The Right Chemistry: Nothing memorable about memory supplements

U.S. President Joe Biden’s supposed memory problems have elicited much media attention. Time to throw science into the mix.

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Imagine what it would be like to lose your memory. Of everything! And even worse, to be unable to form any new ones. That is the nightmare Englishman Clive Wearing has been living since 1985, when the herpes simplex virus — one that normally only causes skin blisters — attacked his hippocampus, the brain structure where memories are stored. Actually, he can’t even remember that he is living a nightmare, because the only memory he has is of the past 30 seconds. The exception is that he recognizes his wife, but if she leaves the room and returns a minute later, he greets her as if she had not been there before at all. Even more curious is that Clive, who had been a musician and conductor of note before his affliction, has retained his ability to read and play music. 

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Wearing’s case is extremely unusual, perhaps even unique. However, memory loss to a greater or lesser extent with aging is common, and the hope of prevention has stimulated a great deal of research. It has also stimulated a multi-billion-dollar industry of “brain health supplements,” mostly of highly questionable efficacy. There has also been much interest in the possible role of specific foods and diets in preventing age-related memory loss.

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As far as supplements go, the weak or nonexistent evidence is dwarfed by the overly exuberant hype. Personal testimonials from people who seem to have only an initial for a second name abound with rosy accounts of regained mental clarity and vague references to clinical trials. Of course, just having carried out a clinical trial says nothing, unless that trial produces a positive result. To be sure, there have been trials galore, but most have used either cultured cells in the lab or rodents navigating mazes. Any human intervention studies have been small, with results of doubtful practical significance. While there are literally hundreds of brain supplements on the market, they all make use of one or more of some 20 ingredients.

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Rationale for their use can sound seductive. The most common justifications include increasing levels of the neurotransmitter acetylcholine (huperzine, choline, lecithin, alpha-glycerophosphocholine, bacopa monnieri), decreasing the formation of proteins such as tau and beta-amyloid that interfere with neurotransmission (lion’s mane, turmeric, ashwaghanda, cinnamon), strengthening myelin, the protective sheath around nerves (phosphatidylserine), improving the fluidity of cellular membranes to improve neurotransmitter function (omega-3 fats), preventing cell death (ginger), nebulous neuroprotective effects (vinpocetine), modulating calcium levels in the brain (apoaequorin), or serving as antioxidants (ginkgo biloba, coenzyme Q10, polyphenols derived from tea, cocoa or fruits). Many of these ingredients claim to have a combination of these effects.

There is no question that free radicals generated from oxygen during normal metabolism can damage nerve cells through what is termed “oxidative stress” and that antioxidants can mitigate this effect. Neither is there doubt that neurotransmitter activity is critical to cognition, or that beta-amyloid deposits impair memory. But demonstrating that “brain enhancers” can affect these processes in a clinically positive way requires evidence. While they do appear to be safe, such supplements have shown either no or marginal benefit when subjected to randomized double-blind trials. Ginkgo biloba, omega-3 fats, turmeric, and green tea and cocoa extracts are prime examples of failures.

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One of the most popular substances, apoaequorin, sold as Prevagen, is advertised as being backed by clinical trials. That “backing” took some imaginative data mining. The company clearly admits that “no statistically significant results were observed over the entire study population,” but torturing the data yielded a subgroup of participants who showed a mild benefit. In all probability, this was a statistical quirk since apoaequorin is a protein that is likely to be digested before it has any chance of making it into the brain. There is also hype about apoaequrin occurring naturally in jellyfish. This feeds into the myth that “natural” means safe and effective. Actually, the apoaequrin in Prevagen is not extracted from jellyfish but is made in the lab, not that this matters. What matters is the lack of evidence of efficacy and the numerous reports of side effects and the launching of federal lawsuits against the company.

There is no shortage of studies that have examined the role of specific foods on brain health. In one randomized study, one group of subjects consumed 60 grams of walnuts, pistachios, cashews and hazelnuts per day while a control group ate no nuts. The nut group showed increased blood flow to the brain and outperformed the control group by 16 per cent on a verbal memory test. In another study, participants who took 13 grams of strawberry powder daily made fewer errors on a word test and reported fewer symptoms of depression. “Eating more kiwi fruit could boost your mental health in just a few days,” claims a headline above an article that reports on a study that purported to show subjects who eat two kiwi fruits a day show an improved mood after just four days. Pretty soft stuff.

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Now let’s turn to some studies with somewhat harder evidence. The “Cocoa Supplement and Multivitamin Outcomes Study (COSMOS)” found that a group of subjects over age 60 who took a multivitamin-mineral supplement showed a modest benefit in cognition compared with a placebo group. However, other studies, such as one that tracked 6,000 male physicians over 12 years showed no difference between those who took a multivitamin or a placebo. The Nurses’ Health Study that has followed some 48,000 nurses since 1984 found that subjects who had adequate protein intake during middle age, especially plant protein, had better health outcomes, including mental health, as they got older. The researchers suggest nuts for snacks and several meals a week featuring beans, lentils, peas, tofu and whole grains.

The same Nurses’ Health Study also furnished perhaps the most compelling evidence that links diet to a successful battle against cognitive decline. In this case, the focus is on dietary flavonoids, a general family of compounds found in plants with some common features in their molecular structure that account for their antioxidant activity. Intake of flavonoids was calculated from food frequency questionnaires and related to “subjective cognitive decline” as ascertained from questions such as “do you have more trouble than usual remembering recent events,” “do you have more trouble than usual remembering a short list of items,” or “do you have more trouble than usual following a group conversation or plot in a TV program?”

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While such observational studies cannot prove as cause-and-effect relationship, the data do suggest that including several daily servings of foods high in flavonoids such as oranges, peppers, apples, strawberries and blueberries can slow cognitive decline by as much as 20 per cent. 

What then is the overall conclusion about slowing memory decline? There is not enough evidence to back any memory supplement. Better spend the money on flavonoid-rich foods. Making sure that daily protein intake is at least 0.8 grams per kilogram of body weight — preferably in large part plant protein — is important.

And how many studies did I tussle with to come to these conclusions? I can’t remember. Better stock up on berries.

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Joe Schwarcz ([email protected]) is director of McGill University’s Office for Science & Society ( He hosts The Dr. Joe Show on CJAD Radio 800 AM every Sunday from 3 to 4 p.m.

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