What to Know About Jellyfish (Apoaequorin)

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.

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.

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 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.

However, the study was flawed for many reasons, particularly in the way its participants were selected. For example, the ages of participants varied by as much as 50 years. Self-reported "memory problems" is also a vague criterion. Memory problems can be caused by any number of things, not just 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.

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) or magnetic resonance imaging (MRI) would be the best 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.

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
  

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?

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.

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 diet that 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 rich in brain-healthy nutrients like vitamin K, lutein, folate, and beta-carotene.
• Fatty fish: Salmon, tuna, trout, mackerel, and sardines are rich in omega-3 fatty acids, healthy unsaturated fats that have been linked to lower blood levels of beta-amyloid—the protein that forms damaging clumps in the brains of people with Alzheimer's disease.
• Berries: Blueberries, strawberries, raspberries, and blackberries contain flavonoids that give berries their brilliant hues and research shows help improve memory.
• Walnuts: Walnuts contain several components that have antioxidant and anti-inflammatory effects. Animal and human studies suggest that consuming walnuts regularly may improve cognition and reduce the risk and/or progression of mild cognitive impairment and Alzheimer's disease.

Exercise

Regular physical activity has been shown to improve memory and reduce the risk of cognitive decline, including dementia. One study found that cognitive decline is almost twice as common among inactive adults compared to those who are active.

For the most benefit, adults need at least 150 minutes of moderate-intensity physical activity weekly or 75 minutes of vigorous-intensity activity.

Examples of moderate-intensity activity include:

• Walking briskly (a 15-minute mile)
• Light yard work (raking/bagging leaves or using a lawn mower)
• Actively playing with children
• Biking at a casual pace

Examples of vigorous-intensity activity include:

• Jogging/running
• Swimming laps
• Rollerblading/inline skating at a brisk pace
• Cross-country skiing
• Jumping rope

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) significantly impacts brain function. A healthy amount of sleep is vital for “brain plasticity,” or the brain’s ability to adapt to input. Researchers also believe that sleep may promote the removal of waste products from brain 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.

A minimum of seven hours of daily sleep seems to be necessary for proper cognitive 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.