A Pharmacists' Guide to Recommending Prevagen®

Pharmacy Times, November 2021, Volume 87, Issue 11

Declines in cognitive function often occur as adults age and can include memory loss.1 Pharmacists can support the brain health and well-being of older adults in the community setting by understanding age-related cognitive function changes and the dietary supplement options available that can promote healthy brain activity.

Prevagen® is an OTC brain health supplement clinically shown to be safe and to improve memory and support brain function, such as mild memory loss associated with aging.*

Apoaequorin, the Unique Ingredient of Prevagen

Neuronal calcium dysregulation is an established contributor to age-related deficits in learning and memory.2,3 Apoaequorin is a calcium-binding protein found in luminescent jellyfish (Aequorea victoria) and is the unique ingredient of Prevagen. Calcium-binding proteins play an important role in the regulation of intracellular calcium homeostasis integral to neuronal cell function.2-4 It has been proposed that age-related declines in the expression and concentration of intracellular calcium-binding proteins and their altered distribution throughout the central nervous system may contribute to cognitive decline, as well as enhance susceptibility to neuronal cell damage and death.2-4 Given the role of calcium-binding proteins in the pathophysiology of age-related neurocognitive decline, there may be benefits to the administration of the exogenous form of apoaequorin.

Results from several animal studies support the hypothesis that apoaequorin treatment may be neuroprotective.5-9 In a study of aged canines, apoaequorin treatment improved memory- and performance-related behaviors, including measures of learning and attention.10 As apoaequorin treatment modified markers of cognitive decline in preclinical studies, Prevagen was further investigated in an in-human clinical trial.

Clinical Efficacy

The Madison Memory Study was a randomized, double-blinded, placebo-controlled trial that investigated the effects of Prevagen on cognitive performance in adults with self-reported memory and cognitive concerns.11,12 The trial enrolled a generally healthy population of 218 adults aged 40 to 91 years, without a history of neurologic or cognitive illness. Participants were randomized (3:2) to receive one 10-mg capsule of Prevagen or placebo daily for 90 days. A total of 211 participants completed the study.11,12

At baseline, participants were stratified into distinct cohorts based on their level of self-reported cognitive impairment as measured via the Ascertain Dementia 8 (AD8) screening tool. The AD8 is a validated, interview-based, 8-question screening tool that differentiates those with cognitive changes attributed to normal aging from those with early signs of dementia.13 An AD8 score of 2 was used as a cutoff value to identify the populations with normal cognitive function (AD8 0-1) and very mildly impaired cognitive function (AD8 0-2) from those with higher levels of impairment (AD8 3-8). Because Prevagen is a dietary supplement intended for healthy, nondemented individuals, results from participants in the AD8 0-1 and AD8 0-2 cohorts are most relevant to the efficacy of the product.11-13

To assess the effect of Prevagen compared with placebo, changes in cognitive function were quantitively assessed at baseline and at 8-, 30-, and 90-day time points using tests from the Cogstate Research battery, a widely used and validated tool to assess verbal and visual learning, memory and working memory, executive functioning, and psychomotor function and attention via
computer-based maze learning and recall tasks.11,12 Although no statistically significant results were observed over the entire study population, the Prevagen-treated participants in the AD8 0-1 and AD8 0-2 cohorts achieved statistically significant improvement in the Cogstate mean test scores measuring aspects of cognitive function compared with the placebo treatment group (TABLE).11,12

As a result of the findings, it was concluded that dietary supplementation with Prevagen enhances cognitive function among healthy adults with normal cognitive aging or very mild impairment.


The unique ingredient in Prevagen, apoaequorin, has undergone extensive safety testing for toxicity and allergenicity. In human clinical trials, apoaequorin was well tolerated for up to 90 days.11 In animal safety studies, apoaequorin was found to be safely consumed in doses much higher than the recommended dosage (4000 to 16,000 times the recommended daily amount of Prevagen Regular Strength) and without adverse effects when taken orally.14,15 Apoequorin is not a known allergen and is not likely to be cross-reactive with any known allergens. In a separate safety study, apoaequorin exhibited a digestibility profile similar to those of other nonallergic dietary proteins, without any significant risk of allergic reactivity when ingested orally.16

Role of the Pharmacist

According to the 2021-2022 Pharmacy Times® OTC national survey, Prevagen is the number-1 pharmacist-recommended memory support brand among pharmacists who recommend memory support products. If asked for a recommendation, pharmacists can provide information about Prevagen’s safety, efficacy, and clinically tested ingredient. In a clinical trial, a subgroup of adults with mild, age-related cognitive impairment taking just 1 Prevagen a day, over 90 days, achieved improvements in measurements related to memory.11,12,*

As with any new dietary supplement, pharmacists can be a helpful resource for information and can answer questions regarding the use of Prevagen. Prevagen is available in Regular Strength (10 mg) and Extra Strength (20 mg) dosages as a once-daily oral capsule or chewable tablet. Note that it is recommended to take Prevagen for 90 days to fully gauge its effectiveness. In addition to recommending Prevagen, pharmacists can provide education on lifestyle choices that can promote cognitive health, such as regular physical and social activity.1

*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.


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  2. Nikoletopoulou V, Tavernarakis N. Calcium homeostasis in aging neurons. Front Genet. 2012;3:200. doi:10.3389/fgene.2012.00200
  3. Calvo-Rodriguez M, Hernando-Pérez E, López-Vázquez S, et al. Remodeling of intracellular Ca2+ homeostasis in rat hippocampal neurons aged in vitro. Int J Mol Sci. 2020;21(4):1549. doi:10.3390/ijms21041549
  4. Fairless R, Williams SK, Diem R. Calcium-binding proteins as determinants of central nervous system neuronal vulnerability to disease. Int J Mol Sci. 2019;20(9):2146. doi:10.3390/ijms20092146
  5. Detert JA, Adams EL, Lescher JD, et al. Pretreatment with apoaequorin protects hippocampal CA1 neurons from oxygen-glucose deprivation. PLoS One. 2013;8(11):e79002. doi:10.1371/journal.pone.0079002
  6. Adams EL, Ehlers VL, Michels SC, et al. Orally administered apoaequorin protects neurons from oxygen-glucose deprivation. Presented at: Society for Neuroscience Annual Meeting; November 9-13, 2013; San Diego, CA. Accessed October 4, 2021.
  7. Ehlers VL, Adams EL, Fettinger NB, et al. The neurotherapeutic effects of the calcium binding protein apoaequorin. Poster presented at: Society for Neuroscience Annual Meeting; November 15-19, 2014; Washington, DC. Accessed October 4, 2021.
  8. Hochstetter EL, Detert JA, Lescher JD, Moyer JR Jr. Apoaequorin protects neurons from ischemia and alters cytokine mRNA levels in rat hippocampus. Poster presented at: Society for Neuroscience Annual Meeting; October 13-17, 2012; New Orleans, LA. Accessed October 4, 2021.
  9. Smies CW, Moyer JR. Neuroprotective effects of apoaequorin on ischemic stroke. Poster presented at: Society for Neuroscience Annual Meeting; October 19-23, 2019; Chicago, IL. Accessed October 4, 2021.
  10. Milgram NW, Landsberg G, Merrick D, Underwood MY. A novel mechanism for cognitive enhancement in aged dogs with the use of a calcium-buffering protein. J Vet Behav. 2015;10(3):217-222. doi:10.1016/j.jveb.2015.02.003
  11. Moran DL, Underwood MY, Gabourie TA, Lerner KC. Effects of a supplement containing apoaequorin on verbal learning in older adults in the community. Adv Mind Body Med. 2016;30(1):4-11.
  12. Lerner KC. Clinical Trial Synopsis QB-0011: Madison Memory Study: a randomized, double-blinded, placebo-controlled trial of apoaequorin in community-dwelling, older adults. Published August 1, 2016. Accessed October 4, 2021.
  13. Galvin JE, Roe CM, Powlishta KK, et al. The AD8: a brief informant interview to detect dementia. Neurology. 2005;65(4):559-564. doi:10.1212/01.wnl.0000172958.95282.2a
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  15. Bauter MR, Mendes O. Subchronic toxicity of lyophilized apoaequorin protein powder in Sprague-Dawley rats. Toxicology Research and Application. 2018;2:1-15. doi:10.1177/2397847318756905
  16. Moran DL, Tetteh AO, Goodman RE, Underwood MY. Safety assessment of the calcium-binding protein, apoaequorin, expressed by Escherichia coli. Regul Toxicol Pharmacol. 2014;69(2):243-249. doi:10.1016/j.yrtph.2014.04.004