Precision Medicine and Functional Approaches to Alzheimer’s: Dr. Dale Bredesen on Personalized Treatment, Trial Results, and Key Drivers
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Dr. Ben Weitz introduces the Rational Wellness Podcast and interviews neurologist Dr. Dale Bredesen about a precision medicine approach to Alzheimer’s, arguing cognitive decline reflects multiple interacting drivers rather than a single disease. Bredesen explains why a randomized controlled trial was needed to convince mainstream medicine, describes the ethical challenges of a declining control group, and reports statistically significant improvements in memory, executive function, processing speed, and neurocognitive index, including benefits for APOE4 carriers and preliminary improvement in APOE4/4 patients. He outlines key contributors— inflammation, toxicity, energetics, plus neurotransmitters, trophic support (including BHRT), and stress—along with common factors like metabolic dysfunction, mycotoxins, sleep apnea, infections, and heavy metals. The discussion covers early detection with blood biomarkers, individualized treatment variability by site training, diet (Ketoflex 12/3), stress-reduction tools, targeted supplements, and applications to other neurodegenerative syndromes.
01:03 Alzheimer’s Precision Medicine
02:29 Why an RCT Matters
04:18 Ethics and Pushback
06:57 APOE4 and Site Results
09:40 Network Model Big Drivers
12:40 Training Makes the Difference
13:44 Trial Baselines and Outcomes
16:34 Personalized vs One Size
18:50 Top Root Causes to Address
21:56 Early Screening Blood Tests
25:56 Amyloid Tau as Defense
29:20 Sponsor Break Apollo Wearable
30:54 Personalized Infection Treatment
32:30 Hormones and Brain Support
34:49 Progesterone for Men Too
35:54 Beyond Alzheimer’s Parkinson’s
36:18 Detox Reverses Corticobasal
37:49 Posterior Cortical Atrophy Turnaround
39:33 Network Failure and Evolution
41:57 Prions as Immune Defense
44:10 Stress Reset Strategies
46:00 Targeted Supplements and Genetics
51:37 Curcumin and Anti Amyloid Caution
54:28 Ketoflex Diet and Metabolic Flexibility
01:00:31 ApoE4 Nuance and Future Therapies
01:05:06 Closing Thanks and Podcast Outro
Dale Bredesen, MD, is an internationally recognized neurologist with specialty expertise in the mechanisms of neurodegenerative diseases. He is the senior director of Precision Brain Health at Pacific Neuroscience Institute® and the Chief Scientific Officer at Apollo Health. Dr. Bredesen has written a number of books, including the NY Times best-seller The End of Alzheimer’s, The End of Alzheimer’s Program and The First Survivors of Alzheimer’s. The website for Apollo Health is ApolloHealthCo.com.
Guided by his philosophy and belief that Alzheimer’s disease it is not just preventable, but reversible, Dr. Bredesen’s innovative research has helped explain the physical mechanism behind the erosion of memory seen in Alzheimer’s disease. His decades of clinical study and neurological research have opened the door to new approaches of treatment leading to the ReCODE Protocol™. Also known as the Bredesen Protocol, this methodology has emerged as a viable attempt to prevent, arrest, and reverse symptoms of cognitive decline associated with conditions such as Alzheimer’s disease, dementias, and mild cognitive impairment.
Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure. Dr. Weitz has also successfully helped many patients with managing their weight and improving their athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111.
Transcript:
Dr. Weitz: If you’re looking for clinically useful insights, not wellness hype, then this is the place for you. Welcome to the Rational Wellness Podcast, the podcast for functional and integrative practitioners who wanna practice with greater clarity and precision. I’m Dr. Ben Weitz, and each week, I sit down with the leading clinicians, researchers, and lab innovators to explore the science, lab testing, and clinical reasoning behind modern root cause medicine.
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Hello, Rational Wellness podcasters. I’m very excited today to be having a discussion on a precision medicine approach to Alzheimer’s disease with Dr. Dale Bredesen. Alzheimer’s disease has long been viewed as a progressive, irreversible, neurodegenerative condition, with conventional treatments offering little more than modest slowing of decline. But what if cognitive decline is not a single disease process, but rather the downstream result of multiple interacting root causes? Metabolic, inflammatory, infectious, toxic, hormonal, and lifestyle related. In today’s episode of the Rational Wellness Podcast, we’re joined by Dr. Dale Bredesen, who’s a neurologist, neuroscientist, and pioneer in precision medicine for neurodegenerative diseases.
And Dr. Bredesen is here to discuss his recent randomized control [00:02:00] trial demonstrating that a personalized functional medicine approach can lead to meaningful cognitive improvement in patients with cognitive impairment and Alzheimer’s disease. This, the paper for this trial is being submitted for publication soon, and hopefully we’ll see it in publication in the near future.
Dr. Bredesen, thank you so much for joining us.
Dr. Bredesen: Great to be here, Ben. Thanks for having me.
Dr. Weitz: So you’ve been working on this precision medicine, functional medicine approach for several decades, and you have considerable data with various cases showing patients improving, in fact, continuing to improve for more than a decade. But why was it so important to do a randomized controlled trial?
Dr. Bredesen: Yeah, it’s a great point. And the idea is that’s the gold standard to convince the medical establishment that what we’re doing works. Of course, we all [00:03:00] ultimately just, we wanna see, you know, positive outcomes, the best outcomes we can see. And as you mentioned, this has been a disease for which there hasn’t been anything, and the research that we did over 30 years showed us that underlying pathophysiology could be attacked, but probably best not to attack it at a single point with just a drug, that you really need to look at this as a network insufficiency, and you need to then identify all the different chronic infections and toxins and just the things that you mentioned, and go after those in order to see improvement.
And so we actually had the first patient treated back in 2012. She’s still doing well 14 years into this. So the idea, we started with some anecdotes, which we published firstly in 2014. Then we did more anecdotes. Then we did in 2018, we published 100 cases of documented improvement in cognitive decline. And then people said, “Well, you need a trial.” So then we did a proof of concept trial next. So each one has been [00:04:00] kinda putting the bar a little higher. And then after you finish the proof of concept trial, which we published, it’s freely available online, that was from 2022 in the Journal of Alzheimer’s Disease now this is a randomized controlled trial.
So now we’re looking at people who were randomized to either the treatment with precision medicine or to standard of care. We would send them back to their physicians and say, “Please give them standard of care for Alzheimer’s disease.” Now, one of the issues has been, what about the ethics? Once you see people get better, it’s very hard to say to somebody, “You’ve been randomized into something that we know doesn’t work, and we’re gonna withhold what we know does work for nine months.”
So people had to wait nine months in the control group. After that, they could get on the protocol. But during that time, as we saw, many of them declined. And so, you know, this is the problem. It’s becoming increasingly unethical to do this type of control group.
Dr. Weitz: Well, but it’s important to be able to demonstrate convincingly [00:05:00] that this kind of a approach is gonna work, and you’ve obviously been facing lots of criticism over the years with people claiming that the approach is not proven and you need a randomized trial, and, you know, it’s kinda sad that medical, conventional medical community has been having such a tough time accepting that this is an approach that might work. And I think part of that’s because it’s so paradigm shifting.
Dr. Bredesen: Yeah, it’s tough because you’re going against a, you know, a typical pharmaceutical approach where the goal is to make over $100 billion. I mean, that, that supports a lot of people. And so to say, “Well, that really doesn’t work. Here’s a different approach that’s gonna make you zero money because we’re gonna be doing all these other things,” and that, that is gonna be tough.
And so we have a lot, as you can imagine, a lot of bias. The reviewers, if they are reviewers that are consultants [00:06:00] or are paid by groups that are trying to sell you a drug for Alzheimer’s that doesn’t work then it’s gonna be tough for them just to look at this with an open-minded, in an open-minded way.
It’s sad because, you know, I think a lot of people, with all this pushback, it has led a lot of people away from something that could have helped them, and allowed a lot of people to, to decline needlessly unfortunately. There’s also, it’s not just about commercial interests. There’s also, as you well know, a lot of groupthink in medicine.
So there’s somebody blesses one particular thing, and then they haven’t blessed the precision medicine approach yet, which is why we need to continue to put out you know, to do trials and put out the results of the trials. I think there’s gonna be a lot of data mining. We have a tremendous amount of data from epigenetics, genetics biochemistry, microbiology imaging, all these sorts of things that are gonna be really helpful as we go through and look.
One of the things we’ve seen already, which has been very [00:07:00] helpful we’ve seen that people, whether you’re APOE4 positive or negative you benefit from the precision medicine approach. Whereas, as you know, in almost all of the drug trials, the APOE4 positives did worse than the APOE4 negatives. We’re seeing that both improve, which is wonderful to see. The other thing is we’re seeing that-
Dr. Weitz: That is wonderful because so many people see that APOE4, especially the 4/4 variant, as a death sentence
Dr. Bredesen: Right. And by the way, we just have looked at now the thousands of people that have come through reCODE protocol and look, reviewing their data, and looking just at the 4-4s, and Dr. Ram Rao is going through this right now. The great news, preliminarily, he’s already taken a look and seen that the 4-4s are clearly improving. They’re improving in their cognitive scores, executive function, processing speed, all of these things. So the good news, I think, is that all of these are, you know, are getting better.
The other thing that has come out of this which has been fascinating, there were [00:08:00] six different sites for the current trial, the trial that we’ve just finished. Four of them got spectacular results. Two of them did not. So it really does make a difference what team you’re working with. So I recommend to people, if you’re gonna go see someone, first of all, ask if they’ve been trained, and then second of all, ask ask to talk to one or two people that have been through that particular site and done well to prove that, yes, here are some people that actually responded very well, because there are groups that are getting a very… You know, everyone to get better, and groups that are getting almost no one to better. One… A couple of our sites every single person who came through and got on a precision medicine approach got better, which is really wonderful to see.
Dr. Weitz: So one of the things you’re pointing out is the importance of individualized care, where not every patient gets the exact same treatment. And in the functional medicine world, we’ve been dealing with this for a long time, and fighting against… [00:09:00] In conventional medicine, e- essentially an approach that was designed to treat infectious diseases, where you have this condition, you take the one drug that treats that condition, and we’ve been… Y- you know, medicine has been trying to apply a very similar approach to chronic diseases.
Yeah. These chronic diseases are major killers for today, as we all know. Heart disease, cancer, neurodegenerative diseases. And that one drug for one pathway approach is n- not been shown to be effective for any of these chronic diseases.
Dr. Bredesen: Yeah, that’s such a good point. So, you know, before we saw the first patient in back in 2012 the standard of care and it’s still the standard of care unfortunately, but the standard was you bring people in, it’s, you treat them with something, it’s a monotherapy, so it’s gonna be typically one drug.
It has nothing to do with what’s actually causing the decline. It [00:10:00] is impersonalized, so it doesn’t matter who you are. It’s uniform. You’re not giving, you know, a different dose for this person or that person. You’re just giving everybody, it’s one size fits all, and it doesn’t work, and people simply go downhill, no surprise.
The research is what really showed us, hey, this is a network that you’re dealing with. This is an amazing and beautiful network within your brain of all these synapses. There are about 500 trillion or so synapses in your brain, and we’re dealing with all these things. So we’re looking at all of the things that are supportive and all of the things that are causing them to pull back.
You really have this beautiful balance between supply and demand. And so when you look at this, there are, you know, three major players and three more modest players, and the three major players are, as you said, inflammation from anything, chronic infections, sinusitis, changes in oral microbiome tick-borne illness poor poor diet, any of [00:11:00] these things, leaky gut, all these things are inflammation.
Toxicity, so things like biotoxins or metallotoxins or organic toxins. And then of course energetics, cerebral blood flow, oxygenation. This is why sleep apnea is so important and such an important risk factor. Mitochondrial function. These are all critical pieces. Those are the big three. And then the more moderate three are neurotransmitters.
You gotta have enough acetylcholine, dopamine, et cetera. And, Trophic support, so that’s hormones, nutrients, and growth factors. And then stress. And as a scientist, I have to say I, I never thought stress was gonna be a big issue for people with cognitive decline, but it’s turned out that you can’t ignore the data.
Stress is a huge player. In fact, has some some of the related pathways are intimately related to what’s happening in Alzheimer’s disease. So, you know, the, you can s- begin to see how this network is set up and why it [00:12:00] fails in so many people. You know, it’s now the number one cause of death in the UK, which is really remarkable. It is slated epidemiologically predicted to kill 45 million of the currently living Americans.
Dr. Weitz: Wow.
Dr. Bredesen: So yeah it’s a huge problem. It dwarfs the pandemic, and so we really need to do everything possible to make sure that this does not kill so many people. And now that we have a way to prevent and reverse decline, especially when you start early, and we encourage everyone, please don’t wait then we should be able to make a dramatic reduction in the global burden and the societal burden of dementia.
Dr. Weitz: So some of the trial some of the locations didn’t get as of good results or very little results or no results. Do we have any insights what was done that was, that didn’t work?
Dr. Bredesen: Yes. We think that we understand this now. In both of those cases [00:13:00] they had s- essentially sub-investigators where the people were relegated to people who were untrained. And they frankly did not know what they’re doing. And this is very much, as you know, functional medicine, precision medicine, very similar to surgery. You have to be good at it. You have to be trained. There are people who aren’t so good. You have to be thorough. You have to do the right things at the right time in the right way, and there are people who are really good at it, which is, as I mentioned where every single person got better in the trial.
When you start sending people to to sub-investigators who really aren’t so good it, you see, you know, you can’t hide. The data show that you simply do not get people being better.
Dr. Weitz: Right. I looked at the data for the people in your trial, and we know that only 12% of Americans are metabolically healthy. But the participants in your study, when they started, were [00:14:00] much metabolically healthier than the average Americans. In fact when I look at the data the results were that the average vitamin D level- was 43, whereas- Yeah … the average 65-year-old in the US has a vitamin D level of 25.
Yeah. hs-CRP of .6, whereas the average in the United States is two to 2 and a half. Fasting insulin of 5.9, whereas the average is nine. Triglycerides 77 versus 150, and a BMI of 24 versus the average of 29. I suspect that if you had average Americans, your results, which were fantastic, would have been even more amazing.
Dr. Bredesen: Exactly. And, you know, we noticed the same thing. So essentially there was a lot of cheating on the side of the control group. So you’re absolutely right. So with our previous trial, it’s just what you said. The average [00:15:00] hs-CRP when they started was 2.3, more like typical American. And so and then we brought it down to less than one.
With this one, as you said, they came in at .6. So what happened was people had been reading up on this and trying to do stuff themselves. And we had already said in the exclusion criteria, “If you’re on any version of this, of course you can’t be part of the trial- … you’ve already done it.” So, unfortunately, people would just kind of say no, we didn’t do that.”
So the reality is, yeah, that’s exactly right. When you take people who are really metabolically more typical of America as a whole, you get even better results. You get even a bigger effect. But even taking these people who started, they- they interestingly, they came in with normal blood pressure, normal hs-CRP, normal fasting insulin, which is, you know, again, rare for Americans.
Dr. Weitz: Yes.
Dr. Bredesen: They still got highly statistically significant improvements in their [00:16:00] memory, in their executive function, in their processing speed, in their overall neurocognitive index. So I think where we suffered on that was the imaging. The imaging, which last time showed improvements in the volumetrics, showed stability.
Now, it didn’t get worse, but it was stability.
Dr. Weitz: Right.
Dr. Bredesen: And I think that is because you’re right, they were healthier than your typical American. So there’s, the, again, there’s no question, there’s so much that can be done, and getting, you know, getting on an optimal program makes all the difference.
Dr. Weitz: And it’s also important to understand that your program is individualized to each person, and you point out somewheres in, in your writings that when your trial is compared to a trial like the ORNISH trial, where people ate healthy, exercised, did some stress reduction, but everybody got the same program, [00:17:00] that those results were not as good as when they’re on an individualized program for that person looking at the biomarkers that show why their physiology is struggling and addressing those particular pathways and endpoints.
Dr. Bredesen: This is a good point. And, you know, so we showed in the paper, if you look at that final figure in the pre-print, it’s a forest plot, and what it’s doing is comparing the outcomes to other con- to other trials. And so this led to the best outcomes in any randomized controlled trial for Alzheimer’s disease and even for people in early stages, MCI or early dementia.
And so it was two to three times better outcome for those who were on lifestyle. Lifestyle’s been the second-best in terms of overall outcomes. And it was four to seven times as great of an improvement as people who went on [00:18:00] non-lifestyle sorts of approaches. So, yeah, I think you’re right.
It’s, you’ve gotta dig in there, and you’ve gotta look for what are the drivers, and sometimes it’s surprising. You know, it may be that someone has undiagnosed sleep apnea, or it may be that they have undiagnosed you know, P. gingivalis or a tick-borne illness. These are sorts of things we see all the time.
Of course, one of the most common is exposure to mycotoxins which has not even been recognized yet as a contributor to Alzheimer’s, and it’s turned out to be one of the most common contributors to cognitive decline. So you’ve gotta look for it, you’ve got to identify it, and you’ve got to address it for best outcomes.
Dr. Weitz: Interesting. Yeah I would say that’s not on the radar for conventional medicine, and they’re very skeptical-
Dr. Bredesen: Right …
Dr. Weitz: when we mention it. Of all these various factors, besides mycotoxins, which are some of the other factors that you have found tend to be super [00:19:00] important for restoring brain function?
Dr. Bredesen: Yeah. Well, as we alluded to earlier, the biggest one, and the most common one, is meta- metabolic dysfunction. These are people who are… typically have metabolic syndrome. So they have gained some weight. They have high triglyceride to HDL ratios. They have high HOMA-IR, so they’re insulin resistant.
They often have an hs-CRP that… anywhere from, you know, one to three or four. So they have some degree of inflammation. They may have a leaky gut associated with this. So it’s that metabolic derangement is the big one, and the good news is it’s the easiest one to treat. People get better fairly quickly when they address that.
You mentioned mycotoxins, which is another big one. Then beyond that, sleep apnea is a surprisingly common contributor to cognitive decline. You are– You’ve got both the situation where you’re driving adrenaline and degrading your sleep patterns during the night, which is why we recommend, you know, get a [00:20:00] wearable.
So I check mine each morning. You wanna go for at least seven hours of sleep, at least 90 minutes of REM, at least 60 minutes of deep sleep, and at least 94% oxygen saturation. If you can hit those four parameters, you’re doing pretty well, but so many people aren’t. The sleep apnea, of course, also is dropping their oxygen saturation repeatedly.
It’s increasing risk for vascular disease. It’s increasing stress. It’s increasing blood pressure. It’s got a lot of problems, so that, that’s another one. And then leaky gut, another common one. Changes in oral microbiome, chronic sinusitis, tick-borne illnesses some metallotoxins. We see a number of people that are high in their mercury.
That’s the common one and the one that’s the most associated the metal that’s most associated with Alzheimer’s disease. So most of us don’t realize we’re walking around with a lot of these risk factors already. And so we’re doing fine, but we are not thinking as well as we could be. And as a great example, we went [00:21:00] into a assisted living group.
There’s a wonderful group led by Dennis Bakopoulos. This is out of, out of the vineyards down in Fresno, California. They’re doing a fabulous job of bringing in this sort of appro- program to their assisted living people and getting wonderful results. Now, o- one of the employees went on this.
He said, “Well, you know, I just wanna see how I’m doing here. And just to kind of test this thing out, how does this program look?” Well, we found out that his memory co- function, even though he’s, you know, he’s functioning day to day, but his memory percentile was 10th percentile.
Dr. Weitz: Wow.
Dr. Bredesen: So things were not as good as they could be for him.
He went on the protocol. Five months later, 91st percentile.
Dr. Weitz: Wow.
Dr. Bredesen: And he had significant metabolic syndrome. By the way, he lost 50 pounds during that five months. So just doing the right things made all the difference. And this is some… So I think it’s important for people to understand, [00:22:00] this sort of approach is not just for people with diagnosed Alzheimer’s.
It’s for everybody who’s over 35. Get checked out, and now of course we can look into very easily with a simple blood test. You can look at the status, just as you look at your hemoglobin A1C to see that, okay, diabetes could be in my future. Let’s avoid that. You can now also look into the brain with a blood test.
You look at p-tau217, GFAP, and NFL. I just had mine checked at my kitchen table a few months ago. And with mobile phlebotomy, it’s easy to do. So I recommend everyone, we work with a group that call, which is called NeuroCode, that has the most sensitive. And you can go online, getabrainscan.com, and get this blood test very simply.
See where you stand. You only need to check it every five years or so. See where you stand. Don’t let it sneak up on you. So you can find out where you stand. You can also get a free [00:23:00] cognitive assessment, mycqtest.com, free cognitive assessment for everybody, so that we know, you know, are we beginning to slip?
Because as you know, this will sneak up on people. They don’t, they’ll say, “Oh, well, you know, I’m just getting a little older, and so I expect that things aren’t so good.” No, you really wanna know where you stand.
Dr. Weitz: I saw there’s an, a newer test called microtubule binding region tau 243 test. I guess they’re trying to come up with newer tests is-
Dr. Bredesen: Yeah.
And that’s a reasonable test. There, there are multiple different tests that can all be helpful. The ones that are best validated are the ones I mentioned. Okay. Are the the p-tau 217, and actually the NeuroCo that I mentioned, that particular group has the most sensitive version in the world, so that’s a really good one.
But they’re coming out with a new one called super p-tau, so that’s gonna be helpful. There’s also now a brain-derived tau. You mentioned the microtubule binding region. There’s also one which [00:24:00] I think is quite interesting, which is called VeraBind. So the p-tau 217 correlates beautifully with the total amyloid burden in the brain.
The VeraBind correlates with the total tau in the brain. So these two together- Huh … really give you a very good look. Where do I stand with amyloid? Where do I stand with tau? And they’re in earl- and they both pick things up quite early. So I am really hopeful that, you know, we’re gonna be able to see this coming just as, you know, just as Pap smears changed the whole landscape when it comes to death from cervical cancer and made this much more uncommon.
Things like PSA changed. Hemoglobin A1C really allowed so many people to catch pre-diabetes early. And so this is gonna be the same thing in the brain that we’ll be able to look very early and make it so that very few people ever go on all the way to dementia, because that’s really a fourth phase.
The first phase, you’re asymptomatic. Second [00:25:00] phase is called subjective cognitive impairment, SCI. That averages 10 years, so you’ve got a wonderful window of opportunity to reverse decline. In that one, you know that something’s not quite right, but you’re still able to score normally on cognitive tests.
The third phase is called MCI, mild cognitive impairment, where now the testing is abnormal, but you’re still able to care for yourself. And then the fourth and final phase is the dementia phase, and during that time, of course, you’re beginning to lose the activities of daily living and ultimately, you know, can’t take care of yourself.
So if everybody would get into those first two phases or even early in the third phase, we see virtually everybody getting better. As you go to that late third phase, in our trial we just looked at third and early fourth phases, and even in that 90% of the people showed improvement. But you don’t wanna wait if you can.
If you can help it, get in early because virtually everybody gets better then.
Dr. Weitz: You mentioned toxins and infections, and for those who are [00:26:00] listening to this who are might be wondering how could that really play a role, the reality is we’ve learned in the last several decades that these toxins and infectious organisms can actually get into the brain, and- Yeah
th- what’s seen as the pathology of Alzheimer’s, which is this buildup of the amyloid and tau proteins in the brain, those proteins are actually trying to protect the brain, and they’re protecting the brain against inflammation, against toxins, against infections. And so what you’ve brought to understanding is that we need to realize the reasons for the amyloid and correct those and not just try to correct the amyloid, and that’s one of the reasons why these drugs that effectively remove amyloid don’t really get people better
Dr. Bredesen: Exactly.
And you know, what has been called Alzheimer’s in terms of the pathology, seeing the amyloid, [00:27:00] seeing the phospho-tau, it has turned out that these are both antimicrobial species. The an- amyloid is an antimicrobial peptide, and the phospho-tau is an antimicrobial protein. So these things are made as part of our immune systems to respond to various pathogens and insults.
What’s interesting is that these things are not only made when you have a pathogen there, but they’re also made when you are reducing your support for the brain. So what’s amazing, this goes back to what, you know, Dr. Jeffrey Bland has talked about over the last several years, immunometabolism. So you’re looking at something that’s related to the, to, to the immune system, but you’re also looking at something that’s related to metabolism and energetics, and these things are intimately intertwined.
In fact, there was a very interesting study that came out where they were looking the group was looking, this is out of University of Arkansas, looking very interestingly at what’s in these plaques, and in [00:28:00] addition to Aβ and tau, they’re also seeing that in these aggregates is interaction between hexokinase and 14-3-3 protein.
So hexokinase, directly related, it’s the thing that converts glucose to glucose 6-phosphate. So it’s, you know, metabolism 101 interacting with 14-3-3, which is there to move things around and activate certain proteins, and triggers things related to the immune system. So again, you can just see this intimate relationship between the metabolic, the energetic side, and the and the defense system for your body.
And so what we see as Alzheimer’s disease is really, again, your body trying to protect you, but also responding to a reduction in energetic support, which is why when we see patients, we want to improve that. We want to improve the energetics. We want to reduce the toxicity. We want to reduce the inflammation.
We want to get rid of any of the things that are causing the inflammation. We often [00:29:00] hear, “Oh, you just need an anti-inflammatory.” Well, it’s not that simple. We want to find what’s causing that inflammation, whether it’s gonna be leaky gut or Borrelia or Babesia or Ehrlichia or P. gingival, what have you. Herpes simplex, by the way, being a relatively common one, and we want to address that to get the best outcomes.
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So go to Apollo Neuro and use the promo code WEITZ today. And now back to our discussion. So the practitioners in these different locations my understanding [00:31:00] is they treated some of these infections differently. Some used antibiotics, some used natural approaches. Right. But most of them got good results, which is interesting.
Dr. Bredesen: Absolutely, and yeah, different ones had… So the goal here was not to do everything the same. Right. The goal here was to identify what the problems are and use your most effective approach to rid the body of those problems. I should mention there’s an interesting article that’s just been accepted for publication, so it’s in press now from Dr.
Richard Horowitz, the Lyme expert, and he’s, in his study, he’s sh- showing this is a patient who has Lyme disease that happened to have a high p-tau217. So again, this person’s making amyloid to protect himself or protect herself from, in this case, the Borrelia. And with treatment with Dapsone, he found that the p-tau came back, which was very nice.
So, you know, again, these are responses. We need to understand [00:32:00] what’s driving them.
Dr. Weitz: That’s probably gonna make it harder for some to accept the result of your trial, is the fact that everybody didn’t get the exact same treatments.
Dr. Bredesen: Right. Again, it was personalized, and it was pr- Right This is what precision medicine is all about.
And, you know, I’ve found it so hard to imagine over the years why it is that anybody would do a trial where everybody got the exact same thing- … and had nothing to do with what was causing the problem. That’s a little strange.
Dr. Weitz: How important is hormone replacement for,
Dr. Bredesen: Yeah …
Dr. Weitz: these patients?
Dr. Bredesen: Very important. And optimizing their hormones, you know, that is another of the things. By the way, that n- not only supports energetics for the brain. Of course, estradiol, very important for energy use in the brain. But progesterone, very important for detoxification in the brain. So, so these are very helpful.
And of course, testosterone also has been shown for years, even in animal models of Alzheimer’s, [00:33:00] testosterone works very well. So again, optimizing hormone support for the brain, very helpful. And in particular, it’s interesting, for reasons we don’t quite understand yet BHRT, you know, bioidentical hormone replacement is even more important in people who have toxin-related Alzheimer’s disease.
They respond really well to BHRT, and they respond very poorly to reductions in hormones. And in particular, they respond to switching over toward cortisol and away from the sex steroids that support brain function. So this is a very important area.
Dr. Weitz: Interesting.
Dr. Bredesen: Many of the experts, like Dr. Anne Hathaway, will tell you, even in their older patients, they c- see improvements in their cognition with BHRT.
Dr. Weitz: And that’s a controversial topic. Finally, the medical profession is starting to recognize the importance of, and the safety of, [00:34:00] hormone replacement therapy, especially for women after menopause. But starting women on hormones in their, sometimes in their 70s or even older, is considered very controversial.
Dr. Bredesen: Very, yeah. It is. And of course, you know, it’s controversial in part because they’re not focusing just on people who have Alzheimer’s. Right. When you look at, you know, do you wanna risk this? Well, if the if the alternative is dementia care then you, that changes the equation. So th- you know, this is why I think it’s so important to see a real expert, whether it’s Dr.
Anne Hathaway you know, Dr. Prudence Hall, D- Doctor you know, Dr. Felice Gersh. So many of these really outstanding hormone experts who understand this and who can make sure that the, you know, the right things are given to the right person.
Dr. Weitz: So on the topic of hormones, one of the hormones you mentioned that I find really interesting is progesterone, and progesterone has even been used for men with [00:35:00] concussion.
I wonder if that’s something that might be beneficial for some men with with cognitive issues.
Dr. Bredesen: No question. And we see all the time men with cognitive decline who have very low pregnenolone and progesterone. And so, and sometimes, as you know, just resupplying, just normalizing pregnenolone, since it’s the upstream hormone for these various you know, various neurosteroids, can be very helpful, and they may normalize all the others from that.
In other cases, of course, as you said, you know, you really have to look more at the progesterone itself. And this has turned out to be helpful. And by the way, it also, as you know, it is a parasympathetic support, so it helps people to sleep better, it helps people to relax better, it helps people to detox better, as I mentioned earlier.
So yeah it’s a very important neurosteroid.
Dr. Weitz: What do we know about your approach for other neurological diseases, say, [00:36:00] like Parkinson’s disease?
Dr. Bredesen: Great point. So we just came out, and actually this is also freely available online, you can see the first example of reversal of corticobasal syndrome. This is a r- another one of these neurodegenerative syndromes.
It’s relatively uncommon. And this was a patient, a m- a pr- a marine who had been seen by Dr. Craig Tonio down in southern Florida. And this person had already been told that, you know, there’s nothing to do. You have corticobasal syndrome. Nobody’s ever gotten better from this. You’re gonna die.
Then she saw Dr. Tonio the next year actually. And he looked and found, oh my gosh, you have significant toxic burdens. This is a person who had been overseas and had been exposed to burn pits, and so had, in association with that, very high levels of several different toxins. And so he put her through a rigorous detox, put her through many of the same things we use on our protocol, got her on the [00:37:00] right diet and she improved dramatically.
Her her MoCA score went from 21, which is right on the border of dementia between d- MCI and dementia, to 28, which is a normal MoCA score. Her hand, as is typical for this syndrome, often you have an what’s called alien hand. You can’t really use one hand. You can’t control it. By the time he finished treating her, she was able to stack quarters and stack pennies with that hand.
I mean, just- Wow. Incredible … striking improvements. And then he also did quantitative EEG and showed these dramatic improvements in her quantitative EEG. So he had a very good criteria for showing that she had been improved. And as I say, this is now freely available online, just been published. There was also a pre-print on this a few months ago.
Just wonderful to see. We also have a case of posterior cortical atrophy. This is from Kerry Rutland in New York and with c- consultation from Dr. Neil Nathan in California. And again, [00:38:00] something that has never been reported to get better before. About 5 to 10% of all Alzheimer’s patients begin with this posterior cortical atrophy syndrome.
These are people who ty- typically have problem with reading and recognizing things. Something where called simultanagnosia, where they can’t look at two objects at the same time. If they do, they just see one of them. They don’t see the other one. So it’s a visual processing problem because it’s back in the parietal lobe and occipital lobe.
This person had A volumetric MRI with her parietal lobe being less than the first percentile.
Dr. Weitz: Wow.
Dr. Bredesen: Carrie worked with her. She had a follow-up that was about a year later and… or a little over a year, I guess, later and was 22nd percentile. Wow … so again, just dramatic improvements. She went from not being able to read to being able to read again, in fact, is reading [00:39:00] voraciously, not being able to use her computer to being able to use her computer.
So, you know, it’s wonderful. This is a new era, to be able to see people who had nothing. Now, we do have people with Lewy body disease who’ve gotten better. We have some people the that we’re seeing in a clinic we worked with in Texas. And just with some improvement, just the beginnings, some improvement in macular degeneration, improvements in dar- dark adaptation in one patient, for example OCT in a second patient.
So very excited about that. And so, you know, this approach should be adaptable to all of these different ones with the idea that they’re each driven with different pathophysiology, but at the heart is a network insufficiency for each one of these. And, you know, evolutionarily, if you look at this, what’s happened is over the evolutionary eons, we humans have Always selected, and as other organisms [00:40:00] do, for performance over durability.
So if we can outperform others, we can do well. And so w- but we do that, as I say, at the expense of the durability. So now we are, unfortunately, we have these Achilles’ heels. We have these remarkable nervous systems. You know, neuroplasticity, which goes awry in Alzheimer’s. You can… You’ve got more storage capacity in your brain than in over 2,000 home computers.
Wow. It’s truly remarkable. Then you have a separate system for motor modulation, and as you know, you know, be- being into sports it’s incredible what people… I mean, look at hitting a baseball at 100 miles an hour. I mean, it’s just unbelievable what humans can do. Look at what Simone Biles does in the Olympics.
I mean- Absolutely … humans have this amazing ability. That’s the system that goes awry in Parkinson’s, and as you know, it’s dramatically requiring of mitochondrial complex I. Then you look at what happens in ALS, another sports-related [00:41:00] problem, increase in athletes. That’s a system that’s associated with amplification of signal, and it’s dramatic ampl- You get about the same amount of amplification when you go from a thought to maximal muscle contraction as you do when you stomp down on your accelerator and floor it.
That’s how much amplification you get. But it’s at the expense of you’ve got this glutamatergic system, where you often have excitotoxicity, especially if there’s any trouble with reuptake of the glutamate. So all these systems are slightly different, but they all ultimately suffer from an insufficiency because of this evolutionary selection.
This is called antagonistic pleiotropy. It’s the same thing that’s well accepted for what happens in aging. And so we’ve, again, we have now the ability to look at these systems earlier and to be able to address them before you have major problems.
Dr. Weitz: When it comes to Parkinson’s, is the [00:42:00] alpha-synuclein that’s found there, is that an antimicrobial in some way similar to amyloid?
Dr. Bredesen: Absolutely. So interestingly, each one of these things has as part of it an antimicrobial peptide or protein or response, and each one is a prion, prions being these in- proteinaceous infectious agents. Of course, that Dr. Stan Prusiner won the Nobel Prize in 1997 for his discovery and characterization of this phenomenon.
And so, you know, why would this be? Why do we have these infectious agents? And it looks like one of the interesting possibilities is that these are anti-infectious. They’re all… Although they, yes, they are proteinaceous, and they can you know, they can beget more of themselves, they are, they also function as anti- various anti-pathogens, essentially, anti-infectious agents.
So that’s one of the intriguing things. [00:43:00] Why do all of these diseases have this? And I think one of the possibilities is when you are calling out a response, and the response is to pathogens that th- that themselves are dividing, don’t you have to have a system that’s growing with the pathogens that’s, you know, now going to address them until you’ve gotten rid of them?
And of course, then you can begin to degrade these responses and reset the machinery. But if you’re overwhelmed by these things, of course, you’re just gonna be in a system where you’re making more and more of these things, and you then die of a prion disease, whether it’s Aβ, whether it’s Phospho-tau, you know, whether it’s PrP, whether it’s something else.
So these, I think we’re getting better and better looks at the fundamental nature and causes for these various neurodegenerative conditions. And it has some- something to teach us about things like schizophrenia and autism spectrum disorder. As you know, there’s some literature recently saying that there are [00:44:00] some similarities that you see between autism spectrum disorder and Alzheimer’s disease.
So these things are all kind of coming together with precision and functional medicine.
Dr. Weitz: You mentioned stress as being a big factor. What were some of the effective ways that the practitioners dealt with stress with their patients?
Dr. Bredesen: Yeah, this is such a good point, because you get these people who are kind of locked into this sympathetic little vagal tone, massive stress, high cortisol, poor sleep.
These things all really degrade the nervous system. So we, you know, we dealt with that and the practitioners were using heart math. So for some biofeedback to relax people they… We worked with health coaches and did some bre- you know, breathing to relax. Some of them are interested in additional things like yoga like, transcendental meditation or other forms of meditation, even things like music or shinrin-yoku and things like that, forest, [00:45:00] you know, forest bathing.
Any of these things to bring that down and to make sure that the, that you are minimizing the contribution from that. That include you know, improves blood pressure, it improves cardiovascular status, it improves neuroplasticity, and all of these things are impacted by reducing stress. And of course, part of it was optimizing progesterone levels as well.
That’s another piece that can be helpful there. And then some like to use, you know, additional, you know, supplements and things like that. So there are so many approaches. The good news is, in the armamentarium, there are things for any contributor. So if you identify those contributors, you’ve always got something you know, you’ve got something in your in your arrow sh- arrow bag you can pull out and really help that person, and this is why I think there have been such good outcomes.
As I mentioned in the trial, 90% of people showed improvement.
Dr. Weitz: That’s awesome. I can’t wait for that trial to get published.
Dr. Bredesen: It’s [00:46:00] coming.
Dr. Weitz: You mentioned nutritional supplements.
Dr. Bredesen: Yes.
Dr. Weitz: So I’m a big believer in nutritional supplements, but nutritional supplements have been one of the ways that people who are antagonistic to your approach have attacked you as being- unproven and-
Dr. Bredesen: Right …
Dr. Weitz: wasteful. But I wanted to tap your brain into some of the supplements that might be especially helpful, besides the ones that everybody knows about that are contributing to maximizing trophic support and the pathways like omega-3 levels and vitamin D levels and B vitamins for lowering homocysteine and things like that.
There’s some supplements that have recently shown some really interesting benefits, and one of them that I’ve been reading about is low-dose lithium orotate.
Dr. Bredesen: Yeah. So, and it’s important to point out, you know, lithium has been used for years. None of these as a monotherapy [00:47:00] is a cure. Right.
Of course not. Now, people have said, you know, they… When they criticize what we’re doing, they say “There’s no supplement that’s a cure for Alzheimer’s.” Of course there isn’t. We never said there was.
Dr. Weitz: Right.
Dr. Bredesen: So they’re criticizing something that we didn’t even say. What we said was, “If you’re going to get best outcomes, don’t forget that there’s, there is a supplementary approach to everything else you’re doing, to the diet, exercise, sleep, stress, you know, brain stimulation, detox.
In addition to the basics, in addition to looking for those infections and looking for those toxins, yes, there are, of course there are targeted supplements.” So if you’re low in your vitamin D, you better be adding some. If you’re low in your omega-3s, you better be adding some. If you’ve got some inflammation and you’re addressing these various pathogens, you better think about some СПМs that are so help- the resolvents that are so helpful for resolving inflammation.
If you’ve got mitochondrial issues, think about some Urolithin A in addition to the CoQ and the usual sorts of things. Yes, if your homocysteine’s high, just as you said, you better be [00:48:00] thinking about some activated Bs, some, you know, methyl B12 and methylfolate and P5P which most people tolerate well.
There are those few people, by the way often with vitamin D receptor mutations and/or COMT mutations, who actually get more you know, they get more aggressive, they get more irritated when you put them on methyl Bs. So you have to give them non-methyl Bs. So just keep an eye out for those rare, the, those occasional people that will come through with that.
Dr. Weitz: That’s interesting. Are those people that have different genetic variants? Do you know what those are?
Dr. Bredesen: Yeah, so C- it’s typical COMT. Yeah. So what’s happened is they’re hypermethylators instead of hypomethylators.
Dr. Weitz: Ah.
Dr. Bredesen: And so now you bring in these methyl, and it’s just too much, and they tend to, as I say, they tend to get irritable.
And they don’t do so well. You just have to recognize it and say, “Oh, yeah, let’s… So we want to give you non-methylcobalamin. We want to give you hydroxocobalamin and adenosylcobalamin, that sort of thing. Adenosylcobalamin. So th- those are the sorts of things you can do instead. [00:49:00] So I think those are all excellent.
And s- and, you know, again, comes back to energetics. So the various ways to drive up NAD, and there was just a paper, everyone’s quoting this paper. You know, they made some mice better with s- with an NAD-increasing approach. Yes, we’ve been doing that forever. And yes, it’s it’s helpful, but the vast majority of things that make mice better don’t make humans better.
So it’s not a very good model, unfortunately. It’s mouse-heimers, it’s not Alzheimer’s. So yes, NAD very up. So whether you use nicotinamide riboside, NMN you know, NAD. Some people like NAD infusions and do very well, especially people who have some contri- contribution from chemotherapy, chemo brain.
They tend to do very well with NAD infusions every m- you know, month or couple of months. What
Dr. Weitz: i- what is chemo brain?
Dr. Bredesen: Chemo, from chemotherapy Oh,
Dr. Weitz: chemo.
Dr. Bredesen: Oh,
Dr. Weitz: okay.
Dr. Bredesen: Okay … through chemotherapy which can often- Sure … damage the brain- Yeah … and give them problems with cognition over the [00:50:00] long haul. So there’s another, again, another way where, you know, can be very helpful.
So all of these things can be very helpful. You mentioned the lithium orotate. We typically use and a number of the people had it in the trial lithium orotate, typically at 5 or 10 milligrams.
Dr. Weitz: Right.
Dr. Bredesen: And yeah, so there was that nice work that came out, again, related to mice a few months ago out of Harvard, and so everyone jumped on this and said, “Oh, this is now the, you know, the big treatment for Alzheimer’s.”
Well, it’s been around for a long time. As part of an overall protocol- Right … absolutely, and especially we tend to think about it when people have any sort of affective you know, people who are having issues with depression or a bit of mania those sorts of things. As you know, the old epidemiological studies showing people where the water was low in lithium had more, you know, crime and murder and things like that.
So yeah, just getting it to normal is a good thing. So again, you know, we c- it comes back to the same thing. Nature is good. [00:51:00] We gotta optimize the natural pa- the natural physiology to get out of that pathophysiology, and if we’re gonna use drugs, and great, I think the future is now bringing targeted pharmaceuticals together with precision medicine, but you wanna use them judiciously and know, you know, why are you targeting something?
What is it, and is it right for this person? Because as you know, there can be side effects when you ignore Mother Nature. So I think that, you know, this is an exciting time. We’re seeing such progress in the whole area of chronic complex illnesses like Alzheimer’s disease and other neurodegenerative conditions.
Dr. Weitz: When it comes to inflammation, you mentioned ATMs. What about some of the specialized forms of curcumin? I found-
Dr. Bredesen: Yeah …
Dr. Weitz: some of those to be very helpful.
Dr. Bredesen: Yeah, you wanna be careful in that you don’t wanna go too high on the curcumin, but it has two interesting effects. Of course, it’s got an anti-inflammatory effect, especially around half a gram, and out of that.
Once you’re getting up [00:52:00] to five grams and s- and more, it does, it binds amyloid. In fact D- Dr. Greg Cole and Dr. Sally Frautschy from UCLA showed very nicely, you know, this is interacts with amyloid even at very low concentration. This is a tight binder to amyloid, and by the way, p-tau as well.
But now you’ve got… You’ve lost that anti-inflammatory effect. Right. So this is why we use lower amounts. You do have to be careful for people who have congophilic angiopathy, which is the amyloid associated with the blood vessels, where these people, if you go in and you rip this out, for example, with an anti-amyloid drug, you can get some micro hemorrhage.
And, you know, I wanna make one pitch here which is that there are a lot of places that when they find out someone is APOE4/4, and there are about 2 million Americans… Sorry, 6 million Americans. It’s about 2%, so about 6 million Americans who are who are a- amyloid, who ha- who have APOE4/4, and therefore at increased risk.
When [00:53:00] those people go on these anti-amyloid drugs, they they don’t do very well typically, unfortunately. And in fact, in the lecanemab trial, they actually did worse than control. So worse than getting nothing. So be careful. And yet, at so many clinics and universities across the country, they are recommending these drugs for people who are APOE4/4, despite published information saying that…
I mean, I still don’t understand that. I would worry about malpractice if you had something that you knew made you worse, and you were recommending that as a treatment. So, I hope that there will be more judicious use of these of these drugs for people who have, especially for people who have APOE4/4.
Dr. Weitz: I wanna make a point about the curcumin, and I wanna talk for a minute about the diet. So- Mm-hmm … on the curcumin one of the things that it may also be helpful i- at the higher dosages is chelating [00:54:00] iron. And 30% of the population has at least one of the genes that makes them store iron, hemochromatosis.
Yeah. And I think that can be a contributor as well, and a higher dose curcumin can be effective at that. And the form of curcumin that I’ve found to be helpful, which i- is effective at a lower dose, and there’s some work out of UCLA, is the Theracurmin, the water-soluble-
Dr. Bredesen: Yeah … curcumin.
Dr. Weitz: Sure. Mm-hmm.
When it comes to diet you mentioned ApoE4. There was just a paper showing that patients who have ApoE4 who eat red meat, meaning that more of a of a of a keto type of diet might be effective for them in reducing heart disease. I know you recommend a mildly ketogenic diet. What do you think about, can you explain why a mildly ketogenic diet potentially is more beneficial than a strict keto diet? And what about [00:55:00] diet for these ApoE4s?
Dr. Bredesen: Yeah, great point. And, you know, for all the different things that we do to help people with cognitive decline, diet is right there as one of the very most important things.
So we u- And we’ve looked at, you know, all the different pieces of what fits the biochemistry of the pathophysiology of the disease, where have we had the best you know, best results. So what we use is something called Ketoflex 12/3. That, I mean, that is a plant-rich, not plant only, so there, you know, fish, ch- you know, w- pastured chicken is fine.
Non-CAFO meat is fine. You know, you wanna have- Non what? Non- non-CAFO. So in other words, you don’t want these feeding lots- Oh, okay … where you’ve got these, all these sick animals. Right. You don’t want that, right? You w- you know, you wanna have these you know, these pastured-
Dr. Weitz: Pasture raised, yeah
Dr. Bredesen: yeah, exactly. So those are all fine. And so it’s a plant-rich, mildly ketogenic diet, and it does many things. First of [00:56:00] all, your brain is like a Prius. It’s only got two things it can run on, and it can run on glucose, and it can run on ketones. When you are metabolically flexible, you go back and forth. And actually, my wife, who’s an integrated physician, told me this years ago, “You gotta have both.
You gotta be metabolically flexible, be able to go back and forth.” And now what’s happened, so we use- You know, ketones, as I mentioned, and glucose. But for most of us, when we are metabolically dysfunctional, we lose both of those. We can no longer u- use the glucose optimally. And in fact that’s the signature on PET scan of Alzheimer’s disease.
You have a reduction in glucose utilization in the temporal and parietal regions. So now you’ve got this insulin resistance, you have metabolic syndrome, you can’t use that. But you’re now pouring out this increased insulin level, and that prevents you from making ketones. So you’ve got the worst of both worlds.
So when we see people with cognitive decline, we recognize they are– their brain [00:57:00] are sputtering. Their brain is sput- So we wanna get back their insulin sensitivity and their ability to make ketones, to be able to be metabolically flexible and go back and forth, and we see just dramatic improvements with that.
That’s the beginning of getting better. Then when you have a plant-rich, mildly ketogenic diet, you get the polyphenols. Polyphenols alone have been associated with cognitive improvement. You get the high fiber diet, the prebiotics. You’re improving your gut microbiome. You’re improving your detox.
You’re improving your gut function. You’re improving any degree of leaky gut. I mean, just multiple things. Now you’re making it so your glucose is not spiking and troughing, so we recommend people use CGM. Of course, continuous glucose monitoring has become so popular because it’s so helpful. You can see, are you peaking and troughing?
You don’t want either of those. You want a relatively stationary, a pretty smooth glucose. Yes, it goes up a little when you eat, it can go down a little while you’re sleeping, [00:58:00] but w- then you should be bringing in some ketones. So you should be able to keep your brain energized twenty-four/seven, and that’s the thing that works best is that combination of the plant-rich, mildly ketogenic diet for all the reasons I mentioned.
You know, exercise regularly. By the way, both strength training and aerobics. And if you can get some HIIT in there, which we also used in our trial, very helpful. If you wanna use KAATSU bands very helpful as well. And I really like EWOT, exercise with oxygen therapy. So let me ask you, as an expert in this area, do you recommend or do you ever use KAATSU bands?
Do you ever use EWOT for your patients?
Dr. Weitz: I do sometimes. I’ve used the bands. But I, I find in general if they’re doing the strength training and they’re doing some high intensity burst training along with the cardio, that usually is pretty effective
Dr. Bredesen: Yeah, great. [00:59:00] So yeah, so, so that’s the sort of diet approach we’ve taken. And of course, you know, organic, we want to minimize your exposure to toxins because, you know, people do get a toxic burden over their lifetimes, and, you know, their organs are just filled with this stuff. We wondered years ago why it is that we saw so many relatively young women typically f- you know, 49, 50, 51, 52, right around the time of menopause, that would show up with toxin-related Alzheimer’s.
And of course, it’s turned out that you’ve got this stuff stored in your bones. You go through that osteoclastic burst for about seven years or so, and you are re-releasing these things back into the bloodstream. And so, so many people would show up with Alzheimer’s diagnosis at that time. And so now we need, we, you know, we realize, okay, we’ve got to look carefully at toxic burden, and we need to detox people.
And as you know, you can’t go too quickly. The more toxic you are, the slower you have to go to detoxify, as Dr. Neil Nathan has [01:00:00] t- has taught us.
Dr. Weitz: I wanted to point out, I think the the restricted blood flow can be especially helpful for patients who have orthopedic injuries, where they find it difficult to do i- intense strength training.
So I think those bands are able to be effective for those patients in particular and to be able to get that same kind of stimulus.
Dr. Bredesen: Exactly. No, I think that’s what’s been so helpful about them. You get more bang for your buck, basically.
Dr. Weitz: Absolutely. And so for the diet, you think this the ketoflex is optimal for the ApoE4s as well?
Dr. Bredesen: I do. And i- what we suggest is ApoE4 tend to absorb fat a little better. They tend to also have more of a pro-inflammatory state. And we studied ApoE4 in the lab for years. Dr. Ram Rao and others did a beautiful job showing that this thing actually enters… So ApoE4 binds to specific receptors.
That had been [01:01:00] known before. But what he discovers, it, it enters the cell, and it actually enters the nucleus and interacts with DNA itself, and this has now been confirmed by other labs. And it is a transcriptional repressor, so it’s slowing down, it’s reducing the production of certain things, 1,700 different genes.
So it’s a controller of a number of f- factors coming from your cells. And what it does is it reduces the things that normally would mitigate the pro-inflammatory response. So now what you end up with is a more brisk inflammatory response. And so we’re very excited now. We actually have a targeted drug candidate that negates the effect of ApoE4 to increase your risk for Alzheimer’s.
That’s been published, freely available online as well. And very excited about that. We are just currently raising support to take that into human trials. So I think that we understand what’s going on, you know, better than [01:02:00] before. And all these things contribute. Now, you mentioned this, th- this finding with the meat diet.
I would like to see a little more data on that because, you know, you’ve got this whole literature, and then the one thing will come out and say, “Oh, good.” You know, there is a fair
Dr. Weitz: amount- I know so many of the dietary studies- Yeah … are so problematic. Yeah.
Dr. Bredesen: Yeah. So, you know, it, it’ll be interesting. If it’s the case, okay, so be it, but let’s make sure the data fit that.
Dr. Weitz: So when you say the ApoE4s absorb fat are you saying that it’s good for them to have the fat, or that they might, say, have increased cholesterol as a result of absorbing the fat, or what is the significance of that?
Dr. Bredesen: Great point. So, and it’s, again, it’s not that it’s good or bad, it’s that it’s different under different conditions.
So in other words, you take an ApoE4 positive, an ApoE4 negative, you starve them both. The ApoE4 negative will die first. The ApoE4 positive will, will survive because they are better. They’re more efficient at keeping it. So what we, all we do is [01:03:00] we recommend go more towards 16 hours of fast at night if you’re ApoE4 positive, and more toward 12 to 14 if you’re ApoE4 negative.
And yes, be a little more on the anti-inflammatories if you’re ApoE4 positive. And, you know, follow your lipids. So all of these are important in terms of understanding. And that’s not that one’s better than the other, it’s that they’re diff- they’re made for different scenarios. Now, I should mention, you know, if you go to the Chimane Indians who…
down in Bolivia, in the Third World, they d- no question do better as ApoE4 positives. Something similar has been shown in Africa as well. But with-
Dr. Weitz: Why do they do better as ApoE4s?
Dr. Bredesen: They… looks like because they are exposed to a lot of microbes, and you have a more brisk pro-inflammatory response.
Dr. Weitz: Okay.
Dr. Bredesen: So again, you go out and you go back to, you know, 5 to 7 million years ago, the first hominids, when we diverged from our [01:04:00] simian ancestors, we came down out of the trees, and we start walking around, and you’re puncturing your feet. You’re fighting with your food, all these things. You have an advantage as an ApoE4 positive, and that in fact was the primordial gene.
It wasn’t… You know, you have to fast-forward here, 96% of hominid evolution, we were all ApoE44. Just in the last 220,000 years, ApoE3 appeared, and in the last 80,000 years, ApoE2 appeared. And so now the… You know, f- if you’re living in a First World country, where having this pro-inflammatory response is not as helpful, then you can have a little advanced aging.
That’s been shown. As you mentioned, cardiovascular disease, of course increased risk for Alzheimer’s. All right. Well, you can recognize that. You can reduce that risk by getting in early and, you know, taking the appropriate steps, having the appropriate diet, et cetera. So again, it’s not that one’s good or bad, it’s that they’re there [01:05:00] for optimal times in different you know, different scenarios.
Dr. Weitz: All right, Dr. Bredesen. Awesome information. Thank you so much for spending some time with us. I hope one day you get a Nobel Peace Prize for the work you’re doing, and I also wanna thank you on behalf of the functional medicine community for all the work you’re doing, because not only are you helping to validate an effective approach for helping patients with neurodegenerative diseases, but it’s helping to validate a functional medicine model, which has also been much attacked over the years.
Dr. Bredesen: Yeah, it has. Yeah. Very good point. Well, thank you so much, Ben. I always enjoy talking with you. Great to talk, especially after the clinical trial. We’ve got so many positive results out of that. It’s
Dr. Weitz: so exciting.
Dr. Bredesen: I look forward to to getting that out, so thank you very much.
Dr. Weitz: Thank you for making it all the way through this episode of the Rational Wellness Podcast.
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