Apoaequorin: Uses | Side Effects | Dosage | Research Studies | Products

What Is Apoaequorin?

Apoaequorin is a recombinant protein composed of 196 amino acids. This protein was initially extracted from a particular type of Jellyfish—known as Aequorea victoria. When Apoaequorin is disclosed to calcium, the protein and calcium bind, producing blue light.

Apoaequorin is now synthetically produced as a recombinant protein extracted from dried, purified, and concentrated bacteria called E.coli. Because getting the purified protein from the Jellyfish requires strenuous procedures and may lead to a preparation that may be toxic and harmful to the study organism. According to a patent, 2 tons of Jellyfish generally yield approximately 125 mg of the purified aequorin protein.

This protein has been considered a supplementary treatment for dementia with memory problems and minimizes progressive loss of cognitive function. In addition, this jellyfish protein has been used as an alternative treatment for those who have Alzheimer’s disease.

Most people take it to improve their memory function and brain performance. They also used it for enhancing thinking skills that come with aging, but there is no concrete and scientific evidence to support their use in these or other conditions.

Apoaequorin supplement comes in 3 strengths of 10, 20, and 40 mg tablets under the brand name Prevagen. This product is manufactured and marketed by Quincy Bioscience.

JellyFish (Apoaequorin)
JellyFish (Apoaequorin)

Apoaequorin History

This protein has been used in laboratories for more than five decades to determine how calcium works inside the cells.

In 1921 an American zoologist named Edmund Newton Harvey started working on aequorin, but he failed to exhibit classical luciferase-luciferin reaction. He only proclaims that light can be produced from dried photocytes. 

Then in 1961, a Japanese chemist named Osamu Shimomura began working on this project. He harvested thousands of Jellyfish from the dock in Washington to prove that light could be produced in the presence of seawater and calcium. As a result, Shimomura and two other scientists were awarded a Nobel prize in 2008 to work on green fluorescent proteins.

Apoaequorin has a calcium-binding ability and has been used as a calcium sensor for many years. However, many individuals also used this protein for memory enhancement and other antiaging effects. Because the elevated calcium level in neurons is linked with aging, disruption of synaptic functions, and cell death, anything that can maintain a healthy calcium level inside the cell has been chased as a potential therapeutic target. 

About the Company Who Manufacture It

Quincy Bioscience is a biotechnology company based in Madison, Wisconsin. This company manufactures Apoaequorin in the form of Prevagen. The company advertises this product for memory improvement and clear thinking. 

However, there are some concerns about the Prevagen false advertising claims from the Federal Trade Commission (FTC)—an independent government agency committed to promoting fair trade and protecting and educating consumers. In 2017, the FTC filed a lawsuit against Quincy Bioscience for false advertising claims.

In 2020, a separate class-action lawsuit was filed against the company that makes up the product. The company agreed to partially pay the people who bought the product and changed the product label details.

Apoaequorin Benefits

It is used for different conditions, but there is insufficient evidence to support these claims. However, here are some of the expected health benefits of taking Apoaequorin.

  • It is most commonly used for improving brain health, memory, and mental functions. Studies suggest that taking 10 mg per day will enhance your cognitive abilities and mental processes. 
  • Some studies also suggest that taking 20 mg of this supplement every 3 hours may help you slow the progression of Amyotrophic lateral sclerosis (ALS). 
  • It is also used for improving sleep quality. For example, taking 10mg daily may also improve your sleep health. 
  • The manufacturer also claims that this protein can treat or prevent Alzheimer’s disease, Dementia (age-related), Parkinson’s Dementia, and Vascular Dementia. Please note that there is very little evidence that this protein can treat or prevent the above conditions. 

Please note that the FDA has not approved this protein for the above conditions. In addition, human clinical data is limited, so more concrete evidence is needed to rate this supplement’s effectiveness for the above conditions. 

What does the research say about this protein—apoaequorin studies?

1. A study [1] sponsored by the Quincy bioscience indicates a strong relation between Apoaequorin and improved mental performance.

— Findings of this study

  • Total participants were 218 aged 40-91
  • They were divided into intervention (Apoaequorin) and controlled (Placebo) groups.
  • The intervention group took 10 mg of Apoaequorin for 90 days, and the controlled used a placebo therapy.

After 90 days of studying both groups, the intervention group significantly improved verbal learning and recalled the ISL and the ISL-DR.

According to another study, Apoaequorin is tolerated well and is safe to use with no side effects.

Here is what they found?

  • 10-16% improvement in verbal learning and memory in the intervention group.
  • But the control group showed a more modest (3-8%) change that was not significant.

One of the drawbacks of this study was that the author failed to compare both the groups and concluded that the Intervention group worked better than the controlled group.

Also, The authors of this study are affiliated with the company producing this protein in the form of Prevagen. So we can’t fully trust a company already advertising this product.

2. Another animal study [2] assesses protein safety and the potential adverse events of Apoaequorin.

The tested animals were rats, and they were also divided into two groups and were given this protein for 90 days.

— Results Of the Study:

  • There were no reported adverse effects and no mortality associated with this Apoaequorin use. So this means that the protein is safe to use with no serious side effects. 
  • However, no human data is available on this protein’s safety, concluding that the protein is 100% safe.

3. Another study [3] suggests that the intrahippocampal infusion of this ingredient may reverse aging‐related deficits in hippocampus‐dependent context fear memory.

4. Another relatively new study suggests that taking Apoaequorin can improve verbal learning in adult individuals. According to this study, both Apoaequorin and calmodulin contain Ca+ and cholesterol binding sites. They also have many serine protease cleavage sites, many guarded by cholesterol—this may hold back proteolysis and encourage blood-brain barrier uptake.

How does Apoaeqourin Works?

Human calcium-binding protein (Calmodulin) and Apoaequorin have the same structure. Calmodulin is thought to play a vital role in age-related mental decline and memory.

This Apoaequorin is structurally similar to the human calcium-binding protein. Therefore, it is believed that it might help regulate calcium in the brain and reduce memory loss and mental decline.

In 2008, researchers received a Nobel prize in chemistry to disclose green fluorescent Protein (GFP). GFP is like a jellyfish protein and has applications like those of Apoaequorin.

Scientists attached these fluorescent proteins to different other proteins. When connected, they serve as noticeable markers that scientists can easily distinguish as the body’s combined proteins change. And this has proven beneficial in advancing the scientific understanding of how proteins work.

How does Apoaequorin affect the brain?

Different chemicals affect a person’s memory. These include amyloid, acetylcholine, glutamate, and calcium. In particular, increased calcium levels in neurons are linked to their deterioration and lack of function. In addition, the production of this calcium-binding protein in neurons decreases with age.

Apoaequorin binds to calcium in the laboratory environment, lowers calcium levels, and prevents neuron death. Therefore, scientists hope that its benefits can be extended to human neurons in the real world from the lab.

Since calcium deposits in the brain are thought to contribute to Dementia and Alzheimer’s, protein from Jellyfish has been suggested as a potential prevention and treatment strategy.

However, according to some experts and pharmacologists, Apoaequorin degrades into amino acids by the stomach enzyme (Pepsin) and may not reach to brain. That’s the reason it is relatively safe to use, but at the same, this property also makes it inactive.

If Apoaequorin can’t reach the brain, it is useless because we need to transport it into the brain without degrading it into amino acids.

This problem can be solved only when the Apoaequorin is bound with cholesterol molecules to protect it from stomach acid. Also, cholesterol can help Apoaequorin absorb into the lymph system and help reach the brain by crossing the blood-brain barrier. [4]

Does Apoaequorin Work?

It is unclear whether taking Apoaequorin by mouth will make you smarter or not but one study by Prevagen’s manufacturer suggests that the supplement can help with memory. However, there’s no concrete evidence to back up the idea that Apoaequorin taken by mouth can boost memory. 

It’s no surprise that this study didn’t show any major benefits from Prevagen; it is a small, early-stage, double-blind, and placebo control trial. Experts usually don’t reach conclusions based on one data point and would need multiple larger studies to confirm such findings with more reliable results before drawing solid conclusions. 

Is it safe to use—Apoaequorin Side Effects?

While it is still unknown to work for memory improvement, some in-vivo and in-vitro studies suggest that the protein is tolerated well and may not cause severe toxicity.

Some animal studies also suggest that this protein is not a known allergen and doesn’t cause allergic reactions.

If you look at the 90 days study above suggests that this is safe to use and has no reported toxicity after oral administration.

Although the protein is tolerated well, the manufacturer’s most commonly reported side effects were dizziness, headache, nausea, etc. At the same time, the less common side effects include insomnia, anxiety, and memory problems.

Other infrequent side effects reported include heart and nervous system toxicity in a few cases.

Also, pregnant and breastfeeding women should not use it because there is not enough data about the safety of taking Apoaequorin in pregnancy. So it’s better to avoid it.

Following are some of the Apoaequorin side effects;

  • Nausea
  • Headache
  • Constipation
  • Dizziness
  • High Blood pressure
  • Chest pain on high doses
  • Edema
  • Increase heart rate.
  • Some severe side effects like hypotension and depression with suicidal thoughts may also occur in people with multiple sclerosis. [5]

There is no known interaction with other medicines and foods supplements. However, it’s always a good idea to consult your doctor before using this or any other ingredient.

Dosage Of Apoaequorin

Apoaequorin is not approved by the Food and Drugs Administration (FDA). So, there is no recommended dose of this protein because it is still under observation, but according to one study, 10 mg per day is tolerated well and don’t cause any side effect.

However, it’s always better to consult your health care provider and pharmacist for dose adjustment. The recommended dose also depends on many factors, like the age and health of the patient. 

  • The usual recommended dose for cognitive and memory function is 10 mg per day.
  • The usual daily suggested dose for amyotrophic lateral sclerosis is 20 mg every 3 hours. This is off label use of Apoaequorin.
  • The usual recommended dose for better sleep quality is 10 mg per day.

Always consult your Doctor or Pharmacist before taking Apoaequorin or any other supplement or medicine, and follow the direction on the label.

Bottom Line—Apoaequorin

Although Quincy Bioscience widely advertises Apoaequorin for memory improvement, there is less evidence to rate its effectiveness in treating other mental conditions.

It has still not been clinically proven effective in the above conditions.

The problem with this protein is that there is still minimal data available on humans. The company that manufactured this protein conducted some trials, but they didn’t meet the scientific standards.

Some lawsuits are also against the company for false advertisement and cognitive improvement claims.

In 2012 the US food and drug administration (FDA) also issued a warning letter to the manufacturer for the wrong therapeutic claims on their official site. According to the FDA guidelines, this product did not meet the definition of a dietary supplement but, alternatively should be considered a drug [2]

If you are looking for a brain-boosting supplement, why not select a supplement that contains some proven and premium ingredients.

Some ingredients that can help you improve your cognition are L-theanine, Creatine, Bacopa monerie, Ginkgo biloba, Panax ginseng, Rhodiola Rosea, and many other supplements.

Before buying any nootropic supplement, always do your research and check all the ingredients and the research behind each component.

References 

  1. Effects of a Supplement Containing Apoaequorin on Verbal Learning in Older Adults in the Community: [Internet],[Cited February 2021], Available From https://pubmed.ncbi.nlm.nih.gov/26878676/
  2. Safety assessment of Apoaequorin, a protein preparation: subchronic toxicity study in rats: [Internet],[Cited February 2021], Available From https://pubmed.ncbi.nlm.nih.gov/23470325/
  3. Apoaequorin differentially modulates fear memory in adult and aged rats: [Internet],[Cited February 2021], Available From https://onlinelibrary.wiley.com/doi/full/10.1002/brb3.1832
  4. Computational comparison of a calcium-dependent jellyfish protein (apoaequorin) and calmodulin-cholesterol in short-term memory maintenance: [Internet],[Cited February 2021], Available From https://pubmed.ncbi.nlm.nih.gov/28159636/
  5. Apoaequorin: [Internet],[Cited February 2021], Available From: https://www.ncbi.nlm.nih.gov/books/NBK552157/

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