PREVAGEN® for Memory

Background

Patients are asking whether the oral supplement Prevagen improves memory. They are hearing that it protects the aging brain, supports a sharper mind, and leads to clearer thinking. This article summarizes what clinicians need to know about Prevagen.

What It Is

Prevagen contains apoaequorin.1 Apoaequorin is a part of a photoprotein, aequorin, found in the bioluminescent jellyfish Aequorea victoria.2 Apoaequorin is comprised of 189 amino acids, and has three calcium binding sites.3 When apoaequorin binds calcium, aequorin becomes an active enzyme catalyzing a reaction that releases blue light.3 Aequorin can be produced using recombinant DNA technology and is used in research as a marker to monitor cellular processes and in analytical assays.3

What It Does

A certain range of neuronal calcium levels are necessary for optimal neuronal function. Sustained high intracellular calcium levels can be neurotoxic. Calcium binding proteins help regulate intracellular calcium. Alzheimer’s disease, as well as normal aging, is associated with reduced levels of neuronal calcium binding proteins. Apoaequorin has been shown to confer neuroprotection in an animal model of brain ischemia when infused directly into the brain. The mechanism is thought to involve more than just calcium binding.4

In a human study performed by the manufacturer and published as an abstract, 222 patients age 40 to 91 years with memory complaints were randomized to apoaequorin 10 mg or placebo.5,6 Patients underwent cognitive function testing using a computerized testing system from CogState Research five times over three months.5 At 90 days, significant differences between groups from baseline were seen on tests of verbal and visual learning, memory, and delayed recall (International Shopping List and Groton Maze Learning Recall)(p<0.05).5 The manufacturer has done other human studies, but the results are unpublished in primary literature.6 Safety Based on a subchronic toxicity study in rats, the “no observed adverse effect” level for orally administered apoaequorin is 2000 times the expected human exposure, and the acceptable daily intake was set at 666.7 mg/kg/day (the highest dose tested). Apoaequorin is not likely to cause allergic reactions based on its structure and simulated digestion studies that show it is easily broken down by pepsin.7 Over 2000 adverse effects associated with Prevagen have been reported to the manufacturer. At least 26 have been deemed serious by the manufacturer. Most were neurologic or cardiovascular events (e.g., stroke, seizures) in patients with predisposing conditions. The manufacturer did not attribute any of these adverse effects to Prevagen.8 Because apoaequorin is a protein, it is likely broken down in the gastrointestinal tract by pepsin to amino acids before it can be absorbed.7,8 Prevagen has been under investigation by the FDA, and was the subject of a 2012 FDA warning letter.9 In the letter, the FDA alleged the product’s therapeutic claims made it an unapproved drug (as opposed to a dietary supplement), and that the manufacturer failed to file an investigational new drug application (IND) before conducting human research. Conclusion Due to lack of high-quality efficacy and safety data for Prevagen, advise patients with memory concerns to save the $40 or more (U.S.) per month they would spend on Prevagen. Instead, encourage exercise, control of cardiovascular risk factors, and participation in mentally or socially stimulating activities. Also advise them not to count on other memory supplements (e.g., vitamin E, ginkgo). These products do not have enough high-quality evidence to recommend.1,1