Illustration: Jaedoo Lee

The Predatory Scam of Memory Supplements

What the federal lawsuit against Prevagen says about the American supplement industry and the brain

About one month went by until Mary realized she no longer had trouble remembering other people’s names. Jim says it only took three weeks for him to notice an improvement in his memory. Meanwhile, Sue experienced perhaps the most profound effects: She’s less absentminded, a better multitasker, and her recall of people’s names and faces has only gotten better. Her co-workers have noticed, too.

Folks like Mary, Jim, and Sue have been highlighted in commercials, radio spots, social media posts, and earnest-sounding infomercials produced by Quincy Bioscience, a Wisconsin-based supplement company. The television spots have aired on prominent cable networks such as CNN and Fox News. They might even be familiar to you.

In most of the spots, a narrator makes an argument that people who take drugs and supplements for their hearts, joints, and digestion are missing a critical organ: the brain. Each TV spot then pivots to the testimonials of everyday people who claim they no longer forget names, repeat the same stories, or misplace their car keys. They’re held up as veritable—and verifiable—success stories, the chief beneficiaries of one specific supplement: Prevagen.

“We see probably 60 patients in our office a day. The doctor asked several of us if we remembered this certain patient, and I was the only one that could come up with her name,” says Sue in one such infomercial. “They just are amazed at my memory at work.”

For nearly 15 years, Quincy Bioscience has made a name for itself by making and marketing Prevagen, a supplement for improving memory. Founded by Mark Underwood and Michael Beaman in 2004, the company came into being just as the wider market for brain-health supplements started growing rapidly. From 2006 to 2015, sales of products that purportedly boosted, improved, or maintained a person’s memory doubled to $643 million in the United States, according to data collected by the U.S. Government Accountability Office.

Quincy Bioscience alone made up a sizable chunk of that market share: From 2007 through the middle of 2015, sales of Prevagen totaled about $165 million. Still commonly found in drugstores like Walgreens and CVS, as well as through online retailers like Amazon, a 30-day supply of Prevagen pills can sell for anywhere between $16 and $70, depending on the seller and the dosage. (There are regular strength, extra strength, and “professional” formulations, each with 10, 20, and 40 milligrams of supplement per pill, respectively.)

While ginkgo biloba, coenzyme Q10, and fish oil are some of the most commonly marketed memory supplements, Prevagen, on the other hand, is known for an entirely different main ingredient: apoaequorin, a protein isolated from the Aequorea victoria jellyfish that the company says supports brain function as people age. In its advertising materials, Quincy Bioscience touts Prevagen as a safe, clinically proven way to improve memory within 90 days and even reduce the mild memory problems associated with aging.

Such cognitive benefits seem too good to be true — and, in the estimation of the Federal Trade Commission (FTC), they are.

In an ongoing lawsuit now entering its third year, the FTC, along with the New York state attorney general, is seeking refunds for customers, alleging that Quincy Bioscience violated federal law by making unsubstantiated claims about the efficacy of Prevagen. In the federal agency’s view — which it lays out in a 32-page complaint submitted in 2017, complete with transcripts of past Prevagen commercials — the company is engaging in false, deceptive advertising.

Although a judge initially dismissed the FTC’s lawsuit in September 2017, a federal appeals court revived it in early 2018, arguing that federal regulators plausibly alleged that Quincy Bioscience made false claims about Prevagen’s effectiveness. In 2019, the court dismissed all claims about company co-founder Michael Beaman. But the action continues against the company as well as co-founder Underwood. So for now, the case — and the debate — drags on.

Prevagen has been underneath the federal microscope before. In 2012, the Food and Drug Administration (FDA) sent a letter warning Quincy Bioscience that it was violating federal law regarding how supplements are marketed and sold in the U.S., alleging that the apoaequorin in Prevagen was synthetically produced, not naturally extracted. The agency also documented more than 1,000 “adverse events”: Between 2008 and 2011, people who had taken Prevagen reported having symptoms like chest pain and vertigo. Some people, according to the FDA, also experienced seizures.

Across the whole market of memory supplements, many are purchased and consumed by seniors. A survey of more than 800 adults over 50 conducted by AARP last year found that more than one-quarter take some sort of memory supplement. According to the FTC, claims that Prevagen will improve memory are just opportunistic sales pitches hawking an unproven product to older Americans.

As the lawsuit is ongoing, the parties in the case declined to comment directly to Elemental. In answers filed with the U.S. District Court of the Southern District of New York, both Quincy Bioscience and Underwood deny engaging “in any deceptive business practices or false advertising.” Over the years, Quincy Bioscience has pointed to dog studies and a human clinical test it carried out a decade ago to prove that Prevagen works.

“Memory is not one process, but many different processes in the brain, involving a multitude of brain regions, cell types, and molecular mechanisms.”

Certainty over the effectiveness of any drug or supplement for the brain draws skepticism. Researchers who study human memory note it’s a complex amalgam of different functions and brain regions. Can a drug really be designed specifically to improve memory?

“The answer is no. There’s definitely nothing out there,” says Kostas Lyketsos, MD, director of the Memory and Alzheimer’s Treatment Center at the Johns Hopkins Hospital. “Whether it’s possible is unknown.”

Memory science is a developing field, and its investigators are still piecing together our molecular understanding of what memory is, how memory is formed, and how memory is lost. That makes the prospect of finding a drug or treatment for memory a fraught prospect at best — regardless of any one company’s product claims.

Some 100 billion neurons are inside the brain, and each neuron is capable of making tens of thousands of connections with its fellow brain cells. As a result, they communicate in webs of networks. Making a memory doesn’t involve merely one area of the brain or one specific network. Rather, it involves a number of networks working in tandem, an elegant choreography of crashing electrical signals and chemical transmissions.

“Memory is not one process, but many different processes in the brain, involving a multitude of brain regions, cell types, and molecular mechanisms,” says neuroscientist Alcino Silva, director of the Integrative Center for Learning and Memory at UCLA’s Brain Research Institute.

Signaling events — the molecular mechanisms that Silva mentions — are also taking place. Mouse studies and memory-simulation experiments have identified, for example, that cellular calcium is important for memory formation. Calcium signaling prompts the growth of dendritic spines in neurons, the formation of which is associated with learning. Studies also show that increased levels of calcium in brain cells can lead to synaptic disruption, which in turn can hinder healthy memory formation.

About 15 pages of the FTC’s complaint against Quincy Bioscience are reprints of advertising materials and company literature. Of interest is that the company takes special note of calcium and how the apoaequorin protein — the active ingredient in Prevagen — influences it: “The core technology of the company is the innovative application of the calcium-binding protein apoaequorin. Using this cutting edge protein originally discovered in jellyfish… the company focuses on alleviating the consequences of impaired calcium homeostasis (the imbalance of calcium ions) which can lead to mild memory loss associated with aging.” Company literature also mentions that apoaequorin “helps support brain cells by supplementing the proteins… that are diminished as we age.”

In other words, this is how Prevagen supposedly improves memory: It maintains the balance of calcium in the brain while presumably augmenting the effectiveness of other brain proteins, like calmodulin and neurogranin, which are key in providing the right amount of calcium signaling as memories are formed.

Making such a claim relies not only on Quincy Bioscience providing evidence that apoaequorin does, in fact, balance calcium levels. It also relies on the company proving that Prevagen’s main ingredient traverses the blood-brain barrier in the first place. The barrier is simply a collection of vessels that regulates the movement of molecules and cells between the blood and the brain; it also protects neural tissue by blocking toxins and pathogens from entering.

To prove that apoaequorin is capable of crossing the barrier, Quincy Bioscience cites a study of the cerebrospinal fluid and blood plasma of dogs who swallowed doses of apoaequorin. According to Quincy Bioscience, the samples “showed quantifiable evidence that the supplement was present in the nervous and circulatory systems of the animals.”

The FTC, in its complaint, says this is not nearly good enough and goes on to argue that Quincy’s claims that Prevagen improves memory “rely on the theory that the product’s dietary protein, apoaequorin, enters the human brain,” but that the company does not have “studies showing that orally-administered apoaequorin can cross the human blood-brain barrier.” (In their respective answers filed in court, the company and Underwood both deny these allegations.)

“If you have something that you say helps memory, you have to show you’re getting it into the brain and you’re engaging some target in the brain that is relevant to memory,” Lyketsos says. “If I get a substance from jellyfish that I claim improves your breathing because it increases your heart rate, I still have to show that if you take it in your mouth, it gets into your bloodstream.”

The best evidence the company has about how orally-administered apoaequorin interacts with the human body is a safety assessment, one in which company executives, including Underwood, are cited as co-authors. Yet that assessment shows that most of the protein is broken down in the gut during digestion, long before reaching the brain.

“Even in the unlikely event a small amount of the protein survives the digestive tract,” wrote the Alzheimer’s Drug Discovery Foundation in an independent review of apoaequorin, “it is highly doubtful that a 196 amino-acid protein would cross the blood-brain barrier and enter the brain.”

What’s known for sure, according to Lyketsos and Silva, is that there is no single aspect of memory to influence that would improve a person’s overall brain health.

Supplements designed to support memory function suffer such scrutiny primarily because pinpointing exactly where in the brain any supplement might positively affect memory function is a nearly impossible task.

For instance, as you read this text, neurons in your hippocampus (which plays a role in our conscious memories of stories and events) are being activated, which in turn causes changes in the synapses of those neurons. Those synaptic changes created while you read this article enable your brain to recall the words on the screen. But other regions influence other types of memory: The amygdala plays a key role in our emotional memories (the pain you feel after touching a hot stove), while the striatum is central in our procedural memories (you remember how to ride a bike even if you haven’t touched handlebars in years).

So basing a memory claim on the effects of one intervention would be tricky even in a research setting — let alone the loosely regulated world of supplements. On the clinical side, a drug for memory loss remains elusive, while many companies have nothing to show but billions of dollars spent on failed tests in attempts to develop drugs for treating Alzheimer’s. And while it’s true that two drugs, donepezil and memantine, are currently being used to ease memory deficits in people with Alzheimer’s, they’re not drugs that reverse symptoms or halt the disease: They generally just postpone a person’s need to enter a nursing home for several months.

“It’s really hard to develop a drug to do something specific unless you have either a good model system or a solid understanding of the biochemistry of what you want to accomplish,” says Matt Kaeberlein, pathology professor and researcher at the University of Washington Alzheimer’s Disease Research Center in Seattle. “We don’t have either in this case.”

Deciphering the brain, in short, is a tricky task.

Supplements designed to support memory function suffer such scrutiny because of one primary reason: Pinpointing where in the brain any supplement might positively affect memory function is a nearly impossible task. By nature, the brain is redundant and connects to other regions in various ways. If you’re manipulating one area of brain circuitry, are you indirectly harming another area of circuitry?

“Although the last 20 years have seen a true renaissance in studies of memory, the science is relatively young,” Silva says. “There has not been enough time to translate most of the functional insights we have acquired concerning memory mechanisms into possible treatments.”

The Global Council on Brain Health, a collection of scientists and policy wonks, argues that most supplements for the brain do nothing. Some vitamins, like B12 and B9, may positively affect brain health. But, as the council wrote in a report published in 2019, lots of ingredients that are packaged and sold in supplement form — ginkgo biloba, curcumin, melatonin, and also apoaequorin — produce “no benefit in people with normal nutrient levels.”

Nonetheless, the market for brain supplements is big business. In 2016, global sales hit $3 billion, a figure projected to rise to almost $6 billion in the next three years.

Despite outside skepticism, Quincy Bioscience, before and during the lawsuit, has insisted that research it has conducted demonstrates that Prevagen is safe and effective for treating memory problems. Even the presiding judge in the case initially dismissed the FTC’s complaint, writing that all the federal agency managed to do was “point to possible sources of error.”

“There has not been enough time to translate most of the functional insights we have acquired concerning memory mechanisms into possible treatments.”

In its answers to the court as well as in its advertising material, Underwood’s company repeatedly talks up the Madison Memory Study as justification that its claims about Prevagen are true. Conducted from 2009 to 2011, the study enrolled 218 people from ages 40 to 91 with self-reported memory problems. Over 90 days, participants were given either a 10-milligram dose of apoaequorin or a size- and color-matched placebo pill every day. At days eight, 30, 60, and 90, all the people in the study completed a battery of nine computerized cognitive tests. In Quincy Bioscience’s telling, this gold standard of scientific trials — a randomized, double-blind, placebo-controlled test — shows clear evidence that the company’s supplement works.

“Prevagen demonstrated the ability to improve aspects of cognitive function in older participants with either normal cognitive aging or very mild impairment,” writes the study’s author, an employee of Quincy Bioscience. In its advertising materials, the company noted that the group taking Prevagen improved their scores in computerized tests measuring executive function, learning, memory, and word recall.

Digging into the clinical trial itself reveals some significant limitations, however — and not just that a company employee was the principal investigator in the study.

For one, the company specifically mentions that “no statistically significant results were observed over the entire study population.” Instead — as the FTC complaint also points out — the researchers conducted post hoc analyses of the study results, examining data from various subgroups much smaller than the overall number of people in the trial. “This methodology greatly increases the probability that some statistically significant differences would occur by chance alone,” reads the FTC’s complaint. What’s more, some of the company’s advertising material explicitly eliminates results from Day 60 of the trial period. In several of the computerized tests administered that day, the control group outperformed the treatment group.

Underwood and Quincy Bioscience deny that claim in their answers to the court — and, indeed, would beg to differ with the FTC’s overall assessment of their marketing.

The company’s contention, aside from their claim that Prevagen is a proven treatment, is that the FTC is applying an unreasonable standard for their supplement, a standard usually reserved strictly for pharmaceutical drugs. The back-and-forth nature of the lawsuit shows how fraught disagreements over supplements can become between their manufacturers and federal regulators like the FTC and the FDA. Because supplements are considered food, not drugs, they’re exempt from premarket approval of any claims they make — even though the FTC and the FDA ask supplement companies to have scientific support for any claims they make about their products.

For the companies themselves, that simple fact sometimes trips them up. Such was the case for bodybuilding supplements sold earlier this decade by one Texas-based company whose executives pleaded guilty to multiple felonies last year. And just this summer, a federal judge granted preliminary approval in a nationwide class action settlement against Quincy Bioscience that could provide some three million consumers of Prevagen refunds of up to $70. (Lawyers representing the plaintiffs say a ruling on final approval of the settlement should happen in about two weeks.)

Yet while the FDA doesn’t require that supplements prove safety or efficacy prior to being sold, the FTC, in its complaint, is demanding that standard when it comes to Prevagen.

“The marketers of Prevagen preyed on the fears of older consumers experiencing age-related memory loss,” said Jessica Rich, director of the FTC’s Bureau of Consumer Protection, when the FTC announced the lawsuit three years ago. “But one critical thing these marketers forgot is that their claims need to be backed up by real scientific evidence.”

That will be hard to do, considering that developing any drug for memory is a very difficult process. After all, the brain is a complex beast — and we’re still far away from being able to outsmart it.

Writer based near Washington, D.C. Read more: www.AndrewZaleski.com or https://ajzaleski.substack.com/

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