Jellyfish protein (apoaequorin) is a recombinant protein originally extracted from the Aequorea victoria species of jellyfish. In nature, apoaequorin produces a blue light when exposed to calcium.
Apoaequorin is thought to help improve memory and slow progressive loss of cognitive function, but little evidence supports this. Despite this, a lab-made version of apoaequorin is included as the primary ingredient of the dietary supplement Prevagen.
This article explores apoaequorin, why the research on its purported benefits falls short, and whether it is safe to take.
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Apoaequorin for Memory: What the Research Says
Supplement use should be individualized and vetted by a healthcare professional, such as a registered dietitian, pharmacist, or doctor. No supplement is intended to treat, cure, or prevent disease.
Problems with calcium regulation are believed to play a key role in aging-related mental decline.
Because apoaequorin has a similar structure to calcium-binding proteins, some scientists think it can improve calcium regulation and prevent or reverse the calcification of brain tissue.
Despite health claims, there remains little evidence that jellyfish protein or apoaequorin supplements can treat any condition.
Of the currently available research, conclusions are often limited by the small size and/or poor design of the studies. Others are based largely on pseudoscience.
Memory and Verbal Learning
In 2016, the Madison Memory Study evaluated the effects of effects of apoaequorin on cognitive function. Of note, this study was funded by Prevagen manufacturer Quincy Bioscience.
In the study, participants with self-reported memory concerns took either a daily 10 milligram (mg) dose of an apoaequorin supplement or a placebo (nontherapeutic substance). Compared with the placebo group, the participants who took the apoaequorin supplement showed improvements in recall and verbal learning based on cognitive tests taken on days 0, 8, 30, 60, and 90.
The study had flaws in how participants were selected. They varied in age by up to 50 years. They had only undefined "memory problems" rather than a diagnosis of dementia.
Since participants weren't selected based on a common factor, such as an early-stage Alzheimer's diagnosis, the study's conclusions could be misleading or easily misconstrued. Additionally, improvements were seen only in healthy or mildly impaired adults. No improvements were seen in those with significant cognitive impairment.
The way participants were tested is also problematic. Cognitive improvements are expected when repeating tests. Even in people with early Alzheimer's, routine brain exercises will almost always improve memory and cognitive function.
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Conclusions and Controversy
Shortcomings like these have enabled manufacturers to make claims that far exceed what the research actually reveals.
With Alzheimer's or any other form of dementia, a brain scan such as computed tomography (CT) ormagnetic resonance imaging (MRI) might be a better way to evaluate the effects of apoaequorin. To date, there has been no such research.
In 2019, the U.S. Federal Trade Commission (FTC) sued the manufacturers of Prevagen for misleading advertising. This was the second such lawsuit.
In their lawsuit, the FTC accused Quincy Bioscience of making "false claims" that Prevagen can improve memory "within 90 days." The FTC pointed to the Madison Memory Study in which even the researchers said the improvements were not statistically relevant.
What Are the Side Effects of Apoaequorin?
Little is known about the long-term safety of apoaequorin in any form. Studies utilizing synthetic apoaequorin have suggested it is safe and well-tolerated for up to 90 days.
Potential side effects include:
- Headache
- Dizziness
- Nausea
- Memory problems
- Difficulty sleeping
- Anxiety
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Who Should Not Take Apoaequorin?
There is not enough research assessing the safety of apoaequorin in those who are pregnant or nursing. If you are pregnant or breastfeeding, it is best to avoid this supplement.
Dosage: How Much Apoaequorin Should I Take?
All listed dosages are according to the manufacturer. This information should not be construed to mean that the doses are either safe or effective.
Apoaequorin is found almost exclusively in the United States in the oral supplement Prevagen but is also used as an ingredient in other "memory-boosting" products. Natural apoaequorin derived from crystal jellyfish is not commercially available.
Prevagen is taken once daily in the morning with or without food. It is available over the counter as an oral or chewable tablet in the following formulations:
- 10 mg (regular-strength)
- 20 mg (extra-strength)
- 40 mg ("professional formula")
Despite the use of the term "professional formula," there is no prescription version of Prevagen.
In the United States, the Food and Drug Administration (FDA) does not regulate supplements the way it regulates prescription drugs. That means some supplement products may not contain what the label says. When choosing a supplement, look for third-party tested products (such as the U.S. Pharmacopeia (USP), Consumer Labs, or NSF)and consult a healthcare provider, registered dietitian nutritionist (RD or RDN), or pharmacist.
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Alternative Ways to Improve Brain Health
Instead of trying self-proclaimed brain-boosting supplements, there are other promising ways to improve brain health.
Nutrition
Long-term eating patterns are an important factor in your overall health as well as your brain health. People who eat a Mediterranean-style dietthat emphasizes fruits, vegetables, fish, nuts, unsaturated oils (olive oil), and plant sources of protein are less likely to develop cognitive impairment and dementia.
Brain-healthy foods and nutrients to eat regularly include:
- Green leafy vegetables: Kale, spinach, collard greens, and broccoli are good sources of vitamin K, lutein, folate, and beta-carotene.
- Fatty fish: Salmon, tuna, trout, mackerel, and sardines are rich in omega-3 fatty acids. These lower beta-amyloid in the blood and may help prevent the beta-amyloid clumps in the brain, which are associated with Alzheimer's disease.
- Berries: Blueberries, strawberries, raspberries, and blackberries contain flavonoids that research shows help improve memory.
- Walnuts: The antioxidant and anti-inflammatory compounds in walnuts may bring benefits in reducing the risk or progression of cognitive decline and brain disorders.
Exercise
Avoiding inactivity and enjoying exercise and other forms of physical activity can bring benefits for your brain. Inactive adults report almost twice the prevalence of subjective cognitive decline compared to active adults.
Exercise recommendations are for adults to get at least 150 minutes ofmoderate-intensityphysical activity weekly or 75 minutes of vigorous-intensity activity.
Examples of moderate-intensity activity include:
- Brisk walking
- Light yard work, such as mowing, weeding
- Golf (without using a motorized cart)
- Biking at an easy effort
- Dancing
Examples of vigorous-intensity activity include:
- Running
- Swimming laps
- Competitive sports that include running or sprinting
- Jumping rope
- Bicycling over 10 miles per hour
Activity doesn’t have to happen all in one stretch. For example, moderate-intensity activity could be broken into 30 minutes a day, five days a week, or even smaller bouts that add up to 150 minutes.
Adults also need muscle-strengthening activities two or more days per week. And adults 65 and older need balance activities about three days per week.
Sleep
Sleep (or lack of sleep) affects your brain function. The brain needs sleep in order to process the information it takes in during the day and eliminate waste products from its cells.
Several studies have associated poor sleep or sleep abnormalities with the build-up of biological markers for Alzheimer’s disease, including amyloid beta and tau protein accumulation in the brain.
Aim for at least seven hours of sleep each night to maintain your brain function.
Summary
Jellyfish protein (apoaequorin) is a supplement ingredient claimed to improve memory and cognition. The scientific research supporting this claim, however, comes primarily from a small, poorly designed study financed by the manufacturer.
Apoaequorin is probably safe to take in recommended doses for up to 90 days. However, its long-term safety has not been established, and there are uncertainties about whether it is effective.
