Can You Improve Your Memory With A Jellyfish Protein?

Some colleagues of mine recently asked me about Prevagen, a supplement that is being advertised heavily on television as a memory booster. It's everywhere, they said–but what is it? And does it work?

Both questions are pretty easy to answer. On the first question, the TL;DR version is that Prevagen's primary ingredient is a protein called apoaequorin, which is found in a species of jellyfish that glows in the dark. These jellies produce two proteins, apoaequorin and green fluorescent protein (GFP), that help them fluoresce. It’s an amazing biological system, and the three scientists who discovered and developed the chemistry of GFP were awarded the 2008 Nobel Prize in chemistry.

Cool science! But what does this have to do with human memory? Not much, it turns out.

First let's examine what Prevagen's manufacturers, Quincy Bioscience, say about it. Their website claims that:

"Prevagen Improves Memory* 

Prevagen is a dietary supplement that has been clinically shown to help with mild memory loss associated with aging.* Prevagen is formulated with apoaequorin, which is safe and uniquely supports brain function.*"

Sounds pretty clear, right? But note the asterisks by each of these claims: if you scroll all the way down (or read the small print on their packages), you'll find out that:

"*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease."

You may recognize this language: it's what all supplement manufacturers use to avoid getting in trouble with the FDA. It means, essentially, that the government hasn't approved Prevagen to treat anything, including memory loss.

Despite Quincy’s claims, I see no reason why eating this protein would have any effect at all on brain function. First of all, it’s not even a human protein, so it's unlikely to work in humans. Second, even if it did work in humans, eating it would not deliver it to our brains, because it would be almost certainly be broken down in the stomach. And third, the connection between any protein and memory is very complex, so simply having more of a protein is very, very unlikely to improve memory.

Quincy's website points to a single study that they themselves conducted, which they argue showed benefits for people with mild memory impairment. However, others have pointed out that the experiment (which was never published in a scientific journal) didn't show any such thing: overall there was no difference between people who took Prevagen and those who took a placebo, but the manufacturer's did some p-hacking to extract a subgroup that appeared to get a benefit. As Dr. Harriett Hall and others have pointed out, this kind of p-hacking is bogus.

And what about my observation that the jellyfish protein will simply be digested in the stomach, and never make it to the brain? It turns out that the company itself admits that I'm right. On their website, they have a "research" page pointing to several safety studies, designed to show that Prevagen won't cause an immune reaction. One of these studies explains that

"Apoaequorin is easily digested by pepsin."

Pepsin is the chief digestive enzyme in your stomach. So Prevagen's main ingredient never gets beyond the stomach, which is why it's probably quite safe. (Joe Schwarcz at McGill University recently made the same point.)

Back in 2015, I asked Ted Dawson, the Abramson Professor of Neurodegenerative Diseases at Johns Hopkins School of Medicine, what he thought of Prevagen’s claims.

“It is hard to evaluate Prevagen as to the best of my knowledge there is no peer-reviewed publication on its use in memory and cognition,” said Dawson. “The study cited on the company’s web site is a small short study, raising concerns about the validity of the claims.”

Finally, a word to those who are still tempted to try Prevagen: it isn't cheap. Their website charges $75 for a bottle of 60 pills, each containing 10 mg of apoaequorin, or $90 for 30 pills of the "Professional formula," which contain 40 mg. (Note that there's no evidence that taking a higher dose will work any better.)

The FTC sued Quincy Bioscience in 2017 for deceptive advertising, arguing that claims that Prevagen boosts memory are false, and that claims it can get into the brain are also false. Just a few months ago, a judge ruled that the case can proceed. Meanwhile, though, the advertising and sales of Prevagen continue. The FTC case states that Quincy sold $165 million worth of Prevagen in the U.S. from 2007 to 2015.

So the bottom line is: jellyfish proteins are very cool, but eating them won't improve your memory. If you're interested in brain food, perhaps you just eat more fish, which might actually work.

(Note: I wrote about Prevagen in 2015, and some elements of this article are based on my earlier one.)

FTC steps in where FDA fears to tread - on homeopathy

Here's a label that the FDA should require.

The federal government is probably wincing right now from the after-effects of the election, but one agency deserves a robust round of applause: the Federal Trade Commission. This week, the FTC announced, in a strongly-worded report on homeopathic advertising, that homeopathic drugs should "be held to the same truth-in-advertising standards as other products claiming health benefits."

The FTC can't prevent homeopathic marketers from selling their products; only the FDA could do that. But starting very soon, they will require that homeopathic products include statements that:

• There is no scientific evidence backing homeopathic health claims
• Homeopathic claims are based only on theories from the 1700s that are not accepted by modern medical experts.

Admittedly, this might not effect sales very much. Over at Slate, Alan Levinovitz argues that these claims might even backfire, because some users of homeopathic drugs don't trust modern medicine, or because they might belief that hey, if it's been around that long, it must work. But old medicine is not good medicine. (And in the FTC's defense, they also recommended that the FDA "subject homeopathic drugs to the same regulatory requirements as other drug products," but they can't force the FDA to act.)

But wait: does this mean homeopathic drug makers didn't have to be truthful in the past? Well, yes. As the FTC report explains, in 1988 the FDA–the agency in charge of regulating drugs in the U.S–basically struck a deal where they agreed that homeopaths could be self-regulating, as long as they included a disclaimer that their claims haven't been evaluated by the FDA. To put this more bluntly: the FDA's agreement with homeopaths (you can read it here) is basically a license to lie.*

For example, the widely-sold homeopathic product Oscillococcinum, which is nothing more than a sugar pill, says on its packaging that it "Temporarily relieves flu-like symptoms such as body aches, headache, fever, chills and fatigue."

Helpful hint to potential victims customers: Oscilloco doesn't do anything of the sort. Oscilloco escapes having to prove their claims by a tiny asterisk, which (after much digging through the website) is attached to a disclaimer that '*these “Uses” have not been evaluated by the Food and Drug Administration.' Interesting how they place the word "uses" in quotation marks.

Homeopathy is the most obviously fake alternative medicine you're likely to see in your local pharmacy. This may seem like a pretty strong statement, but look at what homeopathy claims:

• That infinite dilutions of a substance, to the point where not a single molecule remains, have a medical benefit
• That water "remembers" the substances that were in it in the past
• That a substance that causes a symptom will, when diluted, cure that same symptom. Thus (for example) poison ivy can cure itching.

These claims violate basic principles of physics, chemistry, and biology. The idea that water remembers what was in it is so confused that it's not even wrong–and it also implies that every sip of water you take "remembers" virtually every substance on the planet, although homeopaths appear not to recognize this. Yet homeopathic "drugs" are a multi-billion dollar business today; the FDA estimated that consumers spent $2.9 billion on homeopathic remedies in 2007, the last year for which they reported numbers.

The FDA held a public hearing last March, and the FTC held their public workshop in September. They solicited and received over 500 comments, both pro and con. Most of the pro-homeopathy comments boil down to "it worked for me" or "people have been using this stuff for years"; in other words, anecdotes and testimonials. The con-homeopathy comments described scientific studies showing that homeopathy simply doesn't work. These include a thorough review conducted by the Australian government last year, which concluded:

"There are no health conditions for which there is reliable evidence that homeopathy is effective."

Despite Alan Levinovitz's concerns that warning labels won't help, I'm with the FTC here. If the FDA won't (or can't) stop homeopaths from selling their modern snake oil, at least we can slap labels on them saying they don't work. If consumers want to buy a product that the government says doesn't work, well, it's their money.

*Well, they're not really lying if they include a disclaimer, are they? So I'm not really calling them liars.

Feds arrest dietary supplement makers for fraud

In the largely unregulated world of dietary supplements, it's like the Wild West. Dramatic claims abound, most of them unsupported by evidence, and it's hard to know if any of them can be trusted. Supplement manufacturers claim their products cure cancer, Alzheimer's disease, arthritis, and more. They promise miraculous weight loss results, nebulous "boosting" of your immune system, and anti-aging benefits.

Once in a while, though, they get caught. This week the U.S. cracked down hard on several of the more egregious offenders, announcing indictments against half a dozen supplement makers, including criminal charges against one.

It's about time. Consumers everywhere should applaud these actions and encourage more. Here's what happened.

On Tuesday, November 17, the U.S. Justice Department indicted USPlabs, a major supplement manufacturer whose products include Jack3d and OxyElite Pro. The Justice Department alleged that USPlabs "doctored packaging, labeling, and other paperwork to defraud others about what the product was." Further, the indictment points out that USPlabs claims that their products are made from natural plant extracts, when instead, as one USPlabs defendant put it:

"lol stuff is completely 100% synthetic."

The fraud runs even deeper: according to the Justice Department, after an outbreak of liver injuries associated with OxyElite Pro, in which some consumers needed liver transplants to save their lives,

"they [USPlabs] promised the FDA and the public that they would stop distributing the product at issue. They didn’t. Instead, they undertook a surreptitious, all-hands-on-deck effort to sell as much of the product as they could."

The criminal indictment, which led to the arrest of six USP employees and consultants, is just one of a sweeping set of actions over the past week. The Justice Department also filed six civil cases against other supplement makers for illegally claiming their products could cure diseases. The allegations include:

• Clifford Woods LLC illegally sold Taheebo Life Tea, Germanium, and Organic Sulfur as treatments for Alzheimer's and cancer.
• Optimum Health (aka Lehan Enterprises) illegally sold a product called DMSO cream for arthritis and cancer.
• Regenica Worldwide (aka Vivaceuticals) illegally sell their RegeneSlim as a disease cure, and in addition RegeneSlim contains DMAA, an unsafe food additive under the federal Food, Drug and Cosmetic Act, but does not declare DMAA as an ingredient.

Just to be clear: none of these violations have yet been proven in court. But to be even more clear: none of these products treat or cure cancer, Alzheimer's, arthritis, or any other disease.

In addition to the DOJ actions, the Federal Trade Commission indicted three more supplement manufacturers for illegal advertising claims (that's the FTC's purview). One indictment, against Chrystal Ewing and her two companies, Health Nutrition Products LLC and Classic Productions LLC, alleged that:

"In ads for W8-B-Gone, CITRI-SLIM 4 and Quick & Easy diet pills, the defendants featured bogus weight-loss experts. Citing fake scientific studies, the defendants also deceptively claimed to have clinical proof that consumers would experience a 'RAPID FAT meltdown diet program' that lets them shed five pounds in four days with one pill, or up to 20 pounds in 16 days with four pills."

Needless to say, none of those products deliver the results they claim.

It's a jungle out there. As the FTC's Jessica Rich said, "People looking for a dietary supplement to improve their health have to wade through a swamp of misleading ads. Be skeptical of ads for supplements that claim to cure diseases, reverse the signs of aging or cause weight loss without diet or exercise.”

It appears that major supplement retailers such as GNC have dropped USPlabs like a hot potato: I couldn't find OxyElite Pro on any of their sites. However, despite the indictments and arrests, USPlabs is still marketing OxyElite Pro on their own site, where they tout it as the "#1 Selling Fat Burner", with a long list of other claims. What about the liver toxicity cited by the Justice Department? The OxyElite website claims:

"OxyELITE Pro shows no side effects in well over 99% of its users. In fact, USPLabs and GNC have stated that there’s been over a billion servings of Jack3d and Oxy ELITE Pro safely taken with no problems!"

The FDA apparently disagrees: in March of this year, they issued a Medication Health Fraud notice that OxyElite Pro contains a hidden drug ingredient, fluoxetine. Fluoxetine is a type of selective serotonin reuptake inhibitor (SSRI), used for treating depression and other conditions. According to the FDA,

"SSRIs have been associated with serious side effects including suicidal thinking, abnormal bleeding, and seizures. In patients on other medications for common conditions (aspirin, ibuprofen, or other drugs for depression, anxiety, bipolar illness, blood clots, chemotherapy, heart conditions, and psychosis), ventricular arrhythmia or sudden death can occur."

Caveat emptor: these supplements might contain harmful ingredients. There's only one safe way to take supplements: ask your physician. Unless your doctor specifically recommends one, stay away. You'll feel better and your wallet will benefit too.

Can a cosmetic lotion turn back time? Not yet.

A few years ago, L’Oréal introduced two new product lines that used “gene science” to "crack the code" and make your skin young again. The new products were supposed to boost the production of “youth proteins” in your skin, making it look years younger. According to L’Oreal’s ad campaign, the benefits were clinically proven.

Except they weren’t. Last week, the FTC announced that L’Oréal had settled charges that the advertising for these products, Youth Code™ and Lancôme Génifique, was deceptive and misleading.

In a statement, L’Oréal responded that these claims "have not been used for some time now" and "the safety, quality, and effectiveness of the company's products were never in question."

What did L’Oréal claim? Here are some quotes from an ad for Lancôme Génifique:

"At the very origin of your skin's youth: your genes. Genes produce specific proteins. With age, their presence diminishes. Now, boost genes' activity and stimulate the production of youth proteins."

This sounds pretty amazing - and expensive, as much as $132 per bottle for Lancôme Génifique. L’Oréal Youth Code™ makes similar claims: on of its ads asks "Imagine: what if you could grow young?" and then goes on to promise "Even though you can't grow young, we now have the knowledge to help you begin cracking the code to younger acting skin."

The FTC apparently disagrees with L’Oréal's statement that the effectiveness of these cosmetics was not in question. Here is just one claim from a L’Oréal's ad that was highlighted by the FTC:

Génifique Youth Activating Concentrate is clinically proven to produce perfectly luminous skin in 85% of women, astonishingly even skin in 82% of women, and cushiony soft skin in 91% of women, in seven days.

This claim appears in a very scientific-looking bar graph in ad for Lancôme Génifique. It must be science - it's a graph! Alas for L’Oréal, the FTC states that science doesn't support this claims and that it is "false and misleading."

When I asked what studies supported the claim that these products could activate genes, a L’Oréal spokesman pointed me to two published studies, here and here. These are indeed peer-reviewed studies in high-quality journals. However, they don't support the claims made for these skincare products. Instead, they examine which genes are activated when the outer layer of skin is stressed by tape stripping, UV radiation, and washing with detergent. Neither study provides any evidence for a lotion that could activate the same genes, nor do they show that activating those genes could restore skin to its youthful state.

Can skin cream possibly make your skin young again? Well, it's plausible. A baby's skin does behave differently from an adult's skin, and much of that difference may be due to genes being turned on or off. But today, even if we knew the identity of these "youth proteins", we don't have the technology to turn them on.

To their credit, L’Oréal does invest significantly in research, so maybe they will find a youth-restoring cream one day. But not yet.

It's easy to find dramatic claims for products that restore youthful skin. Procter and Gamble's Olay® has many webpages devoted to anti-aging products, and you can be pretty certain that none of them will make you young again either. Like L’Oréal, P&G makes claims about genes:

"That discovery [the human genome] led P&G Beauty Scientists to explore how skin-related genes respond to aging and environmental stress at the molecular level."

As a geneticist myself, I can't help liking the idea that we might somehow convince skin cells to turn on a set of genes to restore their youthful state. Perhaps one of these companies will someday develop a lotion to do this - I hope they will. But they haven't done it yet. So for now, save your money: expensive skin creams are no better than inexpensive ones.