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 Drugs 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 robust 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 Atmosphere Mission Operations. His analysis has been supported by the Workplace of Naval Analysis, the Division of Protection, the Nationwide Institutes of Well being, non-public 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 Drugs and Dentistry of New Jersey. He then accomplished postdoctoral coaching in Neuroscience at Wright State College’s Boonshoft College of Drugs in 2004 and at College of South Florida Morsani Faculty of Drugs in 2006.
Transcripts could comprise just a few typos. With many episodes lasting 2+ hours, it may be tough to catch minor errors. Get pleasure from!
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Dr. Dominic D’Agostino — All Issues Ketones, Easy methods to Defend the Mind and Enhance Cognition, Sardine Fasting, Weight-reduction plan 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 in touch right here and there with texting, however yeah.
Tim Ferriss: A lot of texts. And why not? This is without doubt one of the textual content threads I might most likely truly make public in my life with out some sort of mutually assured destruction with a lot of my pals.
I’ve been revisiting all the things ketogenic and definitely taking a look at exogenous ketones for various causes.
And one in all which we had been chatting somewhat bit earlier than recording, is that I’ve various family 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’d have doubtlessly a, let’s simply name it two and a half X, larger chance of growing one thing like Alzheimer’s, despite the fact that information would possibly change. Who is aware of?
Nonetheless, I’m seeking to throw as a lot doable at this from a preventative perspective. What information do we now have, and if there’s somewhat little bit of hypothesis of all them, wonderful with that too by way of future instructions for analysis and what would possibly come up for functions of, say, the ketogenic food 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 feel you’re conscious, we talked beforehand of the case studies which are on the market that acquired put this on all people’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: Typically 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 feel, and that was dropped at my consideration truly by Dr. Mary Newport and her husband, Steve Newport, was the topic truly 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 pricey to my coronary heart. I truly coincidentally hosted her for dinner final night time on the home and had her over right here. And he or she’s an in depth buddy of mine. We co-teach collectively at USF. She’s a visitor instructor.
Apparently, I noticed Steve Newport in 2008 or ’09, and I witnessed the commentary. 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 seemed 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 rapidly transitioned to that after assembly, however he was taking coconut oil and MCT oil. And he would carry 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 wonderful tremors once more. After which he would turn out 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 instances a day with meals.
In order that was my first commentary. And it was clear to me that there was not less than a metabolic — inside the Alzheimer’s spectrum, I similar to to — Alzheimer’s is sort of a fuzzy prognosis and —
Tim Ferriss: Positive. Very fuzzy.
Dr. Dominic D’Agostino: Yeah. And I similar 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 heart once we met. She was working below a man who studied tau. Then there was individuals 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 characteristic 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 potential to make use of glucose as an power supply decreases over time as a consequence of they thought perhaps 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 complicated, which is absolutely the governor or the speed limiter of glucose metabolism in neurons. That’s PDH, pyruvate dehydrogenase complicated.
And the manufacturing of — when you take 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 part. So all this stuff sort of contribute to metabolic dysregulation, but in addition an enormous driver is neuroinflammation.
And I do consider, as does Dr. Mary Newport, who’s the creator of that paper with a case report and various different leaders within the area, 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 most likely 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 arduous with that. But additionally individuals who have shingles that I feel they’re in danger too. We all know Epstein-Barr virus, you’re 4 or 5 instances extra threat for issues like MS. It’s triggering the immune system.
So I feel there’s a renewed curiosity in taking a look at Alzheimer’s illness, wanting on the root trigger. And I feel metabolism is central, however the metabolic hit that could be contributing to dysregulated metabolism and neuroinflammation might be an an infection. And I feel there’s accumulating proof for that. I used to be skeptical 10 years in the past, most likely, once we talked. Nonetheless, this stored placing on my radar. After which I used to be in an NIH sponsored workshop on this taking a look at varied features, and the information introduced by various totally different labs was very compelling for this.
So what does that imply? Our immune system is — there’s the 4 horsemen that our buddy Dr. Peter Attia talks about. I feel 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 plenty of longevity clinics are actually taking a look at that.
Tim Ferriss: What’s your most popular machine for measuring ketones as of late?
Dr. Dominic D’Agostino: For publications, we’ve used the Abbott Precision Xtra as a result of traditionally we’ve used that. Nonetheless, once I suggest a meter to individuals, I typically suggest the Keto-Mojo machine 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 now have 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 all the things else. However the Keto-Mojo constantly provides us numbers which are extra in keeping 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’ll inform me how ridiculous I’m in off base or fact-check as wanted. Are you able to remind me of tips on how to pronounce this Dr. Thomas? Is it Seyfried? Am I getting that proper?
Dr. Dominic D’Agostino: Yeah. He’s an excellent buddy 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, when you might, with out getting an excessive amount of within the weeds, however I’m questioning what the ketogenic food plan does that exogenous ketones don’t obtain? After which I’m questioning what fasting does that the ketogenic food 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 perhaps 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 doubtlessly purging precancerous cells and so forth, I used to be like, you recognize what? I just like the aesthetic apply — 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 feel there’s conditions the place I feel I’ll profit from fasting or from simply inducing a state of an power deficit. So you may do caloric restriction, time restricted feeding, dietary restriction. You may do a restricted ketogenic food plan, a cyclic ketogenic food plan, modified, a modified supplemented ketogenic food 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, truly his title was Dr. Fred Hatfield. So he was sort 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 pals. 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 stepping 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 carry him issues, and he was testing issues. And he liked sardines. So I feel he steered me onto sardines in perhaps 2007 or oh eight or one thing like that. In order that was my love for sardines was most likely from him.
However he would do low-carb. He referred to as it ketogenic, however I feel it was simply extra of a low-carb food plan. After which he would do 5 days, he would do a fasting mimicking food 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, perhaps one can of sardine per day for per week. So we referred to as it sardine fasting. And that was simply as I used to be stepping into this. And primarily what occurred is that he went into fast remission and the docs didn’t actually know. Fred ended up passing away perhaps eight years later of one thing utterly 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 suppose “Demise sentence.” Metastasized prostate most cancers, they suppose, “No approach, you’re completed.” Am I exaggerating? I imply, how frequent is it that individuals have full remission of one thing like that? Perhaps I’m exaggerating issues.
Dr. Dominic D’Agostino: Yeah, there’s a variety of components just like the Gleason rating and his was not good in various components. So he was given, I feel he informed me three months to reside, 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 appear to be?
Dr. Dominic D’Agostino: Yeah, he stayed ketogenic, after which I might go over there and encourage him to do this, and he liked to do it. He was like, “Okay, I do that and now I really feel higher once I’m doing it.” Fred additionally surprisingly, would smoke somewhat bit, and I acquired him to perhaps cease that too. So we acquired him to dial again on another behaviors and perhaps 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 food plan. After which for years, he did the sardine fasting and we communicated and I simply inspired, “Hey, maintain sending me your medical studies.”
And I used to be like, “Perhaps there’s something to this.” So that truly steered me into similar 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 outstanding tales. I steered him to the ketogenic food plan and it was a outstanding. He acquired off all meds and it labored approach higher than the meds. So Fred, however that was prostate most cancers. However then I began partaking with different sufferers after which linked with Thomas Seyfried quickly after that.
Tim Ferriss: How incessantly was Fred doing the week-long sardine fasts, when 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 food plan. I feel 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 sort of seemed ahead to doing.
Tim Ferriss: Sardine quick. I can’t watch for that to turn out to be a factor. That’s going to unfold. I don’t need to gloss over what you personally do. So for you, for example, I came upon not too long ago — and all people 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 hassle swallowing each now and again. I assumed it was like, ah, perhaps it’s similar to I’m consuming too rapidly 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 feel additionally associated to the phrase hiatus etymologically. I’m going to get the definition fallacious, I’m positive. However mainly out of your esophagus to your abdomen, sometimes there’s a pleasant sort of sphincter or ring, and mainly the abdomen is sort of pushed out of that ring. And there’s truly a variety of scarring in my throat from acid. And so I used to be informed that perhaps not this bluntly, however that places me at some elevated threat of throat most cancers or esophageal most cancers, some sort of most cancers.
And I used to be like, “Shit, that’s not sometimes what kills individuals in my household. Often it’s the cardiac stuff.” And I really feel like I’ve that. My lipid profile may be very effectively below management, which is why going again and doing analysis for this dialog, and I’ve additionally completed fasting over time, I’ve thought, “Okay, effectively, along with taking the proton pump inhibitors and all the things 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 danger.”
And also you had been saying you quick episodically, was that the phrase that you simply 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 variety 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. Sometimes 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 at all times one or two on a better carb food plan.
Tim Ferriss: So individuals would possibly acknowledge CRP, proper? I imply, C reactive protein is a marker of irritation. I imply, when you get your annual blood take a look at or no matter, likelihood is 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 similar 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 feel, 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 need them to keep away from a water-only quick within the context to stop 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 have got the omega-3s and mainly you have got all the things your physique wants, particularly nutrition-wise in sardines. You would possibly need to add somewhat little bit of vitamin C or magnesium or one thing. However primarily it’s like you have got satisfactory diet and you then create a caloric deficit, you create caloric restriction, after which with caloric restriction come an entire host of helpful issues. The protein’s low sufficient that you simply’re suppressing insulin, mTOR, and possibly activating AMP kinase. And when you try this in a protracted approach and you’ll obtain a glucose ketone index of 1 to 2 for about three to 5 days, that the constellation of issues that when you measure that might correlate with inducing and maximizing autophagy. In order that was the rationale for me to do this. Lots of people speak about autophagy and it’s sort of a nebulous time period. We measure it. We take a look at the autophagosome. So we’re a lab that truly does take a look at issues like that. There’s p62 and different issues that you may measure, however there’s no commercially accessible — I feel one of the simplest ways to measure to recommend 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.
Once I in contrast my Keto-Mojo to an oral glucose tolerance take a look at the place I used to be having blood drawn each half-hour, the glucose readings I acquired from the Keto-Mojo had been considerably larger than the blood take a look at, 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? Perhaps it’s a nasty machine. Perhaps 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? Perhaps it doesn’t matter a lot, nevertheless it 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 machine or any caveats associated to particularly the glucometer facet? What I do like that’s good about it’s it does provide you with that glucose ketone index, the GKI as a readout proper there on the machine or within the app not less than that accompanies the machine.
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 most likely 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 machine, which to not throw them below the bus. It might be operator error or only a single unhealthy machine. I’ve pals who’ve used it very efficiently on the ketogenic food plan, which is why I ended up shopping for it as a result of Precision Xtra is sort of a ache within the ass to come up with, not less than on Amazon. In order that was my expertise and I used to be like, “Okay. Effectively, difficult, difficult, difficult,” as a result of if I’m actually making an attempt to not pop above a sure degree, if the machine I’m utilizing day after day is 20 factors above the place perhaps 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 below perhaps 100 with the CGM. So the meters are inclined to development somewhat bit excessive, about 10 % excessive. I feel they had been 10 to twenty. Keto-Mojo was 10 % larger than our assays, and the Precision Xtra was 20 % larger than the assays that we do once we pulled blood from the animal. So if that helps, I feel you need to in any respect. You need to take a look at your insulin ranges, your hemoglobin A1C, hs-CRP.
Tim Ferriss: Yeah, we acquired all of it. Only for individuals, public service announcement, do an oral glucose tolerance take a look at, ask your physician, speak to them, get your insulin measured, as a result of my family metabolic dysfunction was missed for a really very long time, partly 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 family, 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 assume, one of many first advisors for Ranges. I’ve labored with them on a analysis entrance. I feel 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 sort of metabolic optimization platform. I imply, there’s others rising too, however merely carrying — I imply, now they’ve the Stelo machine that got here out, so CGM’s are over-the-counter now, however the analytics from that and in addition the biomarkers that when you’re a part of that program that you may measure, which embody many issues that we might speak about, however that might seize your family in case your family put a CGM on. That’s actually necessary, however what you noticed is fairly regular and to not most likely 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 perhaps simply missed it, if somebody is utilizing ketones on a continuous foundation, are there long run 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 bored stiff of the food plan.
Dr. Dominic D’Agostino: It’s arduous.
Tim Ferriss: Yeah, I did three weeks of let’s simply name it sort of textbook — protein additionally fairly low, like 10 to fifteen % let’s say, so perhaps 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 speak about 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 perhaps per 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 food 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, sometimes 11:00 a.m., 1:00 p.m. if I’m doing podcast recordings and issues like that.
A part of what I’m making an attempt to determine is given I’m APOE3/4, scared to loss of life of Alzheimer’s, and perhaps 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 good things, from a dietary perspective, making an attempt to determine, okay, how lengthy does keto reminiscence final if there’s an expiration date? In the event you had been in my footwear, how you’d take into consideration not simply the exogenous ketones, however fasting and ketogenic food plan? Do you have got any ideas on that?
Dr. Dominic D’Agostino: Effectively, yeah, you’re doing a variety of stuff there, and I might suggest following a protocol that you may 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 may comply with a baseline food plan, which is a low-carb Mediterranean-like food plan. Mediterranean is sort of a fuzzy time period, I hate it, however low-carb Mediterranean fashion food plan that primarily retains biomarkers in test 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 dwelling in a state of getting a GKI of even 5 can be, I feel, trending in direction of being extra metabolically versatile and having larger fats oxidation. Then you definately need to, because it sounds such as you’re doing, simply retaining test of your metabolic biomarkers, so complete metabolic panel, CBC, after all, when you’re utilizing totally 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 most likely 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, you could do that take a look at.” He’s a really sensible, aggressive or proactive sort of man and advised this take a look at. He’s like, “I feel 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 exploit an ezetimibe monotherapy for that. Ezetimibe was offered 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 food plan. I had the skyrocketing LDL ApoB, however then I put that again in test. I’m of the opinion that I want extra information to return out. There’s a bunch of those that suppose 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 that I consider are credible after which engaged on that entrance, wanting on the lipid power mannequin. With the lipid power mannequin, LDL and ApoB is a service for fats to peripheral tissues, however we don’t need to go there.
Tim Ferriss: Dodge it for now.
Dr. Dominic D’Agostino: Yeah. In case your LDL pops up, then a pescatarian Mediterranean-like food plan that’s low-carb that’s ideally below 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 making certain that the carbohydrates that you simply’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 perhaps 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 important to exit and steal out of your neighbor’s patch?
Dr. Dominic D’Agostino: Effectively, yeah, we now have a blueberry — surprisingly, blueberries develop nice in Florida — however we now have a blueberry farm proper by us. It’s a vineyard, so that they develop blueberries after which make blueberry wines and issues like that and have large festivals, however we get from there. However yeah, you possibly can 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 feel perhaps 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 perhaps about half of the bitter cream, but in addition simply switched out the eggs. I feel the eggs had been attending to me as a result of eggs have a variety of ldl cholesterol, and I used to be consuming a dozen a day.
Once I put together my meals within the morning, my canines 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 canines. Then as a substitute of floor meat, which I used to be consuming a variety 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. In contrast to a king mackerel, that are larger, chub mackerel are small fish.
Tim Ferriss: Yeah, don’t bioaccumulate as a lot rubbish or —
Dr. Dominic D’Agostino: Yeah. So that they’re actually low on the heavy metallic listing, which I are inclined to test as a result of I eat a lot of it. One can is nearly a pound, and there’s three fish in every. I take a fish and provides my two canines every a fish. It’s acquired a variety 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 canines?
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 canines?
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 mounted. 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 an enormous pit bull they usually sort of immobilized for some time. I used to be going to make use of it for a most cancers cachexia research, and it’s ostarine, I feel. So I began giving it to them and it looks as if they’re leaner, stronger. We now have 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 similar 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 truly utilized in analysis. So it developed out of that was varied salts, and the thought 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 truly was an I-Corps NSF program by the college that acquired that began.
Tim Ferriss: Query, do you give rapamycin to your canines or to your self. Do you at the moment take or give your canines rapamycin?
Dr. Dominic D’Agostino: I’ve gone backwards and forwards. I comply with Matt Kaeberlein’s work fairly intently and trip. I’ve determined to not simply due to the immune suppression. I do know I acquired a couple of handful of those that use it, and I might say half of them get sores within the mouth. That may’t be an excellent factor.
Tim Ferriss: That’s tremendous, tremendous widespread, the mouth sores.
Dr. Dominic D’Agostino: Yeah. The info’s too early for that. I feel the identical factor will be achieved in a larger — a much bigger lever can be sardine fasting for one factor and simply beta-hydroxybutyrate and well-formulated low-carb supplemented ketogenic food plan, by definition, a food plan that elevates ketones and train, so train and an entire host of different way of life issues. I’m not prepared to tug the rapamycin set off on my — something I do with my canines, excluding the SARM, I haven’t used that, however seeing the results and taking a look at their blood work, it seems to be excellent. So there aren’t any unintended effects with that and it appears to be serving to with their superior age.
Tim Ferriss: Can you’re taking only a paragraph, clarify what this SARM refers to for individuals?
Dr. Dominic D’Agostino: Yeah, there’s a selected androgen receptor modulator that hits the androgen receptor however doesn’t have the androgenic-like qualities.
Tim Ferriss: It’s not going to provide you a 3rd Adam’s apple, nevertheless it’ll assist with muscle progress.
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 canines are mounted too. We now have discussions with varied 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 mounted, as a result of that can enhance the standard of their life, particularly as they age. Our canine look — I can’t detect any lack of skeletal muscle mass even once I take a look at photos —
Tim Ferriss: For readability, your canines are all male?
Dr. Dominic D’Agostino: Yeah, we now have two male canines and each of them are thought of 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 sort of lion’s mane and a reishi, perhaps cordyceps and some different issues, after which I give them creatine monohydrate. Yeah, they’re fairly optimized as canines. I feel the massive factor is that we reside on a farm they usually get a variety of exercise too. They get two non-negotiable walks daily. I try this for me too. That’s a part of my artistic downtime is to do a non-negotiable stroll morning and night time. So that they get a variety 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 perhaps you’re so tailored at this level that you simply don’t expertise this, however definitely once I’ve completed water fasts, and even when I’m following a decrease calorie ketogenic food plan, I can have a extremely robust time sleeping, not less than for a handful of days, proper? I’ve simply fast coronary heart price. I don’t know if that’s making an attempt to compensate for decrease blood stress as a result of I’m simply shedding 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’re taking or advise individuals take if they’re making an attempt a ketogenic food plan for the primary time or fasting? Perhaps the solutions are totally 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 likely be used two to 3 instances per day. At nighttime, once you go together 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 individuals.
Tim Ferriss: Yeah, I really feel such as you simply ran up three flights of stairs once you’re making an attempt to fall asleep. Yeah, it’s disagreeable.
Dr. Dominic D’Agostino: Yeah. Yeah. In order that’s much less with a sardine fasting as a substitute of zero energy. So the sardines would then be eaten at nighttime sometimes. I keep in mind doing this repeatedly, and what I might do is take somewhat little bit of GABA at night time, and on one or two fasts I took simply 25 milligrams of diphenhydramine.
Tim Ferriss: I feel that’s the precise or near the precise dose of 1 or two Benadryl, proper? I’d have to have 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 rapidly crosses the blood-brain barrier. You may be somewhat bit groggy the following 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 snug with taking 25 milligrams of diphenhydramine at night time after which giving a lecture the following 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 suppose diphenhydramine and these over-the-counter sleep aids used each night time by varied individuals which are emailing me, I imply, it’s creating dementia, I feel. I imply, the information’s fairly clear on that. You may have an older individual getting 50 milligrams each night time, each week is unhealthy.
So melatonin, magnesium, a small dose, I assume for my dimension, it could be a half dose of diphenhydramine, after which GABA. So you may take GABA within the type of GABA that you may get over-the-counter, or there’s additionally phenibut GABA, which I’ve however are inclined to haven’t used shortly.
Phenibut I might simply need to put on the market generally is a actually nasty drug for individuals. It might be addictive. You construct a tolerance actual quick, and coming off of phenibut will be very problematic for individuals. I imply, it’s like coming off of GHB, I feel, nevertheless it might be a device 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, sort of, however when you take 250 milligrams or 200 milligrams of phenibut, which is a small dose — I imply, theoretically, you may take that two or thrice per week and by no means actually construct a tolerance or get, however I might not advise individuals to do this. However when 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 hearth once I do the primary day of fasting, somewhat little bit of GABA or phenibut, diphenhydramine, magnesium. I’ve at all times 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 regularly? As a result of I keep in mind there was some dialog floating across the ether and by no means seemed too intently 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 most likely once I began utilizing creatine in 1993, the outdated phosphagen once I was in highschool.
Tim Ferriss: Again within the day.
Dr. Dominic D’Agostino: Yeah. Yeah.
Tim Ferriss: Yeah. EAS is that approach 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 feel 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 may 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 most likely 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 test my endogenous melatonin, and there was no suppression. Melatonin in animals which are hibernating, like little gerbils and issues like that, when you give them melatonin, it may possibly suppress endocrine operate together with testosterone manufacturing.
Huberman talked about it. I 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 feel when he talks about it, I don’t suppose he references a human research, however he does reference legit research. Yeah, Andrew Huberman is an incredible scientist and he places out superior data on the market, nevertheless it 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’m going and measure the following day, my melatonin is off the charts, that means that I take 5 milligrams at night time, the following 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 unhealthy?
Dr. Dominic D’Agostino: I feel it’s good. So I take melatonin to not sleep, however as a neuroprotective agent that has an entire host of helpful 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 below 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. Really, my LH and FSH had been trending excessive finish of regular, which is one other matter that I can get into. However the factor is that it didn’t set off an endocrine response in me. I don’t suppose there’s any information in people, though particular animals are very delicate to melatonin, and when you give it to them, it may possibly 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 truly profit from taking melatonin, however I largely reduce it out due to among the murmurs, nevertheless it does assist me sleep. Is that this a real assertion that you don’t do any fasting at the moment or recurrent pure water fasting, however as a substitute do that situational sardine fasting? I imply, is that kind of 99 % of the bang for the buck and there isn’t actually any purpose to transcend one thing like that as a fast-mimicking food plan, or are there advantages that you simply suppose 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 truly surfaces. So solely once they situationally pull the set off and begin water-only fasting does it utterly 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 taking place there? Do endogenous ketones, and subsequently, might you simply take a bunch of photographs of exogenous ketones, or what’s truly taking place to have that suppression?
Dr. Dominic D’Agostino: I feel we’re augmenting metabolic management of immune regulation within the context. You may have the innate immune system, which is at all times sort of operating round. Then analysis work we’re doing now with the Moffitt Most cancers Middle is mainly utilizing ketone metabolic remedy to reinforce the adaptive immune system. So the adaptive immune system is extra particular. It’s sort 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 research that used a vegan food plan versus a ketogenic food plan, and this acquired placed on my radar by quite a few individuals who then needed to analysis this. A vegan food plan truly augments and enhances the innate immune system and a two-week ketogenic food plan, and this was revealed in Nature Drugs, 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 feel it’s restoring or stopping. Once we eat one thing, we now have issues going into circulation that’s retaining our immune system sort of lively, proper? So if we’re not consuming something, our immune system turns into hypervigilant after which in a approach that it turns into hypervigilant to assault issues, however on the identical time, it’s suppressed.
So inflammatory markers go down and since the immune system is like a military, you have got 100 thousand guys in a military within the immune system they usually’re all working when you’re consuming and also you’re pressured and environmental toxins and issues like that. Once we quick, we allocate extra of that immune system to be extra vigilant to assault issues. However on the identical time, our basic irritation state goes down. It turns into extra vigilant, however inflammatory cytokines, chemokines sort of go down.
So I feel that’s a part of it in that it’s stimulating, I feel cancer-specific immunity but in addition simply typically suppressing irritation. And that’s taking place for various totally different causes. Partially as a consequence of elevating beta-hydroxybutyrate, which is an endogenous metabolite that performs a job in inflammasome suppression.
So I do know guys, perhaps Eric Verdin and like the blokes on the Buck Institute, they’d sort of taking a look at that. After which our colleagues, Dr. Deep Dixit at Yale, kind of formulated a food 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 following research was giving that as a complement with a standard food plan to see if that might then additionally suppress the inflammasome and it did. And that was revealed in Nature Drugs, 2015.
So I formulated the food plan for that research and I’m a center creator on that. So I feel that performs a job in that. However I feel it’s multifactorial and I feel it’s simply one in all this stuff that must be studied as a result of it’s sort of universally accepted. It’s sort of taking place, however you additionally need to be in an excellent, wholesome state.
In case your dietary standing is low, it depends upon your baseline traits, your therapeutic response to fasting, and I feel that’s actually necessary, particularly for individuals who have most cancers, perhaps getting chemotherapy the place they’ve compromised dietary state in some methods, then it’s important 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 food plan appear to be now? Simply sort of the set it and neglect it model of Dom’s food plan. What does that appear to be?
Dr. Dominic D’Agostino: Yeah. It’s situational, however at all times most likely 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, truly. 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 appear to be?
Dr. Dominic D’Agostino: This morning it was eggs and chub mackerel and that’s it. So mainly simply protein and fats. And for lunch, I sometimes have beef, hen, or fish, normally fish. These days I’ve been consuming a David bar. So Peter despatched me a few of these and I’ve sort of combined opinions about it. It pops up on the CGM somewhat bit, however I feel it’s sort of an attention-grabbing path 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 night time and final night time hosted Mary Newport and normally have beef, hen, or fish with a vegetable, like at all times broccoli. I’m an enormous fan of broccoli. It labored. I might eat three kilos of broccoli has no fuel or bloating impact for me in any respect. So one way or the other my physique is simply broccoli. My physique loves broccoli, so our canines do too. So I give them somewhat little bit of that, salads, however normally a couple of pound of beef, hen, or fish at dinner. In order that’s my huge meal.
Tim Ferriss: Wow.
Dr. Dominic D’Agostino: And over time we now have 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 sometimes have, each different night time, 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 sort 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 at all times do a night stroll. I feel I sleep higher, I feel.
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 learning wine. In the event you go to the research on wine, truly, reveals as soon as, the primary one which got here up is definitely lowering most cancers threat.
After which I seen that once 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 happening right here.” After which I went to PubMed and it’s truly 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 feel which will issue into — we simply acquired again from Greece they usually had the ouzo and all the things, then we went to Sardinia. So we went to those blue zones they usually simply, at night time after their dinner, the males will do a shot of alcohol, normally wine, however generally ouzo they usually’re all of their 90s and a whole bunch, 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 part too. I keep in mind there was this ebook that was like, Why French Girls Don’t Get Fats or one thing and approach again within the day, I keep 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 ebook.” And he talked about a few different issues, like, who is aware of? I feel —
Dr. Dominic D’Agostino: Yeah. Dwelling 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 most likely the largest lever. And getting solar. So that they’re exterior within the solar, all people, it’s multifactorial, nevertheless it doesn’t appear to be hurting them, let’s put it that approach.
Tim Ferriss: If somebody is, let’s simply say they need to take a look at out the ketogenic food plan, and definitely they are going to word, they’ll be like, “Wow. Dom doesn’t eat a variety of greens aside from a pound of broccoli at dinner — “
Dr. Dominic D’Agostino: I can tolerate that however I’ve, most likely it comes out to 30 to 40 grams of fiber a day, which is fairly excessive, however that’s broccoli. And I normally have a small apple too. Typically we now have apples after which a cup of untamed blueberries. So it comes out to about 30 grams. That’s perhaps a better, generally 10 or 20 however I attempt to shoot for about 30 grams of fiber.
Tim Ferriss: Yeah. Bought it. Okay. If individuals need to kickstart the ketogenic food plan, any ideas for getting over the hump to start with? It could generally have a little bit of a tough time earlier than they sort 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 wonderful. That’s simply me on a Precision Xtra. However for individuals who want to give it a shot and perhaps haven’t given it a shot, any ideas for novices?
Dr. Dominic D’Agostino: Yeah. I might do fasted low-intensity cardio. For me, that might simply be going for a protracted stroll. Waking up within the morning, and when you’re going to start out your ketosis experiment or no matter you’re doing that morning, getting out within the solar, staying effectively hydrated, you may 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 in your ketogenesis to ramp up as a consequence 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 mainly 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 may 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 % larger after two weeks in a rat, for instance.
I feel the purpose for most individuals is that when you begin fasting or ketogenic food plan and to avert the keto flu, you need to hydrate, get in electrolytes and in addition elevate ketones as a lot as doable. And to do this with MCT, when 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 individual ketone manufacturing, particularly if it’s a dose-dependent factor. However my recommendation can be low depth cardio, hydrate electrolytes, after which small quantities of ketone electrolytes with MCT. So MCT will stimulate your individual Ketone manufacturing too so it sort 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 suggest?
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 approach. If I’m having espresso, I can put within the MCT powder within the espresso and blend that up and that might be 10, 20 upwards of 30 grams and work by Stephen Cunnane truly confirmed that when you take MCT within the context of caffeine or espresso, you possibly can enhance 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 truly 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 below the model title of Keto Brainz, and that’s the MCT powder that I exploit. The bottom of it’s MCT, however then it has sprinkled onto that theanine, which has a pleasant calming impact, which most likely good to make use of on the primary day of fasting. Alpha GPC, if I take an excessive amount of of it provides 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, once I first acquired Alpha, once I first acquired Keto Brainz and did like six scoops and I used to be like, “Oh, my God. I acquired to have a nasty headache.” However one or two scoops.
Tim Ferriss: I 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 food plan additionally, however no offense to the mushrooms, however I even have some attention-grabbing thought on a few of them extra mushrooms. A few of them are very strongly antiviral and immunomodulatory. And so once I’ve talked to various very credible mycologists, so like, “Yeah. It’s most likely greatest to not take that stuff daily. 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 may deal with that.
Dr. Dominic D’Agostino: Until you’re constipated.
Tim Ferriss: It depends upon the airplane. Yeah. What different simply MCT oil, powders would possibly you suggest or have you ever used?
Dr. Dominic D’Agostino: Quest MCT powder. I feel you will get that in like CVS and Walgreens now too. And Amazon, simply the Nutricost. So I purchased simply straight up MCT. In addition 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 mainly 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 take a look at drives. I’m about to go to, not tremendous excessive altitude, however I’ll be coming from sea degree to about 8,000 toes on common and we’re going to be doing a variety of intense train. So perhaps my morning dose of espresso, which I’m positive will likely be some shit prompt espresso, nevertheless it’s going to style scrumptious once you’ve been freezing your balls off all night time, perhaps I’ll add some KetoStart and MCT powder to that as a result of these can 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 scorching 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 making an attempt to determine, as a result of I went again by all of our conversations, which covers a variety of technical element as you’d 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 excited by neuroinflammation and the inflammasome, the interaction with the microbiome and the way the microbiome can seemingly affect or mediate a few of, for example, the anti-seizure results of the ketogenic food 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 tasks or realizations, findings, something have captured your curiosity or pleasure as of late?
Dr. Dominic D’Agostino: Yeah. I feel simply rapidly go down the listing. Ketone metabolic remedy for most cancers, so is one. And we now have a reasonably complete assessment that describes the framework for ketone metabolic remedy for glioblastoma, which is a most cancers that’s largely proof against the usual of care. So approach a lot to speak about. It was truly like a 200 plus web page paper that was going to be submitted. And we needed to mainly put a variety of information and issues as supplementary figures.
I feel there’s like six supplementary figures that inform particularly all of the totally different metabolic medicine that focus on glucose, glutamine, GKI calculator and a variety of issues. So yeah, simply Google ketone metabolic remedy framework for glioblastoma and its open entry. In order that has stimulated analysis at totally different locations. However I’m enthusiastic about analysis that we’re doing with Moffitt Most cancers Middle, which is the most important most cancers heart.
We’re one of many largest in Florida, a tier one most cancers heart the place we’ve acquired varied tasks, glioblastoma, perhaps a breast most cancers, but in addition lung most cancers. So was particularly utilizing ketone metabolic remedy to reinforce 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 research with CAR T remedy and checkpoint inhibitors. So ketones are inclined to develop the T-cells which are related to CAR T remedy. So simply sort of enhancing that remedy. And with the checkpoint inhibitors, it tends to simply improve most cancers particular immunity that’s augmented by PD1 inhibitors. So that they’re particularly learning that.
So I’m enthusiastic about that. In order that’s on the most cancers entrance. After which we will soar, if in case you have no questions, I might soar to different, the Alzheimer’s, the metabolic psychiatry.
Tim Ferriss: Let’s speak, yeah, let’s speak about 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 food plan after which shifting to sort of a paleo-ish food plan has produced among the greatest labs I’ve ever had and in addition the very best oral glucose tolerance take a look at that I’ve ever logged.
And from a temper stability standpoint, and I’m additionally for not less than the previous couple of 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 sort of mind-blowing, to be trustworthy. 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 individuals to take heed to Chris Palmer who you, I sort of put in your radar. I don’t know when you keep in mind. I despatched you the hyperlink to the metabolic —
Tim Ferriss: Yeah. Yeah. Yeah. Respect that.
Dr. Dominic D’Agostino: So I used to be like, “You’ve acquired to observe this, Tim. It’s going to alter kind of the panorama of psychiatry.”
Tim Ferriss: Yeah. I keep in mind that was a recording from a convention, I consider, the place he was interviewing one in all his sufferers on stage. Yeah.. I keep in mind that.
Dr. Dominic D’Agostino: The Metabolic Well being Summit, which is a part of Metabolic Well being Institute, which is you will get instructional 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 rapidly went into sturdy remission.
Tim Ferriss: Who’re well-known from Roblox.
Dr. Dominic D’Agostino: Effectively-known from Roblox. Yeah. Form of billionaire philanthropists which are altering, truly, in the end perhaps the usual of look after psychiatry. And I feel they single-handedly are funding metabolic psychiatry with Shebani Sethi, she’s at Stanford, Chris Palmer at Harvard, and I work with them intently as an advisor. There’s not less than a dozen different institutes which are doing metabolic psychiatry analysis for schizophrenia, bipolar, main despair, anorexia nervosa, which is a psychiatric dysfunction that kills extra individuals than another dysfunction and a spread of various issues and anxiousness issues and alcohol use issues, alcohol withdrawal syndrome. So that they’re doing analysis on that.
So with metabolic psychiatry, there’s a variety of pilot research, principally bipolar, taking a look at a spread 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 includes ketogenic remedy, but in addition way of life 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 making an attempt to suppose.
Tim Ferriss: Yeah. Higher on the science than the branding, I assume.
Dr. Dominic D’Agostino: Yeah. M-E-T-P-S-Y.com, MetPsy. So I feel they’ve their web site up. So that they’re mainly of their onboarding section. So they need to go reside fairly quickly. However I’d like so as to add that the Baszuckis, I keep in mind that they’re funding an enormous research 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 way of life therapies too.
So metabolic psychiatry is quickly rising in a quantity, and this ties into work we did. I assume my spouse did. I used to be on the paper however she ran the research. We had been doing seizure research with exogenous ketones, and probably the most efficacious one for this software was the racemic ketone salts within the MCT. We had been gavaging them and she or he was —
Tim Ferriss: What does gavage imply?
Dr. Dominic D’Agostino: Oh, so it’s mainly like tube feeding the animal. So as a substitute of blending the ketones in with the rat chow, they eat it. And so it’s taking a syringe and primarily based on the burden 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 you then 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 3 instances extra regular and it induces a seizure. However what we noticed once we put the animals in ketosis is that as a substitute of them making an attempt to chunk 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 making an attempt to chunk us.” And my spouse’s a behavioral neuroscientist and she or he was like, “Effectively, we should always do some behavioral research as a result of I feel 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 may possibly come out into the open arm within the elevated plus maze, which is exploratory conduct. They’re extra extroverted if they arrive out and extra introverted and sort of like their worry response in the event that they go into the cave.
So we acquired outcomes that we revealed. The title is like “Anxiolytic Impact of Ketone Supplementation.” We revealed I feel three papers and confirmed the mechanisms and stuff too. In order that was an early paper over 10 years in the past, simply mainly 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 when you take 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. So that they’re much less fearful to be in setting and making them extra like a social lubricant, perhaps like Benzo or one thing. So it had that impact within the animals.
And once we take a look at the blood work and even take out the hippocampus within the mind, the degrees of GABA to glutamate are larger. After which in one other research we did with Angelman syndrome, we seemed on the mechanism of that and there’s an enzyme referred to as glutamic acid decarboxylase, and a variety of anti-seizure medicine sort of goal that.
So the protein ranges had been larger, 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’re taking earlier than mattress. Yeah.
Dr. Dominic D’Agostino: Yeah. Yeah. In order that was, and quite a lot of totally different research, we additionally checked out adenosine receptor signaling. That’s somewhat bit extra sophisticated to explain, however there’s various totally different results contributing to that. So there’s a transparent rationale, I feel, for despair. 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 feel an necessary factor to say within the context of bipolar, you possibly can have a hyper glycolytic impact. And Dr. Iain Campbell from Edinburgh College has revealed some elegant opinions and is doing a little work on that entrance in describing the analysis there. However I feel it’s necessary as a result of among the suggestions popping out, and I feel 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, perhaps one to 2. I wouldn’t go above three, most likely 1.5 to 2 millimolar vary. That appears to be a degree of ketones that safely doesn’t produce a metabolic acidosis. So what we do see that once you get above three, it begins to alter blood pH.
So it appears to perhaps 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 awesome, so ketones are acidic and once you ship it into an ester type, there’s nothing to buffer that. While you give a ketone salt, the electrolytes are sort of like a buffer for that.
So you have got the metabolic impact, you have got the altering of the mind neuropharmacology, and in bipolar, you throw anti-epileptic medicine 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 might be an infectious agent, that might be a virus, that might be T. Gandhi. I imply, it might be like a micro organism. There’s varied issues that might trigger psychiatric issues. Numerous infectious brokers create that neuroinflammation. So I feel neuroinflammation, after which when somebody has a seizure too, the inflammatory state of the mind will get a lot larger.
So I feel ketogenic therapies are working by a number of mechanisms, roughly in synergy to supply that. It’s not one mechanism. Once we revealed the NLRP3, I acquired requests from Genentech and varied pharmaceutical corporations to go there and provides a chat on the mechanism so they might drugify. And I might throw up an enormous stream chart of all these mechanisms, and I feel they might get annoyed. And it was like, “Effectively, inform us the mechanism so we will make a drug out of this.”
However I feel the fantastic thing about ketogenic therapies is that it’s pleiotropic, proper? Which suggests it’s many mechanisms working in synergy. You may say Metformin, GLP1 medicine are working by metabolism, they usually’re sort of pleiotropic additionally.
Tim Ferriss: Do you utilize both of these?
Dr. Dominic D’Agostino: I’ve experimented with metformin, and that may be a approach for some sufferers to extend their ketone ranges. So we’ve revealed 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 learning that. And I feel metformin can improve, enhance AMP kinase, perhaps enhance insulin sensitivity and has a really weak impact at lowering blood glucose if in case you have a standard glucose. Nevertheless it does have a tendency to extend ketones somewhat bit.
And I feel there’s about 150 research on clinicaltrials.gov proper now on metformin, as a way to reinforce most cancers remedy. So I feel that might be a device within the toolbox for some individuals. Once 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 once I took it as much as two grams per day, I had a photosensitivity. So once 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 Could. 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: Could 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 feel you talked about Dale Bredesen on an episode of STEM-Speak. However particularly, for people with the APOE4 genotype, like yours actually, do you suppose metformin could also be extra attention-grabbing? However let’s assume in my case, let’s name me metabolically wholesome. So perhaps sure, perhaps no. I keep 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 fallacious, from Northwestern. He was like, “Ah, when you’re doing a bunch of train and getting your food plan straight,” he’s like, :I don’t suppose that you simply’re going to see a variety of profit.” However he didn’t have the APOE4 data on me. After which berberine I’ve written down for some purpose. 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 may contemplate when you don’t need to take metformin. I’m of the opinion that for the overall inhabitants, consuming an ordinary American food plan that’s averse to understanding and simply making an attempt to essentially modify their food plan, metformin I feel is a really doubtlessly 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 cut back your incidence of most cancers, particular sorts of cancers like pancreatic most cancers. I feel the information’s good on that, and I feel it’ll shift metabolic biomarkers that we now have traditionally good information on in the suitable path.
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 totally different medicine. However individuals who take metformin and one gram to 2 gram dose, two grams is excessive. However once they try this, they have an inclination to eat much less energy. So it does create —
Tim Ferriss: I see.
Dr. Dominic D’Agostino: A little bit little bit of, for me, GI points. Perhaps somewhat little bit of unfastened stools to start with, and that might be factoring in there. So it does have a tendency to enhance metabolic biomarkers throughout the board when 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 partly, a gentle gastroparesis and lowering gastric emptying time. But additionally works on the mind, and I feel has a variety of helpful results. I feel it’s a game-changing drug that’s going to alter the entire panorama of metabolic therapies. And I feel —
Tim Ferriss: Yeah, appears to have a — from what I’ve learn, and perhaps 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 principle purpose I might be taking a look at doubtlessly low-dose GLP-1.
Dr. Dominic D’Agostino: Yeah, I just like the low dose. I like that you simply preface it with low-dose as a result of I feel larger doses are usually not studied sufficient long-term to avert potential unintended effects that we don’t learn about.
Tim Ferriss: Yeah. And do you’re taking berberine or is it superfluous due to the food 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 apparently, after a couple of week, I began to get a headache. After which I acquired off — I don’t know if it has a vasodilate or perhaps it impacts liver metabolism in a approach that was — who is aware of? Perhaps 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. Really, 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 seems to be like a thermos, mainly.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: Okay, acquired it.
Dr. Dominic D’Agostino: Comparatively robust espresso. I try this and pour one cup, and I normally 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 faculty in our diet programs we’re educating.
After which the SGLT-2 inhibitors are additionally a reasonably attention-grabbing class of drug that I feel has a variety of potential. So if somebody making an attempt to carry their glucose ranges down, for instance, making an attempt to get that — these are pharmaceuticals. So after all, go to your physician. However that’s a reasonably good lever to tug, particularly if somebody’s proof against 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 device 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 stop them from consuming bagels. Which perhaps you are able to do. Simply all of the meds within the morning after which one injection per week or no matter it may be. Do you’re taking any dietary supplements or drugs with the specific purpose of mitochondrial well being or perhaps simply the facet impact of mitochondrial well being?
Dr. Dominic D’Agostino: Yeah. Effectively, I feel ketones shine there. The D, each the D and the L, beta-hydroxybutyrate. In order that’s in the beginning. And we’re doing analysis with NAD.
Tim Ferriss: These injectables?
Dr. Dominic D’Agostino: I can’t speak in regards to the analysis that we’re doing in depth. However we’re working with Metro Worldwide Biotech. So 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 variety of that. After which the muscle tissue are — so a variety of it’s perhaps not attending to the mind.
But when individuals 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 an entire 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 suppose — for sure functions, we didn’t see an impact. However on the identical time, they’re — for functions like non-alcoholic fatty liver illness, perhaps Alzheimer’s, perhaps inflammatory issues, enhancing. If used for a protracted time period, markers of mitochondrial well being I feel enhance. So NAD, individuals could know NAD is mainly a substrate for the sirtuins and varied enzymes. There’s 500 totally different enzymes. So a category of proteins which are referred to as sirtuins rely closely on NAD. So this is a vital factor to think about.
Tim Ferriss: And this sirtuin is only for people 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 important to do is drink wine, however perhaps 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 all the things that we research. So 5 to 600 metabolic enzymes want NAD for gasoline. In order that’s necessary to think about. And DNA restore is solely tied to NAD ranges. So keep in mind I discussed reductive stress with D-beta-hydroxybutyrate?
Tim Ferriss: Yeah.
Dr. Dominic D’Agostino: Reductive stress signifies that the NAD to NADH ratio would drop. So that you get extra NADH relative to NAD. That might be problematic as a result of the provision for NAD is probably not 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 feel it’s impacting the redox stability, which is getting us to revisit the varied ketogenic formulations and to check this, in cell-based methods, animal fashions. It’s arduous to do in people. You may 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 have a look at like phosphocreatine, ATP, pH, and in addition NAD to NADH ratios. So that is a method. Really, we do have that at our Alzheimer’s heart, and that’s on the listing of to-dos, to have a look at this reductive sort of stress factor.
So NAD, I’m simply throwing that on the market. I feel there’s a variety of criticism in direction of NAD now. That occurs on occasion. As a result of shifting science from cell-based methods to animal fashions to people, there’s a large studying curve there. We’re studying that with among 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 range dependent upon the scenario that you simply’re making an attempt to deal with. And likewise individually, I feel persons are going to have. In order that opens up this complete personalised precision ketogenic metabolic remedy, or the NIH is throwing some huge cash on personalised medication primarily based on genetic markers, and primarily based on biomarkers that a few of them that you may measure in actual time. Like steady ketone monitoring, steady glucose, and perhaps 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 most likely going to mispronounce this. However idebenone, extra observable model of CoQ10. Perhaps that’s a good description. Perhaps it isn’t. Do you continue to take that or not?
Dr. Dominic D’Agostino: Yeah, I feel CoQ10 is on the brief listing of 5 dietary supplements that I might suggest to individuals. Though I don’t take it, I do get fairly a bit from the meals that I eat. I eat a variety of coronary heart, liver, animal merchandise which have CoQ10 in it. However when you’re on a statin, when you’re on metformin and different medicine, they might doubtlessly deplete you. After which CoQ10 has a strong monitor report for cardiovascular well being. So idebenone is a drug stabilized type of that. After which once 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 effectively over a decade in the past, was given two or three years to reside. She’s alive and effectively right this moment, 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 feel it turned a drug.
So idebenone turned the usual of look after Friedrich’s ataxia, and you then couldn’t get it on Amazon. However I feel ubiquinol, or CoQ10, it could be an excellent substitute for that. And I don’t use it myself. However I feel that’s when you’re older in age and you’ve got cardiovascular coronary heart issues in your loved ones. Nonetheless, with that stated, we truly 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 all the things below the solar. Nevertheless it was this sudden facet impact. Then I went to the literature and confirmed that it’s such a robust antioxidant in some methods, and it perhaps 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 varied kinds which are extra mitochondrial particular. We’re utilizing stronger types of the CoQ10. So it is probably not much like the commercially accessible kinds.
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 can be the staple factor that I’ve used since I used to be an adolescent. Firstly, exogenous ketones, and the information is rising on that, I feel that’s going to be the following creatine for that. However creatine, for Alzheimer’s illness, we didn’t speak about it. However a dosage of 10 to, even when you’re bigger, 20 grams. And that’s not a misspeak there, 20 grams of creatine. Unfold out perhaps 5 grams, three to 4 instances a day for superior Alzheimer’s, when you can tolerate it. [inaudible 02:20:12]
Tim Ferriss: I’m taking 20 grams right this moment simply because I didn’t get superb sleep final night time. I simply discover it to assist with recovering from, let’s name it sleep deprivation. However yeah, acquired to observe the cut up dosing.
Dr. Dominic D’Agostino: Yeah. Vitamin D, however it’s important 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 most likely like 60 to 80, can be an excellent degree of vitamin D and getting that checked. However I feel you must test it first. It’s bizarre. I reside in Florida, I get tons of solar. But when I’m not supplementing vitamin D, I development to be low 30s. It might be development — however so once I complement it, I mainly keep within the mid-60s to 70s. So vitamin D and melatonin, I feel 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 linked 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, effectively, I’ll take away omega-3s from my food plan after which add it again in with a dose.” And it popped me again as much as a degree much like if I’m consuming tons of sardines per day. So when you don’t like sardines and also you don’t like consuming a variety of fish, I feel 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 may do the OmegaQuant take a look at. I feel there’s a lot information on EPA and DHA that I feel in the end, the omega-3 ranges will likely be a part of customary blood work. There’s a lot information rising on that, that I feel most likely inside the subsequent 10 years, once you get complete metabolic panel, CBC, DHA, and EPA will most likely 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 airplane for this spherical. And I do need to ask, after all, if there’s anything that you simply’d like to say or level individuals to. Something you’d wish to suggest, formal complaints you’d wish to lodge? Individuals you’d wish to safe in entrance of a giant viewers? No, I’m kidding. However something that you simply’d wish to say or level individuals to? Any assets, something that you simply’re as much as, the place they’ll 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 individuals 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 training platform. So all the things that we’re speaking about right here, we now have audio system and we create a medical training platform, so individuals can study metabolic psychiatry. Individuals can study metabolic primarily based therapies and metabolic medicine, like GLP-1 medicine and hormone optimization and issues like that. So I might point out that. The model of ketones that I exploit that I typically get requested is Audacious Vitamin KetoStart. In order that developed out of our work with most cancers, neurodegeneration and seizures. We’re doing work at Byrd Alzheimer Middle on most likely 20 or extra ketogenic compounds in improvement which are principally alcohol-free. So I feel all of them are literally. We now have some actually attention-grabbing research on Alzheimer’s and a variety of different — so hopefully within the subsequent 12 months be capable to share a few of that preclinical animal mannequin work. Hyperbaric oxygen, so we now have a 28 million research —
Tim Ferriss: That’s large.
Dr. Dominic D’Agostino: On the College of South Florida. I’m simply peripherally concerned in that or simply know the individuals operating that. And it’s primarily developed out of the DOD work that seemed 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 feel there’s a variety of attention-grabbing research that’s going to emerge. By the point this airs, I feel they are going to be on PubMed. Basically, displaying that hyperbaric oxygen remedy protocols, extra gentle hyperbaric oxygen at 40 to 60 classes, and those that 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 feel this work popping out of Israel, I want to see it replicated. I want to see — the work that’s totally different on the College of South Florida is that it’s very revolutionary and that it’s utilizing a sham.
As a substitute of utilizing hyperbaric air because the management, they’re utilizing — they mainly pulse stress to start with to make individuals suppose 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 suppose that oxygen is a robust drug, and I’m enthusiastic about that analysis, when you ask me. I’m excited if it proves it or disproves it. I feel we’re going to get an unambiguous reply to this query about hyperbaric oxygen for a traumatic mind harm, and other people 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 might increase and improve hyperbaric oxygen remedy, and reduce the potential for threat of an oxygen toxicity seizure, which fits up. In the event you’ve had a traumatic mind harm, your threat of oxygen toxicity seizure would enhance 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 helpful impact from that, then after the experiment, they’ll be capable to get that without cost service. So there’s six — like quarter to half one million greenback hyperbaric chambers. So the arduous shell chambers, there’s six of them on this facility. And it’s probably the most elaborate hyperbaric oxygen remedy research that has ever been completed. And it’ll reply the query in regards to the efficacy. In order that’s ongoing now, and I’m enthusiastic about that. I’m additionally enthusiastic about doubtlessly utilizing that facility, as a result of it’s subsequent to the Moffitt Most cancers Middle for sufferers which are present process varied most cancers remedies that might be enhanced with hyperbaric oxygen remedy. As a result of it augments the immune system and it’s truly an FDA accredited software for radiation necrosis. So when you’ve had radiation, then your insurance coverage would truly cowl it. However it may possibly improve sure therapies that we’re engaged on now. Yeah.
Tim Ferriss: Yeah. Wonderful.
Dr. Dominic D’Agostino: Yeah.
Tim Ferriss: All proper. Effectively, we’ll hyperlink to all of these issues within the present notes as at all times. And I encourage individuals to test all of these out. I’m going to test all of them out. And Dom, thanks a lot for the time, as at all times.
Dr. Dominic D’Agostino: Good to see you.
Tim Ferriss: I took a ton of notes. I’ve perhaps much more questions on prime of that for extra textual content messages. Sorry upfront. And so good to see you once more.
Dr. Dominic D’Agostino: Yeah. You too, Tim. Yeah, thanks for having me on. I respect it.
Tim Ferriss: Yeah. Completely. And folk, present notes will be discovered at tim.weblog/podcast. Simply search Dom or Dominic and a variety of them will pop up. Simply search for the latest. And till subsequent time, be a bit kinder than is important. It issues, it helps, to others and to your self. And as at all times, thanks for tuning in.