Alan S. Green, M.D. is one of the nation’s only doctors who practices anti-aging medicine using rapamycin. Dr. Green has expanded his practice into the prevention of Alzheimer’s disease, and believes that rapamycin may be one of the best means available to prevent it, especially in high-risk patients, and he’s written a comprehensive website on this use of rapamycin. In the service of getting the word out and explaining this important concept, we again interview Dr. Green.
P. D. Mangan: Why did you set up your new website, Prevention of Alzheimer’s Disease in APOE4 Carriers?
Alan S. Green, M.D.: The most vulnerable medical group today are the 20 million Americans in the 40-70 age group who are APOE4 carriers. They are at high risk of Alzheimer’s disease.
Since 2010, there have been studies with excellent mouse models of AD with human genes for AD showing rapamycin will prevent AD. The most important study was a 2015 study in which mice were given human genes for APOE4.
It seems like the attitude in clinical medicine is what happens in the research laboratory stays in the research laboratory, at least as far as generic drugs like rapamycin are concerned.
Many people are having genetic testing and finding out they are APOE4 carriers. The APOE4 community need three things. (a) The need convenient access to the best current scientific information. (b) They should be able to see a physician who’s main interest is providing the best prevention plan and (c) they need access to what looks like, in the basic science laboratory, the most effective medicine in preventing AD in APOE4 carriers, even if that use is “0ff-label”.
PDM: Can you briefly summarize your website?
ASG: The website provides a current understanding of the etiology and development of AD in APOE4 carriers. The websites highlights all the basic research and mouse studies showing rapamycin will prevent AD in APOE4 carriers. The website discusses risk and lifestyle required to lower that risk. It lets people looking for help know there is a medical office with the primary interest of prevention of AD in APOE4 carriers, using all the tools currently available, even if medication is “off-label”.
PDM: You are offering rapamycin “off-label” prior to human clinical trials proving that rapamycin prevents AD in humans in APOE4 carriers; when do you think traditional medicine will have results from human clinical trials showing rapamycin is effective to prevent AD?
ASG: My opinion is that is at least 10 years down the road. The problem with that is many APOE4 carriers don’t have 10 years to wait. Even if rapamycin works in early stage to prevent AD; it will not work in late stages. Prevention is absolutely required because chance of cure of established AD is extremely remote possibility.
PDM: How will you know if the treatment is working?
The best test is PET scans to study any changes in cerebral blood flow.
However, we can also follow progress with psychological testing to see small impairment or improvement in memory. Decline in memory is a very sensitive early indicator of cognitive decline.
PDM: With the current interest in prevention of AD, why has progress with rapamycin been so slow ?
Rapamycin is a generic drug. There is no pot of gold at end of the rainbow for rapamycin.
PDM: Since our last interview in May 2017, how have you been doing? Do you still feel that rapamycin has been crucially important in your return to health?
ASG: I will turn 75 this February and have now been on weekly rapamycin for 2 years. I have not had any significant side-effects from weekly rapamycin. As regards aging, I feel like I am now in “remission”. I am very happy about the function of my brain and heart. I credit Mikhail Blagosklonny and rapamycin for giving me a new lease of life. I consider rapamycin the most important new drug since discovery of penicillin 90 years ago. [Emphasis added – PDM]. The failure of the medical community to have widespread use of rapamycin to prevent age-related diseases including AD is an enormous loss to older people.
PDM: How is your rapamycin-based practice for prevention of age-related diseases going ?
ASG: For the past eight months, I have treated a fairly small number of patients. The remarkable thing is that average distance from where patients live to my office is probably around 1000 miles. I have seen patients from UK, Canada, Cayman Islands, and about 20 states including California, Texas, Florida, Massachusetts. Most patients fly to NYC. They are a remarkably knowledgeable group.
Weekly rapamycin is very well tolerated and only a few patients have had any side-effects.
PDM: As a physician in the anti-aging field, what do you consider the most important development is for 2017?
ASG: Matt Kaeberlein’s experiment with old companion dogs. He gave old dogs intermittent rapamycin for 3 months and showed improvement in cardiac function. Some of the dog owners said their old dogs were running around like puppies.
[This short video shows the remarkable results of a dog on rapamycin – PDM]
However, in my opinion, for the most part, the anti-aging field is dominated by quack medicine and junk science.
PDM: How can people discern real science and results in treating aging?
ASG: Mikhail Blagosklonny said aging and age related disease were connected like smoke and fire. This means an anti-aging drug should both extend the lifespan of all different organisms tested including yeast, flies, worms, and mice; but should also prevent almost all age-related disease including cancer and heart disease.
PDM: How big an effect do you think rapamycin will have on human lifespan ?
Rapamycin has one effect, it decreases mTOR. Elevated mTOR appears to play a very major role in age-related disease. I expect rapamycin will have a huge effect on preventing age-related disease and keeping people healthy in their seventies and eighties. Other than that, we will have to wait another 20 or 30 years to see the full impact of lowering mTOR.
PDM: Getting back to your new website, what should APOE4 carriers know?
ASG: First they need to understand their real risk and the things they should do to lower their risk.
Everybody knows APOE4 carriers are at increased risk; but the increased risk is greatly minimized by how the numbers are presented. Overall APOE4 carriers have a 3.2 fold increased risk; but their mean age of onset is 10 years sooner than non-E4 carriers. In the 60-69 age group, they have a 5.6 fold increased risk, in the 70-79 year age group a 4 fold increased risk. The increased risk is only 1.7 fold in the 80-89 age group. When averaged together the large number of cases of AD in 85 plus age group who are non-E4 carriers with the AD cases in E4 carriers in the younger age group, it creates a false impression. It is not that the lifetime risk in non-E4 group is 9% and lifetime risk in E4 group is 29%, it is the 10 years sooner mean age of onset that makes the huge difference in impact.
The impact of lifestyle on APOE4 carriers is very large; in contrast, lifestyle seems to have a small impact in non-E4 carriers as regards risk of AD. Any statement about lifestyle as regards risk of AD in general population is worthless and dangerously misleading as regards APOE4 carriers.
There are very many dramatic examples of this: High saturated fat diet increases risk of E4 carriers 11 fold; but has no significant increased risk for non-E4 carriers. Frequent alcohol intake increases risk 7 fold vs never drinkers in E4 group; but actually lowers risk in non-E4. Overweight, obesity, diabetes greatly increase risk in E4 carriers compared to non-E4 carriers. The benefits of physical activity is much greater in E4 group. A sedentary lifestyle with overeating, eating large amount of red meat, overweight combined with moderate alcohol intake might be reasonably safe for non-E4 carriers; but very high risk for APOE4 carriers. Information reported might be correct for non-E4 carriers; but very different for E4 Carriers. Therefore, E4 carriers they must know their E4 status so they can take appropriate steps to minimize their risk.
PDM: What basic science should they know?
The website deals with this in two sections; Basic Science and Mouse studies.
AD in APOE4 carriers is a 2 hit disease. (Zlokovic theory) The first hit is deterioration of the vascular system. The 1st hit develops decades before the second hit and decades before first onset of cognitive changes. PET scans of cerebral blood flow shows deterioration starts in the 20-39 year age group in E4 carriers. The damage to cerebral blood flow results in accumulation of amyloid. The accumulation of amyloid then triggers the second hit which has been called the amyloid cascade. The second hit includes accumulation of hyperphosphorylated TAU, which is extremely damaging to nerve cells. The accumulation of amyloid is first noted age at mean age 56 in E4 carriers, compared to age 76 in non-E4 carriers.
The 2 hit theory, shows that deterioration of vascular system precedes hit 2 and amyloid cascade by decades. This provides excellent opportunity to prevent deterioration of vascular system in E4 carriers.
APOE4 is not a mere risk factor; but rather the cause. The specific etiology on a molecular level is that in APOE4 carriers the ApoE4 lipoprotein fails to combine with transport protein LRP1. [weak ligand] This results in activation of proinflammatory substance CypA which then activates the usual suspect NF-kB which activates MMP9 which then breaks down BBB (blood-brain barrier). The important thing to understand is that there is a specific pathway and rapamycin blocks this pathway which prevents damage to BBB and cerebral blood flow.
The Mouse studies section looks at 8 mouse studies with transgenic mice with human genes for AD. The most important study was a 2015 study in which mice were given human APOE4 genes. [Spoiler alert]. In every study rapamycin prevents development of AD like pathology and cognitive deficits.
The basic science details very many precise steps in two hit development in which rapamycin lowers mTOR and blocks the various steps.
Examination of the human brain from APOE4 carriers with AD, shows these same finding in the mice who were given human APOE4 genes are also present in the human brain.
PDM: What do we know about human APOE4 carriers that suggests rapamycin will prevent development of AD in this group?
ASG: Everything that raises mTOR in human APOE4 carriers, very much increases risk of development of AD. High calorie diet, overweight, obesity, diabetes all increase mTOR and all very much increase risk of development AD. Things like exercise and low calorie diet which reduce mTOR, lower risk of AD.
PDM: What methods are some APOE4 carriers now using to decrease their risk?
ASG: Many of them are using a regime that includes fasting, avoiding sugar and red meat. These are all methods to lower mTOR.
PDM: Would you expect rapamycin to protect against AD in non-E4 carriers?
ASG: Yes. Rapamycin would be expected to protect against AD in non-E4 carriers by the following mechanism:
Rapamycin protects against hyperphosphorylation of Tau by many mechanisms as discussed in the Tau section. Tau is major player in AD.
Rapamycin would prevent accumulation of amyloid by increase in autophagy.
Increase in amyloid causes increases in mTOR which increases Tau, rapamycin blocks this step.
Rapamycin would help preserve cerebral blood flow by decrease in CypA[Symbol]NF-kB[Symbol]MMP9 pathway leading to breakdown of BBB which develops in old age due to very marked age-related decrease in LRP1.
Rapamycin increases cerebral blood flow by increased nitric oxide.
The mean age of AD in non-E4 carriers is 85. Starting rapamycin at age 75 should be helpful to prevent AD in non-E4 carriers. This is in contrast to E4 carriers who, in my opinion, should probably start rapamycin at age 45 to prevent deterioration BBB and cerebral blood flow.
PDM: What is the effect of rapamycin on the normal aging brain?
Based upon mouse studies rapamycin might prevent memory decline. Age 60 is probably a good age to start to protect the brain from age-related memory decline.
Rapamycin increases catecholamines in the mid-brain which may prevent against age-related depression.
PDM: Many people have asked me whether rapamycin might impair muscle anabolism (growth) in resistance training. What do you think?
ASG: It might. mTOR builds large muscles.
However, rapamycin would help prevent against sarcopenia (muscle wasting in aged) by decreasing inflammation.
Rapamycin may also help preserve muscle strength by an increase in number of mitochondria by preserving mitophagy.
[See below for more on this. – PDM]
PDM: What effect would you expect of rapamycin on testosterone and sexual performance ?
ASG: Intermittent rapamycin would not affect testosterone levels in contrast high levels daily Rapamycin.
Rapamycin causes an increase of catecholamines in midbrain which might increase sexual interest.
Rapamycin increase in activity of NOS (nitric oxide synthase) and increase in nitric oxide could improve sexual performance.
PDM: Insulin resistance is an important cause of pathology in the diseases of civilization; what’s the relation of insulin resistance to AD?
ASG: You are correct. Major cause of civilization-related disease is through insulin resistance / high insulin / high mTOR pathway. Insulin resistance causes high insulin levels and high mTOR. High mTOR is then the major driving factor in most age-related disease and AD.
Insulin resistance should be viewed as a very serious disease with diabetes just one of the complications of insulin resistance.
Addendum: Rapamycin and muscle
Dr. Green above noted several effects of rapamycin on muscle, some of them opposing each other, so here’s some more information.
Rapamycin-treated mice had endurance equivalent to that of untreated controls, and isolated, permeabilized muscle fibers displayed similar rates of oxygen consumption. We conclude that the doses of rapamycin required to extend life do not cause overt mitochondrial dysfunction in skeletal muscle.
So, muscle endurance is not compromised.
In yeast, life extension by rapamycin seems linked to increased mitochondrial gene expression.
However…
Here we show that rapamycin treatment blocks the early (1–2 h) acute contraction-induced increase (∼40%) in human muscle protein synthesis. In addition, several downstream components of the mTORC1 signalling pathway were also blunted or blocked by rapamycin.
Comment: The subjects in this study took a huge dose of rapamycin, 12 mg, immediately before a workout. Below is concentration of rapamycin in blood by time.
Insulin response was blunted during and after exercise compared to controls, and muscle protein fractional synthetic rate in rapamycin treatment was also blunted.
The type of rapamycin treatment that Dr. Green advocates and prescribes is once weekly and at a much smaller dose. An otherwise healthy man aged about 60 might take 2 mg rapamycin weekly, only 1/6 the amount in the above experiment that blunted muscle synthesis following resistance training.
Here’s a case where timing would be very important. Someone could take rapamycin but do strength training away from the dose, perhaps more than 2 days later. As I understand it, the type of mTOR activation that promotes aging is chronic activation. An analogy is with insulin activity: at times you want insulin to increase and spike to high levels, such as after a meal, but it’s deleterious to health for insulin to be constantly elevated (hyperinsulinemia), as it leads to insulin resistance. With mTOR, spikes in its activity should be fine; chronic, low-level activation of mTOR is what leads to aging. That’s my speculation and I don’t want to speak for Dr. Green.
Update:
A commenter below remarks: “As a patient of Dr. Green I appreciate the spread of information. I currently take 2 mgs of Rapamycin every 2 weeks and have noticed ZERO negative effects on my weight training and strength. BTW – I’m 63 and will be 64 in July.” That’s the sort of information we need but which is necessarily in short supply at this time. Likely we’ll know a lot more about the interplay between rapamycin and muscle in 10 years time, when many more people will have been taking it. Meanwhile, the comment lends some support to my hypothesis that low, non-daily doses of rapamycin do not compromise muscle growth and/or resistance training.
A big thanks to Dr. Green for this interview.
PS: For some straight dope on anti-aging, see my book Stop the Clock.
41 Comments
Very interesting! I have so far avoided any genetic testing as I don’t fully trust what that information might be used for in the future. Higher health insurance premiums? Or something worse? Now in my early 50’s I can already note mild short-term memory issues, but have no idea if I might be an APOE4 carrier. Do you recommend any particular testing service, and is there one that I could strictly limit what they test for?
I believe you could get it tested separately at a (relatively sophisticated) clinical lab such as Quest Diagnostics.
23 n me doesn’t do APOE4?
Yes, they do, but the question was how to do that test alone, and how to avoid a big company having all of your genetic information. I’ve done the 23 and Me testing, ApoE4 negative, and unfortunately (perhaps) they know my genes. Not that it bothers me really.
You can always do a 23andme test under a pseudonym and pay with a Visa gift card.
It does…I have been informed that I have 1 copy of APOE4, which they claim is a minimal risk…What does the Doctor say about that?
APOE4 testing done by Life extension and 23&me. I suggest pay for test yourself and use an alias. @$100
Full disclosure: I take weekly rapamycin and I know Dr. Green.
Very nice post and I suspect that Alan is right about its role in Alzheimer prevention, as well as all age-related diseases for that matter. A recent study in mice showed that it also rejuvenates adult stem cells.
Of course mTor comes in 2 flavors, TOR 1 and TOR 2, wherein TOR 1 activates TOR2, so chronic daily inhibition of TOR 1 with rapamycin would lead to immunosuppression via TOR 2 inhibition. This suppression does not occur with transient inhibition of TOR1 with weekly low doses of the drug ( the half life is about 60 hours).
After 6 months I do indeed feel younger in almost every way with muscle maintenance but not growth.
I have a slight uptick in blood sugars along with a decrease in insulin and IGF1 levels. No immune issues.
There are other ways to inhibit mTOR but these are more indirect such as AMPK activators like metformin , hesperidin, and berberine. Another way is calorie restriction and fasting. I suspect that none of them are quite as potent or effective.
PD is quite right that there are many instances where you can go overboard in attempts to inhibit certain things like insulin and TOR. This is also true of inflammation, where only the chronic form is dangerous; ditto for free radicals and the use of antioxidants.
It is now my opinion that rapamycin is the best disease preventing and anti-aging drug that we presently have at our disposal.
I wonder if Rampamycin also reverses CVD as well. Any thoughts on this ?
Hi Bill,.Rapamycin in animal lab studies prevents atherosclerosis and prevents destabilization of plaque which causing acute MI. Also rapamycin helps prevent age-related deterioration of heart muscle.
The Matt Kaeberline companion dog study noted here showed 3 months on rapamycin and old dogs had improved cardiac output on echocardiogram and owners report old dogs running around with much more energy. I would rank protecting heart and protecting brain from age-related decline two main reasons. Preventing AD in APOE4 carriers just a special reason in high risk group.
All the age-related diseases are closely related on molecular level which is why all happen in same age group.
As a patient of Dr,. Green I appreciate the spread of information. I currently take 2 mgs of Rapamycin every 2 weeks and have noticed ZERO negative effects on my weight training and strength. BTW – I’m 63 and wil be 64 in July.
Charles, thanks, that’s the kind of data we need to know and which is obviously very limited at this time. I suspect in 10 years time, we’ll know a lot more about this aspect of rapamycin.
It would be good to know at this point, of everyone presently on weekly rapamycin, are they:
1. Having a significant beneficial effect of some sort
2. Having some significant side – effect
Even this limited data would be helpful at this stage of the game even though one would not necessarily feel the beneficial effects of the drug.
Got something for ya PD, Ivor Cummins brought up ferritin in his latest keynote:
https://youtu.be/OvuGm8VYkQY?t=7m59s
Great, thanks Matt.
There are now 2 studies that I know of linking excess iron in the brain to Alzheimer”s.
” Ferritin levels in the cerebrospinal fluid predict Alzheimer”s disease outcomes and is regulated by APOE. Nat Commun 2015, 6;6760.
” Pulling iron from brain may offer hope in Alzheimer”s fight” Bloomberg.com, 11/29/17
Thanks, Paul. Leo Zacharski (who wrote the preface to my book) and colleagues wrote a good review of iron and Alzheimer’s in Getting the iron out: Phlebotomy for Alzheimer’s disease? I also wrote about it here.
That was a very interesting read. I think that we are now very close to preventing this horrible disease.
Keep ferritin under 100
Curcumin
Exercise
Rapamycin
And a very promising new drug under development called J147
We’re very close
???? I heard lactoferri in 2 months helps a lot, but then you have to stop
Hi.
I’m a “partly” ApoE4 carrier (e3/e4).
It seems therefore that my risk for Alzheimer is “only” 2x or 3x times higher and not 11x higher as for the “fully” ApoE4 carriers
(https://www.snpedia.com/index.php/APOE)
I get from the article that it’d be better for us ApoE4 carriers to abstain from saturated fats (“High saturated fat diet increases risk of E4 carriers 11 fold”) and red meat.
As i’m on a very low-carb diet, eating all my calories from red meat, eggs, cheese and butter I am a bit worried.
Thanks a lot.
Marco, I’ll put in my 2 cents, and Dr. Green could respond also if he wishes. Alzheimer’s disease has been called type 3 diabetes, and is characterized by (among other things) insulin resistance. Therefore it seems that a low carbohydrate diet, along with exercise, metformin if necessary, ought to be the best prevention. I don’t know about the data that says E4 carriers who eat saturated fat have 11-fold higher risk, but they’ve been saying similar things about atherosclerosis for decades, and it’s turning out to be untrue. Whether there’s a different dynamic at work with E4, I don’t know, however.
Yes, I mean, we have to eat something! And I cannot stay well eating a lot of carbs, despite my exercising 7 days a week….I eat a fair amount of fish, but now my mercury levels are probably too high…
One thought on this — maybe saturated fat intake corresponds with Alzheimer’s because of iron. One of the biggest sources of saturated fat is red meat, and red meat (perhaps not coincidentally) is one of the best sources of heme iron. A couple of the papers linked above suggest there may well be an association (possibly even causation) between elevated iron and Alzheimer’s pathology, so maybe saturated fat intake is just a proxy for higher iron intake/levels.
Hi Marco,
You should look at paper “Apolipoprotein E e4 magnifies lifestyle risks for dementia: a population based study.” Kivipelto 2008. 21 year follow-up 1449 individuals.
Look at Table 2.
ApoE4 carriers divided into 4 quartiles regarding saturated fat intake. 1st quartile risk 1. 4th quartile risk 11.29.
Expected reason: saturated fat usually means a diet high in animal protein as in red meat. Red meat means high mTOR.
This is very high quality study as followed for 21 years and divided into APOE type.
All information about lifestyle related risk factors should be based on high quality epidemiologic studies and specific for APOE4 status.
Hi Marco,
In this same study Odds Ratio for E4 was increased risk 2.83 after adjustment after adjustment for lifestyle and vascular factors. The point is that in APOE4 carriers lifestyle intervention may greatly modify the risk. It should be noted that being sedentary increases risk compared to active 2.43 fold and smoking vs non-smokers increases risk 1.97 fold. Group with highest intake saturated fat compared with lowest quartile was biggest factor in increasing risk.
This may be of interest, Alan: The possible role of vitamin K deficiency in the pathogenesis of Alzheimer’s disease and in augmenting brain damage associated with cardiovascular disease.
Also, I asked a knowledgeable friend and fellow saturated fat skeptic about apo E4 and he did not dismiss the idea, FWIW:
Here is an interesting and relevant study. Diabetologia. ” HbAiC ,diabetes and cognitive decline”. Zheng
This was a longitudinal study that demonstrated and increase in the rate of cognitive decline associated with increases in blood sugar levels. This is interesting in that other studies have shown an increased risk of Alzheimer’s in both type one diabetes , where your pancreas can’t make enough insulin, and type 2 where you have insulin resistance. In both cases the treatment is often the same- insulin.
There is an enzyme which breaks down insulin, and this very same enzyme also breaks down amyloid in the brain. So this makes one wonder if the true culprit here is insulin. In the case of type 1 diabetes the pancreas can’t make enough insulin, nor does it make enough of this critical enzyme to break down amyloid.
In type 2 excess insulin is given to lower blood sugar levels, so the enzyme is overwhelmed with breaking down all of this insulin, and is therefore unable to break down amyloid. So excess insulin leads to excess amyloid, and of course most people with excess glucose levels also have insulin resistance and excess insulin levels , thus too low levels of this critical enzyme.
This brings us back to rapamycin, which while elevating glucose levels, also lowers insulin levels, which would allow for higher levels of the all important amyloid busting enzyme to do it’s job preserving cognitive function.
The failure rate of AD drugs from 2002 to 2012 was 99.6%. This phenomenal failure rate means most people have totally wrong theories. If theory predicts wrong results, theory probably wrong. In absence of proof of prevention, all theories are suspect. When all theories are suspect, everybody free to come up with whatever crazy ass theory they like.
For me, sticking with idea that the perfect sTORm is mTOR and by decreasing mTOR with rapamycin, can prevent half dozen steps leading to AD.
Paul, I’m curious why you do not site the mechanisms of Dr. Bredesen’s protocol as shown in the table in the center of the following study:
https://www.aging-us.com/article/100690/text#fulltext
I don’t follow dementia all that closely, but his protocol and his clarifications when I’ve heard him describe it seem to be head and shoulders above anyone else in terms of approach to the condition. For example he stresses that it is not just one “disease” but multiple, sometimes overlapping conditions with over 30 different and distinct pathways.
The mTOR pathway seems to be completely consistent with his work since insulin is a signal for mTOR and his number one intervention is to lower insulin and extend the unfed state, so he’s essentially lowering mTOR through other means.
Also, I remember that he has a lot to say about APOE4 but unfortunately I don’t remember the details, although he is a big supporter of MCT oils and/or coconut oil to raise ketone levels.
I don’t think hi follow-up study to the 2014 one has been published but from what I’ve heard it has been very successful, much better than any other interventions. Since the study above was done he has apparently revised the protocol to extend the daily fasted state to 16 hours for APOE4s.
Thanks Drifter. Very informative article and I wasn’t aware of his work. Very impressive. Clearly attacking this from all angles gave some rather remarkable results. To my mind all age-related illnesses have certain things in common and mTOR is certainly one of them, but I’m not willing at this point to dismiss or ignore the influence of inflammation, insulin, diet, exercise, senescence, SIRT1,sleep, and even heavy metals. My feeling at this point is that TOR inhibition is necessary but perhaps not sufficient.
Hi Drifter,
Thanks for posting paper. Paper presents program which includes diet, exercise and fasting plus lot of other stuff. Says 9/9 persons with memory problems, but not AD had subjective improvement. Presents 3 cases histories. All had very marked diet changes and vigorous exercise. One person lost 20 pounds, other person 10 pounds and 3rd person did not give weight change.
Possible suggestion of study is that diet and exercise can improve memory in middle age persons with memory decline.
For this to be anything in the slightest bit approaching something called “Science” would need to compare diet and exercise alone compared to diet and exercise plus other stuff and a bit more than subjective improvement and more than 2 cases histories in which give amount of weight loss.
My impression is Bredesen formula combines somethings with a rational basis (diet and exercise which reduces mTOR) with a huge amount of junk science.
A bit off-topic, but related:
https://neurosciencenews.com/kyna-alzheimers-reversal-8435/
“The researchers found that by keeping KYNA levels low throughout the worm’s life, they could prevent the onset of age-related decline – the worms kept learning. In older worms already impaired, lowering KYNA levels could counteract the impairments – raising hope that interventions later in life may be effective in reversing neurological decline.
The reason that KYNA increases with age is still a mystery, but the new study offers an intriguing hint, by linking KYNA buildup in aging worms to elevated levels of insulin, a hormone that controls blood sugar in both worms and humans. In contrast, earlier experiments by Ashrafi’s team had found that fasting, which has been linked to longevity, reduced levels of KYNA in worms and improved learning and memory.:
PD, do you recommend a particular Vitamin K product?
See my recent post. I don’t recommend a particular brand, and it’s still debatable whether MK4 or MK7 is the best form of K2.
Got it, thanks.
That is a great post and does provide a potential resolution to what I thought was conflicting information. I have read about mTOR on multiple sites being a key player in aging, mitochondrial dysfunction, possibly cancer as well as AD. However, was always confused because mTOR is very crucial to muscle anabolism. And you want muscle, not only to look good, but lean muscle itself also correlates with overall survival. So how do we maximize muscle, and also reduce aging/chronic disease? How to find that perfect balance?
AJ, thanks. In my opinion, the kind of mTOR activation in aging is chronic. Similar to insulin, it should be activated when necessary, and turned off when not. Therefore we can maximize or at least optimize muscle as well as have anti-aging.
Has there been any studies on the effects of Rapamycin with animals or people who are already in early or mid stage AD? Do you think it could stabilize amyloid plaque and tau accumulation?
Dr. Green?
Could a major factor in the benefit of using Rapamycin be that it increases autophagy besides just the prevention of amyloid?
I will continue to give blood 3 times a year and hopefully I will work up the resolve to fast sometimes.
Hi Bruce: yes, rapamycin increases autophagy, since mTOR is a negative regulator of autophagy.