Fisetin and Brain aging

Nutrients derived from plants have been shown to protect against changes in the brain that lead to neurological disorders.

In 2021, two review articles identified fisetin as one of the most promising.^1,2

Preclinical studies show the potential of fisetin to reduce the impact of stroke, mild cognitive impairment, and dementia.^1,2

A Multifunctional Nutrient

The flavonoids are a group of plant compounds with health-promoting properties.

Fisetin is a flavonoid with dozens of biological mechanisms that support neurological health.²

Fisetin is found in many fruits and vegetables, but only in very small amounts. Most commercially available oral fisetin has poor bioavailability.³

Scientists have overcome this problem by coating the fisetin in a form of fiber found in the fenugreek plant.

This helps protect the fisetin from getting broken down, leading to about 25 times more fisetin being absorbed into the body.⁴

Promise for Neurological Conditions

In pre-clinical studies, fisetin has shown promise for a range of neurological disorders that include:^1,2

• Alzheimer’s disease,
• Brain aging and cognitive decline,
• Stroke,
• Neurological complications of diabetes,
• Depression,
• Traumatic brain injury,
• Parkinson’s disease,
• Huntington’s disease,
• Amyotrophic lateral sclerosis (ALS),
• Neurotoxicity (damage to the nervous system caused by toxins),
• Schizophrenia,
• Vascular dementia, and
• Other forms of neurodegenerative disease.

Additionally, in a clinical trial, fisetin improved response to treatment in ischemic stroke.⁵

Fighting Against Neurological Disease

A review published in 2021 found that fisetin modulates 37 different biological pathways.²

All these actions could reduce the risk and severity of age-related neurological conditions.

Five ways that fisetin protects the brain and nervous system are:

1. Preventing Toxic Brain Deposits

The plaques and tangles deposited in the brain are made of toxic proteins called beta-amyloid and hyperphosphorylated tau. In preclinical models, fisetin prevents their accumulation.^6,7

In another study, fisetin increased autophagy, a form of cellular cleaning, which helps clear existing toxic proteins from brain cells.⁸

2. Antioxidant Activity

Oxidative stress is a significant contributor to neurological disorders.

Fisetin is a potent antioxidant that can scavenge harmful compounds before they do damage.¹

It has been shown in preclinical models that fisetin increases intracellular levels of glutathione, a free-radical scavenger important for cell survival.⁹

3. Reduced Chronic Inflammation

Chronic inflammation contributes to most chronic disease in the brain.

In preclinical trials, two forms of fisetin blocked activation of nuclear factor-kappa B (NF-kB), a master regulator of inflammation.^10,11 This action prevents the release of pro-inflammatory compounds.

In a study in a particular strain of mice susceptible to Alzheimer’s-type neurological degeneration, feeding them fisetin in early to mid-life prevented learning and memory decline.

Fisetin also limited levels of inflammatory compounds that are elevated in Alzheimer’s disease and other neurodegenerative disorders.¹²

4. Memory and Learning Support

A protein called CREB helps brain cells adapt to experiences over time, a process known as long-term potentiation.¹³ This is a critical component of memory formation.

Fisetin increases activation of CREB and enhances long-term potentiation in preclinical studies.^13-15

5. Blocking Glycation Damage

Glycation occurs when glucose attaches to proteins, DNA, and lipids, forming toxic compounds.

Damage caused by glycation has been associated with cognitive dysfunction and neurodegenerative diseases like Alzheimer’s disease.¹⁶ Glycated beta-amyloid is even more damaging to brain function than non-glycated forms.¹⁷

In mice, fisetin was shown to reduce glycation and its damaging effects.¹⁸

Summary

The flavonoid fisetin acts in multiple ways that may help improve nervous system health and reduce risk for neurological disorders.

Two recent reviews amalgamate mostly preclinical evidence supporting fisetin’s abilities.

These include the prevention or management of neurological conditions such as stroke, Alzheimer’s, Parkinson’s, and cognitive decline.

Material used with permission of Life Extension. All rights reserved.