How could I resist this tease?   I’m the guy, after all, who needs to stir his little grey cells to recall the name of that beautiful shrub growing at the northeast corner of our house.   Eureka, I’ve got it! – it’s called viburnum.   I’ve always attributed my lapses in memory to the likelihood that my noodle is crammed to the utmost with 10 to the 10^th to the 10^th factoids ranging from the particulars of Addison’s disease to Zollinger-Ellison syndrome.   If I keep all those things stored in my cranium, it’s difficult to cram any more in there.

So I found this hard to put down.

“UCLA neuroscientists develop incredible brain age-reversing  breakthrough! 

Top research shows this…

1-Hour “Brain Lift” Helps STOP Age-Related Memory Loss

Now YOU can use their same powerfully simple technique at home to help improve your memory by 700% in just 1 HOUR, plus so much more…”

Having checked up on a considerable number of promotions of this sort, I start out with a skeptical turn of mind.   The notion of improving my memory by 700% in just one hour strikes me from the outset as a colossal exaggeration, even if there is some merit to whatever it is that these UCLA neuroscientists came up with.   And let me say that the single disclaimer line that introduces the tease doesn’t do anything to make me more of a believer.   Here’s the disclaimer:

“These statements have not been evaluated by the FDA.   This product is not intended to diagnose, treat, prevent, or cure any disease.”

Many people, including quite a few Gumshoe denizens, will take that disclaimer as basically meaningless, based on their firm conviction that the FDA is just a toady for the pharmaceutical industry rather than an honest government agency dedicated to making sure that there is legitimate evidence supporting the claims made by the makers of products that are meant to contribute to the health of our nation.  

I note that one of the comments appended to a previous Doc Gumshoe posting asserted that pharmaceutical companies had to hand over to the FDA the sum of two billion dollars in order for the FDA to move forward with the approval of a candidate drug.   This is simply not so.  Here’s what the FDA says:   

“For fiscal year 2018, drug application fees are: $2,421,495 per full application requiring clinical data, $1,210,748 per application not requiring clinical data or per supplement requiring clinical data.”

That’s million, not billion.   

What particularly piqued my interest was the statement that the source of this miracle brain booster was UCLA neuroscientists.   That assertion was repeated numerous times in the presentation, and it was not tempered in any way.   Here’s a typical repetition:

“No—this easy, UCLA-patented “Brain Lift” technique can improve your memory by a whopping 700% just 1 HOUR from now. …

“It took the most respected neuroscientists, at the most prestigious memory lab in the world — UCLA’s neurology research center— and a decade of trial and error to develop.

And ever since—in study after study—this brain lift technique has shown miraculous memory-boosting results.

Like in a groundbreaking 2014 study, where researchers put the brain lift breakthrough to the test on a group of seniors 60 and over.

The scientists separated the seniors into two groups—a test group that would get the brain lift—and a placebo group that wouldn’t.

Then, on that very first day… just 1 hour into the study…

The researchers ran a few tests and discovered something they never expected…

The men and women who got the brain lift were ALREADY IMPROVING AT A RAPID PACE…

In fact, their memory was working SIGNIFICANTLY better than it had just 60 minutes earlier…

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

So much so that they had blown past the placebo group at a staggering clip…

Scoring a WHOPPING 700% BETTER ON MEMORY TESTS just 1 HOUR into the study.

But that wasn’t all the researchers saw in that first hour …

After the scientists pulled their jaws off the floor, they ran another test…

And discovered that the brain lift not only boosted memory and recall—it also improved how well these seniors were thinking.

Giving them a MEGAWATT SURGE IN BRAINPOWER and enhanced, LASER-LIKE FOCUS IN JUST 1 HOUR.”

So, what’s the brain lift?   You have to persevere with the presentation for a while before you get even a hint.   First, you have to listen to a recital of the terrible things that happen when your memory begins to get faulty.   The spokesperson introduces herself and also brings her mother into the story.   Of course, it’s her mother whose ability to remember things is getting more than a bit faulty.   And we get to hear how immensely improved her mother’s memory becomes after the fabulous one-hour brain lift.   Finally, we come back to the UCLA neurology department and learn that what they accomplished was improving the bio-availability of curcumin.   

Curcumin!   Curcumin, yet again!   Curcumin is a yellow substance in the rhizomes of the turmeric plant, Curcuma longa.   Those rhizomes, which are sort of root clumps like ginger, are cooked, dried, and used as spices in many Asian curries.   Curcumin is also used in cosmetics mostly because of its color, and has recently become one of the darlings of the supplements industry and its spielers, several of whom have come to the attention of Doc Gumshoe, including the notorious Dr Al Sears.   

Does curcumin itself have demonstrated health benefits?   Yes, it does, but these are limited.   The one medical use for curcumin for which there appears to be reliable evidence is osteoarthritis.   A small randomized controlled study (53 subjects) compared a supplement containing curcumin plus glucosamine and chondroitin with placebo; both groups of subjects also received exercise therapy.   No surprise, the patients taking the supplement had less pain than those on placebo.   The glucosamine-chondroitin combination has been reported, in some cases, to provide relief of joint pain by, in effect, lubricating the joint.   

Also, curcumin has been reported to have some anti-inflammatory effectiveness.   As to the way curcumin exerts these anti-inflammatory properties, the landscape is shrouded in dense fog from which vague outlines of potential anti-inflammatory pathways may be tentatively inferred.   There appears to be evidence, mostly in animals, that treatment with curcumin reduces the presence of some markers of inflammation, such as tumor necrosis factor alpha (TNFα), which is a malefactor in rheumatoid arthritis, and also of the enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), both of which are implicated in liver damage.   A suggested mechanism whereby curcumin achieves this result is through upregulation of peroxisome proliferator-activated receptor gamma (PPARγ), which has been associated with anti-inflammatory effects.   I would point out, as a cautionary note, that this particular mechanism was described in a journal entitled PPAR Research, suggesting a certain predisposition. 

However, there is one important problem with using curcumin as a drug: it is very difficult to get enough of the active ingredient into the circulation to have any therapeutic effect whatever.   It is very poorly absorbed when taken orally, and it has a very short half-life, meaning that the duration of action is brief.   

Returning to the promotional piece:

“For years, curcumin was a huge disappointment to the medical community—great on paper, but nearly useless in real life.

That is, until an elite team of UCLA neuroscientists got their hands on it.

It took a decade of research, and testing almost 200 different variations—but these scientists finally struck gold…

With a solution that was right under their noses the whole time!

You see, for thousands of years Indian doctors prescribed their patients turmeric (the root curcumin comes from) mixed into some kind of fat—like butter or cream.

So the scientists got the idea to try creating a similar mixture—but at a molecular level…

By adding phospholipids (fat molecules) to curcumin molecules.

And when they tested it—this enhanced curcumin stunned them all…

Because people could absorb it 6500% better than regular curcumin!”

A bit of sleuthing produced results.   A 2018 paper entitled “Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial” was published in the American Journal of Geriatric Psychiatry, and every single one of its sixteen authors was in the UCLA Department of Psychiatry and Biobehavioral Sciences.   (Small GW.   Am J Geriatr Psychiatry 26.3 March 2018)

The trial did report some benefits with the bioavavailable curcumin formulation, but nothing like the 700% better memory in 60 minutes touted in the promotion.   

The paper reported that previous research had demonstrated that healthy volunteers consuming 30 mg of a bioavaliable curcumin formulation had 27 times the blood concentrations of those consuming standard curcumin powder.   The study evaluated 46 healthy volunteers with normal aging and at most mild cognitive disorder, but not dementia.   Based on research that indicated that curcumin had positive effects on memory, the trial chose several validated instruments as primary outcome measures after 6, 12, and 18 months of treatment.   Of the 46 subjects, 40 were included in the data analysis of the memory and cognition testing.   Of these, 21 were assigned to the curcumin group and 19 to the placebo group.      

For verbal memory, the Bushke SRT was the primary outcome measure.   This test presents 12 words to the subject, who is asked to recall immediately as many words as possible.   The examiner then presents words that the subject was unable to recall without prompting and repeats the procedure until the subject can recall all 12 without prompting.   Other measures include the Consistent Long Term Retrieval score, which is based on the number of words that the subject recalls and indicates how well the subject consolidates information during the learning phase.   

Other measures include the Brief Visual Memory Test-Revised and a test that measures sustained attention, termed the Trail Making Test.  Because mood can influence cognition, the Beck Depression Inventory was also used.     

The trial also conducted procedures aimed at measuring brain deposition of amyloid plaques and tau tangles with positron emission tomography (PET) scans, using a proprietary marker developed by the UCLA researchers.   This marker is named Flortaucipir; in that paper the method was identified with the label F-18 FDDNP.   

The outcome measures used in the study included the scores on each measure as well as the effect sizes (ES), which calculate the difference in the effects of the curcumin versus placebo as measured by each of the memory and cognition tests.   For the Bushke SRT, after 18 months, subjects in the curcumin group showed significant improvement of 28.1% from the baseline score, versus 2.6% improvement in the placebo group.   The effect sizes in the curcumin versus placebo groups were highly significant, 0.63 vs 0.06 (P = 0.002).   For the primary visual memory outcome measure, at 18 months the ES was 0.50 for the curcumin group versus 0.26 for the placebo group (P = 0.2), not attaining significance.    

(Note: the P values indicate the likelihood that the result was reached through chance.   For example, the P value of 0.002 indicate that on the SRT test, the likelihood that the difference in effect sizes between the curcumin and placebo groups were reached through chance was two in a thousand, therefore highly significant.   But on the primary visual memory test, the P value of 0.2 indicates that the likelihood that the difference between curcumin and placebo groups were reached by chance were one in five, therefore not considered to be significant).

As to the mechanism through which the bioavailable curcumin improved some aspects of memory, researchers investigated its effects on the amyloid plaques and tau/neurofibrillary tangles that have been found in the brains of persons with memory and cognitive disorders such as Alzheimer’s disease.     

The measure of brain deposition of amyloid plaques and tau tangles differed significantly between the curcumin and placebo groups as measured by PET scans of different brain regions.   In the amygdala region, deposition levels decreased significantly in the curcumin group (ES = – 0.41, P = 0.04) but not in the placebo group (ES = 0.08, P = 0.6).   

In the hypothalamus, the decrease in deposition in the curcumin group was not significant (ES = – 0.30. P = 0.02).   However, there was a significant increase in deposition in the placebo group (ES = 0.26, (P = 0.05).    

The authors carefully stated conclusion was that daily oral administration of their bioavailable curcumin “may lead to improved memory and attention in non-demented adults,” adding that “symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory.”

That paper makes it clear that the bioavailable curcumin they used in the trial was Theracurmin.   But that’s not the bioavailable supplement touted by the “One Hour Brain Fix” promotion.   That ballyhoo goes to some lengths to make it clear that the particular curcumin preparation that they are boosting is not the specific one developed and patented by UCLA.   

“There’s just one snag.

It’s really difficult to get this special UCLA-patented optimized curcumin.

And almost no one but scientists and researchers like me even know about it.

But after seeing the astonishing research, and watching how it’s helped my mother get sharper and more confident with each passing day—I knew I had to get the word out.

Because EVERYONE should be taking this stuff.

So I reached out to some insiders I know affiliated with UCLA and was able to secure a small supply of their optimized curcumin.

That’s why I’m writing you today—because now you can finally try it yourself in Gold Leaf Nutritionals’ revolutionary brain health formula Brain Support Plus.

It delivers the exact same 400 mg dose of optimized curcumin used in the research studies.”

Presumably, what the “One Hour Brain Fix” folks did was copy the UCLA optimized curcumin as closely as they could.   But their version, from Gold Leaf Nutritionals, is certainly not the preparation that was used in the above-mentioned clinical trial.

However, having essentially claimed for themselves the benefits delivered by Theracurmin, they go on to make further claims of near-miraculous proportions.

“But as incredible as optimized curcumin is—it didn’t actually deliver those results all on its own.

Because Brain Support Plus also includes one other crucial ingredient for both a powerful memory—and LIGHTNING-FAST THINKING.

And legend has it, that this secret was guarded for centuries as a sacred memory herb…

You see, going all the way back to the 6^th century—medical books described how ancient scholars would use this potent herb to improve their intellect, and to memorize epic stories, and lengthy scriptures.

Now, modern science is proving just why this early “smart pill” was so effective.

You see, this herb—known as bacopa—is a powerful brain rejuvenator.”

So, having appropriated the evidence for brain boosting that was actually garnered by Theracurmin, they go further.   This promotional piece claims that it is faster and more effective than the so-called “UCLA patented” version, because it contains another miraculous ingredient – bacopa. 

What is bacopa?   Well, bacopa monieri is a member of the figwort or snapdragon family, and it has been used in Ayurvedic medicine for epilepsy and asthma.   There’s a certain amount of evidence supporting bacopa’s effectiveness in matters related to brain function.   I was able to turn up eight animal studies, mostly in mice and chronically-strained rats.   And then there were three studies focusing on cognition or memory in humans.   One found that it was safe in a population of children and adolescents, resulting in significant cognitive improvements in the language/ behavior/cognition domains.   A second was a meta-analysis of nine studies concluding that bacopa had the potential to improve cognition but with the caveat that well-designed studies were needed to compare bacopa with alternative medications.   And a third study tentatively concluded that bacopa monieri, coupled with cognitive training, might ameliorate age-associated cognitive decline. 

The Brain Support Plus promotion isn’t quite done with its claims at that point.   Yes, there’s more!

“I still haven’t told you about the most important thing it does…

Because it can also CLEAR OUT THE BRAIN SLUDGE GUMMING UP YOUR MENTAL GEARS .

You see, as you get older, a nasty gunk called amyloid protein starts building up inside of your brain.

This sticky sludge slows blood flow to your brain cells—so they don’t get all of the oxygen and nourishment they need to stay healthy and work their best…

It also blocks up the pathways your neurons use to relay messages in your brain…

That means your thinking slows down…

You struggle to pull out the right word…

Or match a name to a face…

You lose your train of thought…

You forget what you were just doing, or why you walked into a room…

You drift off, you zone out, you slip up…

It takes some time to notice, but amyloid sludge slowly makes you foggy and forgetful.

And here’s the really scary part—EVERYONE HAS IT.

That’s right, it doesn’t matter how healthy you are—it’s just an unavoidable part of aging.

So if you experience any of the symptoms I mentioned—it’s likely amyloid sludge build-up starting to slow you down.

But now—for the first time ever— you have a way to fight it.

Because remarkable preliminary research shows that optimized curcumin can actually help clean out that brain gunk…

I won’t get into all of the complicated science, but basically, studies show that once optimized curcumin gets a hold of amyloid sludge, its potent antioxidant power dissolves it.

Like Mr. Clean for your brain!”

We note that the Brain Support Plus folk make no claim about Alzheimer’s.   Of course, the statement about optimized curcumin “cleaning out that brain gunk” is  a reference to the paper by the UCLA team that we discussed earlier.   But that was about Theracurmin, not Brain Support Plus. 

An additional item of interest in connection with that UCLA paper is that Dr G. W. Small, the first-listed author, received a letter from the FDA calling the method used in that study into question.   Here’s a bit of what the letter said, after quoting a number of the claims made by the UCLA team:

“The above claims and presentations make numerous conclusory statements about the safety and effectiveness of FDDNP, such as suggesting that it has a “high safety profile” with “no reported adverse effects,” and that it’s the “only available non-invasive method to measure the distribution and level of brain tau…” to improve brain diagnostics in various neurological conditions that control memory, thinking, and mood. Thus, these claims and presentations suggest in a promotional context that FDDNP, an investigational new drug, is safe or effective for such uses, when FDA has not approved FDDNP for any use. 

Conclusion and Requested Action 

For the reasons discussed above, FDDNP is misbranded under section 502(f)(1) of the FD&C Act and in violation of section 301(k) of the FD&C Act. The claims and presentations in the website are concerning from a public health perspective because they make representations in a promotional context regarding the safety and efficacy of an investigational new drug that has not been approved by the FDA.

OPDP requests that UCLA immediately cease violating the FD&C Act, as discussed above. Please submit a written response to this letter on or before March 6, 2015, stating whether you intend to comply with this request and explaining your plan for discontinuing use of such materials.”

As it happens, a paper has just been published in JAMA Neurology reporting the results of a very small case control study using that same Flortaucipir to assist PET imaging to detect Alzheimer disease pathology.   The study reported that visual reads of these PET scans corresponded with postmortem examinations of the brains of Alzheimer’s victims with regard to neuropathologic change, which describes a combination of neurofibrillary tangles and amyloid plaque.   

So, even though Dr Small and his UCLA colleagues got their wrists slapped for using the Flortaucipir F-18 FDDNP technique to track the effects of Theracurmin, there may be a reason to believe that the modified curcumin, whether in Theracurmin or in Brain Support Plus, actually reduces the action of either amyloid beta or tau.   We’ll leave that as an open question.   The UCLA group has a certain amount of mud in its eyes, but in their defense, treading the line between seeking approval for a drug and promoting a supplement is a tricky business.

The claims about bioavailable curcumin, bacopa, and the effects on amyloid don’t exactly translate into 700% improvement in memory and cognition in 60 minutes.   How the Brain Support Plus folks got there is a mystery.   Whether it’s speculation or multiplication or fabrication I can’t say.   All I can say is that Doc Gumshoe has been unable to unearth any evidence whatever for that claim.

This brings us to an inevitable question.

What would constitute reliable evidence for a claim of that sort?

Of course, we recognize the “1-Hour Brain Lift” piece as advertising, and as such we put it in the same category as a lot of the over-the-top advertising that comes at us every day, including the teases that Travis decodes and the ads for everything from household cleaners to retirement communities in Florida.   Yes, they’re exaggerated, but there might just be some truth in them.

Certainly, when I hear that a particular remedy has been used in Ayurvedic medicine for a millennium or two, my immediate reaction is skepticism.   I temper that reaction with the understanding that the basis for using that remedy is not simply pure superstition, but experience.   Which is to say, at some point, somebody used that particular herb or root to try to alleviate the illness of some afflicted person, and it worked.   Or seemed to work.   That is, the sick person drank the infusion and felt better.   The improvement in that person’s symptoms came after taking the infusion, so it must have been the infusion that did the trick.   Must have been.   

Or could it have been something entirely different?   

With repetition of the beneficial effect, as the infusion is given to more persons with similar afflictions, the chances that it really was the infusion that led to the cure seem to improve.   So if this remedy continues to be used for century after century, it’s likely that there is at least some benefit.

In other words, I am not ready to dismiss any remedy stemming from Ayurvedic or other folk medicines as simply examples of the post hoc propter hoc fallacy, which Doc Gumshoe has discussed before in these pieces.   Some obviously have merit.   For example, willow bark infusions were used for centuries to relieve pain, and it was based on the effectiveness of this brew that aspirin – acetyl salicylic acid, Salix being Latin for willow – was developed.   First somebody observed that folks who took willow bark tea experienced pain relief, and so, post hoc propter hoc, it must have been the willow bark tea that provided that benefit.   And after several centuries, that conclusion has been borne out.

The problem is that a huge number of post hoc propter hoc assumptions have not panned out.   It’s for that reason that in order to be accepted as a genuine drug that can be used to treat pain and illness, some proof is required, and the only way that any one has figured out to confirm or refute those assumptions is a rigorously conducted clinical trial, in which the proposed remedy is compared against a placebo, in a sufficient number of persons to minimize the possibility that the results are due to chance or to other factors.   

That’s not easy, and it tends to be extremely expensive.   One of the arguments that the promoters of supplements usually make is that clinical trials are too expensive if the proposed drug cannot easily be patent protected.   

We see that in the conflict between Theracurmin and Brain Booster Plus.   It looks, judging by the clinical trial conducted with Theracurmin, that the UCLA group is shooting for eventual FDA approval, while Brain Booster Plus is looking to hitch a ride on whatever evidence UCLA is able to summon up.   

The evidence, such as it is at this point, strongly favors Theracurmin over Brain Booster Plus.   The latter throws bacopa into the mix, but the evidence for that is meager.   I would say that Theracurmin is definitely worth considering.   

As for myself, for now, at least, I’ll stick with these writings to keep my brain busy and active, and rely on your comments to keep me on track.   Thanks to all, stay well and be well.   Michael Jorrin (aka Doc Gumshoe)   

(Ed. Note:  Michael Jorrin, who I dubbed “Doc Gumshoe” many moons ago, is a longtime medical writer (not a doctor) who shares his thoughts on health and medicine with our readers a couple times a month.  He does not offer personal health or investment advice, and does not generally write about investment ideas, but has agreed to our trading and disclosure rules)