Torofy Blog

Depression and Heart Disease

Dr. Dale Bredesen on Preventing and Reversing Alzheimer’s Disease

[Rhonda]: Hello everyone. I’m really excited to be sitting here with
Dr. Dale Bredesen, who is internationally recognized for his understanding of the mechanisms
of neurodegenerative disease, particularly Alzheimer’s disease. He holds faculty positions at University of
California Los Angeles and the Buck Institute for Research on Aging. In fact, he was the founding president and
CEO of the Buck Institute back in 1998, so that’s really kind of cool. And he also is an author of a “New York Times”
best-selling book called “The End of Alzheimer’s Disease,” which I’m sure we’re going to talk
quite a bit about today. It’s got a really interesting multi-pronged
protocol for preventing and also helping treat mild cognitive dementia and Alzheimer’s disease. So thank you so much, Dale, for having me
here at your place. [Dale]: Thanks very much, Rhonda. [Rhonda]: So maybe we can start a little bit
by just talking about some of the characteristics and pathological distinguishing features of
Alzheimer’s disease and maybe what your thoughts are on what can cause Alzheimer’s disease
or leads to it. [Dale]: Right, so it’s a good point because
cognitive decline, very common, and Alzheimer’s is the most common cause of cognitive decline,
ultimately dementia. And by definition, this means that you have
amyloid plaques in the brain and phosphorylated tau tangles. So those are the two main pathological hallmarks
of Alzheimer’s. But as you can see, that doesn’t tell you
why you got it, it just is something you look at the brain, and of course, you can get something
that looks virtually identical without the amyloid and you can get amyloid without the
cognitive decline. So, it’s a marker but it’s an imperfect one. [Rhonda]: Yeah, that’s a really good point
you brought up. And do you have any thoughts on why there
are some people that do have amyloid plaques in their brain that aren’t demented and then
some others that just don’t seem to handle it? [Dale]: Yeah, it’s a great point. So, here’s the thing, the whole world is turning
upside down now when it comes to our understanding of Alzheimer’s. It’s been over 100 years, of course, going
back to Alois Alzheimer’s publications back in 1906 and 1907, and there hasn’t been a
good understanding of this disease. And of course, amyloid has been for years
vilified and there’s no question, it is a neurotoxin. It does have toxic effects. The surprise has been that this is also a
protectant. It’s actually something that is made by your
brain when you have specific insults. And for example, Professor Rudy Tanzi and
Professor Robert Moir of Harvard a few years ago showed that it is an antimicrobial. It also, as Professor Ashley Bush showed a
number of years ago, it’s actually quite a good binder of divalent metals like copper
and zinc, and things like that, iron. And we showed a number of years ago, it is
also a response to a reduction in trophic support, so you actually get a change in signaling. So, there are multiple different insults and
metabolic changes that lead the brain to produce this stuff. And so I think there’s been confusion because
it’s clear that when you produce it you’re at this increased risk for having a degenerative
process, but as you indicated, there are many people that produce it and they successfully
are protecting themselves, they don’t actually have the downsizing. What’s often been stated is those who then
have inflammation on top of that seem to be the ones that do worse, and that’s a very
general idea, but really it is a set of things. And we identified and published, a number
of years ago, 36 different factors that all contribute to this, but they actually break
down into just a couple of categories. So, any sort of pathogens, anything that’s
giving you inflammation, whether you have it because you have a leaky gut or because
you have P. gingivalis in your brain, or because you have Borrelia of Lyme disease, or you’ve
been exposed to specific fungi, things like that, all of these things can engender that
response. And in fact, we think more and more of amyloid
as being like napalm. You got the bad guys coming across the border,
so you’re now going to put down stuff that kills the bad guys, the napalm but in so doing
you’re now going to reduce your arable soil. You’re now living in a smaller country, and
that’s exactly what’s going on in the brain, you are downsizing the overall network. So, that’s what we call type 1 or inflammatory
or hot Alzheimer’s. And I should mention, it turns out ayurvedic
physicians from thousands of years ago who recognized dementia that was related to something
that was hot, that was abnormal and ultimately inflammatory, as well as that was related
to dryness, which is what we call type 2, where you have decreased trophic support. It can be nerve growth factor, brain-derived
neurotrophic factor, estradiol, testosterone, pregnenolone, progesterone, thyroid, vitamin
D, all of these things are critical to support of synaptogenesis. So we think of the signaling as being a ratio
of synaptoblastic activity where you’re actually sending signals to make and store synapses
(just like you think of osteoblastic activity) versus synaptoclastic activity where you’re
actively pulling back and you’re reorganizing. And of course, this is going on all the time. You’re actively forgetting the seventh song
that played on the radio on the way to work yesterday and you’re actively forgetting a
lot but you’re remembering the key things, like where your keys are and where your son
is and all that sort of stuff. And so, there is a change in that ratio in
Alzheimer’s disease because of type 1 with inflammation or type 2, which we call atrophic
or cold, because you don’t have the support for those synapses, so you’re literally…it’s
a little bit like someone saying, “I’ve got five children and I can only feed four. I can either watch all five starve slowly
or I can put one in a foster home and feed four,” and that’s basically the downsizing
that’s happening when you cannot support the neural network that you have. And then we have a type that’s actually type
1.5, which is glycotoxic. And we named it that because it has features
of both type 1, inflammatory, and type 2, atrophic. So what happens is you develop insulin resistance,
so you now have a change in signaling that actually occurs because of this chronic high
insulin. So you actually phosphorylate your IRS-1,
as shown very nicely by Professor Ed Goetzl over at UCSF. So you change the ratio of the serine/threonine
phosphorylation to the tyrosine phosphorylation and you’re literally changing your response
to insulin, so that gives you the type 2 because you no longer have insulin as the supportive
trophic factor to the extent it was previously. But of course, you’re also glycating proteins
with…and we measure this, of course, as hemoglobin A1C. But you’re glycating many proteins, so you
get now a response to that as well. So you have an inflammation in an atrophic
and so that’s why it’s 1.5. And then type 3 turns out to be completely
different, and that is a response to toxins. So there is a toxic form, which we call toxic
or vile Alzheimer’s disease. In addition, there are people we called type
4 who have more of a vascular component and then type 5, which is more of a traumatic
component, but they’re really both related to these other ones. It’s really about, do you have inflammation? Are you fighting something off? Do you have trophic support, and are you exposed
to specific toxins? [Rhonda]: Wow, and so in all of these different
subtypes of Alzheimer’s disease they all sort of have some of the same distinguishing pathological
features like amyloid beta plaques, tau tangles between all of them. [Dale]: So they all have amyloid plaques,
they all have, by definition, tau tangles, but the presentation can be different. Now there are some overlaps, the type 1s and
the type 2s are typically amnestic presentations more common with ApoE4, and that’s true for
the type 1.5s as well. The type 3s, the toxic ones are quite different. They often present with a non-amnestic presentation. It’s executive dysfunction, problems with
calculation, problems with visual perception, problems with word finding, so-called primary
progressive aphasia, all of these things, they are really bi-parietal presentations
as opposed to bi-temporal presentations, essentially. So these have often been called cortical presentations,
which have been noted for years by people like Professor Mario Mendez, to be typical
in younger presentations of Alzheimer’s and often in ApoE4 negative individuals. [Rhonda]: I think I also read one in your
papers where you did this metabolic profiling there was a very prominent zinc deficiency
in that. [Dale]: Yes, so for reasons that we don’t
entirely understand yet, many of the people with the type 3, the toxic sub-type have low
serum zinc, high copper-zinc ratios, and low triglycerides. The low triglycerides may turn out to be related
to malabsorption, we don’t know for sure yet, but we don’t really understand why the people
often have these low copper-zinc ratios. [Rhonda]: What does that mean, the copper-zinc
ratio, what is that? [Dale]: The high copper-zinc ratio, low zinc. [Rhonda]: Low zinc, yeah. [Dale]: Yeah, so as, you know, copper and
zinc actually are competitive, for example, in their absorption. And so, too much of one actually is often
associated with too little of another. And then typically in our society, as you
know, most of us are deficient in zinc. There are actually about a billion people
on Earth is the estimate for zinc deficiency. It’s a very common problem because if you
have poor gastric acidity, which is common as we age, if you’re taking PPIs for GERD,
if you’re taking something for reflux, you won’t absorb the zinc very well, if you have
copper piping which most of us do, the copper will often compete with the zinc. And so many people have a little too much
copper and a little bit too little zinc. And in fact, it was noted over 30 years ago
that people with high copper-zinc ratios tended to have dementia more than those with normal
copper-zinc ratios. [Rhonda]: Wow. So does this have something to do with it? I know there’s like over 300 to 500 different
enzymes in the body that require zinc. So does copper then bind to those enzymes
and then sort of mess up the function or is that like the theory? [Dale]: So, no. The theory is that, as you know, copper is
a generator of free radicals. You know, copper can act like iron in that
sense. It has a free electron in the D orbital which
does not occur with zinc. So in general, as you indicated, in these
various enzymes, and it’s hundreds, just as you said, it is an important structural component
and it has a very specific architecture with the enzymes that it serves, so it is a structural
thing in general. And copper, to my knowledge, doesn’t actually
replace that. But for example, zinc is important in many
things that are related to cognitive decline, it’s important in diabetes, it’s important
in functioning of insulin, it’s important, of course, in the trophic activity of insulin
and, you know, on and on. It’s important in immune responses. So, it actually has many effects that are
related to cognition. [Rhonda]: So it may even just be a biomarker
for something underlying going on right in the toxic insult type of Alzheimer’s disease
you’re talking about. [Dale]: It something to keep in mind when
you see that, and especially if the person presents, and these people tend to be very
distinctive, the people who have type 3. So, they tend to be young, and we see them
in their late 40s, mid 50s very commonly. We’ve seen them as late as starting their
first symptoms in the mid-60s, but typically, their first symptoms are currying in the 40s
and 50s. They are often women, they are often ApoE4
negative although not always. There are certainly people who are ApoE4 positive
to have this. As you mentioned, they often have the low
zinc, and then they typically present in a non-amnestic way. Interestingly, unless they are homozygous
for E4, in which case they do present typically with an amnestic presentation, but the ones
who are E4 negative typically present with problems, as I mentioned earlier, executive
dysfunction problems. And so I always ask people, are you having
trouble organizing things? We had one person, for example, who was known
for her tremendous organizing capability and as she started to get the problem she just
lost it. She could not organize things that she could
do before, it’s a very common complaint. Or as I said, people will say, “Oh, I can’t
calculate a tip anymore, or I can’t pay the bills anymore,” anything that is math-related
or visual perception or word finding, things like that. [Rhonda]: You mentioned the ApoE4 a few times. Can you talk a little bit about just for people
listening and watching, you know, what ApoE4 is, and it’s a gene, and so why it plays a
major role in Alzheimer’s disease. [Dale]: Yeah, so, Apolipoprotein E is a really
fascinating story, and of course, Professor Robert Mahley discovered this decades ago,
and it has turned out to be the most important genetic risk factor for Alzheimer’s disease. Seventy-five million Americans have a single
copy of ApoE4. And when I say that what I mean by that is,
everybody has two copies of either 2, 3, or 4, and the most common one is ApoE3. So it’s common for people to be a 3,3 as an
example. However, about a quarter of the population,
so about 75 million Americans have one copy of ApoE4, and that’s actually the primordial
one. It’s the one that was present for about 96%
of hominid evolution. If you look at a chimp for example, it does
not have ApoE4 but the hominids do, and still about 25% of the population today. Then about seven million Americans have two
copies, so they’re homozygous for ApoE4. Now, if you have zero copies, so if you’re,
for example, a 3,3 your overall lifetime risk for Alzheimer’s is about 9%, so not terribly
common disease but not zero. On the other hand, if you have a single copy
of ApoE4 your lifetime risk is about 30% or so. If you have two copies, if you’re homozygous,
your lifetime risk is over 50%, and in some studies as high as 90%. So most likely you will get it. And of course, the vast majority of people
don’t know. Now, in the past people said, “Don’t check
because there’s nothing you can do about it,” and that has completely changed. So there is a tremendous amount, and the reality
is Alzheimer’s should be a rare disease. It should essentially decrease to a very low
level with the current generation. If everybody gets checked, we recommend that
everybody 45 or over get a cognoscopy, it’s a silly term but it’s easy to remember. Everybody knows when you hit 50 you should
get a colonoscopy, and if you hit 45 or over you should be getting a cognoscopy. You should be doing some testing and see where
you stand, what are your risk factors, are you ApoE4 positive, do you have high homocysteine,
methylation issues, inflammatory issues, nutrient issues, toxin issues, all these things, because
they can all be addressed, and we can decrease the overall global burden of dementia. [Rhonda]: So there’s a variety of biomarkers
that you are suggesting people can go and get measured? [Dale]: Yes. [Rhonda]: You know, to, this, what did you
call it? The… [Dale]: The cognoscopy. [Rhonda]: Cognoscopy, yes. That’s a nice term. So, including the genetic factor, ApoE4, seeing
the ApoE4 and then you have a variety of biomarkers that you kind of just mentioned. Some of those, I think you also have published
on before, talking about the insulin sensitivity as well, looking at insulin sensitivity and
glycated hemoglobin. So maybe we can talk a little bit about some
of those biomarkers and how…so you have this wonderful protocol, let’s see, the MEND
protocol. [Dale]: Right, so it’s now called ReCODE,
so MEND was the very first addition, that was Metabolic Enhancement for Neurodegeneration. But as we have made 2.0 and 3.0 and we have
made it more sophisticated, as I mentioned in the book, it’s become ReCODE, which is
for reversal of cognitive decline. And we now have over 3,000 people who are
on this protocol with unprecedented, and we’ve published a number of the results. We actually have another thing that’s just
finishing up that reports another 50 people who have shown improvement. [Rhonda]: Fifty, wow. So the publications that I had read you had
shown, I think it was about 10 patients. [Dale]: There was 10 and then there were another
10. [Rhonda]: Another 10. [Dale]: A different 10, yeah. [Rhonda]: Right, and you showed that you were
able to basically take a person that had Alzheimer’s disease, some of them had to leave work because
of their issues, and you put them on a protocol and they were not only were able to some of
them return to work but they also seem to have brain mass returning and just so it was
really phenomenal. So, some of these, some of the very complex
diet/lifestyle intervention that you did here, maybe we can talk about some of the key ones
starting with like this diet overhaul that… [Dale]: Yeah, and I should say, you know,
it goes back to one very simple principle. We’ve been trying to treat this disease without
knowing what causes it. So I usually tell people it’s as if you took
your car into the mechanic because it wasn’t working well, and the mechanic said, “Oh,
Rhonda, no problem. This is called car not working syndrome and
your car is going to die.” And you say, “Well, wait a minute. I mean, shouldn’t you figure out why, why
something, what went wrong with it?” And I said, “Well, no, you know, the testing
isn’t reimbursed so we’re not going to do that.” And that’s the unfortunate situation we’ve
been in. People say, “We don’t know what causes it,
there’s nothing you do about it. There’s nothing we can do, and you’re going
to die.” And medicine is changing in the 21st century,
as you know. It is becoming less about mono-therapeutics
and more about programmatics. And at the center of this is to understand
why complex chronic illnesses occur. When you have something like there’s a simple
illness like pneumococcal pneumonia, you find the pneumococcus, you treat the pneumococcus,
and all the other underlying things, alcohol, diabetes, anything that could have been contributing
is less important because you’ve got at the pneumococcal pneumonia, that’s not the case
with complex chronic illnesses. With Alzheimer’s there are dozens of things
that can be contributing. And so what we want to do is address all of
those. Yes, if you have pathogens, many people have,
for example, Borrelia from Lyme disease or a Lyme co-infection like Bartonella or Babesia
or Ehrlichia, things like that, then those need to be addressed. And of course, you need to change the underlying
biochemistry. So as you indicated, there are specific biomarkers. So we want to know you are hsCRP, it’s a marker
of inflammation, of course, we want to know your homocysteine, the marker of methylation. If you’re not methylated appropriately and
your homocysteine is high, then you are at increased risk for neurodegeneration. And of course, it’s been published that you
have a more rapid decline in your cerebral grey matter volume and hippocampal volume
if you have a high homocysteine. [Rhonda]: Is that because of vascular reasons
or what’s the homocysteine mean? [Dale]: Well, the publication did not distinguish. It just simply followed people over years
and looked at the rapidity of the decline in volume and could show that not only was
it more…and literally, you could put the rapidity of it on a graph with homocysteine,
and it fit very nicely. But then if you improve the homocysteine and
brought it back to normal and they’re looking at less than seven as being normal not less
than 13, which is often used in the labs. [Rhonda]: Less than seven? [Dale]: Seven as being normal, then in fact
what happened was people actually stopped their decline and leveled off. So it suggested that this is a causal relationship,
that it is a mediator of cognitive, well, of change in cerebral volume as well as cognitive
decline. [Rhonda]: Independent of other biomarkers? [Dale]: Independent of other biomarkers, yes. So we want to know that. We want to know whether you have glycotoxicity. So we want to know what is your fasting insulin. And again, people will accept it way off the
scale. We have an unfortunate situation where classically
we have accepted laboratory values as within normal limits, WNL, very arbitrarily as being
within two standard deviations of the mean. That actually makes no sense physiologically,
it just says that there’s a distribution there, it doesn’t say that that’s optimal for your
health. So we’d like to know what your fasting insulin
is, and optimally, it would be less than five or less than five, although again, within
normal limits goes much higher than that. We’d like to know your hemoglobin A1C, which
again, is a marker of, essentially over the last two months, your serum glucose. We’d like to know your fasting glucose. These three actually give you quite complimentary
pieces of information, all related to this type 1.5 that I mentioned, the glycotoxic
type. And then the atrophic, as you can imagine,
there are lots of things. We want to know your vitamin D, and again,
we want to see that it’s optimal, not sub-optimal but within normal limits. We want to know your pregnenolone, progesterone,
estradiol, testosterone, free T3. And we’d like to know your brain-derived neurotrophic
factor in your NGF. There’s no simple way on a clinical lab test
today to get those, so you have to infer them from other things, you know, what is your
hippocampal volume? You know, what have you been doing? If you change these various things we’ve been
talking about, you’re likely to have a decrease. Have you been exercising? If you’re not exercising your BDNF is likely
to be lower. So we want to look at all of the trophic support
for your brain because these are critical things if you’re going to make and keep a
large network of synapses, you need to have that support. And then again, that balance changes for many
of us as we age, especially if we are ApoE4 positive. ApoE4 gives you an advantage in that you have
a hair trigger, essentially, for inflammation. You are responding…so if you live in a squalid
environment like the Tsimane Indians that Professor Tuck Finch studied, for example,
or the Agana Tribe that Tuck also has studied, you are in better shape if you’re ApoE4 positive. But if you’re not living in a pro-inflammatory,
in an environment that’s parasitic, then in fact you have this chronic inflammation that,
again, good for when you’re fighting things, good for if you step on a nail, good for situations
that should be pro-inflammatory, but in the long run counterproductive. So, you know, as you know, this is so-called
antagonistic pleiotropy. This is something that can help you when you’re
young but actually can put you at risk for diseases that will shorten your lifespan. And typically, cerebrovascular disease, of
course, Alzheimer’s disease and as you know, ApoE4 is actually underrepresented in centenarians. So it has been a short-gevity gene as it were. Again, that is changing and can change by
understanding what’s actually being driven by this. So we want to know all those markers and those
for the type 2, and then of course, we want to know the markers for type 3. So we want to know if there are specific toxins
and especially mycotoxins. So the toxins can be metalotoxins like mercury,
relatively common one, they can be organic toxins like DDE, things like that, they can
be biotoxins like trycothesinson, ochratoxin A, aflatoxin, gliotoxin, these are toxins
produced by various molds species like Stachybotrys and Aspergillus, and Penicillium, which are
literally fighting us. I mean, they’re literally saying, “Okay, I’m
fighting back.” And for example, one of the responses has
been when you have mold growing on treated wood, they’re recognizing something has changed,
mold that have been treated with fungicide. So these are things where just as we’re seeing
increasingly bacteria that are antibiotic-resistant as Professor Shoemaker has pointed out, Dr.
Ritchie Shoemaker who’s done so much work over the years on mold and mycootoxins and
described what he calls CIRS, Chronic Inflammatory Response Syndrome. As we’ve had fungicides, as we’ve had, you
know, buildings with leaks where we haven’t recognized the danger from these. In fact, we’ve had more and more of this mold-related
illness. So we want to know all those things for the
types 3s. And of course, we also want to know have you
had a history of head trauma, we want to know if you have vascular compromise, all of those
things are critical. Now, you mentioned the diet. So, yes, we want to start with the basics,
but again, ultimately, it’s a program that is customized to you based on what’s actually
causing your cognitive decline or your risk for cognitive decline. And so, the nutritional part we call Ketoflex
12/3 and it’s for a very simple reason. So keto, so we want people to be in mild ketosis
because that actually turns out to work better for cognition, and many people do better with
their cognitive decline, just as Mary Newport showed, of course, with using coconut oil
then that may or may not be the best way to do it for some people, other people like caprylic
acid, MCT oil, other people are very good at generating endogenous ketones, which if
you can do it, it’s the best way to do it. And so we want to drive you into mild ketosis,
which means a very low carbohydrate, high fat, good fats, diet, things like avocados
and nuts and seeds and things like that. And there is a caveat out for people who are
ApoE4 and a caveat for people have very low BMI, so we can talk about that. The next piece is flexitarian, so you can
be a meat eater or not. In general, we see meat as a condiment, but
you know, again, as we evolved we tend to eat relatively small amounts of meat but that’s
fine. If you do, if it’s going to be chicken, it
should be pastured chicken, if it’s going to be beef, it should be grass-fed beef. If you’re going to have fish, great. Make sure it’s wild caught not farmed fish. You don’t want to have the fish with high
mercury. Those are the large-mouthed, long-lived fish,
tuna, shark, you know, swordfish, things like that, you want to stay away from those because
they can contribute to your cognitive decline. In fact, one of the people who called me a
couple of years ago was a very successful businessman who had early Alzheimer’s and
already had PET scan proven, and they told him, “Come back in a year because you’re not
doing that badly yet, you’re still in the NCI phase,” but you could already see the
signature of Alzheimer’s on his PET scan. And when I listened to his story I said, you
know, “You’ve got type 3, and you need to find out if you’ve got exposure to any toxins.” And he said, “No, everything’s great.” Well, it turned out that he was eating large
amounts of tuna sushi, and he happened to be genetically a poor excretor of mercury,
also happen to have some dental amalgams. So he had extremely high organic mercury from
the seafood, extremely high inorganic mercury from the amalgams, and then as well as…so
he had the perfect storm. And his mercury’s actually 7 times the 95th
percentile for our country, just massive, massive mercury exposure, and he’s done well
with removing that. So we want to know those specific ones. And again, for fish, you want to think about
the smash fish. And my wife, who’s a family practitioner,
you know, reminds me about this, you know, salmon, mackerel, anchovies, sardines and
herring, and she is a real expert on the nutritional side and on the integrative medicine side. She told me 25 years ago, “Whatever you guys
come up with in the lab, in your test tube…” I’ve spent my whole career looking at what
is driving the molecular signaling that leads to neurodegeneration. She said, “You know, whatever you come up
with, it’s going to have something to do with what you’re eating and your exercise.” And I said, “No, no, no. It’s going to be one domain of one molecule
and we’re going to get a drug for that thing and it’s going to be over…” And of course, I should have listened to her
25 years ago, that she was right. It does have to do with programmatics not
mono-therapeutics. So then the 12/3 part of Ketoflex 12/3, a
minimum of 12-hour fasts between when you finish dinner and when you start breakfast
or brunch or lunch, if you are ApoE4 positive you’re actually a better fat absorber, as
you know, so you want to make that 14 to 16 hours. If you’re ApoE4 negative, 12 to 14 hours. And be careful, if you have a very low BMI,
you can lose weight on this Ketoflex 12/3 diet and so you have to liberalize typically
once a week, have some sweet potatoes or something that’s a little more carbohydrate-related. And of course, in the book we talk about the
various things that you want to do with this diet, but 12 hours, that gives you time for
autophagy, it gives you time essentially at night to induce your ketosis, to clean out
your brain, of course, the glymphatic system, you actually have a change in the architecture
of your brain as you’re sleeping, you’re actually essentially sweeping this stuff out, it’s
kind of amazing, actually. And so, if you’re eating with these very small
windows of sleep and very small windows of fasting you’re actually doing yourself harm
and putting yourself at greater risk. And then similarly, you want three hours before
bed after you finish your dinner. You don’t want to eat right up until bedtime
because your insulin’s high, and again, that’s hurting your cognition. That’s again, giving you the same sort of
insulin resistance problem, storing fat, you’re doing all the things that are not helpful. So that’s the dietary approach. And of course, you want to have organic. There are toxins in our food, it’s unfortunate. We’ve got a tremendous a life-long exposure
to toxins. Of course, Bruce Ames, with whom you’ve trained,
developed the Ames Test, which allows us now to look at carcinogens, but nobody has ever
told us, “Well, hey, what about dementogens?” You’re exposed every day to various dementogens,
things like mercury, things like some of the organics that are in some of the health and
beauty aids, and things like biotoxins. If you’re living in a home that has leaks,
you are exposed to dementogens and you need to know about that. So that’s the Ketoflex 12/3. We want it be…it’s a plant-rich diet that
Mark Hyman calls plant-rich as opposed to plant-based, but either way it is a plant-rich
diet that can use some animal products, it’s up to you. You want to be vegetarian, that’s fine, you
don’t, that’s fine too. That minimizes the toxins, you want to have
a high, typically 70% or so calories from fat, and you can start out with using things
like MCT oil or coconut oil to get your ketones up. We’re finding that people who have higher
ketone levels, 1.5 millimolar to 4 millimolar more beta-hydroxybutyrate tend to do better
than those who are down lower. [Rhonda]: ApoE4 positive or negative? [Dale]: And ApoE4 positive or negative. Now interestingly, for the ApoE4s what we
typically suggest, and this was actually originally suggested by Julie G. who started the website, You essentially start with using the MCT oil
to help you get your ketosis, but then switch after a month or two to more monounsaturates
and polyunsaturates. Now you can essentially balance, so you have
the best of both worlds. You follow your LDL particle number, your
LDLP. You want to keep it below 1,000 so you can
adjust how much MCT oil and how much of the monounsaturates and polyunsaturates so they
have the best heart outcome, the best cardiovascular outcome, at the same time have the best cognitive
outcome. Be careful, if don’t get your ketones up and
you get your carbs down you’re starving your brain, and so then people will say, “Oh my
gosh, I just have no energy.” So you want to use that. You want to basically be changing over to
a more ketone-based metabolism for your brain. And then, as you indicated, you want to go
back more toward the monounsaturates and polyunsaturates to make it heart healthy. [Rhonda]: So for this, for the ApoE4 positive
people you do recommend lowering the saturated fat intake because of the LDL. [Dale]: After you become insulin sensitive,
so after you want to drive yourself into insulin sensitivity, so you’re able now to convert,
because it takes a few weeks, as you know, to convert from a largely carbohydrate-based
metabolism to a largely fat-based metabolism. So if you try to do it in a day you may end
up with so-called keto flu, and it takes some time and you’re now producing, it’s a whole
set of things you’re producing, it’s going to be less inflammatory, you’re lowering your
reliance on glucose, you’re becoming metabolically flexible, and you’re now essentially developing
a use of the ketones and it does takes a few weeks. And it’s helpful to do things like exercise
and things at that time to help you convert. [Rhonda]: And then the fasting, the overnight
fasting of at least 12 hours, or like you said, if you’re ApoE4 positive possibly even
increase that to 14 hours. That’s interesting that you’re talking about
why you’re sort of transitioning into the becoming more ketogenic that you may actually
have to increase your saturated fat intake because you have to really…it is kind of
hard to go into ketosis without really just having a lot of fat. And so, it’s something I have not experimented
with yet. I found out I had an ApoE4 allele and so I’ve
definitely become extremely interested in Alzheimer’s disease and what I can do to prevent
it because, as you mentioned, you know, not everyone with one ApoE4 gets Alzheimer’s disease. It’s a very complex diet-lifestyle interaction,
at least it appears to be. [Dale]: And no one should, and that’s the
key. This should be largely ended with the current
generation. Everybody should get checked, everybody should
get an optimal personalized program, that is the medicine of the 21st century. [Rhonda]: Yeah, I wanted to ask you about
this because, so a colleague of yours, Dr. Eric Verdin at the Buck Institute, I spoke
with him a few months back on a very interesting paper he had published, I believe was cell
metabolism, where he had given animals a cyclic ketogenic diet, and there was just, you know,
improvement in health span in general but what was really, really robust was the improvements
in cognitive function and brain aging and it was just, you know, hands down like clear
that that diet really helped delay brain aging. And so, you know, of course, those weren’t
ApoE4 positive mice but… [Dale]: But this is the exact same thing we’re
seeing with people, and especially people with early cognitive decline. Now, as you go later and later, it’s more
and more difficult, but we have seen people even with MoCA scores of zero show improvement. So, yes, I think the work that you quoted
supports that notion, that in fact, having ketones is actually quite helpful for cognition. [Rhonda]: Beneficial. Do you think, and here’s a couple of questions
related to that, and that is, you know, is that…you know, probably multiple things,
but one, because you’re obviously going to have improved insulin sensitivity, you’re
not going to have high blood glucose levels and all the inflammatory processes associated
with that. Also the ketones, as you mentioned, are used
by the brain quite nicely. And interestingly, it actually spares…are
you familiar with the glucose sparing, what happens with the…yeah, so glucose gets spared
to make NADPH, a precursor for glutathione so that helps repair damage. But I’m wondering if people like myself, I
don’t really practice a ketogenic diet but I also don’t…I eat a very healthy diet. I definitely try to make sure I don’t eat
anything refined, no refined carbohydrates or processed food or things like that. But the thing is, is that my…so my fasting
insulin’s really good and my blood glucose and all that’s really good. So, for me going on ketogenic diet, do you
think there would still be more benefit even though the whole, you know, insulin sensitivity
thing…maybe it would still improve, I’m not sure. [Dale]: Well, I think the only way you’re
going to know is to try it. [Rhonda]: To try it, yeah. [Dale]: And you know, you can even do so all
sorts of online evaluations for your own cognitive ability. And I do think that many of us are sub-optimal
in our metabolism, and we know this. One of the problems, of course, is that there
have been a lot of assumptions made during the 20th century. Yes, it’s fine to have processed foods, it’s
just as good, you know, it’s fine to have more sugar, on and on and on, which just simply
have turned out to be wrong. And it has to do with sleep, it has to do
with exercise, all sorts of things. We were built, as human creatures, to do certain
things well and to do other things we weren’t built for. If we all were jumping out of a third-story
windows as something to do that would be fun that would not go over well for us. And to some extent, we’re doing the same thing
with the way we’re living. So, obviously, you’ve managed to stay fit
and to have a good fasting insulin and all these sorts of things. However, a little bit will depend on what
you’re actually doing, for example, where is your hemoglobin A1C? For example, is there some inflammation there
or not? The bottom line is that we were not made as
human organisms to consume the amount of simple carbs that we typically are exposed to. So to some extent, just as we’re being exposed
to all these other toxins, of course, sugar is one of them. And whether you try to be exposed to it or
not often we are exposed to it from all sorts of different foods and things like that. [Rhonda]: Going out to eat, you never know. [Dale]: Going out to eat…there’s also the
whole issue of leaky gut. So many people…and this wasn’t even known
as a problem when I was in medical school but it’s become very clear that it’s very
common. It does contribute to chronic inflammatory
conditions like arthritis and like cognitive decline. So, I think that having a high-fat diet has
been helpful for many people, but what you can suggest is, look, if you ever have any
cognitive decline get in as early as possible and then consider this. In your case, of course, as you indicated,
you’re interested in prevention because you already know that you’re ApoE4 positive, so
it might be worth trying it just to see, but you know, obviously, you’re doing a lot of
other things right currently. [Rhonda]: And measuring a lot of different…you
know, other cardiovascular-rated biomarkers is also good so you’re going to measure things
like LDL particles, number and size, and triglycerides, and all those things as well to make sure
that the changes you’re making are actually going to be good for you. I think that’s very important. So the diet and then exercise and the sleep
is really important. You mentioned the glymphatic system, you know,
there’s…to my knowledge, really, is there two major ways that amyloid beta plaques are
cleared from the brain, one is the glymphatic system? [Dale]: Well, of course, there are multiple. There’s the ratio of formation to clearance
is critical. And of course, you’re going to be forming
more and keeping more if you actually have a state of inflammation or of responding to
a pathogen. So actually, you know, there was a really
interesting test developed by Professor Milan Fiala at UCLA, developed about almost 10 years
ago now. And what he was looking at was taking peripheral
blood mononuclear cells, so you’re essentially taking the blood macrophages, and you’re now
simply challenging them. He would give them amyloid, and just look
to see how good are they at phagocytosing, at eating and getting rid of the amyloid. And the surprise was, all the people who have
Alzheimer’s are very poor at eating and getting rid of this amyloid. It was as if they’re literally trying to keep
the amyloid around. Then we realized, yeah, this is a state. So, as you know, it’s become clear that you
change, your cells change states. You have the metabolic flexibility, you have
burning this, burning that for fuel, one of the states you change back and forth between
a pro-inflammatory state, essentially an NF-KappaB-mediated state, and on the other hand, an anti-inflammatory,
a state that is involved more with SIRT1. These two actually have multiple sites of
mutual inhibition. So you’re literally flipping back between
these different states, and the people who had cognitive decline are poor at getting
rid, they’re literally keeping this amyloid around. And he looked at their M1 to M2 ratios, essentially
inflammation to resolution, he saw two patterns. The people who don’t eat the amyloid and who
have the cognitive decline either have a pro-inflammatory state where they have a lot of M1 and very
little M2 or he found that they literally had an atrophic state, the same thing we saw
as type 2, where they simply could not produce enough of this to resolve. So they literally had very low levels. And so in fact, getting the right levels,
about two-and-a-half to one, was associated with the best outcomes. So, you do have this phenomenon, and so yes,
as you know, you’ve got everything from insulin degrading enzyme, Neprilysin, macrophage clearance,
glymphatic system, and on and on and on. There are multiple ways but as long as you’re
in that state where you’re using multiple mechanisms to keep this stuff around, you’re
not going to be very good at metabolizing it. [Rhonda]: This paper that you are referring
to, I do remember reading a paper that you had published a few years ago where you had
taken this, essentially, I guess, you can use that as a biomarker if the people with
Alzheimer’s disease are not clearing amyloid beta plaques via phagocytosis with their monocytes
effectively, that’s sort of kind of a surrogate marker for what’s going on in the brain potentially,
right? [Dale]: Right, and this is Professor Fiala’s
test. [Rhonda]: Right, and you had done a small
study where you had given people some omega-3 supplements along with some antioxidants and
vitamin D, and it improved their phagocytosis of the amyloid plaques in the periphery, and
also I think their cognition, some individuals had improved cognition, ApoE4 negative ones,
I remember. [Dale]: Right, and so I was a co-author on
that paper with Professor Fiala. So again, he invented the test and he’s now
doing, you know, the small number of things that you described there. What we’re doing is a much larger set where
we’re doing more of a program but clearly that is an important part of it. And of course, Professor Serhan [SP] from
Harvard has shown that resolution is a critical part. You have the inflammatory part but then you
have to have the resolution part. And if you don’t have that resolution part,
again, a change in mode, then you’re stuck with this chronic inflammatory state. And so things like omega-3s and omega-3 derived
maresins and things like that are actually involved with the resolution, resolvins, named
for that very event. [Rhonda]: Of resolving inflammation? [Dale]: Right. [Rhonda]: I remember in that paper, and I’ve
also done some reading on this because I have a paper that hopefully will be published quite
soon on ApoE4-related Alzheimer’s disease and particularly with respect to omega-3. So there’s some evidence that for whatever
reason, fish, when people that have ApoE4 are given fish or eaten fish they’re protected
against Alzheimer’s disease, but DHA supplementation, it’s not the same at least for ApoE-positive
individuals. And it’s kind of been mystery as to why that
is. [Dale]: And by the way, Professor Paul Clayton
from Oxford has discussed this numerous times and written about this. And his argument is that, of course, fish
have much more than just DHA and EPA and things like that, so they have antioxidants, things
like the secoiridoids and things like this, whether you find them in plants or animals
that actually are protective, because you have to remember you’re looking at something
with multiple sites of desaturation so it’s very sensitive to oxidation. And so you have to protect that, and you’re
absolutely right. Again, this idea that we had in the past that,
you know, fish, hey, it’s just as good just to get that oil out, it’s not just as good. And although the oil can be helpful, you better
make sure that it’s not oxidized, and you know, better to get it in its appropriate
setting. [Rhonda]: Very interesting, some interesting
papers had come out from a few labs, one from Salem Norman. Norman Salem, sorry. He had shown in animals, if you take animals
and give them a human ApoE 3, 4, 2, and then feed them DHA orally, there was a transport
defect in DHA across the blood-brain barrier. And so I kind of review this work on a variety
of other papers as well, you know, where there’s a couple of major mechanisms by which DHA
is transported across the brain. Are you familiar with some of those? One is the through a free fatty acid and the
other one’s through an actual transporter called the Mfsd2a transporter, which is actually
in a phospholipid form, DHA is in a phospholipid form. And so, it appears that there may be different
ways, you know, that DHA gets across the brain, and one of the ways is potentially not working
quite as well in ApoE4 individuals, at least that’s my writing theory. But once the paper’s accepted I’ll send you
a copy. So it’s super, super interesting. [Dale]: Yeah, and of course, as you know,
I mean, Professor Wurtman from MIT has spent years looking at what does it actually take
nutritionally to make synapses? And his point was you need the DHA and you
need acetylcholine as well. And so again, if you’re going to be helping
people to change that balance toward the synaptoblastic you want to make sure that they have plenty
of those precursors as well as the appropriate signals, reduction of inflammation, all these
other things that are actually part of an overall orchestrated event. [Rhonda]: The other interesting thing is that
DHA, and I didn’t know this previously until I had been digging into the literature, it
also seems to be important for some of the glucose transporters on the blood-brain barrier. And so if you’re DHA-deficient those glucose
transporters aren’t working as well and you’re not getting glucose into the brain, which
is another real hallmark of Alzheimer’s disease. So that’s another interesting thing. So, a couple of interesting things I wanted
to ask you about were kind of off-topic but not particularly. You mentioned this type 3 sub-type. Would the herpes virus fall into that? [Dale]: So, yeah. So herpes virus could give you type 1 or type
3 depending on what you’re actually responding to. If it’s just a chronic inflammation then it
would be a little bit more like a type 1 with chronic inflammatory, but you’re right. You know, again, many groups have said, “Okay,
it’s about herpes. Okay, it’s about P. gingivalis, it’s about
Fusobacterium nucleatum, it’s about Candida. And the reality is, all of these are capable
of inducing the signal, this change where you’re making the amyloid as part of a protectant. As you know, it’s essentially part of your
innate immune system. So if you’re responding in that way it can
be any of those things, it’s not just one every single time, as far as anyone knows. So, yes, you alluded to the recent work on
herpes and especially, of course, six and seven. And so, yes, not surprisingly. You know, one of the things we see frequently
with the various patients is chronic exposure and chronic presence of the various herpes
family viruses, CMV, EBV, HSV, HHV, all those things. [Rhonda]: The last thing I kinda wanted to
mention just because I wanted you to know about it in case you weren’t aware of it,
there’s some really interesting research coming out of Finland. Are you familiar with saunas and the protective… [Dale]: Of course. [Rhonda]: Oh, okay. [Dale]: Yeah, of course, dramatic effects,
and fits very beautifully with everything we’ve been talking about. And certainly, what happens when you have
a sauna, yes, you may induce some heat shock protein, great, that’s important, and it can
be important in folding of proteins, but what also happens, of course, is that you detox. And these people who are doing this repeatedly…you
know, some nice work by Dr. Genuis from Canada who showed that if you look at composition
of sweat compared to the blood there are certain toxins that are very high, cadmium being the
big one, over 1,000 times increase in sweat, so a good way to get rid of cadmium, but a
good way to get rid of other things as well. [Rhonda]: Mercury as well, right? [Dale]: I think you’re right with mercury. [Rhonda]: Yeah, BPA comes out as well. [Dale]: BPA, especially the hydrophobic toxins,
the non-hydrophilic stuff tends to be very good in the sweat, but others as well. And so that’s why it is very helpful, and
many of us don’t do enough of that sort of thing. And as has been pointed out, whether you’re
doing it through sweat and exercise or whether you’re doing it through saunas, whether you’re
doing it through other mechanisms, yes, it’s good to get. And then you want to use a non-emollient soap
immediately thereafter, things like Castile soap or whatever you like that’s non-emollient
and get rid of the stuff so that you don’t get re-penetration. [Rhonda]: Yeah, the other thing is that cardiovascular
effects with the sauna and that may also be related to dementia as well. So, is that something that you’d consider
using in your protocol? [Dale]: Oh, it’s part of the protocol. [Rhonda]: It is part of the protocol? [Dale]: Oh, absolutely. [Rhonda]: Excellent. [Dale]: Now, we recommend that people…and
especially if someone has type 3, that’s even more important. But as a general rule, you know, part of this
is, again, as my wife says, resilience, part of this is resilience. We’re taking people who are sub-optimal in
their metabolism, in their inflammation, in their toxic status, in their lifestyle status,
in their sleep, in their stress levels, these are surprisingly important. One of the first people who came through was
a very intelligent physician. And as we went through each thing he said
to me, “Well, you know, I don’t believe that, you know, that’s not a cure for Alzheimer’s,
that’s not a cure for Alzheimer’s.” He had well documented early Alzheimer’s,
PET scan proven, amyloid PET positive, FTG PET positive, hippocampal atrophy, the whole
nine yards. And as we went through each thing, you know,
he was telling me, “Well, I don’t believe this.” I said, “Look, this is not about one thing,
this is about a program that is optimal for you.” And actually, he’s done extremely well, and
he’s now four years into the program and still doing very, very well. So, it is about changing signaling within
your synaptobalstic to synaptoclastic ratio, providing the right support for that, DHA,
acetylcholine and Vitamin D, and appropriate hormones, and BDNF, and all these things,
and making sure that you don’t have chronic exposure. And as you mentioned, sauna is actually a
very powerful way to help reduce overall toxic burden. It is surprising how much toxic burden most
of us are living with. [Rhonda]: So talking about the importance
of intervening in multiple ways because there are so many different pathways that lead to
inflammation, that can lead to insulin resistance, that can lead to toxic burden, one of the
really…something that made major headlines over the past few years is the failed clinical
trials targeting amyloid beta plaques, multiple clinical trials, I mean, it’s just one after
the other. [Dale]: And actually, we’ve had a number of
people who have tried to remove their amyloid with antibodies who’ve actually gotten worse
with that happening. So you have to go back to, why is there? And it’s tough because yes, it is both part
of the mediator, it’s not the cause of Alzheimer’s, it’s a mediator, and I think that’s been one
of the problems. People want to say it’s the cause, it’s a
mediator, and there are many upstream things contributing to that. So, on the one hand, it’s a mediator of the
pathophysiology. On the other hand, it’s also a protectant,
it’s a response to things like pathogens. And so there’s a double-edged sword there. It’s fine, I think, in the long run, it’ll
be fine to remove the amyloid, but you’ve got to remove the cause of it first. Now, of course, people have just tried to
go earlier, earlier, earlier and can we actually see some improvement? So I think it won’t be surprising if you can
get a little improvement early on, but again, it’s a little bit like saying if we fire the
CFO we can all spend a little more for a while. Well, if we’re still going to go into the
red, we want to make sure that we’re spending for the right things. We want to know why your amyloid is there
to begin with, we want to remove all those things, then remove the amyloid as opposed
to just blindly removing this mediator and leaving the various inducers. [Rhonda]: Right, and with Alzheimer’s disease
it’s so…you know, as you’ve been talking about for the last hour, there are so many
different things that can lead to it, so many causes, so many things in the environment,
in our diet, things that are not present in our diet, that it’s difficult to just find
that one monotherapy and target it. And things are always much more complex. Like it seems like, well, amyloid plaques
in your brain, of course you want to get rid of those. They’re destroying synapses, and well, as
you mentioned, it has a function, it has a really important function. And for the longest time, I remember I was
trying to…this was some years ago, I was trying to understand what the normal function
of amyloid beta, even amyloid precursor protein, like what is it doing? Why is it in there? Obviously, we have this whole elaborate system,
we have these enzymes that cleave it in this right position, and it forms this 42 amino
acid fragment, I mean, that’s all happening for a reason. It doesn’t seem like it would be programmed
into our biology to cause dementia. And so I think it really is important to understand
what the normal function is of the amyloid beta. And also with the tau, phosphorylated tau,
and tau protein as well, is that something that you find quite often in the people that
have the amyloid burden and are affected, they often also have tau tangles in…? [Dale]: Oh yeah. Now, tau imaging is still kind of in its infancy,
so most people, we don’t know. So, they may have an amyloid-positive scan
but they haven’t have a tau scan. However, they are clearly in Alzheimer’s,
and as I say, we do know that many of them do from cerebral spinal fluid. So these people that we’ve reported, I mean,
these people have the low ETI that is associated, you know, amyloid tau index, so they have
a low a-beta 42s in the CSF and they have the high phospho-tau and total tau in the
CSF, the ones that have been evaluated. So, indirectly from that, we can say they
definitely had tau, they’re likely to have phospho-tau tangles. And again, if you look at what this is doing,
it makes a lot of sense. When you are trying to pull back on a connection
then you need to collapse the superstructure. And what is the phosphorylation of tau do? It allows it to pop off the microtubules so
you have a rapid collapse of the structure. So no surprise when you’re in this mode of
you’re trying to fight this off, you’re trying to change, you’re trying to pull back on your
structure, you’re going to phosphorylate your tau, pop it off, the microtubules, and you’re
going to die back, and that’s exactly what you see. So again, it’s not, you know, that the tau
is not the cause of the problem, it is a mediator based on what’s going on genetically with
pathogens, with toxins, with metabolic changes, with innate immune system, and you know, with
trauma. So the things that are driving this are the
things that we want to target. [Rhonda]: Yeah. What percentage of people would you say is
more common to have your sub-type 1, 1.5, 2, the inflammation and insulin resistance
and the neurotrophic? Are those the most common would you say types
of Alzheimer’s disease? [Dale]: And so this is a really good point. So, initially, what we saw was that many people
had this type 1.5, glycotoxicity is so common. In fact, again, Professor Getzel from UCSF
had a nice paper a few years ago showing that everyone he evaluated using exosomal analysis
had the signature of insulin resistance in the nervous system, whether they had it peripherally
or not. It was really striking. [Rhonda]: Exosomal analysis. [Dale]: So this is exosomes that he analyzed,
and specifically, he selected the neural exosomes, which represented about 10% of the overall
exosomes, and showed that they all had the signature. This was this change in phosphorylation of
IRS-1. So clearly that’s a very common thing. But what we’re finding is rarely do people
have purely type 1.5, 1 or 2. So, although type 3, this toxin type represented
only about 15% or 20% of all of the methapure [SP], over 50%, so typically in the 60% to
70% range had at least some suggestion of the type 3. So in fact, most people have some sort of
toxin exposure, pathogen exposure, that sort of thing. So what it’s turning out is that it’s more
about what’s your mixture. Are you predominantly the type 3 with a little
mixture of 1.5? And by the way, the easiest to deal with,
type 1 and 1.5, you can improve that, as you can imagine, with things like resolvants. [Rhonda]: Inflammation and… [Dale]: Inflammation and glycotoxicity. [Rhonda]: …insulin sensitivity. [Dale]: You can improve with diet, exercise,
sleep, stress, stuff like that. Improving the atrophic is a little harder. You’ve got to get all the right things, you’ve
gotta…many people have to go on bio-identical hormones replacement, you’ve got to optimize
the support for your brain. And then the hardest of all is the type 3
because you’re having to find out…for example, some people have very high ERMI scores, that’s
EPA Relative Mold Index. If you’ve got mycootoxins being produced and
you’re living in them, you need to get out of there. Or if you’re working in them, you need to
get out of there. And until you do that you’ve got this chronic
exposure. [Rhonda]: Is there a test people can do to
see if they’ve got this type of mold in their house? [Dale]: Oh yeah. There’s an easy test. In fact, you can go on…I think the government
has set up this so-called EPA Relative Mold Index, and you want to get a score that’s
less than two, again, as Dr. Shoemaker recommended years ago. And you can easily get it, go on They literally send you some little cloths
and you can go around and take x.areas that you are concerned about, send it in, and they
will actually do by PCR analysis, looking for evidence of these various species. And if you’ve got species that happen to produce
a lot of toxins, it’s a concern. Then you can actually measure the toxins in
urine tests. So you can get an idea, and then again, you
can actually see with your detox… [Rhonda]: Is that a consumer product that
you could get? [Dale]: Yeah, so you can get. There are a couple of companies now that do
make urinary mycotoxins tests. [Rhonda]: Okay, and so for people that don’t,
let’s say, you know, they don’t have the toxin exposure, or they don’t think they do, but
they don’t if they’ve done this test, the things that they can do in their diet and
lifestyle to prevent the Alzheimer’s disease would be the major things to reduce inflammation,
which are a lot of things, diet, lifestyle, exercise, sleep, and then again, a lot of
overlap there with improving insulin sensitivity and fasting glucose levels and all that. [Dale]: Getting your hemoglobin A1C down,
all those things, getting on a plant-based…and by the way, you probably know that Dr. Terry
Wahls has published a lot, and actually has done a lot of studies now on using a similar
sort of approach for multiple sclerosis, and has seen excellent results including in herself
with taking this sort of an approach. So, again, looking at the drivers, and looking
at what are we actually responding to, and are we having more of an auto-immune response,
like with MS,or are we having more of an innate immune system response with Alzheimer’s, these
are critical for dealing with these complex chronic diseases. [Rhonda]: Do you look at markers for gut health,
because you were talking about… [Dale]: Absolutely, I mean, gut health is
one of the one of most common things. [Rhonda]: What are the major…inflammatory
markers or the…is there like an actual marker for gut health that’s more direct? [Dale]: Oh absolutely, oh yeah. So, there are a couple of ways to go. There is Genova test, a doctor’s data test,
there are different tests, there’s like stool analysis sort of thing, but you can also do
Cyrex, for example. So Cyrex array 2, Cyrex has a whole set of
different markers for different antibodies. So, if you have a leaky gut you’re often going
to respond to things like LPS coming from your gut. Then there’s a Cyrex array 3 that looks at
various of the domains of gluten and glyodin and so who you can look at that. And then there are various auto-antibodies,
etc. So yeah, these are very helpful to know. [Rhonda]: Can you spell Cyrex? [Dale]: Yeah, its C-Y-R-E-X is the company
that developed these. [Rhonda]: Excellent. I haven’t have heard of that one. So for the Genova diagnostics, is that the
metabolic metabolism test or is there a gut one? [Dale]: There’s a gut health one specifically,
GI effects. And then, so yes, so Dr. Aristo Vojdani, he’s
the one who developed these various assays for Cyrex that are now being used by the Cyrex
company, an excellent immunologist. [Rhonda]: And that’s consumer available as
well? [Dale]: And that’s available, yeah. [Rhonda]: Excellent. I’ll definitely check those out. [Dale]: So the reality is, you know, it’s
an era in which just like I’m going to take an Uber, for example, you don’t necessarily
have to call the taxi anymore. In this era we can actually get a lot more
data, the quantified self is becoming more and more popular and more and more common. And it’s something to some extent of the responsibility
for our longevity and for our health is resting more and more with us. If you want to learn more about the protocol,
please go take a look at the book, and it’s called “The End of Alzheimer’s” from Random
House. And the only thing you can do is, is you can
go to the website,, look at it there. And we are responding too, there are a lot
of comments on the first book that is coming out now in 26 different languages, a lot of
comments saying, “We want more specifics about what URLs do we use? Where do we go?” So we’re actually now putting that in a second
book that will be out next year. [Rhonda]: Excellent. Well, thank you so much for this conversation,
Dr. Bredesen, for your wonderful research. [Dale]: Yeah, thanks very much and then good
luck with your work. [Rhonda]: Thank you.

100 thoughts on “Dr. Dale Bredesen on Preventing and Reversing Alzheimer’s Disease

  1. Hey, guys! If you like this podcast, I would encourage you to check out Dr. Bredesen's book where he goes in much greater depth, and also check out our show notes. Thanks to the support of fans, we're able to really put the energy in and go all out on the notes, so make sure to take advantage of those.

    ▶︎ Get Dr. Bredesen's New York Times and Wallstreet Journal best selling book The End of Alzheimer's.

    ▶︎ Get the episode's show notes and transcript.

    ▶︎ Submit your raw genetic data to run the APOE report.

    This podcast is focused on niche content to say the least, so if you enjoy it, please also consider joining the community the nurtures the very existence of the show through their pay-what-you-can pledges. Learn more about that at Thanks for your consideration!

  2. Hi Rhonda, I have a request for you. Could you apart from iTunes put your podcast on Spotify? I would be very grateful for that, I think other people would be happy too.
    With best regards 😉

  3. 3/4 here, I eat a 90% meat diet (beef, fish, some pork) and actually lowered my inflammation markers. I find the low saturated fat thing and Apoe4 thing sort of a paradox.

  4. Hi Dr. Patrick – You are great. Thank you for all of your content!
    I have one request. Can you please do a podcast or video on chronic inflammation response syndrome and how to reverse it? Basically, more and more people are becoming allergic (or sensitive) to mold due to genes, their environments, and so on. Perhaps there are enough studies done now to conclude on what works and what doesn't.


  5. Wow what a tremendous interview! I could listen to Dr Dale Bredesen all day long and will certainly be reading his book. This really is leading edge information and research. Sorry to all of those peeps chasing a single pill a day for a fix to all health outcomes, as it isn't going to fix this one!

  6. Vitamin b3 defficiency causes dimentia, pellegra was due to lack of b3 in a high-corn diet in the 1490's, were in corn syrup, the daily minimum of b3 to someone that low is like a daily drop of water to a man rescued walking around a dessert dying of thirst. B3 niacin: niacinamide: nicotinic acid, the body can't make ATP in the muscles without it, nicotine works in the same way, that's why the smoker who got some nicotine in a break doesn't feel hungry all of the sudden, and why vitamin b3 deficient purple find themselves eating more, their body is desisted looking for b3 in those potatoes and tomatoes, and so people who smoke are really addicted to vitamin b3 and nicotine is a straight stream of a replacement fuel, it's all the waste that's added as a fertilizer or bug repeller or flavor additive or preservative that kills everyone who smokes

    Every Alzheimer brain studied was gray with aluminium absorption, but that's what we spray for cloud seeeding in the air, the cure is identifying the cause of the disease and prevent exposure, we all know alum. Is bad for the body, but instead we give money to find a treatment program not really stop the cause, instead they start another cause and then ask if you want to give money to find the cure, and the cause, well that's just the advertising campaign.

  7. Thus far this is my #1 Dr Rhonda Patrick video (and I think I may have seen them all at least once). I thought the longevity discussion with Dr. Valter Longo from USC was amazing, but this one on Alzheimer's research by Dr. Bredesen was even more fascinating. Thank you so much for your never ending series on a wide variety of topics that are incredibly relevant to all of us in our search for good science based information on health and disease. Ordered his book already and can't wait to start reading it.

  8. Dr Patrick , what is your type of diet ? I am vegan for over 1 year, for all the reasons attached to it. I try to follow Dr Greger “Daily Dozen” app. What are your thoughts on this?

  9. So … while in ketosis my nose becomes runny and my mucus becomes clear like water, but I feel fine … come to find out this is somewhat common outside what is known as keto flu … very interestingly on vacation I ate some sweets and I became congested … do you know what is up with this?

  10. Hello Dr. Patrick

    You often talk about TRE and Prolonged Fasting for autophagy and cell replenishment what age would you say one should start with this generally ? I have found a study in rodents saying when rodents ate this way and were younger about 1.5-10months old it actually decreased life span.

  11. Dr. Rhonda Patrick, thank you for being awesome. Can you please do a video on mold illness/CIRS? There should be enough studies now, right?

  12. Great questions, Rhonda. It takes experience and intelligence to ask in the way that you do.
    Keep up the good work.

  13. watch @t and email me for more info I am a firm believer this will increase your memory…[email protected]@t this is the only transdermal HGH GEL THAT IS FDA REGISTERED holistic product by invitation only. 30 years of study and 14 years in California

  14. As a 4/4, I am adherent to Dr. Bredesen's suggestions on using meat more as a condiment. I am (was) a big meat eater, however at (28:35) Dr. B. says: 
    as we evolved we ate small amounts of meat…  
    I don't think so. It makes more sense that we evolved on feast or famine. If a tribe was fortunate enough to capture a running critter, (antelope, elk etc) they feasted and ate everything possible that animal provided. When hunting was bad and pickins' were slim and/or slow, they remained in a fasting state.  

    factoid: Anthropologists indicate that, unlike us Americans, they never ate 3 squares a day

  15. Rhonda, I don't know how your videos don't get millions of views in a few months! Some of the best info, on some of the most important topics, often 'from the horse's mouth'! What more could anyone ask for! Thank you 😊

  16. Dr I want to do the test that you mentioned with that fancy name.
    Where is your clinic? Iam in Africa.
    My mother dead of dementia.

  17. Summary: Address toxicity, deficiency, mitochondrial function, inflammation. This will not only help treat and prevent Alzheimer’s but should help treat and prevent all chronic disease.

  18. I am very pleased to see this information freely available on YouTube. Thanks for bringing this valuable data to anyone who wants to help prevent this dreadful disease.

  19. I absolutely love the style of Dr. Patrick's videos – I LOVE the added notes throughout the recording. It is so incredibly helpful and time-saving. Thank you for the great work!

  20. Please encourage guests to drop technical jargon and use terms that people who are not in the industry can easily understand.

  21. Wow, I am so glad I found this video. My paternal grandmother had Alzheimer’s and my Dad currently has it. My maternal Grandfather had Alzheimer’s and my mother as well. I believe it is vital that I get a cognoscopy, to determine my risk. I have already been on a Keto diet for the past year, using grass fed meats and eggs, along with wild salmon and sardines. So hopefully I am on the right path, planning to get Dr Bresendens book too-

  22. Dr.Sebi was right .. mucus in the brain caused by inflammation.. caused by acidic food and toxins.. everything comes from the gut .. so reset the digestive System to reset the circulation system to reset lymphatic system to restore nervous system

  23. Question for Dr Bredesen…. I am a physician following a plant based diet – question for you is concerning the LCHF diet – the longevity of the Okinawans is well documented – their diet was as far from the LCHF diet as you can get – they consumed large quantities of sweet potatoes, seaweed, tofu and small amounts of pork. What is your thought? Also has anyone been on a LCHF diet long enough to know the risk of cancer?

  24. I have heard that you shouldn't take zink without copper. So one should one be tested first before taking either of these minerals?

  25. How does one get to the point they are not insulin resistant? I find that I cannot restrict my carb intake too much because then my blood sugar drops n I get shaky & sick. I try not to eat too many refined carbs, but find sometimes it's hard for me not to have some, especially when my sugar drops. I get so sick, I start to eat anything to make me feel better.

  26. If DHA is necessary for glucose transport in the brain it makes sense that ketogenic diet may work to improve function in the apo e 4 crowd in particular if they are not getting adequate DHA in their diet

  27. Wondering if you have any thoughts on Gilbert Syndrome? At first glance, it looks pretty benign, but if I've learned anything over the years, it's that, when it comes to the body, its just not that simple. It seems like the lack of UGT1A must have some significance up or downstream from just breaking down bilirubin?
    On a personal level, I have been thinking about Gilbert's in relationship to fasting, which is not recommended for those who have it. Anecdotal evidence hints at co- occurring metabolic/gut/dopamine disfunction, (which might benefit from fasting) but this doesn't seem to show up in the medical literature.
    As always, love to hear your thoughts and Thanks for your continued work and diligence!

  28. Relief from Alzheimer: "I placed the MagneMax Necklace on my mother's head for 30 minutes and her Dizziness was gone. Her character also changed. She actually became
    Adorable and even told me that she Loved the lamp I had made for her.
    I'm bringing Crazy-Glue with me tomorrow to Glue this MagneMax Necklace
    to her Neck in so she'll ‘Never’ take it off again. Thank you for this
    absolutely Amazing product." – "

  29. The #1 issue we face is global warming.  

    The key to the solar economy in 2020 is to motivate millions who have lost their homes to fires, like Paradise, Cal., to rebuild, on their land, by building a 4-plex home with 100 solar panels.

    Thus a single home lot becomes a multi-family lot, creating more co-housing & income for the owner.

    Thus a young couple could afford to buy, because they would have income from surplus solar, tenants & charging e-cars. If they have kids, when the kids grow up, each one would have their own home, improving family relationships & providing longterm care for their parents. A prevailing wage mandate in NY would help the economics of #solar, integrating the workers, banks & solar homeowners. Win, win, win.

    We need a policy that requires utilities to pay solar home owners who sell surplus to the grid to inspire millions of new home buyers to buy 4-plex homes with 100 solar panels. Germany has become the fastest growing solar nation because they have such a successful Feed in Tariff that requires utilities to pay $0.99 kwh to solar homes.

    This cash income motivated millions of young couples to buy 4-plex solar homes.

    It is the best investment you can find in the solar economy. It creates housing, eventually lowering the cost of housing over the next 20 years.

    It creates millions of jobs for carpenters, contractors, architects, etc. This is the main plank in the Green New Deal.

    This allowed Germany to shut down all of its nukes by Earth Day, 22 April 2022. This made Germany the greenest nation in the world.
    Paul Kangas is a Democratic Party candidate for President 2020.

  30. Starting at 25:46 reminded me of the Candida auris 'outbreak' that I read about yesterday..

  31. THIS is the peak of the information age, ladies and gentleman. We are so lucky to be able to listen in, as these geniuses discuss incredibly complex and interesting topics. Thank you Dr. Patrick and Dr. Bredesen for sharing this for free with the world. The significance might get lost as the view count rises, but always remember, real people benefit from this kind of content. Real people change their life style, for the better, because of these kinds of discussions which share education.

  32. Watch some parts twice – very informative. As said by another comment, I also loved that you put all this information up on text on the screen which allows us to pause and take notes.

  33. What does it mean to be APOE4 positive or negative? Having a hard time finding it online. I'm E3/E4, is there more to know for the +/- portion?

  34. How applicable is the ReCODE protocol to any degenerative problem. If, say a 26 year old had a liposarcoma successfully removed but was worried about how to avoid future metastatic spread etc. would the ReCODE approach pick up most of everything he ought to be looking at to make sure he maximizes his immune competence and minimizes his inflammation etc?

  35. Hello, as of today, if you research in any medical page, it is said that there is NO cure for Alzheimer's I am trying to understand if this is a research that is giving hints of a cure for the future? or do we have actual people that have been cured? do we have this info? Thank you so much

  36. Dr.Patrick, thank you for bringing so much information to us….Our mother was one of the Americans that got Alzheimer's every 38 seconds….Like everybody that has this affect them or their loved ones, we asked, "WHY?"…Here is her story…1st, I am not an Alzheimer's specialist, just an eye-witness in the discussion…I have been asked to elaborate… I am an M.D..My wife was an R.N. We were both pro-vaccines…My mother and sister were R.N's..They were both pro-vaccines….My 2 brothers were M.D.'s…They were both pro-vaccines…Our mother was an R.N. who was the Head Nurse and ran the largest ER in our medical center..She slept well, exercised, active, and ate well..She was young at heart and ran circles around younger nurses…They had her take 8-9 vaccines to ''catch-up'' with the newest ''updated'' CDC schedule to keep her nursing job after a long career in Real Estate…After her vaccines, she got severe ''brain fog'' within days, then lost her ability to dial her phone or push the elevator buttons or start her car …She went into diapers and then hospitalized and died a terrible, tragic death, drooling and unable to walk, talk, eat or recognized any of her family…None of the specialists and consults could tell her or us what ''just happened'' but all the specialists told us it was ''NOT'' from those vaccines….It was called the ''worst case of acute, aggressive dementia of ''UNKNOWN'' cause the doctors had ever seen''….Folks, what killed our mother just weeks after her vaccines were all from her fatal doses of neurotoxic aluminum and mercury ingredients from those vaccines..She left behind her husband, 5 children, 4 grandchildren, and now 7 great grandchildren… I started a FB site called Vaccine Support Group ( the link is not shown per this site's policy ) in their name..

  37. If you are positive in several Herpes viruses, May it be a good idea a continuous retroviral medications for your brain and health in general? (although you do not have any symptoms)

  38. this sounds incredibly complicated and incredibly expensive….no humans ever lived on a diet of 70% fat…that idea alone surely flies in the face of 20-30 years of long standinv peer reviewed scientific research on things like heart health..cholesterol levels etc?

  39. As a practicing physician for over 20 years I can honestly say that this talk was the most eye-opening discussion on Alzheimer’s dementia that I’ve ever heard.

  40. Our mother was one of the Americans that got Alzheimer's every 38 seconds….Like everybody that has this affect them or their loved ones, we asked, "WHY?"…Here is her story…1st, I am not an Alzheimer's specialist, just an eye-witness in the discussion…I have been asked to elaborate… I am an M.D..My wife was an R.N. We were both pro-vaccines…My mother and sister were R.N's..They were both pro-vaccines….My 2 brothers were M.D.'s…They were both pro-vaccines…Our mother was an R.N. who was the Head Nurse and ran the largest ER in our medical center..She slept well, exercised, active, and ate well..She was young at heart and ran circles around younger nurses…They had her take 8-9 vaccines to ''catch-up'' with the newest ''updated'' CDC schedule to keep her nursing job after a long career in Real Estate and was elected the Vice President…After her vaccines, she got severe ''brain fog'' within days, then lost her ability to dial her phone or push the elevator buttons or start her car …She went into diapers and then hospitalized and died a terrible, tragic death, drooling and unable to walk, talk, eat or recognized any of her family…None of the specialists and consults could tell her or us what ''just happened'' but all the specialists told us it was ''NOT'' from those vaccines….It was called the ''worst case of acute, aggressive dementia of ''UNKNOWN'' cause the doctors had ever seen''….Folks, what killed our mother just weeks after her vaccines were all from her fatal doses of neurotoxic aluminum and mercury ingredients from those vaccines..She left behind her husband, 5 children, 4 grandchildren, and now 7 great grandchildren… I started a FB site called Vaccine Support Group ( ) in their name..

  41. OK what can we do to detox from all the nano- Aluminum from the geo-engineering program?
    I think it might be to eat at least 3 cups of chopped broccoli every day.

  42. Is there even one doctor or qualified health individual that has understanding or interest in this work of Doctor Bredesen's, that is in Australia, or am I going to have to travel overseas to even get the suggested tests done in hope of a reversal or elimination of dementia suggested in my wife? Doctors in Australian have shown no interest in even conducting the necessary basic testing, and assume that as soon as a diagnosis is made based on just a MIR, then there is no hope and carers need to fit in with the prescribed path to the currently accepted final stage.

  43. To technical too long winded too hard to follow at the and you should have a summary for the layman

  44. Thank you so much for all the information you disseminate!

    I became disabled from numerous inflammatory based issues, was taking 11 pharmaceuticals, walking with a cane and mostly bed ridden at age 45! Information such as this as motivated me to construct my diet along my my needs and now I take ZERO meds.

    I, as you, do not follow a KETO diet and I am basically vegan with occasional cheese or maybe piece of cake made with egg BUT I do not religiously follow anything when evidence can point to the contrary.

    Now I wished I had concentrated more on biochemistry than computer science.

    Thank you again,
    Levi Patrick

  45. Among the many things Dr. Bresden mentioned which can negatively impact the brain, I was really happy to hear him mention mercury in large fish with such authority as so many medical experts will not address the issue, and because of this it is not thought by the majority of the people I know to be a real thing. I am one of those people who ignored the warnings and, eating a lot of tuna and swordfish wound up with dangerously high levels of mercury. I have lab tests to prove it, and yet I often find myself relegated to the fringe zone if I mention this to people I know, which is insult on injury! So… kudos to Dr. Bresden. I stopped eating those fish which tend to have high mercury loads about 10 years ago, but I have read that the mercury which gets in to your brain cannot get back out again, and so would welcome hearing whether or not that is true. I wouldn't like to think I am destined for one of these alzheimers types.

  46. Hello. How can we get in touch with Dr Bredesen, is there an official website or hospital we could contact. I live outside US and would like to find out about Recode, and if there is distance treatment available? Please it's urgent

  47. I was diagnosed a kind of brain problem or Chiari malformation suffered a lot of pains even lost my memory like my middle name scary. But then because I find a good omega3 balance oil here in Norway im getting better our brain we need a good nutrients. Dr Paul Clayton Scientists Nutritionist discussed about the Zinzino omega3 balance oil

  48. ApoE-2 Brain-Targeted Gene Therapy Through Transferrin and Penetratin Tagged Liposomal Nanoparticles.

  49. I wonder how I could emty my mind of useless informations. This woul help me become more attentive. Because now I'm listnening to this video and to my thoughts in the same time

  50. The discussion and relationship between chronic inflammation and neurodegeneration is spot on. I have published several books about this relationship and how funneled mistake prone immune arsenal into interstitial spaces increases rather then decreases inflammation which in the case of AD involves the secretion of amyloid by astrocytes. and microglia. #Rejuvenation(2017) #Trafficking(2018) #Rejuvenation2.0(2019)

  51. So how do we get REAL blood tests done from doctors who know what there doing?? I feel like hell and I do eat crappy food all the time but yet my blood work always comes back PERFECT according to the doctor's I go to???? Hey clearly do not know what the fuck to look for in health problems

  52. Mayo clinic youtube radio…*** * All the doctors should get together….. This would further research of eradicating Alzheimer's faster. Dr. Greger…..*****

  53. Thank you for putting so much effort into this video. It's very helpful. Especially the running footnotes. Saves me the trouble of looking up everything into the paper again and again :')

  54. Are there any doctors in the UK following this protocol? I would love to get tested, I've worked with alot of toxic solvents for many years and not always with the best ppe. I'm sure that has affected my mind in numerous ways. I really don't fancy dementia in any form. Brilliant video by the way.

  55. Hi I stumbled across this podcast and found it really interesting as I have had memory issues and I'm only 41 years old. Can someone recommend a video or book or podcast that could explain some of the same information in layman's terms?

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