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Dr. Kat Toups speaks about the Details of How to Reverse Alzheimer’s Disease with Dr. Ben Weitz.

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Podcast Highlights

7:42  Metabolic factors, including fasting glucose, insulin, and Hemoglobin A1C are all important factors in preventing and reversing Alzheimer’s Disease.  Rather than having specific targets for these lab values, Dr. Toups’ goal with her patients is to see how much she can optimize these factors.  Ideally for nutrient levels, we want them in the middle range, but for metabolic factors, we generally want them lower. We know that high blood sugar is destructive to the blood vessels, to the end organs and that has sort of long been known as a factor for dementia and for Alzheimer’s.  They had all the patients follow a ketogenic diet for the benefits of ketones for the brain and the patients were in ketosis for the majority of the time.  This definitely helped to manage the blood sugar and insulin levels.  It is also important to measure insulin to see how hard the patients are working to get their blood sugar to where it’s at. If they are eating too many carbs, their insulin level may end up too high. There are also patient who have had high blood sugar so long that their pancreatic beta cells are not making enough insulin.

16:11  Lipids. It is important to have good blood flow to the brain, so monitoring advanced lipids is important for Alzheimer’s patients.  Most of the patients in the trial saw improvements in their lipids related to the types of carbs and fats that they were eating, as well as due to the exercise, their improved sleep, and the focus on getting them into a parasympathetic or meditative state. Taking statin medications can be a problem for these patients because they can lower cholesterol too much and this can be bad for the brain and it can even cause dementia.  Cholesterol is need for the brain, for the myelin sheath that surrounds nerves, for the phospholipid layers around the cells, and for neuron formation.  Cholesterol is also a precursor for your hormones like testosterone, estrogen, DHEA, and pregnenolone.  Statins can drive the cholesterol level too low, such as down to the 130s.  That is too low to support brain and hormonal health.  Dr. Toups discussed a patient that she had who came to her in his early 90s and his main risk factors for Alzheimer’s were that he had been taking statins for a long time and had cholesterol in the 130s for all that time. He also was taking Finasteride for an enlarged prostate, which can reduce testosterone levels, which can also impact brain health.

22:54  There are a number of medications that can negatively affect brain health, including Anti-cholinergic medicines (which are drugs that block the action of acetylcholine) like some of the older antihistamines like Benadryl and some of the OTC sleep medications and drugs that treat urinary incontinence, antidepressants, antihistamines, some of the nausea drugs, and psych drugs in general. 

25:18  Nutrient status is important for brain health, so Dr. Toups and her colleagues used the NutraEval from Genova, which measures all the vitamins, minerals, antioxidants, fatty acids, amino acids, and even looks at some heavy metals.  She finds that many dementia patients are low in vitamin D and B12.  For vitamin D, Dr. Toups likes to see a level of 50-80 ng/mL.  If your vitamin D level is less than 30, your risk for dementia is increased by 75%.  For most of us, just getting out in the sun a bit is not enough. You still need vitamin D supplementation.  We really should be measuring nutrients levels, including in children because many children are deficient and we need to support our brains and our bodies with the essential ingredients needed.  Unfortunately we grow fruits and vegetables in soil that has been overgrown and is often deficient such as in minerals like zinc and magnesium, as well as having so much toxicity like arsenic and lead and various other chemicals.  All these nutrients like vitamin D are crucial for the formation of our mitochondria, which make the ATP, which is the cellular energy that makes our brain and our bodies work.  Giving your body the right nutrients is like putting gas in your car so that it can go.

32:40  Hormones are also important for brain health.  We need hormones for optimal brain health.  They did a study at Stanford with women who were taking hormones and those that stopped had a decline in cognitive function and had shrinkage of their brains.  There are receptors in the brain for hormones and the brain even makes it own hormones like estrogen.  Dr. Toups has seen testosterone function as an antidepressant for women.  Pregnenolone, which is sort of the master sex hormone, has been studied for dementia and it is an independent risk factor for dementia if it is low.

 

 

 

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Dr. Kat Toups is a Functional Medicine Psychiatrist in Walnut Creek, California and the owner/Medical Director of Bay Area Research Institute, a clinical trials research center in Lafayette, CA.  She served as the principal investigator on over 100 clinical trials for 12 years for failed drugs for Alzheimer’s Disease and she is one of the treating doctors and authors of the paper reporting on the new study showing that a Functional Medicine approach could reverse Alzheimer’s Disease: Precision Medicine Approach to Alzheimer’s Disease: Successful Proof-of-Concept Trial. 

Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

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Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me. And let’s jump into the podcast.

Hello Rational Wellness Podcast listeners. Our topic for today is Alzheimer’s disease with Dr. Pat Toups. Alzheimer’s disease, as most of you know, is a degenerative brain disease, and it accounts for between 60% and 80% of cases of patients with dementia. Patients with Alzheimer’s disease develop difficulties with memory, language, problem solving, and other cognitive skills that affect the person’s ability to perform everyday tasks. So hallmark pathologies of Alzheimer’s are the progressive accumulation of beta amyloid protein that forms plaques surrounding neurons in the brain and twisted strands known as tangles of tau protein inside of neurons. In 2018, near an estimated 5.7 million Americans with Alzheimer’s, and this number is rapidly increasing.  According to one estimate, Alzheimer’s disease is the third leading cause of death in the US. The conventional medical approach to treatment for Alzheimer’s has so far failed. With over 400 failed drug trials, and let’s witness the latest drug that was approved a few weeks ago for this condition, a drug for which I cannot pronounce, but it’s adilumumab.

Dr. Toups:           Aducanumab. I had to practice it quite a bit myself.

Dr. Weitz:            And this is a drug that does not make anyone better. I repeat that. It does not make anybody better. But it merely slows the rate of decline in a percentage of patients, according to how you interpret the data, and the cost is only $56,000 a year. The approval of this drug was so controversial that three of the doctors on the advisory panel resigned over this drug’s approval by the FDA. Because the original report that came out showed there was no clinical benefit at all, despite the fact that the drug helped to clear out amyloid plaque. Yet there’s a study that was just completed and a paper reporting results that has now been published on a pre-print server called Precision Medicine Approach to Alzheimer’s Disease: Successful Proof-of-Concept. And this trial utilized Dr. Dale Bredesen’s protocols with Dr. Pat Toups, one of the treating doctors and the principal author of the paper reporting the results.

In this trial, unlike that drug, patients got better. In 84% of patients with early Alzheimer’s disease, or mild cognitive impairment, showed improvement and reversal of their condition. Dr. Kat Toups, Functional Wellness Psychiatrist at Bay Area Wellness in Walnut Creek, California. And she’s the organizer and administrator for Bay Area Functional Medicine Group since 2012. And at one point, Dr. Toups was the only medical director of Bay Area Research Institute, a clinical trials research center in Lafayette, California. After serving as the principal investigator on over a hundred clinical trials, including 20 failed trials for Alzheimer’s drugs, she realized that the elusive cure for brain and psychiatric illness was not going to be found in a bill. She certified in functional medicine by the Institute of Functional Medicine. Dr. Toups, thank you so much for joining us today.

Dr. Toups:           Thank you. I’m really excited to be here.

Dr. Weitz:            Good, good, good. So I’d like to draw, as you know, I recently got to speak to Dr. Dale Bredesen and we talked a lot about the parameters of this trial, but I’m hoping today that we can really drill down into some of the details of how the patients were managed. But before we get into the details, since it appears to me that you employed a functional medicine approach, why was the approach in this study referred to as a precision medicine approach, as opposed to a functional medicine approach?

Dr. Toups:           That’s a great question. And I actually wondered the same thing. So that was [crosstalk 00:04:56]-

Dr. Weitz:            Is that a more acceptable term?  Will that not get you banned from Facebook or something.

Dr. Toups:           Well, I believe that is kind of precisely what Dr. Bredesen was thinking when he put that title on it. So it is a functional medicine approach. A functional medicine approach is a precision medicine approach, but somehow in the vernacular of general medicine, precision medicine is kind of a new term that’s out there, and I guess more acceptable. I don’t know. I mean, functional medicine has its detractors and its supporters. But it’s the same thing. This is a Functional Medicine approach. I call what I do a functional medicine approach to dementia. So it’s the same thing.

Dr. Weitz:            Good, good, good. So I noticed one of those parts of the program was that patients are assigned specific categories as to the type of conditions that play a role in a causation or a triggering of their Alzheimer’s. How are those categories derived? Are patients put in those categories as a result of history, or is it after the lab tested?

Dr. Toups:           Well, perhaps a little of both. But they’re really pretty artificial and arbitrary. I don’t personally use them in my head the way I think about things. So I think when Dale Bredesen was first conceptualizing these ideas, and he was coming from the bench research side of things, not as a clinician, it’s sort of even more amazing to me how he started to put all this together, not being a clinician. But he was trying to conceptualize what are all the different factors that are affecting the brain. And then, so he kind of came up with those categories, but they’re really arbitrary. And you’d be hard pressed to find someone that only met one of those categories. Most people are a combination of two or three of those categories. So they’re kind of just a general way to maybe talk about things.  So when we say, “Oh, this is a type three patient.” It’s kind of referring to the CIRS patients, the chronic infectious, the mold and the Lyme and the viruses and the infections. But do any of them just have that? No. They’re going to all have some components of inflammatory or metabolic or hormonal or nutritional. So it’s just more a way to make sure you’re kind of in your head, and your investigation’s ticking all those boxes when you’re doing your workup to make sure you investigate all those things. That’s kind of how I think that it’s the most useful.

Dr. Weitz:            Okay. So one of the categories is patients with metabolic blood sugar issues. Right?

Dr. Toups:           Right, right.

Dr. Weitz:            So let’s start by talking about that factor. So what are the, when you’re working with a patient, what are the targets you like to see on lab testing for fasting glucose, insulin, hemoglobin, A1C?

Dr. Toups:           Yeah. I don’t think in terms of what is a specific target, but how good can I get it? And that’s going to vary from person to person. So if someone’s starting out in a hemoglobin A1C of 5.8 or 5.9, well, how good can I get it? I mean, somebody who’s starting lower, they may be able to come into the force, but it’s such a fascinating thing. In this study I have never seen people’s metabolic and inflammatory parameters shift this quickly. And I’m pretty aggressive as a functional person. I always feel like people come to me are so sick and you’re just racing the clock. They’ve been sick for so long. And if they have dementia, you definitely need to get them fixed as quickly as possible because you can’t afford to lose any more brain every day.

Doing full court press in this study, we only had nine months to move the needle. And so we had to test, and I already did this anyway in my practice, like with dementia, I say, “Just test everything upfront.” Some people say, “Well, I’ll work on this. And then they’ll get a little better, then I’ll test that.” And they kind of do it sequentially, but I don’t think that works with this really, there’s so many factors. And if you test everything at once and well, then you have your treatment plan. You have your treatment targets, right? You can figure out, “Okay-“

Dr. Weitz:            In your office, all of them got the testing right off the bat?

Dr. Toups:           Correct. And that was part of the protocol. So we all did the same testing. We came up with a list of tests of all the various things we wanted to look at. There were three investigators, three different locations, and we all did the same testing. And after that is where we diverged. So the treatment plan was individualized based on what was found in that testing. We then used our functional medicine skills and backgrounds to target that.  So some of the patients, I mean, I saw people with A1Cs of 5.8 or 5.9, come down to 5.2 or 5.3 in three months. Seriously.  That was pretty amazing to me how quickly you could shift the needle. People that had high levels of inflammation that plummeted very, very quickly.  So there were a lot of extra benefits of the study besides the cognitive benefits.  But of course, as you’re pointing out, these metabolic parameters are all, whatever happens in the heart and the blood vessels is happening in the brain. So they’re intricately connected there and we have to address those.

Dr. Weitz:            For those who are listening to this podcast, if you’re not really familiar with a Functional Medicine approach, they might not sort of understand what we’re talking about when we talk about some of these lab values.  Because the conventional approach is anything below 5.4 or 5.5 or 5.6, depending on the lab

Dr. Toups:           5.6.

Dr. Weitz:            … you use on your hemoglobin A1C is normal.  It’s not a question of lower. And so in functional medicine, we typically have there’s normal, and normal is just the average person being tested. And then there’s an optimal level. So we’re trying to get people optimal health, not just normal health.

Dr. Toups:           Right. Ideally for things like nutrients, we want them in the middle of the range.  We don’t want them at the top, we don’t want them at the bottom.  We want to be like Goldilocks in that sweet spot. Though with hemoglobin A1C, I guess there could potentially be a too low value, but I haven’t seen it. If you get down to 4.8, 4.9, I think that’s about as good as it gets. The hemoglobin A1C is such a perfect example. My husband had a hemoglobin A1C of 5.6 and it made me crazy.  I’m like, “No, you’re eating too many carbs, blah, blah, blah.”  And he sees an endocrinologist.  He said, “My endocrinologist says it’s fine.”  I don’t treat my husband, of course, but I can nag him a little.  And then all of a sudden, of course, 5.6 is the cutoff.  Above that is called pre-diabetes.  Then all of a sudden, one year it jumped up from 5.6 to 5.8.  That’s when his doctor finally said, “You need to do something.”

And of course he did what his doctor said, not what his wife said.  And he brought it down a few points.  But yeah, so certainly, the blood sugar control, we know high blood sugar is destructive to the blood vessels, to the end organs. That has sort of long been known as a factor for dementia and for Alzheimer’s. So it definitely critical to do that. And in our study, we had everybody do a ketogenic diet. And that was for the benefits of the ketones on the brain and it was a requirement for the study. And there’s many debates. We could have a whole session on whether long-term ketosis is the right thing, the wrong thing. But for the purposes of this study, they all were in ketosis for a majority of the time. And definitely to see the benefits of that for the blood sugar was quite phenomenal. And maybe I’ll jump to another question for you because there’s so many questions about like, “Well, what about the lipids?” You’re putting people-

Dr. Weitz:            You know what? I just want to get a little more detail. Let’s talk about the importance of insulin also as a factor, because typically that’s not tested by normal physicians. The glucose is included in part of the typical panel and that’s all they really pay attention to, but insulin is really important. Maybe you could explain the importance of why we want to measure insulin and why that’s important.

Dr. Toups:           Well, the insulin, we can see it too high or too low. If you’re eating too much sugar and you’re still turning out insulin, you’re going to see the insulin come too high. And sometimes it’s useful instead of looking at a fasting blood sugar to look at a postprandial blood sugar. So after you eat lunch, go and get your lab and see how high is your blood sugar spiking then, instead of the fasting. Because that’s going to be a function of, are you making enough insulin to bring it down? And how high is it getting with what you’re eating? It kind of tells us various things. Some people have had high blood sugars so long that they’re burning out their pancreatic beta cells and they’re not making enough insulin. So the insulin resistance people are putting out lots and lots of insulin and the cells are no longer listening. So it kind of goes both directions with the insulin.

Dr. Weitz:            You can have two patients with, let’s say, they have a fasting blood sugar of 90 or 95, it’s higher than it should be. But if one patient has an insulin level of six, then it’s less of a concern than if your insulin level’s 30. Because a patient who’s insulin level is 30, is working really hard just to get it down to 90. And so that’s more of a problem.

Dr. Toups:           Well, and the whole blood sugar thing comes into play with trying to get into ketosis. Because if your blood sugar’s already high, with ketosis, we’re trying to stop feeding the body the carbs and the sugar as fuel, and shift into burning the fat as fuel, which means you’ve got to get those sugars down. So people with a higher blood sugars have a harder time getting into ketosis. It takes them longer to do that, but there is eventually a metabolic shift. And once they get into ketosis, then it pretty much stays that way.

Dr. Weitz:            Well, let’s get into lipids now. And lipids are important because we have to have a good blood flow to the brain. And so if your arteries are clogged with plaques, then you’re not going to get good blood flow to the brain.

Dr. Toups:           Definitely. That’s yet another factor and so important. So we did advanced lipid panels on all of our patients. We use the Cardio IQ at Quest. It gets into all of the lipid particles and worked on various things with that. I had one patient come in on a statin and was able to get off of that statin. His cardiologist gave him the blessing to get off of the statin because as a consequence of what we did in the study, his lipids came down so beautifully that he no longer needed a statin. I think there were two of them like that. It shows the effect. With the lipids, it’s obviously what you’re eating and the types of fats that you’re eating and the types of carbs and anything inflammatory that you’re eating is going to have a factor on your lipids.

But so do the other factors. So does your exercise, so does your sleep, so does being in a parasympathetic or meditative state. All of these things are things that were components of the study. So they just all came together. And then we saw all these metabolic benefits in the study. We haven’t really even gotten into writing that up, but at some point we need to track what happened. How many people lower their A1Cs, how many people lowered their lipids, how many people lowered their CRP. Well, I can tell you in my 10 patients, a lot of them did. So all of those things come together. It’s not just one intervention that you can do. It’s the stuff that we, our foundational right for health of all kinds of systems.

Dr. Weitz:            So I noticed in your exclusion criteria for this study, you just mentioned statins, but you didn’t really want patients involved in the study if they were taking statins or blood thinners or psychoactive medications like antidepressants. Maybe you can talk about the significance of those.

Dr. Toups:           I think we allowed stable antidepressants. It’s been a while since we first enrolled people now. But the idea is that any unstable medical conditions are not right for a study. Because you could have unintended consequences. And so you kind of want to have people that are stable on their medicines. The idea of no statins, and I think we ended up allowing people if they were going to be able to discontinue those statins. Our concern is that the statins can lower the cholesterol too much. And the cholesterol is so important for the brain. Our brain is like 60% fat, right? You think of that spongy gray material as fat. And so if you don’t have enough fat, then you can’t support your brain. You need it for the myelin sheaths around the nerves, you need it for the phospholipid layers around the cells and your neurons.  And then the cholesterol is a precursor to all your hormones. And I know we’re going to say a little bit about that at some point, but cholesterol turns into testosterone, estrogen. DHEA actually goes directly into pregnenolone, which is so important for the brain. So when people’s cholesterols get too low, it can be actually literally a cause of dementia. I call it iatrogenic dementia. I’ve seen people on statins where they drive their cholesterol down in the 130s. Well, that’s not high enough to support your brain and your hormones. So those were some of our concerns about the statins.

Dr. Weitz:            Now what do you say to conventional wisdom?  Information that seems to be common in the cardiology world, that statins do not negatively affect brain function.

Dr. Toups:           Cardiologists don’t look at brain function. They’re not looking at it. And I had a great case that I started out earlier saying most people with cognitive decline, it’s multiple factors. But I had a gentleman that came to me in his early 90s, and unfortunately it was too late to really move the needle for him. But this gentleman was practicing medicine up until 85, on his second medical career. He was boarded in one area of medicine. He retired at 65. And then he went in and did emergency medicine and got boarded in that and did that for another 15 years. So this guy was doing well. His brain was good. He wasn’t toxic. I mean, to be able to function that long and that well, everything was working well for him. But in his case, there were two factors that I turned up. And one was, he was on the super dose of the statins.  So his cholesterol was in the 130s for a long, long time. And the other thing was that he had an enlarged prostate and he was put on Finasteride for the prostate. And Finasteride can be deadly for the brain. It’s known when it’s given to younger men that can use it for hair loss that they can suddenly develop very severe psychiatric problems. Sometimes even psychosis. There’s been a higher rate of suicide with it. But for our purposes in the older men, it’s blocking the conversion of testosterone to dihydrotestosterone. And it’s blocking the conversion of, I think, pregnenolone to allopregnanolone, or maybe it goes the other way around. I forget right now. But in blocking the testosterone effects, what is that doing to the brain? And we have receptors in our brain for all of these hormones. And interestingly, in his case, his wife confirmed to me that the minute he started on that medicine, their sex life was over.

His sexual functioning was not good anymore. So it was definitely affecting his testosterone system. And for him, I mean, he wasn’t high in toxins his lipids weren’t bad, his blood sugar wasn’t bad. The big thing for him, he didn’t have infections. For him, it was the low cholesterol and a lack of testosterone. I think that it’s pretty clear that these factors are just, we have to watch what we’re taking and what are the downstream consequences. You take a medicine, most of them aren’t affecting just one thing. Our body is interconnected.

Dr. Weitz:            What are some of the other medicines that would be on the top of the list of medications that might negatively affect brain function? Besides you mentioned statins and…

Dr. Toups:           Yeah. Anti-cholinergic medicine. Anti-cholinergic is a type of side effect of a medicine, but there are certain, the older antidepressants, Benadryl, some of the anti-histamines that are anticholinergic. It’s in some of the over to counter sleep medicines. So anti-cholinergic has long been known, especially with aging, aging brain gets actually very confused with anti-cholinergics.

Dr. Weitz:            What are some of the most common anti-cholinergics?

Dr. Toups:           The most what?

Dr. Weitz:            Most common drugs in that category?

Dr. Toups:           I would say the antidepressants, some of the anti-histamines. I think some of the nausea drugs. I mean, psych drugs. You got to watch it with the psych drugs, for sure. But I mean, in the study, one of my patients was taking an over the counter sleep medicine that was anti-cholinergic. And I said, “Oh my goodness. I know you need your sleep, but we have to find another way.” And she confirmed that on the nights that she took it, that she actually was a lot more confused the next day. And she never had put that together with her sleep med. So definitely some of the over-the-counter sleep meds.

Dr. Weitz:            Okay. So what were some of the-

Dr. Toups:           And Benadryl is a huge one. Benadryl. They’ve shown that people, now these days, we have a lot of other anti-histamines that don’t have anti-cholinergic effects, but Benadryl used to be used quite a bit. And they show that when people are taking Benadryl every day, they don’t notice the sedation from it. So if you just take it and you’ve never taken it, you might feel sedated. But when you take it every day, you build a tolerance, but they tested their reaction times. And they found that when people are taking Benadryl daily, their reaction time was as impaired as if they had several drinks of alcohol.  Reaction time was as impaired as if they had several drinks of alcohol.

Dr. Weitz:            Wow.

Dr. Toups:           And people aren’t aware of that. So, if you have an allergic reaction, you need to take some for a day, okay. But chronically, no. It’s going to really affect your brain.

Dr. Weitz:            So nutrient status and nutrient deficiencies are super important for brain health. And I know that you’ve tested certain nutrients. What testing did you do for nutrients and which nutrients did you see most commonly that needed to be supported for brain health?

Dr. Toups:           Right. So for the testing, we use the Genova NutrEval panel, which is an excellent panel as I’m sure you know. It looks at all the vitamins, the minerals, the antioxidants. So it’s a really nice, nice panel to get a big workup.

Dr. Weitz:            I love panels like that, but I often find that medical doctors, in order to try and get it covered by insurance, we’ll just use like a serum B12 and a serum level. What do you think about the efficacy of just doing that?

Dr. Toups:           I think it’s a great place to start and I think there’s certainly more physicians are getting on board. I mean, COVID has helped the general medical population to understand the importance of zinc and vitamin D. We know that people that are deficient in those are much more likely to get a more severe of COVID and much more likely to have mortality. And there again, like when you mentioned the ranges, and the range of vitamin D is 30 to a hundred. And so doctors will say [crosstalk 00:26:50].

Dr. Weitz:            What would you like to see for your patients?

Dr. Toups:           I like to see 50 to 80, is my sweet spot for that. And you know, if you’re at 30, 32, no, you may have some days that you’re in the twenties. And we know vitamin D is such a prime one for dementia and the brain. So if your vitamin D level is less than 30, your risk for dementia is increased by 75%.

Dr. Weitz:            Wow. And that’s gram per milliliter.

Dr. Toups:           I don’t know the units. I just look at the numbers.

Dr. Weitz:            There’s another scale that is different-

Dr. Toups:           Okay. With the traditional numbers that are reported by Quest and Labcorp, and general medical labs. 30 is the cutoff of normal, but really you want to get that up to at least 50 for that. So definitely a lot of this can be done on regular medical insurance. If you have Medicare, actually they cover the Genova NutrEval, so it’s really excellent for the Medicare population to be able to screen them. And of course you have to have the appropriate diagnosis codes for Medicare, but most people of that age have enough diagnosis codes to justify doing a test like that. But you can get from regular Quest and Labcorp, yes, you can get the vitamin G you can get the B12, you can get the B6, you can get some of the genetics. And we get the minerals, so, RBC mag, and RBC zinc, and copper. There’s only so many labs you can get at one time. So doing something like NutrEval is helpful.

Dr. Weitz:            So what were the, some of the most common nutritional deficiencies you saw?

Dr. Toups:           I’d say D and B12 are the most common that you see. And the vitamin D I mean, I live in a San Francisco bay area. You’re in Southern Cal, so a little closer to the equator than us, but even then we evolve to make vitamin D at the equator. Early humanity, we were at the equator with full sun and full sun year around. Well, here in the San Francisco Bay area, we are too far north. I have people say, oh, well, I work in the sun. I’m out all day in the sun. They’re vitamin D’s are not okay. They’re not okay. Yes, get your sun, I mean, that’s still going to help the whole system and is a natural burst of vitamin D, but it’s not enough.

You need to measure those levels. And we need to be measuring this in children because children are deficient. And these are things that are easy to supplement and safe. If we can support, our brains and our bodies with the nutrients that we need, because people will say, well, I eat an organic diet. You know, I’m eating a whole foods, organic diet. Unfortunately, our soils have been overgrown and I’ve seen maps in different parts of the country. Some parts are deficient in this nutrient and other parts are deficient in that nutrient. Unless they’re amending the soil and really checking it, I think the science of crop growing is evolving that direction to have some awareness that we need to put more nutrients back in the soil so that it comes to our plants that we eat. But at this point in our world, there’s so much toxicity and depletion of nutrients that it really bears testing those. I think in the minerals, zinc and mag, or the most common deficiencies that we see in those are really important to check and supplement, of course.

Dr. Weitz:            If I’m not really familiar with the functional medicine approach, let’s say I’m a conventional primary care doctor listening to this podcast think, well, sure you should have vitamin D and zinc and magnesium, but what the hell does that have to do with Alzheimer’s?

Dr. Toups:           Oh, they’re integral for brain function. Vitamin D is really a hormone. And because it exerts downstream effects, it acts as a messenger to multiple systems. And vitamin D I believe, excuse me, it affects like more than 200 systems in the body and the brain. So these factors are just all integral for all of the complex biochemistry that if doctors think back to their training, they have learned biochemistry and physiology at some point. And just looking at our mitochondrial support, the mitochondria are the powerhouses in our cell. They make our ATP, they feel every function in our body. We have to have energy to run the body. And the mitochondria, if you look at the electron transport chain, which are the final steps of making the ATP, there are many nutrients that are conditional for the ATP to make that energy.  So if you don’t have these nutrients, it’s just like putting gas in your car. It’s not going to go, it’s not going to work properly. And whatever happens in the brain, it starts in the body. They’re connected. I trained as a psychiatrist and back in the dark ages, more than 30 years ago, we were pretty much taught like the brain, you just focus on the brain. You give these meds and help the brain. And we didn’t learn in residency training all the kinds of things that I know now are essential to make the brain work. And so everything’s connected. But that isn’t medicine. It sadly has, as medicine evolved specialists, it became more and more reductionistic. Each specialist deals with their little piece of the body. And I think we all have to shift back into becoming generalist and understanding the interconnection.

Dr. Weitz:            Yeah. I think we have to think, what are the things that we don’t have enough of that’s going to allow our bodies to function right? What are the things that are going to allow us to make new neurons and new neuronal connections? And nutrients obviously is super important, having the right input in terms of energy, which means having our brain work more on ketones, rather than glucose, making sure we have proper blood flow. And then we also have hormones which are super important for giving the right impetus for our brains to work. Maybe you can talk about the importance of hormones.

Dr. Toups:           Right. The hormones have become such an interesting and exciting piece. There was a study done some years ago at Stanford. And they took women who were at risk for Alzheimer’s that were older and had been taking hormones. And they randomized them either to stay on the hormones or stop the hormones. And they followed them for two years. And what they found at the end of two years, they did head scans, they did neuro psych testing, and they found that at the end of two years, 100% of the women who stopped their hormones had a decline in their cognitive function. And you could even see it on a head scan. So there was atrophy or shrinkage in the brain. So that is a clue that hormones are doing something there to protect the brain. And in that study, it didn’t matter whether they were on bio-identical hormones or synthetic field, synthetic hormones that are sadly still in use.

Any kind of hormones that they were on, if they stopped them, they saw a decline compared to the women who stayed on their hormones. So what we’ve learned is there’s all of these receptors in our brain for these hormones. We think of the sex hormones, we think, oh, they’re for our sexual functioning, for reproduction and okay. Yes, absolutely. But just like there’s vitamin D receptors in our brain, and magnesium receptors in our brain, there’s hormone receptors in our brain. And even more interestingly, our brains, both men and women, can make their own supply of estrogen. And I only discovered that I think a year or two ago, I don’t know how long it’s been known, but it’s not widely known. And I was shocked to find that it’s so important for the brain that is going to make its own supply.

And so, as long as we don’t have anything bad going on in our brain, that should still work even after menopause and even after andropause. But whenever we have processes disrupting our brain, which we’re having now with all the toxins, and the infections, and the immune problems that our people are having, then it’s going to disrupt that process as well. Men have estrogen receptors in their brain and they have a supply of making the estrogen in their brain, just they make more testosterone than estrogen. Women have testosterone receptors in their brain, same as men. And testosterone is such a fascinating hormone. I call it a wellbeing hormone. It’s hugely important for the mood and motivation. And I’ve seen it work beautifully as an antidepressant, just amazing antidepressant for people. We have all of these receptors in our brain, which means we need these hormones for our brain to be optimized.

So one of the things that we do is we test all the hormones, the whole cascade of hormones. So cholesterol turns into pregnenolone, well pregnenolone has been studied with dementia. And it’s an independent risk factor for dementia when you’re pregnenolone is low. Now pregnenolone, you can measure at Quest and Labcorp. It’s a regular lab that can be easily tested. And I don’t know why, but you can buy pregnenolone as a supplement, but testosterone is a controlled substance prescription. But the pregnenolone will turn into testosterone so it can definitely drive that up. We tested pregnenolone, we tested DHEAS, we tested estradiol in men and women, we tested progesterone in the women. And then we tested testosterone in men and women, the free testosterone, the total testosterone.

And basically what we did was we worked to just optimize all of those hormones in a reasonable part of the range. Now people say, okay, you’re going to give all these hormones to somebody that are older. Well, there’s a range. When we’re in our twenties, our hormones are surging. That’s going to be the highest amount of hormones that we have as young people, because the goal of those hormones is to support our reproductive years. And people will tell me, well, I don’t want to take hormones. It’s not natural. God didn’t make us to take hormones. But you know, the thing is until a century ago, we didn’t live much past our reproductive age. People died in their fifties and sixties. And now in our generation, people easily living into their nineties if they stay relatively healthy.

We have rapidly shifted evolution as far as longevity. And so we can live a third of our life after menopause or andropause. And so we don’t need those hormones then for reproduction. But in my book, we need them for our brain. And we definitely can see for some people, you’ll start the hormones. And some people won’t notice much, but other people will really notice the cognitive benefit. And it’s somewhat insidious as you build up the levels. But when you stop the hormones, if somebody’s been on them and stopped it, which we sometimes see when people have cancer and their doctors say, you’ve got to go off your hormones, people will crash. Their cognitive function can crash when they stop the hormones. So that’s when you can sometimes see how much they’re doing for your brain.

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Dr. Weitz:            So a follow up question on the hormones. So let’s say we’re taking them, a woman say in her sixties or seventies. And first of all, how valuable is it to really measure hormones because we know they’re going to be low if we’re talking about estrogen, progesterone, et cetera. And then B is, we had the women’s health initiative, which came out in 2001, and showed that there was an increased risk in taking a hormone replacement after menopause. And one of the analyses about why there seemed to be an increased risk of heart disease and cancer was because of the timing hypothesis, which is that most of these women didn’t start taking the hormones still on average 10 years after menopause.   Now there are other problems with this study as well. It’s basically from our functional medicine perspective, and the fact that they were given Premarin, which was oral estrogen. It was hormones that were secreted in horse’s urine, so it wasn’t bioidentical and they were given synthetic [inaudible 00:41:28] I bought that says, now you have this woman, she’s 65 years old, she’s in your office, she’s got cognitive impairment. And now you’re talking about putting her on hormones, aren’t you putting her at risk?

Dr. Toups:           Right. So, you know, the problem with the WHY study and all of the big hormone studies that have been done, as you mentioned, they were done … they did not distinguish between bio identical and synthetic hormones. And most of them like the WHI, was mostly synthetic hormones. And we know that synthetic hormones actually increase your risk for cancer. So we don’t want people taking synthetic hormones for starters. They’re not mimicking the way our bodies are meant to work like the bioidenticals are. So we don’t have great data on the bioidenticals, but there is data coming out on bioidenticals. And with regard to the cancer risk, there’s a couple of studies that show that if you’re taking bioidentical estrogen, it will lower your risk for recurrent breast cancer. And I’m actually finding some oncologists in my area that are aware of that and will allow their breast cancer patients to go back on hormone replacement because your breasts need the hormones to function normally as well.

So if your breast doesn’t have estrogen and it’s all atrophied atrophic, it’s going to be more of a risk for some malignancy to happen anyway. And then with regard to the heart condition, so we know that hormones are protective for the heart. We know that after menopause, women have less risk for heart disease before menopause than men. But after menopause their heart disease risk increases, I think never quite as high as a male, but it really starts to skyrocket. And so continuing hormones in the menopause transition should be protective to some degree for heart disease. And then the issue really becomes that some of the studies show that if you’ve been off of them for 10 years or more, and you start them that you’re going to have a higher risk potentially of cardiovascular events in the first six months.

And so that thinking is if there’s some preexisting plaque that’s going to potentially, if you’re inflamed and break loose, that could be a problem. But we don’t have that data at all for bioidenticals yet, we need it. And in my world, for somebody that’s coming in at 75 with cognitive decline, I have to weigh the risk of heart issues versus their brains going down. It’s a sure thing. And we have treatments for heart disease. Definitely some people die from heart disease, it’s still is a killer of people, but kind of weighing the risks and benefits of that. I think in the context of a study, we had to move fast. But if you have somebody coming in 10 years out and they have some inflammation and lipids then work on that, bring it down, start starting their hormones and people have done well.

Dr. Weitz:            What form of estrogen have you used? You also use progesterone. Do you cycle the progesterone? Do you do it daily?

Dr. Toups:           Right. So the the estrogen, the easiest thing to use are the patches, the Vivelle patches, that you change twice a week. They’re more steady state than the Climara patches that are only changed once a week. For people that have Kaiser, Kaiser only prescribes Climara. And what happens with that one is you put on the patch, your level increases, and then over the course of the week, it falls, falls, falls, and then it goes up again. And so it’s not as steady as the ones that you change twice a week.

And one caveat to know is Medicare will not pay for hormones. They consider you’re over 65, you’re dead. You don’t need any hormones. But it’s very affordable for most people to use a good RX coupon and get the the patches, I would say a month’s supply is about $31. And if you’re at a steady dose and you buy, say a three months supply, the cost comes down and in the 20 something dollar range, almost the range of a copay. And I understand for some people, even that is prohibitive, but for most people they’re relatively affordable.

Dr. Weitz:            Do you use progesterone as well.

Dr. Toups:           Absolutely. When you have a uterus and you’re taking estrogen, you’re going to build up a lining and you need the balance of progesterone to keep shedding the lining. Some people say, well, if you’ve had a hysterectomy, you don’t need the progesterone. Well, it’s true. You don’t need it for your uterus, but you do need it for your brain. We have receptors in the brain. We know that progesterone has gaba like effects in the brain and it really affects sleep. And it really affects anxiety. And it’s trophic for the nerves. So after people have strokes, there’s data that high doses of progesterone can help to remyelinate the nerves in the brain.

So progesterone, it’s good for men too, but it’s, typically we don’t replace that in men, we will just normally work on the testosterone, the pregnenolone, and the DHEA. But regarding the cycling and to not cycle, that’s a whole debate, and the risk of cycling your progesterone is that when you stop it, if you’re cycling and you take it for three weeks on, or even two weeks on, you stop it, you could have a bleed, like a period, a menstrual period. And after a certain age, after women stop having menstrual periods, most of them don’t want to have any more periods.

Dr. Weitz:            A silver lining about menopause, right?

Dr. Toups:           And there are some things that are good about menopause, for sure. For the most part, I have my patients pretty much taking it every night.

Dr. Weitz:            So the women get estrogen patch and progesterone Do they get any other hormones?

Dr. Toups:           And let me just say with the estrogen patch, there’s some different ways you can use estrogen. You can get a compounded cream and the cream is more expensive for starters, and you have to put it on one or two times a day instead of twice a week to keep the levels steady, but it works just fine. And occasionally I’ll have people that can’t tolerate the patches. Sometimes as you increase the estrogen it can cause breast tenderness and most people that goes away, but sometimes it doesn’t and they do better on the cream. But patches are easy, inexpensive, they stay on in the shower and the swimming pool and they’re easy to use. So some people will use a what’s called a troche with estrogen. So it’s a compounded estrogen and you put it in your mouth, under your tongue and you’re supposed to let it absorb through your gums.

And I do not like that. The problem with oral estrogen is it definitely has been clearly linked to cancer. And when you take oral estrogen, it’s broken down in the liver into metabolites and can cause cancer. So we want the estrogen to go through the skin where it doesn’t go to that first pass in the liver. Well, when you have a troche, I’ve had people come in on that from their integrative gynecologist. And I say, tell me, do you, when you’re sucking on that thing do you swallow? Because you’re sucking on it, you’re making saliva, you swallow. And they say, yes, of course they swallow. Well then they’re getting oral estrogen.

So that’s one form I do not like. And then the progesterone, you can get bioidentical progesterone these days from the regular pharmacies. There’s generic bioidentical, progesterone. It may have cleaned it up. It used to have peanut oil and things that some women reacted to as allergens. But I would say most people can tolerate just the regular prescription progesterone, which again, if you’re over 65, you can just get a good RX coupon. And usually it’s cheaper to get the progesterone at one pharmacy and the estrogen at another. But if you’re buying them three months at a time, it’s probably worthwhile because the prices can be really different on good RX and different pharmacies.

Dr. Weitz:            Are you recommending testosterone DHEA pregnenolone with women as well?

Dr. Toups:           Yes. For sure. And obviously the.

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Dr. Toups:           Yes, for sure. For sure. And, obviously, the target levels are different in men and women. So the DHEA and the pregnenolone are supplements. And it’s important once you start the supplement a month or two later, be sure you check the level because sometimes they don’t come up and sometimes they’ll come up too high and people’s responses, particularly with the DHEA, can be all over the map.

Some people, like five or 10 milligrams will give them a big boost and some people are on 30 milligrams and not getting enough. And then the pregnenolone as well, that’s kind of all over the map. And both with both of those, sometimes as you correct all other things that you’re working on, you will see their pregnenolone and DHEA levels come up, on their own, from general health and the body getting into a better homeostasis.  So, it’s worthwhile checking those. With all hormones you don’t want too much, right?

Dr. Weitz:            Right.

Dr. Toups:           Now, the testosterone. Definitely some women you want to test the testosterone before you prescribe it because some women make enough testosterone when they’re older. And that testosterone also can change based on the general health. I’ve seen some women that were on testosterone and then suddenly they don’t need it anymore. For men, after a certain age, they’re probably going to need testosterone.

Dr. Weitz:            What hormones do you typically give to men?

Dr. Toups:           So I generally start with the prescription or the compounded testosterone gels. Some men, you can raise the dose and raise the dose and they’re just not absorbing the gels and then you’ll end up needing to go to injections. But it’s easiest and more accessible to start with the gel.

There’s some different formulations of the gel. I have a local compounding pharmacy that makes testosterone in a brand named gel called Atrevis gel, A-T-R-E-V-I-S and they say that there’s data with that that increases the absorbability of the testosterone. And the cost of doing the compounded testosterone is not all that different than the cost of the prescription gels, if it’s not covered. Usually the prescription testosterone will be covered on the commercial insurance for men. Or if you’re under 65, it’s generally covered, but if you’re over 65, sometimes it’s less expensive to get a compounded testosterone cream or gel.

And the injections, they definitely work, but they can drive up the estrogen levels higher and more quickly than the topical will for some people. But they can also be another great option for people that don’t absorb and I definitely use both.

And for the women, let me say for the women, what do you do for women? Well, there is no commercial product of testosterone for women because we just need tiny little doses compared to a man. So the compounding pharmacies do make testosterone in a cream for women and they do make a tablet. I use Belmar Compounding Pharmacy and I usually have women start with a testosterone tablet. And I don’t know if people know what their LDN is like, it’s a little tiny, tiny tablet, and you can use it vaginally. So I have women, when they’re going to bed, pop in that tablet at bedtime and it’ll break down. And things that you insert vaginally are absorbed super well. And so you definitely want to start with a tiny dose. I start with 0.5 milligrams and that tends to be enough for most women.

Again, I’m not trying to get them at the top of their testosterone range, just somewhere closer to the middle of the range. And so that’s a pretty easy treatment for most women. A few women will say that the little tablet doesn’t dissolve. So it’s something with the pH, vaginally, for them. And they’ll find that it hasn’t dissolved fully and then will switch to a compounded cream. But the tablets are super easy and people generally like those.

Dr. Weitz:            And for men, besides testosterone, are there other hormones? Do you ever use growth hormone? Do you use DHEA, pregnenolone?

Dr. Toups:           Yes. I don’t use growth hormones, I’m personally afraid of growth hormones. I feel like it’s turning on something that wasn’t meant to be turned on. I’m not experienced enough to want to mess with that myself. But the pregnenolone and DHEA, yes, there’s pretty well established levels with those things that you can feel safe that you’re supplementing people to the right level. And pregnenolone, I usually shoot for a level of around 100 in people and if it goes a little over that pregnenolone is a pretty forgiving thing, it’s metabolizing into other hormones.

And then the DHEA typically we’ll have men a little higher than women, but maybe a level of around 150 for women and 200 or a little higher than 200 for men. And, again, forgiving, it can be a little lower, a little higher. But if their DHEA comes in at 350, I’ll say, “Oh, you’re on too much, let’s cut you back.” I don’t want to push people to the top of the range.

Dr. Weitz:            Okay. So we’ve been talking about all the things, the inputs that are going to increase brain health. And then we have to talk about the negative things that are going to reduce brain health. So why don’t we start with infections?

Dr. Toups:           Yes. Infections are such a huge thing. And, again, the world is learning about the impact of infections through COVID and the brain. And it’s being reported every day now that they’re doing autopsies on people and seeing that… I just read something yesterday, I believe that they said, there’s gray matter destruction in the brains of people that died with COVID that looks just like Alzheimer’s.

So, what we have been saying and what we do in the functional medicine dementia world is, infections, some of them like to live in the brain. And the ones that go into the brain, when we have an infection, what happens is our immune system gets activated. So, it’s an immune response to an infection that causes the destruction. And that’s exactly what they’re seeing in COVID. They’re saying, “Well, there’s no COVID left in the brain, but we’re seeing destruction in the brain and we know people with long COVID are having brain fog.”  And typically, our patients that seek conventional doctors with brain fog, “My brain’s not working.” What are you told? “We don’t see anything wrong. You have a psychiatric problem. Go to the psychiatrist.” Well, I am a psychiatrist, so I’ve long believed that these people are struggling.

But the world is learning the effects of a virus on the brain from COVID. So maybe that’s one blessing to have the conventional medical community believe that we think it’s important to treat infections, reactivated infections. And one of the things with viruses is in classical medicine, we were taught, viruses, you don’t really treat them. They’re self-limiting and the immune system will keep them in check.

Well, in my world, when I test for all kinds of viruses and typically the IgG antibodies mean a past infection. But when we see the IgG antibody’s really high, in my world we’re thinking, okay, if it’s more than four times the upper limit of normal, that infection has reactivated and it’s waking back up because we know these viruses, they integrate into our body, they live in our body and our immune system keeps them in check, it keeps a lid on it. But if something happens that affects our immune system, which of course happens naturally with aging, things don’t work as well, then the viruses can wake up and start replicating and they’re not kept in check.

So, we’ll test for things like the herpes viruses, the Epstein-Barr virus, toxoplasmosis, cytomegalovirus, mycoplasma, those are all known to affect the brain and live in the brain. And when we see these things elevated, there’s something we’re going to treat.

So I would say, like the Epstein-Barr virus, we know that by age 18, I don’t know the exact percentage, but I would say it’s maybe over 80% of our population has been exposed to Epstein-Barr or mono. And that’s one that we see quite frequently reactivate with any kind of stress and I have protocols to treat it and you can often see people that are fatigued, that are just not functioning great. And when you treat this, you can see people feel so much better. We’ve seen people with chronic fatigue for two years and suddenly their energy’s back and they can do things.

Dr. Weitz:            Do you use antiviral medication prescription? Or do you use natural immune strengthening antimicrobials et cetera?

Dr. Toups:           Yeah. Mostly herbal, except for the herpes viruses. And with a herpes virus is it’s pretty easy to use a long-term suppressive with valacyclovir, or Valtrex. You just have to follow the kidney function in older people because it broken down through the kidney. So you just want to make sure the kidney function is fine and check it a few times a year.  But there was some fascinating studies that came out, I think now it’s been about two years, Dr. Ruth [Az-a-kian 01:00:08] and another one, where they looked at huge populations of people in Southeast Asia and they looked at 20 or 30,000 people, big populations. They found that if people had taken a single course of an antiviral in their lifetime, they had a much lower risk of Alzheimer’s.

Now it didn’t tell us that that antiviral prevented Alzheimer’s, it just says there’s some association here. What we’ve known for more than 20 years, that when they do autopsies on Alzheimer brain, they’ll find like 99% of them have high levels of herpes virus in their brain, and higher than in the general population.  And so there is approved antivirals for treating herpes, which is acyclovir, valacyclovir. The valacyclovir is little less toxic and more effective, from my read and research, then the acyclovir so that’s the one I tend to use. And you just-

Dr. Weitz:            What type of herbal antivirals will you use?

Dr. Toups:           Yeah. I have a beautiful protocol that I’m happy to send you that you can put on the website that I got from Todd Born. Todd Born is a naturopathic doctor who was local in my area until last year and he’s also the medical director for Allergy Research Group, and I sent him a patient that had Epstein-Barr virus to get some IV vitamin C because IV vitamin C is one thing that’s known to help Epstein-Barr. And he wrote me and he goes, “Kat, I could give her this,” but he goes, “I have this great protocol that works for,” like he said, I don’t know, 90, 95% of his patients, I’d say it works for about 80, 85% of mine. And so I gave me this protocol.

And so in all my study groups, we call it the Todd Born protocol since I got it from Todd, but Todd told me, “Well, I got it from someone else,” but he put his tweeks on it so that’s what I call it, the Todd Born protocol. And it’s a combination of some general therapies, which are interestingly homeopathic kind of remedies. And the formula is all available on Fullscript and Natural Partners. And you get three different things, tamarix, acer and… I’m blanking on the third name right now, but it’s three different… it comes in a liquid and you buy a big glass bottle for a few dollars and you pour those three bottles in there, shake it up. And you take a teaspoon twice a day and then we get another product that’s called a Copper/Gold/Silver (Oligo Element), and it’s a little dropper, and you take a dropper of that twice a day.  And one round of that is amazing for so many people. And I tell people, “Look, if you’re getting better but you’re not fully back where you need to be on your energy then do a second round.” And Todd advised to stop it for a while after two rounds, just to give the liver a break.  So, that protocol is usually my go-to. And then I have other protocols where you can use the olive extract and the monolaurin and I forget what the third thing is off the top of my head. These days I have them programmed into my EMR and I put it in a note and say, “Do this.” But that also works well.  So, there’s a lot of herbals that can definitely help the virus and just general immune support. Anything we can do to support our immune systems, starting from the diet on up to the nutrients and the lifestyle factors are also going to help to keep the viruses in check.

Dr. Weitz:            What’s what’s your favorite panel? Do you ever use the Cyrex Alzheimer’s LINX profile?

Dr. Toups:           Yes, we did use that in the study and in practical life it just becomes those cost factors for people, that’s a definitely out of pocket cost. So, for the most part, I’ll order all of the various viruses from Quest or from Labcorp for people and get it that way.  Yeah, I think those immune panels from Cyrex are beautiful and they’re Cadillac panels, you’ve also got to test people’s microtoxins and their metals and their chemical toxins and-

Dr. Weitz:            Let’s talk about toxins.

Dr. Toups:           But before we leave the infections, let’s just say a word about Lyme and tick-borne infections.

Dr. Weitz:            Okay, yeah.

Dr. Toups:           Because those of course reach [crosstalk 01:04:44]-

Dr. Weitz:            How often do those occur?

Dr. Toups:            A lot. Of course it depends on your geography. Where do you live? But here in the San Francisco Bay area, we have become increasingly a Lyme endemic area and especially along the coast up to Mendocino County. And now they’re reporting all the ticks on the beaches that are infected with Lyme here.  So we see it a lot, I would say, in my study, I had 10 patients at my site, at least four of them I treated for Lyme, not one of them knew they had it. And I say there’s Lyme and little letters and Lyme in capital letters. When you have line in capital letters, you’re really sick. I have people come in and they can’t sit up, they have to lay down on my exam table to talk to me, they can’t take the light and that’s Lyme in capital letters.

But for some people, the Lyme will just go right to their brain. And it’s a spirochete, just like syphilis, it’s a relative of syphilis. And we’ve known since the 1800s that with syphilis, you get the sexually transmitted disease, it goes away, you think you’re fine and then down the road, 10, 20 years, you lose your mind. And Lyme does the same thing. It seems to do it faster for people.

So I think any dementia workup should include a good panel of tests for Lyme and the tick-borne diseases. Of course, we see some of the other co-infections as well. And all of those tick-borne illnesses really affect the brain. So that’s something, if you don’t look for it, you may not realize. And our investigator, Deborah Gordon up in Oregon, she lives in Ashland, Oregon, and they apparently don’t have a lot of Lyme there, and she’s like, “Well, I don’t think I should test my patients because they don’t have any risk factors.” And I said, “Deborah, they’re having cognitive problems that you don’t know where they’ve been, test for Lyme.”  So, that is just such a huge factor with dementia. And I really do believe it’s a factor with some of the other neurodegenerative disorders. We need to be testing them with ALS, MS, anything that’s affecting the brain. You’ve got to test those infections. And what happens when-

Dr. Weitz:            How do you treat Lyme?

Dr. Toups:           Oh gosh, that’s a whole long talk and there’s a difference but there was a beautiful study out of Hopkins in this last year and one of my friends and colleagues from my local bay area functional medicine study group was a coauthor on there because he’s a Lyme expert. And they compared a bunch of the herbal medications to the traditional antibiotics use for Lyme. And what they found was what a lot of us already have seen clinically that when you have acute Lyme, when you just got it, take the antibiotics, for sure, no doubt. You go on antibiotics until you get your tick tested, it’s just worthwhile.  But, if you have chronic Lyme, the antibiotics don’t seem to work as well and sometimes people will get better then as soon as they stop, they crash, they haven’t eradicated the infection.  So, using some of the herbal treatments seems to work better. Well, they show that in this study they show that a handful of the herbals were actually quite superior to… they were doing this in cell culture, but the herbals were more effective at killing the virus and they found that cryptolepis could completely eradicate the Lyme persisters.  So a lot of these things will knock down the Lyme, but they don’t get rid of it totally and they’re called Lyme persisters. So, adding the cryptolepis into the protocols is something that I started doing after reading that paper.

Dr. Weitz:            What is cryptolepis? That’s something new to me.

Dr. Toups:           It’s what?

Dr. Weitz:            That’s something new to me. What is cryptolepis?

Dr. Toups:           Cryptolepis? Yeah, and it’s spelled just like it sounds. I wanted to say crypto-lep-sis, but it’s cryptolepis, I-S. And it’s an herb that comes out of Ghana and that herb only grows there so there was a shortage for a while when COVID started trying to get it shipped over here. The herbalist at Woodland Essence we’re at, I’m ordering it from, told me they cannot grow it here. It just won’t grow here. But it’s an earth that’s kind of been in the Lyme toolkit for a while and that was the best thing as far as wiping out the Lyme persisters.  I can send you the link to that study too.

Dr. Weitz:            That would be great.

Dr. Toups:           I think it’s interesting for people to look at because you’ll see some of the other herbs that were quite effective. And I tend to start with things like the Beyond Balance products, they have mixtures of different herbs and you can start with a milder and work your way up so that you don’t make people sick with the treatment. The Byron White products are also effective but they’re more powerful and so some people you can start those and immediately and they’ll have a Herxheimer reaction and feel crummy.  I don’t believe you need to feel worse with the treatment to get better. I think we can do it more gently and help people get better. I do like to give immune support with the Lyme treatments in particular. I use a lot of LDN, low dose naltrexone, for immune disorders, but also immune support for infections.

Dr. Weitz:            So let’s go into toxins.

Dr. Toups:           Yeah.

Dr. Weitz:            So what is some of the most important toxins that you say that negatively affect brain health?

Dr. Toups:           Right. Well, it’s hard to say that one is more important than others.

Dr. Weitz:            We’ve got heavy metals like mercury, we’ve got-

Dr. Toups:           Sure. Yeah. I kind of separate in my mind the metals and the chemical toxins. So we know that many of these metals are neurotoxic.

Dr. Weitz:            Aluminum is one that’s often talked about.

Dr. Toups:           Right, and mercury and lead and, of course, cadmium and arsenic and aluminum, they all can be toxic to the brain. And so we have to be vigilant in our environment. You can test these at Quest and Labcorp. If you get the Genova NutrEval panel they’ll test lead, mercury and it’s cadmium or arsenic.

Dr. Weitz:            Arsenic, yeah. All four of those. Yeah.

Dr. Toups:           Yeah. These can be tested in panels through Quest and Labcorp as well. With the mercury, I don’t like to do the panel on Quest, it does mercury and lead and cadmium and arsenic by itself, because they’ll tell me on the mercury. On that one, they don’t quantify it. They’ll say, “It’s less than four.” Well, if the mercury is three, I’m not going to be happy. The mercury in older people, it should be less than one.  So, less than four, I need to know the number. So I’ll order that as a standalone test, that will quantify the number. And one of my good friends and colleagues looked at all of her patients in one year that came in with cognitive decline and she was saying, “We know what are the factors here?” And one of the things that she found with regard to mercury is that her cognitive patients, on average, their levels of mercury were twice as high as the age match controls. So they might not be sky high, but they’re still higher.  So what does that mean? Well, we know that it actually just reported in this last week that they found in Alzheimer’s plaques, they found metals inside those plaques. And interestingly, they were elemental metals that they were walled off by the amyloid to stop the metals from going willy nilly when they’re charged and damaging things in the tissue.

Dr. Weitz:            That’s bringing up a really important point that is not understood, which is, if you just focus on the amyloid, you’ve not asked, “Why is your amyloid in the brain to begin with?”

Dr. Toups:           Yes.

Dr. Weitz:            As you just mentioned, amyloid is protecting the brain and so, in this case, it’s helping to protect the brain against heavy metals.

Dr. Toups:           Right, exactly. And this is why all of these anti-amyloid drugs are failing, including the new aducanumab. It’s a smoke and mirrors with statistics to say a small group declined more slowly, but they still declined.  I used to run a clinical trials center and I did many trials. And back in, I don’t know, 2008, I did a trial with one of these anti-amyloid drugs. And in our study we could show on the PET scans that it was really diminishing or wiping out the amyloid plaques, but nobody got better. And so there’ve been some drugs that have gone for FDA approval that have been nixed before this one. They’re like, “Well, let’s throw a bone to people and give them this drug because people need a drug.”  Well, no, they don’t need that drug, 40% of people had swelling in their brain with the drug and I think it was 18% of people actually had bleeding in their brain from the drug. Would you give that to your mother? With a 20 to 40% risk of serious brain side-effects and it’s not going to help her?

Dr. Weitz:            Right.

Dr. Toups:           To me, that’s the question. Would you give it to your family? Because I have some doctors saying, “Well, now I have to prescribe it because it’s approved.” No, you don’t.

Dr. Weitz:            If the amyloid is protecting the brain against heavy metals and you don’t remove this heavy metal exposure, then you’re potentially going to make the brain worse.

Dr. Toups:           Which is why we’re seeing the brain swelling and the bleeding. And that was an issue in the study that I did with one of these drugs back then as well. So, we don’t know if we can detox people from all of these factors

PART 3 OF 4 ENDS [01:15:04]

If we can detox people from all of these factors, get rid of their infections, get rid of their toxins, optimize their hormones and their nutrients, maybe then an anti-amyloid drug could help maybe, but not just giving it to somebody where it is protective. That is what Dr. Bredesen’s been saying all along that this is a protective effect. Think of it like a scab, you’re bleeding and then your body makes a scab to wall off that wound so you don’t get infections. When you have an injury, something insulting your brain, it makes the amyloid to protect that neuron. the problem becomes when you have something going on chronically, chronic infections, chronic toxins, metals, then you’re going to make so much amyloid that it just gums up the works and too much amyloid of course, is going to kill the neurons.

Our thinking is, “Well, let’s start downstream, what’s causing the amyloid in the first place?” It brings us to the question of genetics. People know that when you have the APOE4 gene, that you have a significantly higher risk for developing dementia. One of the things that happens with that APOE4 gene is that you will make more amyloid when you have that gene. I have a 33, I don’t have a 4 in my genetics and so, say you had a 24 or a 34 and we got the same infection that went to our brain, your brain would make a lot more amyloid than mine would make. The E4 gene is called a pro-inflammatory gene, it creates more inflammation as well and so people that have E4s, it’s not a death sentence. It’s not inevitable. There are plenty of people that have 44s that don’t get dementia, but you do have a higher risk. We all need to take the steps to prevent these things so we can live a long and healthy life.

But when you have a 4, it’s good to know just so that it’s going to reinforce, you need to really be vigilant about avoiding aluminum in your deodorant or your pans, or these chemicals. Things that you’re putting on your body that have phthalates. I think to me, I use that to just, not to scare people. It’s just like, “Okay, you have this. Let’s make sure we’re doing all the steps so that you stay fine into your old age.” But that is the issue with the E4 is you will make more amyloid with an insult to your brain. Yeah, the thinking of a drug that doesn’t work, hurts people, and we can’t afford is not a wise move in my book. Okay, so we were talking about the metals. I had people, probably a handful of people that had very high mercury in my study, and what do we do about that? Well, the first thing we do is we take them off of seafood because our oceans…

I have some people that say, “I only eat wild caught salmon,” that can still have high mercury levels. Typically, the thinking is if you eat a SMASH fish, and it stands for salmon, mackerel, anchovy, it’s an acronym for small fish, but what you want to do when you eat fish is you want to eat the small fish and avoid the big fish like the tuna. Because the big fish, they live longer, they accumulate more metals from the ocean and they eat the smaller fish, so they’re taking on their metals burden as well. I mean we got everybody’s mercury down in the study, no problem. It was a pretty slam dunk thing. Some people, pretty much I take people off for six months. I’ll check it at three months. Sometimes in three months, it’ll come down. It’s avoiding the exposure and then giving people some liver support to help them with detoxification. I’m a big fan of Avmacol, which is one of the broccoli extracts, sulforaphane with myrosinase. they have beautiful data.  They do a lot of research and they have data even in autism and schizophrenia, showing that, supporting the detox enzymes are helping the brain.

Dr. Weitz:            What product is that?

Dr. Toups:           It’s called Avmacol.

Dr. Weitz:            Avmacol, okay.

Dr. Toups:           Uh-huh (affirmative). A-V-M-A-C-O-L.

Dr. Weitz:            Okay.

Dr. Toups:           Unfortunately, it’s not on Fullscript and Emerson at this point. I know I’ve been nagging.

Dr. Weitz:            Well, there’s other products that have broccoli seed extract…

Dr. Toups:           Sure.

Dr. Weitz:            Are those equivalent or not?

Dr. Toups:           Yeah. I mean I think they’re all good. I know Designs for Health makes one, and maybe Symogen makes one.

Dr. Weitz:            I know that Metagenics has one and there’s [crosstalk 01:20:07].

Dr. Toups:           But I personally like the companies that do research. These guys have research data and this drug first came… It’s not a drug, it’s a supplement, a nutrient. But my friend who runs Intelex DNA is the first one that told me about it and she said, “It’s a slam dunk. When we have people that have brain fog from mycotoxin exposure,” she goes, “We put them on this Avmacol and their brain fog gets better.” I’m like, “Okay, my mycotoxin people need that.” I told my assistant in my office about it, who’s a health coach, and he had had some exposure to mold in his place and he had also been treated before that for Lyme. He and I both got some and I went away to a conference to give a talk and I came back a week later, and I looked at my assistant and I go, “Doug, you look fantastic. What are you doing?” He got a big smile on his face. He said, “It’s the Avmacol.” He said, “It just cleared up things for me.”  I could tell his brain was really clicking, his processing speed was better. He was the poster child for that. For me, it works, I stick with it.

Dr. Weitz:            … glutathione, either liposomal, or IV, or nebulizing?

Dr. Toups:           Yeah. Well, I think all of those things work and they’re all good. The oral one, the liposomal, I mean the jury is still out, even on liposomal. Because if you take it liposomal, it’s supposed to coat the glutathione, which normally is broken down very quickly in the stomach, and how much are you really getting for the expensive glutathione? The liposomal is supposed to coat it and help it get farther along to be absorbed in the small intestine rather than broken down in the stomach, but some people still make a lot of acid and will break it down and they may not get it. I’ve really dug into the research on S-acetyl glutethione, S-A-G and to me, if they’re going to take glutathione, I think that is a better nutrient. They have nice data that with the molecule shape and absorption, that it will get absorbed and they have a nice area under the curve and a nice Cmax with the glutathione. I either use NAC [crosstalk 01:22:38]. What?

Dr. Weitz:            Do you do IV ,or nebulize glutathione to get it directly into the brain?

Dr. Toups:           I have used nebulized glutathione sometimes with acute illness things. All these protocols are already labor intensive enough and expensive enough. But giving some IV glutathione, sure, it’s a good thing. Do I do it regularly for people? No. If they have something acute or they need to detox from a surgery or something, maybe it’s a good thing. But I mean, I’m a big NAC fan and I’m just praying that it doesn’t [crosstalk 01:23:11], that we don’t really lose it from our toolkit with the FDA making noises about taking it off the market. The NAC will, of course just gradually convert into glutathione and it has a much longer half-life and it lowers glutamate, which is an excitatory neurotransmitter, so helps people, with great data, with OCD and bipolar. There’s just so many benefits with NAC that… Okay. Yes, go get an IV glutathione push, sure. It’s fine, but do you need to do that? I don’t think so.  I think you can still detoxify things without it, as we saw in the study, getting the mercury down.

Dr. Weitz:            Do you use binders as well as part of your detox protocols?

Dr. Toups:           Yes. It’s kind of a mish-mash. People that have viruses tend to have mycotoxins. People have mycotoxins and viruses, and this kind of mixed in with the chemicals. Binders of course, are our mainstay for binding the mycotoxins. They also can bind the metals. There’s a variety of binders and sometimes different ones for different things. We didn’t talk yet about mold and mycotoxins, but we know that that is a huge driver of brain degeneration for some people. Some people, it doesn’t seem to bother and other people, it can be deadly for their brains. I will layer in multiple binders. The jury is still out on a urinary mycotoxin panels. We have two companies that are doing urine mycotoxin, Great Plains Labs and RealTime Labs. My friends that are on the board of ISEAI, you know ISEAI, International Society for Environmentally Acquired Illness. It’s a wonderful organization that was just started. I think we’re now in our third year maybe.

Dr. Weitz:            Okay.

Dr. Toups:           But it was looking at environmentally acquired illnesses, so mycotoxins, infections, and toxins. Actually, they did a drive and asked us to donate money, and they’re doing split samples with mycotoxins right now, and looking at the difference between the panels. We need that kind of information. We don’t know how reliable it is. The thing with the urine mycotoxins is that sometimes you’ll see zero, because the people are not excreting anything. They’re not detoxifying well. Nothing’s coming out. It’s all in their system and then, when we start doing things to support their detox pathways, you see this with the mycotoxins and you see it with the chemicals. Sometimes they don’t have chemicals, but as you’re doing more things to excrete those chemicals, you’ll see the numbers go up on the chemical toxins before they go down. In chemical detox, if you have a lot of chemicals, it’s going to be a lifetime thing of what can you do to keep detoxifying your body and trying to get rid of these chemicals?

We know that there are certain genetic factors that make you not detoxify things as well, MTHFR is a big one. That if you have two copies of that, you’re not going to make the same glutathione as other people, and you can have snips in the glutathione genes. There’s multiple things that… Or the panels now have the GST genes, GST yeah. You can look at a panel of your detox genes, but you don’t necessarily need to know that. Some people, I would include myself in this, I’m a poor detoxifier. I accumulate things, so I’m constantly taking things for detox, doing my sauna. The sauna and the sweating is one of the best validated things for lowering our chemical burden and our metal burden. Stephen Genuis is an MD, researcher up in Canada. I think it was a couple of years ago, at Integrative Medicine for Mental Health, he came and he was showing us all his data.

But you can Google his name and he’s got a bunch of papers. I mean he’s looked at how much of these various chemicals and metals do you excrete in your urine and your sweat, and the sweat is the best detoxifier for most of them. That’s a mechanism that, in the past, we had. It gets hot, in the olden days people didn’t have deodorant, and many cultures use sweating, traditions like the sweat lodges, the baths, that’s a purification ritual, but actually has important benefits for our bodies. These days, they’re making inexpensive saunas that you can get, like the little bubbles with the infrared heat source and you sit on a chair. They’re not fancy and you have to look for the ones that are lower in the EMS. But definitely, sweating is a huge thing. Now that the gyms are reopening, sweating as much as possible.

I tell people the caveat though, when you’re sweating, you need to have a towel and wipe off the sweat as it comes out, because you don’t want it to reabsorb it. Wipe it off and then, when you’ve finished your sweating session, go jump in the shower with some soap and wash off because you’ve just now mobilized all those toxins. You don’t want to take them back in. But the sweating and some Avmacol and liver support and binders, all of those things can help to lower the burden. But I would say with the chemical toxins, we did the Great Plains Labs’, TOX test for our study at the beginning and the end and even though people were doing lots of binders and lots of sweating, you would see some things come down, but in nine months they were not gone. Those things have accumulated over a lot of years and it takes a while. I figured at my age, it’s a lifelong thing I needed to keep up with. Detox is going to be an ongoing thing.

Dr. Weitz:            We’re going to have to wrap here. Just a final question. Practically, it must be difficult to get these patients with cognitive problems to take a bunch of supplements and do a bunch of protocols, isn’t it?

Dr. Toups:           Yes. It’s difficult and of course, it’s costly to take a bunch of supplements as we know, and trying to distill things down to what are the most important things to take. That is where you need to individualize and where you could use help of a physician, or a naturopath, or a health coach. Somebody that understands these thing. I’ve seen people, Dr. Bredesen’s first book, he listed all these great nutrients and then I will read the Facebook support groups and see where people are struggling, and I’ll read people saying, “I’m spending $1000 a month and I’m taking all these supplements.” And I just think, “Oh no, you don’t need to take them all.” That’s where it really helps to test and figure out what do you need. Now, everybody needs mitochondrial support. To me, that’s foundational and the mitochondria with aging, they just start declining rapidly. Certainly after 50, they’re going down. [crosstalk 01:31:09].

Dr. Weitz:            What is mitochondrial supports?

Dr. Toups:           There’s a lot of nutrients that are well-validated for mitochondria. So CoQ10, acetyl L-carnitine, lipoic acid, I use the R-lipoic acid form, PQQ. Those are some of my favorites.

Dr. Weitz:            Okay.

Dr. Toups:           There are some combinations of those things available and I’m actually working on a formula, because to me that’s the most important thing of all. I’m pretty close to finalizing with my formulator a product that we’re going to hopefully have available that is going to have all of those things that you can just take a scoop of something instead of five or six supplements.

Dr. Weitz:            Right.

Dr. Toups:           But I think the mitochondria, aging or chronic disease, good for everyone. On NutrEval and even [inaudible 01:32:09], I measure CoQ10 levels. I mean for cardiovascular, the CoQ10 is essential. We want to see that number at least above one, and I know in studying with Alex Vasquez in the old days, I remember this so well, he said, “The dose of the CoQ10 is limited by the size of the pocket book.” Meaning take as much as you can afford. It’s that good of a nutrient.

Dr. Weitz:            Right.

Dr. Toups:           But then, beyond the mitochondrial support, that’s essential and like acetyl L-carnitine that turns into acetylcholine in the brain. That is the one of the primary neurotransmitters involved with memory. But this is where it does help to work with somebody that can test and guide you so that you are taking what’s right for you, and that you’re not throwing away money on something you don’t need. But one of the things that we did with the study, when people have cognitive decline, they need support and it’s true, they can’t do this on their own. What we found is sometimes the caregivers, their spouse, maybe the spouse was great and could really help and sometimes, especially I saw in places where people were living in mold in their homes, that the spouse was struggling as well, cognitively. As part of our study, the patients work with a nutrition coach and a health coach, and an exercise coach. We didn’t even talk about exercise, but that’s a whole other topic. Exercise for the brain and the heart is essential.

Having that kind of support upfront to have people get started on this just made it a Cadillac program. Having an exercise coach, that’s changed my view of… Moving forward, I’m insisting that people get some sessions with an exercise coach, optimize what they’re doing, make sure they learn how to do high intensity interval training, that they’re doing the whole gamut of aerobics and strength training and balance training. We took people that had never exercised in their life. I had one in my study, never exercised, and now he loves his exercise and it has paid off for his brain, of course.

Dr. Weitz:            Right.

Dr. Toups:           Yeah, I think getting guidance. It’s not easy, but once you sort through what you need, then people can get on autopilot. The people that finished my study, they need to be followed up once in a while, but they don’t need a high level of care. They don’t need to take an expensive drug forever.. They get into a rhythm. Once you wake the brain up, it’s just a matter of keeping it there.

Dr. Weitz:            That’s great. Awesome. This was a great discussion, Kat. How can our listeners find out more about you and contacting you?

Dr. Toups:           Yeah. I can give you the links. I have a Facebook page. You can put my name, Kat Toups in. I have the personal one, but there’s one that says, Kat Toups, Functional Medicine, Psychiatry, and Dementia. I try to post interesting and hopeful articles on there, related to the brain and rehab of the brain. I try to stay away from the doom and gloom. To me, it’s like, “What can we do?” There’s so much we can do to get our brains back. My website, it’s a place to stay in touch. I’m going to put something there to start offering people any eBooks, so I have their emails that I can notify people when my dementia book is ready. That would just be dementiademystified.com. That’s the name of the book and that will link you to my website. But I think the Facebook for me, I can’t do all of those different modalities that everyone does, but I try to use my Facebook group to put interesting and hopeful research.

Dr. Weitz:            Awesome. Thank you, Kat.

Dr. Toups:           Well, thank you so much. Thanks for helping us to get this word out. Actually, I’ll give you the link for our dementia study. As you mentioned, 84% of the people in our study got better and the average, we didn’t even talk about the study, but the average… We track the MoCA scores, which is like a mini mental status scores. The MoCA is better for picking up mild cognitive impairment, which we were targeting people with mild cognitive impairment or early dementia. We do have people benefit with more advanced dementia, but you’re peddling farther upstream the more you let your brain go down. The sooner we can get people to take steps first to save their brain from down, but if you’re having memory problems, just know there are things you can do about it and if you think you’re having problems, you probably are. But I’ll give you the link for the study and it goes through all, we’ve talked about a lot of them here, but even not quite all of them. We haven’t talked about brain training. We haven’t talked about meditation, mindfulness kind of thing.  They all come together and what I found was the people that worked the hardest, all those parts of the protocol come together to help you heal and to feel well and so it’s just exciting to know. I tell people, dementia is not a death sentence. That’s what I want to leave people with. If you have a diagnosis, it’s not a death sentence. There’s so many things we can do to help your brain now.

Dr. Weitz:            That’s awesome. Such a positive message. Thank you.

Dr. Toups:           Thank you so much for having me. I appreciate it.

Dr. Weitz:            Absolutely.

 

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Dr. Weitz:            Thank you listeners for making it all the way through this episode of the Rational Wellness Podcast. Please take a few minutes and go to Apple Podcasts and give us a five-star ratings and review. That would really help us so more people can find us in their listing of health podcasts. I’d also like to let everybody know that I now have a few openings for new clients for nutritional consultations. If you’re interested, please call my office in Santa Monica at 310-395-3111. That’s 310-395-3111, and take one of the few openings we have now for an individual consultation for nutrition with Dr. Ben Weitz. Thank you and see you next week.

 

 

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Dr. Joel Gould discusses How Lowering Deuterium Levels Promotes Better Health with Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] 

 

Podcast Highlights

1:22  Deuterium is heavy hydrogen. There are actually three different forms of hydrogen. Normal hydrogen contains a proton and an electron. Heavy hydrogen or deuterium contains a proton, an electron and a neutron.  Tritium contains a proton, an electron, and two neutrons, though this version is rare and radioactive and is often produced in nuclear reactors.

9:04  It is common for elements to have different isotopes resulting from having different numbers of neutrons. Hydrogen is very unusual and this is why deuterium is the rate limiting step in our life.  The more deuterium  you have, it speeds up how fast your life goes. Deuterium dictates lifespan.  If deuterium did not exist in our environment, our bodies technically would be immortal.  This is what the ultimate root cause of aging is, according to Dr. Joel Gould.

11:32  Metabolic syndrome is a big focus of poor health and this is really about your mitochondrial function, according to Dr. Gould. The mitochondria resulted from the incorporation of bacteria-like microorganisms known as archaea into our cells via endosymbiosis.

 

 

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Dr. Joel Gould is a dentist with an interest in Functional Medicine. Dr. Gould graduated from the University of Western Ontario in Canada and practiced dentistry in rural Canada and in Vancouver for 10 years before relocating to Los Angeles. Dr. Gould’s practice is called Modern American Dentistry and he has practices in Manhattan Beach and in Woodland Hills. His website is https://www.modernamericandentistry.com/

Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

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Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting-edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website doctorweitz.com. Thanks for joining me and let’s jump into the podcast.

Hello Rational Wellness podcasters. Our topic for today is deuterium. What is deuterium? What is its significance? How does it impact our health, and what should we do about it?  Here to speak with us is Dr. Joel Gould. He’s a dentist with an interest in functional medicine, and he calls his new health and wellness paradigm Modern Hunter-Gatherers.  Dr. Gould has been practicing dentistry in Canada and the United States for over 30 years.   Dr. Gould focuses on snoring, insomnia, and sleep apnea in a sleep restoration program at his practice in Manhattan Beach, California.  And Dr. Gould is back for his third appearance on the Rational Wellness Podcast. Joel, thank you so much for joining us again today.

Dr. Gould:           Great to be here again. Thank you.

Dr. Weitz:           So, what the hell is this deuterium stuff?  What is deuterium and why should we care about it?

Dr. Gould:           Okay. So, this is one of those things, this is a word it’s called deuterium and it’s named after the Greek word deuteros, for double. So this is, I think, one of the most important topics in all of medicine, because this impacts everything. And this is a hard subject to get your mind around, because even just the word deuterium it’s not on anyone’s vocabulary, it’s not on people’s radar.  But over the last couple years, so last time we spoke about this was a couple years ago and it’s funny because my knowledge and understanding of what deuterium is has really grown a lot. What people need to think about is over the last couple of years since you and I spoke, what’s become more and more popular is the understanding of a couple things.  Number one, a ketogenic diet or a high fat diet. Number two, intermittent fasting. And number three is the understanding that sugar really is a villain and is bad for us. So, those are the things that have slowly started to make their way up into our consciousness from maybe like a a bigger picture.  People are… you can see it on the labels, made with less sugar and then now the last component is we’re having this plant based stuff really creep up. And I definitely call it a green washing. Everybody wants to be healthy and when you call something plant-based, does that make it healthier for you as a person and is that healthier for the planet?  And all these things really intersect in our health when it comes to how we make energy in our mitochondria, and that’s the area that we need to look at when we think about what is deuterium. So, for the majority of your people listening they understand molecular biology and how the different chemicals come together, but I want to do a little refresher course on water and say what is water?  What are the three forms of water that exist on this planet? Because there’s definitely more than one form of water. And this is where it gets confusing for people, because they’re going to call deuterium a molecule. It’s an atom or an element, all right?  So, a molecule is a combination of atoms and water is a great example of a molecule.  It’s H2O, it’s two hydrogen atoms with one oxygen atom.  And we know this and our body is a certain percentage of water and the food that we eat, there’s water everywhere. But that water can take on three separate forms. So when I say three separate forms, this shouldn’t be a big deal, but it is. Everyone’s heard of heavy water. The discovery of deuterium in the 1930s, 1938, by actually a really cool guy, this scientist-

Dr. Weitz:            Has everybody heard of heavy water? I’m not sure a lot of people have heard of it.

Dr. Gould:           Well, I think with the Chernobyl mini series, and heavy water is what’s used to make nuclear weapons. It’s what’s used to make uranium that can be used either to fuel power plants or to make bombs. And the process is the enrichment of uranium, and it’s adding extra neutrons.  So, we have to pause and say to your audience, do this real quick, everything that you see around us, this table, this computer, is made of three basic subatomic particles, electrons, protons and neutrons. You’ve got electrons, which are a negative charge, protons, which are a positive charge, and neutrons which are neutral.  And every single element in the periodic table of elements is a combination of these three subatomic particles. When we take these subatomic particles we get an atom. And where we could break these down, each of these subatomic particles could be broke down further, I don’t really care. Because if you really think about it, Einstein said it best that energy and motion creates mass, and everything is just energy locked into motion.  So, if we keep on trying to break down particles, we’re just going to get smaller and smaller bits of energy that are locked into motion somehow. And there’s a certain aspect to the laws of physics that are kind of magical, because certain things exist. Gravity, we can see gravity with the rise and fall of the tides, so we know gravity exists. It’s kind of like why should it exist? That’s one of the laws of physics that happens to exist in this universe.

So, the laws of physics dictate the way the particles come together. We can look at the periodic table of elements, and we look at hydrogen is the simplest and most abundant element in the universe. Hydrogen is made up of one electron and one proton. Now every single element on the periodic table has isotopes, and an isotope is a different version of that element.  And we know there’s different versions of carbon, there’s different versions of oxygen, but they vary only in the amount of neutrons.  So, when you have something like carbon, you’ve heard of carbon dating, you know that we’re using a different version of carbon so we can see the difference between the two atoms, and we can trace this.  But the thing with a carbon is that, carbon is 16, I believe, or 14, and carbon dating is done with carbon 16. So, there’s two extra neutrons, it doesn’t really change the properties of the atom itself or the molecules it gets incorporated into.   It’s not a big change. So, water is found in our bodies and it’s made of H20, but the hydrogen could be a regular hydrogen, it could be deuterium, which is hydrogen with an extra neutron. And there’s a third form of hydrogen called tritium and that’s radioactive. That’s not naturally found anywhere on this planet, except maybe in nuclear reactors. And that’s something that we don’t have to think about.  We only need to think about the two versions of hydrogen that are here on this planet, on the moon, on Mars, and that is hydrogen, regular hydrogen, called protium and its basic main isotope, which is deuterium. And the biggest issue is that when you add an extra neutron to hydrogen you double the weight of that atom. And when we think about our biologic systems, we are carbon based, we’re organic life.  Carbon is covered in hydrogen. Because of the way carbon is structured, it has the ability to bond with four different atoms. And those are often just hydrogens and we see so much interaction in our biology through amino acids of how proteins fold, hydrogen bonds. So, if there’s hydrogen, if we replace it with a deuterium it profoundly changes the way anything that it’s incorporated into exists.

So, the three forms of water on this plant are H20, HDO, and D20. So, heavy water is very, very infrequently, if ever really found. If you’re looking in the ocean, it’s going to be .000, it’s a very, very small amount. The majority of water is going to be H20 or HDO, all right? And so wherever there’s more deuterium we kind of want to be interested. So deuterium itself is simply the name of a stable hydrogen isotope, and the reason I say stable is because it’s not radioactive, it’s not emitting radiation, and this is normal. Now, scientists know all about deuterium-

Dr. Weitz:            Just out of curiosity. When we look at the other elements, do any of them have neutrons, or is neutrons added or do the versions that contain neutrons just a different… an eccentric version of those elements?

Dr. Gould:           Yeah, so you have to think of mother nature as kind of sloppy, and when the Big Bang happened or when any intense explosion happened, the elements that we have, have a variety of different neutrons. I think carbon’s got a lot of different isotopes. So, isotopes are really normal in nature. Very, very normal. It’s just that hydrogen is so unusual, and I think I said this on one of our podcasts is that deuterium is the rate limiting step in our life.  And so it’s really interesting, because I still see it this way, is that ultimately when you dig into the science there’s a lot more that’s been aggregated and put together now that you can more easily find on the internet. And when you start to read some of these studies, they’re basically the increase in deuterium speeds up how fast your life goes. So, deuterium dictates lifespan.

So, the more deuterium that you have in the environment and coming into your body, the quicker your life is going to pass. And it starts to become a mind-bending understanding of reality, because biologic systems on this planet were designed around deuterium. Because we can’t get away from this, this is the difference between zero and one. If deuterium did not exist in our environment, our bodies technically would be immortal.  This is what the ultimate root cause of aging is. We talk about the theories of aging, the free radical theories. These are all legitimate theories of aging, but you have to understand if you dig deeper one level you’re getting into some of the root cause of why these free radicals are damaging us, and deuterium is there at every turn. And deuterium will change the chemistry of anything it’s incorporated into, because it changes the intensity of the bond, changes the bond angle, it changes some of the properties.

Heavy water and semi-heavy water, they have different boiling points, they have different melting points. And if you have heavy water in an ice cube, if it’s heavier deuterium, it’ll sink to the bottom, it won’t float like regular ice. Pretty interesting stuff. But where this really comes into play is that this is what’s messing up biological systems. So, it’s one of those things that’s extremely important.  And ultimately, so here we go, we’re looking at what has come to the surface of everyone’s health these days? Metabolic syndrome, metabolic disease, number one. And what is that? It’s your mitochondrial function. So, all these things are starting to really come together and more and more people are talking about these metabolic diseases. Of course, because we’ve got COVID.  Who are the people who have the worst results from COVID? Those are the people with metabolic dysfunction.

Dr. Weitz:            Now when we think about metabolic disease, I think a lot of us rather than thinking of mitochondria, we think about blood sugar, we think about insulin resistance, we think about that whole aspect of health.

Dr. Gould:           Right. Well, metabolism and metabolomics, the measurement of your health through metabolism, is really all mitochondrial function. And you have to really think about how we’re formed. If we want to really know where this story starts, aside from the beginning of the universe when all life was created, we need to think about how life evolved on this planet from being unicellular to multicellular.  What was the big invention? What was it that changed life on this planet from a single cell to be allowing for multicellularity and the growth of more complex life? And that is the introduction of the mitochondria, and the idea of endosymbiosis. So, we know that mitochondrias have a double membrane. We can assume that at some point in time one single cell organism engulfed another and that’s endosymbiosis.  And over time the development of the mitochondria, really, this is the universal power source for nature. All nature powers the biologic activity of us and plants through ATP, adenosine triphosphate. This is something we learned about in high school, but you need to understand-

Dr. Weitz:            Is it generally thought that the mitochondria is the incorporation of a bacteria into one of our cells?

Dr. Gould:           That’s right. Right. So, there’s the chloroplasts, the mitochondria are very similar. And the idea is that it’s the archaea, the archaea was engulfed in and over millions of years the system of generating energy really took root. And it all comes down to how does a mitochondria, whether it’s in you, or your dog, or in a plant, how does mitochondria generate ATP?  And ATP is the universal currency of biologic function. How do you do anything? Well, unless there’s osmosis or natural chemical gradients to activate anything, you have to add that phosphate with a high phosphate bond onto anything. And when you add that phosphate onto anything, it changes the actual conformational shape that creates a change in an enzyme, or a protein.  And that’s how we do all work. So, it’s so bizarre that we shrink down to the most micro mechanical level of how we produce energy. And a perfect example I want people to think about is you’ve seen motor proteins. You may have heard of dynein and kinesin. These are the two most known. There’s so many different variants. These are the little motor proteins that walk on the cables that are in our bodies, and this is some real-

Dr. Weitz:            Can you repeat those?

Dr. Gould:           Sure. Dynein and kinesin.

Dr. Weitz:            Okay.

Dr. Gould:           So these are motor protein enzymes.

Dr. Weitz:            Motor protein enzymes.

Dr. Gould:           Right. So, there’s all different types of enzymes and these particular enzymes they use ATP per step. And if you Google this, you can see it’s pretty fascinating stuff. You’ll literally see what looks like feet walking on the cytoskeleton cables, and what’s happening is this motor protein is actually attached to a vesicle that’s transporting something of value down to where it needs to go.  And the best example I can give you, because this is related to my work in sleep apnea, is the production of acetylcholine. So, to make acetylcholine you have to have an enzyme called choline acetyl transferase. This enzyme in the neurons of your brain is actually made in the soma. So, this enzyme is made in volume in the soma, the body of the neuron, and then it’s attached to a vesicle.  And then this little motor protein walks this all the way down to the synapse where that vesicle is offloaded and then the actual enzyme itself goes toward making acetylcholine to be put into vesicles so that those vesicles can move towards the synapse and the nerve can transmit the signal. And if we don’t have enough acetylcholine, we’re not getting proper nerve transmission.

So, this is just one example of one enzyme, choline acetyltransferase, and every step of that motor protein is powered by one molecule of ATP. So, literally a molecule of ATP bonds to this enzyme, causes a conformational change, and this thing takes a step forward. Another ATP comes in and takes another step forward. So every step of this motor motor protein is run by ATP. If you don’t have enough ATP in your body, you’re done for.  No nerve can function properly, no immune cell can transcribe the right proteins to make the right things if you don’t have enough ATP. So, every bit of dysfunction that comes along with the human body is mitochondrial. We are making this ATP on a second to second basis. Cyanide poisoning, how long do you die? In 30 seconds, you’re gone. So, without the second by second production of ATP, adenosine triphosphate, no life exists.  And this energy form is so universal, just think about like when you go to Europe you have to take your adapter, because you can’t plug stuff in. This is mother nature’s currency of life. In this particular universe the way things are ordered, this is the fuel. It’s made by a rotor that spins at 9,000 RPM inside the inner mitochondrial membrane of your mitochondria. Every cell has thousands of mitochondria and all cells have mitochondria, except for red blood cells.

Why do red cells not have mitochondria? Well, red blood cells are subjected to the highest levels of deuterium in the body, and if red blood cells had mitochondria, they’d get killed. Deuterium is concentrated in the blood, and that gets us into a whole host of questions about why? What are we doing with it? Why is this there? But we go back to the mitochondria, that deuterium damages how this actual rotor that spins inside the inner mitochondrial membrane and it slows the production of energy.  Anything that lowers your ATP reduces your health. Anything that increases your ATP improves your health. If you cannot produce ATP, you’re going to become unhealthy, and that’s what metabolic disease is. From powering the sodium potassium pumps in your body, to the active transport enzymes in the blood-brain barrier that are actively taking up vitamins and pumping them into your brain so your brain can function.  Any single system without enough energy is going to work poorly. You could have the best systems, you can get the fanciest house in the world, but when you plug it into the power grid, if you’re getting a weird signal, you’re not getting enough energy, all of your appliances are going to start to malfunction. You just won’t necessarily know. You’d be looking at the hardware saying, “Well, my dishwasher didn’t work, or my TV’s got snow on it,” you’re not thinking about the power source coming in, you’re thinking about the specifics.

Dr. Weitz:            Now, aren’t there a lot of things that affect the production of energy? We have the electron transport chain, we have coenzyme Q10, we have a whole series of factors that affect energy reduction.

Dr. Gould:           We do. But we want to think about deuterium in a completely different way, because when you think about the Krebs cycle, you think about how many enzymatic steps is there to produce ATP? You’ve memorized that at some point in your career and you’ve probably hopefully forgotten it, but so awfully expensive and big series of steps. Each one of those enzymes has been specifically designed to deliver and replace a hydrogen that could be deuterium, with one that your body knows is not deuterium.

This is how all life evolved on this planet. It evolved around deuterium. It evolved around this stable hydrogen isotope that’s a part of our world. And why? What’s so bad about it? Well, it slows life down. When deuterium gets incorporated into enzymes, they slow down their function. But worse than that, you know that enzymes all function based on their shape.

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Dr. Weitz:          I mean you can tell me that deuterium slows down my mitochondrial production of ATP. Is there data that really shows unequivocally that that’s what happens?

Dr. Gould:           Yes. Not only that, there’s some good scientific evidence out there and there’s never proof of anything, but I want you to understand something. So, we’re going through all these series of what’s the hot topic now. I think that you’ll agree at this moment in time, industrial seed oils are now the new villain, because everyone’s looking into this massive increase in obesity, chronic disease, diabetes, cancer, heart disease, and dementia.  These are the modern diseases. When we look at populations that live for a long time, where this whole deuterium stuff originally came from was in Northern Russia, in Siberia, in the Hunza, a population in the high Pakistani mountains, there were populations that were living a very long time. There was a lot of people who were reaching the age of 100, and they went and measured the water, the deuterium content of the waters people were drinking, and it was 90 parts per million.  What does that mean? Water that you’re drinking from the tap is 150 parts per million, ocean water is 155 parts per million. Your body is at 130, 135 parts per million, depending on how healthy you are. And so if you drink water that’s low in deuterium, we see this literally translate into living longer and healthier, less cancer. There’s a lot of experiments out there where they gave animals with cancer low levels of deuterium in their water and seeing a decrease in the cancer rates.  This is something that is called the kinetic isotope effect. You can Google it. The kinetic isotope effect is the idea that when an enzyme is functioning, if we can slow down the actual reaction rates and times of the enzyme by increasing the deuterium in the water that the enzyme is functioning, because everything in your body is happy in an aqueous solution. So, when you flood your body with deuterium, and that’s sugar and carbs, especially high fructose corn syrup, you’re overwhelmingly water.

Dr. Weitz:           And they notice it because they have a lot of water in them, is that why?

Dr. Gould:           No, because they’re very high in deuterium. Those are the foods.

Dr. Weitz:           Why are sugar and carbs high in deuterium?

Dr. Gould:           Well, that’s a great question. So, when did we start eating sugar, carbs and grains? When did that happen?

Dr. Weitz:           Well, it depends who you talk to.

Dr. Gould:           Right. Farming. So, maybe 10,000, 12,000 years ago we used to eat a diet that was primarily ruminants. And we’re omnivores, so we’ll eat seafood, we’ll eat almost anything, but this is where we’re coming into the big discussion of the plant-based life. And what I’m saying is that all misinformation aside, anything that you put in your body that has a lower level of deuterium is healthier food than with a higher level.  If your body is at 130 parts per million and you’re eating foods that are much lower than that, you’re literally allowing your body to get rid of more deuterium because of the osmosis effect. So, deuterium hydrogen exchange at a very reliable rate. In fact, deuterium hydrogen exchange is what all physicists and chemists use to gauge reaction rates. This is something that’s very [crosstalk 00:24:59].

Dr. Weitz:            So, we have a glycemic index, right? You can look at a chart and you can see what the blood sugar effect of different foods are. So, I can look at a glycemic index chart and see that the glycemic index of rice is 80. Is there a chart somewhere that will show the level of deuterium in different fruits?

Dr. Gould:           So, some of that information is available. You have to understand that there’s only a specific amount of people who are working on this. I have seen very conflicting results, so just what are the lowest deuterium foods on the planet? Beef tallow. I’ve heard it called to 105 parts per million.

Dr. Weitz:            You’re talking about beef fat?

Dr. Gould:           Yes, beef fat. The fat from beef. And so, again, let’s simplify this. So, you’re seeing this and you’ve been hearing this carnivore diet, when I gave up vegetables, when I gave up carbs, I got so much healthier. What is it that is when people-

Dr. Weitz:            Your fellow dentist, Al Danenberg, who is using a carnivore diet as part of his anti-cancer approach, and it seems to be working really well.

Dr. Gould:           Why is it anti-cancer? Because carnivore, but it’s got to be grass-fed ruminant meat, so not chicken and pork, they’re mono-gastric. If you feed them high-deuterium foods, they’ll put on extra deuterium.

Dr. Weitz:            Monogastric gastric?

Dr. Gould:           Mono-gastric, yeah.

Dr. Weitz:            What does that mean?

Dr. Gould:           So, how many stomachs they have. So, humans evolved eating the meat of ruminants. Started out when we cracked the bones open, this is the food that is the lowest in deuterium, and that’s why we had a terrible crash in our health when we went from being hunter-gatherers to being farmers.

Dr. Weitz:            So, you’re not just saying that we ate a percentage of meat, but we ate a percentage of cows?

Dr. Gould:           Well, so initially we-

Dr. Weitz:            Didn’t it depend upon where we lived?

Dr. Gould:           It does, but so ruminants that-

Dr. Weitz:            I mean if you were a Greenland Eskimo, you didn’t eat any ruminants?

Dr. Gould:           Sure you did. Sure you did.

Dr. Weitz:            Are whales, or-

Dr. Gould:           No. No, no, no.

Dr. Weitz:            … seals are ruminants?

Dr. Gould:           So, no, but I’m talking about the evolution of hunter-gatherers with red meat.

Dr. Weitz:            Right, but I mean some of us ate red meat, and catching animals was not an easy thing back then either.

Dr. Gould:           Right, right. My point is that, ruminants eat green growing grass, and they have multiple chambers in their stomach that will take away the deuterium. The bacteria will use it as their food source, and the meat that gets onto ruminants is extremely low in deuterium. That’s why beef and grass-fed animal fats are so healthy. You feed an animal, so that’s their natural food.

All these ruminants, they evolved on the grasslands, the savannas of Africa, the North American Plains, the buffalo, these are the animals that are eating food, they’re chewing their cud, they’re really filtering all the food, and so that’s why their meat is the healthiest.

Dr. Weitz:            Or maybe because they’re high in Omega-3s, because grass is very high in Omega-3?

Dr. Gould:           That’s correct as well. So, we’ll go back to the actual mitochondria, and so the rotor that spins is generating energy. And the more deuterium you come in, the slower that energy is generated. So the actual damage… Now there’s an added secret culprit here that I don’t know that you and I have discussed before, I’m sure that you’ve had people on your show talking about glyphosate?

Dr. Weitz:            Sure.

Dr. Gould:           Okay.so, the problem is I don’t think that you can buy a lot of refined carbohydrate processed foods that aren’t also containing glyphosate, because-

Dr. Weitz:            Well, I mean the cow’s probably exposed to glyphosate too. Everybody on the planet is, right?

Dr. Gould:           Yes. So, you can’t spray glyphosate on grass, because the grass will die. You could do that, but no one is taking grass and desiccating it with glyphosate and feeding it to a cow. But in any event, it’s the corn grain and soy. Corn specifically, your corn fed animal. Now, it’s still the healthiest food on the planet to eat red meat, even if it’s corn fed, it’s just that if you had a choice it’s better if they’re grass fed. So the glyphosate is going to get into that cow, but less-

Dr. Weitz:            So they’re healthier to eat than broccoli?

Dr. Gould:           Yeah, I believe so.

Dr. Weitz:            Okay.

Dr. Gould:           And it depends, it’s much more nutrient dense. For how many months out of the year do people in northern countries… if you’re hunting reindeer and there’s no broccoli growing up at that time of year. So, broccoli and where’s it coming from? Is it organic? Is broccoli healthy? It depends on what you mean by healthy.  Are vegetables healthy? In my opinion a lot of them aren’t healthy. You know a lot of vegetables have anti-nutrients, you know the carnivores are saying vegetables are trying to kill you they have all-

Dr. Weitz:            Yeah, except there’s more studies showing the health benefits of fruits and vegetables than there are of anything else.

Dr. Gould:           Okay. So, I’m going to suggest that the-

Dr. Weitz:            And you think the animals want to get killed? They’re not using similar strategies?

Dr. Gould:           I’m not sure. I’m not sure what you mean when you say that. Of course animals don’t want to get killed.

Dr. Weitz:            Well, I mean there’s this theory that the plants are trying to keep getting eaten so they produce these chemicals.

Dr. Gould:           Right. Well, okay, listen, you follow the same circles that I do and you know that we’ve really drilled down on what’s… Okay, so I want to ask you this. So, is sugar the root cause of heart disease? Is that the root cause? Is sugar the root cause of heart disease?

Dr. Weitz:            Well, I don’t know that’s the only cause, but I think it is a cause.

Dr. Gould:           It is a cause. So, I think we’re both in agreement that health is very multifactorial, and to say one thing causes one thing, or one thing causes everything, scientists don’t think that way. But we’re always looking for a scientific study to take one thing and one variable and say, “This is it.”  So, when it gets to some of the studies on how healthy vegetables are, we can go back to the Ancel Keys days who fudged all of his data, saying that all of these people in the blue zones they’re not eating meat, they’re eating all these vegetables. You cannot trust the majority of scientific studies, especially if they were done by the industries that are promoting certain things, and you know that.  Right now you can’t trust companies that are basically supposed to be self-policing and there’s a profit to be made. They’re going to work hard to show you the data that’s going to show what they want so you can buy their product.

Dr. Weitz:            But there are thousands and thousands and thousands of studies on the health promoting benefits of various phytonutrients, and phytonutrients do not exist in animals. There are plant-based nutrients like curcumin and resveratrol and bioflavonoids, and we go on and on and on.

Dr. Gould:           Right. Okay, so from a nutrient density perspective, animal meat, animal fat is one of the healthiest things that you can eat.

Dr. Weitz:            But it doesn’t contain any phytonutrients.

Dr. Gould:           Well, the animal that ate those foods may have those phytonutrients in them. When you’re eating an animal, you eat what it eats. So, what do people who don’t eat any vegetables throughout most of the year, where are they getting their phytonutrients from? Why aren’t they all dying?  And again, these days I don’t know that you can find a population that’s not been tainted by western food, but-

Dr. Weitz:            Well, you can say the same thing about vegans, right? Why aren’t vegans dying, because they’re not eating any meat?

Dr. Gould:           Well, some of them are, just you know. A raw vegan diet-

Dr. Weitz:            I think some of all of us are dying, but-

Dr. Gould:           Well, that’s true. So, what I want to make clear is that, and again, this is just my opinion, I’m only bringing forward the scientists work that I discovered, because it’s important. So, the discussion about is this food healthier than food, if we pull 100 people off the street and say, “Is broccoli healthier than red meat?” They’re all going to say broccoli’s healthier.  But in my opinion they’re most likely wrong. And then depending on how you’re going to look at the question, well, can you eat only broccoli and survive? Absolutely not. Can you eat only meat and survive? You can. You don’t need any broccoli to live. You do need meat to live. The fats that you can’t make. Now, start to look at the structure of Omega-3 and Omega-6 fats, and no one’s studying the stuff when it’s related to deuterium itself.  So, there are some studies that are showing that deuterated PUFAs and MUFAs, because I know that’s the language you want to talk. Everyone wants to blame all these oils, is that there are studies that show that fortification with deuterium actually strengthens the lipids in the cell membrane, so it’s actually good for you. Which I think is really confusing, because we don’t want to do that.

Dr. Weitz:            Say that again one more time? Deuterated-

Dr. Gould:           Deuterated PUFAs and MUFAs.

Dr. Weitz:            So, you’re saying essential fatty acids that have higher levels of deuterium are what?

Dr. Gould:           There’s a few studies out there, because I don’t want people to see conflicting evidence here, that they strengthen the actual fat itself, because it makes it harder to oxidize the fat at the double bond. Because that’s what everyone’s talking about, they’re talking about Omega-3, Omega-6, but what I’m saying is let’s go a level deeper to deuterium.

So, if you eat a food that’s low in deuterium, grass-fed beef or grass-fed fat, beef tallow, it’s much lower in deuterium than beans, much lower. So, if you said to somebody, “Are beans healthier than red meat?” and even if you’re taking aside the fact that most beans are loaded with glyphosate depending on where they came from, you’re going to find the deuterium content of beans is going to be higher than red meat. Anything that lowers your deuterium level makes you healthier.

Dr. Weitz:            But essentially what you’re saying is, Joel Gould is saying that the healthiest food you can eat is beef fat?

Dr. Gould:           Yes. And I stand by that.

Dr. Weitz:            You stand by that. Okay.

Dr. Gould:           I stand by that, yeah.

Dr. Weitz:            Okay.

Dr. Gould:           And somebody you may want to want to investigate this with is Dr. Laszlo Boros, and he is one of the foremost experts in this field. And there are a lot of studies to support this, there are some good websites out there. And deuterium depleted water is being incorporated into a lot of different therapies now. And you’re going to see, I know the-

Dr. Weitz:            Okay. So, let’s stop for a second.

Dr. Gould:           Sure.

Dr. Weitz:            What is deuterium depleted water?

Dr. Gould:           It’s water that has a lower level of deuterium than tap water. So, it’s water-

Dr. Weitz:            How do they do that?

Dr. Gould:           So, there’s two ways to have lower levels of deuterium. You can go to a water source that has a lower level of deuterium, or you could do it artificially.

Dr. Weitz:            Which waters have the lowest levels of deuterium?

Dr. Gould:           All the glacial waters, so the higher up you go and the further north you go, the less deuterium you have. The closer to the tropics that you are and the lower down you are elevation wise, that’s going to have the highest level of deuterium. Even if you go lower, you go to the Sahara desert, the brown water there’s going to be 180 parts per million, whereas the water in glaciers at the top of high mountains is going to be 90 parts per million.

And that’s a very big difference. The amount of deuterium in the environment is tied to solar radiation, latitude, and elevation, and those are the things that affect sunlight as well, and that’s why Vitamin D and deuterium are also related. So, in the areas where you have a lot more deuterium naturally, solar radiation is much higher and it’s in balance. In the areas where there’s very little solar radiation, there’s less deuterium.

And life on this planet evolved over millions of years here, and all of our biologic systems are designed around the chemistry that the molecular biology that makes our bodies work. So, anything that slows down your production of energy is going to decrease your overall health, period. And I stand confidently behind that statement that red meat is the healthiest food on the planet. I didn’t say that eating it with a bun with cheese made from corn fed animals and with french fries fried in industrial seed oils is healthy.

You take that meat, and if that’s all you eat, that is the healthiest. So, that’s why so many people will have an improvement. Why does your brain fog go away? Why do kids stop having seizures when they go on a ketogenic diet? The reason is a ketogenic diet is a deuterium depleted diet. That’s why it works.

Dr. Weitz:            But there can be negatives too, right?

Dr. Gould:           Of what though? So, think about the foods-

Dr. Weitz:            So, let’s say the person goes on a ketogenic diet and their LDL particle number and their small dense LDL goes through the roof, and now they’re at greatly increased risk of atherosclerosis and dying of a heart attack or a stroke.

Dr. Gould:           Okay, so what you just said is one of the most important things that anyone could say. You believe that saturated fat is the root cause of atherosclerotic plaque? You believe that?

Dr. Weitz:            No, I didn’t say that. You put that in there.

Dr. Gould:           Okay. So, hold on.

Dr. Weitz:            I’m saying that some people, and I think there’s more than one cause, but I think some people they go, and I can document this for you, there are some people that go on a keto diet, eat a lot of red meat and animal fat, and their unhealthy lipids go way up and they’re increasing, I believe and I think the studies show, they’re increasing their risk of heart disease and stroke.

Dr. Gould:           So, what’s the mechanism of action for that? So, saturated fat, when you say saturated fat, and why would beef fat be the lowest in deuterium? Well, specifically these animals are eating green growing grass, which is extremely low in deuterium. So, don’t get me wrong, salads can be very healthy if you’re not talking about the plant toxins that are trying to kill you.

But the animals that are building this up, this is molecular biology, this is quantum physics. So, when you have a hydrogen atom, you have to understand that when you get into the mitochondria, we’re talking about a lot of quantum physics, there’s proton tunneling. So, at a very small scale things get much closer together and we get into the magical world, but what I’m saying is let’s look at the world 15,000 years ago. There wasn’t any processed foods.

You could never go to any grocery store. If you went to a grocery store you’re just going to find meat, you’re going to find seafood, you’re going to find tubers, you’re going to find the things that animals and humans ate on this planet. Humans are successful because we’re omnivores. We really will make a go of whatever we can get our hands on. But we evolved to eat the meat of ruminants that ate green growing grass.

That’s where Vitamin K2 comes in, and so we see that. So, if you’re telling me, if you think you can create a perfect ketogenic diet and control what someone’s eating, that’s not necessarily going to happen. But if you decrease the deuterium load that somebody’s taking in, you’re going to have an improvement in all their metabolic functions. Why is that? Because their deuterium burden has been lowered.

Now, the other component to that I want people to understand is that deuterium doesn’t act alone. It has a villain counterpart and I call them the tag team of terror. It’s glyphosate, and glyphosate and deuterium they run together, because they’re found in all of the high deuterium foods are also the ones with the high levels of glyphosate. Corn, grain and soy, wheat, these products, these are all GMO products.

And when they’re not GMO, they can still desiccate any crops that they want with glyphosate and they don’t have to tell you. It’s odorless, colorless, you can’t see it, you have to be specifically looking for it. What’s the big deal? Those two really work together, because the enzymes that are involved in the electron transport chain in the preparation for your NAD and your FADH to get into the electron transport chain, these enzymes are being profoundly damaged by glyphosate.

And it’s destroying specifically the phosphate bonding portions that activates everything. So, the disruption you’re getting this toxin with an unnatural level. The glyphosate is a toxin, deuterium is natural. You cannot say there’s unnatural deuterium. And the amount of deuterium on this planet is relatively finite. The problem is that we’re putting it all together and amplifying it. The plants, they control their deuterium. And they want to drop, they put it into their fruit.

That’s what makes fruit sweet. They concentrate the deuterium and it drops, the animals eat it and that deuterium gets taken away. A coconut is extremely low in deuterium. The coconut meat itself, it’s a fat. So, coconut oil is one of the healthiest oils on the planet, only second to beef tallow. And the reason is it’s extremely low in deuterium. Coconut water, it’s a great replenishment for your electrolytes and it’s delicious. That’s where the plant’s putting its deuterium, it’s getting rid, it’s making that coconut water so sweet.

So, why does this happen with fats? Fats are, especially saturated fats, their carbon chains boom with hydrogen, hydrogen, hydrogen, all packed in. Sugar is a circular molecule and there’s more opportunity to replace the hydrogen with deuterium, but the sugar itself that’s created in plants is created specifically as a higher deuterium product. Because plants make different things and there’s a different level of their deuterium.

Deuterium is what basically all life is working around to get rid of it, to deplete and reduce the amount of deuterium, because it messes up everything.

Dr. Weitz:            So, if I want to have the most effective anti-aging program, if I want to decrease my risk of chronic diseases, cancer et cetera, what should I eat? What should I take?

Dr. Gould:           Number one, intermittent fasting. It’s deuterium depleting. Number two, exercise depletes deuterium. Number three, being in the sun will decrease your deuterium burden. I would eat only, if possible, organic grass-fed ruminant meats. Buffalo-

Dr. Weitz:            No chicken, no fish?

Dr. Gould:           No. So, fish, yeah. So fish, they’re eating the plankton. There’s low deuterium seafood products as well made by mother nature. The algae is going to be low in deuterium. So, any fish that eat the algae, it’s like an animal eating grass.

Dr. Weitz:            Which fish are those?

Dr. Gould:           So, fish with scales. This is where we get into a more philosophical religious discussion. The kosher foods are the low deuterium foods. So ruminants, animals that chew their cud, those are low in deuterium. Fish with scales, those are low in deuterium. They basically-

Dr. Weitz:            Which fish have scales?

Dr. Gould:           Any kosher fish. So, fish with scales are salmon. Fished that aren’t kosher-

Dr. Weitz:            They would get scales when they go to temple?

Dr. Gould:           Exactly. Exactly. Well, it’s an easy way to… shellfish is in kosher, but it’s quite high in deuterium, because they’re filter feeders. So, it’s going to have possibly the same content as ocean water at 155 parts per million. Now is shellfish unhealthy? I don’t think so. I think the benefit’s there.  So, how much deuterium is in Doritos? I don’t know, it’s probably 165 parts per million. So, when it comes down to it you have to understand that the body doesn’t know anything other than the actual biochemical processes that it’s going through. So, it doesn’t matter what the diet you think is healthy, if you have diet A and diet B, if diet A is lower in deuterium, unless there’s some additional toxins and-

Dr. Weitz:            Okay, so what’s a low deuterium diet? It has grass-fed red meat, it has some fish.

Dr. Gould:           High in fat.

Dr. Weitz:            High in fat. Ketogenic. 75% fat diet.

Dr. Gould:           Yes. I mean just fish with scales.

Dr. Weitz:            Do we eat a lot of vegetables as well, or not?

Dr. Gould:           It just depends. Some vegetables are much higher in deuterium than others, and those [crosstalk 00:46:16]-

Dr. Weitz:            Which vegetables are high in deuterium?

Dr. Gould:           The starchy ones. All the ones that the more delicious the taste is, the higher the starch.

Dr. Weitz:            So, don’t eat root vegetables you’re saying?

Dr. Gould:           I would limit your root vegetables just depending.

Dr. Weitz:            Okay. No grains, no beans?

Dr. Gould:           I personally prefer to stay away from those for two reasons. Again, grains… now listen, we live in a world where it’s funny, because when I hear people talking about the different diets, I live in the real world. I’m hyper aware of this and it’s still really hard to make really good choices throughout your day. I’m very specific about what I do. This is really hard stuff.

So, if you gravitate towards unprocessed foods, natural foods, grass-fed organic foods, you’re going to be cutting out a massive amount of the toxins, the glyphosate. But I’ve personally tested some protein powders based on peas. Peas and beans and oats, and I don’t eat oatmeal. You’re going to find that everyone who uses a continuous glucose monitor when they oatmeal they’re like, “Oh my god, my blood sugar went crazy.”

It’s because this is where the glyphosate is. This is when you’re starting to absorb, this is getting incorporated into your enzymes. Your body is switching out those enzymes and the actual enzyme complexes in the electron transport chain. In your mitochondria every 40 minutes you’re getting new, and that’s why intermittent fasting is so powerful if you decrease the deuterium load. You eat a little bit of sugar and fruit all throughout the day, it’s one of the least healthy things you can do.  Now people who snack on food all day, they’re literally keeping their body in a state of deuterium overload. It’s not natural. We are only ever designed to eat a ton of food-

Dr. Weitz:            How much vegetables and fruit should we eat?

Dr. Gould:           I don’t believe that anyone has a particularly great… I have no formula for you. I personally, the vegetables that I like are the broccoli, cauliflower, Brussels sprouts. I like the cruciferous vegetables, because they’re high in sulfur. I think they’re also very, very… they have a low glycemic index. They’re also low in deuterium as well. But beans and corn and grain, these are the foods that we cultivated because they’re more convenient. You can feed all these people with this. It’s way harder to have a hunter gatherer’s diet and lifestyle.

Dr. Weitz:            How about fruits? Should we be eating fruits? No fruit?

Dr. Gould:           So, in my opinion-

Dr. Weitz:            Not even berries?

Dr. Gould:           So I love berries and I always consider fruit as a treat. So, berries should be eaten in season, in the location that you found them with your clothes off, because that’s how we evolved.

Dr. Weitz:            You have to fly to Alaska at a certain time of year, pick your raw berries, and then you can have them for dessert. Otherwise no.

Dr. Gould:           Otherwise no. Well, and losten, we’re all choosing-

Dr. Weitz:            How about nuts and seeds?

Dr. Gould:           So, hold on. So, let’s finish with fruit. So, the more sugary a fruit is. the less healthy it is. The more chance of a fruit being infected with glyphosate from the ground water, the more unhealthy it is. Sugary fruit should be eaten where the sugary fruit is grown to be safe. If you fly a pineapple up to the North Pole and eat a bunch of pineapple, it’s a deuterium overload.  Being in the sun will literally decrease the burden. It’ll increase your Vitamin D, it will decrease the viscosity of the water in your mitochondria, so those rotors can spin faster and make up the difference. So, yes, so fruit-

Dr. Weitz:            But I can eat the blueberries that grow in my backyard whenever I want.

Dr. Gould:           You sure can, and especially if you’re not in California and when you grow blueberries, I grew up in central Canada, raspberries come at the end of the summer guys. There’s different seasons and that’s when you eat all these. You didn’t have them all year round. They’re flying in sugary fruit from the other hemisphere. So, fruit is not healthy. It’s not. It’s delicious and I like it and there’s some really good nutrients in it, but it’s full of sugar.

Dr. Weitz:            How about nuts and seeds?

Dr. Gould:           Some nuts are much higher deuterium than other nuts. So, I don’t believe drinking almond milk is particularly healthy. So, nuts have a lot of Omega-6 oils.

Dr. Weitz:           If I get almond milk from the almond milk tree in the backyard. Just kidding.

Dr. Gould:           Right. So, be careful what… exactly.

Dr. Weitz:           Which type of milk?

Dr. Gould:           So, are nuts healthy? Yeah, nuts are healthy, but not three pounds micro processed that you’re drinking and feeding your kids all day long.

Dr. Weitz:           Right. But raw, uncooked, unsalted almonds or-

Dr. Gould:           Yes, there you go. And just think about this is, if you’re a hunter-gatherer you still got to shell those nuts, you still got to pick them up. When we go and buy this whole bag of completely… and they’re using chemicals to take those, they’re putting in a big machine. So, when we process food, we make it unnatural and unhealthy.

 

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Dr. Gould:           My favorite discussion is hot dogs. Now if you had asked me 20, 30 years ago… so let me ask you this, are hot dogs healthy? Yes or no?

Dr. Weitz:            Generally not.

Dr. Gould:           Probably not. What’s that?

Dr. Weitz:            No.

Dr. Gould:           No, no. It’s ridiculous. So, how could a hot dog be healthy? Now think about this. When I thought hot dogs weren’t healthy-

Dr. Weitz:            How many people followed a ketogenic diet and think that means that they should be having bacon every day?

Dr. Gould:           Well, I’m going to argue that bacon could be quite healthy if the animal… I’m going to argue that if you get bacon from a pig that is eating acorns in Italy-

Dr. Weitz:            What? Who the hell gets bacon from a pig that eats acorns in Italy?

Dr. Gould:           Well, you’ve had good prosciutto, right?  So, you are what you eat. So, when an animal eats something, especially if it’s monogastric, you eat what they eat. So if you eat a pig and the bacon from a pig that is eating nothing but industrial feed full of corn and full of soy, very high in glyphosate and deuterium, they’re mono gastric, they eat something, it goes on to their tissue, and you eat that.

Take that same pig and compare to one that comes from the wild, a wild boar from Hawaii, completely different meat. So, when it comes to monogastric animals, chicken and pork, I only want to eat organic meat that comes from somewhere I know that they fed the animal organic feeds. When it comes to meat, when I go anywhere, I’ll go to any restaurant anywhere around the world and eat a steak or a hamburger, because the beef is still the safest food on the menu.

It’s still the healthiest food. And I’ll say it again, red meat is the healthiest food you can put into your body. Why? Most nutrient dense, gives you the most of everything. So, back to hot dogs. So, how do they make a hot dog? Well, they take the carcass and they use a high power suction thing and they suction off every last little bit off the bones, and they grind it up and they form it into a hot dog.

Now, it sounds disgusting and I used to think that was the worst thing that you could eat, but if you get a grass-fed organic hotdog done at a regenerative farming location, now you’re honoring the animal by eating a hot dog, because your kids are going to eat that hot dog. And what are you getting? A bunch of collagen. Why? Because they’re suctioning off all the connective tissue and all the gross stuff, and that sludge is being made into a hot dog. So, a hot dog, maybe some main brand one, not so much.

But I love a really well done organic grass-fed hot dog. And if you have kids, how easy is that? I think it’s one of the healthiest foods you could eat. Now, if they’re adding a bunch of junk in there, all bets are off. But if you just took the meat, a hot dog is just fine.

Dr. Weitz:            So, Joel Gould’s food pyramids go-

Dr. Gould:           Hot dog at the top.

Dr. Weitz:            … beef tallow, hot dog and broccoli way at the top of the food that should be eaten the least of, potatoes, or rice, or something.

Dr. Gould:           100%. 100%.

Dr. Weitz:            Okay.

Dr. Gould:           And I’ll stand by that.

Dr. Weitz:            So, should we drink the deuterium depleted water? And if so, what kind and how much?

Dr. Gould:           Well, so that’s a great question. Do I think the average person needs to drink it? No. The water that you drink it can affect you, but the food you eat is much more important. Why? because the water that we make inside our mitochondria oozes out of the mitochondria and is the primary hydration tool for the cell. So, the water that’s getting into the cell is actually being created from the oxidative phosphorylation, because the final electron acceptor is oxygen.

It gets added on two electrons and now you have H2O, and that’s inside the inner mitochondrial membrane. That’s deuterium depleted water. That is the fountain of youth. So, that is the difference, is that when you drink water it’s going to get transported, but the water that you create from the food that you eat is going to ooze out and fill your cells. Now who should drink deuterium depleted water?

Maybe somebody with cancer, maybe somebody who has a severe obesity issue, maybe a multi-millionaire who has nothing better to do with their money. At this moment in time it’s expensive. My prediction, I don’t think things have progressed enough because of the powers that be, this is hard to get your mind around. In a good way you’re kind of challenging and mocking me saying, “Joel, come on, red meat’s the healthiest thing? There’s thousands of studies to support this.”  I don’t believe that. I believe that the majority of studies that are supporting this vegan, plant-based lifestyle, are funded by big food, the agrochemical industry, and the massive industry that we have. This is the same industry, and I don’t want to be a conspiracy guy-

Dr. Weitz:            By the way, of course the vegans say the same thing, that all the research that you’re looking at for the ketogenic diet et cetera is being funded by the-

Dr. Gould:           The what? The beef industry?

Dr. Weitz:            … beef industry. Yeah.

Dr. Gould:           And they’re right. And to a certain degree there is no scientific study that doesn’t come without bias. It just doesn’t happen. None of our groups that are supposed to be independent are. None of them. Every study is flawed for multiple reasons. So, I’ve looked at the evidence, and again, everyone listening to this is going to be-

Dr. Weitz:            So, by the way, how should we measure our deuterium levels? Should we measure them?

Dr. Gould:           So I think we should measure them? If you have done everything possible-

Dr. Weitz:            Should that be part of our lab work up?

Dr. Gould:           Honestly? Absolutely. How easily you deplete deuterium. You have to understand that we’re living in a false paradigm for a million different reasons. The medical doctors are treating diabetes with insulin, metformin, they’re not treating the root cause. Diabetes is staying out of the sun and eating the wrong foods, and that’s something that I’ve said before and you can quote me on it. That’s really what it is.  We’re not going to find diabetes in people who are eating one meal a day, nothing but nose to tail animal meat that they caught out on their hunts. That’s just not going to happen. It’s the processed foods and the glyphosate. People are saying, “Oh, it’s insulin resistance.” It’s glyphosate and deuterium poisoning, that’s what it is.  This stuff is messing up our bodies. We were never designed to… it is our primary fuel, is fat. It’s not carbohydrates. We store fat, because that’s-

Dr. Weitz:            So, how do we measure deuterium? Is there a blood test that we should get?

Dr. Gould:           There are blood tests that you can. At this point in time-

Dr. Weitz:            Is that the best way to do it?

Dr. Gould:           Well, I’m not recommending that. I’m recommending lifestyle changes to lower your deuterium. And then anyone who’s really concerned about their health can contact, yes, you can have your deuterium tested. It’s real. Athletes may have a much lower deuterium level than a-

Dr. Weitz:            There’s also a breath test, right?

Dr. Gould:           Yes, correct.

Dr. Weitz:            So, what’s the best way to measure?

Dr. Gould:           I cannot endorse anyone. I’m not currently working with any deuterium, no company, so I can’t tell you that. I don’t think it’s important. But I do want to go back to the idea that, we never finished our talk on saturated fat, cholesterol, and atherosclerotic plaques, and that I don’t believe there’s a single scientific study to accurately show that that buildup of cholesterol is caused by eating organic saturated fats. Not coconut meat, not beef tallow, not red meat, I don’t believe that.  I don’t believe that you can faithfully trace back the vilification of red meat to causing heart disease. I don’t believe you’ll find that. Heart disease is caused by multiple deficiencies and a lot of it’s mostly… there’s a massive Vitamin D component, but eating the wrong food, staying out of the sun, lack of Vitamin K2, lack of magnesium. There’s major systemic dysfunction in how our biology is working, because our doctors don’t understand how our bodies work.  You can’t fix or repair something unless you understand how it works and know why it broke down in the first place. And until people understand what this deuterium does, deuterium dictates lifespan. It tells your body how long you have left to live. That’s the way it works. And this is a quantum physics issue, because of how things resonate. It’s a stereo structural issue, because of how enzymes work.  The more deuterium that gets incorporated into your enzymes, the slower the reaction time. The slower the reaction time of your enzymes, the less healthy you are, period. It’s just an equation.

Dr. Weitz:            Are there any nutritional supplements that will lower deuterium levels?

Dr. Gould:           Not that I’m aware. Aside from Vitamin D, not that I’m aware of. This hasn’t been brought to the forefront in a meaningful way, because it sounds ridiculous, it sounds like crackery, but this is the basement level of health. And you’re going to see the carnivores are going to continue, the vegetarians, vegans, they can do whatever they want. You cannot get rid of that extra neutron unless you know where it is and how to avoid it.

And I’d love it if people could be speaking about this and we could have some real scientific interest in this, that would be great, but the real problem is that you have to think about who funds scientific studies. The people who fund the studies they want the money back, and you can’t trust the larger organizations because they’re corrupted through money and investments.

Medical schools, you really can’t trust those. I want to actually, because I know we’re getting to the end of our time here, but I wanted to say something really bold, is that deuterium is at the core of cancer as well. So, that’s where the connection is between sugar and a ketogenic diet and cancer. Red meat is not the root cause of cancer. In fact, it’s the opposite. If you ate nothing but red meat, you would greatly decrease your cancer incidence, and those studies exist.

I encourage anyone to Google Laszlo Boros and some of the studies that he’s published. It’s not proof, but we have a mechanism of action, we have evidence, we have quantum physics, and we have common sense thinking about who is it in our society that’s getting fat? Who is getting heart disease? These are the people eating the processed foods, and what is it? It’s not just sugar, it’s these toxins coming together that are destroying the mitochondria’s ability to generate energy.

That is what metabolic disease is, period. It’s the metabolism and your metabolism is your mitochondria. Those are the equations that we can’t change and I’ll be excited when more… I’m glad you challenged me, but I’ll stand by every… we can pull this up again and I’m really waiting for more research on Omega-6 and Omega-3 um fats, but I can guarantee you when it comes down to it, there’s going to be some enzymatic issue with deuterium.

And I’m sure almost everything falls to deuterium, really. When the dust clears, deuterium is going to be there as the root cause for a lot of things. So, I don’t mind you giving me a hard time.

Dr. Weitz:            So, it’ll be interesting if there was a study that compared people with lower and higher deuterium levels to see if they had a difference in… the latest data on anti-aging is to measure something called a methylation clock. And so this is the latest cutting-edge way to measure your biological aging.

Dr. Weitz:            And so it would be interesting to see if people with higher and lower levels of deuterium, how they came out on this methylation time clock.

Dr. Gould:           That’d be great. So, I would recommend that, that’s a great question. And like I said, Laszlo Boros, he’s a busy guy, but he’s one of the foremost experts on deuterium. And the other, Robert Slovak, is also highly knowledgeable on this. He’s been involved in this. And these are great questions. The problem is this is new stuff, but we’re seeing this. You can see it, if you give up, if you go on a carnivore diet and you get healthier, how many studies do you need to show you what the root cause is?

Now, I think it’s unlikely that people who get extremely fit and they’d be able to maintain this are going to look back in 20, 30, 40 years and say, “Wow, that was a giant mistake to eat what my ancestors ate.” I don’t think we’re going to say that. Hunter-gatherers didn’t evolve with cutting boards and washing vegetables and soaking them and cutting them up. We didn’t have pea protein, we weren’t supplementing, we weren’t making smoothies. Hunter-gatherers ate what they ate. So, I don’t know believe them.

Dr. Weitz:            But on the other hand, we can go around and around on this, but just one more challenge is that hunter-gatherers, depending upon where they lived, ate different fruits. And some ate ruminants and some didn’t.

Dr. Gould:           Right. Their biology was tied to that geographic location.

Dr. Weitz:            Right. And they ate what they could to get the most calories possible so they could survive another day.

Dr. Gould:           Right. But when you say that, that’s painting all hunter-gatherers over a couple hundred thousand years with one stroke. There were hunter-gatherers who probably struggled a lot with their diet. And the hunter-gatherers that lived along the seashore where there was easy pickings, they probably didn’t have those same issues with famines. But keep in mind there was ice ages where I don’t know where all the vegetables came from during the ice ages, but man survived on eating animals and seafood.

Dr. Weitz:            !Kung Bushmen basically ate mongongo nuts, because that’s what they had. They gave them a lot of calories.

Dr. Gould:           Right. It’s interesting stuff, but I look forward to listen maybe in three or four years we can see how far this paradigm has come. But I think that there’s going to be a lot of pushback, especially in the cancer arena. And to anyone listening to this, cancer is not a genetic disease. It’s not. I know that everyone wants to believe that there’s these gene therapies and that, and they can absolutely work to some degree. But root cause of cancer, sorry guys, it is not a genetic disease-

Dr. Weitz:            It’s metabolic.

Dr. Gould:           … it’s a metabolic disease. And if you know who Thomas Seyfried-

Dr. Weitz:            Yes.

Dr. Gould:           Yeah. So, I did a podcast with him, he put it as plain as day. We took the genetically messed up DNA and put it in a fresh cytoplasm and the DNA repaired itself, oh my god. This is really a deuterium issue, sorry. Deuterium will change how DNA and RNA polymerases work, because those enzymes when they’re deuterated, they do not create the same accurate copies of your DNA.

The more deuterium you flood into your body, the quicker you’re going to age. And I stand by that and all the contents of this podcast. And I really appreciate you peppering me with those questions. And to anyone who wants to know more about this, I think this is really going to be the root cause of disease, because it’s obvious to me. You see behind me, I’ve got my posters in that, I’ve got some books. My website is Modern Hunter-gatherers. That’s basically where I want people to go check it out.

They can download my free ebook that shows you this cartoon character, because this is confusing stuff, and this is confusing to scientists. You’re a highly knowledgeable guy and you’re skeptical about this, which is good. This is really good, but skepticism, I’m pretty sure that it will all come out in the wash, but I’m going to stand by that red meat stuff and beef tallow. And there’s some different signaling aspects of the different fats and what is stearic acid, is a signal of the abundance of summer.

There’s lots of meat and everything. So, I think that ultimately it comes down to a lot of different things, but at the very basement level you’re going to find deuterium there every time.

Dr. Weitz:            Cool. Thank you Joel.

Dr. Gould:           All right, I look forward to it. Thanks a lot.

 

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Dr. Weitz:            Thank you listeners for making it all the way through this episode of the Rational Wellness podcast. Please take a few minutes and go to Apple Podcast and give us a five star ratings and review. That would really help us so more people can find us in their listing of health podcasts.   I’d also like to let everybody know that I now have a few openings for new clients for nutritional consultations. If you’re interested, please call my office in Santa Monica at 310-395-3111. That’s 310-395-3111, and take one of the few openings we have now for a individual consultation for nutrition with Dr. Ben Weitz. Thank you, and see you next week.

 

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Dr. Felice Gersh discusses Hormone Replacement Therapy to Prevent Heart Disease with Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] 

 

Podcast Highlights

3:27  As an OBGYN, Dr. Gersh was taught mainly about the benefits of estrogen for reproduction but she was not taught and what is not well understood is the role of estrogen in maintaining cardiometabolic homeostasis or metabolic health.   Estrogen and the rhythmic secretion of estrogen helps keep women healthy up until menopause.  Estrogen is the reason younger women have lower risk of heart disease than men.  Women need to have adequate amounts of estrogen, and ideally the hormones should be a normal rhythm to really to optimally be healthy. 

5:25  Nature made it that women’s bodies will functional optimally so that reproduction will be successful, which is the prime directive of life.  But once reproduction ends, nature can be cruel and it winds women’s bodies down, with their hormones dropping and menopause is nature’s exit strategy for women.  Nature winds women down by taking away her hormones. 

9:00  Since we know that naturally women’s bodies are designed to wind down, we should be super smart and not wait for the body to have problems have to have stents and start replacing organs.  In order for our cells to function optimally, they need the proper hormones, so Dr. Gersh believes in giving estrodial and progesterone to restore her vitality, since they are no longer being produced by the ovaries. There are receptors in virtually every organ and cell for estradiol, including in the arteries, the myocardial cells, and the mitochondria.  If there is no estrogen, all those cells with estrogen receptors will not be getting the information they need to function.  The goal of Hormone Replacement Therapy is not just to suppress symptoms like night sweats and hot flashes but to try to maintain the metabolic state as close as we can to a woman at her optimal health, which would be, for example, in the early 20s.

14:16  Estrogen is important for reducing a woman’s risk of heart attack. Women are more likely to die from their first heart attack than men and cardiovascular continues to be the number one killer for women. Unfortunately, most of the research on cardiovascular disease has been done with men, but women’s cardiovascular risks are different than mens’.  Women’s hearts contain many mitochondria and without estrogen, the mitochondria in the heart become energy deficient and their hearts tend to become stiffer.  Women’s hearts may continue to pump well, but may be unable to relax and fill normally.  This is called mild diastolic dysfunction.  When women have heart attacks, it’s usually related to blockages in the microvasculature rather than due to blockages of the major arteries supplying the heart.  This difference has not generally been well appreciated by doctors and researchers.

20:41  Angiograms do not analyze these smaller vessels, the microvasculature.  Levels of microalbumin might indicate that you have leaky arteries.  You can also see decreased blood flow on functional testing of the heart, like stress echo or radionuclide stress testing.  Even when women have large vessel blockage, the stents that have been developed for men, who have larger coronary arteries, in women can break off plaque and create heart problems.  And even stenting for men is controversial, since prophylactic coronary artery stenting has not been shown to lengthen the lives of these patients.  If a patient is found to have blocked arteries but does not have symptoms, this has not been shown to make people live longer, though if stenting is done because you are in the middle of a heart attack or have a coronary syndrome, stenting can be life saving.

23:38  One of the most popular blood pressure medications for men, the ACE inhibitors, that affect the renin-angiotensin-aldosterone system, which is also known as the RAAS.  But women are better served with taking an ARB, an angiotensin receptor blocker, as opposed to an ACE inhibitor.

 

 

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Dr. Felice Gersh is a board certified OBGYN and she is also fellowship-trained in Integrative Medicine. Dr. Gersh is the Director of the Integrative Medical Group of Irvine and she specializes in hormonal management. Her website is IntegrativeMGI.com, and she is available to see patients at 949-753-7475.  Dr. Gersh lectures around the world, and she has written two books, PCOS SOS: A Gynecologist’s Lifeline to Restoring Your Rhythms, Hormones, and Happiness and PCOS Fertility Fast Track and she has recently published a paper in the prestigious journal Heart, which is part of the British Medical Journal family of journals: Postmenopausal Hormone Therapy for Cardiovascular Health: the Evolving Data.

Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

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Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting-edge health information. Subscribe to the Rational Wellness Podcast for weekly updates, and to learn more, check out my website drweitz.com. Thanks for joining me and let’s jump into the podcast.

Hello, Rational Wellness podcasters. Today, our topic is the use of hormone replacement therapy in postmenopausal women to prevent heart disease with Dr. Felice Gersh. We all know that heart disease is the leading cause of death for men, but what about women? Well, prior to menopause, women do have a lower risk of cardiovascular disease. But after menopause, their risk go up dramatically.

Menopause, on average, occurs around age 54 and while there’s ample evidence that this increase in cardiovascular disease after menopause is likely due to the loss of estrogen, the American Heart Association website states, “A decline in the natural hormone estrogen may be a factor in heart disease increase among postmenopausal women. Estrogen is believed to have a positive effect on the inner layer of artery wall, helping to keep blood vessels flexible. That means, they can relax and expand to accommodate blood flow.”  Despite the benefits of Estrogen, the American Heart Association recommends against using postmenopausal hormone therapy to reduce the risk of coronary heart disease or stroke because some studies have shown, it appears to not reduce the risk. A similar position is taken by the American College of Obstetricians and Gynecologists. This is why I’ve asked my friend, Dr. Felice Gersh, to join us, since he has recently published a paper in heart which is part of the very prestigious British Medical Journal, family of journals, entitled Postmenopausal hormone therapy for cardiovascular health: the evolving data.

Dr. Felice Gersh is a board-certified obstetrician and gynecologist and she’s also a fellowship-trained in integrative medicine. Dr. Gersh is the director of the Integrative Medical Group of Irvine where she continues to see patients. She also lectures and writes on various topics relevant to women and she is the bestselling author of two books, PCOS SOS and PCOS SOS Fertility Fast Track. Dr. Gersh, thank you so much for joining us.

Dr. Gersh:           Well, it’s my pleasure and I just love your introduction. It shows the paradox in terms of the data versus the recommendations and that’s really my mission is to put those two together to actually create an evidence-based sensible way to deal with cardiovascular disease and all the other married issues that face women during their many years of life, during the menopause.

Dr. Weitz:            Absolutely, you are the foremost supporter of the benefits of estrogen of anybody I’ve ever spoken to.  So, before we get into some of the studies related to hormone replacement therapy after menopause, perhaps you can explain some of the benefits of estrogen.

Dr. Gersh:           Sure.

Dr. Weitz:           Especially with respect to improving cardiovascular health.

Dr. Gersh:           Well, the fundamental takeaway always has to be recognizing that estrogen and the other hormones, I deal with a little bit.  They’re like the secondary but the main focus is on the primary, we’ll say the top of the pyramid, which is the estradiol.  So, reproduction, which every woman knows, involves estrogen, and that’s all I was taught about as an OB-GYN in training was the role of estrogen in reproduction.  Well, it’s involved in having a menstrual cycle and you need to have it during pregnancy, and it’s made by the placenta in different forms.  So, of course, everyone understands that there’s a role of estrogen in reproduction, but what is not well understood even by OB-GYNs and by cardiologist is the role of estrogen in maintaining cardiometabolic homeostasis, basically, metabolic health, which is about creating, maintaining, and use of energy in the body so that every cell can function and then the organs that are comprised of the cells can function and everything can work as a cohesive whole in the body to support reproductive success.  You can’t have a reproductively successful woman who has an unhealthy body.  And so, it turns out that you need to have adequate amounts of estrogen, and not just having estrogen, you have to have the rhythm to really to optimally be healthy, you have to have the rhythms of estrogen because we now know that everything in life is about beautiful rhythms. So that is the foundation of the health of the female body. So, nature made it so that estrogen, you can think of as the glue that glues together all the metabolic processes of the body with the reproductive processes, and many of the processes like the enzyme systems and so on, that people know of that are involved in metabolic and cardiovascular health and so on, are replicated within the reproductive tract.  So all of these same systems and enzymes and peptides, they’re all existing and working in all the systems of the body to help a woman to be ultimately reproductively successful because that is, whether we like it or not, as a human species, the prime directive of life is successful reproduction and that brings up that nature is very wise.  It makes it so that women will have all the hormones that they need to be reproductively successful and have a healthy body, but when reproduction ends, nature, although wise, can also be cruel because that is the nature of life on Earth, that we have reproductive cycles and then animals are not here anymore. That is how it is.  Many species of animals, once their reproduction is over, like an octopus or a salmon, they may lay their eggs, and then they just die.  So that’s where nature is wise.  It does what it needs to reproduce the species and survival, but for the individual, nature can be cruel.  So once you recognize that menopause is nature’s exit strategy for humans, for human females and it is what it is. So, nature winds us down.  So, it takes it away.

Dr. Weitz:            Essentially, what you’re saying is, is based on the whole concept of evolution and survival of the species, etc, after reproduction, essentially women are destined to just expire.

Dr. Gersh:           Well, we’re one of the lucky species that we don’t immediately die when our reproductive capabilities end, but we become more metabolically dysregulated with the ultimate, of course, is death.  It’s not a happy story, but here’s the thing, we are really clever.  So, recognizing the naturalness, the universality of menopause, and what it means to every organ system of the female body and, of course, the cardiovascular system, which allows nutrients and oxygen to be distributed and toxins to be eliminated, and all of that, you can’t have a healthy functioning human without a really robust cardiovascular system as a foundation for health.  So once you understand that menopause is not something that women benefit from. That’s just a foundational truth and then we can say, “Okay, so what are the bad things that happen, and what are they due to?” Well, most everything that we know as aging is really about deficiencies and the deficiency, including nutrient deficiencies, hormonal deficiencies, occur when you age and then you have the profound effects to many of the other organ systems that are even more profound deficiencies that add to the problems of the aging female.  So, what we do is, okay, I hear that nature is what can also be cruel for the individual. So what am I going to do? I’m going to be super smart and not just wait to replace organs or have stents, all those things. What medicine has focused on is handling each individual problem as it arises. I want to be as proactive to prevent those problems in the first place by providing the body the foundational needs so that it can function.  So every cell needs to function optimally.  And in order to do that it needs to get the right information, is the hormones, is the information delivered.

So my goal is even in menopause to produce from the natural source obviously, we’re adding it into the body because the body is not producing it from the ovaries, the hormones that maintain metabolic homeostasis, and like I said, the top of the pyramid, the most important of all, is estradiol, the dominant estrogen. So there are receptors in virtually every organ and cell for estradiol. That was a profound understanding that I acquired quite a number of years ago because I was not taught that. I didn’t know that the American Heart Association references that the arteries have estrogen receptors, the myocardial cells have estrogen receptors, the mitochondria are filled with receptors for estrogen. So, when you don’t have enough estrogen, not one cell involved with estrogen receptors, which is virtually every cell, maybe not blood cells, but just about every cell in the body, so that cell is not going to be able to get the information than it needs to then produce the desired effect.  I recognize and we should all recognize, we’re not going to have yet, maybe this will come, the ability to create the health in a 60-year-old woman or a 55 year old to that of a 25-year-old woman, because were not really replacing her ovaries. That would be really, yeah, I wouldn’t mind a new fresh pair. But what we are trying to do is basically, often the blow of not having any hormones like estrogen and progesterone bumming them in doses at aren’t just like teeny, [inaudible 00:11:39] of hormones, to try to suppress a couple of obvious symptoms like night sweats and hot flashes, which don’t require as level two as we take, for example, or maintain the vascular system.  So that’s not the goal. The goal isn’t just to suppress a few symptoms, but actually to try to maintain the metabolic state as close as we can to a woman at her optimal health, which would be, for example, in the early 20s. So the theory behind hormone replacement therapy, the conventional doctors are not using those words anymore because those have been tainted by the Women’s Health Initiative. But now they use menopausal hormone therapy.  I don’t like those words, either because it’s also implying that you’re just giving some hormones to try to treat some symptoms, because that’s really predominantly how it’s used. So, I would just rather call hormones. I know, semantics are always an end game plus, they imply certain kinds of uses. So I just really would, even if I could, go back to the original, which is hormone replacement therapy.

 

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Dr. Weitz:            Interesting. I’ve really been enjoying this discussion, but I’d like to take a minute to tell you about a new product that I’m very excited about. I’d like to tell you about a new wearable called the Apollo. This is a device that can be worn on the wrist or the ankle, and it uses vibrations to stimulate your parasympathetic nervous system. This device has amazing benefits in terms of getting you out of that stressed out sympathetic nervous system and stimulating the parasympathetic nervous system. It has a number of different functions, especially helping you to relax, to focus, to concentrate, get into a deeper meditative state, even to help you sleep, and there’s even a mode to help you wake up. This all occurs through the scientific use of subtle vibrations.

                                For those of you who might be interested in getting the Apollo for yourself to help you reset your nervous system, go to apolloneuro.com and use the affiliate code, Weitz10. That’s my last name, WEITZ10. Now, back to the discussion.

 

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Dr. Weitz:           Part of what you’re pointing to is that, in general, our current medical system is designed to treat symptoms. It’s just not designed set up to say optimize a person’s health and so, therefore, for things to go through the medical system, to get approved by insurance, etc, etc, you have to be treating a symptom instead of trying to optimize your health.

Dr. Gersh:           Absolutely.  My goal isn’t just to suppress a few symptoms.  I really want women through their menopausal years to live optimally, to have robust zest and energy, and so on.  And that really requires having optimal hormones.  Optimal hormones are just downright essential for the health of every system with a key focus on cardiovascular.  As you implied instead, in the very beginning, hormone problems are really the foundation of what is the number one killer of women, that is cardiovascular events.  And so, women are very prone to dying from a heart attack, they’re more likely to die from their first heart attack than are men. And this always drove me crazy because the conventional medical world has always referred to the symptoms that women experience when they have heart attacks as atypical, it’s like, “Get out.” It’s not atypical for women, they’re typical for women, there may be more atypical for men. And that has also been a huge problem because most of the research that has been done on, for example, medications for hypertension, have been done in males until 2015, it wasn’t even required to have women in studies.  And so, therefore, they didn’t have them. And even when they were included, they didn’t break it out. So, you didn’t know what works for women, what doesn’t work for women. And now that I’ve been doing a lot more research into it, there really is a difference, even with blood pressure medications as to which ones may be better suited to which gender.

So, that’s actually a big deal. And understanding women and heart failure is quite a very important thing because women have a totally different onset of issues involving heart failure than men. Even cardiologists don’t realize this, and they ignore very key findings on echocardiograms. They just say, “Well, that’s just typical for women.” It’s like, “This is a sign that the heart is energy deficient.” And what I’m talking about is what’s called mild diastolic dysfunction. This is a very common problem for women’s hearts after menopause. And it’s not even appreciated by most of the cardiologists, they don’t even call it out or pointed out.

And what it means is that in a woman’s heart, there are, of course, many mitochondria. And because the heart is one of the most energy needing of all the organs. There’s the brain and the heart, and they both need enormous amounts of energy produced in the mitochondria. The energy in the mitochondria to be produced properly requires estrogen.  Now, in a male heart, they have estrogen, they make it on-site, they transform it from testosterone, they can make it on-site. Well, women have very low levels of testosterone. So, after the ovaries no longer are making estrogen, then the mitochondria in the heart become energy deficient. So the heart as a whole becomes energy deficient. And this is a really key thing. So when you have an energy-deficient heart, the heart actually becomes stiffer.

And so they can actually see on an echocardiogram that when the heart is relaxing and filling that it doesn’t relax in a smooth appropriate way. It’s like a stiffer heart as it opens up to allow the blood to flow in. And that is what they call mild diastolic dysfunction. It’s a key indicator of a heart that is energy deficient. And it’s so important, and they always talk about that, well, these hearts are still pumping well. So, it’s a different kind of a heart problem because the contracting is fine. It’s the relaxing, that’s the problem.

And so, it’s really a different category of heart failure. But ultimately, it goes from the stiffness that is involved in the diastolic phase or the relaxing filling phase, and ultimately, it involves the systolic or contracting phase, and then it becomes more of a conventional look like the passage into heart failure for women is quite different than from males. And for females, the heart attacks are quite different as well. For males, their heart attacks are in the main coronary arteries that end up having the blockage.  Whereas in female hearts, it’s usually involved with what they call the microvascular system, the very small vessels of the heart become dysfunctional and women have a very sensitive autonomic nervous system. And estrogen is key to relating the autonomic nervous system which involves having blood vessels contract, it’s about the stress response. It’s about maintaining blood pressure and pulse and temperature and so on.  And so, emotional changes or stressors of any kind are much more likely in women to cause a vasoconstriction and a very significant number of women’s heart attacks, if they die and they do an autopsy, they don’t even find significant amounts of plaque. But they had vasoconstriction with small vessel disease. And estrogen maintains the vascular system and the small vessels are very key. So with loss of estrogen from the ovaries, the small vessels, and this is throughout the whole body, they become less functional, and you have smaller amounts of these very critical small theater vessels that go to the organs. And so you have this microvascular disease.  So, women are quite different than men and this hasn’t been well appreciated. And the good news is-

Dr. Weitz:           How do those microvessels even get analyzed? Because I don’t think the conventional testing we have really looks at those.

Dr. Gersh:           Well, when we do things like an angiogram, no, they’re not looking at those small vessels. Exactly.

Dr. Weitz:           That’s what I mean they’re looking at the major vessels.

Dr. Gersh:           That’s right. Most of this data has come from more like autopsy data when you can actually look at that. Some of the different tests that may be more useful in women might be looking at levels of microalbumin, which look at the essentially leaky arteries, which show vascular disease on a smaller scale. And all very understandable when you understand what is involved in…

Dr. Weitz:           Can you see this small vessel disease on an MRI?

Dr. Gersh:           Well, what you can see is when you have loss of blood flow. So, once you get to a point where the blood flow is impaired, then you can see that. And you might see it on functional testing where the heart may not be contracting as well. But you can easily see the changes in terms of-

Dr. Weitz:           Like functional testing would be like a stress echo?

Dr. Gersh:           Well, sometimes the stress echo and maybe more like some of the radionucleotide type of testing as well. So, it’s very important, actually, you bring up a good point because these tests that have been developed, were all developed for looking at male hearts. That is true. And even when you talk about stenting. So, stenting has been a big issue even for males because doing prophylactic coronary artery stenting has not been shown to lengthen lives, it’s really can be life-saving, if you do it in the middle of a heart attack, or maybe a coronary syndrome, like when you’re impending heart attack. But if it’s just done for like, “Oh, we’re just testing and we found that you have 80%, 90% blockage, but you’re functioning, there’s nothing really happening.” And you just put stents in, that actually has not been shown to lengthen the lives of those people.  But in women, because most of the problems are these microvessels, these very small vessels of the heart, obviously, those can’t be stented. And when they stent women, a lot of the stents that were made were made for the larger coronary arteries of men, and then they put them in the smaller coronary arteries of women. And they actually can break off plaque. They actually can create heart attacks and problems and damage the vessels by putting in stents that weren’t even designed for women’s arteries, which are considerably smaller.

So, there’s just been a real, we’ll say insufficiency of research and data and treatments for women. Like I said, for example, one of the most popular forms of blood pressure medication are the ACE inhibitors. And then there’s the other group that are called the angiotensin receptor blockers. These are all involving blocking key areas involved in what’s called the renin-angiotensin-aldosterone system, which is also known as the RAAS. I’m very excited, this is a preview that I didn’t have another.

Dr. Weitz:            We all know about ACE now because the ACE receptors are how the Coronavirus gets into our bodies.

Dr. Gersh:           That’s right, the ACE2, part of the RAAS, and the ACE2 receptor part of the branch of the RAAS that is actually anti-inflammatory. So it’s like everything in the body is the Yin Yang so it’s the pro and the anti, and the pro-inflammatory branch of the RAAS is the target of many of these blood pressure medications. And just as a preview, I just had a paper on estrogen and the RAAS that was accepted by Mayo Clinic proceedings. So, I’m very excited about that.  But in terms of the RAAS and blocking it as far as blood pressure meds, there’s data that shows that women are better off, better served when they have an ARB, an angiotensin receptor blocker as opposed to an angiotensin-converting enzyme inhibitor, an ACE inhibitor. And very few doctors are aware of that. And there’s actually some published data showing good news, if you give estradiol and you give an ARB, you get an even better effect.  So, there is research out there, and we need to get so much more. And that’s why I have done some programs with the American Heart Association on educating the public and doctors on the importance of screening and recognizing the importance of the cardiovascular system in women, and how it differs from men. I’m really hoping to get more understanding that giving hormones in a… I’ve actually changed the wording.  So, a lot of times the words that we use are bio-identical hormones. And that is also been maligned a lot and because people think bio-identical means that it’s coming from a compounding pharmacy, and it’s uncontrolled, it’s unreliable. Now, that is not true because compounding pharmacies can be incredibly reliable and most hospitals, their pharmacies are actually like compounding pharmacies, they do a lot of mixing and special kinds of formulations.  

But when it comes to the hormones, I gave up the bio-identical because that also comes with too much baggage and I’ve recoined it as human identical because we got to get people thinking freshly about this. So I don’t want them bringing their old conceptions into the mix here because we got to put the old studies like Women’s Health Initiative, we got to put that in the drawer and close the drawer and lock it and just say historical interest only because they used all the wrong products in all the wrong patient.

 

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Dr. Weitz:                            I’d like to interrupt this fascinating discussion we’re having for another few minutes to tell you about another really exciting product that has changed my life and the life of my family, especially as it pertains to getting good quality sleep. It’s something called the chiliPAD, C-H-I-L-I-P-A-D. It can be found at the website chilisleep.com, which is C-H-I-L-I-S-L-E-E-P dot com.

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If you go to chilisleep.com and you use the affiliate code, Weitz20, that’s my last name, W-E-I-T-Z, 20. You’ll get 20% off a chiliPAD. So, check it out and let’s get back to this discussion.

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Dr. Weitz:            In one of your talks I heard you talk about how estrogen reduces oxidized LDL and that’s through its inflammatory effect on the PON1 receptor and interestingly, I just had a discussion with Dr. Mark Houston and there’s been… some of the latest research on HDL is that the key factor now is HDL functionality and one of its functions is its effect on PON1 and its antioxidant and the anti-inflammatory effects when he’s working, he just developed a nutritional product to help increase the HDL functionality by positively affecting PON1 and I heard you say that estrogen also affects PON1.

Dr. Gersh:           So, there are many nutrients that can be helpful and beneficial. When you actually get down to the nitty-gritty which I actually look into them, almost all of them are phytoestrogens. Like a lot. So, it’s amazing. Every time I look for the link, I find it’s a phytoestrogen in some fashion. So I’m not against that at all but I say give the primary, give the estrogen, and then you can give because no matter what we do, we’re not giving back the ovary. So we need all these other adjunctive helpers. So I’m all for it. It’s really their phytoestrogens and estrogen has so many effects. So I love that you brought that up.  So yes, estrogen maintains the viability of the antioxidant status of LDL. And that’s really the foundation because it’s only oxidized LDL that gets into artery walls. So, the only way you get plaque is you need to have oxidized LDL, and you need to have damage to the [inaudible 00:30:20]. So you need to have a damaged lining of the artery. So, estrogen is involved in maintaining the health of both of those. So when you have adequate estrogen, you not only reduce oxidized LDL, estrogen also maintains the LDL receptor functionality on the liver so that you can then have the docking of the transporters that have the LDL cholesterol to dock with the receptors on the liver for it to then be taken back into the liver for disposal or recycling whatever the body needs.

Dr. Weitz:            It sounds like estrogen is going to promote HDL functionality because that’s what [crosstalk 00:30:58]-

Dr. Gersh:           Yes, absolutely.

Dr. Weitz:            … LDL back to the liver. Yeah.

Dr. Gersh:           So this is really important. Estradiol, we can do just on estrogen, why I love it. Because estrogen maintains the apolipoprotein A1, which is a part of the HDL complex. And apolipoprotein A1 is also known as reverse cholesterol. So it’s the little carrier particle that takes cholesterol and brings it back from the arteries, walls, and other places, brings it back to the liver for disposal.  Without adequate estrogen, you’re not going to have adequate functionality and levels of the Apolipoprotein A1 which is all about the functionality. So, estrogen is key for that. And then the other thing estrogen maintains the function of and health of the artery lining, as you mentioned in the beginning by maintaining adequate levels of nitric oxide.

So, estrogen is key to the functionality of the enzyme endothelial nitric oxide synthase, which is what produces adequate amounts of nitric oxide as well estrogen reduces the inflammatory cytokines because it controls the immune cells in it. And it modulates inflammation, prevents chronic inflammation. And it turns out that elevated levels of inflammatory cytokines like tumor necrosis factor alpha also interfere with the production by interfering with the way that the whole ADMA is made. And it then acts as a blocker.

So, it controls the inflammation, which actually then is an interference to the production of nitric oxide. So there’s a few both direct and indirect ways that it maintains nitric oxide levels which are so critical for vascular dilation and health of the lining of the arteries. It actually is key to the production of what are called prostacyclins, which are also promoting, their anti-inflammatory promote the health of the vascular system, and suppresses endothelin-1, which is a very potent vasoconstrictor.

So, we know how estrogen maintains the health and function of the heart, how it maintains the health and function of the arteries. So that’s why it’s so ludicrous to me to think that all of these things that happen in women in the menopause, which are due clearly to a deficiency state of estrogen being not produced any longer from the ovaries, and the solution is not to give estrogen [crosstalk 00:33:38].

Dr. Weitz:            So when we’re getting to the next part of the talk, I want to set it up with a question, Felice didn’t the Women’s Health Initiative study first published in 2001 and show unequivocally that taking hormone replacement therapy after menopause increases the risk of heart attack and stroke.

Dr. Gersh:           Well, it proved unequivocally that you shouldn’t give Prempro. And in fact, they even had that in their article, they said, “The results of this study apply only to the product that was studied.” But somehow that totally got lost in everything that followed. So, it turns out that there are [crosstalk 00:34:20]-

Dr. Weitz:            In other words, Prempro-

Dr. Gersh:           No.

Dr. Weitz:            … for listeners who are not aware is estrogen meds excreted in a horses’ urine, combined with synthetic progestins.

Dr. Gersh:           That’s right. So, it’s a combination of what are called conjugated estrogens. And what happens is when estrogen is to be eliminated-

Dr. Weitz:            Conjugated equine estrogen.

Dr. Gersh:           That’s right. Equine because from a pregnant horse, so what it is, is when estrogen is going to be eliminated in the body, that’s right. So, a girl has her first period and she’s 13, those hormones that are in her body at that age, they’re not there when she’s 40, they get eliminated and replaced. So the way that the body gets rid of the old estrogen is by going through the liver and there’s a process that sometimes people refer to as detoxification. But it’s a process that goes through different phases and ends up with conjugation. So, it’s altered. So it’s a chemically altered now product.

And what it does is it takes something that’s fat-soluble and turns it into water-soluble, so then it can be excreted in the urine, and some of it gets excreted in the poop, and so on. And so the part that gets excreted in the urine is now conjugated, and when it’s a horse, it’s equine. So, these are the hormones that the horse doesn’t even want anymore. This is their old yucky old estrogen, they’re trying to get rid of it. And it comes out in the urine, but it comes out with a whole bunch of other stuff too.

So it’s not like just pure anything. It’s like there’s at least a dozen different compounds. Androgens are thrown in. And then what they did, they dried it and they made it into a tablet. And that’s the best they could come up with many, many decades ago, before they could synthesize human identical estradiol. But that’s what they gave to women to try to relieve their hot flashes. And it actually did work.

But here’s a very important point, estrogen has three types of receptors. Well, it’s now known that estradiol, the estrogen produced by the ovary has a balanced effect on all the different receptors. And these receptors have similarities and very major differences. They have different concentrations in different organs, they actually can up and down-regulate each other. So there’s interactions between these receptors, and estrogen from the ovary, the estradiol is a balanced approach and it does exactly what is needed in each organ at the right time.

Well, when you take the Premarin which was named after the pregnant mare Premarin, and so the conjugated equine estrogens, when you give that orally, and it gets into the bloodstream, it gets in predominantly overwhelmingly as a variety of these different course estrogens and also as estrone. There’s actually four but we’ll say there’s three main types of estrogen in the female body. There’s the estradiol, there’s estrone, and there’s estriol.

So estradiol, the dominant estrogen produced is a balanced effector on the different receptors. Estrone, which is the more dominant estrogen of the menopause, which is made in peripheral tissues like fat tissue is predominantly effective on the receptor alpha, and estriol, which is made in the placenta in very large amounts in pregnancy is predominantly effective on the beta receptor. And they create very different effects. So, compared to having the balanced one, which is estradiol, so when you take an oral estrogen, it goes to the liver, and it comes out into the bloodstream as predominantly estrone, which has very different effects throughout the body.

So it’s like a totally different chemical that you’re giving. And as well, when it goes through the liver, it up-regulates some of the liver production of coagulants, procoagulant. So, clotting factors like thrombin. So, it actually is a promoter of blood clotting. So, it’s a totally different product. It’s really like night and day. And so, my analogy is if you did a study with strawberry flavored jelly beans, and then the results were that it gives you cavities and diabetes and obesity, then you draw the conclusion, you should never eat organic strawberries, you’d say, “Well, that’s crazy.” But that’s what they did with this study. And they didn’t give progesterone, they gave a progestin which is a man-made word for an endocrine disruptor for progesterone.

So it turns out that the endocrine disruptor that they gave medroxyprogesterone acetate can bind to progesterone receptors, but depending on the organ, because it’s like a pro and an anti, that’s what they call an endocrine disruptor, it has different effects. It’s either a promoter, so it’s like an agonist or it’s an antagonist. So it either blocks the progesterone receptor, or it actually activates the progesterone receptor. So it has different effects in different organs. And it’s been shown now to increase bad things like breast cancer, like heart disease. So, it actually has a negative effect in like the breast tissue.

So, we have all kinds of problems and the other thing is that when you have in the breast, it’s predominantly the alpha receptor. So when you give predominantly something like an alpha receptor agonist like estrone, that comes from Premarin, you’re going to have a greater impact on the breast tissue. You don’t have the balance because you’re not getting any of the beta effect. So, you’re just giving the wrong thing. Something that increases blood clots, something that then, of course, was shown to, well, it increases dementia.

Well, how can estrogen in the form of estradiol increase dementia when the brain loves estradiol? It monitors the immune system of the brain. It regulates the [crosstalk 00:40:38]

Dr. Weitz:            Let me just stop you for a second right here on the breast cancer, estrone, and the estradiol thing. I wanted to ask you about the best form. I know we’re not done with critiquing the Women’s Health Initiative, but in terms of the best form of estrogen to be prescribing to women say, I wanted to point out that we have the three forms of estrogen. We have the E1 estrone, we have the E2 estradiol, we have the E3 estriol.

And because estriol, as you just pointed out, works more through the beta receptor, it’s believed to be safer in having less risk of breast cancer. And so, this has led, especially doctors in the integrated world, who recommend hormones to postmenopausal women to recommend estriol or a combination of estradiol and estriol often in a cream that has a higher percentage of estriol. And that’s because estriol is a weaker estrogen, and because it works. The beta receptor, we think it’s going to have less risk of breast cancer, but you think that E2 really should be your preferred form of estrogen?

Dr. Gersh:           Well, I think that this is a really well-intentioned but very misguided approach to hormone therapy for menopausal women. So, estriol is the dominant estrogen of pregnancy. So people think, “Oh, well, why don’t we create a more pregnancy-like effect?” Well, that is actually the exact opposite that we want. So, most people don’t understand pregnancy. Remember, I’m OB-GYN so I’ve dealt with pregnancy my whole career.

So, pregnancy is actually a pro-inflammatory state. So, with this is like the opposite of what we would want to create for a menopausal woman. So what happens in pregnancy? As soon as a woman becomes pregnant, and she starts having higher levels of estriol, her gut microbiome changes immediately and it becomes more dysbiotic, it actually becomes more pro-inflammatory and pregnant women develop a leaky gut, and then they end up having more inflammation, as you have the endotoxins, the lipopolysaccharides are leaking through.

Now, people, they’re like, “What the heck, why would that be happening?” Well, this is nature’s way of helping women to actually survive and for the baby. So, if you think of it this way, what happens is when women become pregnant and they become a little inflamed, now, this should be like a controlled fire, it’s a little inflamed. And we know that when you have more inflammation, you develop insulin resistance. And that is intended in pregnancy to promote fat production, fat storage, and higher glucose levels so that you have more glucose being transported to the baby to help the baby to grow and then become fatter.

Most people know this, that pregnancy is now recognized as a stress test for women. pregnancy is a time when women who had no evidence of any cardiovascular or metabolic dysfunctions can develop gestational diabetes, pregnancy-induced hypertension, preeclampsia, these are all vascular conditions that are related to underlying inflammation. Women who are pregnant are more prone to blood clots.

So, that’s because nature creates this low level of inflammation in pregnant women to promote insulin resistance to enable women, remember, we evolved during millennia ago, when food was scarce, to allow pregnant women to put on more fat and to deliver more glucose to the baby to grow the baby. We don’t want to do that in not pregnant women.

Dr. Weitz:            Isn’t it the case that women who have babies earlier have a lower risk of breast cancer because they have fewer periods?

Dr. Gersh:           No, it’s not because they have fewer periods. It’s because there’s… Nature is amazing. So, if you have pregnancies starting at a young age, even women who have their first baby before the age of 19 have incredibly low risk of getting breast cancer their whole lives. It’s only endocrine disruptors that mess with this whole natural system because nature made it that way. There’s tremendous hormonal changes that occur that actually reprogram genes. So we have epigenetic modification during pregnancy.  So, absolutely, I’m very pro pregnancy at the proper ages and nursing. Nursing as well is very protective, both cardiovascular protective and breast cancer. But this situation cannot be replicated in a 50-year-old woman, it’s not going to happen so that when you are pregnant, you are in a pro-inflammatory state. But the hormones do so many different things, and we’re talking about incredibly high levels of progesterone as well, which we’re not replicating in these postmenopausal women.  So we’re creating a state that never exists. When you give Biest, this is not like how pregnant women have their hormones. It’s just giving us some extra estriol but estriol is not the same as estradiol. By the way, estriol does not help the brain. So it’s estradiol that the brain loves, not estrone, and not estriol. That’s why they sometimes talk about mommy brain. We don’t want that.

So, we have to recognize what nature is doing. So also, when women are pregnant, they have an altered immune status, which is very important so that the immune system of the body doesn’t attack the baby. We don’t want that happening. So that’s why women who are pregnant are more likely to have serious outcomes and mortality and morbidity from infections like the flu or if they got chickenpox or COVID.  So, why is that? Because the innate immune cells of the body, the macrophages, the neutrophils, the mast cells, they all have estrogen receptors. Remember, everything has estrogen receptors, and they’re alpha, they’re the alpha receptor. Remember, estriol is all beta. And when you have high amounts of beta, it actually downregulates the alpha receptor. So what you’re doing when you have high amounts of estriol, this is all the beautiful wisdom of nature. Nature is wise when it comes to reproductive success.

It just is cool when it comes to getting old. But reproductive success. So the estriol with the high beta is now down-regulating the alpha. So the innate immune cells of the body are less active. That’s why a lot of women who have certain types of autoimmune diseases, they have remissions during pregnancy because you’re down-regulating the ability of these cells to make all these inflammatory cytokines, but the whole thing is very modulated and balanced so that you actually have this inflammatory state that promotes insulin resistance, but yet your immune cells are less capable of attacking. And that’s why women who are pregnant are living on the edge. That’s why it’s a really interesting stage.

Dr. Weitz:            So, for all these reasons, you recommend transdermal estradiol not oral estrogen?

Dr. Gersh:           Yes, because we don’t want to mess with the immune systems of postmenopausal women. We don’t want to create dysbiotic gut microbial populations, don’t do it.

Dr. Weitz:            And one of the reasons why the Women’s Health Initiative was wrong was not only that they were using Prempro, but also because of the timing hypothesis, right?

Dr. Gersh:           Well, I really am going to in the end, not now, because I have to take it stepwise. But the timing hypothesis is that you have this window of now they’re saying 10 years, 10 years that you can give hormones and after that, it’s too late. Now, I actually go along with that right now. But I’m telling you, I don’t, in my heart, totally believe that. But I have to go by steps.

So, in the Women’s Health Initiative, because they had certain caveats, they needed to use women who did not have hot flashes or any obvious symptoms of menopause because they were trying to make this a double-blinded study. I can tell you, every woman who got the active hormones figured it out right away because they all had immediate breast tenderness. And some of them had bleeding. They all figured it out. They couldn’t really blind it. Everybody figured out what they were taking.

But the idea was that they were not going to be giving something that suppress symptoms like night sweats and hot flashes to give it away. So, they had to use women who were not having any symptoms. And so the average age was 63. They went all the way up to starting women at the age of 79. And many of these women, they said healthy women, that was not true. So, some of the women had already, they’d been on a blood pressure medication, lipid-lowering drugs, they’d already had problems.

So, this was like standard Americana, women in their 60s and 70s. And they were not healthy group. The BMI was really high. So most of them were overweight and obese. I mean, it’s like, what kind of healthy population are you talking about? So they already had pre-existing conditions and now you’re giving them a drug that is going to increase their clotting propensity. So, yeah, that’s what actually happened.

So, in the very beginning, so the first year, and this happened in the [inaudible 00:50:09] study that came before this, so they had an increase of events in the first year because they took women who were on the edge of having some sort of a cardiovascular event, and then they pushed them into it. But once you got out by four years, you’ve already gotten rid of the ones that were living on the edge. And now you were actually starting to see some benefit.

So that’s like the most incredible thing is that even giving this really bad stuff, the actual incidence of problems was really statistically quite low. And in the group of women, which was only like 10% of the study population, that were in their 50s, they actually had overall lowered mortality of all causes, all-cause mortality was lowered by about 30 or so percent, which is amazing. So here you’re giving the wrong thing and you actually had really good outcome in women in their 50s.

Just think if you actually had done that study using the right stuff what you might have shown. But what it did is the study totally caused women to become scared to death, that they were going to get breast cancer and heart attacks and strokes and dementia and all this stuff. And they were all taken off of their hormones. There have been some estimates that as many as 90,000 women died unnecessarily because they were just taken off over the next few years because they were discontinued from using even the wrong stuff.

It also then poisoned the minds of researchers for future studies as well. All the studies shut down, there was no action, nothing, no further progress. And then even when study started creeping back in because this had affected everyone’s mentality, and so the dogma became, if you’re going to use hormones, use the tiniest dose for the shortest period of time. So that became the mantra, the smallest dose, the shortest time. So even when they created new studies, they followed that philosophy by using really low doses, obviously, for shorter periods of time, so it didn’t always show great results because you can’t use… it would be like doing a study of vegetables, and you eat one bite a month, and then you say, “What’s the point of eating vegetables? They obviously do nothing.” That’s the problem.

But then the conclusions that they drew from these studies in one, in the [inaudible 00:52:40] study, that they actually looked at the levels, the serum levels of estradiol, and they practically didn’t deviate from the levels of the women who were in the control group who didn’t get hormones. So, you get such low doses that there was almost no difference in the levels of estradiol in either group. And then it didn’t show great benefit. Well, duh. It’s like, drive me crazy.

Dr. Weitz:            I have about 20 more questions, but neither you nor I have any more time because we both have patients. So, it’s the nine o’clock hour is [crosstalk 00:53:20]. So we’ll have to do a part two.

Dr. Gersh:           Well, I would love that. If there’s interest, I am here. Because we’re both passionate about this, which I love it. I love how knowledgeable you are, and how interested you are in this. It’s not just academic. This is like real lives are at stake here, real lives. And we’re just touching barely the surface of what this really can mean for women.  Once we accept that menopause is actually what it is, universal and universally harmful to women’s global health, it just is what it is. And that we can do a lot to change the outcome instead of just doing the whack a mole of trying to deal with each symptom as it arises and each complication, whether it’s with joints, or whether it’s with bones, or brain or heart or vessels. So we can do so much more if we just wake up to reality here and then sweep all this other bad stuff under the rug, close the door, and never go back and then look to the future.

Dr. Weitz:           Great. So how can listeners, viewers find out about you? And also get your books and do you have any training courses for practitioners?

Dr. Gersh:           Well, I’m thinking about that. If there’s demand, let me know.

Dr. Weitz:           I’m sure there is.

Dr. Gersh:           Well, I love to help both patients and practitioners. So my office, for people who want to either come or refer, I have a regular brick and mortar. I’m sitting on my examines right now in Irvine, California called the Integrative Medical Group of Irvine and I can do quite a bit with telemedicine as well. And I have an Instagram Live show at dr.felicegersh, which I try to do weekly. Every once in a while, I miss a week, but I’m trying. And I do have my two books on PCOS which have a lot of lifestyle advice, and I am almost finished with a book on menopause. And that will be coming out in the relatively near future, has to get cover and package and all that sort of stuff. So I am doing that.  Honestly, if people are interested in courses and so on, let me know because I’m very open to helping in any way I can. And if some people have suggested shadowing, I’m open to ideas. I’m mostly what I do is try to educate and care for patients. I look forward to doing more with you.

Dr. Weitz:            Sounds good.

Dr. Gersh:           You’re a gem, by the way.

 

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Dr. Weitz:            Thank you, Felice. Thank you listeners for making it all the way through this episode of the Rational Wellness Podcast. Please take a few minutes and go to Apple Podcasts and give us a five-star ratings and review, that would really help us so more people can find us in their listing of health podcasts. I’d also like to let everybody know that I now have a few openings for new clients for nutritional consultations. If you’re interested, please call my office in Santa Monica at 310-395-3111. That’s 310-395-3111 and take one of the few openings we have now for a individual consultation for nutrition with Dr. Ben Weitz. Thank you and see you next week.

 

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Dr. Dale Bredesen speaks about the Reversal of Alzheimer’s Disease with Dr. Ben Weitz at the Functional Medicine Discussion Group meeting on May 27, 2021.

[If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] 

 

Podcast Highlights

12:10   Traditional medicine currently has nothing effective to offer for the treatment of Alzheimer’s Disease, but yet is not open to the model that Dr. Bredesen is showing can reverse the condition.  There are over 400 failed trials with drugs to treat Alzheimer’s Disease. Dr. Bredesen has spent 30 years and he has published over 220 papers in peer review journals figuring out the fundamental nature of the neurodegenerative process to be able to design an effective treatment approach. Dr. Bredesen’s challenge to the traditional neurological community is “Look, you line up the people that you’ve made better, I’ll line up the people that we’ve made better, and let’s take a look at the lines.”  Dr. Bredesen’s group of practitioners has seen hundreds and hundreds of people improved.  Dr. Bredesen has just published a clinical trial that demonstrates the effectiveness of his approach with 25 patients treated by three different doctors.

20:37  The single drug approach has repeatedly failed for Alzheimer’s Disease and when Donanemab, which is another antibody that removes amyloid, was approved eight weeks ago, it was hailed. Yet, it doesn’t reverse or even stop the progression of Alzheimer’s Disease, but merely slows the decline and Eli Lilly stock went up 20 billion dollars. The reason for this failure is that Alzheimer’s is not a simple illness like a viral infection.  Rather Alzheimer’s is a complex, chronic disease and such a simple approach is doomed to failure unless it is possibly combined with a systems approach.

21:13  There are a number of theories about what causes Alzheimer’s Disease, including the amyloid cascade theory, which has been the target of numerous failed pharmaceuticals, including Bapineuzumab, Crenezumab, Gantenerumab, and Aducanumab and the list goes on and on. Some people say that amyloid is not important, but rather it’s tau that is the problem.  But Dr. Bredesen explained that both amyloid and tau are both mediators of a downsizing of the brain and they are both physiological responses to various insults to brain health.  Here is the full list of theories of the cause of Alzheimer’s disease that Dr. Bredesen discussed: 1. Amyloid cascade, 2. Tau, 3. Prion, 4. Type 3 diabetes, 5. Chronic herpes simplex infection, 6. Gingipain produced by P. gingivalis, 7. mercury toxicity, 8. Metal binding by amyloid, 9. Reactive oxygen species, 10. APP amplification, 11. Cortical demyelination, 12. Vascular leak. 

24:55  The amyloid hypothesis says that you have too much amyloid but it doesn’t consider why and we know now that when you remove it, you don’t get better, and some patients get worse.  The amyloid is a protective response by the brain to infections and other insults.

25:17  The problem is that if you go to a conventional Alzheimer’s center, they’ll tell you that we don’t know what the cause is, and that we’re going to give you a monotherapy, whether it be Aricept or Namenda, and it will be ineffective, and you’re going to die. 

25:51  The research findings show something completely different.  They show that there are dozens of contributors to the cause of Alzheimer’s disease and these can be broken down into subtypes.  Some patients have more of an inflammatory type of Alzheimer’s, while others have more of an atrophic type.  So we personalize the program for each person and as we treat patients we continue to optimize all the factors that can contribute to cognitive decline.  Some patients will improve and then they’ll plateau and then we find another contributor to their condition and we address that and then they improve further.

26:31  The conditions that are associated with cognitive decline include the following:

            1. Alzheimer’s disease, the most common form.  BTW, the term mild cognitive impairment, MCI, is really the third of four stages of end-stage Alzheimer’s, so this is not an accurate term to use. It is like saying mildly metastatic cancer.

            2. Lewy Body Disease. The classic version of this involves visual hallucinations but otherwise looks a lot like Alzheimer’s.  They tend to sleep late and have periods where they are very good and very bad.  They are very sensitive to drugs and can die if you give them anti-psychotics.

            3. Parkinson’s.  There are about a million patients with Parkinson’s disease in the US and it is on the greatest rise now.

            4. Vascular dementia.

            5. Normal pressure hydrocephalus. These patients usually have urinary urgency. An MRI would show enlarged ventricles and no atrophy.  

            6. Frontotemporal dementia, which a cousin of ALS.  They both involve a protein called TDP-43.

            7. LATE. Limbic-predominant age-associated TDP-43 encephalopathy.  If you have someone with a slowly progressive Alzhemier’s that didn’t start till they are over 80, esp. if they have a negative amyloid scan.

            8. Multiple Sclerosis. Patients with MS have cortical shrinkage of about a few percent per year. Dr. Terry Wahl’s protocol addresses the key points for MS.

            9. PSP. Progressive supranuclear palsy.  You can diagnose these patients by asking them to look up and then look down. They have trouble with vertical gaze.

            10. Corticobasal degeneration. This is another Parkisonian-like presentation and these patients have something called alien hand.

            11. CTE, which is chronic traumatic encephalopathy.  These patients often have the triad of depression, aggression, and dementia.

            12. TBI. Traumatic brain injury.

            13. Post-COVID-19 related encephalopathy?   Many patients report brain fog and other cognitive issues after COVID.  One feature of COVID-19-related encephalopathy is that you have multiple small vessel occlusions and there is an autoimmune aspect where patients are reacting to the virus and viral antigens.  There are some interesting parallels between Alzheimer’s and COVID-19, including that you have a mismatch between the innate immune system, which is activated, and the adaptive system, which is not able to clear the pathogens.  The adaptive immune system is supposed to take over at a certain point, but is unable to do that.  Patients with COVID-19 may have a cytokine storm and can die from it acutely, whereas patients with Alzheimer’s have a cytokine drizzle that goes on for years.

            14. CJD. Creutzfeldt-Jakob disease, which is a prion disease.  These patients tend to progress much more rapidly with patients getting worse week to week instead of over  months or years.

            15.  Subdural Hematoma.  This can be ruled out with mri.

 

35:46  The Stages of Alzheimer’s Disease.  There’s a pre-symptomatic stage that can progress for years and you have no symptoms but you have the pathophysiology going on. Then you progress to SCI Subjective Cognitive Impairment, which is when you have symptoms but the tests are not showing anything wrong and on average this stage lasts 10 years.  The next stage is MCI Mild Cognitive Impairment, which is when neuropsych testing is now abnormal and this tends to progress at about 10% per year.  

 

37:22  Dr. Bredesen’s Sub-types of Alzheimer’s Disease:

            1. Type one Inflammatory. 

            2. Type two Atrophic. 

            1.5 Type 1.5 Glycotoxic or sweet type. 

            3. Type three is Toxic.

            4. Type four is Vascular. 

            5. Type five is Traumatic.                                            

The biggest thing to note is someone presenting with an amnestic syndrome where the biggest problem, and the first problem, is really about learning new information. That’s classical Alzheimer’s and that’s typically not type three. Type three is often a little different, but that’s classical Alzheimer’s.  It’s more APOE4 positive Alzheimer’s, and it represents about two-thirds of Alzheimer’s.  You typically see a reduction in glucose utilization in the temporal region of the brain if you look at a PET scan.  But about a third of people will come in with non-amnestic presentations and they will have problems with executive function and may have primary progressive aphasia.  PCA, which is posterior cortical atrophy. So these are the people that have trouble with recognition of faces and objects.  Prosopagnosia, problems recognizing faces, executive dysfunction, dyscalculia, apraxias, agnosias, depression.  These patients will typically have a reduction of glucose utilization in the parietal region of the brain on PET scan.

39:18  Beware the patients that present with depression because they often are the ones that have exposure to toxins and these are often type three.

39:30  When we look at the molecular biology of Alzheimer’s disease, Dr. Bredesen has discovered that the neurofibrillary tangles and the senile plaques and the brain atrophy are all a result of environmental factors that promote synaptoclastic activity over synaptoblastic activity in the brain.  This results from how these things affect APP (Amyloid Precursor Protein), which sticks out of a cell and is the molecular switch that controls Alzheimer’s disease that senses whether we are in a brain growth mode or a brain shrinkage mode and this affects the way that this APP switch works. For example, estradiol binds to its receptor and enters the nucleus and turns on a bunch of genes.  Estradiol, which is a good thing, cleaves APP at one site, which leads to two peptides that are growth and maintenance. But if you have Herpese Simplex virus, which is a bad thing, or pathogens from your mouth, or Lyme disease, or leaky gut, or not getting enough sleep, or having too much stress, then APP recognizes those things and you cleave APP at three sites–at the beta, the gamma, and the caspase site and these peptides all stimulate brain shrinkage and protection mode.  Amyloid protein is being laid down to protect your brain from all these insults. Our job is to flip the switch and put your brain back into growth and synatoblastic mode and out of the shrinkage and synaptoclastic mode. The fundamental nature of Alzheimer’s is a network insufficiency of the subsystem of the brain that controls neuroplasticity.  If you have a network insufficiency of the brain that controls the stabilization of motor movements, you get Parkinson’s disease.

42:52  We know that most chronic diseases are signaling imbalances. Take osteoporosis, where you have osteoclastic activity outweighing osteoblastic activity.  With cancer you have cytoblastic activity of cancer cells outstripping the cytoclastic activity of the immune system.  With Alzheimer’s, anything that causes inflammation, whether it be leaky gut, poor oral health, chronic sinusitis, metabolic syndrome, toxins, mercury, air pollution, organics like formaldehyde, toluene, benzene, or glyphosate or biotoxins like trichothecenes or ochratoxin A.  When we talk about having too little energetics there are four major contributors: blood flow, oxygenation, mitochondrial function, and ketones, as well as sleep.  When it comes to trophic support we have growth factors like NGF and BDNF, hormones like thyroid, estradiol, testosterone, pregnenolone, and progesterone and nutrients like vitamin D and omega 3 fats.

47:47  APOE4 is the most common genetic risk factor and about 1/4 of the population has at least one copy and this confers a 30% increased lifetime risk of Alzheimer’s disease.  If you have two copies of APOE4, you have a lifetime risk of more than 50%.  Dr. Bredesen’s research shows that a critical part of your ApoE enters the nucleus and binds to 1700 different gene promoters and if you group these, they tell a story for Alzheimer’s disease.  So ApoE4 promotes inflammation and its involved with disassembling your microtubules and synapse dysfunction.  When we treat patients with Alzeimer’s, we want to resolve their inflammation. We want to know their energetic status. We want to identify if they have insulin resistance and get them sensitive again.  We want to know the status of their trophic support. We want to treat pathogens and if they have toxins to detoxify them.  It helps to provide them with some mild stimulation like infrared light or other forms. We want to improve the adaptive immune system and reduce the innate system.  After we have done the things above, then we want to remove the amyloid, but removing the amyloid at the beginning is a bad idea because it’s protecting you. And then ultimately, we want to use things like stem cells and trophic factors to promote regeneration. 

57:27  Dr. Bredesen and his group just completed a proof of concept trial with 25 patients with MCI or early dementia with MoCA scores of 19 or above to prove that his Functional Medicine approach to Alzheimer’s Disease is effective and the first paper was published on a preprint.  Precision Medicine Approach to Alzheimer’s Disease: Successful Proof-of-Concept Trial.  Kat Toups, Ann Hathaway, Deborah Gordon, Henrianna Chung, Cyrus Raji, Alan Boyd, Benjamin D. Hill, Sharon Hausman-Cohen, Mouna Attarha, Won Jong Chwa, Michael Jarrett, Dale E. Bredesen.  A larger randomized clinical trial is now planned.  This trial looked at MoCA scores at the beginning, at three, six, and nine months, as well at CNS vital signs, at AQ-21, which from the patient’s partner looking at how many complaints they have, and they also did MRI with volume metrics at the beginning and at nine months and the results were striking.  They tried to achieve insulin sensitivity, mild ketosis, healing the gut, treatment of identified pathogens, detox for those who needed it, reduction of inflammation, optimization of hormones, nutrients, and trophic factors, vascular status, some degree of brain stimulation, optimization of SpO2, and then stress management, and improved heart rate variability.  76% of patients significantly improved their MoCA scores and 84% improved their Neurocognitive Index score.  Brain training scores improved in all 25 subjects.  They would have had even better results if the pandemic had not have happened during their trial.  They saw the grey matter volume of their brain went up and the hippocampal volume decline normally seen in Alzheimer’s patients improved. It is typical for someone with Alzheimer’s hippocampal volume to decline about 2.5-3.5% per year, whereas a normal individual sees a decline of about 1.7% per year, while these patients only declined by 1.29%.  So for these patients with MCI or early dementia, cognitive decline was reversed, which has never been shown in any drug trial! 

59:24  Compare Dr. Bredesen’s approach, which actually makes people better, with the announcement of this new drug for Alzhemimer’s, Aducanumab, which was just approved by the FDA and is considered the big success in drugs that are antibodies to amyloid, which did not make people better but merely slowed the decline by about 1/3.  The day this was announced the value of this company increased by $20 billion in one day. 

1:03:15  Dr. Bredesen believes that they may be able to modify this Functional Medicine approach for other neurodegenerative diseases, including Lewy body disease, Parkinson’s, Frontotemporal dementia, for ALS, for macular degeneration, etc..

1:05:07  While some anti-aging biohackers recommend taking rapamycin to inhibit mTor, which can be beneficial in promoting health, and improving biological aging and brain function, Dr. Bredesen recommends intermittent fasting and a ketogenic diet to inhibit mTor rather than taking a potentially toxic drug like rapamycin.

1:08:00  Strategies to increase oxygen to the brain, like hyperbaric oxygen, can be helpful for promoting brain healing.  Dr. Bredesen believes that hyperbaric oxygen seems to be helpful, esp. for patients who have vascular disease or head trauma as one of their contributors. He is not sure that it will help as much with patients who have glycotoxicity or just inflammation. He prefers EWOT, which is exercise with oxygen therapy to hyperbaric where you just lay in a tank. 

1:09:41  The diet that seems to work best is the KetoFLEX 12/3 that seems to drives the biochemistry towards synaptogenesis and synaptic maintenance.  The diet is very plant rich with lots of phytonutrients and fiber with fish and pastured chicken and grass fed beef and 12 to 16 hours of intermittent fasting.  You want to become insulin sensitive and get into ketosis.  If you have severe vascular disease, you might want to go vegan.

1:11:20  Statin drugs are often prescribed for patients with vascular issues and high cholesterol, but they can be problematic for brain health. They do lower inflammation, but cholesterol is important for neuronal formation and brain health and there are better ways to reduce inflammation. If you have inflammation, let’s correct the underlying cause of the inflammation, such as leaky gut or gut dysbiosis or issues with oral health.

1:14:36  Red or infrared light therapy with a frequency around 40 Hz seems to be helpful to stimulate brain healing as is 40 Hz sound.  There is Vielight and there’s magnetic stimulation or MeRT. These ways to stimulate the brain will not likely be effective until you have fixed all the issues that were keeping your brain from working well and now this type of therapy can help to stimulate neurons to fire and push your brain to heal.

1:17:56  ProLon, Dr. Valter Longo’s Fasting Mimicking Diet 5 day program, can be used to get patients to start to feel what a ketogenic diet is like, though it may not work if the patient is very thin and frail.  In such cases, you want to cycle such patients in and out of ketosis and give them a rest day, say once a week. Alzheimer’s is a disease of insufficiency, though we often get there by excess.  Patients who are very thin don’t have a lot of glucose around and may have trouble generating ketones.  We have to have that fasting period without getting them further into insufficiency.

1:21:52  Peptides like Cerbrolysin, Thymosin alpha one and beta four can be helpful when used at the appropriate time.  Intra-nasal administration may be helpful in getting them into the brain. There are also peptide fragments of nerve growth factor and BDNF.  Like pharmaceuticals, once you address all the things causing the problem, then they can be used to help the brain to regenerate, but not before.  Dr. Bredesen also believes that stem cells can be helpful, once you have corrected all the things that have been making the brain worse. If you simply apply peptides or stem cells or medications as a monotherapy, it is like trying to rebuild a house as it’s burning down. You’ve got to put out the fire first and then the conditions will be ripe for rebuilding.

 

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Dr. Dale Bredesen is a neurologist and an internationally recognized expert in the mechanisms of neurodegenerative diseases like Alzheimer’s Disease and the Chief Science Officer at Apollo Health. He is the author of the best selling books, The End of Alzheimer’s, and The End of Alzheimer’s Program, as well as the soon to be published, The First Survivors of Alzheimer’s. Dr. Dale Bredesen’s career has been guided by a simple idea: that Alzheimer’s as we know it is not just preventable, but reversible. Thanks to a dedicated pursuit of finding the science that makes this a reality, this idea has placed Dr. Bredesen at the vanguard of neurological research and led to the discoveries that today underlie the ReCODE Report.  Dr. Bredesen offers training for doctors and practitioners in his ReCODE system at his website at ApolloHealthco.com.

Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

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Podcast Transcript

Dr. Weitz:                            Hey. This is Doctor Ben Weitz, host of the Rational Wellness podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness podcast for weekly updates. To learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast.

                                                Welcome everyone, and thank you for joining our Functional Medicine discussion group meeting. I’m Doctor Ben Weitz, and our topic for tonight is the Prevention and Reversal of Alzheimer’s disease with our special guest Doctor Dale Bredesen. I’ll start by making some introductory remarks, including introducing the topic.

                                                The topic for tonight is Alzheimer’s disease. As most of you know, it’s a degenerative brain disease, and it accounts for between 60 and 80 percent of cases of dementia. Patients with Alzheimer’s disease develop difficulties with memory, language, problem solving, other cognitive skills that can affect a person’s ability to perform everyday tasks. The hallmark pathologies of Alzheimer’s are the progressive accumulation of beta amyloid protein in the brain that forms plaques outside neurons in the brain, and twisted strands known as tangles of tau protein inside of neurons. There are an estimated 5.7 million Americans living with Alzheimer’s disease as of 2018. Obviously, it’s higher now because it’s rapidly increasing, especially as the population of Americans 65 and older is projected to grow from 53 million in 2018 to 88 million by 2050.  According to one estimate, Alzheimer’s disease is the third leading cause of death in the U.S., according to the Alzheimer’s Association. According to the Alzheimer’s Association website, and this is a quote, “While there is no cure for Alzheimer’s disease, or a way to stop or slow its progression, there are drugs or non drug options that may help treat symptoms.” Our goal for this evening will be to prove that the Alzheimer’s Association is wrong. Now, I’d like to invite Heather Ngo [now Heather Sunshine] from Cyrex Labs, which is one of our sponsors for this evening, to give us some information about Cyrex Labs. Heather, are you here?

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Heather Sunshine:         I am here. Thank you so much, Doctor Weitz. Hello, everyone. My name is Heather Sunshine, Territory Manager of Cyrex Labs. Our lab is based in Phoenix, Arizona, and our niche is environmentally induced autoimmunity. We are CLEA certified, and our innovative test provides advanced clinical tools to identify and measure immune and possible autoimmune reactivity. We have essential barrier testing evaluating the intestinal and blood brain barrier integrity. We have predictive antibody testing, identifying markers and possible precursors of autoimmune disorders. Environmental triggers, identifying reactivity to environmental triggers, which include dietary proteins, chemicals and heavy metals. We also have a mucosal immune saliva test.

                                                What I would like to share with you today, since it’s relatable to Doctor Dale Bredesen’s presentation, is our Alzheimer’s Linx panel. Alzheimer’s disease, cognitive decline, dementia, whatever name we use, the diagnosis is a heavy one. It comes with enormous financial and family burden, so ideally, you want to avoid this disorder. Environmental factors are far more influential than genes, and it if plays the larger role in Alzheimer’s disease, we have the opportunity to prevent it. We change our environment. We avoid certain foods, chemicals. We reduce stress. We make our bodies inhospitable to pathogens. We learn a new language, take dance classes, play brain games to regenerate neuronal tissues. We can protect our blood brain barriers. All of this means we are reducing inflammation. The sub clinical signs of inflammation, antibody production against triggers and tissues, can be found up to 20 years before the onset of disease. Therefore, in the more common form of environmentally induced Alzheimer’s disease, the late onset, people should be tested as early as age 40.

                                                Here’s how Cyrex is going beyond tau amyloid beta. We assess proteins, growth factors, pathogens, chemicals, enteric nervous system, enzymes, neuro peptides and foods. Alzheimer’s links can be used to identify targeted tissues, triggers and blood brain barrier integrity during the early onstage of Alzheimer’s disease when recovery is possible. Test at the first sign, especially if the patient has family history. We do have a video of Doctor Dale Bredesen with our brilliant Chief Scientist Advisor, Doctor Aristo Vojdani, along with his brilliant son, Doctor Elroy Vojdani. You can view this video on joincyrex.com. It’s under our media section. If you would like to schedule a one on one education, or have any questions, if you want me to send you a catalog of services, we do have some new bundling prices and specials, or if you just want me to send the link to the video, please email me at heather.s@cyrexlabs.com. Thank you so much, Doctor Weitz, for the opportunity to discuss Cyrex and providing us an insightful forum, as always. We are excited to listen to Doctor Dale Bredesen’s presentation tonight.

 

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Dr. Weitz:                            Thank you, Heather. Now, my friend Steve Snyder from Integrative Therapeutics. Steve, you have the floor to tell us about Integrative Therapeutics professional line of supplements.

Steve Snyder:              That was really good. I don’t think I can do that well. One of the things I wanted to mention, Doctor Bredesen, was … By the way, I’m Steve from Integrative Therapeutics. Most of you know me already. I’m the L.A. rep for Integrative. Doctor Bredesen mentioned Gary Small over at UCLA. They actually did a nice study on our theracurmin, the high bioavailable curcumin, showing improved memory and decreased amyloid tangles and tau proteins. It wasn’t Alzheimer’s patients, it was age associated memory decline, but some pretty interesting outcomes, and they’re continuing to look at that. I don’t know where that fits into your protocols, but it was a really good study for that particular product for us.

                                                Then the other thing that I was just going to mention really quickly, some of you saw this on the Facebook page. There has been a lot of chatter about there about NAC, or nac, being banned. I just wanted to let people know that’s not what’s happening. The FDA sent out some warning letters last year, basically trying to say that NAC shouldn’t be considered a supplement because it was originally researched as a drug back in the early 60s. It’s not a policy change, it’s not anything out of legal change, they’re just sending out these letters. The Council for Responsible Nutrition is pushing back on it pretty hard. There’s a great letter you can Google that talks about it. It’s also on Doctor Weitz’s Facebook page.

                                                The reason people are getting excited is because Amazon pulled NAC containing products, and Whole Foods Market will probably follow that because they’re owned by Amazon. We’re not sure why they’re doing that, but we are not discontinuing any NAC containing products. We don’t think it’s going to end up coming to that. It’s business as usual. Right now Full Script has over 1500 bottles of our product. We have about 8000 bottles of our product, so it’s not in short supply. If you need it, you can get it.

                                                The other thing is, if it ever does come to that, Integrative Therapeutics will still be able to make it because we are a drug manufacturing facility even though we don’t make drugs. Not every supplement company is that, and that will affect some people, but it won’t affect us. We will continue to make NAC. We have a stand alone NAC that’s 600 milligram per cap. It’s under 20 dollars retail for 60 caps. It’s a great option. Don’t panic. Don’t believe what you’re reading, it’s not getting banned. If you have any questions you can reach me at steve.schneider@integrativepro.com. Thanks.

Dr. Weitz:                    Thanks, Steve.

Steve Snyder:              Yeah.

 

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Dr. Weitz:                            Our speaker for tonight, who really needs no introduction, is Dr. Dale Bredesen. Dr. Bredesen is an internationally recognized expert in the mechanisms of neuro degenerative diseases like Alzheimer’s disease. He’s the author of the best selling books, The End of Alzheimer’s and The End of Alzheimer’s Program, as well as the soon to be published, the first Survivors of Alzheimer’s.  Also wanted to let everyone know that Dr. Bredesen, Dr. Kat Toups, and associates, have just published a paper documenting their trial with 25 patients showing the effectiveness of his protocol for Alzheimer’s disease. The paper is entitled “Precision Medicine Approach to Alzheimer’s Disease, Successful Proof of Concept Trial”. Doctor Toups posted it on the Facebook page, so you can get a full copy of it there.

                                                I’d like to tell you one more quick anecdotal story. I’ve been organizing these Functional Medicine meetings for about five years, and about four years ago I decided I wanted to discuss Alzheimer’s disease. I tried to get in touch with Doctor Bredesen because I had heard him a few years earlier on Doctor Bland’s Functional Medicine Update audio show, to see if he could join us. I was not successful, so I sent out a copy of Doctor Bredesen’s 2014 paper to our members to use as a basis for our discussion. Then I contacted the UCLA Alzheimer’s program that Doctor Bredesen was associated with to see if perhaps another neurologist might want to join us. When I called, the woman who is the administrator of the program said that she would ask around the neurologists there, but she let me know right up front that they don’t agree with anything that Doctor Bredesen talks about.

                                          Doctor Bredesen, thank you so much for joining us tonight.

Dr. Bredesen:                    Okay. Thanks for the invitation here. Let me go ahead and share my screen here. Okay, there we go, share that. Can everyone see that okay, hopefully? Okay, there we go. It is interesting to me, having trained as a neurologist, and very classically training, Cal Tech and MIT, and Duke, and Harvard, and all this, where we have nothing. Classical medicine has nothing to offer Alzheimer’s disease, and as you indicated earlier, the Alzheimer’s Association is basically saying, “There is nothing to offer, but maybe we can have a symptomatic effect.”   As I’ll show you today, that is completely wrong, and in fact, we need to be looking at what actually moves the needle. We’ve spent 30 years, we’ve published over 220 papers in peer review journals, and the whole point of the laboratory research was to understand the fundamental nature of the neuro degenerative process well enough that we can begin to fashion the first effective treatments. As you know, this has been the area of greatest biomedical therapeutic failure. As they say, “Everyone knows a cancer survivor, no one knows an Alzheimer’s survivor.” There are some interesting parallels with what’s happened with Covid-19, as well, and we’ll get into that.   The bottom line is, it continues to amaze me that people who have absolutely nothing to offer are complaining when there’s something to offer. When people say this sort of stuff to me, I always say the same thing, “Look, you line up the people that you’ve made better, I’ll line up the people that we’ve made better, and let’s take a look at the lines.” We’ve had hundreds and hundreds and hundreds of people improved. As you’ll see from the trial, very exciting results with the trial.

                                                This is essentially a pandemic without a vaccine. Just for some perspective, and let me just minimize this here so I can see all the slides a little better. Covid-19 has killed now, we just passed 600,000 people in the United States. Alzheimer’s will lead to the death of nearly a hundred times that many. If you look at all the currently living Americans, about 45 million will die. As Ben mentioned earlier, about 5.7 million are already recognized. Of course, younger people, we don’t know. We have two daughters who are 29 and 31, we don’t know if they’re going to get it or not. If you take everyone who’s currently living, statistically, about 45 million will die of Alzheimer’s. This is a huge, huge pandemic.

                                                The problem is a fundamental one, and we don’t hear enough about this. We’re always told, “Well, it’s something about the plaques and the tangles, and we’re trying to figure that out, and maybe the next drug is going to work.”, and of course, there are over 400 failed trials per drugs. The fundamental problem is not talked about enough. The fundamental problem is, for example, Covid-19 is a simple disease, we know what causes it. We even have sequence from the virus. We have sequence from the mutants. All these things, we know what to do for prevention. We have vaccines developed, some people like them, some people don’t. At least we understand the disease itself. That is not the case for Alzheimer’s. It is a chronic, complex disease of unknown etiology. People keep on, as I’ll show you, they keep on thinking it’s going to be one thing, “We’re going to figure out what causes it, and boom, we’ll be able to do something about it.” That’s not the way this disease works, and it’s important for us to understand that.

                                                No surprise, billions of dollars, over 400 failed clinical trials. We really need to take a completely different look. What I ask you to do today is, forget what you know, forget what you’ve heard about Alzheimer’s for just a few minutes, and we’re going to look at this from the ground up, and look at what actually this disease represents, which is what our research had been all about. We want to develop a model that is consistent with all the papers published. There are over a 150 thousand published papers about Alzheimer’s. None of them has led to any successful treatments. We want to reconsider this, and look at what we can do. Can we develop a model that is predictive, that tells us what’s going to work, and tells us what’s not going to work? That would be such a helpful model. As you may have heard, if you look at something like Aducanumab where there’s been very little help trying to get rid of amyloids. If you could simply have a model that would tell you what’s going to work and what’s not going to work it would be exceedingly valuable.

                                                The day that Donanemab, which is another antibody that removes amyloid, it just came out about eight weeks ago. What they showed was, it doesn’t make people better. It doesn’t stabilize people, but it slows the decline. In the trial it slowed the decline by about one third. The day that came out, the stock in its company, Eli Lilly, went up by 20 billion dollars in total company value. To be able to say, “We understand this disease. We know what’s going to work. We know what’s not going to work, and we know when to use it.”, would be a very, very important thing. Let’s talk about that.

                                                I think everybody here, anyone who’s interested in functional medicine, and I have to say I really appreciate Jeffery Bland’s contributions over the years to this whole idea, everyone understand that there’s a fundamental difference between simple illnesses and complex chronic illnesses. Here’s simple illness, which we all dealt with in medical school. You got someone with pneumococcal pneumonia? Yes. If they’ve got alcohol onboard they’re at increased risk. If they have diabetes melitis they’re at increased risk. If they have abnormal B cells, for example, people with multiple myeloma do poorly with pneumococcal pneumonia. There are lots and lots of other contributors. We, as physicians, have gotten away, over the years, with because of the fact that the pneumococcus itself is so much more important than any of these other variables, we’ve gotten away with writing prescriptions for penicillin, amoxicillin, cephalosporins, what have you. That’s been good enough, even though it doesn’t address all the contributors.

                                                That’s great for a simple illness. However, here’s the problem, in the 21st Century we are virtually all dying of complex chronic illnesses. Alzheimer’s, and cancer, and cardiovascular disease, and Lewy Body and Parkinson’s, all these sorts of things. Therefore, when you look at those, they are fundamentally different than these simple illnesses. Let’s look at Alzheimer’s for a minute. Insulin resistance is one critical risk factor. Various pathogens, everything from Borrelia to Bartonella and Babesia, to Herpes Simplex from the lip, to P. gingivalis from the oral microbiome, these are all things identified by the neuro pathologists in the brains of Alzheimer’s disease patients. These are critical. NfkB, which is simply activated in your cell when there is ongoing inflammation, turns out to be important, and I’ll show you why.

                                                Mercury, inorganic and organic mercury, turns out to be important in your risk. Various micro toxins turn out to be important. Various organic toxins, high homocysteine, poor methylation, and we could go on and on. There are dozens and dozens of contributors. The good news is, it appears there are not thousands. There are dozens and dozens, somewhere probably fewer than 100, but it’s not one or two. As you can see here, the big difference between pneumococcal pneumonia and Alzheimer’s disease is that there is no one of these that outstrips the others the way the pneumococcus did for pneumococcal pneumonia. Therefore, we can’t simply write a prescription that says, “Here’s a prescription to treat your homocysteine.” It’s not that simple. Therefore, we need to flip the script. We need to look at all the different contributors in each person, and then address those with a systems medicine, or precision medicine, approach.

                                                Therefore, no surprise, you can go at trial, after trial, after trial that has failed. As an example, here in the middle, Semagacestat. That was from Eli Lilly. They spent over 500 million dollars developing Semagacestat.  Not only did it not help, it actually made the disease worse.  Donanemab, here you can see, they didn’t believe it when it failed the first time. They did another trial, this time with Aricept, it failed again. There’s something fundamentally wrong about the way we’re going about this, when you’re seeing such failure time, after time, after time.

                                                Here are theories of Alzheimer’s, and there are others. These are many of them, but not all of them. There are ones, bottom line is, none of them has led to an effective treatment for Alzheimer’s. What the heck is wrong? We have to understand that. The dominant theory over the last 25 years has been the amyloid cascade theory. That came about basically for two reasons. There are people who have mutations in the amyloid precursor protein, and they develop familial Alzheimer’s. That’s rare, fewer than one in a thousand has the APP mutation that is associated. There are several of the mutations that are associated with this. It’s literally, it’s about just over 100 families worldwide, so it’s not a common cause. The idea was, “Okay, this amyloid is bad stuff, and we’re going to get rid of the amyloid, and you’re going to be all better.” Then, this has been tried time and time again with various pharmaceuticals. Bapineuzumab, Crenezumab, Gantenerumab, Aducanumab, Donanemab, the list goes on and on and on. Nothing. They have not had success.

                                                Tau, and other people just say, “Okay, amyloid is not important, but tau is important.” Well, yes. They’re both mediators of what I’ll show you is happening that is a mediator of a downsizing of the brain. It’s actually a physiological response to various insults. Then, of course, prions, and actually, my mentor, Professor Stan Prusiner, discovered prions and was awarded the Nobel Prize in 1997 for his discovery of prions. Again, these are mediators of the disease, but in general are not getting this because they’re catching prions. We believe that this is actually part of the downstream signaling. Type three diabetes, we hear that term all the time, and there’s no question, most… Type three diabetes, we hear that term all the time. And there’s no question most of the people with Alzheimer’s do have insulin resistance. But you don’t have to have that to get Alzheimer’s and you don’t have to have diabetes to get Alzheimer’s. You don’t have to have Alzheimer’s to get diabetes. So, the bottom line is it’s neither necessary nor sufficient. But yes, it’s an important overall player.

                                                Chronic herpes simplex, nice studies out of Taiwan, showing that people who actually treated their chronic, their recurrent herpes simplex oral, labial here, they actually had a reduced risk for Alzheimer’s.

                                                Gingipain. So there’s a whole company that is arranged around the idea that we’ve got these P gingivalis, which are associated with poor oral health. So they get into the brain and they’re producing a protease called gingipain. And that’s what’s doing the damage. Likely that’s part of it, unlikely that that’s the whole story.

                                                Mercury toxicity. Again, treating mercury has turned out to be helpful for a number of people. Metal binding by amyloid. This goes on and on. Reactive oxygen species, APP amplification. That’s some nice work out of UC San Diego. Cortical demyelination, vascular leak. It just goes on and on. None of these has led to a successful treatment for Alzheimer’s, and that’s really ultimately the asset test.

Dr. Weitz:                          Doc

Dr. Bredesen:                    So here’s the problem. Sorry, Ben. What’s that?

Dr. Weitz:                          Yeah. Can I just make a comment about the amyloid?

Dr. Bredesen:                    Sure.

Dr. Weitz:                          I think the amyloid, nobody’s asking, why is there amyloid there in the first place?  And you just mentioned the amyloid binding to the metal. And we’ve learned that amyloid is a way to protect the brain against infections and inflammation. And that’s really the key, is asking the additional question, what’s the root cause?  Why is the amyloid there in the first place?

Dr. Bredesen:                    Yep, absolutely. I think it’s critical to understand that. And the amyloid hypothesis just says you have too much amyloid for some reason, and that’s why you get Alzheimer’s, and it really doesn’t give you any insight. And we know now, if you remove that, you don’t get better. And in fact, what we found a number of people actually get worse when they remove the amyloid. Because again, as you said, it is a protective response to these various insults.   So here’s the problem. If you go to an Alzheimer’s center or an Alzheimer’s center of quote “excellence” today, what they’ll tell you is that there’s a cause, we don’t know what it is. There’s some cause that’s unknown. This is a disease called Alzheimer’s. There is a treatment. It’s a monotherapy, Aricept or Namenda, you can also use Exelon. It’s the same idea. It’s one phase. We’re going to give you the same thing each time. We’re going to stick with it and it’s going to be ineffective and you’re going to die.  And it’s just a horrible, horrible state of affairs. I have to say, it’s pretty barbaric right now.

                                           The research findings on the other hand, show us something completely different. What they say is there are dozens of contributors. As I mentioned earlier, we initially identified 36. There are a few more, low forties, but it’s not thousands. Therefore, no surprise, there are subtypes. You see people who have more of an inflammatory type of Alzheimer’s, people who have more of an atrophic type, and we’ll get into the subtypes in just a minute. And therefore, no surprise, there are many personalized programs and you’ve got to keep optimizing for the person.   We have people who will improve and then they’ll plateau and then find another contributor. And then we address that, they improve still further. This happens all the time. So some of the causes. When you do see people with cognitive decline. And since I assume that most people here are seeing some people with cognitive decline, let’s talk for a minute about what causes cognitive decline. As Ben said earlier, the majority, the most common Alzheimer’s disease. And let me just take a moment. This idea about mild cognitive impairment, this is the third of four stages to end-stage Alzheimer’s. So we really need to find new nomenclature for this idea of mild cognitive impairment.

                                                This is just like saying mildly metastatic cancer. Yeah. Okay. Well it’s already metastatic cancer. That’s a very late stage of cancer. And it’s the same thing with Alzheimer’s. MCI is a late stage of the problem. You go about 10 years of SCI before you ever get to MCI. Now Lewy body disease, about a million people in the country. Parkinson’s also about a million people in the United States, and actually Parkinson’s is the disease in neurological degenerative diseases that is on the greatest rise right now.   It seems to be linked to various toxins. So these things are critical. Lewy body, of course, the classic is people with visual hallucinations. Otherwise, it looks a lot like Alzheimer’s in many respects, they have a few other features. They tend to sleep late. They tend to have something that’s called showtime where they get really good and they get really bad. They’re very sensitive to drugs. They can, if you give them classical anti-psychotics, they can actually die. So you have to be very careful about those people. Keep an eye out for those. Vascular dementia, of course, very common as well. And especially if you have people who have sudden stroke-like changes, something to look at. An MRI can be very helpful at picking up that.

                                                Normal pressure hydrocephalus. It’s been claimed that one out of 10 patients with dementia has normal pressure hydrocephalus. I myself think that’s too high. I would argue more like a couple out of 100 maybe. Not common, but you will see it at some point. You don’t want to miss it because it’s very treatable with a shunt. And the classic, the thing to ask and the thing to look for, if these people don’t have the triad of gait apraxia, urinary incontinence, and dementia, simply they must have some degree of urinary urgency. If they don’t have urinary incontinence or urinary urgency, very unlikely.

                                                Again, if you get an MRI that shows that you’ve really got these blown up ventricles and no atrophy, it’s something to think about. So you don’t want to miss that one. Frontotemporal dementia, interestingly, is a cousin of ALS. These things often run together. They both involve a protein called TDP-43. It’s a tough one. It’s only about one-twentieth as common as Alzheimer’s. So not terribly common, but again, something to keep an eye out for.

                                                And then there’s a new one that was just described about a year ago, called late limbic-predominant age-related TDP-43 encephalopathy. That’s a mouthful, but essentially it is like frontotemporal dementia, but it’s in people who are over 80. So this is the one, it affects the limbic system and it affects the temporal lobes. So different place than frontotemporal dementia, but same pathology with a TDP-43, which is present in ALS and frontotemporal dementia and LATE.

                                                So if you see someone who has slowly progressive Alzheimer’s, that didn’t start until they were over 80, good chance that that’s LATE, especially if they have a negative amyloid scan. Then of course, multiple sclerosis. Interestingly, people with multiple sclerosis have actually cortical shrinkage of about a few percent per year. So they actually do, over time, often develop some degree of cognitive decline. And that’s why things like Terry Wahl’s protocol, I think is fantastic. Really addresses the key points for MS.

                                                And then PSP, progressive supranuclear palsy. Another thing that can present with cognitive decline. These people, the classic, have them look up, have them look down. These people have trouble with vertical gaze. And then corticobasal degeneration. This is another Parkinsonian-like presentation. These people often have something called alien hand. So these are less common things, but something to keep your eye out for.

                                                And then CTE and TBI. So trauma. Huge, huge player. NFL players, people who’ve been in the war, blasts, traffic accidents, even repetitive, mild head injuries. People who head soccer balls, all these sorts of things can give you chronic traumatic encephalopathy. The triad to think about for that, so if you hear this triad, so it’s depression, aggression, and dementia. So what happens to the football players? They beat up their families and then they commit suicide. They have both aggression and depression, as well as the dementia.

                                                COVID-19 related. This is something for all of us to keep our eyes out for. A lot of people with COVID report some brain fog, even after the COVID. And so there’s concern of many coroners, are we going to see more and more cognitive decline as a post-COVID effect? We just don’t know yet. Of course everyone’s concerned thinking back to post-encephalitic Parkinson’s of 100 ago, and we’ll see what happens with COVID-19, but it certainly, again, behooves everyone to get on appropriate prevention.

Dr. Weitz:                          Hey, Doc.

Dr. Bredesen:                    Yeah?

Dr. Weitz:                          Just a second. What would you speculate would be the mechanism if we see brain related issues related to COVID? Do you think it might be related to decreased oxygen getting to the brain? Do you think there’s an autoimmune attack on the brain? What do you think might be the mechanism?

Dr. Bredesen:                    Yeah, so there’ve been multiple neuropathological studies already published on COVID-19-related encephalopathy, and it actually has several features. So just what you said. One is you do see multiple small vessel occlusions. So there is some degree it’s not major vessels typically. Now sometimes it is major vessels, but more commonly it’s small vessels. There was an interesting publication from … what’s that?

Dr. Weitz:                          This is the clotting and the vascular component of COVID?

Dr. Bredesen:                    Yeah, this is one of the contributors. Then the second thing is there is an autoimmune effect. So there’s a little bit of an MS-like phenomenon. So you’ve got people reacting to virus and virus antigens, and then you’ve also got the previous damage where you had from hypoxemia, depending on how severely, were they on a respirator? Were they not on respirator? Those sorts of things. So there are multiple mechanisms.    And I do think this is something where everyone who’s had COVID-19 should be on active prevention. And certainly if they develop more than just brain fog especially, then you really want to jump on them early and evaluate them and do everything possible to optimize, to give them the appropriate immune status.

                                                Interestingly, there are some very interesting parallels, as I mentioned earlier, between Alzheimer’s and COVID-19. And one of the more interesting ones is that, one of the problems with the disease is that, both in COVID and in Alzheimer’s, you have a mismatch between the innate immune system, which is activated, and the adaptive system, which is not able to clear the pathogens. In one case, we know what the pathogen is, in the other case, it can be all sorts of different pathogens with Alzheimer’s. But it’s been known for years that Alzheimer’s people aren’t particularly good at phagocytosis. They are not particularly good at antigen presentation. So part of the job of the adaptive system is to turn down the innate system and say, okay, I’m going to take it from here, but it doesn’t succeed in doing that. So what happens, as we know, people with COVID-19 have cytokine storm and can die from that. People with Alzheimer’s have cytokine drizzle, it’s not an active cytokine storm, it’s years and years of this.   And by the way, the amyloid we associate with Alzheimer’s is part of the innate immune system. That’s the whole point. So as long as your innate immune system is chronically activated, you’re going to continue to make that amyloid. You are protecting yourself against an insult. So it’s our job to find out what these insults are and go after them and target them.

                                                And then CJD, Creutzfeldt-Jakob disease, which is a prion disease. Typically, that is much more rapid. So you see people getting worse week to week instead of months and months and year to year. And then of course, don’t miss the subdural hematoma. Of course your MRI should help you with that. But these people tend to wax and wane and they can have, or they can present with something that can look like Alzheimer’s disease.

                                                So what about stages, subtypes, and presentations. Four stages. So there’s a pre-symptomatic stage. You already have the pathophysiology going on, and that can last for several years, but at the time you don’t notice any symptoms. Then you progress to SCI, which on average lasts 10 years. So again, I would argue that we should start calling this pre just like pre-diabetes, this is pre-Alzheimer’s and SCI is early Alzheimer’s. Because everything has been focused on the end stage of this, which really makes no sense. So SCI is subjective cognitive impairment. By definition, that means you know there’s something wrong, but the tests are not showing it yet.

                                                That progresses to MCI, so-called mild cognitive impairment. But as one of the patients said, it’s anything but mild. This means that you’ve progressed far enough that you’re neuropsych testing is now abnormal. And so you are relatively late in the process and you really want to jump in and get treated optimally.   And then that progresses at the rate of about 10% per year. The MCI patients will progress to full-on Alzheimer’s, which is really end-stage Alzheimer’s, which is, by definition, when you begin to lose activities of daily living. Well, as you know, when you’re losing activities of daily living, you are very, very late in this process. So we recommend everyone, please either get on active prevention when you turn 45, or think about, the very earliest when you have symptoms, please get on treatment.

                                                So, as I mentioned earlier, there are subtypes. Type one is inflammatory, type two is atrophic, type 1.5 is glycotoxic or sweet, type three is toxic. And as I’ll show you, it often presents very differently. Vascular type four, and then traumatic type five. And so, depending on what type you have or what combination of types you have, you need to treat them differently. No surprise.  The biggest thing to note is someone presenting with an amnestic syndrome where the biggest problem, and the first problem, is really about learning new information. That’s classical Alzheimer’s and that’s typically not type three. Type three is often a little different, but that’s classical Alzheimer’s. It’s more apoE4 positive Alzheimer’s, which represents about two-thirds of Alzheimer’s.

                                                But about a third of people will come in with non-amnestic presentations. So they have problems with executive function. So here, non-amnestic. So for example, the primary progressive aphasia, that’s a relatively common one. PCA, which is posterior cortical atrophy. So these are the people that have trouble with recognition, recognition of faces, recognition of objects, things like that. Prosopagnosia, problems recognizing faces, executive dysfunction, dyscalculia, apraxias, agnosias, depression. So these are all things typically that are parietal.  If you look at a PET scan, you see a temporal and parietal reduction in glucose utilization. Classical Alzheimer’s is more of a temporal heavy. It’s memory. The non-classical, the non-amnestic is really more of a parietal presentation. Those are the PCAs and the apraxias and the dyscalculias and things like that. And beware the ones that present with depression, because they are often telling you, “I’ve got exposure to toxins,” and that’s a common presentation of the ones that are going to turn out to have type three.

                                                So let’s now go back to the molecular biology. We’re going to go all the way back to the beginning and look at what this thing actually is. And that’s our research over the years was could we understand the fundamental nature of this disease? How do we explain the neurofibrillary tangles and the senile plaques and the atrophy and all this sort of stuff? And the genetics and all the other things in these 150,000 papers.   And the intriguing thing here is the amyloid precursor protein, which sticks out of a cell, so this is a cell membrane I’m showing you here in this diagram. Here’s the extracellular space. Here’s the intracellular space. And amyloid precursor protein turns out to be a fascinating protein. It is a little bit like the president of your country. So let’s say that you’re living in Mybrainostan and you’ve got a president, President APP, and the president is looking at, are things good? Are we going to build roads and build bridges and do all these sorts of things? Obviously things that our current president and our last president were thinking about. What do we do? There’s a pandemic on the one hand, but we got to keep things going. Are we going to go into a recession? That’s the same sort of thing.   And by the way, this, again, is a good analogy. What happened with COVID-19?  We were all told there is SARS-CoV-2, there’s an insult.  So we’re going to shelter in place.  We’re going to downsize.  And of course we had a recession. That’s exactly what your brain is doing with Alzheimer’s. It’s saying there are insults around, I’m going to switch from growth mode to protection mode. So interestingly, APP senses both of those.  So you can literally trace the molecular pathways.  So when things are good, whether it’s in your country or your brain, if it’s in your brain, APP senses things are good.

                                                And again, as an example, estradiol binds to its receptor, enters the nucleus, turns on a whole bunch of genes. And one of the genes that turns on is the one that cuts right here. So it’s saying, okay, we’re going to cleave APP at one site. It leads to two peptides that are growth and maintenance. These are saying, go ahead, times are good, make new memories, grow, keep your brain doing well.  Now, this same thing, when it’s exposed to all the things we talked about, to herpes simplex and to pathogens from your mouth, to borrelia, to leaky gut, to staying up too late, to too much stress. You can go on and on and on. When it recognizes those things, it has a completely different outcomes. So it’s now, just like your president, saying, we’re going to protect ourselves and we’re going to downsize.  And again, you can trace a direct molecular pathway. So you then cleave APP at three sites. This is the beta site right here, the gamma site, and the caspase site. And these four peptides all say, pull back, pull back, protect yourself and pull back. And so that’s the fundamental difference. Everybody with Alzheimer’s has got too much on this side and too little on this side. So it’s our job to figure out what’s driving that and to increase the things on this side and decrease the things on that side. And that’s what actually works to make people better.

                                                Okay. So what we realized over the years of research is that chronic illnesses are typically signaling imbalances. As everyone knows, if you’ve got osteoporosis, your osteoblastic activity is being outstripped by your osteoclastic activity. If you have cancer, your somatic mutations typically are giving you more cytoblastic effect because you’ve got oncogene activation and you’ve got tumor suppressor gene mutation. You’ve lost that function. Therefore, cytoblastic outstrips cytoclastic, and you make too many cells.   What we found in the lab, Alzheimer’s no different. There are all sorts of things that contribute to synaptoblastic signaling, and that is being outstripped by synaptoclastic signaling from exactly what I just showed you with APP. That’s recognizing this.  So the point here is that the fundamental nature of this disease that we call Alzheimer’s is actually a network insufficiency. So you have subsystems of your brain. You have a subsystem that is there for stabilization of motor movements. When that goes awry, you get Parkinson’s. You have a subsystem that is very good with neuroplasticity. When that goes awry, you get Alzheimer’s. And so each of these has its own supply requirements and its own demand requirements. In all of these diseases, you’re outstripping. The supply is not meeting the demand.

                                                In the case of Alzheimer’s, there is a set of things, as I mentioned, synaptoclastic. So let’s just quickly go through this. Your probability of Alzheimer’s is proportional to, over time, you’re integrating a whole sum of things that are, and I’m going to talk about what they are here, synaptoclastic signaling over synaptoblastic signaling. So that tells you a lot about what Alzheimer’s actually is.   That’s why your brain shrinks when you get Alzheimer’s disease. That’s why it acts like it’s trying to protect itself. Now the good news is, although we can’t send a lab test for this one, I don’t think that there’s any sort of tests we can do. I know Dr. Vojdani may be at work on something like this. He’s made some great tests, but the reality is we can measure these things. So this is approximately equal to four different things.   So the things that are on the bad side here, and then here are the things that lower the risk. But, when you have too little of them, you’re in trouble. So anything that’s causing inflammation is going to increase your risk for Alzheimer’s. So whether, again, whether it’s leaky gut, whether it’s poor oral, whether it’s poor dentition, whether it’s chronic sinusitis, whether it’s a metabolic syndrome, just go on and on. Any toxins, and these come in three general types, the inorganics, things like mercury, and air pollution, air pollution is a huge one. And then things like organics, things like formaldehyde and toluene, benzene, glyphosate. And then of course the biotoxins, things like trichothecenes and ochratoxin A, and things like that.

                                                Now, too little energetics, that’s the third of the four things, and the energetics are basically four major contributors: blood flow, oxygenation, mitochondrial function, and the actual ketones that are actually going to be burned as a substrate. So that’s one thing we want to optimize as well, so anything that reduces that, people who have sleep apnea, people who have some degree of vascular disease, people who have poor mitochondrial function, people who are incapable of getting into ketosis, all those things. And then finally, trophic support, and that’s, again, three things. That is growth factors, NGF, BDNF, things like that. Hormones, estradiol, testosterone, pregnenolone, progesterone, all that stuff. Then nutrients, things like vitamin D. Those are the big four. Each one has groups and you can literally go through and figure out what each person has that’s giving them this problem.

                                                What that means is, the perfect Alzheimer’s drug… And we spent years screening for Alzheimer’s drugs. The perfect drug would have to do this, which makes it really difficult to get a single drug. And I do think the drugs are going to be very helpful in the long run, as part on the backbone, basically, of a functional medicine or systems medicine sort of approach. We always tell the patients, imagine you have a roof with 36 holes, you’ve got to patch many of them before you’re going to see any real effect. And of course, we have to train a new kind of position who understands both systems biology, the basic, the traditional Chinese medicine sort of approach, as well as DNA, RNA, larger data sets, all of the modern things, and so we really need to get… This is obviously… This group is very well aware of that.

                                                So I’m just going to spend a couple of minutes here on ApoE4 because it is the most common genetic risk factor. What the heck? Why would this give you Alzheimer’s? It’s so incredibly common. Even though about a quarter of the population has it, it represents, because of this increased risk, about two thirds of all Alzheimer’s patients. So if you have zero copies of ApoE4, and that’s three quarters of our population, you have about a 9% risk. It’s not zero, but it is relatively low. If you have one copy, that’s 75 million Americans, the vast majority don’t know it. They have a chance about 30% during their lifetime, and if you have two copies, your chance during your lifetime is well over 50%. That’s 7 million Americans. Most likely you will develop it.

                                                So we recommend please, everybody, check out where you stand. People used to say, “Doesn’t affect me.” The standard claim today from the experts, “Don’t bother to check it because there’s nothing you can do.” Which is just… It just drives me crazy. There’s a tremendous amount you can do. Please, everybody find out where you stand, get on active prevention. So-

Dr. Weitz:                          Hey doc, do you have an opinion about ApoE2 versus ApoE3?

Dr. Bredesen:                    Yeah. So ApoE2 actually reduces risk. It’s relatively uncommon. ApoE3 is the most common, and that one, the risk is going to… That’s the one that’s set as the standard. And so yes, if you’re a e2/3, you do have a slightly lower risk, the 9%. However, if you’re a e2/3, be careful. You are also susceptible to some of the toxins. More than the ApoE4 people are. So the ApoE4 tend to get a more vascular and inflammatory and glycotoxic type of disease. The ApoE3s and 2s, in general, they tend to get a more toxic, sometimes vascular as well, but they tend to be more on the toxic side.   So what had been known is that ApoE4, some sort of risk factor, not clear how that works. ApoE is a little bit like your butcher. It’s the guy that carries around the fats. And so what the heck does that have to do with Alzheimer’s? And so we started in the lab over a decade ago looking at “How do you turn ApoE4 into Alzheimer’s disease? Why is this association?” And it had been claimed in the past, “It’s simply because you clear your amyloid less well,” and yeah, you do clear less well, but that’s not the only reason by far, as you’ll see here. It turns out to be a fascinating story. So what happens is, this ApoE4 was the primordial ApoE. So when the hominids appeared from the simians between five and seven million years ago, there actually aren’t that many differences, as you probably know, between the simians and the hominids. The DNA is over 95% similar.

                                                And so, as I told my wife, “My DNA is actually more similar to a male chimp than it is to yours.” And she said, “Well duh, of course, you guys both like ESPN. You both like The Three Stooges.” We get it, okay. So the bottom line is, yes, there are a lot of similarities between the simians and the hominids. And of course God touched us all with DNA, made a small number of changes, and lo and behold, we became what we are today. And we all had, for 96% of human evolution, everybody was ApoE4/4. And so these are interesting. ApoE3 just appeared 220,000 years ago, so relatively late in hominid evolution. Nobody knows why it appeared then. One of the interesting possibilities is that ApoE4 is a very pro-inflammatory gene, so it’s great for if you’re eating raw meat and things like that. And that as people became able to be eating cooked meat and things like that with fire, they didn’t need that, and so they ended up with ApoE3, which is now the more common one.

                                                So you can see here what happened, ApoE4 looks like columns on a house, and that’s because this arginine 61, which is positively charged, interacts with glutamate 255, which is negatively charged. And interestingly, this arginine 61 is not present in the chimp ApoE. Now what happens is, 220,000 years ago, cystine 112 appeared right here and swiped right on the arg 61, and you can see here, these two guys interact now. So this now swings free, and so now it looks much more like a nutcracker than it does like these columns. So very different look, and as I mentioned, this is just a relatively late change. ApoE3 just appeared late in our evolution, ApoE2 just 80,000 years ago.   And here’s the big surprise. People had known that it binds to receptors, several different receptors, actually, but what we discovered was really fascinating. It actually interacts with part of NF-kappa B, RelA, and enters the nucleus. The reason that hadn’t been picked up before is, it’s not all of it that enters the nucleus. It’s a subpart, it’s about 10%, but it’s a critical part of your ApoE that enters the nucleus and it binds to 1,700 different gene promoters. And if you group these, you could not tell a better story for Alzheimer’s disease. So it’s involved with inflammation, it’s involved with disassembling your microtubules. So it has this interesting pro inflammatory effect. And so okay, we can find out who has it. We can actually make an impact on this.

                                                So the bottom line here is, when we treat people, we want to understand what’s causing the problem. We want to know what their energetic status is. We want to identify whether they have insulin resistance and get them to be sensitive again. We want to know the status of their trophic support. We want to resolve inflammation, treat pathogens. If they’ve got toxins on board, we want to detoxify them. We found that people do better if they have some mild stimulation, whether it’s light, whether you like to use magnetic, defocused laser. Any of these things. We want to improve the adaptive immune system and reduce the innate system. That’s one of their problems. And then we can remove the amyloid. Removing the amyloid at the beginning is a bad idea because it’s protecting you. So address the things, it’s root cause medicine, no surprise. And then ultimately we want to think about regeneration, things like stem cells and trophic factors.

                                                So here’s an example of a guy. Did very well. You can see these dramatic improvements in his neuropsych testing. He actually started back in December of 2013, so he’s done very well for a long time. And that’s the most important thing. People have stayed very good. This is a guy… Classical Alzheimer’s, ApoE4 positive, both parents died, and you can see, as a functional medicine physician, you can see the problems this guy has. Now he himself is a very smart doctor, and I was trying to explain to him, “Look, this is why you have Alzheimer’s.” And he said, “Well, addressing these things, none of these things is a cure for Alzheimer’s.” No, not by themselves, but you have to look at the overall system.   And by the way, he did absolutely great. Responded metabolically, cognitively, volumetrically, and his neurologist said he’s now normal. You can see his hippocampal volume… Just dramatic improvements, and you can also see, he’s not perfect with his metabolism. His fasting insulin is much better, it’s not perfect. His hs-CRP, much better, it’s not perfect. His homocysteine, pretty good. His vitamin D, pretty good. So he was improved and you can see here his gray matter actually increased by 23%. What’s that?

Dr. Weitz:                          I’m sorry. What would be your goals for the fasting insulin and those other parameters?

Dr. Bredesen:                    Yeah, fasting insulin… we usually go with what Mark Hyman has always suggested. We want to be in that kind of four to five range. I worry when I see people down at one, unless they’re doing really well. If they’re at one and their hemoglobin A1C is at six, they’re just not able to make enough insulin. And by the way, they often get better as they start being treated, and they’re now able to make more again, but yeah, four or five. I like to see their HOMA-IR right around 1.0 and his HOMA-IR was something like 13, or something. It was just way off scale. So we published a number of papers on this, and of course, everybody pushed back and said, “Yeah, these are anecdotal. You got to do a trial.”   So we actually tried to do a trial back in 2011. It was turned down because it was multi-variable. We got turned down again in 2018. We finally got approved in 2019, and we just finished the trial, and I’ll show you the results from that. Published a couple of books about this to document some of these. And so, as you know, functional medicine has improved outcomes for many illnesses. It’s really been striking. And of course, this is not taught in medical schools, typically. One leader of one of the medical schools, a very well-known medical school in the United States, said, “We’d like to teach this new kind of medicine, but we can’t do that until all physicians accept it.” Well, of course all physicians won’t accept it until you teach it, so it’s a really very backwards approach. So clearly, if we’re all going to make functional medicine the standard of care, it’s going to be important to perform clinical trials to prove efficacy.

                                                So therefore, we proposed a proof-of-concept trial, which as I mentioned, I just finished up, and we just published the first piece on one of these preprint servers called medRxiv. And I’m really honored to have done this with Dr. Ann Hathaway, Dr. Kat Toups, and Dr. Deborah Gordon. I’m sure a number of you know them. They’re absolutely fantastic physicians. And we all worked on this together, along with the Four Winds Foundation that funded the trial, a question, which a CRO. Dr. Cyrus Raji, who was the neuroradiologist and Alan Boyd, who is the neuropsychology guy that provided the CNS vital signs. So it’s the first trial in which we flip the script and say, okay, let’s find out what causes I mentioned. It was denied a few times. It’s a small proof-of-concept trial, 25 patients with MCI or early dementia, MoCA scores of 19 or above, compares a personalized precision medicine approach to historical outcomes. Now we’re following this up with a larger, randomized controlled clinical trial.  So we look at MoCA zero, three, six, and nine months. We look at CNS vital signs because it’s more sensitive. We look at AQ-21, which is from the patient’s partner looking at how many complaints they have. We look at AQ-20, which is basically the partner saying, “Did they improve? Did they not improve?” in 20 different areas. A little improvement, a lot of improvement, none, or were they actually worse? And then we did MRI with volume metrics at zero and nine months, and really striking results. So we tried to achieve insulin sensitivity, mild ketosis, healing the gut, treatment of identified pathogens, detox for those who needed it, reduction of inflammation, optimization of hormones, nutrients, and trophic factors, vascular status, some degree of brain stimulation, optimization of SpO2, and then stress management, and improved heart rate variability.

                                                And I just want to say a word about the semantics of success. We hear this almost every day, “Oh, someone did a trial, someone made a mouse better, or someone slowed up the decline.” So here’s an example, Aducanumab, which is the big success in the antibodies of the drugs. What it did was, it didn’t make people better, it didn’t stop the decline, it slowed the decline by about one third, a little less than a third, actually. And so you can see here, here’s no treatment… Yes, you go downhill. With this big success, and this thing, by the way, the day this was announced, the value of this company increased by $20 billion in one day. So here you can see, it slowed it by a third. Whereas, in our trial, we didn’t just slow the decline, we made people better. And here’s an example on the Neurocognitive Index, you can see where they were baseline- what’s that?

Dr. Weitz:                          What was the change in the market value of Dr. Dale Bredesen as a result of the trial?

Dr. Bredesen:                    I think three more arrows in my back. That’s what happened. That was the result of that one. So yeah, there’s no market value here.

                                          So here’s just from the NCI data and the significance of this P<.001. So everything I’m showing you here, it turned out to be significant statistically. So here you can see. MoCA, <.001, 76% of patients improved. Neurocognitive Index, <0.001, 84% of the patients improved by their NCI. Cognitive subtests, verbal memory improved, executive function, psychomotor speed, cognitive flexibility, and others. Interestingly, the partners said the same thing. Yes, they said these people have improved. Again, a P value for that <.005. Brain training scores improved in all 25 of them. No question, the pandemic affected this. We had seven people who had already improved by six months, the pandemic hit, and then they actually went down a little bit at the end. But the good news is, the other ones improved so much that it was still statistically significant as a group, but there’s no question. They would have done better as a group if the pandemic hadn’t intervened.

                                                Now, here’s what’s interesting. The MRIs improved. So if you look at the overall MRIs, they improved both with respect to gray matter volume, and with respect to hippocampal volume… There we go. Hippocampal volume itself… So hippocampal volume in someone with Alzheimer’s goes down about 2.5%-3.5% per year. If you’re a normal individual, it still goes down about 1.7% per year. The hippocampal volume actually did go down a little, 1.29% per year. So these people actually did better than the normal controls with their hippocampal volume change. And interestingly, their gray matter volume actually went up by 0.3%. So implications, cognitive decline is reversible for most people with MCI or early dementia.

                                                Now we’re very interested in looking at later dementia. What about people who have MoCA scores of zero to 18? We’ve seen anecdotal evidence of improving them, but it may take more to get them to improve. We’ll see. For those with cognitive decline, likely contributors should be obvious. One of the interesting things that came out of this was, there are only three who didn’t improve who declined. We should be able to tell why. And we could see one of them, for example, lived in a very moldy house with lots of mycotoxins and just said, I’m not leaving. Okay. This person continued to decline. So the good news is, we could tell with these people what was actually wrong, and the other ones that did the right things actually improved. So one of the issues here is how feasible is this to do with everyone? So we need to continue to work on the practical nature on this. The good news is, the results really strongly support doing a larger trial, which is what we’re setting up now.

                                                I’m excited about the idea that we may be able to modify this for Lewy body, modify it for Parkinson’s, modify it for frontotemporal. Each one has its own subsystem with its own neurochemistry, so we should be able to modify this, and we’re already doing this. In fact, I just had a meeting today on the three-month followup of the first couple of patients with macular degeneration, and it’s the same story. They have their own separate neurochemistry, and we can now begin to look at improving them by combining the appropriate things. So the good news is, if you combine the results of this trial with what’s already been known, that there’s a decades long pre-symptomatic and early symptomatic period, the fact of the matter is Alzheimer’s is now something that is optional. It’s not that anybody has to get it.

                                                So please, get on prevention or early reversal. You don’t need to get this disease. Just as for leprosy and polio, which were scourges in their time, Alzheimer’s disease shall become a former scourge. And one of my favorite sayings is actually from a rabbi who said, “You’re not expected to complete your life’s work during your lifetime. Neither are you excused from it.” And I recognize that this is going to be going on… I’m just about to turn 70, this is going to be going on long after I’m gone. But my hope is that we’ll keep making this better and better, and we really will reduce the global burden of dementia. So let me stop the sharing there, and happy to go to any questions that anyone would like to ask and thanks again to Ben for the invitation.

Dr. Weitz:                            So the first question I’d like to ask is, I found a paper that you wrote about rapamycin and its potential for inhibiting mTor and playing a role in prevention and treatment of Alzheimer’s. Can you talk about that?

Dr. Bredesen:                    Yeah, mTOR is one of the several, as you know, sensors. So these are all about nutrition and energy. And when you are eating, when you’ve got a lot of protein around especially, mTOR is active, and so you want to inhibit this, and that’s what you’re doing by fasting. Rapamycin has been touted by some as, “Here’s the way of the future. Let’s all take rapamycin and inhibit mTOR, and we’ll age less rapidly.” And I should mention there’s a great paper that just came out recently from Kara Fitzgerald, another integrative physician who used a similar sort of approach to what we do, but instead of asking the question, “What happened to cognition?,” Said, “What happened to aging parameters based on the methylome?”   And what she showed, that these people aged backwards by essentially by 3.26 years. So I think we’re all trying to have that impact to improve brain function, to improve biological aging. I don’t think you need to take a drug like rapamycin that has side effects to get that. You’re getting it by doing things like fasting appropriately. Look, if you want to try the fasting mimicking diet, that’s what it’s for. If you know, doing exercise, getting appropriate sleep, minimizing your stress, having a mildly ketogenic plant rich high fiber diet with plenty of phytonutrients. These are all ways to get at mTOR without taking a toxic drug.

Dr. Weitz:                          Kara mentioned in her article about this test to measure biological aging based on methylation. I’m sure you’re familiar with that. Is there a correlation between the outcome of that test and the risk of Alzheimer’s?

Dr. Bredesen:                    Great question. We don’t know yet. We’re actually going to be working with Kara. Just been talking to her the last few days. We’re going to be working with her on this next trial to see what happens, as I think it’s highly likely that we will see reduced biological age given everything that we’ve seen so far with cognition and what she measured in her trial. So I’ll be very interested to see what happens with that. But again, this is a biomarker of biological aging. We don’t yet know if it’s going … hey, if we impact that and we reverse it, are there going to be… Presumably they’re going to be some good things that happen, but are there also going to be some negative? We don’t know yet.

Dr. Weitz:                          What about strategies to increase oxygen to the brain? Like hyperbaric oxygen, ozone, there’s several others.

Dr. Bredesen:                    Yeah. You know, there’s a group in Israel that is claiming that they’re getting some very good results with hyperbaric. You know, I think for the appropriate people, it seems to be very helpful for people who have vascular disease as one of their key contributors, or for people who have head trauma as one of their contributors. Whether it’s the best thing for the people who have glycotoxicity or just inflammation, I don’t know yet.   I actually like EWOT a little bit better, the exercise with oxygen therapy, because you’re now active, as opposed to HPOT, where you’re inactive. But yes, I think for the appropriate people and especially in those two groups I mentioned, I think it’s fine. As you know, it’s expensive. And so, we’re looking at how do we get this to the greatest number of people. And by the way, Aducanumab, which failed was turned down by the FDA, but now has been pushed by Biogen for the FDA to reconsider it, and they’re going to issue a response by June 7th. Even though it failed in trials, one dose in one trial, it seems like it might have slowed a little. Again, it didn’t make people better, just slowing the decline. It will cost people a minimum of $30,000 per year. So again, we can do far, far better. And by the way, the average person with Alzheimer’s will spend $350,000 before death. Mostly to things like nursing homes and medical care and things like this. So for a tiny fraction of that, we can do much, much better.

Dr. Weitz:                            Several questions came in about some of the particulars of the nutrition program and parameters related to the type of intermittent fasting that you’re recommending.

Dr. Bredesen:                    Yeah. Great point. And so we use… And I wrote about it in the books; KetoFLEX 12/3. So again, we’re agnostic about what to use. It’s how do we drive your biochemistry and neurochemistry toward the best places for synaptogenesis and for synaptic maintenance? That’s the key. And, so far the diet that seems to be working best is… you would say high, or plant rich, no surprise. And again, for people who have truly severe vascular disease, maybe you consider going vegan. For people who don’t have a significant amount of vascular disease, you want to do more fish and some pastured chicken maybe, and maybe some grass fed beef, but not as major parts. So, it’s a plant rich, high phytonutrient, lots of non starchy vegetables, high fiber diet. You want to optimize microbiome, no surprise, and have appropriate prebiotics.   Make sure you don’t have dysbiosis. That’s one of the most common contributors to systemic inflammation in Alzheimer’s disease. And then as you indicated, some fasting 12 to 16 hours we recommend. And then it’s key. I see this again and again and again, if you can get in… become insulin sensitive and get yourself into mild ketosis, you do better than if you are insulin resistant and you don’t get yourself into ketosis. So, that is an important part of the overall approach.

Dr. Weitz:                          I know vascular issues is one of the categories that could affect decreased blood flow, et cetera, blockages.

Dr. Bredesen:                    Yeah.

Dr. Weitz:                          On the other hand, is there a danger with some of the medications like statin drugs? And is there a danger lowering the cholesterol too much, given the importance of cholesterol for neuronal formation?

Dr. Bredesen:                    Yeah, absolutely. And I worry about this all the time. And the problem is that in studies… that the studies were done to try to show that the statins are going to save us from Alzheimer’s. And of course, no surprise, they showed the opposite. However, they didn’t show much in either direction. And I believe that is because they do have an effect on a reduction of some degree, of reduction of inflammation. Well, we can do much better. We don’t need statins to reduce inflammation. So again, we want to use what is most natural, what is most physiological. You can reduce inflammation. Let’s find out why you have inflammation, and let’s remove that. Is it leaky gut? You know, is it oral…dentition oral microbiome? Whatever it is, let’s fix that and then you won’t need those sorts of things.  Lowering your cholesterol is horrible and everyone wants to lower their cholesterol to zero. And it’s just crazy. We’d like to see, if you’re concerned about that, please check your LDL particle number or your sdLDL or your oxidized LDL, whatever you like.   We also like to look just simply at a TG:HDL ratio, your triglyceride HDL ratio, another good marker. Not total cholesterol.   And yeah, I really dislike the use of statins because they have negative impact. You can get the positives… And by the way, many of the people who’ve gone on this… And the three physicians who were seeing the patients notice the same thing. People came off their anti-hypertensives, they came off their antidiabetic drugs and they came off their statins because they no longer needed these things.

Dr. Weitz:                          So, all the neurologists who were pissed off at you, now you got the cardiologists upset.

Dr. Bredesen:                    Yeah. Well, yeah. I… So it’s interesting, but I was just, we were just talking about a patient earlier today, and that very thing came up. This person had significant vascular disease. And I said, okay, well, are they seeing cardiologists? Yes. They’re seeing a cardiologist. Okay. What did the cardiologists do?  The answer was statins and hydroclorothiazide.   I mean, nothing about diet, nothing about exercise, nothing about stress, nothing about sleep. This person could have had sleep apnea for all the cardiologists know. It’s… I’ll tell you, it gets to the point where it is criminal negligence.  It’s unbelievable.  So my argument is, we need to now form new departments in each medical school called the Department of Modern Neurology.  That’s really what we need to do because there are so many departments that are just stuck in the 20th century.

Dr. Weitz:                          Well, we mentioned earlier, before we started that it takes approximately 17 years for a new idea to get incorporated into medical practice.

Dr. Bredesen:                    Yeah. Absolutely.

Dr. Weitz:                          What do you think about some of the ways to increase using red or infrared laser to stimulate the brain?

Dr. Bredesen:                    Yeah, absolutely.  So there’s a lot of research going on as you know, on this.  And what comes up again and again, is frequency around 40 Hertz stimulation seems to be helpful.  Now, unfortunately, some of this stuff, what they’re trying to do is see if they can simply remove amyloid.  And once you understand what the disease is all about, it’s not about removing amyloid.  It’s about removing what’s causing the amyloid, then getting rid of the amyloid.  But it is true, even interestingly 40 Hz sound seems to be helpful and 40 Hz light.  And so that’s the birth of violight, for example. There’s also magnetic stimulation that seems to be helpful. Things like MeRT, and Dr. Jeralyn Brossfield over in Palm Springs has done some really nice work with that as others have. And then of course, Dr. Robert Hedaya has done some really nice work with laser.  So yes, there does seem to be an advantage when you’re now getting… you’re doing all these appropriate things. You’re now saying to the brain, okay, we’ve now fixed all the issues that were stopping you. Now let’s start kind of pushing you back into work again, let’s get your Brain-derived neurotrophic factor firing again, let’s get your neurons firing again. Again, you don’t want to do it at the beginning because you’ve got to get things fixed, but once you do that, it’s no different than, an athlete who’s been out for six months with a broken leg. After it’s fixed, so get them start-up slowly get them back on the track again, that sort of thing. So yeah, that’s… This is the sort of thing that is again and again, proving to be helpful or get, him or her back on the track again. So this is, again, the way our brains work, is it any surprise that it’s not just one molecule? Really? Are we really surprised by that?

Dr. Weitz:                          Is it an appropriate analogy to compare amyloid with cholesterol?  The reason why cholesterol, just like, it’s often not asked why is cholesterol there?  Let’s just find some way to reduce it.  You know, when we really look at it from a root cause standpoint, we realize that cholesterol is there to coat the artery wall to prevent damage from inflammation, from oxidation.  You know, the body doesn’t just do harmful things for no reason. And is it an inappropriate analogy that the amyloid is being laid down in the brain to protect the brain, much the way cholesterol is being laid down in the artery to protect the artery?

Dr. Bredesen:                    I think that the work that came out several years ago from Dr. Robert Moyer, the late Dr. Robert Moyer, and Dr. Rudy Tanzi that showed that the amyloid is an anti-microbial peptide.  I think that’s really interesting and really important and fits perfectly with what we’ve been saying here.  You are responding to these various insults, the insults of modern life.  And so, as long as you’ve got those insults there, you’re going to be making this stuff.  And so we want to remove the insults before we remove the response to it.

Dr. Weitz:                          Somebody asked about using ProLon for Fasting Mimicking as a version of intermittent fasting.

Dr. Bredesen:                    Yeah.  And I think it’s fine.  Some people prefer to go on a more kind of standard ketogenic diet, which is fine.  Some people like to start out with, a few days, several days of ProLon.  Be careful, some people just hate the taste of that stuff, or they just don’t find it very palatable. Others are fine with it.  So, absolutely it’s a reasonable thing to do. Now be careful, what we find is that people who are very thin have a very low BMI, they sometimes do poorly when you try to get them on a fasting mimicking diet. In fact, Valter himself, Valter Longo says be careful if you’re elderly or if you’re frail, or if you’re too thin, be careful about this. So, what you want to do then is cycle people, give them a rest day and then cycle them in and out of ketosis about once a week. And then the rest of the time, keep them on ketosis. Because we do have people who will actually do more poorly with their cognition when they start trying to do this kind of a ketogenic diet. Because… you have to remember, this is an insufficiency, this is a disease fundamentally of an insufficiency of a plasticity network.   So therefore, if you’ve got someone who’s very thin and can’t generate the ketones and doesn’t have much glucose around, et cetera, you’re now really hurting them. So you’ve got to be careful. So that’s the paradox, it’s a disease of insufficiency. And yet we got it often by excess. And so we’ve got to now bring these together, and we’ve got to have that fasting period without getting people to get farther into an insufficiency.

Dr. Weitz:                          Do you ever include acupuncture in your protocols?

Dr. Bredesen:                    That’s a great point. You know, we haven’t, we didn’t use it in the trial, but absolutely, appropriate things that we use, other approaches for things like stress reduction and things like that. But yeah, it’s certainly reasonable. And there are many things as a scientist in a scientific position, I never believed. I thought all this stuff was crazy 15 years ago, but I can’t argue with the data. There’s no question. You have things like TM, which actually clearly helped neuroplasticity, clearly helped blood pressure clearly helps stress.  We had a patient only, just a couple of weeks ago. I was talking to the husband of one of the patients and we’ve been through, she had a lot of tremendous mycotoxicity. She’s slowly getting better, and then she started to go downhill again. I’m like, what the heck? We’re looking at all the different parameters, and it turned out the biggest issue with her, she was under a tremendous amount of new stress. And just addressing that, she then started getting better again. So there’s no question, these things have very clear impacts on our cognitive function.

Dr. Weitz:                          Yeah. So trying to get into more of a parasympathetic state is beneficial.

Dr. Bredesen:                    Yeah.

Dr. Weitz:                          Yeah, you might look into, there’s a number of devices… I’m wearing something called the Apollo, which uses vibrations to put you into a parasympathetic state.

Dr. Bredesen:                    Interesting.

Dr. Weitz:                          I mean, not very effective for some of my patients.

Dr. Bredesen:                    Well, so let me ask you a question then, because one of the things I always worry about, people say, well we’re going to put you into this state or put you into that state. Well, if it’s not the right state for me, I’m not sure I want to be put into that state. So, you want to be habit appropriate. In other words, you don’t want to be put into a parasympathetic state in the middle of shooting a gun at something, you’re in Iraq or something.

Dr. Weitz:                          Absolutely. So this device, they give you an app on your phone. There’s a wake up mode, there’s one for concentration and focus, there’s one to relax. So-

Dr. Bredesen:                    Oh nice.

Dr. Weitz:                          Different frequencies and intensity of vibration has a different effect. What do you think about peptides for reducing, preventing Alzheimer’s. There’s a number of peptides-

Dr. Bredesen:                    Yeah.

Dr. Weitz:                          Cerebrolysin, selank-

Dr. Bredesen:                    Cerbrolysin, sure.

Dr. Weitz:                          What do you-

Dr. Bredesen:                    Thymosin Alpha one, beta four, all that sort of stuff. But I know Jill Carnahan has been very big about using these and she’s done a great job. So yeah, I actually think they’re going to be one of the most important things going forward. And I think that especially intra-nasal administration where you’re really getting things into the brain, things like ADNP.   There was a trial of a fragment of ADNP called davunetide a few years ago. And unfortunately they did the trial as a monotherapy, nothing else. And no surprise, it was a negative trial, didn’t work. I think that’s one particular peptide… it’s a tremendously neurotrophic peptide. Doing that in the right setting, I think is going to be tremendously helpful. Same for nerve growth factor, same for BDNF, same for peptide fragments of these, same for things like cerebrolysin and Thymosin alpha one and beta four. So I think that these things can be very helpful. And I would put these very much, as I said earlier, pharmaceuticals are going to be helpful when used in an appropriate setting. But please remember to address the things that are actually causing the problem. That’s the place to start.

Dr. Weitz:                          What about stem cells?

Dr. Bredesen:                    Yeah. And so I actually just talked to a guy today who just had given stem cells to someone yesterday and we’ll see how they do. Here’s the thing about stem cells. And as you know, there are trials-

Dr. Weitz:                          What type of stem cells and how did he administer them?

Dr. Bredesen:                    These are the ADRC’s, and this is with blood-brain barrier opening, and this was actually done in LA.   So, here’s the thing. The issue with giving these, again, as a monotherapy, it’s like trying to rebuild a house as it’s burning down, it doesn’t make sense. So please stop the fire first, get all the appropriate things. Then I think for rebuilding the synapses that have been lost… Because let’s face it by the time you have a diagnosis, you’ve lost a lot of synapsis and you need now. Now, initially these synapsis become non-functional but they’re still anatomically present. But then you lose them and then ultimately you lose the neurons themselves. So my argument would be… Great, stem cells should be very helpful at the appropriate time and, with the appropriate treatment and, the appropriate protocol. So we’ll see, I think the data will tell us over the next several years.

Dr. Weitz:                          So what is the best imaging for understanding where the neurons in the brain is growing or shrinking?

Dr. Bredesen:                    Yeah. Great point. So there are several different ways to go. PET scanning has been the most helpful for telling you if you actually have Alzheimer’s because there’s a signature on FDG PET. And then of course there’s amyloid, and now there’s now Tau PET as well. So it’s a very neurochemically oriented approach, and so that’s helpful for diagnosis. However, for following and what we did in the trial was to use MRI with volumetrics. So you want to have, whether you like NeuroQuant or you like Neuroreader, you want to have a computer-based algorithm to look at do you have hippocampal atrophy? Do you have parietal lobe atrophy? Do you have frontal lobe atrophy? Temporal lobe? These sorts of things. Various regions of the brain, do you have normal pressure hydrocephalus? Do you have big ventricles and no atrophy, that sort of thing.   So that’s helpful, but that doesn’t tell you if you have Alzheimer’s or not. You can infer that you probably have it. And I think some people have argued, we should quit talking about Alzheimer’s just talk about cognitive decline, it’s all going to be related. And so you could argue that… I think I like having an idea of, is this Lewy body? Is this Alzheimer’s? Because that simply tells you where you should focus more attention. If you have Lewy body, most likely you have toxin exposure. So you really want to focus more on that. If you have Alzheimer’s, you’re likely to have insulin resistance, you better focus on that. You know, all the things we talked about for that, each one is a little different. But again, you could look at just cognitive decline. So that’s the second kind of imaging.

                                                Then of course, there’s this group Darmyian, which is trying to look at, can we essentially infer a histology from looking at different regions of the brain? And that’s going to be interesting we’ll see. That’s early days, very little published about it. And so, lots of claims, not much in the way of publications yet. So I think it’ll be very interesting to see, they may be correct. And maybe we’ll see in the next few years, some very striking outcomes with that where we really can infer underlying pathology, which would be fantastic.

Dr. Weitz:                            I knew you prefer the Montreal Cognitive Assessment tool for assessing patients with Alzheimer’s among other questionnaires. Is there a good questionnaire when patients have subjective cognitive impairment?

Dr. Bredesen:                    Yeah. You know, this is such a good point because you can use SLUMS, which is the St. Louis one, which is similar to the MoCA in terms of sensitivity. MMSE is another one that’s been used over the years, but that one is not very sensitive at all. So that’s really… each one has its own dynamic range. When you have someone who’s got relatively severe dementia, you want the MMSE. The MoCA was developed specifically for MCI. But as you indicated, as we talked about earlier, you really want something that’s hypersensitive for SCI so that you can really catch people early and see if you can improve them. And I should mention parenthetically, we do have people coming in saying I’m here for prevention. And they score 23 on the MoCA. They already have fairly significant MCI. And they’re thinking they’re there because it comes on so slowly.   And so these people typically get right back to 30 when they do the right things. So I happen to like CNS Vital Signs, but there are others there’s, Cogstate, there’s Cambridge. We have used the CNS Vital Signs because you can do it over the internet, it only takes about 35 minutes or so. It’s pretty easy, in fact, we even have a shorter version called CQ, which is easy to do. And it can really give you a pretty sensitive… much more so than the MoCA scores, pretty sensitive indicator of where you stand cognitively. And also it does multiple domains.

Dr. Weitz:                          Great. Awesome. Thank you so much, Dr. Bredesen and we all thank you. Excellent presentation, we learned a lot. It was incredible.

Dr. Bredesen:                    Yeah. Thanks for the invitation. Appreciate it. And I look forward to hearing more great things. I hope everybody out there will help to prevent and reverse cognitive decline. That’s I think, this is the way that everything’s headed. So thanks very much.

Dr. Weitz:                          Yeah, we’re all on that mission with you. Thank you everybody and we’ll see you next month.

 

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Thank you listeners for making it all the way through this episode of the Rational Wellness podcast. Please take a few minutes and go to apple podcasts and give us a five-star ratings and review, that would really help us so more people can find us in their listing of health podcasts. I’d also like to let everybody know that I now have a few openings for new clients for nutritional consultations. If you’re interested, please call my office in Santa Monica at (310) 395-3111 that’s (310) 395-3111. And take one a day, a few openings we have now for a individual consultation for nutrition, with Dr. Ben Weitz. Thank you and see you next week.

PART 4 OF 4 ENDS [01:30:04]