Brain-Boosting Supplements: All Hype or Some Hope?

Medscape

2 days ago

Media consumers are bombarded daily with aggressive, testimonial-driven ads for pricey supplements purported to sharpen memory, focus, and working brain function.
Some even claim to stop or slow the development of dementia.
Patients, especially older adults, may express interest in these supplements during clinic visits.
Most claim to be 'clinically tested.' However, since the FDA exercises only limited regulatory control over these products, they are not held to the same purity, safety, and efficacy standards as are FDA-approved drugs.
'Manufacturers have a lot of leeway to market them as they want,' said Pieter Cohen, MD, director of the Supplement Research Program at the Cambridge Health Alliance in Somerville, Massachusetts, and an associate professor of medicine at Harvard Medical School in Boston. 'That's not to say they haven't been studied — there might be small studies posted online done in, say, 100 people in another country, for example.'
Pieter Cohen, MD
Cohen, therefore, does not generally recommend that his patients take them to improve brain health, 'although I do recommend supplements to patients who need them to treat medical conditions,' he told Medscape Medical News .
Many contain dubious or unlisted ingredients, he noted. In a 2021 study of over-the-counter (OTC) cognitive enhancement supplements, Cohen and colleagues identified unapproved drugs (omberacetam, aniracetam, phenibut, vinpocetine, and picamilon) — as well as compounds not listed on the label and with unknown health effects. For those products with ingredient quantities provided on the labels, 75% of declared quantities were inaccurate.
These OTC brain enhancers may feature, alone or in combination, nonpharmaceutical ingredients such as vitamins (including vitamin E), minerals like magnesium, omega-3 fatty acids, turmeric, and herbal compounds like ginseng, Ginkgo biloba , and coffee fruit extract. Some feature alleged boosters of brain performance that are less familiar, including alpha-GPC (L-alpha-glycerylphosphorylcholine), huperzine A, the Chinese mushroom lion's mane, L-carnitine, and the Ayurvedic medicine compound Bacopa monnieri .
Some ingredients are more exotic. The memory enhancer Prevagen, for example, contains apoaequorin, a lab-made version of a protein found in the bioluminescent jellyfish Aequorea victoria .
In 2024, the Federal Trade Commission and a federal district court in New York State ordered Prevagen's makers to stop their claims on the grounds they lacked reliable evidence.
Jayne Zhang, MD
The brain health supplements all have one thing in common, noted Jayne Zhang, MD, an attending neurologist specializing in cerebrovascular disease at Johns Hopkins School of Medicine in Baltimore — uncertain evidence of claimed efficacy.
'There is some modest support for a benefit from these products in people who already have nutritional deficiencies or mental degeneration, but there's not a lot of strong evidence from rigorous trials,' she told Medscape Medical News .
Added Alejandra Sánchez López, MD, an assistant clinical professor of neurology and geriatric medicine at the Mary S. Easton Center for Alzheimer's Disease Research at the University of California, Los Angeles, 'Weak evidence of benefit usually comes from studies with small sample sizes and sponsored by the manufacturing company.'
Alejandra Sánchez López, MD
Like Cohen, Sánchez López recommends that her patients not take the brain supplements. 'They come with palpable GI [gastrointestinal] side effects such as nausea and diarrhea,' she said.
Zhang is more open to patients' hopeful inquiries. 'I try not to be dismissive. Instead, I ask them what they're hoping a supplement will do for them, then I reveal what we know about them and talk about safety.'
Zhang uses these encounters with OTC nootropics to talk about improving cognitive function in other ways: good nutrition, exercise, sleep, alcohol reduction, and social engagement, as well as proven medical therapies that mitigate cognition-impairing conditions such as depression, hyperglycemia, and hypertension. 'Patients need to understand there is no magic pill for brain health,' she said.
The old-fashioned multivitamin tablet shows some promise, however. In a large National Institutes of Health-funded, placebo- and comparator-controlled randomized trial, Baker and colleagues found that older adults given a multivitamin had higher global cognition scores than those who did not take it. Specific effects on global cognition, episodic memory, and executive function were noted. The improvement was most pronounced in those with a history of cardiovascular disease.
Safety
Potential toxicity must be an issue with any loosely or unregulated OTC supplement, especially if taken over the long term.
A content analysis of 12 cognitive supplements found the majority had at least one ingredient listed but not detected or, conversely, contained compounds detected but not reported on the label. And as noted, they can contain unapproved and potentially dangerous drugs.
Drug interactions are another safety issue. Some dietary supplements can affect the pharmacokinetics of prescription drugs, altering their absorption, metabolism, or excretion and decreasing or increasing their potency.
So, clinicians need to urge patients to be cautious, Sánchez López said. 'I always ask my patients to show me what supplements they're taking, and I go over the ingredient list.'
A Dietetic Approach to Cognitive Health
Emma Laing, PhD, RDN, a clinical professor and director of dietetics at the University of Georgia in Athens, Georgia, noted that a safer, proven alternative to commercial cognitive supplements can be found in the kitchen. 'While genetic predisposition, medical conditions, and environment are strongly linked to brain health, consuming a wide variety of nutrient-dense foods can improve cognitive health and reduce your risk for chronic disease,' she told Medscape Medical News .
Emma Laing, PhD, RDN
Minimally processed, nutrient-dense foods have been shown to support neurologic health, along with coffee and tea, Laing added. And even a small reduction in alcohol intake can improve cognitive function.
Both the Mediterranean diet and the 'brain-healthy' MIND Diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) — a hybrid of the Mediterranean and DASH (Dietary Approaches to Stop Hypertension) regimens — have been well studied for their potential role in supporting cognitive function, memory, and alertness.
Nootropics with cognitive potential are under ongoing evaluation, but until large scientific studies establish a positive effect of commercial brain health supplements on cognition, a healthy lifestyle may deliver more solid benefits to the brain.