If the answer to those two questions should turn out to be an unequivocal “Yes!” that would definitely be cause for champagne and fireworks.   Sorry to say that for now, at least, we have to put the champagne and fireworks on hold.   But, who knows, might there be something – a few snippets of fact – behind this promotion? That possibility, remote as it is, set me to looking into these questions.

A Gumshoe follower put me on to the promotion, which leads off like this:

“3 years ago, my poor grandchild was almost roasted to death because of my wife’s memory problems…

It all started out so innocently… She was burning cookies, forgetting her keys, forgetting a name now and then… I didn’t expect her to suddenly get full blown Alzheimer’s. I realized something was terribly wrong when she forgot our 2-year-old grandchild Liam in the boiling hot car, at 120 degrees during one of the worst Texas heat waves that hit the state in the past 100 years…almost roasting him to death…

Not only that, her memory became so bad…she started having some real difficulty remembering my name or the names of anyone in the family after that.

I cried like a child when it happened, but it was that precise moment that led me to uncover why we lose our memories, why a real solution to memory loss was never found until 2019 (HINT: scientists were looking in the wrong places), and how we can STOP our minds from degenerating, declining, and succumbing to memory diseases.”

There we have the basic premise of this promotional piece in a nutshell.   A dire but familiar threat that hangs over most of the population, and a simple solution that will protect us from the effects of that threat.

A few words of background on Alzheimer’s disease: we’re familiar with these facts, but let’s put them front of mind. 

Currently, about 5.8 million Americans have AD.   That number is expected to hit 14 million or so by 2050.   AD is the sixth leading cause of death in the US, killing more people than breast cancer and prostate cancer combined.   The current annual costs of AD are about $305 billion, and may breach the trillion dollar mark by 2050.   And, as we very well know, the essential cause or causes of AD are still murky – amyloid beta (Aβ), tau protein tangles, or some combination of these.   And as far as effective treatment for AD, there have been marginal successes at best.

So there’s no exaggerating the impact of that threat, and if it should really turn out to be true that AD is caused by bacteria and can therefore be treated as a bacterial infection, that would be world-changing in more ways than one.

The presentation continues:

“In the next 5 minutes I will show you the undeniable scientific truth:

• Why are there people with perfect memory well into their 90s while others experience forgetfulness in their 40’s
• The real root cause of memory loss – How a common bacteria will decide whether you’ll lose your memories at 40 or at 60 years old
• The simple breath test you can do tomorrow morning in order to see if you’re at risk or no
• The 2019 buried Harvard study that showed the real root cause of memory loss (and why nobody dares to talk about it)
• And the simple 30-second method that can bullet proof your brain cells against the memory-devouring bacteria.”

The presenter then identifies himself and describes how he was crushed by the realization that his wife had AD.   But he is undeterred by the lack of a medical solution, and determined that he himself must carry out an investigation into AD.

Here’s what he says:

“That night I realized there was no way I was going to wait for a medical breakthrough to make my wife better…

I needed to create one myself…

Or could no longer call myself a man and a father again!

I didn’t care that the doctor said there was no real solution for Alzheimer’s…I wasn’t going to let it happen. So, after tossing and turning in my bed all night…

I spoke with my university and took an extended leave of absence…

I went to the bank, to take out a mortgage on our house and a small business loan to fuel my own research efforts. I knew I had to do it.

I knew that a solution for my wife will not come from the Big Pharmaceutical industry. Think about it: It takes at least 12 years for a drug to be approved by the FDA. Who cares about the patient?

I then began spending every single moment of every day pouring over Alzheimer’s research.
I just knew there had to be SOME solution to stop this madness, and I was going to be the one who found it.”

Are you getting our free Daily Update
"reveal" emails? If not,
just click here...

How is this guy supposed to solve one of the most consequential medical mysteries – a problem that the best scientific minds on the planet had made very little progress in solving?   Why does he need to mortgage his house and take out a business loan? 

Along about this point in the presentation, he introduces himself.   His name is Carl Henderson, and a bit of Doc Gumshoe sleuthing reveals that he is a professor of psychology in Austin, Texas.   And he is the founder of an outfit called ProMind Complex.   So it looks like he’s doing something beyond solving the mystery of Alzheimer’s disease so he can help his wife – he’s hoping to make a few bucks while he’s at it.

“I’ll spare you my months of continuous struggle and take you directly to the one study that changed everything we knew about memory loss… A study which most doctors would have never heard of!

You see, memory loss does not start in the brain as every brain doctor would claim…

It starts somewhere else…
In your gums!

A 2019 “buried” Harvard study confirmed this unexpected conclusion:”

He then provides a screen shot of the title and authors of an article in Science Advances entitled “Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors.”   (Dominy et al., Sci Adv. 2019;5:eaau3333 23 January 2019).   This, by the way, is not a “Harvard study.”   It is a long, dense, carefully-stated paper covering a good deal of research.   There are 23 authors listed, only one of whom has any Harvard affiliation  – not that the lack of a Harvard affiliation invalidates the study.   My guess is that Carl Henderson figured that calling it a “Harvard study” gives it more legitimacy.   As it turns out, most of the authors work for a biopharmaceutical firm in San Francisco called Cortexyme.   You can make of that what you will.

That bacterium, Porphyromonas gingivalis (P. gingivalis) is an oral anaerobic microbe that is involved in the pathogenesis of periodontal disease, which attacks the gums supporting the teeth, leading eventually to tooth loss.   It’s not at all clear why this would have anything to do with memory loss, or, indeed, any brain function.   

But let’s have Carl Henderson continue with his presentation.

“Until recently, the entire medical community believed that there is a gene that is present in certain people, that can trigger the development of the disease – the APOE gene that basically devours your brain-proteins.

But that still made me wonder…

What triggers the gene in the first place?

Why are there people with perfect memory well into their 90s while others experience forgetfulness in their 40’s?

What scientists hadn’t figured out was WHY this happens only to some people…

And why some people with no family-history of this disease can still get it. I mean my wife’s parents were still completely independent and lucid despite being in their late 70’s!

So by that train of thought she shouldn’t have gotten such an aggressive reaction in the first place…

But there it was, in plain sight:

A cutting-edge new study, published by the researchers at Harvard University that proved all memory-impairment diseases are linked to an infection in your gums caused by a bacteria called P. gingivalis.”

Here’s my summary of what that study – neither of whose senior authors have anything to do with Harvard – actually says:

P. gingivalis has indeed been identified in the brains of patients with Alzheimer’s disease.   In genetically-modified mice that have the ApoE4 gene, infection with P. gingivalisresults in brain infection, and in mice that have the mutated human amyloid precursor protein, infection with P. gingivalisimpairs cognitive function and increases the deposition of Alzheimer’s disease typical amyloid beta plaques.

P. gingivalis produces major virulence factors called gingipains.   There are at least three types of gingipains, linked to different amino acids – lysine gingipain (Kgp), arginine gingipain A (RpgA), and arginine gingipain B (RgpB).   These are transported to the outer bacterial membrane surfaces and released into the extracellular fluid.   Gingipains are essential for the survival of the bacterium and play critical roles in host colonization, inactivation of host defenses, nutrient depletion and tissue destruction.   

Treatment with broad-spectrum antibiotics rarely eradicates P. gingivalis and may lead to antibiotic resistance.   However, blocking the activity of gingipains with agents that can break down proteins (proteolysis) reduces the virulence of P. gingivalis.  They report that they have created a library of potent small-molecule gingipain inhibitors.   Two of these, designated COR286 and COR 271 are irreversible inhibitors of the three above-mentioned gingipains.   These inhibitors were able to block neurodegeneration in mice injected with gingipains. 

Based on their investigation of P. gingivalis and gingipains, the authors conclude that small-molecule inhibition of gingipains has the potential to be disease-modifying in AD.   

There is a rather big difference between the actual conclusion of the authors of that study “small-molecule inhibition of gingipains has the potential to be disease-modifying in AD,” and proving that all memory deterioration problems are caused by P. gingivalis and implying that there is a simple and effective solution to these problems, which Henderson will reveal in the next few moments.

“If this bacteria was so powerful and dangerous, was there anything that could banish it?

In the end this could happen to anybody… our spouses… our parents and grandparents…

I couldn’t risk seeing the love of my life becoming an empty shell who would forget when and if she needs to go to the toilet…

And eventually forget basic functions like chewing her food…

I could not afford to let anyone take this away from me!   So after working alone as a wolf…

I realised I needed someone who would understand and be there at least to help me figure out how to go from here on out.

So, I decided to make some phone calls.   In the end, I kept hearing one name: Dr Jack Lane.

You see, Dr Jack was well known in his field because he set up the basis of good oral hygiene in half of the third world countries with his NGO.

And what drew me to him was the fact that he accomplished that without expensive equipment… Without expensive medicine…

Dr Jack did it all through God’s green bounty: plants!”

This has to be pretty familiar territory to Clan Gumshoe.   Serious problem, mainstream medicine doesn’t deal with it, big pharma has other fish to fry, but alternative medicine will find the way!

(Incidentally, there are dozens of Dr Jack Lanes, but I could find none who meet the characteristics of the one cited by Carl Henderson.)

Carl Henderson goes on to reveal the ingredients in his proposed “simple 30-second method that can bullet proof your brain cells against the memory-devouring bacteria.”

“I needed something that could disinfect the teeth and slow down the multiplication rate of the bacteria.

So for phase one I knew that a first step was to:

Eradicate the bacteria.

That’s when Dr Jack suggested Huperzine.. You see, according to one 2005 study, Huperzine provides an antibacterial action on the surface of your brain. In this clinical study, Huperzine destroyed microbes and bacteria much like your hand sanitizer coats and protects your hands. So, not only is Huperzine important for killing the dangerous dental bacteria that travelled to your brain…

But it’s also important for “coating” the brain in a “bacterial-proof vest”!

Not only that, but several clinical studies have revealed this herb can stabilize your cognitive function at any age due to better communication between neurotransmitters.

Studies have also shown the nourishment from this herb can reduce inflammation in a matter of minutes.”

I was able to dig up a couple of papers about huperzine in Alzheimer’s disease patients.   Huperzine A is an alkaloid derived from a plant called Chinese club moss.   It acts as an inhibitor of acetylcholinesterase.   Here’s what I said about acetylcholinesterase in the first Doc Gumshoe piece about Alzheimer’s disease, back in August 2013.   

“A handful of drugs are FDA-approved for Alzheimer’s disease, and the best any of them can do is slow the progress of dementia.   The mechanism of action of most of these drugs is inhibition of the enzyme acetylcholinesterase, which breaks down acetylcholine in the brain.   Acetylcholine (ACh)  is vital to brain function, and one of the things that happen in AD is a decline in the numbers of cholinergic brain cells, so any means of increasing the amount of circulating ACh is a potential boost in brain functioning.”

So huperzine A is another acetylcholinesterase inhibitor, like Aricept and Exelon.   Is it any better?   From the papers I could find, the answer is “no.”   One paper, which reviewed 20 studies of huperzine A found a slight improvement in cognition as measured by the Mini-Mental State Evaluation; however, one trial showed no improvement on the Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog).   Another trial found zero cognitive improvement.   The review paper mentioned that “the findings should be interpreted with caution due to the poor methodological quality of the included  trials.”    (Yang G. PLoS One 2013 Sep 23;8(9);e74916.)

Another review stated that preliminary  data suggest that huperzine A may improve cognition, citing improvements in the Mini-Mental State Examination score of 1 to 5 points.   This review also cited weak study design, and noted to the need for large scale randomized, placebo-controlled trials to establish the role of huperzine A in the treatment of AD.   (Desilets A. Ann Pharmacother 2009 Mar 43(3);514-8)

That seems to be it for huperzine A.   No big randomized trials.   Most of the citations in PubMed are several years old.   It seems to have faded from notice, except for Carl Henderson.   So what’s the next component of the potion that he was proposing to banish Alzheimer’s?

“Well, remember back to your mid-20s when your mind was as sharp as a tack? Back when you could stay up all night partying and having a good time, then make it to work on time, and do your job without getting fired, even though you were dead tired? Why can’t you do that nowadays anymore?

Well, because as we age, our brain blood flow gets weaker…
And as more and more plaque builds up…So does the mental fog!

Vinpocetine opens up your brain’s blood vessels, pumping your head full of oxygen and sparking nerve cells back to life. This new blood flow also flushes out cerebral toxins and helps your neurons fire faster so starting fast your memory recall processes! In one study, participants at the University of Leeds in England used Vinpocetine and experienced less memory fatigue and improved reaction times in a matter of days.”

Vinpocetine is somewhat controversial.   Its structure is somewhat similar to that of the familiar periwinkle plant (Vinca minor).   It is at the same time entirely synthetic, a man-made chemical, and marketed as a supplement despite the FDA’s doubts as to whether it really is a supplement.   According to Wikipedia, an analysis of 23 brands of vinpocetine dietary supplements reported wholesale labeling errors.   Only 6 of the 23 provided accurate dosage levels, and another 6 of the 23 contained no vinpocetine at all.  In June 2019, the FDA issued a warning that vinpocetine may be unsafe in women who are pregnant or who may become pregnant. Some people have anecdotally noted that their continued use of vinpocetine reduces immune function.

Vinpocetine is a phosphodiesterase inhibitor (PDI).   The best known PDI, Viagra, works by increasing blood flow to the penis.   The hope expressed in Carl Henderson’s presentation is that vinpocetine will similarly increase blood flow to the brain, improving brain function and cognition.   There seems to be no substantial evidence that this is so.   I found one study, conducted in Nigeria, which reported that treating subjects with vinpocetine improved memory function and concentration in patients with epilepsy and dementia, although the authors reported that the efficacy was minimal in demented patients.

With that exception, the studies of vinpocetine relating to cognition were overwhelmingly in rats and mice.

Here’s Carl Henderson’s third step:

“Bulletproof the entire brain and gums against the bacteria.

And that’s when I stumbled upon an interesting study published in 2014 in China on the effects of Ginkgo Biloba on gum-disease.

Sixty patients with moderate to severe periodontitis were selected and split up in a control group and a group who received Ginkgo.

They were periodically swabbed for a bacterial test and the results were absolutely insane! Ginkgo significantly decreased the detection rate of periodontal disease pathogens in just 1 week after treatment!”

Gingko biloba keeps coming up in alternative treatment discussions.   Nobody has come up with evidence that it is highly effective in any of the many ways that have been suggested, which include improving blood circulation and combating memory loss.   There are warnings against actually eating the leaves or seeds of the Gingko tree, which may be toxic.   I found one clinical trial which concluded that Gingko biloba extract may boost the effectiveness of standard periodontal drugs in treating periodontal disease.   That’s a far cry from bulletproofing the whole brain and gums against the bacteria.  (Cheng Q. Chin J Integr Med. 2014 Oct;20(10):729-36). 

Carl is now getting to the point of his presentation, which is to promote the supplement made by the company he founded.

“My question to you is this…

DO YOU WANT A SHARP, RESPONSIVE MIND… OR A DULL, SLUGGISH BRAIN THAT EVENTUALLY GIVES UP COMPLETELY?

I think you already know the answer and you’re beginning to see how these 3 ingredients can start to make a difference in your life.

You see, in the past few minutes I’ve demonstrated to you how one hidden bacteria can completely destroy the precious memories you hold so dear…

How one tiny intruder can rob you of your independence and dignity…

And why no matter how well you brush and floss, no matter how good your dentist is…

You will never get to it and it will continue to mock you as it makes its way up to your brain.

And I’ve presented three all-natural ingredients that can increase cerebral brain flow, reduce age related cognitive decline, and boost energy in your brain.

The problem is, it’s nearly impossible to get them from diet alone… and your body isn’t producing enough of them itself, which is why your mind has slowed in the first place.

And that’s why I’d love to introduce you to the fastest, safest, most effective way to recharge your brain, get your life back and protect your mind and gums long-term…

We’re Calling This Formula

ProMind Complex”

So, ProMind Complex contains Huperzine, Vinpocetine, and Gingko biloba.  But that’s not all.   He then throws in a bunch of other natural ingredients.

“…in addition to these wonderful mental health benefits, we’ve also added several more brain-boosting herbs we think you’re going to love.

In fact, when I began formulating ProMind Complex, I wanted to make sure it supported your brain health in every possible way, from every possible angle.

That’s why, along with the perfect dosage of Huperzine A, Ginkgo biloba Leaf, and Vinpocetine, we’ve also added 4 more mind-clearing ingredients to support and enhance the results you’ll experience…

Like: Phosphatidylserine, St. John’s Wort, Bacopa monnieri and N-Acetyl-L-Carnitine!”

Here’s what the Mayo Clinic says about the first of those:   “Phosphatidylserine is a dietary supplement that has received some interest as a potential treatment for Alzheimer’s disease and other memory problems.    Several studies with phosphatidylserine indicate improved cognitive abilities and behaviors.   However, improvements lasted only a few months and were seen in people with the least severe symptoms.”

We have discussed St. John’s Wort before, in the context of depression.   The Mayo Clinic points out that it is generally considered safe when taken in appropriate doses, but warns that anyone who takes prescription medications should stay away from St. John’s Wort.    There are a number of side effects, mostly not life-threatening, and a great many possible drug interactions.   St. John’s Wort mostly impairs the effectiveness of these drugs, because it reduces their activity by acting as an agonist of the hepatic channel through which those drugs are excreted. 

We have also discussed Bacopa monnieri in previous posts.   As with many other plant-derived supplements, the evidence supporting its use for any medical condition, including AD, is somewhat slim.   It is classified as a nootropic, meaning an agent that stimulates brain function, and it has been used for that purpose in Ayurvedic medicine.   There does appear to be some evidence that Bacopa monnieri reduces the concentration of a couple of agents that are known to cause inflammation in the brain, these being tumor necrosis factor a (TNFa) and interleukin 6 (IL6).   The study reporting those effects confirmed them only in vitro, did not conduct any trials in humans, and limited itself to a suggestion that extracts of the plant might be useful in delaying dementia related to brain inflammation.   (Nemetchek M. J Ethnopharmacol. 2017 Feb 02;197: 92–100).

Finally, Acetyl-L-carnitine, which can be used for a wide variety of mental disorders including AD, age-related memory loss, depression, and thinking problems related to alcoholism, Lyme disease, or poor liver function.   It is sometimes used in Down syndrome patients, bipolar disorder, amyotrophic lateral sclerosis (Lou Gehrig’s disease), attention deficit disorder, multiple sclerosis, fibromyalgia, and facial paralysis.   The evidence supporting the use of acetyl-L-carnitine in any of these conditions is dubious.

Then Carl Henderson, having named (and touted!) the seven ingredients in his ProMind Complex, goes on to extol its amazing benefits.

“In a nutshell, what I can promise with ProMind Complex, is that you can be more creative, think faster, listen better, respond to situations lightning-fast, and concentrate with deeper focus than you did when you were studying for your SATs back in high school.

Go from forgetting where you left your keys or your purse… To being able to write your family memoirs!
Tell stories to your friends and family in detail so vivid, they’ll think they were there with you!
And if that weren’t enough, the nutrients from ProMind Complex will also better fuel your brain to help you…
Prevent embarrassing “senior moments” so you can keep your confidence and your sanity…Dismantle negative feelings and anxiety that keep you from achieving your goals…
Easily go from a chronic gloomy mood to feeling optimistic on a consistent basis by increasing healthy production of your “feel good” hormones in your brain…

If you’ve tried other formulas that have let you down in the past or have cost you an arm and a leg for cheap “filler” ingredients that only left you with very little or no results at all…

YOU’RE GOING TO BE IN FOR A NICE TREAT WITH 

ProMind Complex.”

After more glowing celebrations of just how sharp your mind will be with ProMind Complex, Carl goes on to quote prices – $69 for a one-month supply down to $49 per bottle for a six-month supply.   And of course an absolute iron-clad money back guarantee if you aren’t completely sure that ProMind Complex is the best thing you’ve ever come across.

Why am I dubious?   My skepticism comes in several flavors.   The promotion starts out by asserting that Alzheimer’s disease and related memory problems originate in periodontal disease.   There may indeed be some relationship between gum disease and brain dysfunction, but at most it’s only a small part of the story.   And besides, most of the seven ingredients in ProMind Complex have no conceivable effect on gum disease.   

Considered individually, each ingredient has possible beneficial effects, even though the evidence is not strong.   It’s hard to say whether there may be interactions between these seven ingredients.   They all have some effects on our physiology, and it is possible for these effects to be harmful when they are contained in the same pill.   Also, it is not possible for buyers of ProMind Complex to know for sure what they are getting.   I recall a couple of studies – one in Canada and one done by the Harvard Medical School (yes, really Harvard!) – which reported that in a surprisingly high percentage of supplements the actual contents of the pill were not as stated on the label.   In some cases, the particular ingredient that the supplement was supposed to contain was entirely absent.   I am not saying that this is the case with ProMind Complex, but the absence of regulation of any kind certainly raises doubts.

Usually, my reservations concerning supplements are that the promotions play on mistrust of mainstream medical practice and, of course, hostility towards Big Pharma.   So, “cures” for common conditions such as type 2 diabetes and elevated cholesterol start out by denigrating widely-used treatment options.   Promoting the alternative “cures” for these and many other conditions has the effect, in my opinion, of persuading the credulous to substitute a form of treatment that most likely won’t do them any good for treatments that seem to work pretty well most of the time.  

In the case of Alzheimer’s disease, that particular criticism does not apply, because there is no established form of treatment that works at all, much less a form of treatment that works “pretty well most of the time.”   ProMind Complex does have ingredients that supposedly speed up cognition and also attack the population of the P. gingivalis in our brains that supposedly leads to the brain-clogging associated with Alzheimer’s and dementia in general.   It probably won’t hurt and might even help.   I can’t say anything more definitive, and I’ll have to leave it at that.          

One more point, possibly important in several ways.   I mentioned above that most of the named authors of the study (the one that was highlighted by Carl Henderson as “proving” that the cause of AD was gum disease) worked for an outfit called Cortexyme (Nasdaq: CRTX).   As it happens, Cortexyme has a clinical trial going in which they are testing the efficacy of those above-mentioned potent small-molecule gingipain inhibitors in Alzheimer’s disease.   The trial (GAIN) has enrolled more than 400 volunteers and is due to announce interim results next month.   Doc Gumshoe will be on the alert.

* * * * * * *

Should I have put that conclusion of mine right up front, so that you could be spared reading this longish (but I hope not tiresome) discursion?   I’m not sure.   At least one Doc Gumshoe commenter suggested that I should include a one-paragraph summary of the whole post and put it at the head, so that busy readers could just get the gist of where I was going without all the tiresome steps in the way.   But I want you to see and understand how and why I got to that conclusion.  

In any case, this was a little holiday from COVID-19, to which I shall return in my next piece.   There’s actually quite a lot of news, some of it quite favorable.   Best to all and thanks for all comments, of all flavors.   Michael Jorrin (aka Doc Gumshoe)