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

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

July 27, 2019 100 By William Morgan


[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,
apoe4.info.
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 mycometrics.com.
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, drbredesen.com, 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.