I think first and foremost it's weight loss. So it's very satisfying to go into a state of ketosis because you do see the scale change pretty dramatically, and that's due in part to some fluid loss associated with a reduction of fluid volume. It does have a diuretic effect. Ketosis does, ketogenic diets, and obviously fasting, and also a natriuretic effect where you dump out some sodium. Your blood volume will contract a little bit. So if you have high blood pressure, that will likely go down. So if you're on blood pressure medication, you have to think about that. But first and foremost, it's an effective way to get your body to lower the hormone insulin. If you have insulin resistance and shift your metabolism to burning fats, and as we burn more and more fat, that stimulates the production of ketones.
Dom, happy holidays. Nice to see you.
Great to see you, Tim. Thanks for connecting.
Definitely. I suggested we hop on the phone because I have been harassing the living hell out of you with so many questions via text message, and I thought, you know, this must be pretty annoying. So rather than answer me once, why don't we hop on and record a bunch of the details because the details are so fascinating. And for people who are just tuning in who might not know the good Dr. D'Agostino, Dominic, we should establish some basics. And I, at this point, have been quote-unquote in ketosis for 18 days now, and we'll dig into a lot of questions around that, tactical, practical questions. But before we do, why would someone—and we can talk about what it is and so on—but first let's just give some of the, let's call it established benefits, ideally in human studies but could extend to animal models, and then if there's anything on the horizon, say in the next few years, because you're at the cutting edge, if you think there's anything that might plausibly be established as a benefit, what could that be? So what would you put on the bullet list of benefits of intermittently or for extended periods of time being in ketosis?
There are many benefits to being in ketosis, and a ketogenic diet, if we're going to go there, kind of has the benefits of fasting. And there, you know, for millennia we know the benefits of fasting without the baggage, without the metabolic baggage, you know, the muscle loss, the fatigue. Obviously you can't live in a, you know, that level of caloric deficit. But in regards to the practical applications of it, we know that being in a state of ketosis really quiets the mind, and I think that has major implications. And this was, you know, from centuries we knew this, and now over the past decades this has been like a term kind of used, and it's backed up by experimental data to show that there's an elevation of GABA. Obviously it's silencing a broad array of seizures independent of the etiology: temporal lobe seizures, Lennox-Gastaut syndrome, Dravet syndrome, rare forms of epilepsy. The ketogenic diet just quiets the brain, lowers glutamate and elevates GABA, a brain-stabilizing, calming neurotransmitter. And you know, that's why people gravitate towards alcohol, right? The GABAergic effects of alcohol and benzodiazepines.
So you can sort of, in a very gentle way, transition your physiology to a state of ketosis which changes the neuropharmacology of your brain to sort of quiet it down. And that, I think, really echoes its broad application for metabolic psychiatry, which is everything from major depression to bipolar to schizophrenia to anxiety disorders to anorexia nervosa. So that's a very interesting and rapidly expanding application of ketosis that's being funded largely by the Bazuki group.
Yeah. You just interviewed—had David on.
Yeah. And on the physical side, some folks, if they're old enough, may remember the Atkins diet. Not saying that is what we should hold up as necessarily the end-all be-all in any sense, but why would someone go on this for benefits outside of the cognitive psychiatric? Are there any other benefits that you could list off?
I think first and foremost, it's weight loss. So, it's very satisfying to go into a state of ketosis because you do see the scale change pretty dramatically, and that's due in part to some fluid loss associated with a reduction of fluid volume. It does have a diuretic effect. Ketosis does, ketogenic diets, and obviously fasting, and also a natriuretic effect where you dump out some sodium. Your plasma volume, your blood volume will contract a little bit. So if you have high blood pressure, that will likely go down. So if you're on blood pressure medication, you have to think about that. But first and foremost, it's an effective way to get your body to lower the hormone insulin if you have insulin resistance and shift your metabolism to burning fats. And as we burn more and more fat, that stimulates the production of ketones, ketogenesis. And ketones have a broad array of applications, metabolic signaling, epigenetic, that have real-world applications. And that's why the whole field of exogenous ketones has developed, and there's 160 or more registered clinical trials on exogenous ketones on clinicaltrials.gov. And I could go into each of the applications individually if we want to go there.
Well, as we talked about before recording, and I have to act as a bit of a referee for my audience because I know you can go as deep as we want down the rabbit hole into the 17th dimension of biochemistry. So if you get possessed by the organic chemistry demons and start speaking in tongues, I'll rein you in a little bit. However, let me perhaps provide a personal example first for folks because some of this will be familiar to people who have listened for a long time, maybe to other episodes of the two of us, but a lot of it's going to be new. But I want to establish some priors just so people are aware of what this might look like in practice. So I have experimented with the ketogenic diet, also extended fasting. You can arrive at some similar places, but like you said, there can be some pretty heavy taxes to pay with extended fasting. The ketogenic diet I've experimented with all the way back to the '90s. Some of you weren't even born probably who are listening, but some of you will remember the '90s. And I was using it specifically for mood stabilizing. This was towards the end of college, but also to lean out while building muscle on something called the cyclical ketogenic diet.
So we're going to get to that later in the conversation, but it was effectively, let's call it, six days of focusing on a ketogenic diet with one day or a half to three-quarters of a day of glycogen depletion and then loading with more carbohydrates, lower fat, etc. The reason that the ketogenic diet became doubly interesting to me is that when I had Lyme disease the second time, which came with all sorts of co-infections like babesiosis and so on. And this isn't chronic fatigue or depression searching for a diagnosis that is external. I feel like sometimes the cottage industry of diagnosing and treating people for quote-unquote Lyme disease can be shady at best. But in this case, I'm coming from Long Island. Everybody in my family has had tick-borne disease. Wow. And was credibly diagnosed. So the second time I had Lyme, I got to a point because I did not see the bullseye rash, assumed I did not have it, which is a mistake because sometimes you don't see the dermatological response and you nonetheless have contracted something like Lyme disease. I ended up weeks later slurring my speech, took me minutes to get out of bed because my joints hurt so much, forgetting friends' names. And my assistant said, 'Tim, you really need to see someone. This isn't fatigue. I've seen you sick. I've seen you tired. This is something else.' And suffice to say, that turned into several months even post-antibiotic treatment, which I do think is important, of we could call it pseudo-dementia. I mean, I really felt like I was operating at 10% cognitive capacity, and basically at my wit's end I said, well, what can I control, because a lot has not done the job, and I went into strict ketosis. What does that mean? That means that I'm consuming moderate protein, probably getting at least 50% of my calories from fat, and keeping my carbohydrates to less than 20 grams a day, probably at that point. And within three or four days—I'd probably say around day three or four because I wasn't very fat-adapted at the time, my body wasn't well trained to use fat because I wasn't doing intermittent fasting, which we'll come back to—and within three or four days, effectively, all of my cognitive symptoms disappeared. And I stayed in that state through nutritional ketosis for a few weeks, had complete remission of any of the cognitive symptoms plus the joint pain symptoms, and those never came back. And I recommended that—and this is not a randomized controlled trial—but over the years, due to various factors, we've had ticks growing in population, also expanding to the coasts and on the west coast that is, and elsewhere—I had three friends replicate this with ketosis after suffering various symptoms from tick-borne disease. And you know, we were texting, maybe even talking about this, but I never had a great explanation for why it worked. I said, I don't know the exact mechanism. Maybe I have faulty glucose metabolism that was somehow—maybe something was impaired by the ticks and therefore I'm giving my brain this alternate fuel that it really likes, ketones. But it didn't explain necessarily the durability of the changes. Right. In brief, do you have a theory or an explanation for why that would work?
Yeah, I'm glad you brought that up because quickly, dozens if not hundreds of people with tick-borne diseases, including Lyme disease and all the tick-borne diseases, have communicated with me. And one of the patients is actually Deanna Tadone, who was diagnosed with ALS prior to 2010 and has basically been stabilized, given three years to live. So I realized that it's underdiagnosed. The tests to do that are kind of controversial, you know, with the CDC testing, the two-tier testing and HAI. So I know I'm going off track a little bit here, but I think it's important to say that the spirochete, Borrelia, that spirochete is essentially 100% glycolytic. And when you limit glucose availability and glycolysis, you are targeting the energy systems of that microbe. So that's one thing to think about. And it's well established now—it wasn't three years ago—but a ketogenic diet, in particular beta-hydroxybutyrate elevated in the blood, stimulates the adaptive immune response. And that's essentially your body's ability to target foreign invaders and neutralize them. And that has become a rapidly growing area of interest. University of Pennsylvania, you know, they're doing CAR-T therapy and checkpoint inhibitors because of the ketogenic enhancement of the adaptive immune response. So, and I think that plays a role. And situationally, I have observed that you go into ketosis if you have an inflammatory process, and Lyme disease is inflammatory. But people who have shingles and herpes simplex and things like that, I have an inbox full of people that do that, and I would like to experimentally go down that direction to understand why. But I think there's two reasons: you're targeting the energy systems and you're augmenting the immune response to keep the spirochete in a dormant stage or maybe eradicating it in some context.
It's really incredible on a whole lot of levels, and I'm just lucky that I had the prior experience with the ketogenic diet to even have it occur to me as a last-ditch effort. And for people, if it wasn't clear—I mean, you explained it clearly—but glycolytic, I'm simplifying here, but it means that something needs to eat sugar or metabolize, you know, carbohydrates to survive, right? And there are also—Dom, correct me if I'm wrong—but particular cancers that are very sensitive to being starved of glucose as well. And for people who want more on fasting, ketosis as it relates to cancer, we may come back to it also, but we've had prior conversations about this and the benefits, some of the incredible effects of fasting prior to cancer treatments of various types. So is it fair to say, do you think most of the benefits that someone would derive from fasting prior to cancer treatments, they could also get from ketosis, or is it dialed back to a smaller percentage of effect?
That's a good question. I think it requires a nuanced answer that we probably don't have time for. But if you are overweight and your BMI, for example, is like as many cancer patients tend to be, like 28, 30, 32, a fasting or a calorically restricted ketogenic diet is the way to go. If a patient is trending towards being lighter, like a BMI, you know, 20, 22, something like that, a eucaloric—meaning like keeping stable caloric level to maintain your weight—is going to be important, and then elevating beta-hydroxybutyrate will be important to get some of the anti-inflammatory effects and also the immune-boosting effects and the neuroprotective effects going into cancer therapy, because there's people studying ketosis for chemo brain, like reversing chemo brain and like managing that. So it has a broad array of applications, not just targeting—it's targeting the tumor growth and putting a brake on it. It's not a cure for cancer. And I cringe when people talk about that online, the ketogenic diet curing cancer. It does slow it down, especially if it's highly glycolytic, which 80% of cancers are. And it enhances and augments the response to the standard of care, that's radiation, chemo, and immune-based therapies. We know that now.
All right. So why have I been in ketosis for 18 days and why am I doing it a few times a year? Well, part of how I implement this does hinge and will continue to hinge on some of the answers in this conversation from Dom, because this is very self-interested. But what I have found is that for mood stabilization—and you mentioned metabolic psychiatry—I've had, and you made the introduction, I believe, Chris Palmer out of Harvard on the podcast to discuss this. But there are certain conditions, whether it's depression, but even more squirrely when you're dealing with something like schizophrenia, for instance, or different types of bipolar, people who have been on dozens of medications who go into, let's call it, remission, or they no longer meet the criteria, right, for the diagnosis of some of these after being treated on a ketogenic diet of one type or another. It is astonishing. And so for my own mental health, I've noticed complete stabilization, and without subduing the highs, right? I've never had mania necessarily. I'm not talking about that. But I'm not muted. I feel just calm, stable, sharp. And that's one reason in and of itself to do it for periods of time. But I seem to feel a carryover effect. Also have Alzheimer's and other neurodegenerative diseases in my family. I have three relatives with rapidly advancing Alzheimer's at the moment. So maybe we could talk also to how these things might intersect. But my feeling is possibly—and I'd love your input here—if I follow a ketogenic diet for a number of weeks or maybe a month and a half or something like that, I'd love to know the timing you might recommend. Let's say I do that two or three times a year, that there could be enduring effects that have protective carryover, right? And I also find it much easier now that I started doing intermittent—I've been intermittent fasting pretty much every day for the last six months, which means I'm eating between typically 2:00 p.m. and like 8 or 9:00 p.m. and having two meals a day. That's it. Not hungry at all. Like I haven't eaten today. It's 12:30 my time. I will not be hungry for another two, two and a half hours. That by itself completely—completely revolutionized—I mean, that's an overused word, but completely polished my insulin sensitivity and metabolic health on a bunch of levels. Like my labs have never been better, my oral glucose tolerance test has never been better. And one question I have for you, which is just for Timmy Tim but will apply to other people, is: is there an argument to be made—and maybe I'm totally off base—but that if you follow a ketogenic diet and make it work for a multi-week period of time, that you're changing your metabolic machinery or just your body in some way that has carryover effects even after you stop the diet? Or is that me just doing some hand-wavy fancy footwork as a muggle? I just—I don't know if there's a there there, but what are your thoughts?
I would say absolutely. I think the science is still working to clarify that and make it less ambiguous, the benefits that we are deriving from that. But that is kind of like one of the pitches for the fasting-mimicking diet by Dr. Valter Longo, who was one of our keynote speakers at Metabolic Health Summit, and he's presented some really compelling research on that that opened my eyes to that five days of fasting can have—I think he presented at the time—even three months of effects on sort of cardiometabolic biomarkers. In his case, this would be the fasting-mimicking diet, so a few hundred calories a day. Yeah, like 600, you know, using his protocol of various foods, kind of gravitating towards more of a plant-based, lower-protein strategy. And I think that it's promoting metabolic flexibility and ramping up fatty acid oxidation enzymes. And much like muscle memory, I think there's a metabolic memory. The more you stay in ketosis, the easier it gets, and the more benefits you derive from it, and the more that you shift your body to being more fat-adapted. Just like you can build your VO2 when you build your VO2 max, or you build up to like a 400-pound bench press and you take like months off and you go back and you can only do like 225 for a couple reps. It only takes like two or three months to get back, but it took you 10 years to get there. You know, that muscle memory snaps back quick. And everybody agrees that there's this metabolic memory. And I think there's a lot of things at play, including, you know, gene programs, epigenetic regulation that comes into play. So first and foremost is changing our mitochondrial function and mitochondrial capacity. So the number of mitochondria increase, and then when you take a break and then get that stimulation again, that mitochondria is kind of there and it responds very rapidly.
So thank you for that, and I want to bookmark—maybe we come back to this—but if people are trying to think about this, understanding that the science right now is maybe provisional or, you know, a hypothesis worth disproving at this point, but that it seems to make sense, right, from an evolutionary perspective, that both muscle memory and metabolic memory would be a thing. Otherwise, it makes sense your body would want to adapt to be prepared for the next famine or whatever it might be, right? I just want to say muscle memory is metabolic memory. So someone—I gave the analogy of like lifting weights, but someone who runs marathons, it's the same scenario. They take time off and then that VO2 max quickly establishes again, and it's muscle but it's metabolic. So I like to use the term metabolic memory.
Metabolic memory. Okay. Yeah. Metabolic memory.
Just so people know where I am at at the moment. And actually, yeah, I'll just tell people like what I'm doing because I know they're probably getting itchy for some just like what does this look like in practice? And then I want to talk a bit about how ketosis or the ketogenic diet may or may not be helpful for maybe not treating, maybe treating. I've certainly seen some interesting effects in some of my relatives when I give them exogenous ketones where suddenly their sentences are three or four times longer 30 minutes later, which is wild to see. But in terms of prevention or staving off the onset of some of these diseases, I'd love to hear your perspective. But let me tell people what I've been doing for the last few months and especially in the last 18 days. So for the last whatever it is, I think I mentioned six months, I've been doing intermittent fasting. And that was after hearing a conversation between Dr. Rhonda Patrick, who I'm a big fan of, and Mark Mattson, M-A-T-T-S-O-N, who's done a lot of research related to intermittent fasting. And the key piece for me, because you see all these different types of intermittent fasting, all these different ways to do time-restricted feeding, and I am going to paraphrase here, so Mark, I apologize if I'm getting this wrong or oversimplifying, but in effect, it's important that you fast. This means no calories. Or we could talk about pure fat, but let's just assume you're not consuming any calories for 16 hours because you want to deplete your liver of glycogen. And once you deplete your liver of glycogen, your body experiences this metabolic switching. And I've certainly felt this just doing intermittent fasting where my meals contain carbohydrates later, that around the end of that fasting period, boom, something switches and my mind is sharper, right? And then when I got to the point of going into the ketogenic diet this time, and also a few months ago because I was doing the intermittent fasting, and it took me about a week and a half for my body to get comfortable with that, at which point it was no problem, but I was a little pissy, a little irritable for a little while, a little foggy. And then when I went into the ketogenic diet this time, it was the easiest transition I've ever had. I did not have any fogginess. I did not have low energy. I did not have what some people might call the kind of keto flu adaptive period, which it seems to be pretty remediated or addressed with electrolytes for a lot of people. But it was incredibly easy, just straight into the ketogenic diet with no problem because I was already doing the intermittent fasting. And then for 18 days, I've been having two meals a day. And you've recommended a few that sound, frankly, pretty disgusting, but that are actually really easy. Like two cans of canned mackerel with about two tablespoons, 30 ml of MCT oil plus apple cider vinegar with some salt and pepper. It's actually delicious. I just love mackerel. Oh, there it is. Yeah, you've got your apple cider vinegar right there.
Cheap stuff you can get on Amazon. So—
Yeah, for people who might think, 'Oh, wow, this is what for fancy people who can do all sorts of expensive things in their diet.' We're talking about like how much does that meal cost? Three bucks.
A dollar a can for that chicken of the sea. And literally you get almost a pound of mackerel. And this is like third-party tested, very low-cholesterol mackerel, the little mackerel.
So $1.50 for almost a pound of mackerel that you can get that for. Like you can't—and the omega-3s are off the charts. The heavy metals are low. You know, I consume pounds of this stuff and I've gotten my blood and my hair heavy metals tested and it's like super low, like non-detectable. So I wouldn't worry about that. People have questions about cost and heavy metals and that's a non-issue, you know, for me.
And maybe you could mention—I'll put links in the show notes as well—but since we're on the topic, any brands that you default to that you like? And that chub mackerel piece for folks, that detail is important because there are mackerel of many different sizes.
Yeah, king mackerel is kind of high. This is Chicken of the Sea. So if you want to do the budget, you buy the case, the more you buy, and then Amazon subscription, and then it goes on sale. You can actually get it for like less than a dollar a can. And I do the same with Chicken of the Sea jack mackerel. Just chub mackerel or jack mackerel. So they're both small fish. And I kind of like the King Oscar brand too. Yeah. Just a little bit more pricey. And Season's brand is pretty good too. But I mean, it's like as cheap as dog food.
I mean, we buy some pretty fancy freeze-dried. We don't buy the kibble stuff, but when you run the numbers, it's very inexpensive. We buy cases of eggs for like $1.20 per, you know, if you do like eggs, fish, beef, and also turkey. You can get turkeys for under a dollar a pound, the whole turkey. And just for people who are like, 'Oh my god, I can't believe you guys are eating mackerel mixed with oil and vinegar in a dog bowl,' that's not all you can eat. Like, there's more that you can eat. You can have like chicken with cheese on it. You can have vegetables. There are certain things you have to watch out for so you're not whacking yourself out of ketosis. But in my particular case, I don't mind. And the fact of the matter is, when I wrote The 4-Hour Body, people were like, 'Oh my god, you want us to repeat the same meals over and over again?' I'm like, 'What did you have for breakfast the last five days?' And they ate the same damn thing. You're just swapping out to fall meals. So my first meal is something typically pretty small, like the mackerel I explained, and then I have a big meal. I might have some more protein in between, but it's like yesterday I had lamb chops that were delicious with some vegetables made in an air fryer. No problem, right? And later on, I might have like a ribeye chopped up on a big gigantic salad with some other stuff added to it, but that's about it. You have to be careful with the macadamia nuts. Those things will creep up on you. But that is in effect the diet, right? And I'm doing my training. I'm doing my rehab. I'm doing my zone 2. I do find I'm a little, let's say, lower performance when I'm in ketosis. But what I wanted to talk about is maybe a false negative that I've experienced. And I'll explain what that is. So how do you know if you're—and I keep putting this in quotation marks, like quote-unquote in ketosis, right? Because most people are, or maybe all people are producing some level of ketones. So there are different concentrations, right, that you can measure with a finger prick, just like you would look at glucose. And at least with the finger prick, I think that's measuring what you mentioned earlier as being so beneficial in a lot of studies, the beta-hydroxybutyrate, BHB.
I also have, because I wanted to run this tracking, a G7 Dexcom continuous glucose monitor on one arm and then a SiBio—apologies, I'm not pronouncing that correctly—continuous ketone monitor on the other arm. And I'm wearing an Oura ring when I sleep to see how all of this affects my sleep architecture and everything else. So I'm gathering all this, but then I notice something really weird, which I've texted you about because I keep feeling like I'm failing at keto. I feel great. I feel sharp. And yet, when I look at not just the continuous glucose monitor, but even with the finger prick, because you do have to often calibrate these things, right? Don't assume that your continuous monitors are accurate. You want to calibrate them. But I'm looking at the numbers and, for instance, my girlfriend freaked out the other night because my phone started screaming. I had earplugs in because I didn't hear it and it was like critical medical alert or whatever the code read was because my glucose was 69. I suppose it's gotten quite a bit lower on ketosis, but you know, usually hovers somewhere between like 65 and 80. And my ketones were 0.2 millimolar. Now, when we've talked in prior conversations about what kind of target you might aim for, it seems like, you know, between 1.2 and 2 millimolar is anxiolytic, right? Lowers anxiety. And then you're looking for this ratio. You could talk about this, but the GKI, there's a ratio of glucose to ketones. And I look at those numbers and I'm like, this makes no sense to me because I'm not getting enough glucose to function well. And if I'm basing it off of the Keto-Mojo finger prick, even the Precision Xtra from Abbott or my continuous ketone monitor, I'm not getting any ketones either if you're taking it at face value. So how am I functioning? How would you answer that? Because I don't think I'd be the only person who feels like they're doing something wrong if they run into this, but how would you interpret this?
I would definitely say you're running lean, and I think what you've done—and your OGTT test is really good. I think you had messaged that.
And the OGTT for folks is just that oral glucose tolerance test where you drink a bunch of dextrose water and then they take your blood every 30 minutes for two hours to see how you're responding to it.
Yeah. The biggest metabolic lever would be you have enhanced insulin sensitivity, and I think that has been the focus. For example, Ben Bikman wrote a book on this, and you know, doing hundreds of podcasts on insulin resistance, reversing insulin resistance, and low-carb ketogenic, you know, being effective for that. So that first and foremost, your insulin sensitivity is very high, your fat oxidation is really high, and your glucose disposal is high. And if you're in a caloric deficit, your ketone uptake is very high. We see this quite convincingly, you know, in older rats where we like gavage, where we tube-feed the rats and they're older, the ketones get to toxic levels, whereas like a younger metabolically fit rodent will dispose of it very quickly. Same with a couch potato human, same with an elite-level athlete. So you have very rapid—so when you measure ketones in the blood, that's a function of ketone production and ketone utilization. And you could have two to five times higher ketone utilization, you know, with high metabolic fitness. And that's due in part to ketogenic enzymes. You upregulate the MCT transporters that could be two or, in rodents, two or three times higher. We—I haven't done that personally, and we have some data in humans we haven't published yet, but that is a real thing and I think that you're experiencing. Also, if you're in a caloric deficit, there's less spillover. I just bought like an antique motorcycle and it's got a carburetor and the float sticks a little bit and it always drips out the carburetor when I'm running it and when I stop, and it's like kind of pouring out the carburetor, so there's spillover of fuel, right? So, but when I'm running it, it's running lean because I'm using the fuel that's kind of going to the carburetor. And kind of the same analogy here is that, you know, for example, it might be good to just sit in one spot and relax and maybe eat a little bit of surplus calories or even eat a little bit of carbs. And what you'll see often is like your ketones spike up. Yeah. So I remember some of my highest ketone levels ever is when I consumed carbohydrates after I was fasting or in a state of keto. It like jumped up to five, six, seven. I was like, what is going on here? But the glucose in that context is ketone-sparing. But the glucose will also shut off ketogenesis. So it'll tank, you know, after, but afterwards.
So it sounds like then, because of probably the intermittent fasting in large part, I would think, if my insulin sensitivity is high enough, that can be paired with higher ketone utilization. So if on the assembly line of my body, right, they're producing 10 units of ketones, if I didn't have good ketone utilization and it was my first rodeo with ketosis, let's just say, or a ketogenic diet, the finger prick might pick up all 10 of those units. I'm simplifying here, right? But if I have high ketone utilization and my body's quickly using eight of those, especially in a caloric deficit, then it's only measuring two and I'm getting the false negative that I'm not actually producing ketones in the first place. Is that a fair, very, very simplified description?
And you're not measuring tissue levels of ketones, which we have done too, even in the brain. And that can shoot up like really high also. And I've done this with Peter Attia too. We were measuring blood and then breath. And it seems like when we were in a caloric deficit fasting, our ketones were like really low in the blood. Low is like one to two, but we're like really deep into fasting, whereas our breath ketones were maxing out the meters. We kind of concluded that after a lot of testing that the breath ketones were almost a better indicator of ketosis, a more accurate, I guess you could say, in a caloric deficit, because when you're in a caloric deficit, you just have very high ketone disposal uptake into the tissues.
It looks like a breathalyzer, right? So is that measuring—what is it? Acetoacetate? No, I'm just trying to repeat words that I've heard once or twice, but it's not BHB.
Acetone. God damn it. All right, I know I was close. That was—it was a 50/50.
Comes from the spontaneous decarboxylation of acetoacetate. Like we'll spit out about 20% of the acetoacetate will kick off to acetone and then you can measure.
We've measured blood levels of each and it's very tricky to do that, but we've done it in the lab.
All right, here's another practical tactical question for you because I've gone back and forth on this and Uncle ChatGPT has confused the hell out of me. So maybe you can help resolve it. Gluconeogenesis and protein intake, right? So you consume, what is it, between like 200, 240 grams of protein a day? Something like that. Is that roughly?
Yeah. On active days. On like less active days, if I'm just behind my computer all day, maybe closer to 180, 200, but yeah, generally speaking.
And people might have picked up when Dom was casually throwing around like, you know, when you've been squatting 400 and you take a break and then you go back and you only could squat 300 pounds. Dom's a pretty big guy who's also deadlifted 500 pounds for like 10 reps before after fasting for a week. So he and I are not the same size. But nonetheless, I'm trying to figure out on one hand how much protein I can eat without my liver taking excess protein amino acids and turning it into glucose. Right? And depending on what I look at—and I have looked at sources outside of ChatGPT—on one hand there are folks who say don't worry about it, if you're consuming enough fat you really don't have to worry about it, and then there are other folks who are like watch out, watch out, if you consume more than X number of grams at a given meal you can very easily knock yourself out of ketosis, which would, if that's true, be maybe an alternate explanation for why I'm getting these low readings if I'm having a small meal around three and then a gigantic meal later on. How should I—and how should listeners—think about this?
If you were to consume protein in the form of liquid, for example, like whey or something like that, then the rapid entry of amino acids into your bloodstream from your small intestine will shut off ketosis. So fat and fiber and salt, because your pyloric sphincter will basically be pretty tight until your stomach—
Pyloric sphincter, where your stomach connects to your small intestine. If you have a very fatty, salty, high-fiber meal, that little—that entryway, we call that the sphincter, it's the pyloric sphincter, will remain shut until like the contents of your stomach become isotonic, which means that your body has to kind of give up water and it's got to churn it and break it down. So you could delay gastric absorption simply with fat, fiber, and salt is pretty good too. You could do ketone salts or just salt electrolytes. So that will delay the entry of amino acids or protein into the small intestine and thus amino acids into the bloodstream. And that's the major regulator of ketosis, you know, having an impact on insulin and also having impact on gluconeogenesis to that rate of entry. And if you can slow that down, you see nothing on the CGM and your ketosis levels can basically stay. You could further augment that by using MCT oil with the protein and the fiber. And so if you have long-chain fats from like a fatty steak and MCT oil and then fiber—and that could be insoluble fiber is pretty good too, soluble and insoluble—that can slow the entry of amino acids and essentially buffer the gluconeogenic response.
So let's say I was stuck in San Francisco late. I'm just taking a rare trip over here, which is a pretty exciting time to be here with all of the mania with AI going on. Everyone's kind of drunk on the Kool-Aid, but that's a separate story. I got trapped downtown because I didn't want to deal with traffic and blah blah blah blah blah. So I ended up having a huge bunless double cheeseburger, like gigantic. This thing, I did not expect it to be as big as it was, right? And so I go online to try to figure out what the protein content of this thing might be. And it's like 80 grams of protein, but plenty of fat, certainly tons of fat, salty as fuck, plenty of salt, not a lot of fiber. We'll give that one a pass. Should I be worried about something like that knocking me out of ketosis?
I think you need to measure. So I kind of default back to like everybody's a unique metabolic entity. But if you eat that and kind of your activity level is high and you're in a bit of a caloric deficit and you were to have that and sort of not overdo it on the total calories—I know my body, I know my body—I could stay in ketosis. But if you have that oversatiated feeling, so we have neurons, we have neuronal pathways to and from the liver and to and from the gut. We call that afferent and efferent signaling, right? And the enteric nervous system, and a big meal will basically tell your brain that you had a big meal. And independent—I talked about the amino acids going into the bloodstream kind of kicking you out of ketosis—but there's also like this, when you have stretch receptors and you have a big full meal in your gut, then that could actually tell your brain to activate the sympathetic nervous system, and then that, by virtue of spilling out catecholamines, can basically—like we're talking adrenal, epinephrine, things like that—that can further augment and enhance gluconeogenesis. So—
Okay, let me just translate that for a second. So people wake up, cortisol's developed this like bad reputation among a lot of like online influencers, but it's like you really need cortisol, right? So when you wake up in the morning and you see a bit of a glucose spike, like it's actually important to get your ass up and moving. If you're in ketosis, it's a different thing, right? So if I'm hearing you correctly, right, outside of how people think about digestion, blood sugar, insulin, etc., that just based on stretching your stomach, etc., right, with these mechanoreceptors taking the inputs, that that signals to the brain, it's go time. So let's basically get things moving with these hormones. And that could in and of itself then trigger the liver to produce more glucose or liberate more glycogen. I guess—
It can if it's above and beyond what you normally eat.
If you train your body to that size meal, but it also activates other gut hormones like cholecystokinin, that's called CCK, and other things that can then activate the parasympathetic nervous system that comes in a little bit after. At the same time, it sort of kind of bifurcates, but then the parasympathetic nervous system is sort of relax, digest, rest and relax, digest. So that kind of comes in after. So you might see a blip and sort of might feel kind of stimulated. Also all the salt, if it's a salty meal, it's going to expand your plasma volume. Your blood volume will increase and that can increase your blood pressure a little bit and that can activate your sympathetic nervous system. So it's always good to go take a walk after a big meal.
Yeah, I do that. Not like a strenuous—not like go squat and deadlift, but just yeah, even a 10, 15, ideally like a 20-minute brisk walk is really good after a big meal.
Let me ask you this on the walk timing. So when I have a big meal—and I will say I think I have trained my body to have big meals and what the exact response is, I can only give you subjectively what I feel and I can give you what the monitors show. But I typically feel pretty good. However, if I have a big meal, whether this is in ketosis or otherwise, I don't see the biggest spike until something like—depends on the meal, right?—but 60 to 90 minutes later, that's when I see the spike. So should I do the walk at 60 to 90 minutes or should I do the walk right after the meal? When should I actually time the walk?
So you eat a meal, you go walk, and then you see the rise 60 to 90 minutes after, or is that independent of the walk?
Okay. So you're not walking, but you see the rise 60 to 90 minutes later. So I'm saying that you might not see that rise 60 or 90 minutes later if you did it right after the meal. Yeah. Just because a little bit goes a long way. So just like walking, actually doing like some stretching and walking too, it activates the glucose 4, the GLUT4 transporters.
That's insulin-independent. So less insulin is dumped, greater glucose uptake. And you're also using sort of the sympathetic nervous system mobilization of glucose through gluconeogenesis during that walk. So it then attenuates the buffering of ketogenesis. A very short walk can go a long way.
Okay, cool. Yeah, the—is it glute? How do you pronounce that? I don't know. How do people say that?
I say glute. I say glute for.
Yeah. For the OGs in the audience, go back and look for glute for in The 4-Hour Body. It's in there. So the other measurement question I want to ask you about, which is, you know, these continuous glucose and ketone monitors are not designed for someone like me, right? They're developed presumably—I don't know about the ketone monitor, but in the case of glucose—to help people with serious conditions not end up in very serious situations. So when I am looking at my ketone levels, right, like right now I feel very sharp. I had some Keto Start—you know this well—exogenous ketone salt-based product not too long ago, just in hot water with a little bit of MCT oil. This was I guess an hour, hour and a half ago. But I'm at 0.4 millimolar. And I guess what I'm saying is whether I have a huge meal or I'm fasting, as I am right now, my range is basically 0.1 to 0.4, 95% of the time. There are a few outlier cases. If I'm just doing like a YOLO, you know, as many grams as possible exogenous ketone party, then maybe I—
could goose it. But we can talk about this. Like once it gets past a certain point, then I might spike insulin and have a subsequent crash. But I guess what I'm trying to say in brief is my range for the most part is 0.1 to 0.4 for regardless of whether I'm fasting or eating a gigantic double cheeseburger. So, I'm not really sure how to determine what effect it's having. I can watch the glucose, but you know, right now I'm 0.4 millimolar concentration on the side bio. And as we've talked about, maybe the Precision Extra would give me an extra 0.1 or two, but they've been pretty close so far. And then ever since my cheat meal, we had this experiment, right? I wanted to see if I did a workout and then had one or two cheat meals last Saturday. It is now Thursday, but my glucose right now is 103, right? Which is higher than the week prior.
But it goes around. It moves around. Last night it was probably 70 something. Do you have any suggestions for how to read the tea leaves or is it mostly just subjective feel? I mean, still thinking about the size of the meal. I guess what I'm saying is if my device is telling me as it is right now, right? 0.4 fat not burning. You're almost not burning fat at the moment. Not in ketone. Like, it's very chastising. So, if I'm to believe this by the letter of the law on the screen, I'm failing at ketosis. Any thoughts on how to kind of read the tea leaves here?
I would kind of ignore that. I think that's sort of an app in the process of being sort of developed, the fat sim. Yeah. So you would need like whole body metabolomics to really answer that question if you're in fat burning or do a metabolic cart and look at respiratory quotient or whatever. But subjectively if you feel good, we have seen like in athletes especially, more advanced athletes, that and we do a very strict keto macros and everything, that basically with a bunch of athletes 0.88 is about as high as we get and that's the average across. Sometimes you get guys like 2.5, 2.6 like every day and the same guy with the same, you know, essentially metabolic phenotype will be running 4.3. He could potentially just have greater ketone utilization. So I think it would be important to measure your blood. So a continuous ketone monitor measures interstitial ketones that can be different.
The bio, I think it's a great device. It's very versatile. I can kind of, you know, jump in and out of salt water. The thing stays on me. It's almost like more reliable than a CGM. But I did notice, and I probably used about 50 of these devices, that the first week is pretty accurate and then it tapers off the sensitivity.
And this is a known limitation of the technology is that essentially the enzyme-based sensor system tends to just degrade and you could get around that conceivably just by having the ability in the app to calibrate it. So, if you were to measure it and the continuous ketone monitor is measuring 1.0, but your blood ketones is 2.0, that you should be able to calibrate it like you can with a Dexcom.
So, they acknowledged that at the company and they said, 'Yes, we realize that would fix the problem, but that's not a feature of the app yet.'
They do have in events, they have blood ketone on the bottom right. I don't know if it actually calibrates it. It may just record the blood ketone at this point. It does not have the ability to calibrate it to my knowledge.
I inputted one measurement on the Keto Mojo and it didn't seem to change it, right? The number stayed the same.
No. So, I think it's just logging it because you can do that with a glucometer.
Well, you can do it with Dexcom.
So, that's a problem with the Abbott Freestyle, too. And that's a feedback I gave them because I put these devices on, it's reading me like 130.
But I measure, I'm like 80. It's literally like 50 because...
Wow. If you are lean and it's stuck in your muscle instead of your adipose tissue, the glucose levels are going to be higher, especially like when you work out and stuff.
So, I've noticed this and that's why the Dexcom is very nice because I can calibrate it too. And I consistently show that and that was a major issue I had.
Let me hop in also and just tell folks this is not going to be very quantifiable, but for what it's worth, part of my reason I avoided intermittent fasting for so long is that I thought I would not be able to get sufficient protein or caloric intake and that I would lose a bunch of muscle mass. I was dead wrong about that. I was very, very wrong. If anything, it seems to have enhanced my ability to put on muscle kind of per calorie or per gram of protein ingested. And so, I admit I was totally wrong about that.
Furthermore, on this ketogenic diet where I've historically found it pretty hard to put on muscle, or I shouldn't say keep muscle because I'm only doing it for a few weeks, but I have been astonished by having one small meal. Like I'll have some oxtail soup after this with some veggies and obviously oxtail. It's a whole separate story. And then I'll go out and have another meal probably in like 3 or 4 hours which will be a much bigger meal. And just with that, and I am watching some of the grams of protein intake and so on, but I have not, looking in the mirror and looking at the weights that I'm putting up in the gym, I don't feel like I have lost any muscle and I feel like I have leaned out. Some of that's losing fluid, but I've been really impressed with how little relative to what I used to do in college, like taking weight gainers and just all this garbage, like how little it actually takes to at least maintain muscle mass.
But I do have a question for you which I've never really been able to answer to my satisfaction and it kind of relates to rabbit starvation. For people who don't know what that is, you could probably give a better description. But if you've ever watched the show Alone, Alone is probably the only reality TV show that I love to watch. Seasons six and seven in particular are outstanding for folks. But what you will notice is that if people are trying to survive in the wilderness to outlast everyone else, that's what the show is. You get to pick a handful of items, you get dropped off, you don't get to choose where you're dropped, and then you just need to survive for as long as possible. Sometimes it's 100 days, sometimes it's last man or woman standing. If somebody is only eating lean protein like rabbits, they will waste away. They will not last. They will have to get yanked out for medical reasons. And that might seem strange to people.
My question though is on a ketogenic diet specifically, can you just consume leaner protein and then rely on body fat for the fat? And some people are like, 'Yeah, everybody knows that doesn't work.' But I really want to understand why that's the case, right? Because I understand dietary fat sort of dampens insulin response, or at least that's my understanding. Maybe there's a rate limiting step in how much body fat you can break down and use, right? And who knows if that's mediated by the kidneys or who the hell, liver, I don't know, right? I guess it would probably be liver. But I'd love to hear your take on it, right? Because certainly in the past, I and lots of people reading The 4-Hour Body have been able to lose more body fat than they are told they are capable of losing as measured through DEXA scans and other things. Can you do a like moderate fat or low-fat protein-based keto diet if your goal in part is to lose body fat or does that backfire?
Yeah, just not indefinitely. So, when I did the ketogenic diet for a year, I was cruising about 300 to 320 grams of fat, sometimes 350 grams of fat per day. And then just experimenting, I would throw in two days per week of protein veggies with about 50 to 100 grams of fat. And in those days of dropping to 300 plus grams of fat to 50 to 100 grams of fat after two days, like I swore I lost like 2% body fat in that and I would just transition back. So I would just periodically throw in protein veggie days. I would cruise on keto and then periodically titrate in the protein veggie days to assist body composition alterations. And if I kept that going, I could get pretty dramatic, like almost scary lean to where it happened very fast. It's almost keto trains your fat metabolism. And then if you just start titrating in, it's just pulling fat out. And I think my body really liked throwing in the veggies with the fiber seemed to help with gut health. And I would do that twice a week and it's pretty dramatic.
Why not do it seven days a week? What happens when you try to do it for more?
If the idea is to stay in ketosis, it was really hard for me to stay in ketosis if I do protein veggies. Like after two days, I would kind of be out, but my metabolism would be cranking.
Mechanistically, why is that the case? Why doesn't your body just break down more body fat?
Well, it's taking body fat exogenously and endogenously. And I think the more fat going to the liver, you know, and the more fat that's in circulation gets sort of shuttled to the liver and then that's sort of stimulating beta oxidation in the liver. You just have a greater fat pool. But actually, I think the day that I would do protein veggie days and then the day I would jump back into ketosis, I would see this big ramp up in ketones like that day. Whereas, if I did like a cheat day and just ate a lot of carbohydrates, it took me like two or three days to get back into ketosis. But if I just did like protein and veggies and cruise back into ketosis, then I would rapidly get back into ketosis and just gave my body a break from the fat. But I think just that short amount of time really stimulates mobilization of fat from your body because your body is used to getting it exogenously and then you're pulling more fat off. But yeah, I think on the protein veggie days, I'm getting higher amounts of calories from protein. So that has a bit of an anti-ketogenic effect. And then shifting back into ketosis on that third day, I always had probably the best, you know, ketone numbers for the week.
I don't want to beat this dead horse too long, but I'd love to just hear you riff on this a little bit more because I guess in my mind I'm thinking, well, on your protein veggie only days, if you're getting not enough protein to satisfy all of your resting metabolic rate, right? Like you're hypocaloric, but you're getting enough protein to not lose muscle. Why wouldn't the body just break down the fat that it needs to continue producing ketones? Right? So, I'm trying to avoid the gluconeogenesis problem where you're having like 200 g at a meal with no fat to offset it. But if you're having smaller amounts that are slowly digested, but it's just enough to keep you from losing muscle mass, maybe you're doing some weight training to help with that, you know, or whatever, then I guess what I'm trying to figure out is why the dietary fat is so important because I think of the body, right? It's like each pound of stored body fat is what?
Right? So 3,600 calories, that's a decent amount of calories, right? And for somebody who's, let's just say you're 150 lb, 10% body fat. Okay, you got 15 times 3,600, you got plenty of body fat to go around. So it would seem to be enough to do a few weeks of ketosis that is low fat, higher protein, but not enough protein to necessarily be hammering your liver with gluconeogenesis if you're dividing it up slowly digested protein. Some people are going to be really annoyed with me dragging this out so long, but why is dietary fat so important?
Because I mean that's the fuel that you are using. You coax your body into using. And I should probably add a little bit of context to my protein veggie days. So I would go from like 125 grams of protein to like 300 grams of protein.
That's a pretty big bolus of protein.
That's a lot. Yeah. And if one was to go 100 grams of protein or whatever and then bump it up to like 170 or 200 or something, they may not, you know, kick out of ketosis, but I remember just lower ketones, but not out of, I was still in ketosis. Yeah.
But typically how I think I did it, my protein veggie days were following like a heavy deadlift or squat workout. So the thinking was that I'm recovering for those two days and the extra amino acids and proteins and mTOR activation is sort of assisting in recovery and regeneration and skeletal muscle protein synthesis and then I would kind of go back. I calculated it in that way. So yeah, I like doubled the protein on the protein veggie days but my calories were about the same or maybe a little bit lower.
Yeah. I need, Sibio, if you're listening, please allow me to calibrate this with a finger prick because I need a little more range. I need a little more range than 0.1 to 0.4 for me to be able to read this type of thing effectively, right? Because technically, if I'm reading this as it is, like I'm never in ketosis. I shouldn't say never. That's not true. But in any case, it would be nice to be able to calibrate.
Let's come back to something I promised that I would ask about which is neurodegenerative disease, Alzheimer's, etc. Could the ketogenic diet benefit people with these conditions? And just as important, certainly for me personally, is it plausible there's a mechanism by which the ketogenic diet regularly done could help delay the onset of any of these diseases or am I just Pollyanna hoping for a pie in the sky?
I think that's a question we don't have an unambiguous answer to, but I think all the science points into the direction that if you improve upon and optimize your cardioimmunometabolic biomarkers instead of cardiometabolic biomarkers, because if you can lower for example your insulin and keep that between 2 to 6 and if you lower your hsCRP below 0.6 and then optimize your hemoglobin A1C, your glucose. And I think also, and I've talked about this with Rhonda Patrick and other people, too, that if you measure your omega-3 fatty acids and look at your omega-3 to 6 ratio, I think that's going to be a biomarker that's probably going to end up in standard blood work because it's so compelling, the data behind it.
And you also measure your B12, too. I think that's important. People coming into the Alzheimer's center that can present as flat-out Alzheimer's disease and then you correct their B12, a B12 deficiency will cause brain atrophy. So, and that could be reversed with B12. So, the things that if you're following ketone metabolic therapy, it's impacting the things that we know are driving age-related chronic diseases and then you know obviously one of them is Alzheimer's. So the level of inflammation, hsCRP now is probably more atherogenic than LDL. Like there's probably people selling statins that don't want to hear that, but we know that the data is emerging on that now. So lower insulin, lower inflammation.
And that's an inflammatory marker, right? The C-reactive protein. What does the HS stand for? Or what is that?
High sensitivity C-reactive protein.
So it measures in that lower range. And I used to trend to like two to two to three. Like my early CRP, hsCRP, when I was like on a high carb, I only had it measured twice when I was on a high carb diet. But, you know, since I've been keto, it's either non-detectable or like 0.2 or when I did extreme environment research on myself, you know, then I could bump it up a little bit. And when I had a bacterial or viral gastroenteritis, it shot through the roof. So because it activated your immune system but generally that hsCRP is a big driver. I used to laugh at it and be like ah it's this non-sensitive thing but now like all the data is pointing to the direction that we need to add that to that and your omega-3 status, your B12, make sure you don't have any deficiencies because that could lead to sort of rapid progression to Alzheimer's disease, your magnesium levels.
But also just in general like exercise.
Yeah. The biggest metabolic lever and your body weight, body composition. Get DEXA scans. I know it might be good for you to do a DEXA scan with your keto experiments, too. So, yep. I was doing once a year, but now I end up doing like three or four times a year because I do these mini experiments to see how acutely some of the things are impacting my body composition because I just get antsy for like an answer to that. It's a long-winded explanation to just basically say that your metabolic health is tightly linked to your brain health and can dramatically delay the onset of Alzheimer's disease. Not that you're going to get it or reverse it altogether before something else gets you in the end.
The metabolic health piece, just to underscore that, I mean, one of my relatives in question, ApoE3, I understand that's not the only risk factor, but there something just seemed to be missing, right? Because the decline was so precipitous, it didn't map to any patient data or clinical data that a number of doctors who are also researchers I was working with had seen. Also, because this person, this relative had been assessed four or five years prior and did not show any indication of predisposition to a rapid decline. I'm ApoE3/4, again recognizing there are other factors at play but when she just kind of disintegrated, a few things came to light. Number one is her local GP had basically missed severe metabolic dysfunction for years and I can't remember the reference range but like insulin, let's call it upper bound of 12, I'm making this up but you'll get the idea, and she was like 43, right? It was just absolutely atrocious.
And her body weight and just general like composition.
Poor body composition. Yeah. Poor body composition. Very little exercise despite my best efforts. Misbehaves horribly dietarily. Not morbidly obese, but certainly...
Smoking, alcohol, other drugs?
But here's the other piece. So she had been diagnosed stage one breast cancer, had a lumpectomy, was removed late 70s, was put on an estrogen, I think it's an estrogen blocker called letrozole. I looked at this and I spoke to a friend of mine who was a radoncologist and she said it is very poorly tolerated by most women from a cognitive perspective like they get smashed by and large.
Guys too, by the way. Guys, too.
Guys that take aromatase inhibitors, you know, for like TRT and things like that. It's not a good thing to do.
So, I was looking at it and I mean it's upsetting that I'm the one who has to kind of find these things. But it's like, okay, well, we think about the oncologist role. It's to prevent my mom from dying of cancer. That's the directive, right? But if she were 30 and had later stage cancer that was really aggressive, it's one thing. But she's late 70s, stage one, all cancer removed. And so got her off of the letrozole with the cooperation and after discussions with doctors and almost saw an immediate turnaround within a handful of weeks after the washout period and everything. But it seems to, I mean look I'm not an MD, I don't play one on the internet, but it seems to have done some real damage. I mean there's the metabolic piece that is very non-trivial but the acceleration of decline was just so absurd over the course of a handful of months. Terrifying to see.
But I guess I'm laying this all in not necessarily to explore this particular case because I've got a lot of people on it for all of my relatives, but it's just to say that I am not going quietly into the night with something like Alzheimer's, right? And so what I'm trying to figure out for myself, I'd be curious to hear your perspective. I will be honest, I find keto pretty goddamn boring. Like I don't find it to be the most diverse diet in the world. I don't really want to do it all year round. I also have some maybe compromising cardiac elements. I'm a cholesterol hyperabsorber. So I do, I use again guys talk to your doc, don't just copy me, but it's like I'm using Repatha, taking ezetimibe. I have been also taking Nexletol but that might end up being redundant, the bempedoic acid with the Repatha. That is a long way of saying like I got to keep an eye on the heart stuff because neurodegenerative disease and cardiovascular disease is what kills everybody in my family. So, for a lot of reasons, I don't want to do keto all year, but I'm trying to figure out like what is the sort of minimal effective dose.
And I know we're going to have to probably take a couple of speculative leaps here, but just as a working hypothesis, right? What does a minimum effective dose of following a strict ketogenic diet look like for me? Assuming the rest of the time I'm still doing intermittent fasting. I'm not eating a lot of refined carbohydrates. But how might you suggest that I think about that? Because I don't know what the durability of kind of keto memory, like metabolic memory is. So, I'm trying to figure out like can I get away with two, three to four week periods a year where there's some carryover of like cancer protective, you know, our last conversation we kind of talked about thinking about ketones as hormones but in terms of neuroprotective, anti-inflammatory, yada yada yada, what are your thoughts?
Well, I think in your context it's hard to say like, you know, to give absolutes, but I would say you can get 80% of the benefits with a low carb diet. Low carb meaning, you know, 100 grams a day, just fibrous, non-starch, non-sugar carbs, low carb Mediterranean, if you want to call it that. And then periodically, maybe one week out of a month, get into a deeper state of ketosis and higher is not better. We know that from the research. When ketones get into that two, three, four, five millimolar range, that creates energy toxicity and something we call reductive stress. And that is not good. I did not know this before getting into this kind of research. But the sweet spot seems to be between one and two for therapeutic ketosis. Unless you're metabolically managing a disorder that's highly responsive to a ketogenic diet, like, you know, neurometabolic diseases and some of the things that we actually study need to be in the two to three millimolar and oxygen toxicity needs to be like four to five because it's a very powerful seizure control. But one to two seems to be the sweet spot for metabolic management of many different things and also just general metabolic health.
And I think what you'd be doing just doing low carb and periodic ketosis is just enhancing your metabolic flexibility and maybe increasing the diversity of food that you're eating to prevent micronutrient deficiencies too. I am of the opinion that plants are good for you to eat. Broccoli, asparagus, salads, you know, colorful vegetables, things like that that kind of fit into a pattern of eating that we've known. Even things like lentils are probably good. Lentils actually have like zero CGM response to me.
