Apoaequorin is a protein isolated from the jellyfish Aequorea victoria. It is the active ingredient in some supplements marketed for memory and brain health (e.g., Prevagen®). Increased calcium levels in brain cells are associated with cell death and aging, so agents that help maintain healthy calcium levels do have potential for promoting brain health and preventing dementia. Apoaequorin, however, has a chemical structure that is likely broken down in the gut before reaching the brain, raising serious doubts about its potential benefit.
There has only been one clinical trial testing the effects of apoaequorin on cognitive function, which was carried out by a supplement manufacturer. Our search identified:
• 0 meta-analyses or systematic reviews
• 1 clinical trial in humans looking at effects on cognitive function
• 1 open-label (uncontrolled) study looking at effects on sleep quality
• 1 preclinical study along with a field of research on protein pharmacokinetics suggesting that apoaequorin is very unlikely to reach the brain
• 1 preclinical study in a model of ischemia/stroke
One clinical trial, conducted by a supplement manufacturer, reported that apoeaequorin improves cognitive function in older adults. But the trial did not directly compare the apoaequorin group with the control, thus failing to produce any evidence that apoeaequorin worked better than placebo . No clinical research has evaluated if apoeaequorin can protect from dementia or cognitive decline. There is strong evidence suggesting that apoaequorin does not survive digestion in the gut  or cross the blood-brain barrier , so is unlikely to have any effect on the brain.
An open-label sleep quality study, also carried out by a manufacturer, reported increased sleep time and quality of sleep with an apoeaequorin supplement . While there is rationale for better cognition with improved sleep, the trial did not provide evidence that apoeaequorin helps to promote sleep any more than a placebo. And since apoaequorin is unlikely to survive digestion in the gut, an effect on sleep is unlikely.
Apoaequorin has not been evaluated as a treatment for dementia in controlled trials. Given the evidence suggesting that apoaequorin taken orally does not reach the brain, it is unlikely to have protective effects in dementia patients.
Widespread consumer use and a 90-day randomized controlled trial in older adults suggest that apoaequorin is well-tolerated . Safety has not been carefully evaluated for doses higher than the standard (10 mg daily), longer periods of treatment, or for vulnerable patients who have existing conditions, health risks, or use other medications and supplements. Like most proteins, apoaequorin is unlikely to survive digestion in the gut , which limits the risk of harmful (or beneficial) biological effects.
NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.
Apoaequorin is widely available in the United States as a supplement. The dose used in the clinical trial was 10 mg daily and deemed safe by the manufacturer that ran the trial. In the sleep study, patients took 20 mg every 2-3 hours while they were awake (up to ~200 mg daily).
Download full scientific report
The Food and Drug Administration (PDF) has detailed analyses of adverse events associated with an apoaequorin supplement.
Details of a class-action lawsuit (PDF) filed in January 2015 against an apoaequorin supplement manufacturer regarding the claims that its product improves memory function. As of June 2016, the results of this lawsuit aren't available online.
A 2017 STAT news article discussing the complaint filed against the supplement manufacturer by the Federal Trade Commission and the NY state attorney general.