarring in my throat from acid. And so I used to be informed that possibly not this bluntly, however that places me at some elevated danger of throat most cancers or esophageal most cancers, some sort of most cancers.
And I used to be like, “Shit, that’s not usually what kills folks in my household. Normally it’s the cardiac stuff.” And I really feel like I’ve that. My lipid profile may be very nicely beneath management, which is why going again and doing analysis for this dialog, and I’ve additionally completed fasting over time, I’ve thought, “Okay, nicely, along with taking the proton pump inhibitors and the whole lot in order that I’m not accumulating extra scarring, is there a spot for doing the fasting, since I don’t thoughts doing it anyway? Simply to additional hopefully lower the chance.”
And also you had been saying you quick episodically, was that the phrase that you just used?
Dr. Dominic D’Agostino: Yeah. Situationally, episodically.
Tim Ferriss: Situationally. Situationally. What does that imply?
Dr. Dominic D’Agostino: If my spouse is touring and it prevents me from being delinquent and I’ve a whole lot of work to do, and I’ve a grant deadline that’s 5 days away, okay, I’m beginning fasting for 5 days till I get this grant submitted. If I’m touring on my own, I’ll do it. Often I’ll get kind of an inflammatory flare up and I don’t know what it’s — I’ll really feel somewhat bit off like mind fog or my joints or one thing like that. It’s fairly uncommon now as a result of my HSCRP is like non-detectable, proper? Earlier than I did, it was all the time one or two on a better carb weight loss plan.
Tim Ferriss: So folks may acknowledge CRP, proper? I imply, C reactive protein is a marker of irritation. I imply, should you get your annual blood check or no matter, chances are high it’s on there someplace.
Dr. Dominic D’Agostino: Yeah, I’d like to attract consideration to that actual fast as a result of HSCRP is a greater indicator of heart problems than LDL ldl cholesterol. We all know that now. If somebody stated that 10 years in the past, they’re identical to, “We predict you’re loopy.”
However yeah, HSCRP is what we name a cardio metabolic biomarker, together with triglycerides and insulin and issues that ought to be included. However that may be a actually necessary biomarker, I believe, to maintain low for Alzheimer’s and most cancers and all the opposite, I name it six horsemen. No. The issues that I discussed. However yeah, so often I’ll use it situationally simply if I really feel my physique, if I really feel like one thing is approaching, I’m getting a flu. However the sardine fasting is, and I counsel it for most cancers sufferers too. I would like them to keep away from a water-only quick within the context to forestall most cancers cachexia.
Tim Ferriss: Muscle loss or muscle losing.
Dr. Dominic D’Agostino: Yeah. And omega-3 fatty acids are very potent mitigators of most cancers cachexia. And so you’ve the omega-3s and principally you’ve the whole lot your physique wants, particularly nutrition-wise in sardines. You may need to add somewhat little bit of vitamin C or magnesium or one thing. However primarily it’s like you’ve enough diet and then you definately create a caloric deficit, you create caloric restriction, after which with caloric restriction come a complete host of useful issues. The protein’s low sufficient that you just’re suppressing insulin, mTOR, and possibly activating AMP kinase. And should you try this in a protracted manner and you may obtain a glucose ketone index of 1 to 2 for about three to 5 days, that the constellation of issues that should you measure that will correlate with inducing and maximizing autophagy. In order that was the rationale for me to try this. Lots of people discuss autophagy and it’s form of a nebulous time period. We measure it. We have a look at the autophagosome. So we’re a lab that really does have a look at issues like that. There’s p62 and different issues that you could measure, however there’s no commercially obtainable — I believe one of the best ways to measure to counsel you’re in autophagy is a glucose ketone index after a interval of fasting.
Tim Ferriss: Which Keto-Mojo will do mechanically. It’ll do the calculation for you. I did have a fast query.
After I in contrast my Keto-Mojo to an oral glucose tolerance check the place I used to be having blood drawn each half-hour, the glucose readings I acquired from the Keto-Mojo had been considerably greater than the blood check, than the blood draw itself and I used to be questioning if that’s one thing you’ve noticed. I imply, who is aware of? Possibly it’s a foul system. Possibly I had an excessive amount of alcohol nonetheless on the finger and I didn’t dry it correctly. I imply, who the hell is aware of? Possibly it doesn’t matter a lot, but it surely appears to matter as a result of common spikes above a sure nanogram per deciliter appear to be indicative of all kinds of issues. Have you ever run into any points with the system or any caveats associated to particularly the glucometer aspect? What I do like that’s good about it’s it does offer you that glucose ketone index, the GKI as a readout proper there on the system or within the app no less than that accompanies the system.
Dr. Dominic D’Agostino: Are you speaking about measuring glucose at the very same time level {that a} phlebotomist pulled blood.
Tim Ferriss: That’s precisely what I’m speaking about. Yep.
Dr. Dominic D’Agostino: Okay. What was the distinction between what was measured there?
Tim Ferriss: Let’s say the height at half-hour out after ingesting this not-so-delicious dextrose water. It’s one thing like this. I used to be bumped as much as in all probability 140 on the phlebotomist drawn blood and it was like 165 on the Keto-Mojo. The return was a lot sooner and a lot better on the phlebotomist drawn blood than it was on the Keto-Mojo system, which to not throw them beneath the bus. It may very well be operator error or only a single dangerous system. I’ve buddies who’ve used it very efficiently on the ketogenic weight loss plan, which is why I ended up shopping for it as a result of Precision Xtra is form of a ache within the ass to come up with, no less than on Amazon. In order that was my expertise and I used to be like, “Okay. Effectively, tough, tough, tough,” as a result of if I’m actually attempting to not pop above a sure stage, if the system I’m utilizing each day is 20 factors above the place possibly it ought to be, then that’s an issue.
Dr. Dominic D’Agostino: What’s your hemoglobin A1C?
Tim Ferriss: I’d have to return and look. It’s trending down, however I must return and look.
Dr. Dominic D’Agostino: In the event you put on a CGM, you’re beneath possibly 100 with the CGM. So the meters are likely to development somewhat bit excessive, about 10 % excessive. I believe they had been 10 to twenty. Keto-Mojo was 10 % greater than our assays, and the Precision Xtra was 20 % greater than the assays that we do once we pulled blood from the animal. So if that helps, I believe you need to in any respect. You need to have a look at your insulin ranges, your hemoglobin A1C, hs-CRP.
Tim Ferriss: Yeah, we acquired all of it. Only for folks, public service announcement, do an oral glucose tolerance check, ask your physician, speak to them, get your insulin measured, as a result of my relations metabolic dysfunction was missed for a really very long time, partially as a result of they had been taking a look at fasting glucose. You may get actually fortunate with fasting glucose relying on once you get that snapshot and the docs weren’t nice to start with who had been monitoring these relations, however as quickly as we checked out OGTT, the oral glucose tolerance system, insulin, oh my God, it was like sky-high out of vary.
Dr. Dominic D’Agostino: Or put a CGM on them. That’s what motivated me to be, I suppose, one of many first advisors for Ranges. I’ve labored with them on a analysis entrance. I believe you’ve interviewed Sam, proper?
Tim Ferriss: Yeah.
Dr. Dominic D’Agostino: However Ranges, I imply, that’s —
Tim Ferriss: Yeah, Sam Corcos.
Dr. Dominic D’Agostino: Yeah, Sam. I imply, that’s like the last word form of metabolic optimization platform. I imply, there’s others rising too, however merely carrying — I imply, now they’ve the Stelo system that got here out, so CGM’s are over-the-counter now, however the analytics from that and in addition the biomarkers that should you’re a part of that program that you could measure, which embody many issues that we might discuss, however that will seize your relations in case your relations put a CGM on. That’s actually necessary, however what you noticed is fairly regular and to not in all probability be of concern, like your —
Tim Ferriss: Yeah. Okay. Cool. Yeah, I simply needed to test it out. Simply to tie this up for me, and I possibly simply missed it, if somebody is utilizing ketones on a continuous foundation, are there long term variations? A part of the explanation I’m asking is that in the latest set of experiments, let’s simply say, I used to be strict keto for 3 weeks, after which frankly simply acquired uninterested of the weight loss plan.
Dr. Dominic D’Agostino: It’s onerous.
Tim Ferriss: Yeah, I did three weeks of let’s simply name it form of textbook — protein additionally fairly low, like 10 to fifteen % let’s say, so possibly I bump it up subsequent time, however simply acquired so bored of it after three weeks, however I need to do sufficient that there may be some improve of the metabolic equipment. We might discuss that as a result of I do know for athletes it may be like six months to 12 months, however went from that to then 16:8 intermittent fasting, nonetheless in ketosis for possibly every week, so 16 hours off consuming between, let’s say, 2:00 p.m. and 10:00 p.m. Then I went to a extra paleo-ish weight loss plan, let’s simply name it, inside that feeding window. Then I did that for just a few weeks after which began layering in exogenous ketones in my fasting state, usually 11:00 a.m., 1:00 p.m. if I’m doing podcast recordings and issues like that.
A part of what I’m attempting to determine is given I’m APOE3/4, scared to loss of life of Alzheimer’s, and possibly there’s nothing to be completed about it, but when there’s something to be completed along with train rights and kicking out the Klotho and BDNF and all that great things, from a dietary perspective, attempting to determine, okay, how lengthy does keto reminiscence final if there may be an expiration date? In the event you had been in my footwear, how you’ll take into consideration not simply the exogenous ketones, however fasting and ketogenic weight loss plan? Do you’ve any ideas on that?
Dr. Dominic D’Agostino: Effectively, yeah, you’re doing a whole lot of stuff there, and I might advocate following a protocol that you could possibly do day in and time out that ought to ideally nearly be easy and mesh along with your schedule, which can be variable if in case you have podcasts and issues like that. I’m of the opinion that you could possibly comply with a baseline weight loss plan, which is a low-carb Mediterranean-like weight loss plan. Mediterranean is form of a fuzzy time period, I hate it, however low-carb Mediterranean model weight loss plan that primarily retains biomarkers in verify after which situationally going the ketosis from time to time to simply optimize it. However you need to comply with an method therapeutically that retains your GKI into that one to 4 vary. Tom Seyfried may be very adamant about one to 2, however the regular GKI of an individual within the US is like 50, or 25 to 50.
So simply residing in a state of getting a GKI of even 5 could be, I believe, trending in direction of being extra metabolically versatile and having higher fats oxidation. Then you definately need to, because it sounds such as you’re doing, simply maintaining verify of your metabolic biomarkers, so complete metabolic panel, CBC, after all, should you’re utilizing completely different brokers on that, however insulin HSCRP, hemoglobin A1C, triglycerides, ApoB you need to measure too, Lp(a) it’s good to know.
Sadly, 30 % of individuals — that is in all probability necessary when navigating what protocol to make use of. I’ve a mutation. I did GB HealthWatch, which checked out my genetics for dyslipidemia. So GB HealthWatch, Dr. Spencer Nadolsky reached out to me as a result of I used to be posting my numbers on-line and he was like, “Hey, it’s worthwhile to do that check.” He’s a really sensible, aggressive or proactive form of man and prompt this check. He’s like, “I believe you’re a hyperabsorber.” I used to be like, “Isn’t one % of the inhabitants hyperabsorber?” However come to seek out out about 30 % of the inhabitants hyperabsorb ldl cholesterol.
Tim Ferriss: That’s me too. I’m in the identical boat.
Dr. Dominic D’Agostino: Okay. I’ve an NPC1L1 receptor mutation that’s a gain-of-function mutation. I take advantage of an ezetimibe monotherapy for that. Ezetimibe was bought as Zetia, and I can get by with half of a pill, which is 5 milligrams, and half my ApoB. It put my ApoB — it reduce it in half, and in addition half my LDL. So I can comply with a ketogenic weight loss plan. I had the skyrocketing LDL ApoB, however then I put that again in verify. I’m of the opinion that I would like extra information to come back out. There’s a bunch of those who assume LDL within the context of optimum metabolic biomarkers that it’s to not be involved about, however that information is rising and there’s teams of those who I imagine are credible after which engaged on that entrance, wanting on the lipid power mannequin. With the lipid power mannequin, LDL and ApoB is a provider for fats to peripheral tissues, however we don’t must go there.
Tim Ferriss: Dodge it for now.
Dr. Dominic D’Agostino: Yeah. In case your LDL pops up, then a pescatarian Mediterranean-like weight loss plan that’s low-carb that’s ideally beneath 100 grams of carbohydrates per day, and that’s no sugar, no starch, fibrous greens and fruits. So my rule of thumb is 25 % of what carbohydrate you eat ought to be fiber, after which that’ll primarily make it non-glycemic, proper?
Tim Ferriss: What proportion did you say?
Dr. Dominic D’Agostino: What I do personally is about 50 to 100 grams of carbs a day and guaranteeing that the carbohydrates that you just’re consuming, about 25 % of that carbohydrate is fiber, so for instance, broccoli, asparagus, after all, cauliflower, inexperienced, leafy greens, however even fruits, I development in direction of wild blackberries, raspberries, blueberries, and purchase them together. Then wild blueberries are about half the scale they usually have extra fiber, much less sugar, so I’ve a cup of that per day. My carbs come from principally broccoli, wild berries, darkish chocolate, and possibly just a few different odds and ends.
Tim Ferriss: The place do you get wild berries? Is that one thing you purchase or do it’s a must to exit and steal out of your neighbor’s patch?
Dr. Dominic D’Agostino: Effectively, yeah, we have now a blueberry — surprisingly, blueberries develop nice in Florida — however we have now a blueberry farm proper by us. It’s a vineyard, in order that they develop blueberries after which make blueberry wines and issues like that and have big festivals, however we get from there. However yeah, you’ll be able to go to Walmart and get the Walmart blueberries, that are the scale of grapes. Then subsequent to that, now Costco and Sam’s and even Walmart now have the wild blueberries.
Tim Ferriss: No kidding? Okay. Simply since you talked about LDL, I may be hallucinating this, so please appropriate me if I’m, however didn’t you at one level dramatically reduce down your LDL labs by swapping dairy out, I believe possibly heavy cream and utilizing coconut cream or one thing else as a substitute, or am I making that up?
Dr. Dominic D’Agostino: I took out heavy cream, however put bitter cream again in, however possibly about half of the bitter cream, but additionally simply switched out the eggs. I believe the eggs had been attending to me as a result of eggs have a whole lot of ldl cholesterol, and I used to be consuming a dozen a day.
After I put together my meals within the morning, my canine get my meals. So I’ll make 10 eggs, however I’ll have three yolks, after which I divide the opposite yolks between my two canine. Then as an alternative of floor meat, which I used to be consuming a whole lot of, I get chub mackerel. I do sardines, often tuna fish, however I get instances of chub.
Tim Ferriss: Chubb just like the insurance coverage firm, C-H-U-B-B? No. How do you spell that?
Dr. Dominic D’Agostino: Yeah, C-H-U-B. Not like a king mackerel, that are greater, chub mackerel are small fish.
Tim Ferriss: Yeah, don’t bioaccumulate as a lot rubbish or —
Dr. Dominic D’Agostino: Yeah. In order that they’re actually low on the heavy metallic listing, which I are likely to verify as a result of I eat a lot of it. One can is sort of a pound, and there’s three fish in every. I take a fish and provides my two canine every a fish. It’s acquired a whole lot of fatty water in it filled with omega-3s, and I pour that on their meals they usually find it irresistible.
Tim Ferriss: The place do I signal as much as be reincarnated as one in all your canine?
Dr. Dominic D’Agostino: Yeah, this morning they acquired — my spouse has an Audacious canine complement, so we give them a — that’s acquired spirulina, ketones and some different issues. We give them that, creatine monohydrate.
Tim Ferriss: Maintain on, I can’t skip over that. Why give ketones to your canine?
Dr. Dominic D’Agostino: Yeah. Effectively, the brain-boosting results, the anti-inflammatory results, the neuroprotective results, and the anti-cancer results, so these are all issues I fear about with my canine. They’re fastened. I do give them a SARM, surprisingly, after they acquired injured.
Tim Ferriss: That is an anabolic, proper?
Dr. Dominic D’Agostino: I do, yeah. I transitioned. They acquired attacked by a giant pit bull they usually form of immobilized for some time. I used to be going to make use of it for a most cancers cachexia examine, and it’s ostarine, I believe. So I began giving it to them and it looks as if they’re leaner, stronger. We’ve a Nice Dane that’s 12 years outdated. That makes him 90 to 100 human years, and he runs 35 miles per hour. He has no signal of slowing down.
Tim Ferriss: What?
Dr. Dominic D’Agostino: Yeah, he’s a Nice Dane that ought to have handed away years in the past and he’s identical to a machine.
Tim Ferriss: You talked about Audacious Vitamin. Only for the needs of transparency, you do have household within the enterprise concerned with Audacious, proper? Simply to verify?
Dr. Dominic D’Agostino: Yeah, I can’t have any firm. I don’t promote something personally, however my spouse determined to create a product that used the ketones that we really utilized in analysis. So it advanced out of that was numerous salts, and the concept was that if that product was created, then we will use it for analysis. And that was the preliminary half.
Tim Ferriss: Cool.
Dr. Dominic D’Agostino: I used to be utilizing it anyway. I used to be like, “Effectively, why don’t you simply make a product out of this? I can’t do it.” Nevertheless it really was an I-Corps NSF program by the college that acquired that began.
Tim Ferriss: Query, do you give rapamycin to your canine or to your self. Do you presently take or give your canine rapamycin?
Dr. Dominic D’Agostino: I’ve gone forwards and backwards. I comply with Matt Kaeberlein’s work fairly carefully and travel. I’ve determined to not simply due to the immune suppression. I do know I acquired a few handful of those who use it, and I might say half of them get sores within the mouth. That may’t be factor.
Tim Ferriss: That’s tremendous, tremendous frequent, the mouth sores.
Dr. Dominic D’Agostino: Yeah. The info’s too early for that. I believe the identical factor may be achieved in a higher — a much bigger lever could be sardine fasting for one factor and simply beta-hydroxybutyrate and well-formulated low-carb supplemented ketogenic weight loss plan, by definition, a weight loss plan that elevates ketones and train, so train and a complete host of different life-style issues. I’m not prepared to drag the rapamycin set off on my — something I do with my canine, excluding the SARM, I haven’t used that, however seeing the results and taking a look at their blood work, it appears good. So there are not any uncomfortable side effects with that and it appears to be serving to with their superior age.
Tim Ferriss: Can you are taking only a paragraph, clarify what this SARM refers to for folks?
Dr. Dominic D’Agostino: Yeah, there’s a particular androgen receptor modulator that hits the androgen receptor however doesn’t have the androgenic-like qualities.
Tim Ferriss: It’s not going to present you a 3rd Adam’s apple, but it surely’ll assist with muscle development.
Dr. Dominic D’Agostino: It helps to stimulate skeletal muscle protein synthesis, after which the context of this drug additionally bone metabolism. Each of our male canine are fastened too. We’ve discussions with numerous vets which are of the opinion — they’re extra progressive that your canine ought to be on like TRT or testosterone in the event that they’re fastened, as a result of that can improve the standard of their life, particularly as they age. Our canine look — I can’t detect any lack of skeletal muscle mass even after I have a look at photos —
Tim Ferriss: For readability, your canine are all male?
Dr. Dominic D’Agostino: Yeah, we have now two male canine and each of them are thought-about superior age, and the black Lab is displaying it somewhat bit. He has {hardware} in his two again legs. We had two knees put in with him, however he was somewhat bit heavier and now we’ve dropped his weight with what I feed him now, which is actually fish, meat, eggs, ketones, and we give him a mushroom complement. That’s a mushroom form of lion’s mane and a reishi, possibly cordyceps and some different issues, after which I give them creatine monohydrate. Yeah, they’re fairly optimized as canine. I believe the large factor is that we stay on a farm they usually get a whole lot of exercise too. They get two non-negotiable walks on daily basis. I try this for me too. That’s a part of my artistic downtime is to do a non-negotiable stroll morning and evening. In order that they get a whole lot of that they usually chase our animals round too.
Tim Ferriss: What are your present emotions on — let’s simply say on the sardine quick, once you’re doing a week-long sardine quick, and possibly you’re so tailored at this level that you just don’t expertise this, however actually after I’ve completed water fasts, and even when I’m following a decrease calorie ketogenic weight loss plan, I can have a very robust time sleeping, no less than for a handful of days, proper? I’ve simply fast coronary heart price. I don’t know if that’s attempting to compensate for decrease blood stress as a result of I’m simply dropping a lot water and electrolytes. Who is aware of? I’ve discovered supplemental electrolytes to assist a bit with that. However what sort of supplementation do you are taking or advise folks take if they’re attempting a ketogenic weight loss plan for the primary time or fasting? Possibly the solutions are completely different. Let’s simply say it’s a sardine quick like, man, Valter Longo coming for you with a sardine quick. What supplementation makes this simpler or extra productive simply from an adaptation perspective?
Dr. Dominic D’Agostino: Yeah, I’ll use sardines and in addition KetoStart, which is actually the electrical sodium, potassium, calcium, magnesium, beta-hydroxybutyrate and that will probably be used two to a few occasions per day. At nighttime, once you go along with a caloric deficit, your sympathetic nervous system is activated somewhat bit, particularly with the water-only quick, so that you get somewhat bit hyper or dysphoric even for some folks.
Tim Ferriss: Yeah, I really feel such as you simply ran up three flights of stairs once you’re attempting to fall asleep. Yeah, it’s disagreeable.
Dr. Dominic D’Agostino: Yeah. Yeah. In order that’s much less with a sardine fasting as an alternative of zero energy. So the sardines would then be eaten at nighttime usually. I bear in mind doing this repeatedly, and what I might do is take somewhat little bit of GABA at evening, and on one or two fasts I took simply 25 milligrams of diphenhydramine.
Tim Ferriss: I believe that’s the precise or near the precise dose of 1 or two Benadryl, proper? I’d have to take a look at it, however isn’t diphenhydramine Benadryl?
Dr. Dominic D’Agostino: Yeah, diphenhydramine is — yeah, it’s a histamine. It’s tends to be lipophilic, which suggests once you take diphenhydramine, it shortly crosses the blood-brain barrier. You possibly can be somewhat bit groggy the subsequent morning. The research present that fifty milligrams of diphenhydramine can lower reminiscence recall if taken acutely, however 25 milligrams, there’s no impact of that. I’m comfy with taking 25 milligrams of diphenhydramine at evening after which giving a lecture the subsequent day within the morning. I really feel razor sharp and since additionally it enhances — it reduces sleep latency, so I get higher sleep, however I might not use it greater than as soon as a month or one thing. Yeah, I do assume diphenhydramine and these over-the-counter sleep aids used each evening by numerous folks which are emailing me, I imply, it’s creating dementia, I believe. I imply, the information’s fairly clear on that. You’ve an older particular person getting 50 milligrams each evening, each week is dangerous.
So melatonin, magnesium, a small dose, I suppose for my dimension, it could be a half dose of diphenhydramine, after which GABA. So you could possibly take GABA within the type of GABA that you could get over-the-counter, or there’s additionally phenibut GABA, which I’ve however are likely to haven’t used shortly.
Phenibut I might simply need to put on the market is usually a actually nasty drug for folks. It may very well be addictive. You construct a tolerance actual quick, and coming off of phenibut may be very problematic for folks. I imply, it’s like coming off of GHB, I believe, but it surely may very well be a instrument within the toolbox as a result of — I imply, we’re speaking about taking two, three grams of phenibut may give you euphoria.
It’s like a benzodiazepine, form of, however should you take 250 milligrams or 200 milligrams of phenibut, which is a small dose — I imply, theoretically, you could possibly take that two or 3 times per week and by no means actually construct a tolerance or get, however I might not advise folks to try this. However should you’re going to quick, say, as soon as a month, one option to avert that, and I get the identical actual factor, I get tremendous hyper and my mind simply goes on fireplace after I do the primary day of fasting, somewhat little bit of GABA or phenibut, diphenhydramine, magnesium. I’ve all the time completed melatonin, 5 to 10 milligrams of melatonin.
Tim Ferriss: Oh, that’s a strong dose.
Dr. Dominic D’Agostino: Yeah, we went on trip and I forgot it.
Tim Ferriss: Do you continue to use melatonin frequently? As a result of I bear in mind there was some dialog floating across the ether and by no means appeared too carefully into it as a result of I don’t use melatonin on a regular basis about some chance of endocrine disruption, or are you able to communicate to that?
Dr. Dominic D’Agostino: Yeah, I’ve been utilizing melatonin in all probability after I began utilizing creatine in 1993, the outdated phosphagen after I was in highschool.
Tim Ferriss: Again within the day.
Dr. Dominic D’Agostino: Yeah. Yeah.
Tim Ferriss: Yeah. EAS is that manner again within the day?
Dr. Dominic D’Agostino: I used to be a beta tester for that. Yeah, I used to be a beta tester when phosphagen got here out. Then 1993, I believe I began utilizing creatine. I used to be an early adopter of creatine. However to get to your query in melatonin, I studied melatonin on the hippocampus on mind slices. You possibly can slice the mind like a bit of bread and utilized melatonin, checked out reactive oxygen species and issues like that. We used it for oxygen toxicity. It wasn’t good for that as a result of it did make the rats sleepy. Melatonin doesn’t actually make me sleepy, it makes me extra calm than anything. I went on a trip the place I forgot melatonin and I slept like a child in all probability as a result of I used to be up each morning. The solar is the last word circadian synchronizer. I acquired off of melatonin to verify my endogenous melatonin, and there was no suppression. Melatonin in animals which are hibernating, like little gerbils and issues like that, should you give them melatonin, it might suppress endocrine operate together with testosterone manufacturing.
Huberman talked about it. I really like Huberman. So I used to be following him and he was speaking about melatonin. So I went to the first literature and I used to be like, “Man, he’s proper. It’s an endocrine disruptor and suppressor.” However then I dug into the literature extra and it was not the case for people. So there was no proof in human. I believe when he talks about it, I don’t assume he references a human examine, however he does reference legit research. Yeah, Andrew Huberman is an incredible scientist and he places out superior info on the market, but it surely did get me involved about it. So I acquired off of melatonin, after which I confirmed that my physique does make regular quantities of melatonin, so I measured that. I additionally confirmed that 5 milligrams of melatonin, if I am going and measure the subsequent day, my melatonin is off the charts, which means that I take 5 milligrams at evening, the subsequent day within the morning at 9 o’clock or 10 o’clock within the morning, my melatonin is tremendous physiological.
Tim Ferriss: Is that good or dangerous?
Dr. Dominic D’Agostino: I believe it’s good. So I take melatonin to not sleep, however as a neuroprotective agent that has a complete host of useful results for the mind, additionally Alzheimer’s illness and in addition most cancers, particularly breast most cancers. So, use it for that. I additionally mega-dosed 20 or 30 milligrams after which checked my LH and FSH.
Tim Ferriss: Milligrams?
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Okay. Yeah. 20 to 30 milligrams.
Dr. Dominic D’Agostino: 10 milligram tablets are just like the gorilla tablets for melatonin. So I chewed a bunch of them after which held it beneath my tongue and I didn’t actually really feel any extra sleepy. I simply slept like regular. My aura ring was regular. However then I went and I acquired lab work completed and I did testosterone, LH, FSH, and there was no suppression. Truly, my LH and FSH had been trending excessive finish of regular, which is one other subject that I can get into. However the factor is that it didn’t set off an endocrine response in me. I don’t assume there’s any information in people, though particular animals are very delicate to melatonin, and should you give it to them, it might trigger endocrine suppression, some intercourse hormones. So it’s a hormone. Yeah.
Tim Ferriss: Yeah. Okay. All proper. Effectively, that’s good to know as a result of I really profit from taking melatonin, however I largely reduce it out due to a few of the murmurs, but it surely does assist me sleep. Is that this a real assertion that you don’t do any fasting presently or recurrent pure water fasting, however as an alternative do that situational sardine fasting? I imply, is that kind of 99 % of the bang for the buck and there isn’t actually any cause to transcend one thing like that as a fast-mimicking weight loss plan, or are there advantages that you just assume are compelling of doing a extra restrictive, say, water-only quick the place you’re allowed black espresso and some different issues maybe, however are in any other case actually not consuming energy?
Dr. Dominic D’Agostino: For me, personally, it’s very context dependent. I used to be speaking to somebody the opposite day that was getting shingles. As quickly as the primary signal of tingling, which is the precursor of getting shingles, they begin fasting and it by no means really surfaces. So solely once they situationally pull the set off and begin water-only fasting does it fully mitigate — it’s a massively efficient countermeasure for herpes simplex flares or issues like that.
Tim Ferriss: Yeah, I used to be going to ask, I don’t know something about shingles, so what’s occurring there? Do endogenous ketones, and due to this fact, might you simply take a bunch of pictures of exogenous ketones, or what’s really occurring to have that suppression?
Dr. Dominic D’Agostino: I believe we’re augmenting metabolic management of immune regulation within the context. You’ve the innate immune system, which is all the time form of operating round. Then analysis work we’re doing now with the Moffitt Most cancers Heart is principally utilizing ketone metabolic remedy to enhance the adaptive immune system. So the adaptive immune system is extra particular. It’s form of like that B-cell and T-cell, augmenting the B-cell and T-cell, issues the place it’s just like the adaptive immune system is just like the Navy SEALs of — there was a human examine that used a vegan weight loss plan versus a ketogenic weight loss plan, and this acquired placed on my radar by quite a few individuals who then needed to analysis this. A vegan weight loss plan really augments and enhances the innate immune system and a two-week ketogenic weight loss plan, and this was printed in Nature Medication, augmented the adaptive immune system and partly by the intestine and partly simply by altering metabolic physiology. This occurs once we quick. If we’re fasting, our intestine is stress-free. I believe it’s restoring or stopping. After we eat one thing, we have now issues going into circulation that’s maintaining our immune system form of energetic, proper? So if we’re not consuming something, our immune system turns into hypervigilant after which in a manner that it turns into hypervigilant to assault issues, however on the similar time, it’s suppressed.
So inflammatory markers go down and since the immune system is like a military, you’ve 100 thousand guys in a military within the immune system they usually’re all working should you’re consuming and also you’re careworn and environmental toxins and issues like that. After we quick, we allocate extra of that immune system to be extra vigilant to assault issues. However on the similar time, our normal irritation state goes down. It turns into extra vigilant, however inflammatory cytokines, chemokines form of go down.
So I believe that’s a part of it in that it’s stimulating, I believe cancer-specific immunity but additionally simply usually suppressing irritation. And that’s occurring for a variety of completely different causes. Partly on account of elevating beta-hydroxybutyrate, which is an endogenous metabolite that performs a job in inflammasome suppression.
So I do know guys, possibly Eric Verdin and like the blokes on the Buck Institute, that they had form of taking a look at that. After which our colleagues, Dr. Deep Dixit at Yale, kind of formulated a weight loss plan to particularly elevate BHB as a result of he had confirmed beforehand that fasting suppresses the NLRP3 inflammasome and the metabolite that’s off the charts with beta hydroxybutyrate. So the subsequent examine was giving that as a complement with a traditional weight loss plan to see if that would then additionally suppress the inflammasome and it did. And that was printed in Nature Medication, 2015.
So I formulated the weight loss plan for that examine and I’m a center creator on that. So I believe that performs a job in that. However I believe it’s multifactorial and I believe it’s simply one in all this stuff that must be studied as a result of it’s form of universally accepted. It’s form of occurring, however you additionally must be in , wholesome state.
In case your dietary standing is low, it depends upon your baseline traits, your therapeutic response to fasting, and I believe that’s actually necessary, particularly for individuals who have most cancers, possibly getting chemotherapy the place they’ve compromised dietary state in some methods, then it’s a must to method it very cautiously.
Tim Ferriss: What number of meals per day do you eat now? How outdated are you, Dom, at this level?
Dr. Dominic D’Agostino: 50s. Yeah. I simply turned —
Tim Ferriss: Yeah. 50s.
Dr. Dominic D’Agostino: In my 50s. Yeah.
Tim Ferriss: All proper. Effectively, congrats. What does your weight loss plan seem like now? Simply form of the set it and neglect it model of Dom’s weight loss plan. What does that seem like?
Dr. Dominic D’Agostino: Yeah. It’s situational, however all the time in all probability three meals per day that I do and I did —
Tim Ferriss: And also you weigh about how a lot at this level?
Dr. Dominic D’Agostino: I simply did a DEXA this weekend, really. I did a DEXA two weeks in the past and I did one other one after I acquired off creatine after which did one other one. So I simply hover proper at 218 to 220 and physique fats final was 9.4 so —
Tim Ferriss: Yeah. You bought some muscle to feed. All proper. So three meals a day. What does it seem like?
Dr. Dominic D’Agostino: This morning it was eggs and chub mackerel and that’s it. So principally simply protein and fats. And for lunch, I usually have beef, hen, or fish, often fish. Recently I’ve been consuming a David bar. So Peter despatched me a few of these and I’ve form of combined opinions about it. It pops up on the CGM somewhat bit, however I believe it’s form of an attention-grabbing route to enter. I take pleasure in them, they style actually good. So I’ve been doing that.
After which for dinner, we went out for Mexican the opposite evening and final evening hosted Mary Newport and often have beef, hen, or fish with a vegetable, like all the time broccoli. I’m an enormous fan of broccoli. It labored. I might eat three kilos of broccoli has no gasoline or bloating impact for me in any respect. So by some means my physique is simply broccoli. My physique loves broccoli, so our canine do too. So I give them somewhat little bit of that, salads, however often a few pound of beef, hen, or fish at dinner. In order that’s my massive meal.
Tim Ferriss: Wow.
Dr. Dominic D’Agostino: And over time we have now transitioned. As a substitute of consuming at 7:00, we eat at 5:00 — 5:00 or 5:30, so we eat earlier. After which I do bodily exercise after that. So if it’s squats or deadlifts, I’ve to do it earlier than I eat. However for urgent actions and exercise, I do after that. And I do farm work for an hour or two within the night after that.
And I usually have, each different evening, wine. So I’ll have a little bit of wine, decrease alcohol, non-sugar Dry Farm wines, which has lower than one gram of sugar. I might by no means drink wine with out doing a little form of exercise after. If wine at 9 o’clock after which attempt to go to mattress, I might by no means try this as a result of I see that on my aura. But when I do a glass of wine in some type of bodily exercise, we all the time do a night stroll. I believe I sleep higher, I believe.
I don’t do two glasses, however I simply do one glass. I do know the present consensus on alcohol is that it’s — however I might push again as a result of none of that’s particularly finding out wine. In the event you go to the research on wine, really, reveals as soon as, the primary one which got here up is definitely lowering most cancers danger.
After which I observed that after I take wine and measure my blood, it’s much less viscous. So wine additionally decreases platelet aggregation. So it makes your blood much less viscous. And that’s well-known. I noticed it and was like, “One thing’s occurring right here.” After which I went to PubMed and it’s really well-known. I didn’t understand it on the time that it decreases platelet aggregation, so much less potential for clotting, for stroke and issues like that.
So I believe that will issue into — we simply acquired again from Greece they usually had the ouzo and the whole lot, then we went to Sardinia. So we went to those blue zones they usually simply, at evening after their dinner, the males will do a shot of alcohol, often wine, however generally ouzo they usually’re all of their 90s and tons of, they’re within the blue zone. So it’s a common attribute. That’s my protocol.
Tim Ferriss: Effectively, there could also be a genetic element too. I bear in mind there was this e book that was like, Why French Girls Don’t Get Fats or one thing and manner again within the day, I bear in mind earlier than his passing, I used to be speaking to Charles Poliquin, he’s like, “Yeah, MTHFR.” He’s like, “That’s why. It’s not one of the different stuff within the e book.” And he talked about a few different issues, like, who is aware of? I believe —
Dr. Dominic D’Agostino: Yeah. Residing by the water, exercise, and social. So the social interplay might be the largest lever. I imply, I simply see them, they’re all out and about strolling round and yeah, that’s in all probability the largest lever. And getting solar. In order that they’re exterior within the solar, everyone, it’s multifactorial, but it surely doesn’t appear to be hurting them, let’s put it that manner.
Tim Ferriss: If somebody is, let’s simply say they need to check out the ketogenic weight loss plan, and positively they are going to observe, they’ll be like, “Wow. Dom doesn’t eat a whole lot of greens apart from a pound of broccoli at dinner — “
Dr. Dominic D’Agostino: I can tolerate that however I’ve, in all probability it comes out to 30 to 40 grams of fiber a day, which is fairly excessive, however that’s broccoli. And I often have a small apple too. Generally we have now apples after which a cup of untamed blueberries. So it comes out to about 30 grams. That’s possibly a better, generally 10 or 20 however I attempt to shoot for about 30 grams of fiber.
Tim Ferriss: Yeah. Bought it. Okay. If folks need to kickstart the ketogenic weight loss plan, any suggestions for getting over the hump at first? It will possibly generally have a little bit of a tough time earlier than they form of click on over. I’m undecided. For me, it’s like as soon as I’m above 1.2 millimolar I really feel completely superb. That’s simply me on a Precision Xtra. However for individuals who want to give it a shot and possibly haven’t given it a shot, any suggestions for novices?
Dr. Dominic D’Agostino: Yeah. I might do fasted low-intensity cardio. For me, that will simply be going for a protracted stroll. Waking up within the morning, and should you’re going to start out your ketosis experiment or no matter you’re doing that morning, getting out within the solar, staying nicely hydrated, you could possibly take MCT and in addition ketone electrolytes like KetoStart or one thing like that. After which that can ease the transition as a result of it takes a short while to your ketogenesis to ramp up on account of you bought to deplete liver glycogen and ramp up beta oxidation fats enzymes.
After which as ketones get into circulation, over the interval of a pair weeks, you’re going to upregulate the ketolytic enzymes, that are principally the enzymes and the tissues which are in a position to make the most of and leverage these ketones for power over time.
Tim Ferriss: How lengthy does that adaptation take, would you say?
Dr. Dominic D’Agostino: I don’t know if anybody has unambiguously answered this query in people, however in rodent fashions you could possibly see the MCT transporter, to not be confused with MCT oil, however the monocarboxylic acid transporter, now there’s one, two, three and 4. That protein is 50 % greater after two weeks in a rat, for instance.
I believe the purpose for most individuals is that should you begin fasting or ketogenic weight loss plan and to avert the keto flu, you need to hydrate, get in electrolytes and in addition elevate ketones as a lot as potential. And to try this with MCT, should you can tolerate it or ketone electrolytes. I might not be guzzling a ketone ester since you’re going to spike ketones up, you’re going to inhibit your personal ketone manufacturing, particularly if it’s a dose-dependent factor. However my recommendation could be low depth cardio, hydrate electrolytes, after which small quantities of ketone electrolytes with MCT. So MCT will stimulate your personal Ketone manufacturing too so it form of —
Tim Ferriss: Yeah. Now are you simply taking tablespoons of liquid MCT? Are you utilizing a powder and mixing it in? What do you personally do or what would you advocate?
Dr. Dominic D’Agostino: For the liquid, generally what I do if I’m consuming tuna fish, which is packed in water. I’ll pour the MCT on the tuna fish and stir it up after which ship it that manner. If I’m having espresso, I can put within the MCT powder within the espresso and blend that up and that will be 10, 20 upwards of 30 grams and work by Stephen Cunnane really confirmed that should you take MCT within the context of caffeine or espresso, you’ll be able to increase your ketone manufacturing by 20 or 30 %. So there’s a little bit of a ketogenic synergy once you ship caffeine with MCT. It’s stimulating lipolysis and in addition fats oxidation within the liver so that you’re ramping out —
Tim Ferriss: What sort of powder do you want to make use of?
Dr. Dominic D’Agostino: Individuals ship me issues however really the powder that I’ve is definitely, it’s Keto Brainz. It’s MCT powder, Alpha GPC theanine, and it has lion’s mane mushroom. So it goes beneath the model title of Keto Brainz, and that’s the MCT powder that I take advantage of. The bottom of it’s MCT, however then it has sprinkled onto that theanine, which has a pleasant calming impact, which in all probability good to make use of on the primary day of fasting. Alpha GPC, if I take an excessive amount of of it offers me a headache so I solely do one or two.
Tim Ferriss: Yeah. I acquired to watch out with Alpha GPC. I additionally get a headache.
Dr. Dominic D’Agostino: Yeah. Oh, actually? Okay.
Tim Ferriss: Yeah.
Dr. Dominic D’Agostino: So that you’re the primary one. I don’t know if I used to be creepy. However yeah, after I first acquired Alpha, after I first acquired Keto Brainz and did like six scoops and I used to be like, “Oh, my God. I acquired to have a foul headache.” However one or two scoops.
Tim Ferriss: I really like that your first go was six scoops. If I simply need it off the shelf, MCT oil, as a result of I really feel like there’s solely so many medicinal mushrooms that I can cram into my weight loss plan additionally, however no offense to the mushrooms, however I even have some attention-grabbing thought on a few of them further mushrooms. A few of them are very strongly antiviral and immunomodulatory. And so after I’ve talked to a variety of very credible mycologists, so like, “Yeah. It’s in all probability greatest to not take that stuff on daily basis. You need to cycle on and off.”
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: But when I simply needed MCT, for functions of journey, as a result of MCT liquid can create such a goddamn mess once you’re touring.
Dr. Dominic D’Agostino: And their pants too. Yeah.
Tim Ferriss: And in your pants too. And for people who find themselves novices don’t do creatine, caffeine and MCT oil out of the gate. You’ve acquired to show to your self that you could deal with that.
Dr. Dominic D’Agostino: Except you’re constipated.
Tim Ferriss: It depends upon the airplane. Yeah. What different simply MCT oil, powders may you advocate or have you ever used?
Dr. Dominic D’Agostino: Quest MCT powder. I believe you may get that in like CVS and Walgreens now too. And Amazon, simply the Nutricost. So I purchased simply straight up MCT. Additionally they have a C8 powder and I’ve examined each of them carrying a steady ketone monitor. And I noticed a pleasant elevation over time after which I mixed that MCT powder with KetoStart, and principally I used to be in ketosis for half the day. So simply dosing twice a day with that.
Tim Ferriss: I imply, I’m going to interrupt my very own guidelines right here, however I’ve completed sufficient check drives. I’m about to go to, not tremendous excessive altitude, however I’ll be coming from sea stage to about 8,000 toes on common and we’re going to be doing a whole lot of intense train. So possibly my morning dose of espresso, which I’m positive will probably be some shit on the spot espresso, but it surely’s going to style scrumptious once you’ve been freezing your balls off all evening, possibly I’ll add some KetoStart and MCT powder to that as a result of these could be simple to journey with I might think about.
Dr. Dominic D’Agostino: Tremendous simple. Yeah.
Tim Ferriss: I’m undecided how KetoStart tastes in espresso.
Dr. Dominic D’Agostino: No. No. Don’t try this. No. They’ve KetoSpike espresso. So Audacious Vitamin has KetoSpike cocoa, espresso and tea. So within the afternoon I don’t do caffeine after 12:00. So I’ll brew. I’ll simply boil sizzling water and simply put, and the KetoSpike espresso is an efficient Colombian espresso and it simply has the BHB electrolytes in it. So I’ve been doing that.
Tim Ferriss: Yeah. All proper. Cool. I’ll test it out. I’m simply attempting to determine, as a result of I went again by all of our conversations, which covers a whole lot of technical element as you’ll think about. And I’m simply questioning what you might be most enthusiastic about. And proper now, I imply, simply to volunteer this. I’m very desirous about neuroinflammation and the inflammasome, the interaction with the microbiome and the way the microbiome can seemingly affect or mediate a few of, as an example, the anti-seizure results of the ketogenic weight loss plan. In the event you do away with Akkermansia or just a few different strains.
Dr. Dominic D’Agostino: Yeah. Yeah.
Tim Ferriss: Lo and behold, doesn’t actually work. And I’m questioning if that applies to different, say, circumstances that metabolic psychiatry may be utilized for, like schizophrenia and others, I don’t know, however appears attention-grabbing as a query. What sorts of questions or initiatives or realizations, findings, something have captured your curiosity or pleasure lately?
Dr. Dominic D’Agostino: Yeah. I believe simply shortly go down the listing. Ketone metabolic remedy for most cancers, so is one. And we have now a reasonably complete overview that describes the framework for ketone metabolic remedy for glioblastoma, which is a most cancers that’s largely immune to the usual of care. So manner a lot to speak about. It was really like a 200 plus web page paper that was going to be submitted. And we needed to principally put a whole lot of information and issues as supplementary figures.
I believe there’s like six supplementary figures that inform particularly all of the completely different metabolic medication that concentrate on glucose, glutamine, GKI calculator and a whole lot of issues. So yeah, simply Google ketone metabolic remedy framework for glioblastoma and its open entry. In order that has stimulated analysis at completely different locations. However I’m enthusiastic about analysis that we’re doing with Moffitt Most cancers Heart, which is the biggest most cancers middle.
We’re one of many largest in Florida, a tier one most cancers middle the place we’ve acquired numerous initiatives, glioblastoma, possibly a breast most cancers, but additionally lung most cancers. So was particularly utilizing ketone metabolic remedy to enhance immune remedy, particularly the checkpoint inhibitors. And that has to do with what I described about ketone metabolic remedy, particularly beta hydroxybutyrate activating the adaptive immune system and making checkpoint inhibitors, which is a category of drug that’s, and CAR T remedy.
So now they really have a examine with CAR T remedy and checkpoint inhibitors. So ketones are likely to broaden the T-cells which are related to CAR T remedy. So simply form of enhancing that remedy. And with the checkpoint inhibitors, it tends to simply improve most cancers particular immunity that’s augmented by PD1 inhibitors. In order that they’re particularly finding out that.
So I’m enthusiastic about that. In order that’s on the most cancers entrance. After which we will bounce, if in case you have no questions, I might bounce to different, the Alzheimer’s, the metabolic psychiatry.
Tim Ferriss: Let’s speak, yeah, let’s discuss these. Let’s hop to the Alzheimer’s and metabolic psychiatry. Would like to dive into that as a result of it’s in entrance of thoughts for me. And simply as a, I’m undecided if I made this clear, doing the couple weeks of strict ketosis, segueing to a kind of 16/8 ketogenic weight loss plan after which shifting to form of a paleo-ish weight loss plan has produced a few of the greatest labs I’ve ever had and in addition the perfect oral glucose tolerance check that I’ve ever logged.
And from a temper stability standpoint, and I’m additionally for no less than the previous few weeks, supplementing with the monoester and a diester, the kind of Q-I-T-O-N-E. However all of these issues mixed, I’ve acquired to say, psychologically from the standpoint of sustained focus and temper, has been simply form of mind-blowing, to be sincere. So I’d love to listen to any and all ideas on Alzheimer’s metabolic psychiatry entrance.
Dr. Dominic D’Agostino: Yeah. So metabolic psychiatry, I might encourage folks to hearken to Chris Palmer who you, I form of put in your radar. I don’t know should you bear in mind. I despatched you the hyperlink to the metabolic —
Tim Ferriss: Yeah. Yeah. Yeah. Admire that.
Dr. Dominic D’Agostino: So I used to be like, “You’ve acquired to look at this, Tim. It’s going to vary kind of the panorama of psychiatry.”
Tim Ferriss: Yeah. I do not forget that was a recording from a convention, I imagine, the place he was interviewing one in all his sufferers on stage. Yeah.. I do not forget that.
Dr. Dominic D’Agostino: The Metabolic Well being Summit, which is a part of Metabolic Well being Institute, which is you may get academic credit by that. So yeah. We introduced Chris in and it was such a compelling story and he handled Matt Baszucki. So Matt Baszucki is the son of Jan and David Baszucki, as a result of he shortly went into sturdy remission.
Tim Ferriss: Who’re well-known from Roblox.
Dr. Dominic D’Agostino: Effectively-known from Roblox. Yeah. Type of billionaire philanthropists which are altering, really, finally possibly the usual of look after psychiatry. And I believe they single-handedly are funding metabolic psychiatry with Shebani Sethi, she’s at Stanford, Chris Palmer at Harvard, and I work with them carefully as an advisor. There’s no less than a dozen different institutes which are doing metabolic psychiatry analysis for schizophrenia, bipolar, main melancholy, anorexia nervosa, which is a psychiatric dysfunction that kills extra folks than some other dysfunction and a variety of various issues and anxiousness issues and alcohol use issues, alcohol withdrawal syndrome. In order that they’re doing analysis on that.
So with metabolic psychiatry, there’s a whole lot of pilot research, principally bipolar, taking a look at a variety of various issues, ADHD too. After which there’s apps which are rising like MetPsy, metpsy.com. That’s a collaboration with Dr. Ally Houston, he’s at Oxford and Georgia Ede who may be good to have on the present. She’s from Harvard psychiatrist. In order that app is extra of a complete app that comes with ketogenic remedy, but additionally life-style stuff after which teaching. So metabolic remedy teaching for psychological well being.
Tim Ferriss: How do you spell the title of the app?
Dr. Dominic D’Agostino: MetPsy is M-E-T-P-S-Y, proper? M-E-T-P — I’m attempting to assume.
Tim Ferriss: Yeah. Higher on the science than the branding, I suppose.
Dr. Dominic D’Agostino: Yeah. M-E-T-P-S-Y.com, MetPsy. So I believe they’ve their web site up. In order that they’re principally of their onboarding section. So they need to go stay fairly quickly. However I’d like so as to add that the Baszuckis, I do not forget that they’re funding a giant examine at Oxford proper now and the Baszuckis will match greenback for greenback any donation and spearheading kind of that. Utilizing the app and utilizing ketogenic therapies together with life-style therapies too.
So metabolic psychiatry is quickly rising in a quantity, and this ties into work we did. I suppose my spouse did. I used to be on the paper however she ran the examine. We had been doing seizure research with exogenous ketones, and probably the most efficacious one for this utility was the racemic ketone salts within the MCT. We had been gavaging them and he or she was —
Tim Ferriss: What does gavage imply?
Dr. Dominic D’Agostino: Oh, so it’s principally like tube feeding the animal. So as an alternative of blending the ketones in with the rat chow, they eat it. And so it’s taking a syringe and primarily based on the load of the animal, you pull within the quantity of ketone ester or this case, it was MCT and ketone salts. We did the esters too, and it did have an anxiolytic impact, anxiousness lowering impact.
And then you definately administer that to the animal and what we’re doing is we do seizure research, put them inside a hyperbaric chamber and we go two to a few occasions extra regular and it induces a seizure. However what we noticed once we put the animals in ketosis is that as an alternative of them attempting to chew us and kill us and never eager to be held, they had been very chill and calm.
So it was simply, “Effectively, that is nice. We are able to deal with the animals simpler and get them into the chamber with out them attempting to chew us.” And my spouse’s a behavioral neuroscientist and he or she was like, “Effectively, we should always do some behavioral research as a result of I believe there’s one thing right here.” So we did elevated plus maze. So on this case, the animals can go inside a closed little cave or it might come out into the open arm within the elevated plus maze, which is exploratory habits. They’re extra extroverted if they arrive out and extra introverted and form of like their worry response in the event that they go into the cave.
So we acquired outcomes that we printed. The title is like “Anxiolytic Impact of Ketone Supplementation.” We printed I believe three papers and confirmed the mechanisms and stuff too. In order that was an early paper over 10 years in the past, simply principally displaying that inducing acute ketosis with this formulation and doing the elevated plus maze produces an impact that was analogous to a dose of benzodiazepine.
Like should you have a look at, I don’t know, Xanax or different issues in elevated plus maze, it was like, yeah, 20 or 30 % extra time within the open arm. In order that they’re much less fearful to be in surroundings and making them extra like a social lubricant, possibly like Benzo or one thing. So it had that impact within the animals.
And once we have a look at the blood work and even take out the hippocampus within the mind, the degrees of GABA to glutamate are greater. After which in one other examine we did with Angelman syndrome, we appeared on the mechanism of that and there’s an enzyme referred to as glutamic acid decarboxylase, and a whole lot of anti-seizure medication form of goal that.
So the protein ranges had been greater, primarily displaying that your mind converts extra glutamate, which is anxiousness evoking, like wakefulness enzyme. It’s changing extra glutamate, which is excitatory to GABA, which is mind stabilizing. That’s like your chill, like alcohol.
Tim Ferriss: It’s what you are taking earlier than mattress. Yeah.
Dr. Dominic D’Agostino: Yeah. Yeah. In order that was, and a wide range of completely different research, we additionally checked out adenosine receptor signaling. That’s somewhat bit extra difficult to explain, however there’s a variety of completely different results contributing to that. So there’s a transparent rationale, I believe, for melancholy. In the event you do an FTG PET scan on somebody that’s depressed, it reveals glucose sort of metabolism.
One factor to say, I believe an necessary factor to say within the context of bipolar, you’ll be able to have a hyper glycolytic impact. And Dr. Iain Campbell from Edinburgh College has printed some elegant opinions and is doing a little work on that entrance in describing the analysis there. However I believe it’s necessary as a result of a few of the suggestions popping out, and I believe you even talked about too, when ketones get actually excessive, what we noticed, if ketones get too excessive, that may trigger an anxiogenic impact.
Tim Ferriss: Yeah. Get extra anxious.
Dr. Dominic D’Agostino: A candy spot, possibly one to 2. I wouldn’t go above three, in all probability 1.5 to 2 millimolar vary. That appears to be a stage of ketones that safely doesn’t produce a metabolic acidosis. So what we do see that once you get above three, it begins to vary blood pH.
So it appears to possibly overwhelm the respiratory and renal compensation and your kidneys put out by carb after which there’s respiratory and renal compensation that regulates your blood pH. However the animals that succumb to ketoacidosis and died from the ketone esters that we gave them in early research needed to do with that acidification of the blood.
So it was simply an amazing, so ketones are acidic and once you ship it into an ester type, there’s nothing to buffer that. Whenever you give a ketone salt, the electrolytes are form of like a buffer for that.
So you’ve the metabolic impact, you’ve the altering of the mind neuropharmacology, and in bipolar, you throw anti-epileptic medication at bipolar sufferers, and it’s largely ineffective. So it is smart {that a} ketogenic remedy would work for that.
And the neuroinflammation too. So issues that set off neuroinflammation, and that may very well be an infectious agent, that may very well be a virus, that may very well be T. Gandhi. I imply, it may very well be like a micro organism. There’s numerous issues that would trigger psychiatric issues. Numerous infectious brokers create that neuroinflammation. So I believe neuroinflammation, after which when somebody has a seizure too, the inflammatory state of the mind will get a lot greater.
So I believe ketogenic therapies are working by a number of mechanisms, kind of in synergy to supply that. It’s not one mechanism. After we printed the NLRP3, I acquired requests from Genentech and numerous pharmaceutical firms to go there and provides a chat on the mechanism so they might drugify. And I might throw up a giant stream chart of all these mechanisms, and I believe they’d get annoyed. And it was like, “Effectively, inform us the mechanism so we will make a drug out of this.”
However I believe the fantastic thing about ketogenic therapies is that it’s pleiotropic, proper? Which implies it’s many mechanisms working in synergy. You possibly can say Metformin, GLP1 medication are working by metabolism, they usually’re form of pleiotropic additionally.
Tim Ferriss: Do you employ both of these?
Dr. Dominic D’Agostino: I’ve experimented with metformin, and that may be a manner for some sufferers to extend their ketone ranges. So we’ve printed on metformin from the context of that it will increase mitochondrial oxidative stress, so it’s a weak toxin to ship. Most individuals didn’t know that once we had been finding out that. And I believe metformin can improve, improve AMP kinase, possibly improve insulin sensitivity and has a really weak impact at lowering blood glucose if in case you have a traditional glucose. Nevertheless it does have a tendency to extend ketones somewhat bit.
And I believe there’s about 150 research on clinicaltrials.gov proper now on metformin, as a method to enhance most cancers remedy. So I believe that may very well be a instrument within the toolbox for some folks. After I take it, and I do actually intense — if I do an intense exercise, I felt sick. A problem with metformin is it might produce lactic acidosis. It’s producing lactic acidosis as a result of it’s a weak — it’s a toxin to the liver, so it’s de-energizing the liver. But additionally after I took it as much as two grams per day, I had a photosensitivity. So after I went exterior, the solar gave me a rash.
Tim Ferriss: You talked about in your wrists.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Am I making that up? Yeah.
Dr. Dominic D’Agostino: Yeah, it tended to correlate with that. After which I acquired off of it. Then I experimented with it once more and it tended to be — on the start — I’m in Florida and it was Might. It’s like when the solar’s actually beginning to crank. Then I simply go exterior all day and it’s like, “The place is that this rash coming from?” So it’s a photosensitivity response that I acquired and that considerations me. So I’ve it, however I don’t use it.
Tim Ferriss: Might I ask you a fast query simply associated to metformin for a second?
Dr. Dominic D’Agostino: Mm-hmm.
Tim Ferriss: Is I used to be wanting again on notes on prior conversations, and I believe you talked about Dale Bredesen on an episode of STEM-Speak. However particularly, for people with the APOE4 genotype, like yours actually, do you assume metformin could also be extra attention-grabbing? However let’s assume in my case, let’s name me metabolically wholesome. So possibly sure, possibly no. I bear in mind a very long time in the past having a chat with Nav Chandel, I need to say, I may be getting the title barely incorrect, from Northwestern. He was like, “Ah, should you’re doing a bunch of train and getting your weight loss plan straight,” he’s like, :I don’t assume that you just’re going to see a whole lot of profit.” However he didn’t have the APOE4 info on me. After which berberine I’ve written down for some cause. I’m simply questioning if there’s something to both of these for APOE4 particularly?
Dr. Dominic D’Agostino: Yeah, berberine is fairly much like metformin’s glucose decreasing impact. In order that’s one thing that you could think about should you don’t need to take metformin. I’m of the opinion that for the overall inhabitants, consuming a normal American weight loss plan that’s averse to figuring out and simply attempting to essentially modify their weight loss plan, metformin I believe is a really probably efficient drug for longevity. It’s going to cut back blood glucose, since most individuals are pre-diabetic, or have sort 2 diabetes which are of their 40s, 50s, and 60s. And it’ll scale back your incidence of most cancers, particular sorts of cancers like pancreatic most cancers. I believe the information’s good on that, and I believe it’ll shift metabolic biomarkers that we have now traditionally good information on in the correct route.
Tim Ferriss: Does metformin do something that taking a GLP-1 like tirzepatide or one thing doesn’t do? I’m simply questioning if it’s an additive impact.
Dr. Dominic D’Agostino: Effectively, they’re completely completely different medication. However individuals who take metformin and one gram to 2 gram dose, two grams is excessive. However once they try this, they have a tendency to eat much less energy. So it does create —
Tim Ferriss: I see.
Dr. Dominic D’Agostino: Somewhat little bit of, for me, GI points. Possibly somewhat little bit of free stools at first, and that may very well be factoring in there. So it does have a tendency to enhance metabolic biomarkers throughout the board should you’re trending in direction of metabolic dysregulation or metabolic syndrome. A GLP-1 works primarily by caloric restriction and simply growing urge for food by partially, a gentle gastroparesis and lowering gastric emptying time. But additionally works on the mind, and I believe has a variety of useful results. I believe it’s a game-changing drug that’s going to vary the entire panorama of metabolic therapies. And I believe —
Tim Ferriss: Yeah, appears to have a — from what I’ve learn, and possibly I don’t need to over interpret right here, however potential neuroprotective results, proper?
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: In order that’s the primary cause I might be taking a look at probably low-dose GLP-1.
Dr. Dominic D’Agostino: Yeah, I just like the low dose. I like that you just preface it with low-dose as a result of I believe greater doses aren’t studied sufficient long-term to avert potential uncomfortable side effects that we don’t learn about.
Tim Ferriss: Yeah. And do you are taking berberine or is it superfluous due to the weight loss plan, you don’t really want something to decrease glucose?
Dr. Dominic D’Agostino: Yeah, I’ve experimented with it and it did lower my glucose in response to a meal. I did dihydroberberine, which is a stronger model of berberine. However curiously, after a few week, I began to get a headache. After which I acquired off — I don’t know if it has a vasodilate or possibly it impacts liver metabolism in a manner that was — who is aware of? Possibly lowering my caffeine metabolism. These are issues that come to thoughts. I’m a quick metabolizer of caffeine.
Tim Ferriss: Yeah, you continue to eat fairly a little bit of espresso. Yeah?
Dr. Dominic D’Agostino: I do. I fill this up. So that is Metabolic Thoughts. Truly, Metabolic Thoughts is a part of the Baszucki’s Group metabolic psychiatry. So I’ve —
Tim Ferriss: All proper. So that you’re holding up —
Dr. Dominic D’Agostino: I do one in all these per day. Yeah.
Tim Ferriss: What’s that? That’s like 16 to twenty ounces, one thing?
Dr. Dominic D’Agostino: 24. I take into consideration 24 ounces.
Tim Ferriss: 24 ounces.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Yeah. Okay. It’s metallic. It appears like a thermos, principally.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Okay, acquired it.
Dr. Dominic D’Agostino: Comparatively sturdy espresso. I try this and pour one cup, and I often end it about now and no caffeine. Yeah, caffeine at 4 or 5:00 p.m. might be going to disrupt sleep latency and sleep timing. However yeah, GLP-1, wonderful class of drug. We’re overlaying that now at med college in our diet programs we’re instructing.
After which the SGLT-2 inhibitors are additionally a reasonably attention-grabbing class of drug that I believe has a whole lot of potential. So if somebody attempting to convey their glucose ranges down, for instance, attempting to get that — these are prescribed drugs. So after all, go to your physician. However that’s a reasonably good lever to drag, particularly if somebody’s immune to dropping their carbs, in the event that they’re consuming some carbs.
Tim Ferriss: Effectively, yeah.
Dr. Dominic D’Agostino: Yeah, GLP-1 and SGLT-2 are nice.
Tim Ferriss: Effectively, that is additionally a instrument within the toolkit with, let’s simply say aged sufferers who’re — even when they needed to conform, could not have the psychological school to adjust to ongoing. And you’ll’t have, essentially, 24/7 supervision to forestall them from consuming bagels. Which possibly you are able to do. Simply all of the meds within the morning after which one injection every week or no matter it may be. Do you are taking any dietary supplements or medicines with the specific purpose of mitochondrial well being or possibly simply the aspect impact of mitochondrial well being?
Dr. Dominic D’Agostino: Yeah. Effectively, I believe ketones shine there. The D, each the D and the L, beta-hydroxybutyrate. In order that’s before everything. And we’re doing analysis with NAD.
Tim Ferriss: These injectables?
Dr. Dominic D’Agostino: I can’t speak concerning the analysis that we’re doing in depth. However we’re working with Metro Worldwide Biotech. In order that they have section two and section three trials for Alzheimer’s. So there’s NR, nicotinamide riboside, nicotinamide mononucleotide. So the issue with these is that the liver is fairly grasping and takes a whole lot of that. After which the muscle groups are — so a whole lot of it’s possibly not attending to the mind.
But when folks simply Google MIB-626, in order that’s one in all their drug types of NAD, that’s a stabilized type of NAD. After which they’ve a complete suite of NAD molecules that most individuals don’t learn about, however are in experimental trials. And we’re doing a few of these preclinical animal mannequin work in our labs. So I do assume — for sure functions, we didn’t see an impact. However on the similar time, they’re — for functions like non-alcoholic fatty liver illness, possibly Alzheimer’s, possibly inflammatory issues, enhancing. If used for a protracted time frame, markers of mitochondrial well being I believe enhance. So NAD, folks could know NAD is principally a substrate for the sirtuins and numerous enzymes. There’s 500 completely different enzymes. So a category of proteins which are referred to as sirtuins rely closely on NAD. So this is a crucial factor to contemplate.
Tim Ferriss: And this sirtuin is only for of us who’re like, “Have I heard that earlier than?” I need to say again within the day when resveratrol was in all places within the information and tremendous mouse and all it’s a must to do is drink wine, however possibly 20 instances of wine. All of that stuff with trans-resveratrol, that’s the place the sirtuins popped up?
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Yeah.
Dr. Dominic D’Agostino: The sirtuins are actually closely reliant on NAD. And NAD is concerned in the whole lot that we examine. So 5 to 600 metabolic enzymes want NAD for gasoline. In order that’s necessary to contemplate. And DNA restore is solely tied to NAD ranges. So bear in mind I discussed reductive stress with D-beta-hydroxybutyrate?
Tim Ferriss: Yeah.
Dr. Dominic D’Agostino: Reductive stress implies that the NAD to NADH ratio would drop. So that you get extra NADH relative to NAD. That may very well be problematic as a result of the provision for NAD will not be there for sirtuins and different — so a redox stability formulation.
Tim Ferriss: I see.
Dr. Dominic D’Agostino: In order that feeds again. I don’t need to get too far into that, however I believe it’s impacting the redox stability, which is getting us to revisit the varied ketogenic formulations and to check this, in cell-based programs, animal fashions. It’s onerous to do in people. You possibly can do a 31-phosphorus MRS if in case you have a 4 or 7-Tesla system like Harvard has. So that is a method to take a look at like phosphocreatine, ATP, pH, and in addition NAD to NADH ratios. So that is a method. Truly, we do have that at our Alzheimer’s middle, and that’s on the listing of to-dos, to take a look at this reductive form of stress factor.
So NAD, I’m simply throwing that on the market. I believe there’s a whole lot of criticism in direction of NAD now. That occurs occasionally. As a result of shifting science from cell-based programs to animal fashions to people, there’s an enormous studying curve there. We’re studying that with a few of the ketogenic brokers. We’re simply on the cusp of actually understanding the dosage, timing, scheduling and type of exogenous ketones that’s optimum. And it’s going to differ dependent upon the scenario that you just’re attempting to deal with. And likewise individually, I believe persons are going to have. In order that opens up this complete customized precision ketogenic metabolic remedy, or the NIH is throwing some huge cash on customized medication primarily based on genetic markers, and primarily based on biomarkers that a few of them that you could measure in actual time. Like steady ketone monitoring, steady glucose, and possibly lactate monitoring.
Tim Ferriss: That’s cool. Yeah, that’s very cool. One final complement query as a result of I’m wanting again at previous notes. And I’m in all probability going to mispronounce this. However idebenone, extra observable model of CoQ10. Possibly that’s a good description. Possibly it isn’t. Do you continue to take that or now not?
Dr. Dominic D’Agostino: Yeah, I believe CoQ10 is on the brief listing of 5 dietary supplements that I might advocate to folks. Though I don’t take it, I do get fairly a bit from the meals that I eat. I eat a whole lot of coronary heart, liver, animal merchandise which have CoQ10 in it. However should you’re on a statin, should you’re on metformin and different medication, they might probably deplete you. After which CoQ10 has a strong monitor document for cardiovascular well being. So idebenone is a drug stabilized type of that. After which after I mentioned that in your podcast, that was within the context of one thing referred to as the Deanna Protocol. The Deanna Protocol is after Deanna Tedone. She has ALS, she was identified nicely over a decade in the past, was given two or three years to stay. She’s alive and nicely at this time, we’re simply emailing me yesterday. So Deanna Tedone had superior ALS after which has been stabilized utilizing the Deanna Protocol, which is included on the time, idebenone. However I believe it turned a drug.
So idebenone turned the usual of look after Friedrich’s ataxia, and then you definately couldn’t get it on Amazon. However I believe ubiquinol, or CoQ10, it could be substitute for that. And I don’t use it myself. However I believe that’s should you’re older in age and you’ve got cardiovascular coronary heart issues in your loved ones. Nevertheless, with that stated, we really ubiquinol, we did excessive doses in our animal fashions, and we noticed some kidney toxicity. We had some animals die. And —
Tim Ferriss: Oh, Jesus. It’s like —
Dr. Dominic D’Agostino: However that was rodent fashions we used. Once more, we use actually excessive dose for oxygen toxicity. We’ve checked out the whole lot beneath the solar. Nevertheless it was this sudden aspect impact. Then I went to the literature and confirmed that it’s such a robust antioxidant in some methods, and it possibly was concentrating within the kidneys. So there was a few papers got here up, after which we expect that that’s why the animals could have died. We had been utilizing a MitoQ, like numerous types which are extra mitochondrial particular. We’re utilizing stronger types of the CoQ10. So it will not be much like the commercially obtainable types.
Tim Ferriss: What are the opposite dietary supplements on that brief listing? You stated 4 or 5 dietary supplements. What are the opposite ones?
Dr. Dominic D’Agostino: That I take. Yeah, so creatine monohydrate could be the staple factor that I’ve used since I used to be a young person. At the start, exogenous ketones, and the information is rising on that, I believe that’s going to be the subsequent creatine for that. However creatine, for Alzheimer’s illness, we didn’t discuss it. However a dosage of 10 to, even should you’re bigger, 20 grams. And that’s not a misspeak there, 20 grams of creatine. Unfold out possibly 5 grams, three to 4 occasions a day for superior Alzheimer’s, should you can tolerate it. [inaudible 02:20:12]
Tim Ferriss: I’m taking 20 grams at this time simply because I didn’t get superb sleep final evening. I simply discover it to assist with recovering from, let’s name it sleep deprivation. However yeah, acquired to look at the break up dosing.
Dr. Dominic D’Agostino: Yeah. Vitamin D, however it’s a must to measure that in your lab. So that you need that to be — you don’t need it over 100, proper? So that you need vitamin D ranges which are in all probability like 60 to 80, could be stage of vitamin D and getting that checked. However I believe you must verify it first. It’s bizarre. I stay in Florida, I get tons of solar. But when I’m not supplementing vitamin D, I development to be low 30s. It may very well be development — however so after I complement it, I principally keep within the mid-60s to 70s. So vitamin D and melatonin, I believe is a superb neuroprotective antioxidant complement to take at nighttime. And I don’t take omega-3 dietary supplements, however simply because I did — Rhonda Patrick related me with the omega-3 man and I attempted the OmegaQuant. My DHA ranges and EPA ranges had been off the charts.
Out of curiosity, I acquired off of fish for a month or so and it went right down to regular ranges. After which I attempted Nordic Naturals, which — it was an organization that reached out to me and I used to be like, “Okay, nicely, I’ll take away omega-3s from my weight loss plan after which add it again in with a dose.” And it popped me again as much as a stage much like if I’m consuming tons of sardines per day. So should you don’t like sardines and also you don’t like consuming a whole lot of fish, I believe Nordic Naturals might be one of many go-to manufacturers. I’m not paid to say that or something, however they’re legit. However you could possibly do the OmegaQuant check. I believe there’s a lot information on EPA and DHA that I believe finally, the omega-3 ranges will probably be a part of customary blood work. There’s a lot information rising on that, that I believe in all probability throughout the subsequent 10 years, once you get complete metabolic panel, CBC, DHA, and EPA will in all probability be added to that.
Tim Ferriss: All proper, Dom. Effectively, we might go for a lot of extra hours, I’m positive. However let’s begin to land the aircraft for this spherical. And I do need to ask, after all, if there’s anything that you just’d like to say or level folks to. Something you’d wish to advocate, formal complaints you’d wish to lodge? Individuals you’d wish to safe in entrance of a big viewers? No, I’m kidding. However something that you just’d wish to say or level folks to? Any sources, something that you just’re as much as, the place they will discover you? Something in any respect?
Dr. Dominic D’Agostino: Yeah, I simply need to point out KetoNutrition. That’s our informational web site, ketonutrition.org. And we’ve hosted a convention the place many individuals, Dr. Valter Longo, Rhonda Patrick, who’s been the keynote audio system, that’s the Metabolic Well being Summit. That’s been the convention, and that’s run by Metabolic Well being Initiative. So I direct folks to Metabolic Well being Initiative, and it’s run by three of us. My colleagues, Dr. Angela Poff and Victoria Discipline run that present. I tag on for the journey.
However that’s an ACCME, accredited medical schooling platform. So the whole lot that we’re speaking about right here, we have now audio system and we create a medical schooling platform, so folks can study metabolic psychiatry. Individuals can study metabolic primarily based therapies and metabolic medication, like GLP-1 medication and hormone optimization and issues like that. So I might point out that. The model of ketones that I take advantage of that I typically get requested is Audacious Vitamin KetoStart. In order that advanced out of our work with most cancers, neurodegeneration and seizures. We’re doing work at Byrd Alzheimer Heart on in all probability 20 or extra ketogenic compounds in improvement which are principally alcohol-free. So I believe all of them are literally. We’ve some actually attention-grabbing research on Alzheimer’s and a whole lot of different — so hopefully within the subsequent 12 months have the ability to share a few of that preclinical animal mannequin work. Hyperbaric oxygen, so we have now a 28 million examine —
Tim Ferriss: That’s big.
Dr. Dominic D’Agostino: On the College of South Florida. I’m simply peripherally concerned in that or simply know the folks operating that. And it’s primarily advanced out of the DOD work that appeared on the muddy waters of hyperbaric oxygen remedy for that. However I —
Tim Ferriss: It’s a great way to place it. The muddy waters.
Dr. Dominic D’Agostino: Yeah, I’ve been a part of reviewing grants and in addition manuscripts, and I believe there’s a whole lot of attention-grabbing research that’s going to emerge. By the point this airs, I believe they are going to be on PubMed. Primarily, displaying that hyperbaric oxygen remedy protocols, extra delicate hyperbaric oxygen at 40 to 60 classes, and those who had traumatic mind harm a decade in the past, can improve cognitive operate, response time, and all kinds of metrics related to mind operate. So I believe this work popping out of Israel, I want to see it replicated. I want to see — the work that’s completely different on the College of South Florida is that it’s very progressive and that it’s utilizing a sham.
As a substitute of utilizing hyperbaric air because the management, they’re utilizing — they principally pulse stress at first to make folks assume they’re being pressurized and on the finish, so their ears pop somewhat bit. And I don’t know each — it’s blinded. Individuals don’t know even what they’re getting. In the event you query them, they don’t know in the event that they’re getting hyperbaric oxygen. However I do assume that oxygen is a robust drug, and I’m enthusiastic about that analysis, should you ask me. I’m excited if it proves it or disproves it. I believe we’re going to get an unambiguous reply to this query about hyperbaric oxygen for a traumatic mind harm, and folks with and with out post-traumatic stress syndrome. So my factor is that in the event that they put sufferers on ketone metabolic remedy, that will increase and improve hyperbaric oxygen remedy, and reduce the potential for danger of an oxygen toxicity seizure, which works up. In the event you’ve had a traumatic mind harm, your danger of oxygen toxicity seizure would improve as a result of —
Tim Ferriss: Now, that is fairly particular to navy? Or what are we speaking about?
Dr. Dominic D’Agostino: Yeah, they’re all vets. And in the event that they do discover out that they get a useful impact from that, then after the experiment, they’ll have the ability to get that totally free service. So there’s six — like quarter to half 1,000,000 greenback hyperbaric chambers. So the onerous shell chambers, there’s six of them on this facility. And it’s probably the most elaborate hyperbaric oxygen remedy examine that has ever been completed. And it’ll reply the query concerning the efficacy. In order that’s ongoing now, and I’m enthusiastic about that. I’m additionally enthusiastic about probably utilizing that facility, as a result of it’s subsequent to the Moffitt Most cancers Heart for sufferers which are present process numerous most cancers therapies that may very well be enhanced with hyperbaric oxygen remedy. As a result of it augments the immune system and it’s really an FDA accredited utility for radiation necrosis. So should you’ve had radiation, then your insurance coverage would really cowl it. However it might improve sure therapies that we’re engaged on now. Yeah.
Tim Ferriss: Yeah. Superb.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: All proper. Effectively, we are going to hyperlink to all of these issues within the present notes as all the time. And I encourage folks to verify all of these out. I’m going to verify all of them out. And Dom, thanks a lot for the time, as all the time.
Dr. Dominic D’Agostino: Good to see you.
Tim Ferriss: I took a ton of notes. I’ve possibly much more questions on prime of that for extra textual content messages. Sorry prematurely. And so good to see you once more.
Dr. Dominic D’Agostino: Yeah. You too, Tim. Yeah, thanks for having me on. I recognize it.
Tim Ferriss: Yeah. Completely. And folk, present notes may be discovered at tim.weblog/podcast. Simply search Dom or Dominic and a whole lot of them will pop up. Simply search for the latest. And till subsequent time, be a bit kinder than is critical. It issues, it helps, to others and to your self. And as all the time, thanks for tuning in.
