Hey everyone, welcome to the drive podcast. I'm your host Peter Atia, this podcast, my website and My Weekly Newsletter, all focus on the goal of translating, the science of longevity into something, accessible for everyone. Our goal is to provide the best content in health and wellness. And we've assembled a great team of analysts to make this happen. If you enjoyed
This podcast, we created a membership program that brings you far more in-depth content if you want to take your knowledge of the space to the next level. At the end of this episode, I'll explain what those benefits are or if you want to learn more now, head over to Peter attea, m.com forward, slash subscribe. Now without further delay, here's today's episode, I guess this week is Rhonda, Patrick, some of you may recall, that Rhonda was one of the original guests on the pilot series of the drive, back in July 2018, when we were trying to figure out if
I really wanted to do a podcast. Well, of course we did and it is awesome to have Rhonda back. Rhonda, also hosts her own podcast called found my Fitness in this episode. We focus the conversation around. A few important Concepts and we talked about Rhonda's current interests along with areas where her perspective is either shifted or evolved over the years. We start the conversation with a deep dive into Alzheimer's disease. We talked about the possibility of a vascular hypothesis for Alzheimer's disease. We also talk about the different
factors that can affect Alzheimer's disease, including type 2, diabetes, Omega supplementation, blood pressure, exercise sauna and more we then go on and talk about the relationship between exercise and cancer and also the relationship between alcohol and cancer. And then finally we talked about protein and aging and we talk about fasting. Time restricted feeding. These are two areas where Rhonda and I have had different points of view over X and both of our views have evolved. I think in some ways we're actually converging at about the same place now. So,
A really interesting discussion, it was really exciting to sit down with Rhonda. It had been far too long and so, I hope you enjoy this discussion, half as much as I did, Rhonda, it is so great to see you, especially on that awesome, remote setup that. I almost shouldn't have said to people was remote because it really feels like we are in person about as close to and person as we've been in a few
years. It's really great to see Peter. It's been a minute.
We'll be together soon in a
Couple of months. So I'm looking forward to that. There's a lot to catch up on over the past few years. We've obviously exchanged a bunch of emails about things that we each find interesting. And I think in the last couple of years, let's just pause it in the last five years. Was the last time we did a podcast just going back to that point. I think both of us have evolved a lot in our thinking and I think we've done so unapologetically that's the nature of science. That's the nature of what we do and we're trying to learn. So in thinking about our discussion today, I think we both agreed it would be
Most enjoyable to, at least spend some time talking about areas where you're thinking has evolved. But I think first we wanted to start with, I don't put words in your mouth, but maybe that, which you're thinking about the most right now with that be a safe assessment. If we were to start to talk about dementia, specifically Alzheimer's disease and maybe the change in, how you think about that?
It would for me personally, I have neurodegenerative disease on my mind quite a lot because Alzheimer's disease and Parkinson's disease.
Both run in my family and I have a genetic predisposition. So for me, understanding everything I can do with my diet with my lifestyle exposure, to, or limiting exposure to certain things Etc, becomes Paramount because I don't want to get Alzheimer's disease and Parkinson's disease. Like as, you know, Peter, the Alzheimer's disease field has been. It's been quite a roller coaster in a way. Like we've had this dominating hype.
Offices this amyloid hypothesis as it's called. So there's, you know, one of the major pathologies of Alzheimer's disease are amyloid plaques in the brain. And there are other pathologies Tau, Tangles also glucose hypometabolism, so glucose uptake into the brain is impaired. And also perhaps even the utilization of glucose as well, these are like three major pathologies of Alzheimer's disease and it seems as though the majority of targeting how science and
Scientists have decided to Target, you know. Alzheimer's disease is through this amyloid anti-amyloid hypothesis. And as you know, we've had quite a few failed trials. Although of recent a little bit more, I would say you know, possible success maybe but generally speaking, it's been are we just trying to treat a symptom here or are? We too far Downstream? Like what's the deal? And I started reading some Studies by beerus off. Slow, go back at USC.
Dr. Axle montaigne. Who was trained with dr. Slavic. And now has his own Lab at the University of Edinburgh. In Scotland, I recently did a podcast with him on my podcast and it was really like when I started to read some of this literature on, I'm going to talk about like what this sort of new it's not even necessarily new but like it's not a new way of understanding it but it is in a way it's because in the public opinion and public mind, it's a new way and this is sort of like okay well what are the underlying causes of dementia? And so there's three major.
ER types of dementia Alzheimer's disease, being the most common. There's small vessel disease cerebral, small vessel disease, and then, vascular dementia. Those are the three most common forms of dementia. But like, is there a common underlying denominator between those and on top of that, like, what sort of Lifestyle factors and genetic factors? Do we know really increase the risk of Alzheimer's disease and dementia? Well, we know having an apoe4 allele so this is a version of a gene that is known to increase.
Risk of Alzheimer's disease. If you have one of them, it increases the risk to fold. If you have to, if you got one from Mom and one from Dad, it could be up to ten fold and this isn't like an early onset Alzheimer's disease, it's more of what's called late onset, which is the normal sort of age-related aggression of Alzheimer's disease. But that Gene really does play a role in someone's risk. The other thing we know is type 2 diabetes. I mean that over, I don't know somewhere between 50 to 80 percent of people with Alzheimer's.
A disease also have type 2 diabetes. That's a lot. There's definitely something going on, right? I
mean, and let's sort of pause there for a moment because I want to go back to sort of the premise of your interest, which is, you are at increased risk. So just even if you just think about this personally and therefore presumably you're interested in quote, unquote prevention. And as you probably heard on my podcast, prevention is still a word that doesn't quite resonate within the field. In other words, up until very recently. I think the NIH didn't even acknowledge
George the idea of prevention as a strategy within this field. And in fact, preventative neurology or preventive neurology. I suppose is really something that is still kind of on the outskirts. Most people are thinking about what to do when you have Alzheimer's disease. Not as many people are thinking about the question that you're asking and that a few other people are asking which is what's in our control because yes, you alluded to apoe4 which I'm sure we'll talk more about. But what you just said about type 2 diabetes would
Suggest that if you believe you can prevent type 2 diabetes, wouldn't that at least suggest you have the probability or possibility of preventing or delaying Alzheimer's disease. Sorry. So I didn't mean it R up to you but I want to highlight the important implication of that
statement. Exactly it's so important I think that looking at Alzheimer's disease and understanding sort of the underlying cause of it opens up. You know, these new avenues for prevention and also treatment and of course there
Are people that do get Alzheimer's disease early in life. I mean, these are people that could come down with it in their 40s or 50s, you know, people are outliers in that case, but it does happen. And there are things that you might do everything right? And still, like, have that terrible genetic combination with respect to the apoe4 and type 2 diabetes understanding. Again, is there something like common going on here that we can sort of understand as a foundation to what are the initial like?
Things going wrong to lead to Alzheimer's disease. And that is where vascular, dysfunction, particularly the blood vessels and capillaries that are lining. The blood brain barrier, seems to be a really, really early event. That is common between all types of dementia and between Type 2 diabetes and apoe4. So people with type 2 diabetes as you
know, can I interrupt for a sec? Rhonda tell folks what the blood-brain barrier is
I think it's obviously going to be an important part of this discussion and not everybody might understand what it is or why it's so
important. I am not a neuroscientist, you know, I am a Scientist but I have interest in this. And so I've done a lot of reading in this field, the blood-brain barrier serves a couple of functions. I mean, one is there's a combination of different cell types than make up the blood-brain barrier and a lot of vasculature, right? And so blood flow, things are brought to the blood-brain barrier and oxygen.
Glucose other nutrients. And they are, you know, transported across the blood-brain barrier. But it also as the word implies barrier provides a barrier to things that you don't want to get into your brain. We don't want red blood cells getting into our brain, we don't want a variety of other molecules proteins that are floating around in our circulation, to get into our brain. And so when the blood brain barrier begins to break down people, I think are a lot more familiar with when the gut barrier.
It's to break down. I sort of become more of a common theme that people are focused on gut health. And so, mostly you hear the word leaky gut. I don't really like that term. I think it's intestinal permeability, but the tight junctions. These proteins that are holding endothelial cells together in the gut. When those open up you get that term we could get or as it really should be called intestinal permeability. Well in the brain you also have and to filial cells and you have tight junctions. And when those tight junctions, also break apart.
We can talk about like what's at the root of that, that leads to permeability of the blood-brain barrier and therefore two things happen. One you are allowing then things from circulation to get in the brain, which, you know, wreaks havoc on the brain and leads this vicious cycle of neuro inflammation, inflammation in the brain, but also you're disrupting the transport of important nutrients, oxygen glucose. I mean, blood flow is disrupted to the brain as well. The blood-brain barrier.
Maintaining that Integrity is very important and both apoe4 and type 2, diabetes lead to permeability of that. And so with type 2 diabetes, people have hypoglycemia, right? They have elevated blood, glucose levels and that over time leads to Advanced glycation, end products. These are basically, like, they cross-linked proteins and a variety of other things that in the vasculature and that basically damages the blood brain barrier and leads to
88. Before, you know, there's a variety of other mechanisms that happen. But essentially you can measure the permeability of the blood-brain barrier, looking at a variety of biomarkers and proteins in cerebral spinal fluid, but also in plasma and these have been shown by a doctor Slavic dr. Montaigne to occur decades before the onset of cognitive impairment. And it's literally, you can find it in more than 50% of all dementias, it's happening independent of amyloid accumulation.
How Tangles as well. So it's, you know, either something that's happening before, well before. And in fact, blood-brain barrier, permeability, the blood-brain barrier is essential for removing toxic compounds from the brain, and I'm a variety of different processes. Like, you know, happen to allow this to occur. So, for example, you activate the glymphatic system during sleep right? In a lot of people are aware of this, your brain, sort, of swells during sleep, and the glymphatic system is pushing this.
Cerebral spinal fluid through the brain, clearing out, debris, amyloid plaques, you know, things like that. Well, that you need the blood-brain barrier to be intact for that to occur. So, I mean, it makes sense that basically, if you have blood brain barrier, permeability happening that you start to have the accumulation of amyloid. So it's sort of like, accumulation of amyloid never
thought of that. By the way, around it, I'd never thought of what you just said, which is if your blood brain barrier, can't hold the back pressure, which is what would be the case, if it were permeable, you would not have the back.
Pressure to maintain the glymphatic flow that never actually occurred to me. So you said that. So, very interesting mechanistic tie to that
problem. And I'm not familiar with all the types of ways of rain. Like, there's other, like, parenchyma and stuff that are like, cleaning out the brain. All of those things are not happening as good when your blood brain barrier is
dysfunctional. And then another point is the ability of things to interrupt and get into the brain that shouldn't. So one of the things, you know, everybody learns in Pharmacology or medical school is that there are certain
Certain drugs that penetrate the blood-brain barrier. There are certain drugs that do not be implication. Being certain molecules can pass through certain molecules cannot. Well, presumably the leakier. That barrier is the more things that maybe we evolved to not have cross that barrier do indeed cross. And perhaps, that's a part of what you just said, right? Which is this increase in inflammation? That is now coupled with an inability or decreased ability to clear out debris.
Exactly. In fact, so work from dr. Montaigne has shown that fibrinogen which is you and I are familiar with this protein, it's something. If you're doing an inflammatory biomarker panel, it's a protein that's involved in blood coagulation. But it's also something that is a marker of inflammation. And fibrinogen is not supposed to be in the brain, but it's found in the brain in people with a leaky blood brain barrier. So what's it doing in there? It disrupts a cell type.
Called oligodendrocytes. These are a cell type that make Milan, sort of fatty white structure. That's important for electric signals being fired throughout the brain. And it's basically toxic to them. So, you basically start to have these, you know, lesions and stuff in the white matter part of the brain, white matter hyper intensities. As you're probably very familiar with a very common in small vessel disease. Also, you can see that in people with Alzheimer's as well, but getting that fibrinogen in the brain like
Like that's happening because it's allowed to get in there. So, the permeability of the blood-brain barrier, basically preventing stuff from getting in your brain that you don't want in there. That's number one, but also the transport, I think you also alluded to this, you're not getting things like glucose into the brain. And in fact, all these Transporters there in the endothelial cells, there in these cells that are making up the blood-brain barrier and when you start to disrupt that blood-brain barrier, those Transporters like are dysfunctional.
For example, one of them is the glute one transporter. This transports glucose into the brain as you start to get a disruption in blood brain barrier, function glucose Transporters, they go down and so you're talking about like not getting enough glucose into the brain which is again. That's one of the pathological features of Alzheimer's disease, right? Not getting enough glucose into the
brain. That's actually an interesting explanation because a very subtle point you made that might not be picked up on everybody. Is you mentioned the glute one transporter as
opposed to the glute for transporter. And if my memory serves correctly, the brain has glute ones as opposed to glute fours. And glute ones are insulin independent. Is that
correct? Yeah. For the most part, their insulin independent that's my
understanding. And why that's interesting is because it seems a bit counterintuitive that a condition that leads to insulin resistance of course. Type 2. Diabetes is the essence of insulin resistance. It seems counterintuitive that that would produce a
Po metabolic state in an organ, whose glucose Transporters are insulin-dependent. Except when you explained it the way you did, which is it's not the insulin resistance of the glute one transporter. That's the problem, the way it is for the glute for transporter in the muscle. Instead, it's the actual mechanical disruption. If I'm understanding you correctly of that transporter because of the way, it's no longer presumably, held in place by the barrier itself that allows glucose to get across that. I understand that correctly.
Correctly, 100% correctly. And this isn't like Dogma. Like this is definitely known, it's definitely where I'm heading. It's my opinion, but there is evidence of it. And I think it's time to explore this evidence, a little closer and a little deeper because you know, you hear the term type 3 diabetes. And I think people think about it in the way of the brain being insulin resistant and you know, maybe there's something to that, but I don't know if that's exactly what's going on. I think the
2 diabetes is disrupting the blood-brain barrier through a variety of mechanisms, including the advanced glycation. End products in the vascular. I mean the vasculature disruption in type 2, diabetes is well known. I mean they've all sorts of problems. Not the neuropathy like all this. I mean, they are disrupting their vasculature including these tiny tiny little blood vessels that are like smaller in size than our, the diameter of a hair. Those things are like disrupted at the blood-brain barrier and when you disrupt them, their blood
Flows decrease and the Transporters are going down. I mean, there's all sorts of problems and so I think fixing the diabetes, obviously would be like, the downstream thing to do, but like it's kind of a new mechanism, right? It's a kind of a new way of understanding
it. It explains the observation. So there's an observation that is unmistakable, which is type 2 diabetes. I don't know the number but I think it approximately doubles your risk of Alzheimer's disease. So in other words, even if you're sitting there walking around with two copies of the, a poet,
Really low having type 2. Diabetes means you might as well have a copy of an E4. Allele from a risk perspective. And what this is saying is Well it's not entirely clear at the surface. Why type 2 diabetes would impact the brain through the lens of traditional, thinking of glute for Transporters, which are insulin-dependent. In other words, it isn't just an insulin resistance problem. But I think these two other things matter, what you said about the microvasculature, what I think, a lot of people don't realize it.
How destructive type 2 diabetes is to the kidneys. Because those tiny, tiny blood vessels. People are familiar with amputations and things that occur in digits because of that, impotence, all of these things where blood vessel is essential in small blood vessels and so there's that which feeds into the vascular path that you've discussed. But it's this also this disruption of glucose transport directly across that transporter. So I think it's actually a very compelling thesis for how type 2 diabetes could be acting via those two.
Needs to ultimately result in
hypometabolism, I do too. And then, of course, the Cascade of inflammation that happens after that. So the other thing that's also very interesting is so we were talking about type 2 diabetes and very big implications are for the prevention of Alzheimer's disease. There's a lot you can do as you've talked about, to prevent and even treat with diet and lifestyle, right? Type 2 diabetes. But also, what's really interesting? And I was sort of on this Trail years ago, I published sort of integrated.
Of review on the role of the omega-3 DHA, transporter MF s D2 a in the brain, what's really interesting that animal studies, when you disrupt that transporter, it causes like 50% breakdown of the blood-brain barrier and like greater than 50%, loss of Omega-3 in the brain. So in my opinion, you know, that's animal evidence. Of course, there's human evidence where m f SD to a Transporters, decrease, with age, particularly
In Alzheimer's disease, and with apoe4. So there are genetic abnormalities and mutations that occur in that transporter, where people have less of it and they have microcephaly. So they have like smaller heads and they also have cognitive dysfunction, sort of cognitive impairment, things like that as well.
How do we know that Rhonda? So, that's, let's even put the pathology aside, this would of Latter category. But let's just talk about. Well, again, what you've said, explains something, we've empirically felt
Is true and the evidence suggests that this provides a mechanism, right? Which is apoe4 carriers need a higher level of EPA and DHA to get the same benefit that appears to be empirically correct. That would provide an explanation, something else you said, you know, we talk about amino acid or protein resistance, basically, antibiotic resistance as a person ages, they need more and more protein to get the same effect. It's almost like you're saying aging itself could create some resistance.
To dietary EPA and DHA that might require more as time goes on. Do you think there are also just genetic differences within the variant of normal quote-unquote IE non-pathological, where one person would need more EPA and DHA to afford them. The same benefit of protection is another
person I do. I know there's at least a couple that are known and so like some people have certain Gene variants that actually they respond better to for
Sample, omega-3 supplementation and others. Don't where they would actually need a higher dose. And I think there's many more to be explored like we haven't unlocked all of that yet when I say we I mean the scientific Community. Not me, not me personally, but with the omega-3 and this again really hits home. The preventive role here that we can have in our Alzheimer's disease risk. So with the MF s D2 a like these
Transporters are actually lost. So there's a type of cell called parasites Perry with an i not to be confused with a parasite. They basically have these like big feet that wrap around the endothelial cells at the blood-brain barrier and they serve really to important many important. But two main important functions one is, they're basically constricting and dilating. And like, helping squeeze like the flow of blood. So they're like regulating blood flow to the brain, but they also are very important for that barrier.
And they start to fall off with age these parasites and inflammation plays a big role in that, but the MF s D2 a Transporters are concentrated on those cells to. And so you see hot spots of where the parasites once those parasites start to fall off? That is when basically immune cells and everything starts going into the brain. It's like the start of the vicious inflammation, cycle in the brain of the leakage amyloid accumulation, just everything Downstream.
Something there with those Transporters of a mega three that are right at the same site of where you lose those parasites, which is also really interesting. And again, there's a lot of animal evidence that suggests the role of that transporter in blood brain barrier Integrity. Also again you can kind of like Connect the Dots here where you think? Okay well this is DHA and phospholipid form. So it's like, okay, there's got to be something here with the omega-3 and I know there's a variety of scientists that are investigating this
But I'm sort of excited. I am now going to be part of a team, so I joined the fatty acid Research Institute, which is dr. Bill Harris's, Research Institute and as a research associate and we are secured a small Grant to look at the role of omega-3 with blood brain barrier, integrity and biomarkers. And people a variety of different people that have small vessel disease that perhaps go on to get Alzheimer's disease. And so I think
Needs to be more research in this area because the implications here I think are really important. There's two main lifestyle interventions. I think that are important with respect to the blood-brain barrier. Three actually three. So basically not getting or fixing your type 2 diabetes and then the omega-3 intake and like defining that will be sort of tricky but. Most people in the United States. They're not eating enough fatty fish and they're not supplementing with omega-3 which is sort of an alternative. I think it was like a toy
2012 study out of Harvard that identified, omega-3 low omega-3 intake, from fish. So the Marine type of Omega-3 not plant AOA as one of the top six preventable causes of death. So it was up there with smoking. It was smoking and blood pressure and obesity and being sedentary low omega-3. It blew my mind and I'm not a biostatistician but there was some calculation done with estimating the number of deaths caused by not getting enough.
Three each year. It was like the same number of deaths. It was like eighty four thousand deaths a year from low omega-3 intake from fish.
I wonder though if that's also just a marker for poor health, that's the challenge of all of those studies. How totally in some cases would smoking. It's pretty obvious that there's causality there. I think there also is with blood pressure but you could argue that never in the history of the world has there been a person who has a making being a bit facetious who has a high
High omega-3 index who eats junk food and fast food all day. Those can't coexist. I want to ask one clarifying, question, Rhonda. Certainly I know that when you're talking about Omega-3s, you're referring to the Marine variant of which we have EPA and DHA, but the transporter if I understood correctly, is it a transporter, only for DHA and it's phospholipid form and if so, what is the importance of EPA in
this great question. So the MF s D2 a transporter
That I've been referring to is specific to DHA and the form of DHA is lie. So phosphatidylcholine DHA. So we make it when we take in DHA from fish, or from a supplement, the higher amount of DHA that we take in, we add that lie. So phosphatidylcholine group to the DHA. We also have DHA and free fatty acid form bound to albumin. And albumin is not that doesn't get into the brain but
But it takes it to the brain, blood brain barrier and the free fatty acid can sort of diffuse passively cross the blood-brain barrier as well. Same with EPA.
Oh I see but because the phospholipids on the DHA, it needs a dedicated transporter. Whereas the unphosphorylated not phosphorylated the one that doesn't have a phosphatidyl lipids. Phospholipids sidechain can diffuse without a
transporter exactly. So it's free fatty acid bound to albumin and it can just diffuse across the brain. Yeah. So that's how EPA is generally getting in the brain.
Then second question for you on that thread. Feel free to go into.
Much depth as possible. Because I know this is actually very important topic that is somewhat controversial. What do you see as the relative importance of DHA and EPA? The conventional thinking I think is that EPA probably more important in the heart DHA. Probably more important in the brain. I'm sure that's a gross oversimplification. But can you expand on that?
I can try, I don't know that it's really known. So the way I personally think about,
Both EPA and DHA. There's a variety of metabolites and of DHA that are involved in resolving inflammation. So these are resolved ins, the Maris ins, the spms, protect ins, and EPA also has some of those metabolites as well. And it also plays a direct role in inflammation through the, I don't want to say inhibition but like dampening the prostaglandins and
Leukotrienes. And a lot of the other inflammatory process is. So it's kind of like an approach where you're affecting inflammation from multiple ways, right? It's like a multi-pronged approach and I mentioned fibrinogen earlier about like fibrinogen. It's an inflammatory protein while it's involved in quite galatian but it's something that we do measure as a marker of inflammation. So their studies showing that people that are exposed to particulate air matter, their fibrinogen goes up. But if they have a higher dose,
S of Omega 3 or higher intake of Omega-3, it blunts that effect again through the inflammation, right? So, both DHA and EPA are important in my mind for the brain as well. I mean there's a variety of studies that have looked at even depression. You can induce depressive symptoms in a person by injecting them with what's called lipopolysaccharide, which is a component of the outer cell membrane of gram-negative bacteria. We have billions of those in our
Got in fact there's about one gram of lipopolysaccharide or LPS for short is also referred to as endotoxin is about one gram of that in our gut. Well you can inject people with a low dose of that, something that actually would be somewhat, you know, I would say equivalent to someone with intestinal permeability and it can cause depressive symptoms in people compared to those given a placebo and you can blunt that depressive symptom effect with EPA probably because of the inflammatory the blunt.
King of the inflammatory response. And there have been some, this is a field that's again, understudied underfunded but some preliminary evidence randomized, controlled trials, small randomized, controlled trials that need to be, of course, repeated with larger sample sizes. They're basically showing that supplementation with EPA can help with depression.
Yeah, this is such a frustrating thing for me and I obviously I know it is for you and for many others, including Bill Harris, if you took the cost of one phase,
Three anti-amyloid failed drug trial, just take one of them. There's been dozens of them. Just take the dollars that were spent on one of those. Guaranteed to fail phase 3 trials, and put that money into a preventive trial that looks at something that's got real feasibility or something. That's really interesting. Like the optimal supplementation of DHA in the right patient.
A group, we could have an answer and yet, for obvious reasons, there is an incentive to do a phase three drug tile on a candidate with an IND. There's not an incentive, from a financial perspective to study these other things. And I think for a disease, like Alzheimer's disease, that's particularly problematic. As I suspect, we will discuss unlike cardiovascular disease where, yes, prevention is still the best strategy. You can come in late to the game and still make a difference. I
I think the evidence is particularly compelling that. That is true for Alzheimer's disease. Now I'd love to be wrong but I have yet to see compelling evidence that you can be a johnny-come-lately to that pathology and have an impact.
It's hard to fix those leaks in the brain once they're started. And that also is why I think there have been failed. Trials. Also with we've been a few with omega-3 supplementation. People that already have Alzheimer's disease and you're giving them like, I don't know what most to G, I've seen studies like 500 milligrams.
I'm like, are you kidding me? You know, patients with high triglycerides or cardiovascular problems. Are giving you 4 grand for. I know, at least for this is something that has the safety of a nutrient, but literally an act like a pharmacological drug, you know, higher doses. I agree with you. I think it is much more challenging to fix when you have Alzheimer's disease. And certainly, like I'm talking about, like, the leeks and the Brain, then what happens after that, the amyloid accumulation, and like, when you start to, get to this level,
When your you've got all of that, I mean, good luck. It's going to be, it is going to be challenging and you're going to have to take. It's not going to just be fixing the amyloid. You're going to have to have a cocktail that are going multiple angles, I think in order to get some improvement, I think the amyloid and perhaps, also fixing this, the blood-brain barrier leaks as well. Maybe at the same time with the cocktail may help a little bit but prevention is the way to go. I mean like it's so much better to not get Alzheimer's disease than to try to fix it once you have it.
Because it is a very complicated disease with lots of things going on. I think that the strategies that can be done and they're not that if a cult we talked about type 2 diabetes, there's no reason why someone should have it. You should be able to.
I would phrase it as I do. Not believe for a moment that type 2. Diabetes is inevitable to our species, whereas I do believe atherosclerosis is inevitable. Of course. I also think most people don't need to die of it. That's a very Stark contradiction.
In the disease is inevitable. And as much as humans will have LiPo proteins that carry a poby, we will get atherosclerosis. But again we have the technology to delay the onset of that disease to the point where it should not be the cause of death. We should be dying with it, but not from it. I would also argue that cancer is inevitable to our species. It is simply a stochastic problem where if you live long enough, and if you accumulate enough genetic mutations and we
We can do lots of things to reduce the risk of that and to delay the onset of that and to detect cancer early and be more successful in treating it. But the incidence of cancer strikes me as something that is inevitable with enough age. I actually don't feel that way about type 2 diabetes. In other words, I think I share your point of view which is it's not something that is necessary. We don't have to eventually get it. And I think that makes it all that much more, tragic that you watch how many people are suffering from this disease and how much
Image. It's causing not just in the disease itself, but as you said, it's such an amplifier of the what I referred to as the Horseman, right? It's what it does to your risk of cardiovascular disease cancer. And Alzheimer's disease is actually why the death toll for type 2? Diabetes is so grossly under
appreciated. Yeah it's accelerating the aging process. The molecular it's gasoline on the
fire of Aging, I'd have to really reflect on it but I can't think of a process that accelerates aging.
Aging more than type 2
diabetes, right? Maybe a morbid obesity but like the probably also type 2
diabetes. I would argue only in the context of insulin resistance, which gets us right back on that path. So the good news there is not that it's easy but we sort of know what it takes to treat it and prevent it and it doesn't necessarily look like the strategies that are being deployed unfortunately at the level of the Ada. When ask you one other thing we haven't talked about but I want to know if it pertains to the blood-brain barrier at all and that's blood pressure. So hypertension.
And I guess hyperlipidemia also pose enormous risk for not just cardiovascular disease where they are two of the three biggest drivers of risk, but they also pose a risk and Alzheimer disease and I under do either of those act specifically through the blood-brain
barrier. It is another really important modifiable lifestyle factor that can affect Alzheimer's disease. Risk maintaining good blood pressure. So, I mean, basically, you want to be systolic below 130 once you get to 130,
T. The Sprint trial would even say,
120 120. Yes, and the blood pressure itself. So getting that blood flow to the brain blood brain barrier. Specifically is so important when you don't have enough, blood flow doesn't basically isn't able to get to the blood-brain barrier. Well, enough, those tiny little vessels start to like, just fall off and it's one of the reasons why exercise also is so. So important. There's been a variety of studies that have looked as you mentioned the observational data is now
It to establish causation, but it's still an interesting point to look at in combination with many other types of
data, especially when it's always in the same direction. Exactly what differentiates the epidemiology around. For example, exercise in blood pressure from the epidemiology around nutrition, the epidemiology and nutrition a. It has very low Hazard ratios and it's always changing the direction. It's moving in suggesting that, whatever is being studied, probably doesn't matter yet. When you look at the epidemiology of smoking blood pressure dyslipidemia,
Sir sighs, much bigger Hazard. Ratios virtually always pointing in the same direction. So it strikes me that the ladder is signal. The former is
noise. Good point. So, you know, 50% of a people adults in the US have hypertension and about 20 percent of young adults. Like, we're talking people aged 18 to 39 have hypertension. That's crazy, right? And actually the high blood pressure, it's the cumulative exposure to high blood pressure, that's really damaging the vasculature. And so, it's the younger people.
People, it's the people that have it earlier in life, that should be the most concern and are the least, right? There's the ones that are like, I'm young, you know, I can worry about it later. But, yeah, so high blood pressure is associated with dementia risk. Particularly when you have it like before 50s, like when you get it in your before the 50s or midlife. Once you start to get high blood pressure, in older age like 70 80, it's not as much associated with Alzheimer's disease and dementia risk. It really does seem like
Cumulative. Exposure is the key factor there again, one of those things that is a lifestyle Factor that's easily modifiable exercise. Improves blood pressure, sauna, improves blood pressure. Those are two basically, low-hanging fruit lifestyle interventions. Some people do have Gene polymorphisms where they're very sensitive to salt intake and sodium intake. And the combination of those people with a higher sodium intake, really seems to Skyrocket blood pressure nutrition. I think it's also
Looking at the combination of genes and diet, most nutrition studies, don't do that. There is an interaction going on, and I do think that's why some of the sodium intake blood pressure. Literature is just a little more I would. Yeah, it's all over the place
located. I was going to ask you a question about exercise, but before I do that I want to actually pick up on something. You just said, how optimistic are you? I don't know what's bracket. This with let's say in the next decade that we will have more of a sense around what precision
Attrition looks like as it pertains to jeans and polymorphisms of them. In other words, people talk the talk like, oh, I did this test and it told me I should be eating this, that, and the other thing, but the reality of it is, there's nothing that's available today. That's come close to offering that type of insight. A, do you believe that, that type of insight is available? You used one example which I would agree with you on which is that there are probably different levels of genetic susceptibility. To sodium that might suggest one
And needs to be eating two grams a day of sodium and another person needs 4 grams a day, but do you think it will get further than that? And How likely do you think we will be to extract that
information? I do think in 10 years we're going to know a lot more about Precision Nutrition obviously Precision medicine as well because there's also an interaction between, you know, pharmacological treatments and jeans as well as you know in 10 years were definitely going to be a lot further than we are. Now, the problem is and this is always the problem.
Problem, we've already alluded to it. A few times is the incentive for funding to study those things that aren't necessarily going to be super profitable, the government, the NIH, there's a certain amount of funding that you can get from them and they often like to study one sort of thing, like the nutrition. When there's like multiple things involved, it's like they're just like too complicated and so there's a lot of funding from Pharma industry for example and then they put in lots of money because they are incentivized.
To do that when it's a drop. That's my one concern with I would say gene diet interaction when it's more on nutrition, but there are people that are, it's a growing field of research, for sure. And I do think with technology is advancing to, I mean, so the point that our technology is advancing with AI and stuff, I think that we're going to start to see an exponential there. Honestly, I am optimistic that in 10 years that's going to be a lot easier to delineate. What a person should eat based.
Off of the genetic makeup versus just what generally we
think. Do you think that that will be at the level of macronutrients or micronutrients? Like, how much heterogeneity do you think there is among people as it pertains to factors like
that? I think both there are differences in the response to macronutrient intake and the response to micro nutrient intake. And there are people, there's vitamin D polymorphisms, right? Where people for whatever
As in so maybe they evolved in a place where they were so much sun or something. Like I don't know what the cause is but like some people they have to supplement with high doses of Omega-3 to be able to convert vitamin D. Cursor to actual the hormone, right? The steroid hormone that's just one example. There's selenium, there's the Magnesium. There's a lot of different micronutrients that are off, and there's a mega three. There's a mega three as well and B vitamins. Exactly, there's B vitamins. Yeah, more people are looking into it and
And with advancement and Technology, things will become cheaper and easier to do and that's going to create an exponential in my opinion, where it's like okay maybe in a couple of years, will start to really see an explosion and then after that explosion exponential happens where people are building off of that because that's how it worked. This kind of where I think it's going, and I'm excited about it. I think that's where it needs to had. I think it's going to clear up as you mentioned all the conflicting data with nutrition. I mean, nutrition. Studies are a mess designing, the right trial. I mean, part of the reason,
For that is because we have, if all these jeans, I'm going to drug with the exception of yes. There's the cyp enzymes and stuff that help us metabolize xenobiotics things that are not a vitamin or mineral or essential amino acids are fatty acid, right? So, I mean, it's foreign to our body, but by and large, when you give someone a drug either, starting with zero levels of that drug in their body, and you give them the dose that you're giving them, it's like clear, you're giving them a dose and it's going to be different than people getting a placebo, right? It's going from zero to something. Whereas, when you do this,
Nutrition study a micronutrient you know, you give them a vitamin or mineral. Nobody starting with 0 for 1, your placebo group could have high blood levels of that and unless you measure something you'll never know and all the trials are sort of. They're trying to mimic that gold standard for randomized, controlled trial with a pharmacological drug. You have to like put in so much more effort with nutrition with the drug. You don't have to start doing blood samples of this and that and then measure the drug and make sure people aren't efficient in that drop. Of course, they're deficient. And right before they start the trial, they don't, it's like a
drug, it's such a good.
Point Rhonda, and I'm going to use two examples to highlight why this is so important because it ties to two things. We've been talking about. If you look at how a blood pressure trial is done, it is exactly what you say. It's titrated meaning it's done the way a Pharma trial is normally not done. So a blood pressure trial says, let's just bring in a whole bunch of people with high blood pressure. Okay? You guys on the placebo or on the low treatment arm, we're going to manage you to a blood pressure of 140.
Over 90 but no lower you guys in the treatment arm, we're going to manage you to 120 over 80 or better. And by the way we're managing to the outcome, not the drug. So I'm agnostic as to whether this person needs a higher dose or a lesser dose, we're checking the outcome here. And so if we did a vitamin D trial, that way, it would be very different trial. And one of my biggest criticisms of vitamin D, trials, and why. I think we don't have an answer as to whether supplemental vitamin D is valuable.
Is they don't do this, take the people. You divide them into two groups. You give one group of placebo, you give one group. Usually a very low dose somewhere between two to four thousand IU daily. But we don't actually know what the level goes to. In other words, a better vitamin D trial would be, we take a bunch of people whose vitamin D is below 30. In one group, we give a placebo and in another group, we give whatever it takes to get them to. I'm making this up but 80 then we would see, is there a difference between this group that's below 30. And
This group that gets to 80 regardless of the dose, it took to get them there because of course that may include part of the problem. So I think your point is an excellent one. And I think it's something that listeners need to be aware of when they're scrutinizing, Trials, of this nature, which is a negative trial, doesn't mean. The thing doesn't work if the trial wasn't designed
correctly, right? And it often, it's a matter of money to write to measure all those things. It's cheaper to just give someone the vitamin D supplement and then look at the outcome.
And go didn't work and then you have another confusing piece of literature out there that people are like oh but says that Vitamin D supplements do nothing. Yeah it's a big problem and I do again, I think as our Technologies are advancing that that's going to become less of a problem as well, at least I hope. I mean I guess you never know.
So when I go back to something you talked about earlier which is you just touched on exercise and I want to kind of visit now the suite of things.
That exercise does because people who listen to this podcast, know if there's one thing I just can't stop talking about it exercise. But I think there's a reason for that, right? It's not just that I love exercise. It's that the evidence is overwhelming that a person who exercises especially at the right amount. We're talking not just 30 minutes a week type thing. But if you're really doing the work, you're having a greater impact on the reduction of risk of Alzheimer's disease than any other intervention you can take. Now, there are lots of interventions that matters. Sleep matters nutrition as we talked about type 2 diabetes. All these
But the risk reduction that comes from exercise is enormous. What do you think? Are the mechanisms by? Which that is happening? Because I suspect there's
many. Oh, definitely many mechanisms happening. And I would, first of all, 100% agree with you, like there's nothing better than exercise. Of course, any exercise is better than none. But for me because as I mentioned at the start of this podcast, I'm very focused on neurodegenerative disease. I specifically sort of
Design my workout routine. Based off of what I think are going to give me the biggest brain benefits. And what I've sort of come to the conclusion of is that intensity does make a difference with respect to the neurobiological effects exercise intensity. There are some mechanistic reasons for that but just talking about what's moderate. Intensity exercise. What's considered vigorous intensity exercise, right? If you look at some of
Recommendations out there by the committee's, you know, there's a team of scientists Physicians, that sort of analyze all this data. And then make these Health recommendations based off of that data, it's 150 to 300 minutes of moderate intensity exercise which I think they Define as like 50 to 70 percent of maximum, heart rate, vigorous-intensity they say 75 minutes, I guess a week. And that would be more of your getting above the
Like 75 to 85 percent max heart rate so that's what they I think defined as something like that vigorous and they have a variety of examples you know there's the World Health Organization. It's a variety of committees that come to that same conclusion for me. I like to go higher intensity. This is something I kind of was looking forward to talking to you about because it has to do with, how do you measure the estimated heart rate, which is what I do. I've estimated, and again, all sorts of problems with that based on your physical
fitness mean.
Estimating your maximum heart rate to take a percent event.
Okay, so basically you know the more fit you are you could be doing a more vigorous intensity exercise but your heart rate like doesn't go as high as someone who's not a fair and then people that are older. So there's of course I would say problems with that but generally speaking, that's one way, but I'm also very interested in lactate and I know you are as well for me. I actually want to get my lactate levels High and the reason for that is the neurobiological
Oil benefits. So lactate, as you know, was once thought to be the sort of end metabolic byproducts. It was like useless. Well, not only just use this actually thought to be
harmful at least two performance,
right? Harmful to Performance, with respect to people thought it was like causing their muscle soreness. As you know, now that it's not lactate, it's the proton. Build up lactate is sort of in homeostasis with lactic acid. In its, the protons that were sort of responsible for that
and neither of them are responsible for
Soreness, you feel the next day, that's the micro. Trauma. Of course, like the soreness and the burn from the hydrogen ion is gone minutes after you stop
exercising. Yeah, exactly. So, the lactate that gets into. So you're generating lactate when you basically are pushing your mitochondria inside your muscle cells to a point Beyond where they can generate enough energy in the form of ATP adenosine triphosphate, then they sort of have
To figure out another way, like, your cell has to figure out another way to get the energy, right? So this is where glycolysis comes into play. So, this is happening outside of the mitochondria, and I'm sure your listeners have heard all this before, but for those that haven't, the lactate generation is then from that, you know, metabolism of glucose outside of the mitochondria. And that's happening. When again, you reach that threshold of, you're pushing your muscle cells hard enough and their mitochondria can't keep up with producing enough energy. So the lactated
Of and these studies date back to like the 70s. It's been shown that lactate that gets into circulation and it's used by other organs as energy source for one as a fuel. Yeah, and the Brain being a big one and this is now Decades of research, but dr. George Brooks has, you know, he was like one of the first to propose is lactate shuttle Theory. And he's of course provided evidence for that as many others have as well where you know during exercise and after exercise the lactate that
That is generated from muscles that gets into circulation. Is consumed by the brain. This has been shown in humans and animal studies, of course, but it's consumed by the brain and also not only is it consumed. It's acting as a signaling molecule and increasing at the blood-brain barrier lactate itself has been shown to be responsible for the production. What's called vegf. It's a vascular endothelial growth factor, vegf
And what it's doing at the blood-brain barrier is it is growing new vessels and repairing damaged one to the brings it back to what we were just talking about. Right? The damage, the vascular, damage at the blood-brain barrier, lactated self is a signal to increase that vegf. It also increases brain, derived neurotrophic Factor bdnf at the brain at the blood-brain barrier and in the brain as well.
Where is bdnf, produced
many places. It's produced in capillaries and the vascular system.
I'm in the heart in muscle is produced in the brain. So exercise increases brain. Derived neurotrophic factor in many different parts of the body, in many different organs and tissues. And it's really interesting because there is some evidence that the sheer force of blood flow. So essentially, like, the more vigorous you are, exercising, your heart's pumping, right? And your blood is just going faster, it's moving faster, well, that Shear force on the actual
Real cells lining, the blood vessels is a signal to increase bdnf as well. Super interesting stuff there. It also increases bdnf in muscle, which it plays a role in repairing damaged muscle. It increases in plasma brain-derived neurotrophic Factor, although, there's a little controversy about this, it can cross the blood-brain barrier and it also is produced in the brain as well. So, all of those things, and brain-derived neurotrophic factor is a really important for many reasons. It's important for long-term potentiation. It's
Horton for neuroplasticity. So, long term potentiation, is basically strengthen the connections of the synapses that are connecting neurons. It's involved in basically long-term memory form retention, but also, it's important for neuroplasticity. So brain, derived neurotrophic Factor plays a really important role in that, and that is also something that decreases with age. I think you're really easy way to think about it is your brains, like, ability to reshape and restructure with the changing environment, like as your aging, things are changing in the brain and like you have to be able to
To that brain responds in a plastic way. And that happens very well when were younger not too well when were older not so well in certain disease States, like depression neurodegenerative disease and so that brain, derived neurotrophic Factor plays an important role in that but I am going for higher lactate and based off of your recommendation, I got the lactate M, the Nova, the one that you have. And I've been using that to kind of try to get my Lactaid higher than typically, what I think you are doing with a completely different type of training.
We do kind of both ends, right? So when the one end of the spectrum, what we want to do is increase our mitochondrial capacity to maximize aerobic metabolism. And there are two ways to do that. Meaning you have to do two things. The way I describe this to people is the way one of my coaches described it to me when I was a fledgling cyclist, your aerobic capacity is a pyramid, and the area of that pyramid is your total aerobic capacity and to
The largest area of a pyramid. You need the widest base and the highest peak a pyramid with a narrow base and a high peak. Yeah. Not as good a pyramid with a very wide base and a shallow Peak, also not great. You want wide base high peak? Well, in that analogy, the base is your Zone to threshold. It's how much work can you do while keeping lactate at that sort of threshold that George Brooks and you go
On the lawn talk about of about to mmol. So what differentiates the best aerobic? Athletes from someone, you know, say with type 2 diabetes which would be the opposite, end of that Spectrum where you have real metabolic dysfunction or rather mitochondrial dysfunction. We're talking about four fold difference in watts per kilo output, and you just have to train at that level you have to get to that threshold and train right there. So you know, this morning, that was the workout I did, right? Was his own to ride where I'm just riding right at a lactate.
All of 1.9 mmol was where I was today, but you do need to do what you're describing is. Well, you have to do the pyramid building, you have to build the peak of that pyramid, those are the vo2max sets and, you know, generally The Sweet Spot for building. Those is 3 to 8 minutes of all-out effort for the respective duration. So obviously, what you can do for 3 minutes and no more is harder than what you might be able to do for eight minutes and no more my favorite are four minutes. So for example,
On Sunday. That was my workout was, I actually did an hour of that zone to, you know, kind of, to mmol stuff. And then, did for minute awful repeats, where it was like much, much higher power for 4 minutes and then I rested for four minutes. And then when again, for 4 minutes, and then rested for 4 minutes. And at the end of those four minute blocks, you know, my Lactaid will be 15 or 16. Wow. And then, at the end of a four minute rest, it might be down to six or
It and then we do it again and do it again and do it again. Yeah, a long-winded. Way of saying, you want both, you want to build that pyramid to be as wide and as tall as possible. What I don't think I appreciated though was that the brain is getting a benefit from those lactate Peaks?
Yes, it's getting a benefit and you know, it's cleared quite quickly. I mean it's minute it's a minute if you do
nothing, it's if you just stopped and of course athletes are even better at this right?
An amazing athlete would clear lactate within they'd go from 10 mmol to to mmol in minutes
for me you know 20 minutes later I'm back to my 0.9 mmol Baseline. That lactate also is important for neurotransmitter synthesis, you're making glutamate the major excitatory neurotransmitter in the brain, it's important for making precursors to that norepinephrine. I mean these are all been shown in human studies also animal studies. So for me I do a lot of Tabata
training so that's even more intense.
Because you're only doing 20 seconds on in 10 seconds off. So that's really intense.
It is and I do 16 of those. So I do, you know, like eight and then separated by like a 30 second break and then I do another
8. So 2 4 minute
blocks, it's a total of about 10 minutes. So the first minute I mean, like Zone 2, and then by, like the end of that minute, I'm like, Zone, 3, and then I go into zone for,
what are you doing this on? Are you doing this on an air
bike? Or I'm doing it on a pallet on, right? And my Apple watch is,
Is beaming my heart rate and my zones onto my screen with their all estimated, of course again. But I do that five days a week. It's for me. The efficiency also. So I'm trying to maximize the neurobiological effects for me with exercise and I really find pretty compelling evidence. That intensity is really important with respect to that for the brain. Not that there isn't a benefit for lower intensity exercise, certainly people doing you know moderate-intensity like the
Time you put in the volume of training is like you're going to probably find some equivalent there. But with the lactate though that's the one mechanism. Like that is really something. I personally am trying to optimize for its Stephen ately consequence of intensity and the fact that it's cleared so quickly and it's transient, like, I'm wanting a lot of it. Like each day, I wanted to keep doing it. There
are other ways to do it that you might want to consider, right? So you might want to say look, I'll do those two bodies, two days a week.
I'll do some longer slower cardio and to be clear like when I'm doing that zone to, it's not trivial like I mean I'm my heart rates still 140 when I'm doing that zone to, but what you could do is use Blood Flow. Restriction, when you're lifting weights on the other days and that will get your lactate through the roof. So, four days a week, you know, I'll do Blood Flow Restriction at the end of every workout. So, two days will be upper body. Two days will be lower body and then especially on the lower body days. So you've got these huge cuffs at the upper part of your thighs.
And I'll do leg presses leg extension leg curl and finish up on an air bike. And by the time you take those cuffs off, all that lactate that's been pooling in your legs for 10 minutes. We'll flush through systemically and your systemic lactate
level surges, what's your levels get too? What's
your low? I mean, I'm not as high as I would get on an all-out Sprint. I mean, like the highest I've ever had. My Lactaid is about an 18 or 19, but I can still hit the mid teens doing blood flow.
Restriction, that's incredibly High.
You know, it's funny when I used to coach athletes at work with an Olympic swimmer, who could get to 26 and still be conscious. I mean, I say that sort of half-jokingly, not that too much lactate would render you unconscious, but the pain that you must be in when your lactate is 26, is comical to me. He could finish a swim race. Something like a 400 individual medley, which is probably the highest lactate generating race there is because it's all-out upper body lower body.
Assault have a lactate of 26 to 24 to 26 mmol and four minutes later. Jump in the pool again and do a race and enter the pool with a lactate of maybe six, it's pretty amazing. That's amazing. So my point is like you could diversify the training a little bit because again you'd still get that lactate hit. But you'd also be diversifying the training because I do think performance, it's hard to make the performance gains. If you're really doing an all out Tabata, five days a week. I think that
Is
hard? What kind of performance gains? Are you
talking about within the Tabata itself? In other words, it's hard to make gains on the power output that you want to be generating because that's when you're doing 20 on 10 off. You're trying to get as much power as you can in those 20 seconds. Those are what we call match burning workouts. Like you're burning. All the matches that
day. Yeah, I'll tell you something. That's interesting. I started I don't have you ever tried doing an aerobic or high? Intensity workout with mouth tape, where you're just breathing through your nose.
So, I mean, you're limited of course. I mean, at some point, you're not going to get to your. You're going to be limited by. For me, at least I can't do my all-out best without mouth-breathing at the end. Once I reach 215 to 220 Watts, I can't sustain maybe 225 Watts. I need to start breathing through my mouth. I need to at least every other breath use my mouth. That would expect, everybody sort of different there.
People are different.
I mean different nasal. I mean like different sinuses and shapes of your nose and everything. I just recently started doing it it was kind of odd because I actually maybe I'm not going. I pr the first time I did it and you know like I wasn't going as hard on my all out but I think on my rests I was going harder on my 10 seconds off. I was like, not really bringing my resistance
down. If you tried doing it, where you do nothing on the off, a pure
off. What do you mean just like, keep going?
Ring. Yeah, don't spin whatsoever. So do the 20 seconds all out, and then the ten seconds. You're not spinning at
all. I've never tried that. That a try.
Well, I think the goal is to make the hard as hard as possible. And so, being truly off for 10 seconds will make it more likely that you can deliver the maximum wattage during the 20
seconds. Okay, I've been trying to do the opposite where I'm like, okay, on my off. I like keep, you know, Zone 3. I like so putting in quite a
Bit of power, right?
That's good too. We used to call that sweet spot workouts where you would go Zone. 3 zone 5 Zone 3 zone 5 Zone 3 zone 5. But what you really probably want to be doing in a Tabata is zone. Six Zone, 16
161. What's zone 6.
It depends on my system. So yeah. Yeah, I mean, so technically the literature on this would suggest that we are only able to hold full maximal effort for 10 seconds. Anything we do, that's longer than
In 10 seconds, we are applying some Governor to the system. So at 20 seconds, even if you don't realize it, you're somewhat pacing yourself. Even if you're trying to
go, I'm not doing maximal. I am not for sure. Like, my husband, like, seems like, he really gets to that all out, but I'm not for sure. I'm definitely not maximal at my 20 seconds. No way
that makes sense. Because I don't think one could do that. Five days a week. I think he would fry yourself,
you know. It's also really interesting Peter, is that though by, like the fourth or fifth day I'll be peering, so, I'm always competing against myself.
Myself and my work that rate will be lower by wattage. Oh, the Peloton. No, no, I'm not nearly as scientific as you. Okay. So what Metropolitan ranks you, oh, based off of? So,
it, doesn't it based on kilojoules or what is it based on average wattage?
But I don't know, all those awesome. You're writing everything down, I'm not doing that, but my Lactaid,
but that doesn't surprise me Rhonda. Because the way to get maximum wattage is to hold your highest constant maximum, wattage and go so zone for held indefinitely.
Produce a much higher average wattage than Zone 3 alternating with five or six, alternating with one. So, yes, if your metric of success is, what is my total? Average wattage over the course of this work out? It will not be a Tabata. It will be a steady state all I can, you know, that's actually what's called FTP. Functional threshold power, which is what technically the Peloton is using to estimate your zones. Have you ever done the FTP test on the
Peloton? Yeah,
that's actually probably worth doing. Okay, so if you go into the Peloton,
Something called I think it's called fitness test and it's going to have, you do, either you get to pick 28-minute, all out, separated, by some rest. I forget how much or 120 minute all out. I prefer the 20-minute all out. I think it's a better test. It will take your average wattage over 20 minutes, it will multiply it by point nine and it will say that is your functional threshold power which is defined as the maximum power. You can hold for one hour and in cycling and pellet.
Uses this system that is the metric by which the zones are set. So zones 1 through 7 are a function of power, not heart rate and they are all a function of that FTP number. Now, again, none of that's necessary for Tabata Tabata didn't rely on knowing those zones. It wasn't about titrating to a given heart rate. It was simply a question of go as hard as you humanly can for 10 seconds and then do nothing for 10 and do that eight times.
So I'm definitely using a
different you're using kind of a slightly different protocol where you're doing our work out where you're going much harder during the rest and then not as hard during the workout because you wouldn't be able
to write. I'm definitely not doing it the way I guess. And
how high are your lactates and you check your liked it at the end of the both sessions after the two
rounds. It's all like what continuous thing like it's you get like a 30-second rest period between the two eight sessions. But like I'm again I'm not resting. Yeah, you're going hard.
Going. I'm like probably Zone 3. Yeah, the end of that. Now, my Lactaid doesn't get nearly as high as yours. I'm typically, like around seven to eight millimolar, so, that could give you an idea of, you know, I'm what I call a committed exerciser, I'm not an athlete, as I would consider you are, I'm
sure it's actually quite different. The best athletes in the world, like, world class. So, both Michael Phelps, and Lance Armstrong. You could argue to the greatest, both actually put out relatively low lactate levels.
So you don't know, you might be one of those people who's so efficient that you don't actually make much lactate. Like, I don't think Michael Phelps is probably even when smashing World Records probably ever seen a lactate above
10. Yeah, but I'm definitely not one of those guys. Well, it would be interesting to differentiate for sure, I mean, for example. So, when you are doing at least a high-intensity interval type of training, which I would say that, this, would, you agree this, this type of person, definitely would fall into that, and of course, people
Generalize this term and stuff but that's a whole other issue but you are sort of forcing adaptations on your mitochondria to make more. Mitochondria, your body's like, oh, I no longer can use my mitochondria to make energy. I got to rely on this other process glycolysis. So as an adaptation to that, you increase mitochondrial biogenesis and that's been shown. Now, in several studies in human studies, you can increase mitochondrial biogenesis. Now also robic training does that as well but
you couldn't really a question.
Of time, it sort of comes down to what you were saying earlier. So if somebody says to me, I've only got 10 minutes a day to devote to aerobic training. What does it need to be? Well, the answer is clearly, it needs to be the type of training that we're talking about here. Now, someone says to me, I don't want the minimum effective dose. I want the maximum result, then I'm going to say, well, would you be willing to give me 90 minutes a day? In, which case we could build you, the biggest pyramid. Basically, I need an hour a day to build you a mega pyramid.
But some people don't have the time or desire or interest to do that in which case, yeah, we would need to just get people to doing. I get asked this question all the time, I think in 10 minutes a day of cardio and probably 30 minutes a day four times a week with strength, you can get amazing results, but you have to be laser-focused and there's no messing around. I'm sure when you're done that 10-minute workout, there's no ambiguity about how hard you've worked.
Not at all, and I feel has to be very vigorous. It does.
Does I do also use Peloton for my strength training as well and there's a lot of like paired sets and supersets and so it's like non-stop training where I'm definitely like, I'm putting effort in but it's not a long session either. I do try to do that. Like I'm probably putting in the minimum amount of strength training that I can personally do which is like 40 to 50 minutes a week. I used to not do any so like even that's
like progress so stuff. We're going to talk about a dinner here because I'm not trying to
Talk you into doing a little bit more but I want to ask you, where do you put your sauna in relation to this, do you dissociate and timing sauna from your exercise? Do you go right into the sauna after you work out. How do you incorporate
that? It varies. I do both a regular with dry sauna, actually, I don't use it as a dry sauna. I do a lot of steam as well, but I do that, but I also do hot tub, so I do jacuzzi as well. And both of those forms of heat stress have been shown to.
Increase heat shock proteins, which is sort of a biomarker of heat stress. And both of them also, been shown to increase brain, derived neurotrophic Factor as well, so heat, I think also plays a role in that like stress response. It depends on the day. So I often will in the sauna. I like to read scientific papers or listen to podcast like the drive, or like, I'll listen to like if someone's on Tim Ferriss is your like, there's only a couple of podcasts that I ever listen to you. Ours is one of them. So it's not like,
That's like my time or my cuz there's no other time if I'm in the car with my child like most of the time I'm listening to Frozen music or whatever you know. Like it's not I'm not listening to the drive so it depends on what I'm doing. But also I like to do hot tubs at night. So typically the sauna will be in the days. I do my workout in the morning, I'll have this on a warmed up and ready to go. And I'll get right into the sauna after my workout. And I either have a paper in hand, or I'm going over a presentation or something. I
Find. It's really interesting. I don't know if you've ever tried this or observed it, but this goes way back to my days, as a graduate student, when I first started using the sauna, I realized that if I would go over a talk that I was going to give like a departmental meeting or whatever, you know, is giving a talk if I went over it and thought about what I was going to say in the sauna, man, did I remember it better? Like it was like, very clear that there was something going on with my memory. And I mean, it's very very
A consistent of course, you know me, I like was diving into the literature like there's got to be something to explain this and, you know, lo and behold there's certain growth factors that you make that in the sauna with heat stress that do affect like memory. So plausible hypothesis there. But anyways, so if I have something going on like a podcast or
presentation, what's your protocol? What's your temperature and duration in the sauna, it depends on how hard
I went on like my workout too or if I'm doing it like right after the workout or if I'm like,
Midday. Just like I'm going to take a break from what I'm doing at my computer and I'm going to go read a science paper in that sauna. So like it really all depends generally speaking. If I go in right after I'm do my Tabata session I probably stay in about 20 to 25 minutes and my temperature is like 175 degree Fahrenheit. If I am not going in right after a training session, then I'll stay in longer. I'll stay in, probably a little bit longer than
30 minutes. I'm pretty adapted to, and my temperature will be, you know, 175 180 sometimes. I also do the humidity, which makes it hotter feel hotter as well, so I guess anywhere between 20 to 30 minutes and my temperatures anywhere between 175 to 180. I used to do really, really hot about like 190, like I was doing 190 and I was getting headaches more easier. I just didn't like it and I didn't feel
good. How long did I desana during your pregnancy? How
Far were you able to? I'm sure women ask you this all the time. I don't know that I have an answer to the
question. So I first found out that I was pregnant when I was touring Finland and everyone was like it was like sauna, right? It was like we were going touring saunas. Yeah,
your ass on a VIP,
I was. And I'm like, holy crap. Like, what am I going to do? I felt, like, at that early early stage? I mean, literally, like, I found out, I was pregnant in Finland. I did do.
A lot of Saint are touring and stuff and old plunging and all that at that stage. But right after when I got on the plane, come back home, Sana was out. And the reason I sort of erred on the side of caution. I mean, you can I talk to women in Finland and they were like, oh yeah I saw on a throughout pregnancy and you'll find those anecdotes certainly in that culture but there is a body of evidence. A mostly looking at like hot tub, it's common knowledge like pregnant women shouldn't get in the hot tub.
Top. And then you go to any Spa like it's like known but there's a body of evidence that it can something might increase the risk of a sort of like a, fetal, alcohol syndrome, wow, sort of thing in Offspring, even neural tube defects. So I was concerned that going in the sauna, perhaps could increase the risk of something like that in. So I decided that it just wasn't worth it. And so I did not sauna at all throughout pregnancy and I even waited a little bit
While breastfeeding and stuff. I waited probably like six months or so before I really got back into sonning now all the while I was exercising throughout pregnancy and so many benefits to that but kind of back to your question the other protocol I do is at night and it's interesting because doing the hot tub at night, we're in that hot tub and it's kind of also a time that my husband and I get together away from our child. I mean, it's like our time, we're like out the Stars dark sky
Like it's nice and that is something that my husband likes to do it. Like literally like he wants to do it every night because it helps his sleep. So tremendously I don't have as much of an issue with my latency or my sleep like in general, but he does like I'm asleep by 9:30 and it's like, no, like I'm asleep in 10 minutes like I get in the bed and like I can be asleep in 10 minutes, he is not that way. And he likes the hot tub that really helps his sleep. So I end up doing that a lot as well and sometimes I'll do like both. I'll do the sauna and hot tub in the same day.
It all depends but exercise is the most important that I have to get. And I go for the vigorous type of exercise, there are studies looking at intensity with respect to dementia risk, cognitive impairment, you'll find all sorts of things. I think, the most common thing that is pretty somatic, is that the more effort you put in the more time you put in the bigger the benefit with respect to cognitive health. So dementia,
A risk and also it depends on how its I'll give you an example. There was a longitudinal study where women who women by the way as you know our I think proximately at a two-fold higher risk for Alzheimer's disease. That's right. Super interesting. But so this is in women and they were studied for decades and I think it was like starting from like the 70s up until like 2010 or something and they came in for a physical leg, put on a bike exercise bike and they're like Fitness was measured was
Empirical data and this was like, I don't know five to seven times. So like over the course of 40 years or something. Exactly, something like that. And the women that were the most fit by their measurements on this cycle test,
they just call me V 0 to Max.
Yes, it was cardiorespiratory Fitness. Those women that were the most fit the reduction in Alzheimer's risk was like so robust. I think there was something like there were nine times as likely to get or something crazy like that.
Ones that were moderate like, so they had like a moderate cardiorespiratory Fitness, they had a 45 fold reduction but then you'll like, look at another perspective, study, same deal with they don't come in and get anything measured, but they come in for a questionnaire, they get a questionnaire every whatever it was over the course of like 40 or 50 years or something. So the answer all these questions like, oh, how often do you jog or bike, or do you play, tennis, or whatever? And you look at that study and there's like no association between physical activity, and
Ensure risk and I'm like hmm that's interesting because this other study where they're actually measuring something showed. I robust reduction in dementia risk, it hits home this like okay what study are we looking at you'll find questionnaire studies that also show, you know, a benefit like people that are physically fit and the more fit they are. There's like a linear dose-response effect where you see, you know, people that put in more effort, they're training for a longer period of time and they're more vigorous or more volume both, right? They have the greatest.
F it with respect to dementia risk which isn't so surprising to me,
the studies that are unambiguous. As you said, are the ones that actually measure VO2 max because there's no denying what you're measuring. It's a very objective measurement and it basically takes out the training component because it captures that benefit its the readout state of the training and it basically says look maybe it doesn't matter if you do five high, intensity.
Scouts a week or two high intensity, five low intensity. Like what matters maybe more is the output. I don't know if that's the case, but there's no denying that people who have a high vo2max are doing something that people who have a low vo2max are not and that's what's being captured in those studies and the numbers are astronomical. I won't go into them again. People in this podcast have heard it too many times, because I can't stop talking about the benefits of having a high VO2 max, but I want to touch on something else. You just said a second ago, which is, you know.
Noted that women are indeed at twice, the risk of Alzheimer's disease to Men, of course, Parkinson's flips, that men are at higher risk, but focusing on Alzheimer's disease for a second. Is there any evidence that there are gender differences in response to exercise? In other words are women more responsive to the benefits or more amenable to the benefits of exercise than men? Because they are at a higher risk
genetically. I haven't seen the
Studies looking at the response to exercise, with respect to, you know, the sex differences. But as you mentioned, like, there's definitely differences with respect to their Alzheimer's disease risk. There are different mechanisms that could so women have different like there's different metabolic responses to exercise. Maybe also hormonal e different. This would make sense, right? Like I don't know that this is all been studied. I haven't seen that data but like hormone.
Really different responses to exercise that would be plausible immune system effects as well. Exercise is affecting the immune system. So we haven't even talked about like my o kinds like these are like molecules being secreted by our muscles. We talked about lactate, that's not a Maya. Kind, that's a metabolite. But physical activity. When we force our muscles to work hard, we're making something called amiyo kind, sometimes it's referred to as an extra kind, but like this is Iris, in is one, il-6 is another, there's other ones as well, but like
Are also affecting the brain and they're affecting cancer risk. There may be differences in respect to like myokines that are being secreted with respect to how the stress of exercise, how that response is happening.
There's also something that let's talk about cancer because Rhonda well I think both of us are I think there are others who share this point of view, completely convinced. In fact I just don't see how one could not be at this point convinced of the benefit that exercise poses to the brain. It seems
Much harder to make the case for cancer. In fact, when you think about some of the things that are such obvious problems, with respect to dementia, for example, disrupted sleep, poor exercise, Etc, clear relationship very hard least for me to make the case that bad sleep is related to cancer. Although I think it is the data are clear. You can certainly make the case that horrible sleep would lead to a weakened immune
A weakened immune system especially the cellular system more than the humoral system would easily lead to an increase in not necessarily cancer initiation, but cancer propagation. But again, the data are so much less obvious. Let's talk about this relationship between exercise and cancer, right? On the surface, it should make sense. Exercise is good, cancer is bad. More exercise should mean less cancer, how compelling are the data? And I'll admit that I haven't gone as deep here as I have
Von cardiovascular disease and neurodegenerative
disease. So it's also another area that I'm very, very interested in. I mean, as you start to get into your fourth decade of Life, you've now had a friend or a family member that is come down with cancer. And you see, I mean, you're a physician. So, of course, you've experienced it on a different level but like, you just see how terrible it is to get cancer, and it really the best best hope is obviously to try to not get it to prevent and there.
As you mentioned, there are things that can modulate that risk. That are a little genetic wise that are harder to kind of move the needle. But overall. So with respect to cancer incidents, it's interesting. If you look at like you were talking about some of these Elite athletes, people winning the Tour, de France and people that are Olympic medalists, or maybe that even just entered the Olympics. I mean, you have to be quite an athlete to just get into the Olympics. There's been a lot of interesting studies quite a few that I have seen these are
Dee's where observational data again, obviously, caveat it. With that you're looking at people that have just entered the Olympics over the course of its, like, from 1912 to 2010 or something like that, like, just decades and looked at all cause mortality cancer related, mortality and compared it to like the general population. So there's a couple of studies that have come out of the US and if you look at both of those studies, one of them was actually looking at medalist and the other ones. Just looking at people that like entered the Olympics, they saved about one and a half to two years of life.
From not getting cancer. They had a five to six year. What you could call lifespan extension compared to the general population, same with like French Olympians as well, very similar where it was like, they lived on average five years longer than the general population. It was attributed that they had basically saved two years of life from not getting, in dying from cancer. I guess I should say dying from cancer because they are two different things. But that would be like, at the elite level, and it's interesting because you go will two years. Like, that's it, that's how I see it. I'm like,
I really like two years. And it's funny, because I remember when I was a postdoc, my postdoctoral mentor Bruce Ames, he had said to me once, or actually more than once, you know, I once read, you know, there's of all the things that you can do, like, if you prevent cancer, you're really only save about two years of your life and I always thought I'm like, no way, no way. But anyways, so that would be like at the extreme end, when you're looking at the actual athletes, the definitely less likely to die from cancer than general population people.
When you're talking about prevention. So there's difference between, if you read a study and it says, people that are Physically, Active are X percent, less likely to die from cancer. Like, so cancer, mortality has decreased this, not necessarily the same thing as not getting cancer, right? That just means you're not dying from cancer. So the study is looking at cancer prevention, really seem to focus on a specific type of exercise and that is aerobic exercise for whatever reason. There's not a lot of
Of literature on strength training and cancer prevention, you can find studies on strength training and cancer related mortality, but with prevention, it's sort of focused on for whatever reason on aerobic exercise. And it does seem like there are certain types of cancer that are more responsive to exercise, with respect to having a reduced risk. And some of those cancers are ones that are we should care about. So breath,
Answer, what's the lifetime risk of breast cancer for a woman? It's about one in eight, pretty high for the average woman, of course, many different lifestyle factors play into that. And exercise is one of those factors colon cancers and other one. That seems to be quite responsive lifetime risk of colon cancer for average woman is like 1 in 23 for a man. It's like when a 25 or something like that, the reason I'm mentioning as you know, Peter if you're talking about like esophageal cancer, some cancer words, like 1 in 500. I mean,
You're more likely to die in a car wreck than get, you know, one of those cancers, I think it was esophageal cancer, but you get my point where the lifetime risk is already kind of quite low for the general person or the average person. So, breast cancer colon cancer, there's a few other cancer types that are quite responsive. But those two in particular, kind of stand up because with prevention, with respect to people that are diagnosed with cancer and have those Cancers and then they engage in physical activity as well. Like, you see a very robust response with respect to reducing cancer mortality.
And also recurrence, you know, it's like 50%. You know, cancer mortality is reduced by 50% cancer. Recurrence is reduced by 50% in those individuals diagnosed with breast or colon cancer colorectal, cancer, that are engaging in more physical activity. So the question is how much and you mentioned like you have a lot more knowledge with respect to cardiovascular disease and I would argue the data, really? I would say suggest that you actually probably need to do more exercise.
Eyes to sort of reap the cancer preventive benefits, then you do cardiovascular benefits even, you know, some of the metabolic benefits. I don't know why that is. It seems as though getting more to that upper limit of what these you know, committees are recommending. So 300 minutes a week of moderate intensity exercise or maybe 150 minutes more of like what they would Define as vigorous, which actually, I think they're bigger ass is a little bit below what my definition would be, but so it seems like
Amount of exercise. You actually have to put in a little bit more time and effort for the cancer but any amount is beneficial. So it's not like oh well I can't do 300 minutes therefore I'm shouldn't even care. Well that's not true because there are benefits even with like any type of physical activity, that's all the observational data and you can find anywhere between a 10 to 20 percent reduction in people, are that they're less likely to get breast or colorectal cancer, ten to twenty percent again, when you're talking about a type of cancer with a higher lifetime,
More risk, it's more compelling. So it's always kind of
in, I'd be curious to see if the data line up with the cancers that are known to increase in Risk, due to obesity. So right after smoking, obesity is obviously the second-leading modifiable risk factor associated with cancer. I've always thought that was an over simplification because we use obesity as a proxy but I think it's probably insulin resistance. That's the true marker. That obesity is serving as a poor man's version of
It would be interesting to see because there are certain cancers, including breast and colorectal, by the way, where obesity amplifies risk. There are other cancers where obesity doesn't seem to play as much of a role. It would be very interesting to align the exercise data with the Obesity / insulin resistance data and see if exercise is disproportionately reducing risk in those cancers for which obesity is a
risk. Such a good point, Peter, and I think there is at least
Just some data to suggest that you are correct with that. So I mean, what is your like 13 or so cancer types that like obesity is known to, it's
either 13 or 17, something like that.
Yeah, yeah. And breast and colorectal cancer are on that list aerobic exercise. I think there's direct mechanism so like you know aerobic exercise is, you know, directly you're making those Maya kinds in. Like you know some of these Maya kinds have been shown to decrease the production of like growth factors.
And cancer cells and they're like they also like are killing cancer cells through a variety of other mechanisms also the anti-inflammatory effect from exercises. Well you're having a strong anti inflammatory response but there is a little bit of that. Okay? Will exercise is also improving insulin sensitivity. Particularly in combination, with dietary strategies, the weight loss itself is basically a important component of the cancer reduce cancer risk. I think it's a combination of these things. Where
It's like the Direct effects from exercise, and it's really interesting because as I mentioned people that even have cancer, it seems like physical activity. Like, I am not an oncologist and, you know, many more oncologist than I do. I don't know how common it is for oncologist to prescribe exercise as an adjunct treatment to, you know, whatever type of treatment whether it's immunotherapy or radiation or chemotherapy, or combination, whatever. I don't know, Common it is, but the data is more.
More compelling. And I think it's become more and more compelling over the years that really exercising. It seems to be very important for reducing cancer metastasis and also dramatically decreasing cancer recurrence. And so, a really interesting mechanism by which, this is likely occurring is literally through that Shear Force mechanism. I was describing for the brain, as you know, you know, cancer cells, tumor cells, sort of
escape the site of the tumor and they make their way into circulation, it's called a circulating tumor cell, or circulating, cancer cell, depending on the study you read, you know, these circulating tumor cells are like traveling throughout the vascular system to just dissing sites and they sort of take camp and then like it's like kind of seed of a new tumor forming in another tissue. Well it's really interesting because cancer cells are so messed up as you know, like they're just completely wonky and very very sensitive to stress any type of
They have these mechanoreceptors on their cell surface that are responsive to force Shear Force. So when you get your blood pumping, it's like a hurricane that leg wipes it out, they died because they can't stand. Just the sheer force of the blood flow, through the vascular system. So you can pair the mechanistic studies and there have been, there have been some studies looking at circulating cancer cells and it's like, people with those are like three times more likely to have cancer metastasis.
And so on. But again, there are studies showing that like physical activity, like dramatically decreases. And this, there's been randomized, trials showing a dramatically decreases, circulating cancer cells and people compared to whatever their other standard treatment that they're being given pairing that data with looking at you know other data where exercise is being prescribed to patients and it is beneficial with respect to their cancer metastasis reduction and also mortality reduction you know like 50% mortality reduction universes.
Parents as well. So I do think there is substantial evidence to suggest that being Physically. Active is a good measure for cancer prevention. And again, there's also a lot of differences, there are sex differences as well. Like, I don't know why, but in some cases, women respond better and there's certain cancer types that respond better. Lots of variables here. Like I'm feel like I'm speaking in a general way but there are
lots of things to consider right. There are cancer types and there are sex effects. And there are, as you mentioned, other covariates, there's obesity and there's, you know, insulin resistance age, as well. So there are lots of nuanced as usual, but I do think that you can make the case that like like what can I do in my life to, you know, reduce my risk of getting cancer reduce my risk of dying from cancer. Reduce my risk of getting Alzheimer's disease, reduce my risk from getting Dementia or
Members from getting cardiovascular disease, reduce my risk for type 2 diabetes. The only Panacea there is exercised its exercise. It is the case. And unfortunately it's the thing that you have to put the most effort in. It's certainly a lot easier to take a supplement to take a pill. I do think there is an argument that omega-3 is one of the getting yourself to a good omega-3 status and defining what that is, is still like being investigated. But I do think that's a low-hanging fruit. That should not be ignored but exercise as
You've talked about many of times is the king, that's the thing that you should focus on. If you obviously, if you're obese, weight loss exercise is part of that program. And like I don't think that anyone that's obese to be worrying about all the other things. Like they need to like lose weight and any personal trainer and Coach like probably is going to help you do that. You eat less like calories in calories out, it like matters to some degree if you're not eating as much
but as you said exercise matters not just on the energy balance side but
Sighs makes you, for example, more sensitive to satiety hormones. So I have kind of a belief here that the person who is overweight, the person who is obese and who is clearly eating more than they should be isn't doing that by choice. Maybe some are. But for the most part it's hard for me to imagine there's someone who's listening to this who's obese who isn't wanting to not be obese and who is otherwise struggling with hunger. And I think that that's one of the
the challenges is why is it that a person who is not in energy balance is not responding to the normal satiety signals and I think there's a lot of reasons on the food science side. We could talk about a whole bunch of reasons why our food has been hijacked. Our food is void of nutrients, our food is hyper palatable, it's far too available, there's a whole bunch of reasons but I think one thing that doesn't get enough attention is this thing which is an exercising person has a better sense.
Of nutrient requirement their body physiologically is more in tune with their repetitive needs. And so even though I don't think exercise matters as much as intake purely on the energy balance side. In other words, I think it's more about reducing input than increasing output. A part of that equation is the feedback loop that exercise brings. So yes exercise just matters. And I also think that especially in this discussion of cancer and breast cancer is the example you
Brought up so many. Women are so petrified of hormone replacement therapy because of this awful study that Women's Health Initiative, which was completely misinterpreted. But just to use one example of what we spoke about, even the people who ran the study, who to this day, some of them at least a subset, still maintain that conjugated Aquinas. Estrogen plus MPA the synthetic progesterone increase the risk of breast cancer. Even those people will acknowledge, it did not increase breast cancer.
Eyetality. So even if you take the most favorable to the Whi, the Women's Health Initiative study reading, the reading is that conjugated echoing estrogen plus MP a increased the incidence of breast cancer by 0.1% in absolute risk, but did not increase breast cancer. Mortality so here you have basically a non-event that has most people panicked senseless, most women Panic sense.
This when confronted with taking hormones during the perimenopausal period And yet at the other end of that Spectrum, we have a treatment that has more than a log fold benefit in the other direction. IE in reducing risk. I wish people would just allow their attention to be, allocated proportionate to the size of the impact.
I'm 100% with you and to kind of just highlight or emphasize what you just said. You know, there are studies with women who are
Doing moderate drinking. Which depending on the study, you read for women. Moderate drinking is like three drinks a day or something. Like it's a lot. Wow. And that literally translates to a lifetime risk of breast cancer is like 1 in 6 or something like that where it's pretty significant but you don't hear about women, petrified of like drinking two glasses of wine and I which some people do it's actually not uncommon looking at like what's going to impact my wrist?
Ask more. What is going to lower my risk more? Like, what should I focus on? Like, what's like the most important thing? I think obesity does absolutely impacts breast cancer. Same with physical activity in the opposite direction. Has really enormous benefits and then alcohol consumption is another one of even mild. Alcohol consumption. I would say that like, I don't want to go there because it's like so it's complicated and I like, I can't even like begin
like, on their Rhonda. I've gone there.
I go out on the limb and I'm going to say it. There is no amount of alcohol, that is healthy. The J. Curve is a misnomer. And what I think I would say is somewhere between zero and one. There's not that much of an increase in Risk, but there is not a reduction in risk or what for mortality in general mortality. Yeah, so, in other words, you know, they talk about this Ridge a curve where complete abstinence is a greater risk than one drink a day. But I think both the mendelian randomization makes that
at clear, that that's not true. And then, secondly, when you look at all the confounders of the people who are drinking zero drinks and what confounds their mortality, I feel very comfortable saying that there is no dose of alcohol that is healthy but at a very low dose, probably four to seven drinks per week, you probably can't quite quantify the harm that would be my take. And so, I'm comfortable saying that. I really feel confident that that is the case and that things like the French paradox, have far better explanations,
One
example, the data is also a mess, you know. Like, can you have your weekend glasses of wine? Like, absolutely. I think you can with respect to the cancer risk. That's considered it smiled. I mean, you're having less than one drink a day. And the only evidence I've really seen against the mild, is on the National Cancer Institute site where they like. It's one of those cancers where it's like 1 in 500. It increases your risk of a cancer that you already have a lifetime risk of 1 in 500. And it's still less than 1% of an increased. Like to me, it's like
Your life tourist goes, you can't measure
it. Like you can't measure it. It's a classic example of the dose makes the poison, but don't confuse that the poison is a poison. Another example would be cigarettes if you smoked a cigarette twice. A week, literally one cigarette twice a week. Would your risk of cancer? Go up? Yes, but you wouldn't be able to measure it, but doesn't change. The fact that cigarettes are
harmful to mention heart disease. Like yeah, that is not a linear but
even just focusing on cancer, right? It really comes down to kind of establishing causality is tobacco causally related to disease. Yes.
It's a harmful thing to take but the dose matters again, just being glib one cigarette a week. It's probably increasing risk but we don't live long enough to see the separation of those kaplan-meier curves. Maybe their natural lifespan was 500 one cigarette a week would be sufficient to see a spreading of those lines but at an 80-year lifespan and you have to get up to 10 cigarettes a day before, we can see where that is. By the way, I'm making that up, I'm not advocating that one can smoke.
Up to nine cigarettes a day. But you know what I'm getting at. Right? And I think that's my point with alcohol. It's simply just a question of that, but I just want to make sure people aren't taking away from this. That look, I probably have anywhere from zero to four drinks a week. But when I'm drinking those four drinks across two or three days, it's not going through my mind that this is healthy. It's like yeah, this is a hedonic pleasure. That's not good for me but it's
enjoyable. Let's enjoy what? How do you feel about apoe4? Carriers and alcohol?
Like
our view in the practice is that they are indeed more susceptible to the deleterious effects of alcohol. And also I would say they're just more susceptible in general to the deleterious effects of poor sleep which is one of the ways that I think alcohol is disproportionately hurting the brain. I think poor sleep is causally driving Alzheimer's risk and cardiovascular disease risk. I'm less clear on cancer but in as much as most people that are drinking alcohol,
Alcohol are doing so in the evening and anybody who's used a sleep tracker, you don't need to be Matt Walker to very quickly. Do the experiment on yourself and compare a night of sleep with no alcohol, a night of sleep with alcohol, they're different. So through that lens, I would just say we have lots of patients with E4 in our practice including a number of e4e forward. Even though those patients represent only 2% of the population, they're probably about seven or eight percent of our patient population. And
Again, we say, look, unless this really means the world to you, it's probably not worth a drink. And if you are going to have a drink, here are some principles for how you might minimize the damage, right? In terms of the number, you might have how long you might have it before bed, that kind of thing
exercise, you know, when I a couple of things just because you brought up the sleep and so I started wearing a continuous glucose, monitor largely, because of
you, I've been a very bad influence on some things you've done the lactate monitor this
CGM. Yeah. Well I started wearing it when I was a new
A mom. So this was, you know, like five years ago
and I can't be a good time to wear a CGM. Although, it must have been interesting, right?
It was extreme. So, here I am coming into this, like I'm going to learn about the foods I eat and how my body responds to those foods and low and behold the biggest and most compelling in most important data point or many points because I had many of them that I sort of learned from wearing my continuous glucose monitor, which I'm sure most of your listeners know about
You're measuring your glucose level, like continuously was the effect that my sleep Interruption had on both my fasting blood glucose and my post-print where I was like, I could get like what we can be considered like pre-diabetic. I was like blown away. It was like, what is this is insane and then what I also, sort of gleamed from this was that when I on days and the effect lasted about I would say like about 48 hours or so when I did
did work out at the time, I was doing a lot of high intensity interval training. I was like an hour-long spin class. I used to go to, you know, they do all this interval training, it almost completely blunted. That effect, even though I was dog-tired, last thing I want to do is go to my damn spin class. This is like it's going to be bad for me. If I go that's how I felt. It's like it's going to be bad for me. But it was completely the opposite where this crazy glucose dysregulation and whatever the cause is for them. Sure. You know, much more about that than I do. It was
Most completely blunted and it was so profound and it was like the one all the food stuff. You know, I learned a little bit of interesting but really that was the thing that for me was like, I have to work out no matter what, no matter what, no matter how I feel it doesn't matter. It's beneficial, it was a really interesting study. Caveat observational data, reverse causation all the problems with any study but it was looking at the Sleep habits and so people that had
Lapped. You know as poor sleep or interrupted sleep. Something of that nature. I can't remember the all the exact things that were measured with respect to sleep but people that didn't sleep as long or had poor sleep, Whatever by whatever measurements had a higher all-cause mortality which is not that surprising. But only in people that weren't physically active and to me, I was like, wow, that's interesting. It's interesting. And it's like, you know, exercise can forgive a lot of things. In many ways, it really can.
So you're talking about your patients with e, 4, e 4, and I'm sitting here going. Oh my gosh, I've got one of those and I'm already like it's a lot, it's a burden. You have to calculate things, you have to be very you know, specific in your actions. You take and like things that you don't do things you do right. And for me, it's like, okay, am I gonna like? I'm having a party. We're going to have some mimosas, whatever. Like, I'm going to exercise, no matter what. Like, and that might take off some of the stress. I personally, I hardly drink and
We because I am you for. I have one allele and I have pretty much come to the conclusion that my brain can't repair damaged as well. As my husband's doesn't have an E4. Allele with that said, I occasionally will. I'll have like maybe a glass or two of wine. Usually, if that's my preference but you know, a week last time I had a drink was like Valentine's Day, you know? So it's been a while but at least I think with the sleet we start with the exercise you know, again it's
Make it does it seems to forgive a lot of sins.
Honestly, I like that way of describing it. I
kind of borrowed that from Stuart Phillips. I think he was the one that said it to me cuz I was like, this is like,
that's right. I remember him saying that, on your
podcast, he gets all the credit and that, of course, brings us into the whole, like protein intake and muscle mass world.
But so let's set this up for listeners because, you know, you and I have talked about this, a lot. In fact, I remember probably the last time this is pre covid, because we were both in San,
Diego. You and your husband were for dinner. I think I cooked up some fresh venison that I had just killed. And we were kind of talking about protein and I think at the time both of us were kind of struggling with two competing ideas in geoscience and those two ideas, that seemed dialectical they seemed at odds was on the one hand. There's this body of mostly kind of animal.
Literature that suggests lower protein intake is associated with a longer life. But on the other hand, there's this literature that says lower protein intake is associated with more Frailty in humans and that's associated with a shorter life. So how do we reconcile these two things and we didn't have a great resolution on that. I mean we both kind of felt like we were sort of scratching our heads thinking. At least, I don't want to speak for you, but my thinking at the time,
So this is again, three and a half years ago, probably, was we just got to find the minimum effective dose. What's the minimum effective? Dose of protein to not undergo mandatory catabolism, and that's what the dose is. And of course, it's not clear. How you find that dose? Theoretically, you would use a metabolic cart and try to identify nitrogen balance and things like that. But, of course, no one can do that outside of a lab. So, it was a bit of a head-scratcher. Now, my thinking has evolved so much on this but I'd like to hear first,
To hear your formulation of the problem that I formulated the way you would and I guess, more importantly, tell me how you're thinking today, so
you actually did a very good job formulating my mentality, with respect to protein intake and Longevity back in 2019, prior to that. But like, even up until now even that long ago to be honest, you know, there's as you mentioned, a large body of animal evidence but also like there was coupled epidemiological data where you think people are looking at a vegetarian.
Ian's or taking in lower amounts of protein. And they're all cause, mortality in their cancer mortality. And it just study after study after study, and they have lower all-cause. Mortality lower cancer mortality, but but only in those individuals who are not obese, not sedentary. Sorry, are sedentary are smoking or, you know, they had some unhealthy lifestyle Factor. So, in other words, the people taking in higher protein, animal protein, who were basically healthy had a similar
Our cancer related. Mortality all-cause. Mortality as these vegetarians, okay? So,
and similarly, studies where they normalized for fruit and vegetable intake, high protein versus low protein. No difference in right, early mortality, right? So, yes, it seemed that a lot of the data that were espousing low-protein, we're confounded by lifestyle choices, and high protein was also negatively confounded by high-calorie as the most
Yes, exactly. And with the animal data and this is probably where my mentality is shifted the most because I wasn't really of the opinion that vegetarian diets were Superior to meat-eating, I guess, omnivore types diets that were healthy omnivore types of diets because of what you were saying like that data was nuance and it wasn't just like that wasn't something. I was that has shifted the way I've been thinking. But with
Back to a lot of the animal data in the mechanisms and you can restrict them Mouse of protein and make it live longer and not get cancer and you know all these things that you see study after study. I mean it's just like the longevity science and that whole field is like dominated by that. Like at least was and there's now I think some pushback going on, but there's still a large group of scientists that are still publishing a lots of animal data and this
This is where I sort of started to look into some of these exercise physiologist people like, Stuart Phillips. I know you've had some way John Lehman on these like Giant in the field that are doing the research and Brad. Schoenfeld is another one where they're looking at protein intake, they're looking at strength training and its effect in humans on muscle protein synthesis. And also, just like looking at data with respect to muscle mass,
And all-cause mortality and Alzheimer's disease, dementia. We didn't talk about that but like shrink training also can modify that risk also cancer.
Mortality. Yes. Strong grip versus weak grip. Monotonic change in grip. Strength, 70% reduction in incidence and mortality from dementia. I mean, 70% reduction in Risk. Remember, people don't understand. You can't reduce risk more than 100 percent. So it's not like increasing risk, which can be
And 200-300, when you're talking risk, reduction 70% is staggering, it is strength matters.
It does as you know and many of your listeners, there's two important signals for your muscle strength. Obviously, a big component of that, he's physically working them, but protein intake plays a role there as well. And I think it was Stuart Phillips like phrased. It this way where the animals that are being studied in these Labs or in a sterile environment, you know, they're in a sterile environment, they're not.
Exposed to influenza and all these infectious diseases. And any of us we've had a parent or relative or someone that has gone into the hospital and maybe had bed, rest, and then come out. And like, I had a grandparent who literally couldn't walk after a back surgery forever. Like that was it that was their downfall. I was like the trajectory just went down completely down. So losing that muscle mass. When you're in older age obviously building up a bigger Reserve in youth in.
Oh adulthood whatever. Like that's very important. But like these animals that people are manipulating the protein restriction in them, they're not being exposed to that. They're not losing. Like I don't know what percentage. It's pretty intense like how much you can lose from like three weeks of bed rest in. Also like as it's been pointed out by people in your pie thing, Matt cabling you know mice are dying from like cancer. They're not dying from the same diseases and it's not even the same type of cancer. That humans give we get a lot of these epithelial like tumors solid tumors there, like
I'm from lymphomas. So there's a lot of differences there as well. Like there's a lot of interesting and I'm the one who talked a million times about almost studies. I think they're important mechanistic data. Like there's things you just one ever get from humans but at the end of the day I started to realize that looking at you know mice and a sterile environment where they're not really being exposed to the same stimuli as humans. Things are very different in terms of Aging. It was falling apart in my mind basically.
Was like all falling apart. I'm like, doesn't make any sense like, this isn't what to be looking at if I'm wanting to really focus on healthy Aging for myself for everyone else. So I think that's kind of what was the Tipping Point for me was just kind of that realization of the importance of muscle mass and how, you know, some of these animal studies. You look, they have a little bit of an improvement in their cardiovascular health and I'm like, exercise. Okay, is that better than exercise know the things that were improved? I was like,
Sighs. Does that exercise? Does that? Like this isn't convincing me that I need to like do that. I think it was just kind of like a shift in the way. I viewed the data like the lens, I was seeing it through.
I'm still waiting for somebody to demonstrate for me, that, if there is an increase in the risk of cancer associated with higher protein intake in humans, I'd like to see that Quantified, but I would like to see somebody demonstrate that if there is an increase in risk that quantify,
I will increase in Risk is greater than the offset of sarcopenia, because that's something for which there is no ambiguity. We have all the data in the world to point to the devastation of sarcopenia on an aging population. And we know full well, that two things have to be true to avoid sarcopenia. Adequate protein intake, which as you age gets bigger and bigger that number
Goes up and up, and up, due to antibiotic resistance, coupled with strength training. So here we have something for which there is no uncertainty. You must consume increasing amounts of protein and you must do strength training to ward off, sarcopenia as you age. And if you don't, here's your mortality trajectory and it's awful. Let's compare it all of that to this questionable risk for which frankly, I don't see data and I'll add one more point to what you said, Rhonda, which is I think this story got confounded
By our good friend C elegans. So let's go back 29 years roughly, call it 30 years, directionally. When some very seminal and interesting work was published, looking at the daf-16 mutation in or maybe it was daf-2, I can't remember who was deaf to first or daf-16, but it was the analog of the igf receptor and if you knocked out that Gene you could double the lifespan from roughly two weeks 24.
Or weeks or four weeks to eight weeks. I forget what it was of C, elegans this warm, the implication of that was profound. I don't want to down play. The most important takeaway from that which was lifespan was malleable that turned out to be very interesting. I could go on my rant about why C elegans is not an organism or a an animal model. That offers any insight into US based on its cell based on a whole bunch of things about its biology. But nevertheless,
Somehow became knocking out that to or daf-16 was tantamount to dropping igf insulin-like growth factor 1 to 0, is the key to longevity and the way to do that is to have no protein and I think that story's is so incorrect, but somehow it's become part of Dogma. I think that's the other piece of this, that just kind of won't go
away. It's funny because I've done those experiments with my own hands. When I
At the Salk Institute and I was in Andy, Dylan's lab, who had trained with Cynthia Kenyon, who made the discovery back in? Was it early 90s or
something? Yeah, so he was 93 or
94. Yeah. And it was very exciting for me at the time because it was like, oh, this is a homologous Gene we have and I'm watching a go from a 15-day lifespan to like a 30-plus day. And not only that, you know, these
weren't span was
remarkable they were youthful. I mean, like, you could see them, you look at him microscope and you see how they move around and is very
Aren't they were acting like a youthful young. Larvae that had not been born long ago, but then you also realize they go into this day, our state. We're like in order to get that lifespan extension there, like, going into this, like, metabolic stasis and like, this thing that we don't do humans. Don't do doubt. It's a completely separate pathway, that is required for that lifespan extension. And I think to your point about the igf-1, the insulin,
And growth factor receptor and also the insulin pathway, their kind of both tied into that. The fact of the matter is, is that that is a growth factor. You and I have talked about this before, you know, growth factors in the context of a tumor can allow tumor cells to override cell death mechanism so they can continue to survive when they otherwise might have been signaled to die. And so there can be a problem with too much igf-1 in the context of a tumor and what causes that high.
F1 is Up For Debate, but at the end of the day, it's not that high ggf one, that is necessarily causing the tumor. I think there are things that you can do on your lifestyle like exercise. Actually causes igf-1 to go in a muscle where you're repairing damaged muscle, it's helping muscle repair. It goes into your brain. It's important for like neurogenesis a little bit of controversy there, I know. But like I am in the camp that you adults are there. Studies showing
in multiple studies showing that you can take an older adult, trained them for a year and their hippocampus will grow. But like one to two percent, like there's multiple studies. Also another study showing this with the subventricular zone. So these are two regions of the brain were. I believe data that says that adult neurogenesis or the growth of new neurons as an adult is occurring and I think exercise is a
bit and do you think that part of the vehicle for exercise to do that is through igf-1?
Uh-huh. Yeah, absolutely. It is interesting. Animal Studies have shown that again.
And we all know that the caveat does it translate to humans, we don't know. But often time you have to take the whole body of evidence the human evidence, coupled it with mechanistic data, with animals, and try to kind of put together a story to the best of your ability. I mean, that's all we're going to get, you always hear about, I want to lower igf-1 but you know it's actually like important for the brain and important for muscle and the way to get it to the brain is through exercise, that's known and it's been shown again in human studies as well. I think also part of the
The problem here is in some respects people that are doing, I mean, really impeccable animal research. Like you look at the data and it's like, oh, they're doing this study gray. This is a good study. I mean like you can't poke holes in it with respect to the animal world but then sort of Translating that to humans. And considering who are we talking to your, we talking to an overweight obese person? Maybe they're probably getting enough protein. Like, I don't know that they have to worry so much about protein intake. I think they need to focus.
Saint losing losing that unhealthy weight. But that's also really important. And I think some scientist and also Health Science communicators, also sort of maybe and I've been sort of guilty that as well like disentangling, who are we talking to we talking to the obese person who clearly needs to focus on weight loss or we talking to the healthy physically active person who's now terrified to take protein in because of they read about some animal study where too much protein.
Increases
mortality. And also, I think age is such an important part of this again. So if you look at that, I think it was Lovin in 2017. Had that study? Where they look at the relationship between protein and igf-1, but stratified, so they certified by protein intake. Low medium high, low medium high and then they looked at middle age people, so 5265 and then people over 65 and in people, aged 50 to 65, there was a
And ship between protein intake and igf higher protein intake was associated with higher. Igf. Now wasn't a huge difference. This gets over stated constantly, but it was statistically significant but what often gets ignored is the people over 65. There was no statistical difference whatsoever between protein intake and igf-1 again, this is taken as Dogma that the more protein you have the higher your igf-1 and in people over 65 that's not the case.
Now why do I harp on that? I harp on that because it isn't exactly that population that I am most concerned with sarcopenia. So if the message is somehow getting transmitted to somebody, listening to this who's 65 or older, that I shouldn't be eating protein. And they might not even know that it's through igf. But somehow high protein is going to give me cancer because someone who telling them that is talking about through the lens of Egypt, the answer is first of all no, it's not. And secondly, the
To risk you face. Again, is going to be the results of low muscle mass and low strength. And even if we believed, which I don't, but even if we believed that in that age in the younger people, eating more protein leads to more igf, which is bad, I would argue that the absolute risk of death is so much lower in that group that the absolute difference in mortality between the younger and the older in
The presence of high protein is no comparison. What I mean is higher protein across the board is going to save more lives than it would ever hurt in younger people. Even if you could convince yourself at higher protein intake was associated with increased mortality. Again, I find these data unassailable, especially in the older population. I think Matt came and I did talk about this on a podcast once, and I worry that as you do that, that information is not making its way.
Early to people of this acceptable
age group, right? And I think also that a lot of people are focused on the recommended daily allowance of protein, right? Well then write like, what are these old-ass studies that were not done correctly using the wrong tracers? Like, what is that telling me about what, how much protein I should take in? And this is also another sort of like I was a turning point for me because I knew nothing
about how the recommended dietary analysis yatterman. Yeah,
I know everything about micronutrients in R&D,
Has. But I knew nothing about the protein. Once I talk to Stu it was clear. He was like oh no we repeated those studies him and many others using different Racers. And I can't tell you all this tracers and stuff because it's not my field, but it was like, no, we determined that the minimum was really more like 1.2 grams per kilogram body weight, not 0.8. And to me, I was like, oh wow, you know, because you know what, you don't store protein, this is important, because, I mean, that's a big difference. And then on top of that, when you start to get into
Physically Active people or elderly population, as you mentioned anabolic resistance where they're basically like their muscle isn't getting that signal as well to increase muscle protein synthesis from the same amount of protein that they're younger self would. So they actually need more of a dose up to like, I don't know. 1.6
1.8, we basically tell people, aim for 1 gram per pound, which would be 2 point 2 grams per kilo. Because the other thing that complicates it Rhonda is not all protein is created equal.
So if you're getting a reasonable amount of your protein from Plants, you're getting a lower bioavailable amino acid, you're also not getting the same quantity of leucine Lysine and methionine, which are probably the three most important amino acids anyway. So you know, one of the things Don Layman talked about was, if you really want to be rigorous about this, you probably want to track those amino acids. And you really want to say, look, make sure you're getting one gram at least of methionine per day to 24.
Grams per serving of leucine and lysine. Now again for a lot of people that's too nerdy but you can go through the math, a couple of times with certain things that you eat repeatedly and you'll realize that's probably more protein in aggregate than a person is used to eating. And as you said, when you start to factor in those two other categories of risk right more demand. So when you're doing those high intensity workouts, you are ripping apart muscle fibers. When you're lifting weights when
You're rocking when you're doing all these other things, we have to do, you're demanding more amino acids for the turnover. And then, of course, anabolic resistance, I think is the biggest issue and something that truthfully up until two years ago, I just wasn't paying enough attention to. I wasn't appreciating that my older patients, had an additional problem at younger patients didn't have with respect to that signal
to point. You grams per kilogram by way that's for me to get 1.6. Like, I'm supplementing I'm taking whey protein like so how many meals
typically for it?
Have to
be yeah it has to be. So for me it's really two meals and two snacks and the snacks are just protein snack so to shake. So one of them is just a whey protein shake and then one of them is I eat these venison, jerky sticks. So five venison jerky sticks is 50, their 10 grams of peace and they're really good, they're super pure venison. It's you know, Wild game amazing product. I should disclose I'm an investor in the company that makes them. By the
way, I was going to ask. Do you make them? Is it?
No.
No, I know that people said, well, I know everything about it and I know the quality is there. So those are two snacks. Otherwise, the relatively low in calories. My whey protein shake doesn't really have anything else in it, except some frozen berries and almond milk. And then the venison steaks, are what they are and then two meals that are going to have protein in for me. Again, A lot of times, like it's going to be an omelet and then protein dinner. So, not going to deny it, it's work. It probably consumes more of my dietary planning and dietary attention than anything else. I don't pay any attention to
Many carbs and fat IE anymore. I'm just paying attention to protein
intake. It's something I never really paid attention to that much at all. Until I would say like last June, or July is when I really started focusing on strength training, you know, both for my muscle mass and also bone mineral density, like that's another thing or it's like you want to reserve of that as well, especially as absolute female focusing on the strength training and also the protein intake and it's been quite challenging. I've always sort of focused on micronutrients. It's still
The focus of mine and like, making sure I'm getting enough of those and I do supplement as well, you know, in addition to trying to eat like leafy greens and getting some of the veggies and stuff. It's either going to be roasted veggies for me or like salad, but the protein intake, it's been challenging. And I find I typically do three meals, one of them is protein meal snack. So, it's some salmon or like a homemade, turkey burger or something like that. But then, the protein shakes also is where I have to do. I guess that I don't really consider it a meal, but it kind of is
It's satiating. The protein, like Shake is definitely satiating, and I'm already is even kind of hard, because when you work out, like, as you mention, your satiety hormones, go up, like, I'm not hungry. Like, I don't necessarily want to eat, it takes a while before I can actually like, even get an appetite. So there's all these like competing things around like trying to get the protein but I'm like, I'm not really hungry and I'm like, I know I need it. So all these little important factors and yet again, Horton to sort of highlight that,
I don't know that someone who is overweight or obese necessarily needs to focus so much on that, right? Do you agree? Turn,
fortunately, most people who are what I call over nourished are also adequately muscled and they can actually in the short-run be okay, losing lean, mass in fact, it's very difficult to lose heaping amounts of body fat while preserving lean mass. So we tend to focus more on the caloric restriction coupled with
The training, we use the training as a way to offset, some of that lean mass loss and then we can come back to it. Now that said, so depends on the strategy, depends on the dietary strategy. So for people who are using tracking kind of the caloric restriction way, we would still set a protein Target that is at 2 grams per pound because of the satiating benefits that you said also you have the thermogenic effect and the benefits of protein over fat and carbohydrate from a thermogenesis standpoint.
But when you have people that are going about, it via dietary restriction or time restriction, as their strategy for cutting calories, it can become a little overwhelming, and when you force high-protein, you sometimes end up getting high calorie with it. So, that's where we would say. Just, don't pay attention to it as much. Just focus on the DRT, our approach, The Other Place Rondo, where we do pay, a lot of attention to protein, is in the few of our patients that are taking glp-1.
Onegin izt. So I've been a pretty public critic might be too strong a word, but I've certainly expressed my reservations about the ubiquitous use and the liberal use of glp-1 agonists, especially in people, just trying to lose 10 pounds, right? Like it's one thing if you're 100 pounds, overweight, and you've tried everything by all means, the benefits clearly outweigh the risks, but I got to get my beach body on for the wedding this summer. I'm going to lose 10 pounds. Let me fire up some semi glue tide or Zappa tide, I think.
A net negative personally and in those patients not that we're giving it to those patients. But in any patient who's on glp-1 agonists, we feel it is so essential to hammer home protein because those drugs are so effective at squashing appetite that we've seen people who basically just want to drink alcohol when they're on it and they'll lose weight like crazy because they're not getting that many calories, but they're like, yeah, I just like whiny muscle. Yeah, I'm just losing muscle. Drinking wine. Yeah. I've
got some acquaintances that.
Our of that category where it's like, stay-at-home mom wants to lose 10 pounds has the means to get it and does it. And we haven't measured muscle and if I look at them and I'm like, you look like you're wasting your mom, like your muscles wasting. If you're not eating, you're not taking in proteins. I mean, like that makes 100% sense. And it also I don't maybe we'll talk about this when you come on my podcast, but like I love to like because you used to do a lot of fasting and you know, you don't do as much at least of the long, long fast. And I would love to get into that and decide whether we should,
Do that next time or or we could talk a little bit now. But yeah. That was also like the biggest, you know, there was another shift in my understanding of fasting and time restricted eating. A lot of people use time, restricted eating, they sort of practice it by skipping meals. And I don't know necessarily that's the way to do it, but people do that. It's just, you know what people do, and when you're skipping a meal, you're skipping your protein, you're basically becoming losing muscle mass because you're not getting that important.
Signal, especially if you're not doing resistance training, then it's like kind of a disaster and that was also something I hadn't thought about a lot and I know you've got a lot of experience in it, both personal and
clinically I'll share with you briefly how we think about that. When the time restricted feeding part, we agree that the greatest drawback is that the patients, get protein deficient. So time, restricted feeding, as a strategy for weight loss, vis-à-vis caloric, restriction is very effective with a small enough feeding window.
So a 16-8, you can eat your way into obesity with a 16-8. But once you start getting down to a 24 or a 22 to basically just doing one meal a day, really getting restrictive it. For the most part, you're going to lose weight. The problem is by definition, you're not going to get enough protein in because even if you managed to scarf down one gram per pound of body weight in a single meal, you wouldn't be able to utilize those amino acids. You kind of tap out at about 40 to 50 amino acids.
Ads per meal. So if you sat there and had 160, you just flushed a bunch of them down the toilet, they're literally not coming on. The toilet are coming out as piece of the urine, coming out of the urea cycle. So the thing that we would counsel people on, if they're going to use time, restricted eating is they have to have protein snacks outside of their feeding window. So if they're going to say look, I'm going to only have a lunch at 2:00 and a dinner at 7:00 will say fine. But you
Have to have two protein snacks outside of that and that becomes challenging. Because those proteins next can't really have much else in them. They have to be very low-calorie otherwise otherwise you're not really doing time restricted, feeding. And of course a lot of people get phosphorylated over this. They say that. Oh my God, that's like outside, in my feeding window. Will that impair autophagy to which I argue? You're not getting any autophagy doing a single day. Time restricted, feeding anyway, it doesn't matter. But if people are getting gut benefits from taking that time off, then, yeah, they're
to miss out on those because you're I just don't see how you can get the gut rest if you're trying to get those amino acids. And so you might have to really start to cycle those things. But yeah, long-winded answer to why I think fasting can really be at odds, with the adequate maintenance of muscle. And as we get older, I'm just entering my sixth decade. This is a very high
priority for me. Oh, really. Wow, you look great. Peter, you're in your late 30s.
No, six decades. So, oh, so you're terrific. Yeah, gotcha.
Yeah,
I love that. You thought I was 60. That's awesome. You know, so I'll take that as a no. I think
Joe Rogan's entering that. And that's kind of what I was thinking and he looks, you can definitely see the people that like, put in the work and work out and they do aerobic, they do strength training. Like you look at them, there was like a study published on that to like bunch of biological markers of aging and biomarkers of Aging were measured and then like, people looked at pictures and like rank their age and their quote unquote biomarker
Logical age. According to all these biomarkers, that's basically say, their chronological age may be older than their biological age, where they looked like their biological agent, their chronological age, that's also
important. Although I sometimes feel like excess exercise can prematurely age you as well. I certainly seen a lot of and I don't know how much of that is the sun damage, because, of course, a lot of exercises done outdoors, and of course, son can play a horrible role in that. So I've taken up more of your time than I said, I would. But I want to ask you kinda just one last thing. Is there any other just sticking with this thing?
Game of things that you believe today that you didn't believe three or four years ago or things that you believe three or four years ago that you don't believe today. Is there anything we haven't touched on because we've talked about some really good
ones. I think those are the really important ones off the top of my head. I definitely don't want to get into the whole covid thing at this point. My view is changed on things as that has progressed and changed as well. So I don't want to like not mention.
It. But I think the most important things would be muscle mass protein intake, also fasting. And I think the effects of time restricted eating on weight loss specifically when you're looking at that outcome being attributed to caloric restriction, I think that is something that I've, you know, wasn't always, you know, buying into that. But it is still, my opinion. There are benefits to eating within your circadian rhythm eating late at night when you're making melatonin.
In two to three hours before bed, you're basically inhibiting, insulin secretion. And there's data showing like glucose levels will be higher with the same exact macronutrient intake as if you eat it earlier. So, there are benefits circadian benefits and I also think you mentioned the gut rest and like digestion, you know, resting? So DNA repair mechanisms you mentioned at apogee like those things happen when you're not digesting and that process, like isn't happening. So you have to have like a rest period for repair processes to occur.
Her. And I don't know that I necessarily I think a tapa G is as good as the markers that we are sensitive assets, that we have to measure it. And I don't know that it's settled. I personally think there's probably even in between meals, there's some amount of a topic. A topic is a happening in us. It is. And it's not like we're not
but is a clinically significant more so than say exercise would
induce, no exercise
is like, that's my point. Like, how long would you need to fast?
Get the benefits. An amazing workout in my thinking is probably a long time. You might have to go a full day without food or a couple days without food to get the benefits of that. But you're right. I think without biomarkers, a lot of this stuff is very difficult to speculate on because we can't really extrapolate from mice on this stuff. It's so nonlinear that I don't think I could and I've never heard anybody offer a very compelling argument either for what the quote unquote
answer is. I agree we can extrapolate from
Mice. And the way I view it though is more of a cumulative effect where I'm thinking, it's better to just eat within a circadian window and do. I think that's going to have a cumulative effect on metabolism. And yes, I think that it's better that I'm not eating within a 15 hour window, which most people in the United States. They actually do their eating from start to finish, like people are eating within a 15 hour period. If you're exercising, maybe it doesn't matter, maybe you're right. Maybe they can't even a 15 hour window, we don't.
Lino. But I tend to think probably the Circadian component does play some role. But the question is, is it significant? I am of the opinion that probably is cumulative
over. No other reason. I think it just is on sleep and sleep. Yeah exactly. Like if you just looked at the benefits of nighttime food, restriction in terms of as you pointed out we're at least insulin sensitive and the negative impacts probably of thermogenesis
Isis and other things on sleep. That's probably the most compelling reason, even if nothing else mattered, if we couldn't measure it, but those are so abundantly clear that's as clear as how alcohol impairs sleep. You know, a late-night meal is a great way to destroy a good
sleep, right? I think most people have it's anecdotally like people realize that as well. So yeah, I think we covered a lot of the things that have my perspective has shifted as any scientist. That's following data. Should
But some people will argue. Oh, you changed, you know, how can I follow you, your change your mind and say, well like when new data comes out, you have to reassess things. Like, I recess the supplements, I'm taking, I mean, the supplements I take Now versus five years ago. Totally different, not all of them. There's some base things, like, I like vitamin D, Omega 3. Like those are like super important, I think. But you have to reassess things because new data comes out and you might have a new understanding of things that we didn't know. We have new tools, it's always getting better.
Sure. So you have to kind of reassess things.
So Rhonda for folks, to follow, you obviously, your podcast, found my fitness, great way to follow amazing content. Also, you put up a lot of content. I think Instagram is probably where you're putting up. Most of your content is that safe to say that. If folks, follow you on Instagram, that's where you're doing sort of thorough analyses and stuff like that. Would you recommend people. Also check out Twitter, where should people be going to see your thinking on a frequent basis?
Well, it depends on what they like to consume. So if they'd like to
Soon, like, in-depth articles. We publish them on my website, found my fitness.com, we have like topic articles that we cover, we cover blood-brain barrier is one. So we cover that in more in-depth. Some people like to read, they like to nerd out on that. So that would be the place for that and then some people just like short little to the point, you know? And that is where if they want, like quick thing, like the Instagram. So I found my Fitness on Instagram and also Twitter as well. It's kind of like a short. I mean, you only get so much time on Twitter. You can't go in depth and nuance. And then
Sort of have a Love/Hate relationship with Twitter. It is kind of a fun place to also like there's other scientists on there as well. And so I'm on Twitter and Instagram
and it's all the same handle. Yeah, I
found my fitness and then the podcast as well which is Apple podcast, Spotify,
Andrew humor and I were talking a little while ago and we were sort of singing, your Praises as truly, the OG Health podcaster when did you start was it 2014?
That was when I started. The podcast was a weekend. I was doing my postdoc in Oakland and I just started, like, Ron Krauss down the hall, George Brooks. So I have a podcast with George Brooks unlocked a like, he was like, my
second was, like, I've heard that I need to go and listen to that one. Yeah, we went all
into the brain. That whole podcast shifted my thinking of like, intensity of exercise and the importance of lactate. I don't know if you know this, but like I train I probably shouldn't like we already talked about where people should.
Find me, but I was a mitochondrial metabolism, researcher grad school, and so, I was looking at the role of mitochondria and cancer. And so, of course, like lactate. I mean, I was thinking about it in a completely different from
am I supposed to? I mean, we now know, it's such an important signaling molecule in addition, to other things, we talked about, you know, we've had at least one guest suggests that. George Brooks is deserving of a Nobel
Prize. His lactate shuttle Theory, it's called a theory and I kind of hate that it's called that because people hear that and you're like oh
it's not
Proven.
Yeah, but it's been proven and in fact, there's like studies like even like there were people looking at this like even before he proposed like they were looking at lactate getting in the brain, in response to physical activity, and it's like beta-hydroxybutyrate to signaling molecule activates bdnf. Like beta-hydroxybutyrate they go through the same transporter mono carboxylate, transport of the MCT transporter to get into the brain. There's also those in mitochondria, but it's so funny because there's a lot of similarities that affects on TBI. So, you know, George Brooks has done some studies.
USC looking at some of these victims of TBI and giving them lactate and it's like improving, whatever their Glasgow rating scores, well, whatever the things that they're looking at. But like I think beta-hydroxybutyrate wasn't there. Some evidence. I think with TBI remember, Dom talking about that like, almost talked about this. Yeah, it's so interesting because also with respect to like Alzheimer's disease and like, through some really preliminary data that, of course needs to be repeated, probably won't because you can't get funding, but like giving beta-hydroxybutyrate bah
HB to people with Alzheimer's disease can help improve. There's some small clinical studies looking at Improvement in like cognition lactates. Like I think similar there's a lot of overlap there. No lactate you can make beta-hydroxybutyrate you make from exercises. Well you like push yourself into ketosis so to be interesting like, you know, if there's Synergy there trying to get the lactate and the beta-hydroxybutyrate, the neurobiological effects of them to me is, it's so important, it's so interesting. And I just
I kind of want more research in that area. And so I like talking about it because I know scientists listen to your podcast, researchers Physicians, it's good to kind of like spread ideas mean, that's part of what the podcast does writing ideas. It's not just like, I'm a communicating, the health ideas and it's like, scientists are listening to this and they're outside of their like lens where they're only thinking about the thing that they research and they hear this. And it's like creativity, they start to go, oh, like, I've seen that happen, scientists like doing experiments based.
It off of like listening to podcasts and stuff. I think it's really great but thank you for the ogi. It was weekend thing for me and I loved it. It took off. I just I love it so much. I know you do as well. I mean, it's like, by the way, phenomenal podcast, it's funny. I don't listen to podcasts much at all as I mentioned. But there's a few people that I trust to really be vigorous in their research and to be critical to
Ali like dive down and like get into the root of things and you are like one of those people and so people will come to me, you know, and say oh prts said this. I'm like okay, you know this is something I should consider or you know, oftentimes it'll be oh yeah, Peter also said that and so I'm like, oh good, you know. So I'm always like, okay what is Peter thinking? Nice to have you as a colleague as a friend like was I'm glad we've reconnected. Thank you so much for inviting me and your podcast. Can't wait to speak with you again soon on your amazing book which I can't wait to read.
And discuss as well in a couple of months.
Well, thank you very much, Ron. I can't wait to see you in person, even though it's been pretty awesome to see you in video. Your setup is, as I said, exceptional, we've treated the people who are watching this to a world-class view of what a home podcast setup can look like
amazing. Thanks Peter,
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