Cognitive decline with aging is a very frequent concern associated with growing older. Brain health and cognitive performance enhancers (BHCPEs) are a booming business with promises of increased power, concentration, or energy, but are these agents safe and effective for their intended use?

A recent paper in the Journal of Alternative and Complementary Medicine issued a warning that many dietary supplements (DS) marketed for brain health may be adulterated and/or misbranded. Investigators from both the U.S. military and University of Mississippi School of Pharmacy performed a scoping review to identify DS marketed for brain health and cognitive performance that are intended to be used by healthy adults, including military personnel. They searched Natural Medicines, the Dietary Supplement Label Database, and popular shopping websites such as Amazon with the purpose of identifying relevant BHCPE products. The researchers also identified all ingredients within these products; if >10 products contained a particular ingredient, the ingredient was considered “frequently used.”

The research team gathered information on 650 unique BHCPE products that contained 72 “frequently used” ingredients. An umbrella review, which is a review of systematic reviews or meta-analyses, and an evidence-mapping exercise were performed to analyze publications in terms of their study populations, interventions, and outcomes.

Among these 72 frequently used ingredients, fewer than half (43%) had some type of systematic review that addressed various populations and looked at dose, administration, and/or a variety of brain-health, cognitive performance–related outcomes.

Investigators also reviewed the questions on DS and their ingredients that were submitted by military personnel through the Operation Supplement Safety ( website, which is an evidence-based information portal operated by the Department of Defense (DoD). The OPSS has developed scorecard to screen DS product labels for potential safety concerns. This scorecard serves as an educational tool within the DoD to teach military personnel how to read DS labels and to identify potential red flags.

Key questions asked in the scorecard, which are each given a point, include whether the product has undergone third-party certification; whether the product contains fewer than six ingredients; if the label is free of words such as proprietary, blend, matrix, or complex; if the ingredient names are easy to pronounced; if the product contains <200 mg of caffeine; or if the label contains questionable claims or statements. A score of less than 4 is a “no-go,” meaning that the product should be avoided.

About 8% of the total inquiries on the OPSS site involved DS marketed for cognitive enhancement; these included frequently used ingredients. About one-quarter of the products made specific claims regarding brain health and cognitive enhancement, and these 12 products were the subject of further investigation. While these 12 products only represented 2% of all of the 650 products identified, they constituted 70% of the most frequently used ingredients. The researchers purchased these 12 products, and a quality analysis was performed on them by the National Center for Natural Products Research at the University of Mississippi to determine whether they included the ingredients listed on the Supplement Facts label. These products were also screened against the OPSS scorecard. Product manufacturers’ websites were searched for evidence-based medicine to support the claims being made about the products.

The 12 products contained a variety of vitamins (e.g., vitamins A, B, C, D,  and E, most commonly B6 and B12), minerals (e.g., calcium, magnesium, potassium, selenium and zinc), amino acids (e.g., tyrosine, carnitine, glutamine and theanine), and herbal ingredients (e.g., Bacopa leaf, Huperazine A), as well as phosphatidylserine, vinpocetine, and coffee extracts. Systemic review evidence found that most information came from older adults and cognitively impaired populations and that overall, there was insufficient evidence to recommend these agents as BHCEs. Of concern, 67% of the products analyzed had at least one ingredient listed on the Supplement Facts label that was not detected through the chemical analysis.

Conversely, 83% of the products analyzed had ingredients that were not reported on their labels; these were mostly amino acids and were “naturally occurring compounds found in plants.” Additional ingredients that were not stated on the label but were found in the BHCEs included caffeine, adenosine, sulbutiamine, which is a synthetic derivative of thiamine used to enhance athletic performance, and vinpocetine, a cognitive enhancer linked to miscarriages and teratogenicity.

Eleven of the 12 products tested were definite “no-go’s.” Interestingly, only one product of the 12 products analyzed contained a third-party certification and this product’s label matched its ingredient content, speaking to the importance of this type of verification.

In general, the products contained between eight and 40 ingredients with an average of 14. Almost 60% of the products were proprietary blends. Eleven of the products had scientifc-sounding claims on their label or product website. None of the products’ websites provided published clinical research to support the DS. One product referred to research that was unpublished; another product referred to research but did not contain an actual reference. On a positive note, 58% of products had a general warning that recommended not to exceed daily doses, to consult a physician before using the DS if taking other medications, or not to use the product if pregnant or breastfeeding.

The investigators concluded that BHCEs are often adulterated and misbranded. This paper was a wake-up for both consumers and pharmacists. Pharmacists are in a key position to educate patients to recognize red flags when purchasing DS and to help identify high-quality DS.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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