Alzheimer’s illness, which is the most typical type of dementia, finally results in the lack to hold out even essentially the most primary of bodily capabilities, resembling swallowing or strolling. It is finally deadly, as standard therapy choices are few and universally ineffective.
Like autism amongst youngsters, Alzheimer’s amongst seniors has reached epidemic proportions, with no slowdown in sight. On the opposite, proof suggests the pattern is worsening. In 2022, Alzheimer’s impacts greater than 6 million Americans,1 and 1 in 3 seniors dies with dementia or different demention. By 2050, Alzheimer’s diagnoses are projected to achieve 13.8 million.2,3
While the U.S. Centers for Disease Control and Prevention lists the illness because the seventh main reason behind dying within the U.S.,4,5 statistics revealed within the journal Neurology in 2014 revealed Alzheimer’s is vastly underreported on dying certificates. In actuality, the illness probably killed 503,400 American seniors in 2010,6 making it the third main reason behind dying, proper behind coronary heart illness and most cancers.7
The excellent news is that opposite to standard claims, there are methods to forestall and even deal with this tragic illness — not by medication, however by food plan and different life-style modifications.
Dr. Dale Bredesen, professor of molecular and medical pharmacology on the University of California, Los Angeles School of Medicine, and creator of “The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline,” has recognized a variety of molecular mechanisms at work in Alzheimer’s, and created a novel program referred to as ReCODE to deal with and reverse it.8
100-Patient Case Report Sheds Light on Treatment Options
One of Bredesen’s publications is a case report9,10 of 100 sufferers utilizing the ReCODE protocol. He had beforehand revealed three case stories, every involving simply 10 sufferers. This fourth case report incorporates 100 sufferers handled at 15 completely different clinics throughout the U.S., all of which have documented pre- and post-cognitive testing.
Not solely did all present enchancment in signs, a few of them additionally confirmed enchancment of their quantitative electroencephalographs (EEGs). Others who underwent magnetic resonance imaging (MRI) with volumetrics additionally confirmed goal enchancment.
“By all the factors, these folks confirmed enchancment, subjective and goal,” Bredesen says. This isn’t any small factor, as there isn’t a standard therapy that may reverse Alzheimer’s. There have been many drug trials to this point, however all have did not reverse the illness. As famous by Bredesen:
“There are a few drugs, Aricept, Namenda … however these have a really, very modest affect. The most necessary factor is their enchancment shouldn’t be sustained. They do not change the result of the illness. You get a bit bump in enchancment, then you definately go proper again to declining.
The most necessary a part of the [ReCODE] protocol … is that the advance is sustained. You’re truly going after the foundation trigger of what’s inflicting the cognitive decline. That’s an enormous distinction.”
Alzheimer’s Is a Protective Response to Inflammation
If one had been to summarize Bredesen’s method in a single sentence, it could be “to enhance the ratio between synaptoblastic and synaptoclastic exercise, which is the mind’s capability to create new synapses versus destroying them.” In different phrases, the therapy permits your mind to create and keep synapses once more. Bredesen explains:
“The molecular biology of this illness exhibits that what we name Alzheimer’s illness is definitely a protecting response. It’s basically a scorched-earth retreat.
You’re pulling again and saying, ‘We’re not going to let this insult kill us, so we’ll scorch the earth so it (whether or not it is micro organism or one thing else) can not take benefit … of what is there.’ You’re actually downsizing [your synapses]. As lengthy as these insults are occurring, you may be downsized.”
Beta-amyloid is a protein that’s extremely correlated with Alzheimer’s. However, all makes an attempt at eradicating it have failed to enhance the situation. Clearly, beta-amyloid in and of itself shouldn’t be the first trigger, so merely eliminating it’s not the reply.
In Bredesen’s paper, he discusses the position of beta-amyloid as an antimicrobial peptide (AMP). Importantly, AMPs are critically necessary for host immunity. They goal organisms resembling micro organism, mycobacteria, viruses, fungi and protozoa. He explains:
“Here is the trick. It seems amyloid beta is admittedly a part of the innate immune system. Its antimicrobial impact was first found and revealed by professor Robert Moir and professor Rudy Tanzi at Harvard.
This factor truly has, once more, a protecting response. Not solely is it an AMP, nevertheless it additionally binds some toxins. For instance, mercury, different divalent metals like iron and issues like that. [Amyloid beta] has a number of results. It is a part of your response to insult.
When you are taking that under consideration, you understand it is wonderful to take away amyloid, however please do not do it earlier than you take away all of the insults. We’ve seen quite a few folks now who’ve had the amyloid lowered and gotten worse as a result of the continuing insults are nonetheless there.”
In 2019, the drug firm Biogen halted its Phase II scientific trial for aducanumab, a drug designed to take away beta-amyloid, and that is the standard story for these varieties of medicine. And then a serious trial of one more method to amyloid removing, the BACE inhibitor CNP520, was halted as a result of the drug was related to elevated cognitive decline and mind atrophy.11
The Protein Refolding Process Is Impaired in Alzheimer’s
About one-third of the proteins your physique makes on any given day are misfolded. Thankfully, your physique has a mechanism by which these misfolded proteins are refolded. Heat-shock proteins play a central position on this course of, and if the misfolding is simply too extreme, the heat-shock proteins assist take away them altogether.
In reality, heat-shock proteins are a corollary of autophagy, the method by which your physique cleans out broken organelles. This pertains to Alzheimer’s, as a result of the refolding course of is certainly one of a number of components that have to work to ensure that your mind to perform. As famous by Bredesen:
“In all of those completely different neurodegenerative illnesses, whether or not you are speaking about Alzheimer’s, Huntington’s, Lou Gehrig’s illness, Parkinson’s illness or Lewy physique, all of them function proteins which might be aggregated and which might be usually misfolded. They usually are not degraded appropriately.
You lose not solely the flexibility to fold however the capability to degrade these proteins. That is a crucial piece. In reality, only in the near past, an article got here out on a typical neurodegenerative situation, newly described, which known as LATE, which is limbic-predominant, age-related TDP-43 encephalopathy.
In different phrases, this can be a little bit like Alzheimer’s … [LATE] options TDP-43, which is a protein that’s concerned in quite a few issues, together with protein folding … We lose that [protein-folding] capability as we begin to downsize [synapses], as you do not have an applicable vitality, you do not have the suitable trophic assist.
You do not have the suitable hormonal and dietary assist … When we goal ketosis, once we goal insulin sensitivity, once we goal mitochondrial assist, that usually lets you generate the suitable capability to refold misfolded proteins …
You can induce the heat-shock response … by doing this mixture of sauna after which [going] into the chilly after which again to the sauna after which again to the chilly …
You are recurrently activating this crucial response [by doing that]. There’s no query it’ll be necessary, particularly in ALS, however probably in the entire neurodegenerative circumstances.”
The Link Between Protein Folding and Cell Death
As famous by Bredesen, there are three sorts of autophagy: macro-autophagy, micro-autophagy and chaperone-mediated autophagy. Each presents a barely completely different option to restore, take away or recycle broken organelles throughout the cell.
Specific proteins, for instance, may be focused for chaperone-mediated autophagy. Bredesen recounts findings of analysis he did to establish the linkage between protein folding and programmed cell dying (apoptosis, the place all the cell is killed off and eliminated):
“If you fail to reform these [misfolded proteins], you actually activate a whole system that originally stops producing extra protein. It’s mainly saying, ‘We’re not maintaining with this. We’re going to close this down.’ It makes an attempt to refold. Then it makes an attempt to destroy the proteins if it could possibly’t refold them.
Then finally, if it can not … sustain … it actually prompts programmed cell dying by way of particular caspases … This is one thing the place you need to intervene upstream; perceive why that is occurring. And then in case you’re unable to maintain up with this, now, not less than enhance your heat-shock proteins in an effort to refold. In this case, you forestall the induction of programmed cell dying.”
Unfortunately, a overwhelming majority of individuals don’t have well-functioning autophagy, for the straightforward purpose that they are insulin-resistant. If you are insulin-resistant, you can’t enhance your adenosine 5′ monophosphate-activated protein kinase (AMPK) degree, which prevents the inhibition of mammalian goal of rapamycin (mTOR), and mTOR inhibition is likely one of the major drivers of autophagy.
The Case for Cyclical Fasting
While autophagy is clearly of crucial significance, you do not need to be in steady autophagy. You additionally have to cycle by way of the rebuilding part. One of the methods in which you’ll management that is by way of cyclical fasting. Bredesen usually recommends an intermittent fasting method.
“You need to use applicable fasting and an applicable food plan to activate this autophagy,” Bredesen says. “We advocate … 12 to 14 hours [of fasting] in case you are apolipoprotein E4-negative (ApoE4-negative) … If you’re ApoE4-positive, you’d need to go longer — 14 to 16 hours. There’s nothing improper with doing an extended quick …
The purpose we advise longer for the ApoE4-positives [is because] in case you are ApoE4-positive, you’re higher at absorbing fats. It tends to take longer to enter autophagy …
Typically, we advocate it about as soon as per week. But once more, an extended quick as soon as a month is a good suggestion. It relies upon so much in your physique mass index (BMI). What we discovered is individuals who have greater BMIs reply higher to this fasting early on. They’re in a position to generate the ketones.
If you lose each the carbohydrates and the ketones, you find yourself [feeling] utterly out of vitality … We are very cautious when persons are down beneath 20 on their BMI, particularly those 18 or beneath. We need to be very cautious to verify to cycle them [in and out of ketosis] a few times per week …
These are those the place, usually, exogenous ketones may be very useful early on … Measure your ketones. It’s easy to do. We need to get you into, finally, the 1.5 to 4.0 millimolar [range for] betahydroxybutyrate. That is the purpose.”
Test Your Ketones
So, to recap, whereas dementia sufferers with extra weight have a tendency to reply favorably to cyclical fasting, not less than initially, underweight sufferers could expertise cognitive decline, as they’re just too underweight to provide ketones in response to the fasting. For those that are underweight, Bredesen recommends utilizing a ketone complement resembling medium-chain triglycerides (MCT) oil.
If that does not convey you into the specified ketone degree (1.5 to 4.0 mmol), or if it is adversely affecting your low-density lipoprotein (LDL) particle quantity, he would possibly advocate exogenous ketones — both ketone esters or salts. “We’d like to take a look at your LDL particle quantity and use that to titrate, to make it possible for your LDL particle quantity shouldn’t be too excessive,” he says.
To take a look at your ketones, I like to recommend KetoCoachX.12 It’s one of many least costly testing units in the marketplace proper now. Another good one is KetoMojo. KetoCoach, nonetheless, is inexpensive, the strips are individually packed and the machine is about half as thick as KetoMojo’s, making it simpler to journey with.
Energy Demands Are Not Met in Neurodegenerative Diseases
Nutritional ketosis, through which your physique produces endogenous ketones (water-soluble fat), is necessary for all neurodegenerative illnesses, nevertheless it’s not an entire cure-all. Bredesen explains:
“What we have come to understand from the analysis over time is that neurodegenerative illnesses, whether or not Alzheimer’s … macular degeneration … Lewy physique, Parkinson’s or ALS, all of them have one factor in frequent. They are associated to particular subdomains of the nervous system.
Each of those has a singular requirement for vitamins, hormones, trophic components, et cetera … In every case, there’s a mismatch between the provision and the demand. For most of your life, you are maintaining with that demand. With all of those illnesses, you may have a repeated or a continual mismatch between the assist and the requirement.
In Parkinson’s illness, it is fairly clear. You can create Parkinson’s illness just by inhibiting mitochondrial Complex I. That particular subdomain of motor modulation, which is what Parkinson’s is all about, is the factor that’s the most delicate to reductions in mitochondrial Complex I assist.
Therefore, when folks have this, it’s worthwhile to convey the provision again consistent with the demand. A crucial method to do this is to produce the suitable ketosis — the suitable vitality.
Now, if the individual is constant to be uncovered to no matter chemical substances are inhibiting Complex I — and it is usually … mold-related biotoxins or natural toxins resembling paraquat or glyphosate — so long as these are ongoing, you are going to get very non permanent aid.
The purpose right here is each to eliminate what’s inhibiting Complex I and to flood the system, to assist the system by giving applicable assist for the energetics … With Alzheimer’s, we’re actually speaking a couple of mismatch in trophic assist. You’ve obtained this ongoing want as you are making neuroplasticity.”
Why Late-Night Eating Is Ill Advised
Although I’m not ApoE4-positive, I choose fasting for 16 hours a day, basically narrowing my consuming window to only 4 to 6 hours. I additionally make sure that to eat my final meal three to 6 hours earlier than bedtime. One of the explanations for this recommendation is as a result of avoiding late-night consuming will enhance your nicotinamide adenine dinucleotide (NAD+) ranges, that are necessary for quite a lot of bodily capabilities.
Importantly, it’s going to additionally scale back nicotinamide adenine dinucleotide phosphate (NADPH), which is basically the true mobile battery of your cell and has the reductive potential to recharge your antioxidants. The largest shopper of NADPH is the creation of fatty acids.
If you are consuming near bedtime, then you definately’re not going to have the ability to use the NADPH to burn these energy as vitality. Instead, they should be saved a way. To retailer them, it’s important to create fats, so that you’re mainly radically reducing your NADPH ranges if you eat late at evening as a result of they’re being consumed to retailer your additional energy by creating fats.
Bredesen’s protocol consists of this technique as effectively. He calls his method “KetoFlex 12/3,” as a result of it generates delicate ketosis and is versatile diet-wise. It may be carried out whether or not you are a vegetarian or not. The 12/3 stands for a 12-hour minimal quick every day, and consuming the final meal three hours earlier than bedtime.
Certain dietary supplements, together with berberine, resveratrol, curcumin, quercetin and fisetin additionally enhance autophagy, and can be utilized along with the dietary timing. Bredesen explains:
“Sirtuin-1 (SIRT1) was recognized as a crucial molecule, each for longevity and has been studied extensively for its results on longevity, but in addition for its results on Alzheimer’s illness …
ApoE4 truly enters the nucleus and downregulates the manufacturing of this crucial molecule, so you’ll be able to see certainly one of its many results on Alzheimer’s illness. Well, when SIRT1 is made, it’s truly made in an autoinhibitory trend. It’s similar to having a gun in a holster. It’s not energetic … NAD prompts the SIRT1.
So does resveratrol. This is why folks take resveratrol [or] nicotinamide riboside. These are each activating this program, which is transferring you from … extra of a pro-inflammatory method to a long life method — a change in your metabolic sample. That consists of activating issues like autophagy and likewise having an anti-Alzheimer’s and a pro-longevity impact …
[Q]uercetin additionally has an fascinating affect on senescent cells … I believe that that is going to become an necessary option to affect a variety of age-related circumstances, together with neurodegeneration.”
The disadvantage, and the explanation you can’t depend on dietary supplements alone, is that the bioabsorption of those polyphenols, like quercetin for instance, is kind of low. Oftentimes, you can’t take up sufficient to get the total advantages.
Limit Electromagnetic Field Exposures
There’s additionally convincing proof exhibiting electromagnetic area exposures (EMFs) resembling that from cellphones and Wi-Fi play an necessary position. Bredesen agrees, and recommends his sufferers restrict such exposures. In abstract, EMFs activate your voltage-gated calcium channels, permitting the discharge of extra nitric oxide and superoxide within the cell, ensuing within the creation of peroxynitrite.
Peroxynitrite causes comparable injury to your DNA as ionizing radiation. It additionally damages your stem cells, mitochondria, proteins and cell membranes. Poly-ADP ribose polymerase helps restore DNA injury by extracting an adenosine diphosphate (ADP) molecule from NAD. Approximately 100 to 150 NAD are required to restore a single DNA break.
While this course of works fairly effectively, issues come up when steady DNA injury requiring steady PARP activation happens, as this finally ends up decimating your NAD+ degree. Bredesen provides:
“This is a crucial space. The huge downside we have had with this thus far is that we will measure your NF-κB activation; we will measure your standing of hormones, vitamins, magnesium, on and on and on. Typically, with our method, we measure 150 completely different variables.
There isn’t any easy option to measure the impact of EMF on a given individual’s nervous system. I sit up for the day once we can do a take a look at and say, ‘Aha. This individual has 27.2 on their results on their voltage-gated calcium channels due to EMFs.’ Because then we’ll actually have the ability to alter that.
For now, one of the best we will say is — simply as we go after biotoxins and chemotoxins — [EMF] is a bodily toxin. The greatest we will say is, ‘Minimize that to the extent you’ll be able to.’ You can definitely measure the publicity. We simply do not have a great way but to measure its impact in your mind.”
More Information
There’s no decline in sight for Alzheimer’s, not less than within the foreseeable future, so it could behoove most individuals to only assume you are headed for it and take motion now, no matter your age, to forestall it. When it involves Alzheimer’s, prevention is definitely far simpler than making an attempt to deal with it as soon as it has set in. As famous by Bredesen:
“This is all about prevention and early reversal. Those are the folks the place we see nearly 100% response. This is why I believe there must be a worldwide effort to lower the burden of dementia. We’re simply now beginning a scientific trial. We’ve been making an attempt to get institutional evaluation board (IRB) approval for years …
It has lastly been permitted, so we’re beginning a trial with Dr. Ann Hathaway, Dr. Deborah Gordon and Dr. Kat Toups, who’re all seeing sufferers. We’re very excited to see what the trial will present with this method. Because definitely, anecdotally, we’re listening to it on a regular basis.
As you talked about, we simply revealed a paper a number of months in the past on 100 sufferers who confirmed documented enchancment … I’m satisfied we might, at the moment, if everybody obtained an applicable prevention, make this a really uncommon illness.”
Bredesen’s case report13 is open entry, so you’ll be able to obtain and browse the total research. His e-book, “The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline,” additionally supplies the small print, and could be a useful reference in anybody’s well being library.
You also can be taught extra about Bredesen and his work by following him on Facebook, Twitter or go to his web site, drbredesen.com. Last however not least, learn his e-book, “The First Survivors of Alzheimer’s: How Patients Recovered Life and Hope in Their Own Words,” which options first-person accounts from sufferers recognized with Alzheimer’s who beat the chances and improved.