Apoaequorin for memory enhancement?

Integrative Medicine

In 2015, the Institute of Medicine (IOM) issued a brief report for clinicians to lessen cognitive aging in older adults.1 Among the report’s tips were formal evaluation of cognition as well as screening for cardiovascular (CV) risk factors, depression, alcohol, smoking, diet, and physical activity. The report advised clinicians to encourage regular physical activity, reduction in CV risk factors, and adequate sleep, as well as to promote social engagement and lifelong learning.

Memory problems a concern

The development of cognitive impairment is a specific concern for many Americans. In a study of almost 96,000 individuals aged 45 years or older from 21 states, 12.5% indicated feeling that they had increasing confusion or memory problems, with only 23% discussing these concerns with their provider.2

Many dietary supplements have been promoted for maintaining or improving cognitive function. Some of these have included ginkgo, bacopa, vinpocetin, huperzine A, phosphatidylserine, choline, omega-3 fatty acids, and vitamins, with variable evidence in humans about their efficacy for this purpose.


A calcium binding protein originally derived from jellyfish, apoaequorin (Prevagen—Quincy Bioscience) is widely advertised for memory enhancement. Although several animal studies on its safety have been published, human data on its efficacy are limited to published abstracts or studies posted on the company’s website.3 Of note, as a protein, apoaequorin is unlikely to be absorbed to a significant degree; instead it degrades into amino acids.

The company-sponsored Madison Memory Study included 218 adults between 40 and 91 years of age who had self-reported memory problems. The objective was to evaluate the supplement’s effectiveness for improving memory and cognitive function and secondarily for its effects on sleep, energy, and quality of life. Participants were randomized to receive either apoaequorin 10 mg daily or a placebo. They completed the AD8 Dementia Screening Interview4 and underwent testing using the computerized CogState Research Battery at baseline, day 8, day 30, and day 90. 

The study reported improvements in executive functioning and delayed recall using the Groton Maze Learning and the Groton Maze Recall tasks. Verbal learning and delayed recall were measured by the International Shopping Recall List. 

Unfortunately, these are not validated tests like the Trail Making Test Part B for executive functioning. It is unclear how these results would compare to standard measures such as those in the Ginkgo Evaluation of Memory trial.5 The report summarizing sleep and quality of life had serious methodological issues, including open-label design, few participants, and nonstandardized assessment questions.

FDA warning

In October 2012, FDA issued a warning letter indicating that multiple product claims violate what can be stated for dietary supplements versus drugs. More importantly, FDA stated that according to existing regulations, apoaequorin did not meet the definition of a dietary supplement, but instead should be considered a drug.6 The agency also noted that many adverse effects from the product were not reported, including seizures and strokes.

What to tell patients

Memory problems are a concern for many older adults. Pharmacists should educate patients that normal cognitive aging occurs and is not a disease. Regular physical exercise, a healthy diet, social engagement and lifelong learning, as well as the avoidance of inappropriate medications, are essential and likely possess additional health benefits. 

Although supplements such as omega-3 fatty acids have been promoted for improving memory, trial results have been mixed. No benefit was shown in a major rigorous study, even with omega-3 fatty acids.7 Human data on apoaequorin are limited to small, company-sponsored trials that do not meet expected scientific standards.


  1. www.iom.edu/~/media/Files/Report%20Files/2015/Cognitive_aging/Action%20…
  2. www.cdc.gov/aging/pdf/2012-brfss-state-summary.pdf
  3. quincybioscience.com/research/

  4. www.alz.org/documents_custom/ad8.pdf
  5. www.ncbi.nlm.nih.gov/pmc/articles/PMC2823569/
  6. www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm324557.htm
  7. JAMA. 2015;314(8):791–801