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High Intensity Health Radio with Mike Mutzel, MS
How Low Glucose & Ketones Benefit Your Immune System w/ Brianna Stubbs, PhD
How Low Glucose & Ketones Benefit Your Immune System w/ Brianna Stubbs, PhD

How Low Glucose & Ketones Benefit Your Immune System w/ Brianna Stubbs, PhD

High Intensity Health Radio with Mike Mutzel, MSGo to Podcast Page

Brianna Stubbs, Mike Mutzel
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29 Clips
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Aug 30, 2020
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Episode Summary
Episode Transcript
0:00
MCTS a relying on your body's ketogenic process ketones salts, they deliver BHB directly into the blood. So you're not getting any of that natural ketogenesis and Esters are this kind of like hybrid between Direct Delivery and well actually depending on the compound you don't get any classical hepatic ketogenesis from those and so some of the stuff we're looking at a buck is fatty acid based Ketone Esters. And so we're trying to get the benefits of both some direct VHB delivery and
0:30
Some hepatic ketogenesis as well. You know, a lot of John Newman's work showed that there are molecular signatures to when the liver actually does make its own ketones. And I think people in the keto Community know that taking misogynist ketones isn't just like a straight swap for being on the ketogenic diet, but we think that maybe with fatty acid based Ketone Esters, we're way of kind of supercharging MCT so that you're actually kind of promoting at least a bit more of that ketogenic process
0:59
that was
1:00
Anna Stubbs PhD in your tuning into high intensity Health radio
1:10
Hey my friend, welcome back to another episode. So we have a lot to unpack today. We're going to talk more about the metabolic signature that's created. We're more in a state of nutritional ketosis or when we intermittent fast or when we exercise or when we take things like MCT oil or powder or if we take exoticness ketones had that metabolic signature helps our immune system and may enhance our body's ability to mount an appropriate immunological defense in the context of respiratory viruses, but other mmm
1:40
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2:10
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2:40
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3:10
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3:41
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4:10
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4:40
Site, be sure to use a coupon hia check out. So just a few announcements before we get back to the show with Briana. I do want to let you know that the paper that we talked about investigating Ketone bodies as immuno metabolic countermeasures against respiratory viral infections. It's linked in the show notes below along with the video version of this interview and related videos. So we've talked at length about this whole concept of immuno metabolism how our immune system and our metabolic system are intimately connected a lot of the Cross talking signaling.
5:10
As molecules Messengers, they're interrelated and they work together immune cytokines, for example, antagonize insulin signaling. They raise glucose. And so what you're going to hopefully learn from this podcast is there so much here so much meat so much interconnectedness, and as people just kind of myopically focus on the single vaccine this one drug one bug kind of hypothesis, but what we need to realize is that if we can all be a little bit more metabolically health
5:40
Z we can enhance your body's immune system because we don't know when the next viral pandemic is going to be or when we're going to get exposed to some sort of bacterial infection in our food or what have you. So we're always exposed to these pathogens. So if we can improve our bodies Baseline level of inflammation and reduce that level of inflammation and improve our body's metabolic tone and signatures by way of possibly ketones and reducing the oxidative stress and so forth as we talked about today, that's a good thing. So,
6:10
I really hope you enjoyed this episode again papers and all that is going to be in the show notes below. But I think it's a good one. So here we go with Brianna Stubbs.
6:25
Great to be with you. It's great to be here. Yeah little bit of a different environment compared to last time. We did a quick little like five or seven minutes shot at metabolic Health Summit. The world has changed a lot since January. Can you believe it?
6:36
I remember traveling to that a meeting and there were my Uber driver had a mask on and she said she paid 60 bucks for and it was like just at that point where it was still you could either believe it or not. Believe it right and that being at that meeting with your hundreds of people now it just kind
6:53
Even imagine what it'd be like to be with that many people but it was right one of the very last things that I did pre covid say so I wonder if the event will happen next year. I mean I was registered but who knows
7:06
I hope so, I mean by May of next year hopefully things will change maybe new Therapeutics. I don't know but it's crazy to think that that all of the things that we used to look forward to events. I know your endurance athlete so cycling running all these events weddings like it's just it's really interesting to
7:23
To think that we're not those are not like normal anymore at least for the immediate future but getting to today's topic. I was so excited when I saw your Twitter feed and you wrote this paper here. I have it right here. I'll show it on the screen investigating Ketone bodies as immuno metabolic countermeasures against respiratory viral infections awesome paper, by the way, I mean, so I did a quick YouTube live and kind of unpack some of the mechanisms. This was when it first to come on
7:47
July the been about a month ago now, okay, so
7:50
July,
7:52
Maybe let's go kind of high level and then dive into all the mechanisms but immuno metabolic countermeasures. That's kind of a big multi syllabic word. But I'm you know metabolism I think is it's I've been so interested in this for a while trying to get people excited but there was no like pandemic to like cause people to be like, yeah, I'm Unity. Yeah. I kind of like taking vitamin C in the winter. But this idea that we can influence our body's metabolic system and therefore effective bodies immunological response super fascinating stuff. So,
8:21
So
8:21
yeah, I think it's not particularly. Well defined term. It's still like a nascent field and I think that there are some Trailblazers who are trying to Pioneer understanding how different immune cells work differently in terms of their metabolism. I think this is a concept this even differences between immune cells, right that's becoming more and more important as we go into covid because for example that immune cells that you want to promote at certain times in the immune response are
8:51
Same as you'd want to be looking at later in the immune response and the depth of balance between immune activation and immune suppression and supporting the metabolism and the metabolic state of those different cells and they transition their metabolism as they go from a resting to an active state. So there's so many different. It's so complicated and I remember studying Immunology at medical school and I remember the question. I always ask was all what is immune response actually start because it would all be so sort of cyclical and interdependent and then also you need the
9:21
the response that shuts down your immune response appropriately as well. So it's just it's very hard to and I think it's very hard to take one pill that could fix your immune system. And so when we started thinking about Ketone bodies, we were really I don't know if scared or trying to be careful because inadvertently you could buy by shifting metabolism dramatically in One Direction. You could have two effects off-target.
9:51
So you wouldn't even necessarily expect to be seeing and also like I was saying a timing effect might be really important as well. So the last thing we wanted to do was to seem like we were making a recommendation that people might then just go, you know go and Implement without without a lot of the basic biology being understood and as we started to dig into it, it was interesting going to the I haven't been rather get quite the right word, but like the human protein Atlas and trying to find out which of the immune cells
10:21
Even express bdh one to metabolize Ketone bodies not all of them, right and which of the cells even you know, which cells are going to be using ketones versus which cells are going to be doing the oxidative protective response and you don't want to you know, there's all kinds of stuff going on. And so the more I got into the topic the less the more complicated it became and the less sure I was about exactly how this was going to work but it's about this very nice sort of program of research.
10:51
Is that the specialist in those field could easily answer? Hmm.
10:56
I mean it's really fascinating and I agree and I even obviously research this to the level and depth that you have but it's very nuanced and complicated and I think a lot of people will say things like, oh the ketogenic diet is is great for cancer, but it depends on the specific cancer subtypes and everything like that. So there's a lot of nuances going on. But if we think kind of bigger picture and what I heard you say what there is it which I think is brilliant. Is that the immune system leverages
11:21
Current metabolites. So as to finance its growth and proliferation at different stages. So and if we think kind of big picture if we look at the comorbidities hypertension diabetes obesity, you know, we can obviously there's different subtypes and ideologies that contribute to the development of those diseases. But if we can paint a big brush stroke metabolic inflexibility could be one characteristic totally and we see glycemic variability so we could surmise that that sort of metabolic signature is is creating some sort of
11:51
It's regulation within the immune system X increasing susceptibility.
11:55
Yeah, I mean there's susceptibility and then there's also as you mentioned there comorbidities and recovery time and your risk of developing complications, if you do become infected as well, so, you know aside from thinking about the molecular interactions and the metabolic interactions of Ketone bodies with the immune system. One thing we tried to address in the second half of the paper is so okay. The worst has happened in urine hospitalized and you have covid
12:21
What are the things that commonly happen to people in intensive care? You know, they have heart damage. They have delirium thing and they have muscle wasting and how can Ketone bodies interact with those comorbid syndromes rather than just thinking just about the immune system and the potential for increasing safety protection against covid. So yeah, there's a lot of layers to this onion it definitely I definitely agree with what you said that mexamerica Pollock inflexibility and
12:51
The increased prevalence of diabetes and poor glycemic control certainly seem to be linked and perhaps as a reason why America has been harder hit than many other places and also people from Minority backgrounds with you know, characteristically poorer Health as well. So it's just it just is just rough
13:09
everyone totally. Yeah. Yeah. I mean what's kind of shocking and I want to make it political or anything along those lines were and I'm not a public health expert but there's been little to no dietary lifestyle recommendations. I mean, it's all about if we look at
13:21
Different buckets and like what we can do to enhance our health and metabolic health and therefore immune health. I think that's one bucket. Then the other bucket is like reducing the transmission or slowing the transmission washing your hands covering your face all at okay. These are they're mutually exclusive things. But we're only focusing on kind of ladder of slowing the transmission which obviously from a public health standpoint. I think it's a very clear easy to articulate message. So she distance wash your hands Etc, but you like wow, we're leaving so much on the table and we have like a
13:51
Good population if we could just make maybe just hey limit your sugar to 20 grams a day, whatever something simple get 10,000 steps. I don't know.
13:58
Yeah, and I mean there's some interesting stuff coming out around sunlight and vitamin D and protection as I mean, it's hard to know what to follow be cut because and I think one of the really interesting things even about publishing this paper and Science in this time, is that a lot and you see it with the Lancet paper there is retracted as well. People are so desperate for answers that they will take any one study either in isolation and is the
14:21
All T of that study as rigorous as usual has the peer review process taken as much time as usual. It's as a scientist. It's it's hard to sift through the the amount of research that's coming out and it's discerned the quality of the research that's coming out given that a lot of the propublica Asian process is expedited for Coronavirus. So you hear things so I was listening to an interesting podcast interview about vitamin D and I was like make sense.
14:51
You know what? I really, you know, I did all of my research behind this paper and write one cup this kind of kind of makes sense, but
14:59
What do you what do you say I mean, so I actually soon after that paper was published. I was reading a can't think of the type of article was but it was it was an article that was talking about complications of people with covid and in type 2 or type 1 diabetics. There was an increased rate of ketoacidosis. So I started to think and the reviewers actually made us put more more about the possible downside of ketones in there because you know, it's important.
15:29
But obviously this even stuff going on with metabolism that are making people maybe more insulin resistant and all kinds of things going on under the hood with this fire. So we don't really understand so
15:41
it's important to exercise caution and not jump to conclusions and expert I think that's I mean, there's a lot of things we don't know for example, there's one paper that showed that individuals who have increased disease severity have a realist sudden drop in cholesterol. So it would be easy to think and you know, hey high cholesterol is protective, but you don't really know that the
15:59
Direction of causality like you know what's going on there, but one thing you said when we first kind of launch this topic of am, you know metabolism, which is so fasting is that the immune system kind of has different flavors or personalities, like if we look at different T helper cells for example, or if you look at the macrophage, it can be polarized to the M1 or M2 and part of that polarization is a unique signature within its substrates which its utilize glucose versus like fat oxidation one is more info.
16:29
Trey one is more anti-inflammatory. How was that pretty exciting for you to kind of dive into that research and realize like wow, there's different immune cells that are you know, they can change their personality and their for their metabolism. And so if we can maybe then affect our metabolism we can affect a personality that immune cell. I
16:45
mean totally it was it was a bit of a baptism of fire really trying to learn, you know, not quite from scratch, but go back and revisit a lot of this basic immunology and we were really fortunate to have Emily Goldberg on the team to kind of
16:59
Provide that oversight on immune metabolism, you know metabolism. That's her specialty and she's just setting up a lab here and UCSF where she'll be looking at the ketogenic diet and I think neutrophil function but even speaking with her there's so many different subtypes of T cells T Helper and she speaks specifically interested in Gamma Delta T cells, which I never really heard of and also we have Peter turned out who's really into T helper 17 cells and so you start to get into all of these.
17:29
Different cell types and you realize it's almost like that at characters in a musical, right? And they've all got to sing in harmony and at the right time and come on and you're just trying to you you've been given the score and it almost doesn't make sense until you see it performed because it kind of trying to work out from just reading the music and unless you were naturally talented. You could probably wouldn't have a good picture of what it was meant to sound like until you see it all in action and so in a way the paper is detecting them.
17:59
music score and we actually don't necessarily know if we took out this harmony or this melody or put in an extra like Baseline here how that would affect the overall performance whether it make it better or worse, but that was kind of part of the fun of the project learning and and trying to pull together what we already know about the mechanisms and it was always there were always certain
18:26
I want to use the word extrapolation but it makes it sound like it was maybe you know not based in evidence. So because there's so little known about the coronavirus. We actually don't know whether any of the weather Ketone biology that we see in other inflammatory situations would also apply in these situations of the coronavirus because it has its own unique metabolic or immune like response fingerprint. It's going to be triggering and as we're seeing this I think in a way the fact that the pandemic has been so
18:57
Crazy is because our immune systems already know how to deal with this and we're seeing very inappropriate immune responses. So delayed First Response and then when we get to an immune response is hyperactive, which is leading to the acute respiratory distress syndrome. And so perhaps our understanding of kind of conventional biology and Immunology isn't quite isn't quite ready to answer those questions about how coronavirus is affecting the body in which the way they're
19:26
He says it's really important
19:27
totally. Well, let's unpack maybe starting with some of the pieces of the paper the nlrp3 inflammasome, which I think for for are non scientists like me like, oh my gosh. This is a big tongue twister we can unpack it and I think that's a really important and you guys highlighted that a lot in the paper and why I think it's important is because there's a Duke University scientist who's been studying the immunological response to coronavirus has and bats and it seems like they have a better variability or ability to regulate this key process and
19:56
that's what enables them to have early and robust initial response and then down regulate the it's basically the exact opposite of what how humans respond to coronavirus has and I thought that was pretty interesting and it seems that maybe children have this similar. I mean a logical response, but what is the nlrp3 inflammasome and is it as straight as it pretty straight forward or is there murky research at this point about it?
20:18
Well, as far as ketones ketones biology and immune nlrp3 goes is not it's not super clear cut, but we can come back to that in a minute.
20:26
So when I think about the nlrp3 inflammasome, I think about it as it's a protein complex that assembles as a result of inflammatory stimuli. So you need a couple of different checks in the boxes before it will get together and do its work and once it's assembled it starts helping to Cleveland process and release a lot of do it doesn't actually do the releasing but it is a essential result anju it for kind of like a cytokine secretion.
20:56
And it's going to direct the immune response. So basically when you when you get the nlrp3 inflammasome assembling your promoting inflammation and BHB ketones in vitro and in various animal systems have been shown to inhibit the formation of the nlrp3 inflammasome. And so they decrease the amount of these pro-inflammatory cytokines. So it's funny because in Ketone research land that was kind of accepted kind of becoming almost Dogma is like ooo ketones inflam.
21:26
Hibbert information via nlrp3 inflammasome information information inhibition, however, recently, there's actually been a couple of papers using human studies where these pro-inflammatory cytokines actually been increased in the context of elevated ketones, which was kind of unexpected not at all the direction we'd have expected it to go in and we don't know whether that's because of the coexisting metabolic State whether these in these human studies whether say glucose levels are higher
21:56
And that's attenuating the effects of ketones on our LA nlrp3 and actually interestingly and I don't want to get too far off topic but you've heard of sglt2 Inhibitors. So there are a type of drug that's used to treat diabetes and they also show reductions in risk of cardio for cardiovascular disease people taking these and a recent really interesting paper looked at I get this right the nlrp3 BHB in glucose interaction. So they
22:26
Titrated up the concentration of B HB in titrated down the concentration of glucose until they found this like sweet spot because at high levels of glucose BHP didn't inhibit the nlrp3 inflammasome because they think that this anti-inflammatory effect could be part of the reason why these sglt2 Inhibitors decrease cardiovascular disease kind of close the loop there. So they think that the Ketone glucose nlrp3 Trifecta has to be just right for these drugs to actually give that cardio.
22:56
Vascular protective effect now if that's also true with coronavirus, then we're not just trading up and down Ketone levels are also as you kind of said mentioned going to have to modulate people's glucose exposure as well. And you know, maybe if we have someone who comes in and they've got raging hyperglycemia, and then you don't want to be putting ketones into that situation because you might then be boosting the immune response which are trying to dampen down. So there's a lot of trust in quite a lot to unpick here, but
23:26
Some neat and we need people doing the basic science to be able to do these experiments in vitro so that we have some idea of how it's going to go up into an in Vivo system and then into a human system, but one of the challenges that we sort of came across when we were thinking about this paper and thinking about if we could do any of this work or self is that even animal immune systems and the mouse responses to the coronavirus and you would all kinds of things are just different between systems.
23:56
So it's is really tough to figure out how to test these hypotheses
24:01
and super I mean, it seems like ever studying like hyperglycemia and an animal or you feed like a some sort of ketogenic chow and look at body composition. That's a much easier question to
24:11
metabolism itself is a little bit easier and a little bit easy to extrapolate between animals and humans. I still wouldn't do it fully because n so in some of the work I've been doing recently. We see differences between rats and mice in how they metabolize ketone.
24:26
We see differences between different strains of mice between how they metabolize ketones. So it's really, you know, I guess I'd caution people and you know for myself as well. We kind of want to read a paper and just assume that that hypothesis that's been tested will hold true up into for ourselves as well. But it's just not always the
24:45
case. It's good to good reminder for people because sometimes we do see papers that come out and it is animal models and people don't really they just they just see the abstract and then the findings and so forth, but
24:56
But let's just for folks that might be confused about the nlrp3 inflammasome if you and I go to McDonald's right now and we get there was one study that looked at this I think it was in 2008 where people had like a sausage McMuffin or something like that. We're going to have probably some post-meal postprandial inflammation part of that inflammatory response is mediated by transcription factors, like one of them nf-kappa B. Where is nld nlrp3 inflammasome. I'm just trying to visualize and maybe this can help people cement the
25:26
Is it Downstream of the transcript so we have this this element that turns genes on or off? That's the transcription Factor. Where does the nlrp3 fit into that? I can't remember or
25:36
well, it is a it when it's assembled as a protein complex. So it's Downstream of the transcription factors that are affecting gene expression. So transcription factors are the things that are turning on and off your jeans the jeans get transcribed and then they form the proteins that Downstream of that.
25:52
Okay, so it's related to that nf-kappa b process. I'm not more down.
25:56
Stream, I'm not sure if nlrp3 is Downstream of nf-kappa B, but it would be Downstream of a transcription factor of
26:02
some sort. Okay, that's super and I mean just to give people an idea of like kind of visualizing how this thing is working. I think it's really interesting. But yeah that Nuance of looking at ketones in the context of glucose because that's where I think, you know, some people can go wrong with the kids and died in general or looking at studies and athletes, you know, I know there's there's a lot of controversy as to whether or not ketones help athletes or not. And that aspects not considered. I know you have
26:26
Thoughts
26:27
on that. Yeah, that could be a whole other podcast where we do that one next time
26:30
we should but let's let's unpack the paper a little bit more, you know, it's been a little while since I've read this but but oxidative stress seems like a big theme that kept coming up in multiple ways and maybe before we get into that exciting that's a big hole the is it nadph this redox sensor? Yeah. That's another one that we've heard about again. I don't want to lose people in the weeds of molecular biology, but this idea that ketones help to
26:56
Effect kind of the energetic status of the cell from a
26:58
redox. Damn. Yeah. I mean this was like a fantastic learning experience for me and the person who started educating me on this was dr. Richard Veach who recently passed away, but he was one of the like kind of grandfather's of metabolism and understanding how this kind of redox biology worked but a colleague of his William Curtis and I had some really really great discussions because he'd really really had a really good grasp of what dr. Veatch had been studying and so really
27:26
He liked the what they call the concept is great controlling nucleotides. So pretty much every reaction metabolism in our cell uses NAD or nadh in some like interconversion and then that's mainly in the mitochondria and then in the cytoplasm of ourselves, we've got nadp and nadph and so shuttling it's almost like a redox buffering capacity and if people want to think about that, I guess it's like too much oxidative stress is bad and
27:56
and then too much reductive stress is also bad yourself kind of is trying to keep itself in this like sweet spot. And so you need to have enough power to kind of keep all of that in balance. And so with coronavirus you can your you need an oxidative response in your immune cells because production of radicals and actually help to kill infected cells or kill destroy and harm the virus, but actually there's a lot of collateral damage when you get that's also for your
28:26
Infected cells and you're not immune cells. You actually need to be able to protect yourself against oxidative stress. And as you start to mount your immune response, the cell gets stressed. It loses some of that buffering capacity and so it can be even more vulnerable to damage and so with Ketone metabolism and I don't again don't want to go into all of this sort of like metabolic pathways, but it can boost their ability in the cytoplasm to be able to absorb some of those homeostatic challenges.
28:56
Has so it kind of is is not only it's just helping it's providing a bit more of a reservoir for ourselves to be able to deal with stressful
29:03
situations. So more resilient and that's one thing that Dom D'Agostino's talked a lot about is helping individual ketones kind of help it under environmental extremes, and maybe we can like in this hyper free radical or excessive amount of oxidative stress is like a cellular environmental extreme of sorts and that I think that's super fascinating. I know that you study ketones a lot the whole nmn.
29:26
And NAD. Yeah, do you take those personally or
29:28
what are you don't take them we're doing an awful lot of research in that the buck. So dr. Eric Vernon's obviously like very his lab research is NAD biology and he has several projects going on looking at different ways that NAD metabolism could be modulated to improve life span. So I'm I'm pretty close to the source. And so I get good information. I mean, I guess that maybe also have these supplements at the moment there. What's out there some of its good quality some of its not so much so there are a couple of companies.
29:56
Knees that I've heard a better that I would use if I was going to use this kind of thing, but it's still kind of expensive and until maybe when I hit 40, I'll start trying to gauge the other way. But oh, I'm still not quite 30 yet. So it's a what point do you start your anti-aging right kind of plan when
30:13
you're doing so much. Anyway, I mean running and fasting and and Kido. It's like, I mean it seems like if you're doing all of that and you don't have any other health conditions is the hundred twenty bucks a month first. Yeah. It's a it's a lot of money if you think about
30:26
What you could do with that money from a Dyson standpoint. But
30:29
yeah, for sure. I mean, I just try and get like good Whole Foods and your balanced diet right now. But you know, I think there's there's a lot of interest in research in the NM n and n are spaced also other companies starting to really push the boundaries of longevity supplements. I think there's an interesting space to be watching and I think especially being at the buck and embedded there you can see how much the research is about to hit on him.
30:56
Flexion Point investment is about to hit an inflection point we're going to have to change a lot of things about how our society Works to cope with this aging population or early so I think longevity is really going to be like the next Hot Topic for everyone and not just those of us who are kind of health-conscious excited
31:13
settled. I agree a hundred percent it and then just looking at one of the biggest risk factors for this virus was age is a big one, right? And so and there's some discs ordinance there with epigenetic age and Horvath clocks and you
31:26
B-47 but biologically maybe you're 60 and so that you know, you see these seemingly young healthy people that maybe have underlying diseases and so forth and I don't know have you gotten into the Horvath clock or tested yours yet or
31:39
no? I would love to I've been reading an awful lot about it and I would love to test it but I haven't had it done just
31:44
yet. I had mine done this three years biologically older than I am chronological too bad. Yeah sounds like alright, that's and I know what yeah sleep is my issue likes. I'm always up late at a ding or researching order.
31:56
Stuff like that with videos and I'm like that to me was like a testing can be a great motivator to affect your lifestyle change because you're like well my it's right here. It's like you're you're older than like you should
32:05
be so we at the buck we have a professor called. Dr. David Furman and he has an inflammatory aging clock which I'm excited to try out as well. And so he he's the director of the Stanford 1,000 immune, ohms project. And so they've using AI they've got a lot of immunological phenotypes thousands of people and they can use that to predict.
32:26
Immune status to predict your
32:28
age as well - interest is it commercially available at this
32:31
point? I think it is actually through a company called
32:33
edifice. Oh my gosh. Yeah, they're gonna show not. Yeah so cool. I'm not the same. That's
32:37
awesome. The Bucks. There's a lot of cool stuff going on at
32:39
the cheese. I know gosh what I mean what like a major, you know career change. I mean that must be so amazing like every day is like like a field day right? It's like you're like on a field trip, but you get to get paid to like do this cool research and work with these great people.
32:53
Yeah. I mean that's certainly challenges I was
32:56
Recently involved in a big Grant application and you know all of this paperwork and all of you know, writing a good research plan, but it's it is pretty cool to be surrounded by people who are at the Forefront of what they do and pushing pushing the boundaries and yeah gets me up every morning for so
33:12
awesome. That's really cool. And there's a few other things on the paper. So we talked about the nadph and free radical stress. Yeah. We talked about the nlrp3 inflammasome. There were some anti key to balak properties that were elucidated and I think we've kind of unpack that and in jakku.
33:26
It's work and yeah, pretty exciting.
33:28
Got to give Andrew like a huge shout out because if he hadn't if he hadn't come along and been like this is really really cool. He's got so much energy and he he turned this from just you know me writing two or three pages just kind of of my own notes into that paper and he really helped to drive it and you know hit the expertise that he brings to the molecular mechanisms of ketones as anti catabolic agent. I mean, I'd really encourage everyone to go and look at his paper that came out earlier this year.
33:56
Year that looked at ketones as an anti catabolic agent for cancer, but also importantly for inflammatory stress triggered by bacterial bacterial threat. And so we think that that when you start getting further Downstream of the virus, if you're just looking at systemic inflammation, then I think it you're on a bit shorter ground to make extrapolation. So you some of the stuff that we talked about in this paper about really obscure like H NR p 3 or a 1
34:26
MRNA interactions, that's like very specific and very close to like the viral replication. But as you start to get to while the virus just triggers lots of cytokine release you get and you get lots of Downstream inflammatory processes muscle wasting is one of those things that's kind of triggered by quite nonspecific inflammation. And so I think that Andrews work showing that ketones were protected it protective against LPS induced inflammation probably has quite a good chance of General being
34:56
a generalizable over to like viral inflammation as well. And you know, we're seeing young healthy people taking weeks and weeks and weeks to recover from this and older people as well. And you know, the more that the longer than older person is hospitalized or a mobile the harder it's going to be for them to recover their function and be able to live independently. So even if ketones being on a ketogenic diet or taking exhaustion as ketones doesn't treat or prevent you getting from the virus it may help with recovery.
35:26
So I think there's a lot of potential for investigation there. But yeah, certainly even just with any other syndromes of Aging I think if Andrews, you know seminal work with dom and dr. Brenda Negan as well thinking about this role of ketones in muscle biology. If some of that can be proven out in human models, that will be fantastic and there is again a some early indications that that might be the case from a few limited human studies, but there's still a bit more work to be done there and Andrew said
35:56
up at the ihmc now. So I hope he has a chance to look at some of that because they have good collaborations with like NASA and all you know, it'd be cool like NASA would fund it because they're lost lots of muscle loss in space. Yeah, that'd be kind of neat. My
36:10
son was an organ of longevity. I mean, it's really exciting to see in that property. And yeah, I mean going back to to some of the earlier papers showing that that that part of what you know, why ketones are made might be to preserve muscle mass and take off that
36:25
but there are starvation mode.
36:26
Like right you won't doubt if you if we were breaking down our muscle to provide glucose or if muscle breakdown happened as quickly as it should happen. Then we would die within days to weeks rather than with Ketone with kin when Ketone metabolism kicks him we can go for much longer without food and Andrew. I'm going to get it wrong, but I'll have a go, but he said that I think it's in the context of low insulin.
36:56
Normally that's like a very low insulin is normally very Pro catabolic but in the ketogenic diet, you've got this low insulin stay and not very much catabolism. There must be something going on and his hypothesis. The Ketone bodies in the context of low insulin are what prevents that becoming like a super catabolic situation. I mean, you should have him on the podcast because
37:19
he did. Yeah, it was years ago and it was outside and but I would love to catch up with him again. He's such a great guy and he walks at walk.
37:25
Any exercises and all these things that so it's great to I love interviewing people like yourself who not only know this but apply it to their life and so like before, you know, you come over here you ran how much
37:38
eight
37:39
miles a miles like most people can't run a in the hill so is undulating
37:44
terrain quite a lot of Hills lot more than I planned
37:46
for. Yeah, that's awesome. Now, that's great. So final question. Do you take MCTS or exogenous ketones?
37:52
I do periodically, but I don't have like a
37:55
Straight regimen. Okay. So I quite like I've been finding that using a little bit of MCTS in like coffee or like a creamy drink definitely curbs my cravings and appetite I quite like using a little bit of MCT, but I mix it with carbs before if I'm going to do a morning workout. That's a bit more intense. So this morning I ran fasted because it was pretty low intensity and I'm still fasted now I try and do some of my some of my lower intensity morning training fasted. But if I'm doing a workout, that's a bit more.
38:25
Tents are normally each of your men actually make this really tasty like MCT and also MCT collagen mixes and I quite like mixing those in with like some banana and or something in a smoothie. So I get a little bit of carbs and also that little boost of ketones as well, but then I'm always tinkering exiled with exoticness ketones. A lot of it's from my own for my work and sort of self-experimentation and I'm looking forward to there being like more options for people to try and from for me to try with different types.
38:55
Of exogenous ketones, but you know that's part of part of what I'm working on to kind of increase the research and also increase the number of compounds and products that there are available for people to try. So yeah, I think is an interesting space a lot of what is there right now? So MCTS are relying on your body's ketogenic process ketones salts, they deliver BHB directly into the blood. So you're not getting any of that natural ketogenesis and Esters are this kind of like hybrid between Direct Delivery and well actually do
39:25
Hang on the compound you don't get any classical hepatic ketogenesis from those and so some of the stuff we're looking at a bucket is fatty acid based Ketone Esters. And so we're trying to get the benefits of both some direct VHB delivery and some hepatic ketogenesis as well. You know, a lot of John Newman's work showed that there are molecular signatures to when the liver actually does make its own ketones and I think people in the keto Community know that taking misogynist ketones,
39:55
Isn't just like a straight swap for being on the ketogenic diet. But we think that maybe with fatty acid based Ketone Esters. We're way of kind of supercharging MCT so that you're actually kind of promoting at least a bit more of that ketogenic process. And you know, I'm starting to get deep into the weeds of ratios between BHP and acetoacetate for example. So again with salts and Esters of the mono Esther BHB in butanediol, you're kind of going much more in the BHB Direction and Dom D'Agostino.
40:25
The acetoacetate diastole which goes more towards the acetoacetate and what happens if you do this more like fatty acid based approach. Is it more physiological so and the more and more and I'm starting over starting to really get into the weeds of what is the difference between BHP and acetoacetate? So Peter Crawford has some really interesting papers showing that acetoacetate does some things that BHP just doesn't do and unfortunately, I see to our state's really hard to measure so when we use the handheld meter, we're only measuring BHB. There's always ketone.
40:55
We're just not really accounting for yeah, it's hard to measure so people don't do it. And so I'm interested in starting to understand the differences there and there's all sort of like signaling metabolism BHB acetoacetate RB H. BS B. HB all different ways that we can play with exoticness ketones and understand the biology so that hopefully as we start to understand disease better we can Target the immuno metabolic countermeasure specifically to that right time and sends
41:25
Type and hopefully improve outcomes, but I mean there's a lot of our research to do
41:31
still. Oh my gosh, people are going to hit the rewind button and re-listen to that a few times because there's so much to unpack right there. And I think that we could talk about that another time. But thank you as always for sharing such great information is great to have you on I'll put links to this paper. Keep up the amazing work. And yeah, I mean if you have new information on acetoacetate BHB ratios in this, I'm sorry to
41:50
just knowledge bomb, you
41:51
know know it's amazing. It's all the good stuff on these podcasts have been doing this.
41:55
For like five years now, they always come right at the end. That's just how it is. Yeah. Have a great rest of your day. Thanks for coming. I so much appreciate it. Well my friend that's it for today. As always. I'm grateful that you're listening all the way to the end. I really hope you enjoyed that episode. I think there was a lot of meats one back there. What I'm going to do as mentioned earlier is put some of the references that we talked about in the show notes. I'll put the video version there as well. And if you enjoy this episode you can always share this as an Instagram story. You can share this over on Twitter just take a snapshot of what you're listening to now and be sure to tag me over on Instagram. It's men.
42:25
Look underscore Mike and brown and stub. She's pretty active on Facebook and also on Twitter so definitely connect with her tweets at her tell her you enjoy the conversation and as always thanks for being here and have a blessed day. I appreciate you doing all the way in and we'll catch you in a future episode Debora.
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