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Supplementation to treat/reverse MCI and ALZ - verification
Rich L
Posted: Wednesday, August 29, 2018 4:40 PM
Joined: 8/29/2018
Posts: 1

Anybody have a link to a database of medicines and supplements and their experimentally-verified ability to treat/reverse mild cognitive impairment (MCI) and ALZ? There are several books out there claiming success, but they spend a lot of time on anecdotal accounts and the literature cited often isn't much better. I also have a hard time finding the few cited articles that, according to their titles, appear that they could be good experimental designs that would actually prove something.

I am under "integrative medicine" treatment with supplementation (not prescriptions) and dietary augmentation/restriction (no grains, sugar, dairy, etc.), but am getting increasingly skeptical. I'd like to see the research or at least an objective review of what I'm taking to justify the substantial expense and inconvenience of 31 pills/day.

Many thanks!

Lane Simonian
Posted: Thursday, August 30, 2018 10:13 AM
Joined: 12/12/2011
Posts: 4420

Could you provide a list of the supplements that you are taking?

Below are links to the studies in which certain natural products have produced initial improvements in cognition that were sustained in early to moderate Alzheimer's disease.  None of these studies used a placebo but that is not a major design error as the slope of decline in individuals with Alzheimer's disease taking a placebo has been well established.  If a person with mild cognitive impairment or Alzheimer's disease improves while taking a placebo either the placebo has a compound in it that is doing some good or the person is taking some kind of medication or supplement that is producing at least a temporary beneficial effect. 

None of these trials and studies were randomized which could be a problem as people progress at different rates early in Alzheimer's disease and randomization would eliminate this compounding factor.  None of them are double-blinded which is a bigger problem as the observer may consciously or sub-consciously produce biased results.

Having said all that I am tired of all the people who say these trials and studies are useless or garbage.  This is often a reflection of their bias against the use of supplements to treat mild cognitive impairment and Alzheimer's disease.  Oxidants (especially peroxynitrite) produce widespread damage in the hippocampus and cortex in Alzheimer's disease and some of that damage can be reversed with particularly strong antioxidants.  For example, the regrowth of neurons can be restarted in the hippocampus and improving acetylcholine  levels in the hippocampus can lead to improvements in certain forms of memory (object recognition, facial recognition, recognition of places, for instance).  The trial results fit (although not prove) the hypothesis and vice versa.  This is very difficult for some people to accept because they adhere to the belief that Alzheimer's disease is a highly complicated disease for which nothing can be done.  

Here are the trials and studies.

Aromatherapy using rosemary and lemon in the morning for cognition and lavender and orange in the evening for relaxation using a diffuser (direct inhalation of clove and bay laurel in the morning may work better, although increased anxiety can occur with clove)

Korean red ginseng (steamed panax ginseng)

Heat processed ginseng (Korean red ginseng steamed at very high temperatures)

Chinese herbs plus conventional medicines

Lane Simonian
Posted: Thursday, August 30, 2018 10:28 AM
Joined: 12/12/2011
Posts: 4420

I should add some of the rationale behind diet in the treatment of mild cognitive impairment and Alzheimer's disease.  Carbohydrates and sugar increase levels of myo-inositol in the brain which is linked to an increased conversion rate from mild cognitive impairment to Alzheimer's disease.

Myo-Inositol, N-Acetylaspartate Are Sensitive Biomarkers for Conversion From MCI to Alzheimer's Disease

Comparison of patients with progressive disease versus those who developed AD for the cingulate gyrus showed the increased myo-inositol-to-water ratio to be 72% predictive for dementia; similarly for the hippocampus, it was 70% predictive for dementia.

The polyphenols in spices, vegetables, fruits, etc. in particular diets (such as a Mediterranean diet or a diet from India) both scavenge peroxynitrite and repair part of the damage that it does to the brain.

Defenses against peroxynitrite: selenocompounds and flavonoids.


The inflammatory mediator peroxynitrite, when generated in excess, may damage cells by oxidizing and nitrating cellular components. Defense against this reactive species may be at the level of prevention of the formation of peroxynitrite, at the level of interception, or at the level of repair of damage caused by peroxynitrite. Several selenocompounds serve this purpose and include selenoproteins such as glutathione peroxidase (GPx), selenoprotein P and thioredoxin reductase, or low-molecular-weight substances such as ebselen. Further, flavonoids, such as (-)-epicatechin, which occurs in green tea or cocoa as monomer or in the form of oligomers, can contribute to cellular defense against peroxynitrite.

 2004 Dec;1030:434-41.

Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning.



The activation of nuclear transcription factor kappaB has now been linked with a variety of inflammatory diseases, including cancer, atherosclerosis, myocardial infarction, diabetes, allergy, asthma, arthritis, Crohn's disease, multiple sclerosis, Alzheimer's disease, osteoporosis, psoriasis, septic shock, and AIDS. Extensive research in the last few years has shown that the pathway that activates this transcription factor can be interrupted by phytochemicals derived from spices such as turmeric (curcumin), red pepper (capsaicin), cloves (eugenol), ginger (gingerol), cumin, anise, and fennel (anethol), basil and rosemary (ursolic acid), garlic (diallyl sulfide, S-allylmercaptocysteine, ajoene), and pomegranate (ellagic acid). For the first time, therefore, research provides "reasoning for seasoning."


Mediterranean Diet and Risk for Alzheimer’s Disease



There were 262 incident AD cases during the course of 4 (±3.0; range, 0.2–13.9) years of follow-up. Higher adherence to the MeDi was associated with lower risk for AD (hazard ratio, 0.91; 95% confidence interval, 0.83–0.98; p = 0.015). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had a hazard ratio of 0.85 (95% confidence interval, 0.63–1.16) and those at the highest tertile had a hazard ratio of 0.60 (95% confidence interval, 0.42–0.87) for AD (p for trend = 0.007).



We conclude that higher adherence to the MeDi is associated with a reduction in risk for AD.


Mediterranean diet and Alzheimer disease mortality

Eighty-five patients with AD (44%) died during the course of 4.4 (±3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence fertile, those at the middle fertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years’ longer survival), whereas subjects at the highest fertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years’ longer survival; p for trend = 0.003).


Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose–response effect.

The answers are not easy and they are not complete, but the idea that we know nothing about Alzheimer's disease or how to treat it is not a reflection of reality

Michael Ellenbogen
Posted: Thursday, August 30, 2018 10:41 AM
Joined: 11/30/2011
Posts: 2113

This may be helpful and is based on my own experience.

Iris L.
Posted: Thursday, August 30, 2018 2:51 PM
Joined: 12/15/2011
Posts: 15635

Thanks for sharing your article, Michael.  None of us knows how much time we have, and it is good to use the time we do have to accomplish what we want to accomplish.

Iris L.

Lane Simonian
Posted: Thursday, August 30, 2018 4:32 PM
Joined: 12/12/2011
Posts: 4420

Thank you, too, Michael.  There has to be a balance between searching for answers, being an advocate, and enjoying life.  You and Iris seem to have found that balance.
Posted: Tuesday, September 11, 2018 11:47 AM
Joined: 9/11/2018
Posts: 2

There is a recently published paper on a supplement called Geneaire Rebuilder - looks promising!



Lane Simonian
Posted: Thursday, September 13, 2018 10:12 AM
Joined: 12/12/2011
Posts: 4420

I am impressed by this clinical trial.  It was a randomized, double-blinded, placebo controlled studies.  The botanicals used affected many of the mechanisms that are involved in Alzheimer's disease and appeared to stabilze the disease for at least one year.  Thank you for posting .  I hope that you don't mind me reposting it elsewhere.
Posted: Sunday, September 16, 2018 1:16 PM
Joined: 2/26/2016
Posts: 139

Lane, why don't you investigate the source and methods before you endorse a clinical trial.


This is not a legitimate clinical trial for the following reasons.


1. There is no government supervision of any kind, not from the FDA, the Canadian government, the EU, or any other government. No legitimate institution such as a university or medical center is envolved. A company run clinical trial is practically guaranteed to get positive results. In fact we don't even know if any trial was actually done. The company could just have created the paperwork and submitted it.


2. What legitimate clinical trial would test a medication with seven active ingredients? How would you know which ingredient is effective and which ingredient causes side effects. Furthermore there is no listing of side effects.


3., the publisher of this so-called clinical trial, is headquartered in Hyderabad, India, and was sued by the Federal Trial Commission in 2016 for deceiving academics and researchers, falsifying information in clinical trial papers and hiding publication fees. This company will publish just about anything for the right price. 


This is not a legitimate clinical trial, but rather a marketing ploy by the American corporation Genescient, using a discredited Indian medical publishing company.


OMICS Publishing Group - Wikipedia 


Lane Simonian
Posted: Sunday, September 16, 2018 5:13 PM
Joined: 12/12/2011
Posts: 4420

Here are the list of authors:

Matsagas K1 *, Villeponteau B2 , Shankle WR3,4, Cruise RJ1 , Morales S1 , Goertzel B1 , Simmon VF1 , Benford G5 and Rizza C1 1. Genescient Corporation, Fountain Valley, California, United States of America 2. Centagen Inc., Boulder, Colorado, United States of America 3. Shankle Clinic, Hoag Hospital, Newport Beach, California, United States of America 4. Department of Cognitive Sciences, University of California at Irvine, Irvine, California, United States of America 5. Department of Physics and Astronomy, University of California at Irvine, Irvine, California, United States of America.

Now some do have a personal stake in the results, but no more so than researchers at pharmaceutical companies.  Furthermore, the clinical trial was placebo controlled (although relying in the end on historical rates of decline in other placebo controlled trials), randomized and double-blinded.  

The seven active ingredients were chosen based on a drosophila model to find the ones that had the greatest impact on pathways associated with Alzheimer's disease.  The positive compounding effect of antioxidants may have their limits, but the expectation that a combination of antioxidants is sometimes more effective than one is not baseless.

The journal in which the study was published does not automatically invalidate the results (although it does provide fodder for those who wish to criticize the results).  Good studies have been published in "bad" journals and bad studies have been published in "good" journals.

Finally several other clinical trials using a similar approach have produced similar results.

A 24-week randomized open-label study with Korean red ginseng (KRG) showed cognitive benefits in patients with Alzheimer’s disease. To further determine long-term effect of KRG, the subjects were recruited to be followed up to 2 yr. Cognitive function was evaluated every 12 wk using the Alzheimer’s Disease Assessment Scale (ADAS) and the Korean version of the Mini Mental Status Examination (K-MMSE) with the maintaining dose of 4.5 g or 9.0 g KRG per d. At 24 wk, there had been a significant improvement in KRG-treated groups. In the long-term evaluation of the efficacy of KRG after 24 wk, the improved MMSE score remained without significant decline at the 48th and 96th wk. ADAS-cog showed similar findings. Maximum improvement was found around week 24. In conclusion, the effect of KRG on cognitive functions was sustained for 2 yr follow-up, indicating feasible efficacies of long-term follow-up for Alzheimer’s disease.

Compared to CT [conventional therapy] alone, CT + H [conventional therapy plus herbs] significantly benefited AD patients. A symptomatic effect of CT + H was more pronounced with time. Cognitive decline was substantially decelerated in patients with moderate severity, while the cognitive function was largely stabilized in patients with mild severity over two years. These results imply that Chinese herbal medicines may provide an alternative and additive treatment for AD.

Now there are always those prone by instinct to doubt all of these results either because they have another dog in the hunt, because they don't believe natural products can treat anything, or because they simply doubt any results unless verified time and time again.

This remains my favorite quote on Alzheimer's disease (all of the botanicals tested in the clinical trials above are peroxynitrite scavengers).

"Clinical trials with over-the counter supplements have concentrated either on items which suppress inflammation, or on antioxidants which scavenger oxygen derived free radicals.  Most of these items have proved to be worthless in the treatment of Alzheimer's disease.  Similarly most drugs used to treat Alzheimer's disease do little to slow the deterioration, but instead offer a mild temporary symptom relief.  However, evidence has been accumulating that the primary driver of Alzheimer's disease is a nitrogen derived free radical called peroxynitrite, which may mediate both amyloid and tau accumulation as well as their toxicity.  Excellent results have been obtained with peroxynitrite scavengers, with reversals of Alzheimer's disease in human clinical trials being repeatedly demonstrated.  IMHO, the only thing which may be preventing the abolition of Alzheimer's disease is the mental inertia of scientists, as well as the bureaucrats who fund them.  Unfortunately, most bureaucrats keep throwing money into repeatedly testing discredited interventions, while ignoring successful ones.  Common sense is anything but....

Posted: Saturday, October 20, 2018 10:29 PM
Joined: 9/11/2018
Posts: 2


Sorry, I've been away for a while...  No, don't mind at all if you repost(ed) my link - if this is as good as it seems, it would be to everyone's benefit to know about it.

I might have been off the discussion boards for a couple of weeks, but I have been keeping tabs on this Geneaire Rebuilder.  My interest in it is more for a family member who has recently been diagnosed w/ early stage dementia.  I'm not a fan of pharmaceuticals (most seem to create more problems than they're supposed to fix), so I've been looking for all types of alternatives - that's how I came across this one.

They have a website and more publications have since come out, including this white paper - - which goes into greater detail on how much of their research has relied on Methuselah Flies and continued genome analysis w/ regards to the compounds being used. 

I also must confess, I decided to give it a try - it just became available on Amazon... Getting one for my uncle, and -- since it is just as much a preventative -- one for myself.  We'll see if it makes a difference.

Lane Simonian
Posted: Sunday, October 21, 2018 10:22 AM
Joined: 12/12/2011
Posts: 4420

Thanks, THK.  I definitely think that it is worth a try.  Let us know if it seems to have some positive effects.

Here is an additional link.

Posted: Friday, November 16, 2018 1:28 PM
Joined: 11/13/2018
Posts: 4

Profound thanks!

Do you ever share your resources?

As you were mistakenly diagnosed - you understand I strongly wish to avoid such mistakes myself. No doubt your first doctors were experienced and smart. Yet not half as smart as the doctor who later accurately diagnosed you.

As yet I have found no neurologist able to diagnose the cause of my dementia.

I need someone bright enough to do a differential diagnosis - BEFORE this gets worse.

I live in Miami - I will travel - but exactly who can I trust to provide an accurate diagnosis?

I am confident you have discovered some of the best neurologists in the world. Unless it violates board rules (Private or Public) you would be profoundly helpful to me if you would share the best that you know - still taking on patients?

Thank you again for all you have done. And I thank you in advance.

My Very Warmest Regards,

 - Tom 

Posted: Friday, November 16, 2018 1:53 PM
Joined: 11/13/2018
Posts: 4

With new studies coming out daily - I highly recommend visiting PubMed.

I search for every antioxidant that may cross the BBB.

You could not be more correct about the inflammatory response. (My father was a dentist I did not get along with - so I have never been to one.) Guess what else is strongly associated with Alzheimer's, Cardiovascular (and countless other diseases?) Gingivitis. I will in short order get this treated and fixed!

I also run searches on anything that might inhibit M-Tor.

Next I look for anything that raises growth factors in the brain.

Finally - find any product that inhibits GSK-3.

One thing I avoid are supplements with choline. For reasons not yet understood - but likely related to gut bacteria supplements such as phosphatidylcholine are too often metabolized into a very toxic substance known as trimethylamine N-oxide or (TMAO).

Posted: Monday, February 4, 2019 7:01 AM
Joined: 4/19/2018
Posts: 97

@Tom Bateson:

So, there is a very likely chance that the Acetyl N Carnitine  I am giving to DH (and considering taking myself) is being converted to TMAO and therefore is toxic?

In DH, the Acetyl N Carnitine brings on an increased responsiveness and a happier demeanor. He has been taking this supplement for one year. I have seen what I would classify as only a slight decrease in mental (thinking) symptoms (stabilizing?)—all of which could just be normal for his stage/age. So I am reluctant to stop this supplement for him.

I purchased phosphtidylcholine (new) and notice that when I take this one the area surrounding my liver hurts. The reason I purchased the supplement in the first place was due to the claim that this substance protects the liver. My surprise diagnosis for my health is”fatty liver.” I may not take this one any more. I won’t be giving DH this supplement for sure. He is a smoker and doesn’t need more toxins.


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