Written by Christopher Kelly
June 23, 2016
Tommy.Wood.on.2016-06-07.at.10.29
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Christopher: Hello, and welcome to the Nourish Balance Thrive Podcast. My name is Christopher Kelly and today I'm joined by my Chief Medical Officer, Dr. Tommy Wood. Hi, Tommy.
Tommy: Hi.
Christopher: We are going to talk about ketone supplements. And the reason we're going to talk about ketone supplements is there have been a couple of podcasts recently, first one on the Bulletproof Podcast and then later on the Ben Greenfield Podcast, where the guest was Dr. Richard Veech and he talked about ketone supplements. And that raised a lot of questions for us because we talked about ketone supplements on the podcast. I've personally been taking ketone supplements for a couple of years at least now.
Dr. Veech said that he wouldn't touch the ketone supplements that I've been taking with a ten-foot pole. And I think it's fair to say that when someone of Dr. Veech's caliber says something like that, you pay attention. So why don't we start by, Tommy, you telling us a little bit about Dr. Veech, his lineage, and the type of research that he's been doing.
Tommy: I mean, Dr. Veech is essentially considered almost the father of ketone research and particularly the ketone ester which we'll talk about a bit more later one. It's not very often that I look at somebody's CV and wish that I had their CV but I wish I had his CV. He went to Harvard Medical School in the '60s and then after doing his residency he went and did a Ph.D. with Hans Krebs at Oxford.
Christopher: Of Krebs, the Krebs cycle. If you've heard me talking about the Krebs cycle on the podcast before, that's this Krebs.
Tommy: Yeah. The same Krebs, the guy who basically discovered the Krebs cycle, obviously. So, this is kind of like he comes from a lineage of some of, I guess, one of the best periods of basic biochemistry where we were discovering what's actually going on in the cell and the mitochondria for quite a long time now, decades, has been running a metabolic control lab within the NIH and looking at particularly ketosis and then the development of ketone esters as an alternative fuel supply in a number of different, for a number of different conditions.
So, he's interested particularly in neurological conditions but just basically degenerative disease in general. And he has done some very interesting research basically looking at the effect of ketones on -- a lot of the data that he quotes is from a paper back in 1995 basically looking at the effects of ketones and insulin on cardiac contractility. So, basically heart contractility and cardiac efficiency. And that's where a lot of his sort of claims about ketones and their effect are coming from. So, they're kind of based from that research he was doing about 20 years ago.
Christopher: Okay. And the things he said about ketone supplements were not general at all. He made some very specific remarks about certain types of ketones. It wasn't the ester that he developed that he was concerned about. It was the ketone salt which I believe the only commercially available product has been designed and manufactured by Patrick Arnold's Prototype Nutrition Company, is that correct?
Tommy: Yeah, I think so. They've been using -- so, that's the one that, obviously, if people are taking exogenous ketone salts, they're probably taking Patrick's product. They have been using ketone salts experimentally and in research and in sort of small clinical and pilot studies for longer than that but I think he's the one that sort of made them popular to the market. But he didn't sort of come up with them for nothing. They've been using them in research in animal studies and in clinical trials in human particularly with some metabolic disorders, inherited metabolic disorders. They've been giving, using ketone salts for a very long period of time.
Christopher: Right. And then certainly in the Ben Greenfield Podcast, I remember that Dr. Veech raised a question mark over whether it was a good idea to consume that much salt in terms of maybe your heart health or blood pressure specifically. And what are your thoughts on that?
Tommy: Yes. So, that's a very interesting question. You're talking about -- so, for the doses of ketones that he's trying to get to, sort of tens or over a hundred grams of beta-hydroxybutyrate, then in order to do that, if you're doing a one to one ratio with sodium, that is many, many grams of salt equivalent far more from maybe ten times at least more than the sort of recommended daily amount or whatever it is. So the problem there is sort of the connection between sodium, salt and cardiovascular disease particularly, which actually probably isn't watertight as we originally thought.
There's plenty of data also showing that if you don't have enough sodium, and actually that within -- if you're eating as much as you're told you should, that little one or two grams a day, then actually some people get problems, cardiovascular problems from that, from eating too little.
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And when you're on a very low carbohydrate ketogenic diet, which a lot of these people are when they're using these salts clinically, then actually they're giving very, very high doses of salt and you actually just end up peeing out most of it, so you don't retain much of it anyway. They've used these salts at very high doses, multiple grams per kilo. So, I'll be taking maybe 100 grams of ketone salts per day equivalent if not more and they're not seeing this sort of negative blood pressure effects.
Obviously, these are in people who maybe have much more serious problems we're dealing with in the short term because they have these sort of inherited metabolic diseases. But at least they're not seeing this hugely negative effect from the salt that's being suggested. But equally, if we look at people who are taking these ketone salts, and you do that when you're racing, you're not taking tens and tens of grams of ketone salts. You're taking maybe one scoop, which is 15, 20 grams, something like that.
Christopher: Yeah, something like that. And then the liquid, the beta-hydroxybutyrate sodium potassium salt liquid, it's only 30 cc, I believe. So, it's not very much liquid. Like how much salt could really even be dissolved in there?
Tommy: Yeah. And that's enough to significantly raise your blood ketones. So I know when you've experimented with this yourself, you've gone from an 0.1 or 0.2 millimole up to a close to one millimole just by taking a dose of that.
Christopher: Yeah, that's correct.
Tommy: So, even without huge, huge doses -- so, some people might need huge, huge doses if you're actually use these ketones as a sole fuel source which you might have to. But, obviously, in just like an athlete or somebody who's just trying to boost ketone levels, then you can take much, much smaller doses and get some significant increases in your ketone levels. So then the salt issue, regardless of which side you come down, it's probably not that much of a problem anyway.
Christopher: So, in conclusion then, the sodium potassium salts, the amount of salt that's present in the liquid or the powder is not going to be a problem.
Tommy: Yes, unless -- I think it could be a problem if you're taking extremely, if you're taking hundreds of grams of this stuff a week and you're taking that in concert with a western style diet where your body is basically primed to retain more sodium through insulin and atrial natriuretic peptide, anti-natriuretic peptide [0:07:32] [Phonetic]. So basically, it forces you to keep more salt from the kidneys. The kidneys reabsorb more salt. Unless you're eating that kind of diet and taking huge doses of this, I don't think there's going to be that much of an issue.
Christopher: That's an interesting point then because I fear that ketogenic junk food is coming and that may be the context, right? That people are taking these supplements in the future. It's something to think about.
Tommy: No, absolutely. I'm not giving huge, huge doses of salt a free ride if they're in the context of an otherwise crappy lifestyle then I would, I would say that they're probably worth thinking about.
Christopher: And is that true of the other part? So, KetoCaNa is calcium and sodium, correct?
Tommy: Yes. That would be the same. Each of the salts are a mixture of sodium with either potassium or calcium. So, the sodium issue is going to be the same with both.
Christopher: And then what do you think about Veech's claims that the ketone salts just don't raise the blood ketone levels enough to have any effect in the brain?
Tommy: Yes. So, he said basically that in order to get physiological benefit of ketones in the brain that you need ketone levels up. I think over four or five millimole, which just isn't -- I mean, that's just not true. Because the uptake of ketones into the brain by the molecule oxalate transporters is basically linear with ketones in the blood up until -- if you've got ketone very, very high through prolonged starvation and you might sort of reach the limit that those transporters can take up. But the average person whose either doing a ketogenic diet and nutritional ketosis or supplementing with something that increases ketones, those ketones will get into the brain and uptake into the brain is basically just linear with blood ketones.
So, anybody who has taken anything to boost ketones like an MCT oil or if they've taken ketone salts, I mean, you can tell when your blood ketones go up. There's a definite cognitive effect. So, you know that they're getting into the brain.
Christopher: Right. So, that statement again is false. It's just false.
Tommy: Yeah, that's just wrong.
Christopher: But there is an interesting point here in that we've noticed this ourselves and you've seen it in the research, that the ketone supplements may not work any better than some of the other products namely MCT oil?
Tommy: Yes. So that, I think, is difficult because this hasn't been done as extensively in humans as it has been done in rats. And I think the best study on this was done by Don D'Agustino, by his group, and actually Patrick Arnold was a collaborator on that project, I guess, because he was helping synthesize the ketone ester they tried as well as maybe the beta-hydroxybutyrate salts they used.
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And this was in rats. But they basically gave five to ten grams per kilos. This was high, high doses of ketone salts or MCT oil or a ketone ester and then looked at how blood beta-hydroxybutyrate track over time. And actually, those doses and MCT oil, a mixture of C8 and C10 actually increased blood ketones more than either the beta-hydroxybutyrate salts or the ketone ester. And actually in rats, at least, the beta-hydroxybutyrate salts, even at very high doses, didn't really make that much of an, didn't really increase blood ketone levels that much.
I am quick to say that the effect is, obviously, different in humans because I know plenty of people, yourself included, who have taken ketone salts by themselves and seen their blood ketone levels go up. So, the effect maybe isn't quite the same. But I'm kind of tempted to say that MCT oil is probably going to be my preferred way to boost blood ketone levels in terms of the effect you get for the dose that you give.
Christopher: I think it's difficult to measure at home. I've checked a few times and sometimes I can get the KetoForce to raise my blood ketones from 0.2 to 1.2 in 45 minutes. But then when I checked more recently I couldn't get KetoCaNa -- so admittedly, this was a different product but still the beta-hydroxybutyrate salts, only raised my ketones by 0.7 millimole in 45 minutes. And that was exactly the same as MCT oil. PhatFibre, for example, does exactly the same thing. I measured that on subsequent days.
And then I measured on another day exactly the same time and saw no difference in my ketones where I didn't take a supplement. It definitely wasn't a fluke. It was always 0.7 millimole, was the amount that both the PhatFibre and the KetoCaNa raised my blood ketones. I would really like to hear from people. There is a comment section on the show notes for this page. If you've done some experimentation and you've compared MCT oil or any other ketogenic supplements and looked at how they raise your blood ketones, I would love to know your data. So, yeah, please do leave me a comment in the show notes for this episode.
So, if you thought this episode was technical so far, you aren't seeing nothing yet. But bear with us. I think it's better for this stuff to maybe go over your head a little bit and my head a little bit too and then listen to it again later and then I'm sure you'll understand it. Perhaps I should link to some Kahn Academy videos that might help you understand this in the show notes for this episode. Because we're going to talk about a little bit of stereochemistry. And when I say we, Tommy, you're going to talk a little bit about stereochemistry.
Because this is super confusing. Compared to anything I've seen in computer science, this is very, very confusing. And to take it back to what Veech said on the podcast, he said that the L form of beta-hydroxybutyrate was harmful and inhibitory. So, before we get into the details of that, we better understand what the differences are between the L form and the D form because this is not specific to beta-hydroxybutyrate, right?
Tommy: No, absolutely not. So, basically, when you make a molecule -- and so this is particularly important. If you're making something in the lab, you're doing organic chemistry, so that's basically making reactions, making compounds like various acids or whatever, it could be more complicated plastics or whatever, in the lab, when you make something, you always form two forms and usually in a roughly 50-50 mixture just because the reaction can go in one direction or another and it just sort of balances out.
And the compounds you produce -- and it depends on the compound whether they have a mirror form but most or many in biology have a mirror form. So, they are basically mirror opposites of one another. So they're not the same. You can rotate them so that they end up exactly the same orientation. But if you put one in front of a mirror you get the picture of the other. And you might not think that that makes much of a difference but in biology we usually only use or make one particular form of something and this is the same with amino acids, with ketones.
And if you make one form, that's usually the most biologically active form and then that's the form that you want, that the body is used to dealing with. And so, in other things where I see this the most is in something like vitamins. So, if you make vitamins in the lab rather than extracting them from food then you're going to make two different forms. So, if you look on your multivitamins and if it has -- so, vitamin E is a common example.
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And you have something called, you'll say dl-alpha-tocopherol, for instance. And if it says DL, that means that it has the D, which is the dextro version, and the L, which is the laevo or the left handed form. So, you have two different forms. And those are made because it's a synthetic form. And the body only uses one of those forms and the other is basically just metabolites then dumped out because it's not useful. Whereas you can then -- you could also look on something is [0:15:29] [Indiscernible] it has just the D form and then you know that it's a natural vitamin E that's been extracted from food and that's the biologically useful one.
But then if we go and take this into the ketone side of things then when you're making ketones in the body, so when you're making beta-hydroxybutyrate or acetoacetate in the body, you will make the D form or the R form. It's two different etymologies to mean the same thing essentially, so you see the D or R, depending on where you look at it.
Christopher: So, if you thought this is complicated so far, they created two different naming schemes.
Tommy: Yeah.
Christopher: And that was even more complicated.
Tommy: Exactly. It's interesting actually because people talk about the D form of the beta-hydroxybutyrate but then when they're talking about the actual chemical, they'll usually put R. So, when Dr. Veech is talking about his ketones, he talks about the D form being important but then when you look at his ketone ester, the ketone ester is listed as the R form but that means the same thing. So, just in case people actually go and read the research, which they should because it's very interesting.
So, when you're making beta-hydroxybutyrate synthetically in the lab you will make a mixture of the R form or the D form and the L form, otherwise known as the S form. So, L and S is the same, R and D is the same. And you'll make a mixture of the two. And it's very expensive and time consuming to separate those out. So, what people do, is if you're making a beta-hydroxybutyrate in the lab, you just have the mixture and the mixture is what you give.
But what Dr. Veech was saying is that if you give a mixture then that's dangerous because the L form or the non-natural form is going to be inhibitory or then cause problems within the cell. And that's kind of where big burden of contention has come up because Dr. Veech has a ketone ester that he's developed which basically breaks down into only R form beta-hydroxybutyrate and then you compare that to somebody else who's formulating ketone ester like Dom D'Agostino and his is a racemic mixture, we call it. So, it's a mixture of the two different types and it breaks down into beta-hydroxybutyrate and acetoacetate.
And so, I think, there's a bit of a politics at least starting to come here because Veech is basically saying that D'Agostino's ketone ester is, not even saying that it doesn't work. It's actually actively saying that it's dangerous.
Christopher: That's the key word that I think you hear everywhere now, this idea of a racemic mixture.
Tommy: Yeah.
Christopher: I wasn't very familiar with it until this story came up. And now it's like Toyota Prius. I see it everywhere. I'm like how did I not notice this before? I think I had seen it in some of the Kahn Chemistry but I just never had a reason to think about it. And then when I did, it was everywhere. So, I think this is an important concept that people should know about.
Tommy: Yeah, absolutely. It's very important. And if you go back to something like the vitamins I was talking about, if you're giving a certain dose of vitamin, if only half of it is useful to the body then obviously something like the recommended daily allowance or the amount that you need is immediately doubled because half of what you're taking isn't useful to the body. And in some cases, it might even compete with the natural form and then you need to take even more. So, the bioavailability of synthetic vitamins is usually 20% to 50% of what the naturally occurring vitamin would be.
Christopher: So, it is important, the general concept of a racemic mixture is important. But in the case of beta-hydroxybutyrate, it's not important.
Tommy: No. And so, there's a number of different issues that come up from this which we'll hopefully try and get through all of them in a way that it makes sense. But the first one is that what we were told initially is that the L form of beta-hydroxybutyrate, first of all, that it was dangerous, that it's having some kind of negative effect on the body. And there is absolutely no evidence for that. I know that you got in contact with Dom D'Agostino to ask about this. And we'd already done some digging and he sent us, he pointed us in the direction of the same papers.
It was absolutely his message was that the L form is definitely not dangerous. And that's because it either gets converted, broken down by beta-oxidation like a fat would be, or it gets converted back into the D form of beta-hydroxybutyrate so the body just deals with it as and then creates the normal form of the beta-hydroxybutyrate and then it can use it as it would normally.
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And they've done this basically using tracer studies. so, if you give some kind of compound, it's usually a carbon that you can trace, then you can see where that carbon goes into other molecules and you could basically see that it goes from the L form and gets switched over to the D form in the body naturally. So, anything that could then happen, there doesn't seem to be any negative effect because you end up using it normally anyway.
Christopher: So, where does the L isomer go when you radio label it?
Tommy: So you can track it and you can see that it basically ends up being metabolized so you just breathe out as CO2, so these are the carbons you label. So it's being beta-oxidized or you then pick it up as part of the D form of the beta-hydroxybutyrate. So you can see that it switched over.
Christopher: Okay.
Tommy: And so then in the first podcast that Dr. Veech, he talked about this one, Bulletproof Radio, and he talked about this. And then after that, I think maybe somebody picked him up on this because when he talked about it a second time, what he said was that it's a problem if the beta-hydroxybutyrate gets beta-oxidized, basically broken down as a fat, because then what it does is it changes the redox state of the cells. So, this kind of then goes to the original work that Dr. Veech was talking about, looking at the effect of ketones on the heart. So, this is looking at the efficiency of the heart.
And what I saw was that when he gave ketones -- he was giving five total millimoles of ketones. It was four millimole of beta-hydroxybutyrate and one millimole of acetoacetate. And what he saw was that basically there are two sort of pockets of sort of electron acceptors and donors that then get moved to the cells. The first one is NAD which gets converted to NADH when it accepts an electron. And that's kind of like probably our main energy carrier within the cell. So whenever we do glycolysis or we do turns of the Krebs cycle, we make NADH and then that NADH is then used to give electrons to electron transport chain which then sort of drives the production of ATP.
So, if you give ketones then you increase the amount of NADH you have. So, you give more electrons to NAD. And when you give electrons you reduce something so then you have a reduced version of the NAD to NADH couple, is how you call it. And then where those electrons end up going is to ubiquinone or Q10 that people would probably have heard of, and that's within the electron transport chain. And that has two states as well. So, you have the Q and then you have QH2 which -- and the QH2 is when Q has two electrons attached to it.
And so, and what you see is that you have more electrons going to NAD and then actually you have a more oxidized Q so you have fewer electrons in Q. And then what that does is you basically have this difference, this potential, energy potential between NAD which is high in Q, which is low and then you have what you call, what he calls the delta G of ATP. So, it's basically the energy from hydrolysis or the use of ATP. And the big difference between those, basically the more potential you have to generate and use ATP. Does that make sense?
Christopher: That's the Gibbs Free Energy equation?
Tommy: Yeah.
Christopher: And I can link to that. There's a very good Kahn video on that, so I can link to that in the show notes too.
Tommy: So, his idea is basically that the reason why ketones is so good at increasing efficiency is because they give lots of electrons that you end up with lots of electrons with NADH but you oxidize Q relatively so then you have a big delta G. That's what he's trying to create. Now, when you beta-oxidize something, you relatively give more electrons to Q. So, he then was saying that if you're beta-oxidizing the L form of the beta-hydroxybutyrate you don't get as big a difference between NADH and Q. Right?
Christopher: Right. And so beta-oxidation is a fancy way of saying oxidizing fats but it can happen to other molecules namely this L form of beta-hydroxybutyrate.
Tommy: Yes. So, well, basically anything where you're producing Acetyl-CoA from that direction, as in not from glycolysis but through the other pathway in the mitochondria.
Christopher: Okay.
Tommy: And the reason why this then starts to become even more complicated is because, yes, that may technically be true but any fat you ever eat at the same time as the ketones that you're taking is going to have the same effect. So, unless you're eating only ketones or only ketone esters, there's no physiological relevance to what you're saying because at some point you're all going to be beta-oxidizing fats at the same time as you are metabolizing your ketones, right? Everybody is going to be doing that. And then if we're trying to figure out why these things become confusing, is because if you go back to the--
[0:25:03]
You need to go back to the original. So, he's talking about 28% increase in cardiac efficiency from the studies that he did which were, they're beautifully done studies. They're just break example of Krebs informed biochemistry looking at the ratios of different metabolites, to look at redox state of the cell, and this is something that [0:25:23] [Indiscernible] a lot more looking at our results from our athletes and the people that we work with. Based on this work--
Christopher: He measured the same metabolites that we measured on the organic acids test.
Tommy: Exactly. So, using the same metabolites and the same ratios that Krebs was doing and then Veech was doing, we can then get an idea of what's going on in the cell. And so that is beautiful biochemistry. I'm not disputing that. The problem is, you're getting these numbers from an isolated perfuse rat heart. So basically, you just have a rat heart and you can measure what's going in to the arteries into the heart and what's coming out of the veins. And you can look at how much oxygen is taking up, how much work is producing, how hard it's pumping, the pressure it's producing.
So you can measure all this in this tiny little heart. But the problem is what you put into what's going into the heart. So, the idea of this original paper was to look at the effects of insulin particularly and ketones and then the combination on cardiac contractility. What's going into this fluid that's going around the heart is ten millimole of glucose, and I don't know anybody who would want their glucose to be ten millimoles, ever, right? So, you already have very high levels of glucose.
And then the insulin states, they wanted to maximally stimulate the insulin pathway, so they used 100 nanomole of insulin. And it doesn't sound like very much but you think about the units that we normally talk about in terms of insulin. So, we're talking about micromoles per mil is how we measure insulin. And we usually want, if people are on a fasting insulin say, we want it to be less than ten, maybe ideally less than five. 100 nanomole of insulin is 14,399 micro units per mil.
Christopher: That's a lot of insulin.
Tommy: That is a lot of insulin. So, again, you're extracting this from something that is just completely so far out of the normal physiological bounds and there's no -- and so many are talking about beta-oxidation interfering with this. There are no fats in this mixture so there's no fatty acids then which could also be potentially used as energy. So, you're automatically removing even more sort of physiological relevance.
So, insulin is really good at increasing cardiac efficiency. And more recently, for a few months before I started my Ph.D., I worked in the toxicology department in a hospital in London. And when people take an overdose of a drug that is toxic to the heart, so something like a beta blocker or a calcium channel antagonist, basically what they do is they give huge doses of insulin. And the reason why is because insulin is really good at increasing the efficiency of the heart. So, actually, this keeps people alive while they metabolize out whatever the drug is.
And as far as I know, they don't really know exactly how it does, but they know that it does happen. So, insulin is really good at that. But when you're then trying to actually convert this into something that's useful for a whole human, then all of a sudden I just don't think it's that physiologically relevant because you're going to be eating something else at the same time and you're not going to have the levels of glucose and the levels of insulin that we used in these studies. Then automatically, everything, the context completely changes.
Christopher: What if I just have jam on my bread and then the ketone ester? Will that be okay? No beta-oxidation, right?
Christopher: No beta-oxidation and you're going to increase your insulin really nicely and your blood glucose. And you'd have to take, maybe take some nicotinic acid which is going to prevent lipolysis. So, you're going to prevent the breakdown of your fat stores so you're not going to have any fatty acids in the blood. That combination, then you're getting close. But I don't think anybody is really suggesting you do that. But it will be an interesting experiment.
So then the next issue that I have with all of this is that probably figured out that if you're going to give exogenous ketones, maybe some of the ketone esters better than the ketone salt. You maybe don't want to give lots of salt to people or if you look at the rat studies, ketone esters increase blood ketones more than ketone salts do. So, when we're talking about reducing the NADH and oxidizing Q, so you get this big difference. And Dr. Veech has talked about using ketone esters or using ketones to basically, he wants to maximally reduce NAD, so make lots of NADH.
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For Alzheimer's, Parkinson's disease, whatever. But the problem is, if you actually look at these diseases, more and more were finding out both in animal models and in actual people, so type II diabetes, that's the same in the liver, Alzheimer's disease is the brain, Parkinson's disease potentially as well. These people already have an overly reduced NAD to NADH ratio. They have lots of NADH already. They just can't do anything with it. And that's because they have some kind of mitochondrial dysfunction.
So, if you're trying to stuff more electrons into NAD, into a system that already can use it, you're going to cause more problems. So, the theory is very nice. You create this delta G of ATP and then you make all these ATP and everything works really nicely. But the people that you're working with, once you have this metabolic problem, the issue is not with the amount of electrons they have on NAD. The issue is then how they process those, say to do with, particularly to do with mitochondrial function. And so, actually, the whole issue just almost isn't relevant anymore because you're trying to fix a problem that is the exact opposite of what you're seeing in patients.
Christopher: So, that's quite a lot of technical stuff to get through.
Tommy: Is there anything that I haven't explained properly?
Christopher: No. I don't think so. I think the only thing that we haven't really explained is why Veech would do this? That's what kind of -- I just cannot get my head around why would he do it? It would seem like the ester has the potential to be a superior product but isn't commercially available yet. And the salt, it almost seems like he's engaging in an anti-competitive practice of presenting this misinformation to people who couldn't possibly question him because of who he is and his credentials. And that's maybe buying him some time while he gets this other product to market. But that's purely speculation. What do you think about that?
Tommy: I can only agree with you. He's talked about how if you've got people to make these esters from a corn base, which you already have access to a lot of in the US, then they can make this stuff very cheaply. But he's also talking about the fact that you have literally millions of Alzheimer's and Parkinson's disease patients who would then take these. So, the amount of money that's there to be made from this is potentially huge and he has the patent for this one particular ester that then would be his intention to use in these patients.
And, obviously, you couldn't get something to market if you couldn't then give it to people and show that it gives benefit. And I think if you're actually increasing blood ketones you will get some benefit. But he talks a lot -- he has two famous taste studies he talks about. He has a friend, somebody who works with him, somebody called Bill with Parkinson's disease who has been vastly improved on a ketogenic diet. But that ketogenic diet is just based on low carbohydrate and adding some MCT oil. There's no keto esters in there. Last time they were talking about it, it was just a basic Bulletproof coffee, MCT oil, low carbohydrate diet.
And very similar with another patient who was actually the husband of Mary Newport and Mary Newport is a doctor who's been doing a lot of research in ketones or MCTs, coconut-based MCT oils to try and increase ketones. And her husband had Alzheimer's disease. And he actually saw a lot of improvement on a mixture of coconut oil and MCT oil. And then by all accounts actually he had, he was part of a clinical -- this is a published case study so it's not confidential or anything.
He then went on a clinical trial and basically I think it was the drug actually caused some issues. That's how the case study reads anyway. And so, the kind of where people are seeing this benefit from a ketogenic diet is just a standard ketogneic diet. It doesn't necessarily mean that you need to just restrict carbohydrates really intensively. You can do something like boost it with MCT oil. And what I like about MCT oil is because when we're talking about the formation of ketones -- So, you have acetoacetate and you have beta-hydroxybutyrate.
And everybody talks about beta-hydrobyxbutyrate because that's the main one that you make. But you make a beta-hydroxybutyrate by making it acetoacetate first and then you convert that to beta-hydroxybutyrate. And to go back -- I'm sorry to get technical again, but when you're making beta-hydroxybutyrate you basically use up an NADH to convert acetoacetate into beta-hydroxybutyrate. And if you go back to Krebs' original papers, they use the ratio of acetoacetate to beta-hydroxybutyrate as a measure of the redox state of the cell. So, basically, how many electrons were on NAD versus NADH.
Christopher: And we could do the same with our organic acids test, right? Both of those metabolites are on the organic acids test.
Tommy: Exactly. So we can then just use urinary organic acid test to look at people's metabolic state. And you kind of might think that it's really important to have all these electrons on NAD making NADH but NAD in itself before it then gets electrons attached to it is also really important signaling molecule.
[0:35:04]
So, it activates certain types of sirtuins which then activate loads of genes that are associated with mitochondrial biogenesis or longevity. And so you need enough NAD. You need a good NAD to NADH ratio for proper metabolic health. And what I really like about giving MCTs or you could also give something that makes acetoacetate rather than beta-hydroxybutyrate is because then when the cell has made these ketones it can decide whether it wants acetoacetate or beta-hydroxybutyrate based on the redox state of the cell. And it's exactly the same, if you convert it, it's exactly the same with lactate and pyruvate.
So we know if you're doing anaerobic exercise and you don't have enough oxygen to accept the pyruvate into the mitochondria and do the electron transport chain you then convert that pyruvate to lactate instead. And the reason you do that is to regenerate NAD. So, you basically use up an NADH and make more NAD because you need that NAD to keep things moving to the cell. And that's why you make lactate.
So, you can do exactly the same thing with the ketones. If you have an overly reduced cell, you have too many electrons, too much NADH, you don't know what to do with it, you could actually make proportionally more beta-hydroxybutyrate and actually that's a beneficial thing because particularly this is going to happen in the liver and we know that if the NAD to NADH ratio drops in the liver that's associated with insulin resistance and all these other problems that you then get fatty liver, stuff like that.
Actually, this gives the liver an opportunity to sort of offload some of that NADH that it hasn't been able to use and then can ship off the beta-hydroxybutyrate into the body. And that's probably where you're getting some of those benefits. I think if you're starting with acetoacetate or you're starting with MCTs you actually give the body the ability to adjust its redox state more easily. You give it more options. And that's probably where you're getting some of the benefit of supplementing with ketones.
Christopher: Interesting.
Tommy: That's my theory. I have no studies to back that up. This is just based on the basic biochemistry.
Christopher: The fun thing about this is we have the data. As soon as I figure out how to pass the data out of the organic acids result, which is sort of PDF format at the moment, we can write some programs that looks at this redox state of the cell and they maybe see if we can find some correlations with other things. That will be an interesting project that we got going. Yeah, I think this is really fun stuff.
Tommy: Yes. I was just going to say we've been doing a little bit of that, just sort of basically looking at the ratios that these are metabolized.
Christopher: Eyeballing it.
Tommy: And at the moment it's just eyeballing it, right. So, even if certain metabolites are within the normal range, you can look at the ratios of them and you can see that say somebody has issues with NAD or they have issues in the mitochondria with Q10 and stuff like that. So even if nothing is not super high or super low, you can sort of see how the ratios of things are basically telling you what's going on inside the cell. And then we also know that in people who have big shifts and stuff you can then look at the basic bloods and then they have elevated blood glucose, they have elevated fasting insulin or a high Hb1c or high triglycerides or something like that.
So, you can kind of see that the two interacts. We're just going to try and find a way to sort of actually predict that based on the actual data rather than having to sort of eyeball it ourselves.
Christopher: So, in conclusion then, the racemic mixtures, the ketone salts are neither dangerous nor inhibitory to the best of our knowledge and you don't need to stop using them.
Tommy: No. And I think somebody we were talking -- because I know you contacted a lot of sort of the experts in this field, Dom D'Agostino, Patrick Arnold, some of the guys who gave a lot of information that we're sort of talking about now.
Christopher: Tons of references, yeah.
Tommy: Yeah. And so we're kind of relying on their expertise as well. But somebody along the way has said that we can't 100% guarantee that the L form of the beta-hydroxybutyrate isn't doing something that we don't know but based on all the data we have there's nothing to suggest that it's dangerous or harmful.
Christopher: And I will, of course, put their citations in the show notes for this episode. And then I will also link to the show notes for Ben Greenfield's interview with Veech where he has updated those with a statement from Dominic D'Agostino.
Tommy: And from Mary Newport as well.
Christopher: And from Mary Newport as well. It's so curious. The tracer studies were done by this guy called Henri Brunengraber, I think is how you pronounce that name. And he's Veech's colleague. It's bizarre. But, yeah, maybe this is a good point to segue over into the study that we're doing with Phat Fibre. So, do you want to talk a bit about that, Tommy?
Tommy: Yeah. So, if anybody hasn't heard already, Phat Fibre is basically something that we put together. It's a powdered MCT oil that uses basically a form of resistance starch to make the powder. So, if people who are having issues with all the other additives and emulsifiers and stuff that you end up with other MCT products, then this is kind of something that is a lot -- it's just two ingredients.
[0:40:00]
And we've tested them on lots of people including those with sensitive guts and seen no problems at all. But what we're going to do is try and sort of quantify the effects. People are going to take this because they want to increase their blood ketone levels. And so, we're actually going to do a study where I think we have--
Christopher: I've got at least 15 people, yeah, recruited so far and I think that will probably do. Do you think that's powerful enough?
Tommy: I think that's going to be. And it's not going to be like a placebo controlled anything. But what we will do is each person, we will measure each person's data and when it goes up it will go up in the website and maybe actually formally published if possible. And you'll get the data for each individual person as well as maybe some statistics.
But basically, what we're going to do is we're going to do basically a Kraft insulin assays. So you basically measure insulin and glucose over time over four hours after the Phat Fibre. And then also we're going to measure ketones at the same time. So, we will get basically a curve, a graph of glucose, insulin and ketones after a Phat Fibre load and see how those all track together. Because ideally, we don't want much to happen to blood glucose or insulin. Maybe they might go down a little bit but we'll get a nice sort of ketone response.
Christopher: And that's one of my most commonly asked questions, is does this thing have maltodextrin in it? Is it maltodextrin sugar? And it's the same word but it's a resistant maltodextrin that we don't have the enzyme to breakdown. So, it ends up being a fermentable substrate or maybe even just poop straight out as soluble fiber. And so we will see whether there is a glucose response to the resistant maltodextrin.
And the Kraft test, I think, is worth mentioning for people that don't know, is a dried blood spot test that you can do at home. So, that's the problem with doing this in a lab. If you send someone to the lab and it's a four-hour test and they have to be sat in the lab to measure their insulin every 30 minutes or whatever it is, six data points, which is super inconvenient. But with this Kraft test, you can actually do it on dried blood spot at home and then mail the samples into the lab.
And we've got a really interesting selection of people to do this study. We've got some researchers. We've got athletes. We both got men and women. We got Ben Greenfield. We've got Robb Wolf is going to do it. I've got Kyle Kingsbury. He's the UFC fighter who's on the podcast recently. And we're going to do it. I'm not sure if anyone listening to this had ever seen some of those old school physiology studies where they put the initials next to each person. I love that. It's really individual variation of what happens to each person.
Because it makes sense. But when you look at one figure and then you see the initials and then you look at another figure that's showing a different data point, being able to see the same initials again, I don't know. It's just nice to see all of the data.
Tommy: Yeah. I think this is something -- I've talked a lot about the [0:43:04] [Indiscernible] of modern day science on the podcast before. But this goes back to when I'm talking about Krebs' original studies, going back to the '60s and earlier, and sort of all the basic physiology, basic biochemistry. Now, what people did is they took some people or maybe they took a dog or they took like stray dogs off the street, that's how we learned a lot of cardiovascular physiology.
And basically, you just did something and you measure, you saw what happens, and then that's the result. There's no statistics. There's no double-blind trials, anything like that. And this is kind of how our basic physiology and biochemistry knowledge came about. And we're kind of losing that in these big groups and really [0:43:48] [Indiscernible] statistics and all this kind of stuff. We're going to try, we're going to do some old school physiology. We're going to give people some stuff. We're going to record what happens and we're going to make all the data available. And then people can decide whatever they want based on the results.
Christopher: And I'm not married to this stuff. It's not like I have 100,000 kilos of it in a warehouse somewhere. We have 100 kilos of it and half of that is gone.
Tommy: Yeah, because you've eaten all.
Christopher: Exactly. I'd be quite happy to eat the rest of it. I love it. I mix it with non Dutch processed chocolate powder and in a two to one ratio of chocolate to the Phat Fibre. And that's like my go to drink. Just mix it with hot water, shake it up in a clean canteen and it's fantastic. Yeah, if people want to check it out, PhatFibre.com. It's spelled PH and then the fiber is spelled RE. So, I'll link to that in the show notes. I think we've got enough people for this study. Because I'm going to be paying for all the testing myself. It's going to get too expensive if I put too many people into the study.
But if you want to check out the Phat Fibre, I'll link to that in the show notes. And then if you've got any other technical questions for Tommy, one thing that you can do is join our Concierge Clinical Coaching group. So, this is a private membership group that you can join and then have access to Tommy asking your technical questions and they can be specific to you.
[0:45:07]
And if you've done any testing with us, Tommy, obviously, has access to all of your data. So, as long as you don't mind the answer being made public, then you can ask questions about your own personal test results.
Tommy: That's public to the other people in the group.
Christopher: Public to the other people in the group. So, you just assume that it's more or less public but, yeah, it is only public to the other people in the group. And then periodically we also do webinars. So, you'd be able to sit down and do a six on one consultation with Tommy. That's been great. It's been really fun, not just for the people that are on the group but also for me to learn in that shared environment.
And some of the people that we've got there are just incredible minds that are digging up all kinds of stuff. Like this whole ketone debacle thing we would have never known about it if not being for Clay Higgins who just scours the internet for interesting stuff to send to us. So, yeah, thank you very much to you, Clay, for digging, for bringing this all to our attention in the first place.
Tommy: Yeah, he's brilliant. He's like this some podcast bloodhound that just finds all this brilliant information. So, actually, we get as much from him as from each other because he's hunting out all this great stuff. So then it brings up a lot of discussion points and stuff like this podcast, which is great.
Christopher: Well, this has been great, quite technical. I'm certainly going to listen to this one at least once again and I'll link to the Kahn Academy videos that I found helpful in understanding all this stuff. But it's fun. It's fun to learn new stuff.
Tommy: Yeah, this is. I mean, I have to admit -- So, Clay posted the original conversation between Veech and Dave Asprey in the group. And actually, I hadn't really thought about racemic mixtures of beta-hydroxybutyrate up until that point. So, this was because you've seen some of the basic studies and they kind of doesn't seem to suggest a problem and then you have this great researcher in the field saying that it's a problem and then you get to go dig another rabbit hole and try and figure out what the truth is. So, this is kind of -- I mean, this is the best bit of what we do really.
Christopher: Yeah, group learning. Group learning is phenomenal. Well, brilliant. Thanks very much for your time, Tommy. This has been excellent.
Tommy: Yeah, cheers.
Christopher: Cheers then.
[0:47:13] End of Audio
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