306. The Alzheimer's Drug With a 25% Brain Bleed Risk - Dr. David Perlmutter

“And specifically maybe related to the microglial cells. Yeah, I will put a huge vote in for vitamin D. Who knew? I mean, It might be one of the cheapest supplements out there these days. Cholecalciferol. Yeah. And why?”

“It's the only vitamin that human beings make on our own. So you got to think, wow, if we don't need to eat, drink, or breathe to make vitamin D, you know, we just need some cholesterol and some sunlight. Cholesterol. I'm oversimplifying about that. No, that's not. You know, that's basically what you need.”

“There are vitamin D receptors on microglial cells. Let's start there. That's wild. And I'll backtrack a little bit because these days people are understanding their genetic profiles and learning that they may have polymorphisms or variations in their vitamin D receptors.”

“or variations in their vitamin D receptors. So it's for all of you who get your genetic material printouts, look for changes in the VDR”

“and you might need to consider a higher dosage of vitamin D, or as you well said, perhaps get a little bit more sunlight. Sunlight is a pretty effective way, but we wear clothes generally outside.”

“Most of us do. Some of us don't, or some people don't. But that said, I don't want to say that everyone should take vitamin D as a supplement out of hand. Get your blood level checked. If you're already between 60 and 80 on your levels, then by all means, you're doing great.”

“Whatever you're doing seems to be working. Maybe you're getting your vitamin D from sunlight, from food, from your multivitamin or wherever. But if it's not, and I'm talking now to most of your, maybe not your audience, but most of the general population.”

“and it was several thousand people. They followed them for 16 years. At the beginning of that 16-year prospective analysis, they measured their vitamin D levels. At the 16-year point, they brain scanned them for tau protein.”

“Let's get back to the vitamin D study. So the vitamin D levels were looked at in juxtaposition to measuring P tau in the brains of people using a special scan.”

“Right. Higher vitamin D, lower tau in the brain. Do I think that's important and therefore supports the idea that we should make sure our vitamin D levels are where they need to be? You bet I think that. Again, that's not what the study allows me to say from a science perspective, but my personal view, which is, I guess,”

“what all of our views are, is that you bet you need to maximize or optimize rather your vitamin D level. It's that important. It reduces inflammation. Vitamin D receptors on those microglial cells make their way to the nucleus and transcribe genes that are doing good things.”

“And there are people that we will talk about perhaps off camera for whom we need to know their homocysteine levels and vitamin D levels and all the things right now. I mean, we talked about the microbiome and all that, all well and good. These other things are very powerful levers and will allow us to really make headway.”

“The older you get, the harder it is to keep muscle mass. You have to work harder. It's more time. It's paying attention to adding creatine to your regimen, testosterone, perhaps to your regimen. All of the things that you've talked about on the podcast. You've interviewed the experts.”

“those kinds of things with creatine. So let's unpack that a little bit. The systemic creatine that you have doesn't really make its way to the brain to any significant degree.”

“And that sort of is this relationship that we're trying to take advantage of. If you can raise your blood level of creatine, though it may not make its way fully to the brain, you're supporting muscle growth. And that's what you want to support your brain. Why? Because your muscles are an endocrine gland.”

“And frankly, there were some cognitive improvements in these individuals. I mean, we need a big trial of creatine as it relates to Alzheimer's. And what they did demonstrate that I think was really quite remarkable is they were able to image creatine levels in the brains and, in fact, demonstrate that it increased.”

“I recommend it. It's one of my key supplements in this book. And is it early for me to be bullish on creatine? Yep, it is. And I'm fully happy to admit that. Do I take it every single day?”

“The story is unfolding. I wanted the readers to be go ahead and start your creatine with disclaimer: your healthcare overseeing all of this. Well, hoping that your healthcare provider has heard of creatine.”

“the mitochondrial tonic that I think it's made out to be. What creatine does is in the presence of an enzyme, phosphocreatine, or rather creatine phosphokinase, that creatine binds to phosphorus, holds on to that, rather, binds to creates a phosphate binding to creatine, forming phosphocreatine”

“So I'm all in. Okay. So creatine, vitamin D, vitamin D3, anything else that is lots. Well, we got time. Third hour. We'll do the third hour. And I'll bring this up because an interesting study published about two months ago challenged the wisdom that omega-3 supplements, fish oil in particular, was good for the brain.”

“So who wouldn't want to do that? Other things input to BDNF as well. There are some research protocols to increase BDNF with various interventions, but even omega-3s, DHA in particular, amps up BDNF production.”

“are managing insulin resistance. Omega-3, high omega-3 fatty acid intake. I would imagine a diet, a lower glycemic diet. But now that we find ourselves in a situation like I'm in with my parent, where I haven't done that image, but I assume that it would light up.”

“Well, we got time. Third hour. We'll do the third hour. And I'll bring this up because an interesting study published about two months ago challenged the wisdom that omega-3 supplements, fish oil in particular, was good for the brain.”

“I mean, I've known for years that we should be taking DHA, fish oil, omega-3s in general, good for the brain, right? Right. It's been our messaging. And for me, it's still my messaging. Why was this study in the face of all of the studies demonstrating correlations between higher levels of DHA in particular and”

“Omega-3s. Right. Right. I mean, what would you tell somebody? My O2 Wiz, my friends are having, I have a particular friend who's having cognitive decline. What should he or she do? Well, omega-3 should certainly be part of that equation.”

“subjective cognitive impairment are going to gravitate to the omega-3s anyway. That's going to skew these results. You've already selected a group of people who may be experiencing cognitive decline. Number one, number two, to be fair, there's a lot of crap on the shelves in the grocery store being sold as”

“Well, we got time. Third hour. We'll do the third hour. And I'll bring this up because an interesting study published about two months ago challenged the wisdom that omega-3 supplements, fish oil in particular, was good for the brain.”

“if you will, with whether they were taking fish oil or not and concluded that fish oil was of no benefit in reducing risk of Alzheimer's and in fact, may have actually slightly increased risk.”

“I mean, I've known for years that we should be taking DHA, fish oil, omega-3s in general, good for the brain, right? Right. It's been our messaging. And for me, it's still my messaging. Why was this study in the face of all of the studies demonstrating correlations between higher levels of DHA in particular and”

“high quality fish oil in a clear plastic container that's been sitting there, probably shipped in a hot truck or who knows what. How was it refined?”

“I couldn't agree with you more. I take an olive oil in the morning, I take phosphatidylcholine in the afternoons, and I also take a fish oil. So, I load up on the EPA and DHA. You know, there are plenty of other things that are not expensive that we should be thinking about, like B complex, a good B complex.”

“So who wouldn't want to do that? Other things input to BDNF as well. There are some research protocols to increase BDNF with various interventions, but even omega-3s, DHA in particular, amps up BDNF production.”

“I mean, I've known for years that we should be taking DHA, fish oil, omega-3s in general, good for the brain, right? Right. It's been our messaging. And for me, it's still my messaging. Why was this study in the face of all of the studies demonstrating correlations between higher levels of DHA in particular and”

“and our understanding of the chemistry of DHA. I mentioned one thing that DHA does earlier in our time together today, enhances the production of brain-derived neurotrophic factor. DHA is a COX-2 inhibitor, i.e., it's an inflammation reducer in the body.”

“in the afternoons, and I also take a fish oil. So, I load up on the EPA and DHA. You know, there are plenty of other things that are not expensive that we should be thinking about, like B complex, a good B complex. Now, might you need a special form of B complex as I do because my homocysteine was slightly elevated.”

“Because we touched on it briefly, but do you have any opinions on the form of creatine monohydrate versus hydrochloride? Have you read the studies where it can mitigate the effects of sleep deprivation?”

Also filed under Creatine

“Do I take it every single day? You bet I do. Do I take? I take about seven grams of creatine monohydrate. I'm seeing the data on better GI tolerance and absorbability of creatine monohydrate, but I'm not compelled by it.”

“We'll watch that. More water-soluble, I think. Yeah. Yeah. And we'll watch that. But creatine monohydrate is widely available. It's really inexpensive. It's tasteless. Yeah, you can have GI upset if you overdo when you first start in. No question. But if it doesn't enhance mitochondrial function in the brain, which is what we're hoping for, but does allow you”

Also filed under Creatine

“And in 2014, I read a book that this gentleman authored called Grain Brain, and it entirely and permanently changed the trajectory of my career. So, Dr. David Perlmutter, welcome to the Well, I'm delighted to be here today.”

“It's true. It's a small world, though. I mean, who knew? It's a small world. But I read Grain Brain. I want to say you wrote it in 2013, but I read it in 2014. So it was published in 2013, wrote it in 2012, obviously.”

“You're in for a long. We still got to go back to Grain Brain. So that was 2013. I know. Pick it up from there. But it's interesting to me, and then I'll get back to my point that this explains grain brain. Because when I wrote Grain Brain, it was about the correlations between elevated blood sugar, elevated A1C, dietary issues, and risk for Alzheimer's.”

“What about metformin? What about red light therapy? What about hyperbarics? We can talk about those things, but the broad strokes are what we've just mentioned. And do them. You've got to do them.”

“There's a future there. Even the drug metformin has a mitochondrial play. So there's not just from its glucophage. It is glucophage. But there's much more than simply the activation of the AMP kinase that it looks like metformin glucophage is doing.”

“taking metformin are gaining, if they're gaining anything, and I think they will, based upon this way of targeting their mitochondria. But guess what? You've got incredibly powerful tools for targeting your mitochondria right now.”

“So, I load up on the EPA and DHA. You know, there are plenty of other things that are not expensive that we should be thinking about, like B complex, a good B complex. Now, might you need a special form of B complex as I do because my homocysteine was slightly elevated.”

“of the fact that we don't methylate. And we can fix that by taking not just B-complex vitamins, but they have to be methylated. Methylfolate, methyl B12, problem solved. My homocysteine went down to 6.8.”

“And we can fix that by taking not just B-complex vitamins, but they have to be methylated. Methylfolate, methyl B12, problem solved. My homocysteine went down to 6.8. Mine was 15. Now it's seven. So if you had a homocysteine of 15, that needed work.”

“First of all, I agree with everything you're saying, the methylated multivitamins, the methylfolate, methylcobalamin version of B12. Some genetic variants need the hydroxy or the adenosyl. Yeah, it's not a big deal. Sam super easy. You know, I look forward to my sublingual B12 because it's sweet. and it's the only, you know, it's my real treat, my sublingual B12.”

“And we can fix that by taking not just B-complex vitamins, but they have to be methylated. Methylfolate, methyl B12, problem solved. My homocysteine went down to 6.8. Mine was 15. Now it's seven. So if you had a homocysteine of 15, that needed work.”

“First of all, I agree with everything you're saying, the methylated multivitamins, the methylfolate, methylcobalamin version of B12. Some genetic variants need the hydroxy or the adenosyl.”

“mitochondrial function. There's a product that's called RNS60 that definitely targets mitochondria. It's a proprietary way that saline solution is hyperoxygenated, creating these nano-bubbles of oxygen that seemingly mitochondria love.”

“Well, that's what the beauty of one of the things I mentioned earlier, this RNS60 instantly just transgresses, makes its way into the mitochondria. What was the RNS60? So RNS-60 is a nanoparticle change of saline, normal saline, hyper-oxygenating normal saline.”

“You can watch it happen if you're looking. So that's a point I want to make. You really want to be metricizing. You want to wear your Oura ring or Apple Watch or Whoop, whatever it may be, and find out what is the duration and quality of your sleep.”

“Now it all comes together. And I'm grateful at 71, finally the pieces came together. I wrote a book years later, several years later, called Brain Maker, and I had the conclusion, strange as it may be, that there's a relationship between, get ready for this, gut health and brain health.”

“duration and quality of your sleep. Very important. What is your blood sugar doing? Wear a CGM continuous glucose monitor from time to time. Get your blood work done. You know, you could do that without a doctor now and get that information. Then you challenge yourself with the question: well, what do I do with this information?”

“exercise by playing pickleball or whatever it would be, or those who did resistance training, weights, tension bands, machines, or even those who decided to do both.”

“I agree with everything you're saying, the methylated multivitamins, the methylfolate, methylcobalamin version of B12. Some genetic variants need the hydroxy or the adenosyl. And it's not a big deal. It's super easy. You know, I look forward to my sublingual B12 because it's sweet.”

“First of all, I agree with everything you're saying, the methylated multivitamins, the methylfolate, methylcobalamin version of B12. Some genetic variants need the hydroxy or the adenosyl.”

“So, don't throw the baby out with the biofuels. I couldn't agree with you more. I take an olive oil in the morning, I take phosphatidylcholine in the afternoons, and I also take a fish oil. So, I load up on the EPA and DHA.”

“There are hacks left, right, and center, and some of them have great merit. We talk about them in the book. You know, what's the future of would rapamycin be something that's in a brain healthy program? What about metformin? What about red light therapy? What about hyperbarics?”

“exercise by playing pickleball or whatever it would be, or those who did resistance training, weights, tension bands, machines, or even those who decided to do both.”

“Yeah, it's not a big deal. Sam super easy. You know, I look forward to my sublingual B12 because it's sweet. and it's the only, you know, it's my real treat, my sublingual B12. Sometimes I might even have two if I'm feeling reward myself.”

“But here's the good news: you can drive homocysteine levels down with B complex. B-complex and TMG. Yeah, trimethylglycine. Trimethylglycine. Or dimethylglycine. Yeah. Unless you have a genetic quirk, which I have, called MTHFR.”

“So I'm all in. Okay. So creatine, vitamin D, vitamin D3, anything else that is lots. Well, we got time. Third hour. We'll do the third hour. And I'll bring this up because an interesting study published about two months ago challenged the wisdom that omega-3 supplements, fish oil in particular, was good for the brain.”

Also filed under Vitamin D

“You can watch it happen if you're looking. So that's a point I want to make. You really want to be metricizing. You want to wear your Oura ring or Apple Watch or Whoop, whatever it may be, and find out what is the duration and quality of your sleep.”