Nutrition

This Summer Fruit Preserves Memory

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What if the secret to protecting your brain from Alzheimer’s isn’t locked away in a pharmaceutical lab—but ripening quietly in your fridge? Scientists have been quietly studying a golden-hued plant pigment with a remarkable array of brain-boosting abilities. But there’s a catch. Because it’s natural, it can’t be patented—making it virtually invisible to big pharma’s radar. That is, until now. A synthetic version may finally catapult this overlooked compound into the spotlight... and it all started with strawberries.

Key Takeaways

  • Fisetin, a naturally occurring flavonol found in strawberries and other yellow-tinted fruits/vegetables, has powerful brain-protective effects in lab animals—ranging from reducing inflammation to reversing memory loss.<

  • A synthetic version called CMS121 has been created to overcome fisetin’s limitations (poor bioavailability and weak brain penetration) and shows promise in reversing Alzheimer’s symptoms in mice.

  • Although clinical trials in humans are still pending, fisetin supplements are already available and may offer some preventative cognitive benefits, according to leading researchers.

The Alzheimer’s-Fighting Secret Hiding in Your Produce Aisle 

A plant pigment that gives color to many fruits and vegetables has multiple protective properties that could shield the brain from Alzheimer's and other neurological diseases.

Being natural, the compound can't be patented, so it’s of no value to drug companies. But scientists have now developed a synthetic version of this plant pigment and are pushing for clinical trials.

Even if successful it could take many years before this treatment becomes FDA approved for use in Alzheimer’s treatment and prevention. Meanwhile, the plant compound called fisetin is already available today in a juicy fruit or in a dietary supplement.

Fisetin is an antioxidant flavonol that gives many fruits and vegetables a yellow hue, such as onions, cucumbers, apples, persimmons and yes, even strawberries right before they fully ripen and turn red.

A Colorful Cornucopia of Brain Benefits

Dr. Pamela Maher from The Salk Institute for Biological Studies, La Jolla, California has been studying fisetin for two decades.

Her team's work has shown this remarkable antioxidant crosses the blood brain barrier. Once in the brain, it is. . .

  • Neuroprotective -- shields nerve cells from multiple toxic insults

  • Neurotrophic -- promotes the growth of neurons while slowing their death

  • An antioxidant -- induces the production of a variety of endogenous antioxidants, in particular glutathione, a key antioxidant enzyme system that protects against damage from free radicals

  • Anti-inflammatory

  • Memory boosting -- enhances learning and memory, including long-term memory

  • Immune modifying -- positively influences pathways of the innate immune system that are involved in the progression of Alzheimer's

  • Protective against Alzheimer's by reducing the brain cell damage caused by amyloid plaques and limiting the accumulation of tau tangles that cause the death of brain cells

  • Reduces the impact of Huntington's disease, a rare, inherited brain disease.

That's an awesome list of brain benefits.

But of course these benefits were all discovered in cell cultures and rodent studies. Fisetin can't be guaranteed to act in the same way in the human brain, since clinical trials are notably absent.

This may change, however, after promising findings of a new synthetic version of fisetin developed at the Salk Institute. A synthetic version can be patented, so lo and behold, the checkbooks come out and there’s a willingness to fund expensive laboratory studies.

Reverses Memory Loss in Animal Studies

The Salk team had already tested the new version, called CMS121, and found it was effective at slowing the degeneration of brain cells and improving the memory of mice.

Following that, it was time for a bigger test using mice specially engineered to get the human equivalent of Alzheimer's. Some would get the drug while another group would not receive it. A third acted as healthy controls.

The scientists tried to replicate how a middle-aged patient might be treated. So at nine months, the equivalent of middle age in mice, when the mice were already beginning to develop learning and memory problems, the researchers gave the active group daily doses of CMS121.

Three months later, all groups were given a battery of cognitive and behavioral tests.

The result of their experiment was that the Alzheimer's mice taking the drug saw their memory improve. They performed just as well as the healthy control rodents. But the untreated Alzheimer's mice performed poorly.

In subsequent pathology analysis, the researchers discovered that the drug reduced neuro-inflammation. In addition, fat molecules called lipids, which play important roles in every cell in the body, differed in the mentally impaired mice who were not taking CMS121.

FASN - Exciting New Alzheimer's Target

In particular, the non-drug Alzheimer's group had higher levels of lipid peroxidation, the process by which free radicals damage lipids in cell membranes.

"That not only confirmed that lipid peroxidation is altered in Alzheimer's, but that this drug is actually normalizing those changes," said GamzeAtes, a member of the research team.

To discover why this occurred, additional research showed CMS121 lowered levels of fatty acid synthetase (FASN), an enzyme that can promote lipid peroxidation.

To see if this happens in humans, they examined brain samples of people who had died of Alzheimer's. Sure enough, they had higher levels of FASN compared to people of the same age who were cognitively healthy when they died. Dr. Maher, who led the team, said that "identifying a new target...is really exciting and opens a lot of doors."

Why CMS121 Was Developed:

While fisetin, a natural flavonoid found in strawberries and other fruits, shows strong antioxidant and neuroprotective effects, it has:

  • Poor bioavailability

  • Limited brain penetration

CMS121 was engineered to:

  • Enhance blood-brain barrier penetration

  • Increase stability and potency

  • Mimic the longevity-promoting and brain-protecting effects seen in fisetin

Getting Fisetin Naturally

While we await human trials of CMS121, fisetin, the natural version, is available. Unfortunately, it's found in meaningful quantities in just one food – strawberries – and you would have to eat a sizable amount each day to secure the benefits seen in animal studies.

Realistically, fisetin needs to be taken as a supplement.

Although there are no human trials, judging from the many years of work conducted on rodents, Dr. Maher believes fisetin is safe to take.

Even though people have been taking it for some years, "I haven't really heard of any negative reports," she said. "I think potentially, fisetin could be of benefit as a preventative."

Summary

Fisetin, a naturally occurring antioxidant found in strawberries and other fruits and vegetables, has shown remarkable potential in protecting brain health and combating the effects of neurodegeneration. Research led by Dr. Pamela Maher at The Salk Institute has demonstrated that fisetin can cross the blood-brain barrier and deliver a host of benefits, including reducing inflammation, enhancing memory, and protecting neurons from damage associated with Alzheimer’s disease. However, due to fisetin’s poor bioavailability, scientists developed a synthetic version called CMS121, which has shown the ability to reverse memory decline and reduce brain inflammation in animal models. While human clinical trials are still pending, these findings suggest fisetin—and especially its synthetic counterpart—could play a promising role in future Alzheimer’s treatments and cognitive health strategies.

Frequently Asked Questions

What is fisetin and where is it found?

Fisetin is a plant pigment and antioxidant flavonol found in strawberries, apples, onions, and other fruits and vegetables.

How does fisetin affect brain health?

In lab studies, fisetin has shown neuroprotective, anti-inflammatory, and memory-boosting effects, helping reduce markers of Alzheimer’s disease in animals.

What is CMS121 and why was it developed?

CMS121 is a synthetic version of fisetin designed to improve brain penetration and stability, showing promising results in Alzheimer’s mouse models.

Is fisetin safe to take as a supplement?

While human trials are lacking, animal studies suggest fisetin is safe, and researchers like Dr. Pamela Maher believe it may offer preventative benefits.

Can eating strawberries provide enough fisetin for brain health?

Strawberries contain fisetin, but not in high enough amounts to match the doses used in studies; supplements are likely needed for therapeutic effects.

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