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Carole Freeman:              Welcome everyone to this episode of, “Keto Chat”. I am your guide, your host, your tour guide, your … I’m thinking of like the cruise ship. Tom, you remember back from, “The Love Boat”? You know, Julie-

Dr Fabian:                            Yeah, that’s going back a ways.

Carole Freeman:              Yeah. That’s what is coming to mind today so … I’m Carole Freeman, your cruise director for this episode, certified nutritionist and creator of the, “Fast Track to Keto Success Program”. I am here today, Dr. Fabian … Tom and I had such a great conversation last time, we’re doing a repeat, not a repeat, but a follow up discussion.

So Tom Fabian, PHD, CNTP, is a functional health expert and former research scientist. He specializes in the areas of healthy aging, metabolic regulation and gut immune brain dysfunction. He provides educational programs and resources for practitioners on the gut, microbiome by his website, microbiome mastery. So welcome back Tom. I’m so excited to have you here.

So, we’re gonna focus today on Ketogenic diet and brain function and neurodegenerative diseases as we age and how the microbiome and gut brain acts and plays into that. So I bet you lost sleep and couldn’t wait to talk about this today. Right?

Dr Fabian:                            Exactly. Yeah. It’s one of my favorite topics.

Carole Freeman:              Excellent.

Dr Fabian:                            Thanks so much for allowing me to be here today. It’s been great and I’ve enjoyed the last time and looking forward to where the conversation takes us today.

Carole Freeman:              Excellent. Excellent. So I’m gonna pause because my neighbors decided to mow their lawn right now, so I’m gonna close my window and … so that we don’t get this … I’ve no idea if it’s coming through on my microphone, but we’ll minimize this. Minimize the extra sound that we have going on here.

So alright. Well just to start out with, you know … Do Ketones help … Well, actually before I dive into some questions we’ve got, can you just kind of talk about you know, the process of the brain aging? Like, what happens as we get older in our brain and what’s normal and what’s a sign of dysfunction?

Dr Fabian:                            Yeah. So there’s actually some kind of ongoing debate about that to some extent in terms of what actually is normal, because a lot of pathologies are sort of happening at the same time, in various individuals. So it’s a little bit hard sometimes to get a take on sort of what’s normal, but by most measures we know that over time we tend to lose neurons as we age, and that starts apparently pretty early and depending on all kinds of factors, including sort of how much we’ve sort of stimulated our brain to learning, etc., we may lose connections as well and I know there are some studies that’s basically show that higher levels of education correlate with more connections and better brain function throughout lifespan, things like that. But we know that in general, of course certain functions start to decrease as we age as well, but again there’s debate over you know, how much of that is normal aging versus precursors to disease like you know, decrease in memory, for example is kind of a common one and just other aspects of cognitive function like just processing speed, etc.

So in general we know there is just a decrease in function and then there’s also some things at the cellular level that we know are changing as well, related to damage. So aging basically involves … It’s kind of this constellation of processes that happen throughout the lifespan that cause damage and dysfunction. So it can be damage to DNA. It can be oxidative stress and inflammation. So those are some of the most common ones and also including the cell loss that I mentioned or either just decrease cell function. So those are sort of the basic aspects of aging in general and some things related to brain aging. You know so that’s … but again you know, there’s really a lot of debate because there’s studies showing that people even into their 90s, or the luckier ones, or who happen to maintain a better lifestyle, or have better genetics, or all of the above, that they have relatively little decrease in their brain function, up until pretty advanced ages. Whereas certain people even in their 50s and 60s can have pretty significant decrease in function and that can be due to a lot of different factors.

One of the things I’ll just mention as a side note, there is a study just published recently about a gene that was discovered, a gene variation, where this gene has a pretty significant impact on normal brain aging. So it’s not a risk factor for like Alzheimer’s, Parkinson’s. It’s basically just involved in normal brain aging, which happens to some extent independently of these diseases.

There’s cross talk but there’s also sort of an independent just basic brain aging process. Of course, I looked mine up and it turns out I have the bad version of it unfortunately. But that to me you know, that adds more motivation to continue to do all the right things.

Carole Freeman:              What’s the gene name? I want to look mine up later too. What’s the-

Dr Fabian:                            It’s a pretty long name. I’ll have to send it to you. But it begins with … So the first part is T-M-E-M and then there’s a long string of numbers and characters and so I don’t remember the details, but it turns out that it’s particularly involved in aging of the forebrain. So it’s really only involved in one part of the brain, and it really mostly has an effect on the balance between pro-inflammatory and anti-inflammatory factors. So again, this implicates inflammation and neuro inflammation as a major factor.

Not only we already know that’s linked to neuro-degenerative diseases, but now we know that’s linked to brain aging as well. And so that’s one of the things that I wanted to kind of focus on today is particularly in relation to Ketogenic diet and Ketones and also the gut-brain access. All those are related to inflammation and ways that we can reduce inflammation and so that’s really a key aspect I think of helping to protect the brain as we age. Because we know this process is gonna happen, but we do have control over how fast it’s gonna happen and we can maintain. You know these examples of people in their 90s, that have really good brain function, I think is a shining example of what is possible if we do all these things to help maintain our brain function.

Carole Freeman:              Yeah, well and send me … When you send me that gene, we’ll put it in the show notes down below so that other people, ’cause their probably curious as well. I did my 23andMe genetic testing couple of months ago and so I’m curious to see what version of it I have now too. So-

Dr Fabian:                            Exactly. Yeah, so I’ll make a note here to make sure I send that to you when we’re done.

Carole Freeman:              Okay. Great. Well also where do you want to go first or you know, is it a logical step for you know, Ketones on the brain, or the gut-microbiome, like where do you want to take this first?

Dr Fabian:                            So when we talk a little bit about ketogenesis, Ketogenic diet and just sort of different ways to increase your ketone production. So maybe back up and then we’ll talk about why that can be important for brain function and certainly chime in, ’cause I know you’ve done a lot of research and working with clients in this area as well. I’d love to hear your clinical perspective on all of this.

But we know that, you know there’s pretty strong evidence of course with regard to epilepsy that Ketogenic diet of course is therapeutic, but over time we’ve also found that Ketogenic diet and other approaches through raising Ketones can also be protective in other neurodegenerative diseases and of the last 10, 15 years there’s now some research that, and even clinical research that suggests that Ketones can help with the symptoms of Alzheimer’s.

It’s not really shown to be any sort of cure for Alzheimer’s, but certainly it can help, because part of the dysfunction in Alzheimer’s is the decrease in the ability of these brain cells to utilize glucose as a fuel, and of course our brains are energy hogs and they need a lot of energy and if they are not getting enough from glucose, but they don’t have any other source, then their gonna suffer, in terms of their function.

So the Ketogenic diet and supplying Ketones in other ways can help overcome that deficit that we see to some extent. So these studies you know … because as you know it’s difficult for some people to really go kind of full boar Ketogenic and there are ways, I’m sure to make that somewhat easier, but people then looking for alternatives to do that and so one of the main ways is just to supply sources for Ketones in the diet, like MCT oil or Medium Chain Triglycerides oil, which is related to coconut oil. And also even forms of Ketones that you know you can take in through the diet, or supplements, which are known as ketone-esters. And so those studies, both in animals and even some clinical trials seem to show an improvement in people.

So they’ve looked at this further and really there’s two main Ketones that are produced in the body. There’s actually three, but one of them is really dissipated pretty rapidly and that’s acetone, which we tend to breathe out and so it’s not as relevant, but one of the Ketones, called beta hydroxybutyrate really has a lot of good research around it, in terms of it’s beneficial effects and there’s a major research paper that came out a few years ago showing that it serves as a major anti-oxidant and anti-inflammatory and it’s able to cross the blood brain barrier and get into the brain and that they’ve even found some, sort of historically they found mostly that Ketones are produced by the liver, but recent research suggests that Ketones can either be produced by astrocytes in the brain, which is a pretty strategic thing for the brain, when the brain needs a fuel to have the cells that are right next to the neurons.

Carole Freeman:              So is it making … the brain making those from fatty acids, you know?

Dr Fabian:                            Yup.

Carole Freeman:              Okay.

Dr Fabian:                            Yeah. Yeah so that was a pretty interesting thing I had never heard of until recently that … It’s not really well, all that well established yet, but there’s growing research that I would say by now, pretty much shows that astrocytes you know, do have a supportive role as far as that goes and are important source for brain Ketones. But this beta hydroxybutyrate really they know by now after studying it so much that there’s really several different ways in which it helps brain cells, particularly in related to aging and neurodegenerative diseases and that’s … Number one by providing an extra energy source, and so when glucose is low, obviously when we’re fasting, for example, or we’re doing super low carb Ketogenic diet, we don’t have the carbs around to make a lot of glucose from, so we need an alternative source for the brain and so that’s what the Ketones provide, especially beta hydroxybutyrate. So, that’s one of the main ways it functions.

Another way is by reducing the production of these free radicals, or reactive oxygen species, is another term for them. So those cause damage to cell components and beta hydroxybutyrate not only reduces those just because of the way that it’s burned in the mitochondria, it’s kind of a cleaner burning fuel, so to speak than glucose is in some ways. But it also acts as a signal to the body that it’s under stress. Because historically, sort of evolutionarily, Ketones are produced primarily in response to vigorous exercise as well as fasting and basically fasting wasn’t so much a choice back then. You know when you had to go for periods without food, that adds stress to the body, so it’s an adaptive.

So basically it signals the body to turn on these protective genes, including anti-oxygenate genes. So it’s really helping to reduce the oxidative stress in, especially in neurons, which are particularly susceptible to oxidative stress. So, that’s a really important factor in terms of how beta hydroxybutyrate functions.

That’s also known to be a pretty potent anti-inflammatory and also increases brain drive, something called brain drive neurotrophic factor, which is really important for kind of maintaining those connections in the brain. So it really has this multi-faceted you know, set of benefits that really are beneficial I think overall for the brain and the idea with regard to aging and protection from neuro-degeneration is, even periods of ketogenesis whether it’s periodic fasting, whether it’s intensive exercise or going to get on a Ketogenic diet periodically that, that’s gonna help reduce some of this oxidative stress damage to the neurons and that, that’s significant and it’s not necessarily … I don’t think it’s necessarily necessary in a lot of cases to go full Ketogenic all the time and there is some debate, which I’d love to talk to you more about, hopefully in this discussion about doing sort of Ketogenic diet periodically or maybe most of the time, but not necessarily all of the time versus doing it just all the time. I don’t think the research has really resolved that debate, but it’s kind of an interesting kind of thing to kind of think about.

So that’s really what I want to say about Ketones, Ketogenic diet in general in terms of the brain, and so far there’s a lot of promising research suggesting these Ketones can really be beneficial.

Carole Freeman:              Yeah. I’m wondering if we can kind of talk about the difference or just briefly kind of define the difference between just age related dementia and Alzheimer’s. I remember from school learning about you know, there’s a couple different kinds of dementia, let’s see, like vascular and then there’s another one I think and then Alzheimer’s you know. Are they all the same thing or how are they different and what different age related brain disease might we be watching out for?

Dr Fabian:                            Well, so that’s a good question. And I first have to sort of issue my disclaimer that I’m not a specialist in Alzheimer’s and neurodegenerative diseases. It’s an area that I tend to focus on in terms of more brain aging in general, but I do know there are different types of dementia, and you mentioned you know, vascular versus Alzheimer’s, etc. And even within Alzheimer’s, there’s subtypes. If you follow Dale Bredesen’s research, he talks about I think, three or four different subtypes of Alzheimer’s and I don’t remember off hand all the different subtypes, but they have to do with sort of the underlying pathology, in terms of what’s going on.

So it’s not … it’s sort of like a lot of things now that we used to label them with one term and think they were one thing and now we’re realizing it’s sort of this spectrum of syndrome, sort of like autism, autism spectrum. It really depends on what the underlying causes are, in that case. And that’s really what I focus on is sort of how do we address these and balance this, especially early on to really focus on supporting the brain as we age.

Carole Freeman:              Nice. Nice. And there was something you said, when you started talking that, about how using … if people don’t want to do a full Ketogenic diet using support, you know exogenous sources of Ketones or things that are quickly converted to Ketones in our body such as MCT oil, coconut oil and the exogenous Ketones. I’m … You know there is a research on a very structured way of doing Ketogenic type diet MCT oil. One that they’ve done with epilepsy, where you can have a higher carb intake and then supplement with enough MCT oil to kind of overcome a normal carb, or not a normal carb intake, but a high enough level of carbs that normally would keep somebody from getting into ketosis and so we have that research that shows that that can be just as effective for preventing seizures for epilepsy as a full regular therapeutic Ketogenic diet.

My concern though is that people that want to just maintain their really high carb, sugar, refined foods diet and not really make much change and then add coconut oil MCT on top of it, thinking that, “Well that’s all I have to do.” Kind of like, “If I have high blood pressure, I’ll just take a pill and then I’m fine.” And so I’m … and more so I’m more concerned too, that we don’t know what happens when you have high carb, high blood sugar problems and you’re adding Ketones on top of that. I feel like that might make for even worse health, than you know just sticking with the standard American diet. What are your thoughts about that?

Dr Fabian:                            I think we’re on the exact same page. I mean studies do seem to show, that you know in these clinical studies, where they did use MCT oil and things like that, clinically on Alzheimer’s patients to see if there was an improvement. Based on the measures that they looked at, cognitive function, things like that. They did detect sort of … and you know most of these are done short term, so these are always short term. They did show that there was an improvement in cognitive function, but again, they’re looking very narrowly and not really looking overall at their metabolic function, especially long term.

And so my concerns really are the same as yours as far as kind of doing these, sort of cheating sort of ways or you know their trying to get the quick results and not have to go the full boar and I think it … my concerns mostly come out of when you … I like to take the ancestral sort of paleo approach, for a lot of things and to put that in perspective, because when you think about how our system evolves, how our bodies evolve, to deal with these things. What the circumstances under which it sort of naturally goes into ketogenesis is fasting, and intense exercise and maybe in certain cultures and certain regions where they have a super high fat diet, that probably wasn’t all that common based on a lot of studies that have come across for hunter-gatherers, that there weren’t very many that would have eaten like they’re literally a Ketogenic diet itself.

So even that, I have a little bit of less concern, but a little bit of concern over kind of long term Ketogenic diet, just because again, it’s not necessarily what our bodies are fully adapted for, versus fasting and intense exercise is kind of a more sort of evolutionary common scenario. But yeah, definitely when we’re trying to do the quick way to trick our bodies into doing things, I think that we may be triggering something that’s you know, unintended.

Carole Freeman:              Yeah. Yeah. We don’t have the … That’s exactly my thoughts on that, is that we’ve never had a natural state of being where we’re gonna have a high carb intake and Ketones circulating in the body, in the brain at the same time, and so who knows what’s gonna happen? That’s just an experimentation and I … I have seen people recommending exogenous Ketones for example as a way of bouncing back after a cheat and so you know, “You can have this high sugar thing and then just drink these exogenous Ketones and you’re right back in ketosis,” As if it’s like an eraser that erases that you know assault that you made on your body and it doesn’t, it doesn’t work that way.

I’m concerned about people using it that way too, we’re in a time where we’re this uncontrolled experiment of these being available to anybody because of the supplement laws in the United States and there really hasn’t been research on using these to overcome cheating and then trying to maintain a high sugar diet or just not make any dietary changes at the same time, and so.

Let’s see. Okay, so let’s go on into so how … Okay, we talked about how the Ketones can help the brain, several different mechanisms for protecting, and also … What I know too, is that it’s able to heal stuff, right? Like it’s able to because you’re promoting autophagy and things like that. You’re actually not only protecting the brain and providing a good environment for optimal health, but you’re able to kind of repair some of that. Is that what you’re seeing in the research too?

Dr Fabian:                            Yeah. And again I think that since Ketones are sort of historically produced under fasting conditions, and there have been a series of really fascinating research articles that have come out in the last few years on … you may have heard of the term, “fasting mimicking diets”?

Carole Freeman:              Mm-hmm (affirmative). Yeah.

Dr Fabian:                            So that’s a diet, it fasts that lasts about three to five days, where a very low number of calories are given so it’s not totally fasting. The idea is kind of to make fasting a little bit more palatable, a little bit more tolerable. But the idea is from these studies, and mostly it had been done in animals and I think there have been a couple of small sort of pilot, clinical trials done to date, but they do have a significant regenerative affect and so I don’t know if that’s really been linked specifically to the Ketones, themselves, but during that process, we know that key pathways that are protective, they’re referred to as, “Stress resistance pathways,” are up regulated and so it has been shown that beta hydroxybutyrate, which is one of the Ketones is directly involved in those signaling pathways and a really interesting connection … There’s actually quite a few different connections and I don’t think I can remember them all right now because of the biochemical complexity, but there’s a lot of interest in something called NAD, these days.

And so that’s a really key component, not only to sort of metabolism in general, but it’s a key signaling molecule. So NAD tends to go high, under conditions of fasting and so basically that’s a key trigger for a lot of these stress resistance pathways and so we know that there’s even supplements as well as some pharmaceuticals that are being explored to increase NAD levels and a lot of those have really promising research behind them in terms of impacting potentially aging itself as well as different types of aging related diseases.

And we know that beta hydroxybutyrate when it’s levels increase, that that results in increases in NAD, and so it’s triggering we know this sort of molecular pathway. Specifically, how it’s triggering these … they’re sort of referred to both as stress resistance pathways and even pro-longevity pathways because in experimental animals, when you increase the activity of these pathways, or alter these pathways in certain ways, it can lead to longevity and so this is another interesting link I think back to not just sort of focusing on beta hydroxybutyrate, but also just thinking about the Ketogenic diet itself and why it works in a lot of ways.

Because the two main pro-longevity pathways, which are also known as stress resistance pathways are basically the insulin IGF pathway and IGF stands for Insulin-like growth factor, which is related to insulin in some ways, and so that pathway is promoted by carbohydrates. Then there’s the M-TOR pathway that’s promoted by amino acids from proteins and so basically when the activity levels are high, that’s … puts the body in sort of an anabolic state, which is good kind of short term, good during development, things like that. But over the long run, for aging, they’ve shown that low activity of those two pathways promotes longevity and so to get low activity, you need low carb and you need low protein. So you’ve probably heard of caloric restriction, that’s a phenomenon-

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