You’ve seen TV commercials for Prevagen on cable news? While you watched the Capitol rampage and the second impeachment trial, a Prevagen ad popped up, surely. Even if you watched for mere seconds before turning it off in horror, you were bound to see a Prevagen commercial.

What is Prevagen? Prevagen is a supplement touted as a reversal for age-related memory loss. The manufacturer, Quincy Bioscience in Madison, WI, claims that in a clinical study Prevagen “…was shown to improve memory in subgroups of participants with normal cognitive aging or mild impairment.”

The main ingredient in Prevagen is a photoprotein extracted from jellyfish, apoaequorin. Apoaequorin plus calcium provide the cool bioluminescence jellyfish enjoy. Like many ingredients, apoaequorin is digested in the human stomach and gets nowhere near the brain, where its function as a photoprotein would… what? Light up the interior of the skull? Sounds like fun, but not useful for memory improvement. Unless the skull is a dark attic, the photoprotein a flashlight, and the missing memory a box of old photos in a corner. They’re not.

The results of Quincy Bioscience’s Prevagen study consist of a bar graph showing a rise in recall tasks over 90 days. But there’s no way to know what these numbers refer to, how many people were studied, or other important details, like what recall tasks? Four words repeated in a row? What did you have for breakfast? Who’s the President of the United States?—scratch this question—it no longer works as a recall task for everyone. And no information is provided about effects on memory after 90 days. The fine print under the graph says that the supplement “improved recall tasks in subjects” without explaining what this means.

The results of the clinical study were not peer reviewed by any member of the scientific literature body nor the FDA. In fact, the U.S. Federal Trade Commission charged Quincy Bioscience with fraud in 2012 (the case is ongoing).

So how is it we still suffer from Prevagen TV advertising as it remains on the shelves of pharmacists who may or may not recommend it to their customers? Because supplement manufacturers are not required to undergo the FDA process required for prescription drugs. That process requires proof of clinical safety and efficacy. The prescription drug manufacturing process and product contents are reviewed and analysed completely. Limits and standards are set for what should be in the drug, and what should not, and are followed over time for expiration dating. Note that the FDA is reviewing the lack of processes in place for supplements with an eye toward increasing rigor.

Supplement makers are allowed to make a connection between their product and the body’s structure and function. Supplement makers currently cannot claim that their product cures or prevents disease. Prevagen’s marketing runs mighty close to the wind with hints about preventing Alzheimer’s or dementia.

The question is, how do they get away with it? Well, there’s no rigorous review of their data and there’s vigorous data massage. And then there’s p-hacking (the p value is the measurement of statistical significance after analysis of data)—or going back in to re-analyze. As Anthony Pearson, MD, reported in https://www.medpagetoday.com/blogs/skeptical-cardiologist/80321, “A great article on the Prevagen case from the McGill University Office of Science and Society summarizes the problems with this re-analysis: This is an after-the-fact, unplanned exploration of the data to see if anything else of interest happened in the trial. Some might call it a fishing expedition. Scientists do this all the time, but with a big caveat: post hoc results are considered tentative, not conclusive. Before they’re accepted as valid outcomes, they need to be confirmed by additional studies.

That’s because random events happen all the time in scientific studies. Some of them may seem statistically significant, but they’re flukes and not the result of cause-and-effect. And the more post hoc analyses you do (like the more than 30 Quincy Bioscience did), the more likely you’ll encounter these chance results.

Scientists guard against accepting them as real by setting a high bar for statistical significance and by not accepting post hoc findings until they’ve been tested again. For a more in-depth analysis, see the deep dive by Jann Bellamy at Science-Based Medicine in “Prevagen goes P-hacking.“

Supplements have strong anecdotal support and Prevagen is no outlier. Unfortunately, when put through a rigorous study that generates peer-reviewed data, there is little evidence of any support or improvement linked to many of them. Prevagen is not an outlier there either.

But let’s get back to the commercials, which add weirdness to this tale. Each Prevagen commercial features a different Prevagen taker or set of takers. The advertising premise is a few minutes spent with a real person(s) really taking Prevagen with good results. They don’t seem like actors and they don’t seem unalike. Middle class, older of course, the majority are white, but there is one Black man, a substitute teacher and inspirational speaker by trade. All of them, however, have a very strange affect, one that at least hints at some sort of affliction already in the works.

In one commercial, the protagonist is an older man. He is a fly fisherman (he has a beautiful cast), has six children and grandchildren. His speaking voice is low and slow. His movement is ponderous. He reports slowly that Prevagen has helped him an awful lot.

In another version, another older man is shown preparing to shoot (but not shooting) a basketball. He praises his own memory. His voice is also low and slow, his movement also ponderous.

In yet another version, an older woman lives in the mountains and has an art studio in her house. Every day she goes to her studio first thing, where she encounters people who praise her artwork (who are they and how did they get into the house?). She speaks and moves more quickly than the two men, her face is more mobile, but she seems quite…off.

Then there’s the older married couple. The couple are shown performing their various happy, healthy older persons’ activities. They walk—she follows him as he moves as though trekking up Denali. They write—laptops in evidence, he says, “We consult, but we also write,” pronounced RRRRiTTTe. Consult about what? Write what? He reads the newspaper aloud while she hangs on his every word. She gets a star turn to announce that after 11 years, Prevagen is still helping her (the company’s answer to what happens after the 90 days). Let’s see, 11 years x 12 months/year x $32+shipping/30 tablets = $4224+ (x2 for “extra strength” Prevagen). More than enough for a super nice pre-pandemic vacation or a super donation to a food bank now.

Prevagen use can’t be to blame for their shared idiosyncrasies, can it? But would any potential customer actually want to behave, sound or move like any of them? Is it a side effect of Prevagen? Doesn’t the ad agency see that? Perhaps they’re taking Prevagen, too.

Some may say, what’s the harm? The consumers in the commercials aren’t cutting back on food in order to take Prevagen. Beyond lifestyle recommendations, science and medicine haven’t offered anything up to seniors terrified of dementia, so why not? The placebo effect is a strong one, so if consumers feel that it helps, why not?…but it doesn’t help and it could harm them further. Severe side effects have been reported as linked to Prevagen use.

Robert H. Shmerling, MD wrote in https://www.health.harvard.edu/blog/fda-curbs-unfounded-memory-supplement-claims-2019053116772 “Unlike prescription drugs, supplements are not thoroughly tested or evaluated. While dietary supplements might provide benefits in certain cases, it’s vitally important that their makers not make unfounded claims to exploit consumers. And, of course, these products should contain only what they’re supposed to contain.”

In other words, aside from the apoaequorin, Prevagen consumers don’t know what they are consuming exactly. What else is in it? They also don’t know the quantity or quality of that mystifying ingredient. Even the origin of the apoaequorin is in question: extracted from jellyfish or engineered in a lab E. coli strain? Only the FDA submission and approval process (and yes, it’s a long, expensive and labor-intensive one) can provide that knowledge by rigorously reviewing both the manufacturing and clinical data required by law.

Prevagen’s producers did not want to wait the ten plus years required for peer and FDA review—and the threat of failure to approve—before raking in millions https://www.wired.com/story/prevagen-made-millions-fda-questioned-safety/. But at what real cost to the consumer?

For more musings on modern life, see https://www.constancegemmett.com/unprecedented/