Untitled Document
For decades, scientists have searched for compounds that can slow degenerative aging processes.
A recent focus is a plant extract called fisetin.
Found in strawberries, apples, and other plants, fisetin has a range of benefits that may increase longevity.
Fisetin has been shown to:
- • Function as a senolytic, clearing away dysfunctional senescent cells and allowing healthy cells to thrive.
- • Protect the brain in various models of neurodegenerative disorders.
- • Improve outcomes in people who have suffered strokes.
- • Help prevent malignant changes in cells.
- • Help fight obesity and type II diabetes.
Several human trials are currently underway.
The challenge up until now was that fisetin is converted to an inactive form in the digestive tract. This means very little is absorbed into the blood stream.
For the first time, scientists have developed a low-cost method to increase absorption up to 25 times higher, thus enabling fisetin to be distributed throughout the body.
What Is Fisetin?
Fisetin, a flavonoid, is found in various fruits and vegetables including strawberries, apples, persimmons, grapes, and onions.
Its benefits overlap with some other flavonoids, including green tea catechins and quercetin. But it has its own unique set of biological properties.
Most notably, a recent study found fisetin to be the most potent senolytic compound among a group of flavonoids that were tested. Senolytics are at the center of today’s anti-aging research.
Fisetin Extends Lifespan
When cells become old or dysfunctional, they’re supposed to die off to make room for new cells. But as we age, many cells become senescent instead.
What this means is that these cells lose their ability to divide or perform basic functions and refuse to die. Some scientists refer to senescent cells as “zombie cells.”
Senescent cells don’t just linger around. They pump out toxic compounds that degrade nearby cells and incite chronic inflammation that causes systemic damage.
Cellular senescence has become a major target for anti-aging research. Preclinical studies indicate that compounds called senolytics remove senescent cells and can slow or even reverse aging processes.
Recent research has found that fisetin is an exceptionally powerful senolytic. When compared to other plant compounds, including quercetin, fisetin was the most effective at removing senescent cells, both in cell culture and in mice.
The effects are dramatic. Mice given fisetin lived an average of about 2.5 months longer, an almost 10% extension of lifespan—even when treatment was started at the human equivalent of 75 years of age.
The Mayo Clinic has begun clinical trials to study the ability of fisetin to reduce senescent cell burden in aging humans.
Anti-Aging Properties
Sirtuin proteins are another anti-aging target. These cellular protectors are found in all cells in the body, and are vital for keeping cells performing at peak level.
Sirtuin function tends to diminish with age. But fisetin activates sirtuin function in cells, countering this decline. In various animal models, sirtuin activation has been shown to extend lifespan significantly.
Fisetin may protect against aging in other ways:
- • It reduces inflammation, a driver of many chronic illnesses and even of aging itself.
- • It mimics some of the effects of a calorie-restricted diet, which has been shown to boost resistance to disease and increase lifespan.
- • It helps prevent oxidative damage that leads to accelerated aging and degenerative disease.
WHAT YOU NEED TO KNOW
Fisetin Promotes Healthy Longevity
- • Fisetin is a compound found in several fruits and vegetables, including strawberries, apples, grapes, and onions.
- • Fisetin is the most potent senolytic compound found among a panel of flavonoids, selectively removing senescent cells and extending longevity in animal studies.
- • This flavonoid has also been shown in preclinical studies to help protect against cancer, type II diabetes, and obesity, and in a human study to improve outcomes in stroke victims.
- • Taken orally, pure fisetin is converted to an inactive form in the body. But scientists have discovered that combining it with galactomannans from fenugreek prevents that from happening.
- • A new formulation boosts the bioavailability of fisetin by 25 times, allowing more of it to circulate throughout the body, promoting health and supporting longevity.
Preventing Obesity and Diabetes
Obesity leads to a skyrocketing risk of metabolic disorders such as type II diabetes. It also increases the risk for cardiovascular disease, cancer, dementia, and many other disorders.
Preclinical studies show that fisetin appears to act as a kind of “metabolism control switch,” reducing fat cell accumulation and suppressing activation of the protein mTOR, which is linked to weight gain. In mice fed a high-fat diet, fisetin prevented increase in body weight and accumulation of harmful white fat tissue.
Fisetin also helped fight fat accumulation in the livers of animals fed a high-fat diet, a common occurrence with metabolic disease that can compromise liver function and lead to fatty liver disease.
Fisetin may provide benefits for those already suffering from type II diabetes.
In rodent models of diabetes, fisetin lowers body weight and leads to improved glucose control with lower hemoglobin A1c levels, a marker of blood sugar regulation over time.
Poorly controlled diabetes often causes disabling or life-threatening complications throughout the body. In mice, fisetin significantly reduces the severity of diabetic complications, including slowing the progression of cataracts, preventing kidney damage, and improving kidney function.
A human trial of fisetin’s ability to protect kidney function, particularly in diabetes patients, is currently underway.
Brain Benefits
People who suffer from a stroke are often treated with medication to dissolve the clot blocking blood flow to the brain. This can save a patient’s life, prevent damage to the brain, and even reverse the symptoms of stroke in some patients.
But ER doctors are working against the clock when treating acute (ischemic) stroke. The best chances of success occur when treatment begins within three hours of the onset of symptoms.41 Many people suffering a stroke are treated too late and suffer permanent neurological injury (and paralysis).
A recent study shows that combining clot-dissolving medication with fisetin significantly extends the treatment window.
Patients receiving fisetin in addition to usual treatment up to five hours after a stroke had neurological outcomes as good as those treated within three hours. This extension of the therapeutic window means that many stroke victims who would otherwise suffer permanent loss of brain function have a better chance of recovery.
Fisetin has also shown neuroprotective benefits in animal models of Alzheimer’s disease, Parkinson’s disease, ALS (amyotrophic lateral sclerosis), and other brain pathologies, reducing the severity of disease and improving cognitive function.
Fighting Cancer
Fisetin has shown potential in preventing cancer and limiting the growth and spread of existing tumors in preclinical studies. Among its anti-cancer properties:
- • Fisetin induces apoptosis, or programmed cell death, in cancer, which can facilitate removal of tumor cells.
- • As an anti-inflammatory, fisetin reduces compounds that contribute to chronic inflammation and cancer progression. In a study of patients with colorectal cancer, fisetin reduced levels of pro-inflammatory mediators.
- • Fisetin enhances autophagy, cellular housekeeping that keeps cells functioning normally. Enhanced autophagy can inhibit cancer cell survival.
- • Fisetin helps prevent angiogenesis, the formation of new blood vessels, in cancer, starving tumor cells of oxygen and glucose.
- • Fisetin helps prevent oxidative damage which can contribute to DNA mutations and cancer development.
- • Fisetin may inhibit cancer cell migration and metastasis, the spread of cancer to a different part of the body.
Improved Bioavailability
In its pure form taken orally, there’s a problem with fisetin: Once it reaches the gut, enzymes in the body rapidly modify it into a form which is inactive and all but useless.
Scientists have discovered a way around this problem. By combining it with natural compounds called galactomannans isolated from the herb fenugreek, fisetin is protected from being modified in the intestinal tract. It remains active and can be readily absorbed into the bloodstream.
In a recently conducted study, researchers found that the newly formulated fisetin-galactomannan combination, using a patented green technology, increases bioavailability (how much is absorbed and circulates) in people by 25 times.
This opens a brand-new door in enabling aging people to derive meaningful benefits by supplementing with a low-cost nutrient.
OPTIONS TO REMOVE SENESCENT CELLS
Most of you are reducing your senescent cell burden by:
- • Two-day-a-week fasting (not eating 2 days each week) or time-restricted eating (fasting 16-18 hours most days) and/or some other form of dietary restriction,
- • Several times a year dosing using dasatinib + quercetin and/or,
- • Weekly dosing using black tea theaflavins + quercetin + apigenin.
Fisetin is arguably one of the most focused, targeted senolytic agents, based upon current science. For the first time, people can obtain it in bioavailable form as opposed to taking over 1,400 mg a day of fisetin by itself and hoping enough is absorbed into your bloodstream.
For those who want to continue with a weekly senolytic program, taking seven capsules once-a-week of bioavailable fisetin along with a black tea theaflavins + quercetin + apigenin formula is an option.
Alternatively, you may also take the bioavailable fisetin dose daily for its other benefits and continue with weekly black tea theaflavins + quercetin + apigenin.
There is potential benefit to daily senolytic as this is how it happens in younger people with strong immune systems that constantly remove senescent cells.
Studies are planned for using bioavailable fisetin on differing dosing schedules to ascertain the ideal protocol to removing senescent cells and reducing the “senescent associated secretory phenotype” (SASPs).
While the longevity data on dasatinib are compelling, some people experience mild flu symptoms or GI upsets, whereas fisetin does not cause these unpleasant side effects.
We look forward to results from human trials to identify the optimal senolytic protocol for aging persons to follow. This may involve several senolytic compounds based on individual response rates as measured by the “senescent associated secretory phenotype,” skin punch measures of senescent fibroblast cells, or other senolytic measuring methods being explored.
Highlights from Recent Study
- • Senescent cell production rate increases with age due to accumulation of mutations, telomere damage, other factors triggering cell senescence.
- • Senescent cells catalyze their own production by paracrine and bystander effects.
- • Senescent cell removal decreases with age due to decline in immune surveillance functions.
- • Senescent cells reduce their own removal rate.
Karin O, Agrawal A, Porat Z, et al. Senescent cell turnover slows with age providing an explanation for the Gompertz law. Nat Commun. 2019 Dec 2;10(1):5495.
Senescent Cell Removal Declines with Aging
Senescent cells turn over in five days in 3-month-old mice but take 25 days in 22-month-old mice. This model predicts a vicious cycle where senescent cells accumulate faster and are degraded slower.
At the point of 30% senescent cell load animals often appear to reach tipping point resulting in death.
Summary
Fisetin is a compound found in many plants, including strawberries and apples.
It is the most effective senolytic compared to a panel of flavonoids, removing aged, dysfunctional senescent cells in preclinical studies. This may help improve function in older age, shield against chronic disease, and increase healthy longevity.
In mice, fisetin alone extended lifespan by approximately 10%.
Extensive research also demonstrates the potential of fisetin to help protect against cancer, stroke, obesity, type II diabetes, and other metabolic disorders.
A new fisetin formula compounds it with fenugreek, which protects it from inactivation in the gut. This allows more fisetin to be absorbed and distributed throughout the body for systemic benefits.
Untitled Document
Fisetin Benefits & Side Effects
Need another reason to enjoy some wine? We’ve got one. Antioxidants found in wine turns out to be fisetin. Sure, this substance seems to be lesser known amongst its more popular antioxidant cousins, but its health properties should not be ignored. If not just another reason to enjoy a glass of wine from time to time, you should know that fisetin can also help fight many health ailments that plague our modern world.
Sounds like a foreign language right? Most of us have never heard of fisetin before. It’s not catchy, and it’s not any food that we can easily recognize. But surprisingly, it’s in most of the foods we love and know. Fisetin is an antioxidant that can be found in all kinds of fruits, veggies and nuts in varying amounts. This compound can help relieve inflammatory conditions, reduce oxidative stress and regulate the growth of our heart cells.
Benefits of Fisetin
Fisetin not only helps improve our immune system and prevent hyperdrive, we also know this nutrient helps protects the health of our nerves, though we aren’t quite sure how it does that.
Fisetin has been seen in the laboratory to have direct effects on our cells. It interacts with proteins on our cell membrane and regulates the ions that move in and out. These ions play a big role, and can influence the process of aging and even propagate diseases like cancer and diabetes. The regulation of these ion movements can also have a huge impact on the health of our nerves. In the lab, this small but mighty molecule has demonstrated effects that heal nerves, fight cancer and soothe inflammation.
Anti-Aging
Who knew that a strawberry smoothie could keep you young? Fisetin, as well as other flavonoids, are present in senolytic foods which help prevent aging. What is this senolytic power exactly? Well, first it’s important to understand what senescence is. Senescence is the process of aging where our cells break down with time. This includes the breakdown of red blood cells that carry oxygen through our blood stream, as well as DNA damage that all our other bodily cells endure daily. The more DNA damage we have, the more cell death and dysfunction. Overall this plays a huge role in the process we know collectively as aging.
Plant flavonoids like fisetin have been found to help slow down senescence. It’s thought that it does this by stabilizing membrane proteins to help red blood cells from dying. It also helps reverse some of the DNA damage in our aging cells. With less DNA damage, cells grow and replicate. All of these effects can help us prevent many age-related diseases, such as osteoporosis, heart disease and the general frail-ness of old-age. Though all flavonoids have powerful effects against aging, it’s been suggested in experiments that fisetin is the strongest anti-aging compounds of them all.
Regulates Blood Sugar
Fisetin can also help people suffering from diabetes in many different ways. Though research is limited, one study on diabetic rats found that month-long supplementation with fisetin lowered blood sugar levels. Scientists aren’t sure how it works, but it’s possible that fisetin helps regulate sugar production in the liver. Other studies have also mentioned preventative effects against diabetes-related damage to the kidneys, nerves and the heart. Fisetin supplementation also appears to help increase insulin secretion in diabetic rats.
May Help Fight Cancer
Fisetin may fight cancer from multiple different angles. As an antioxidant, fisetin, like other flavonoids, can reduce oxidative stress. It’s unique chemical structure allows it to give electrical charges to damaging free-radicals, neutralizing them. This keeps them from damaging our genes and promoting cancer. Fisetin also hijacks cancer’s unique ability to self-replicate indefinitely by blocking an “immortality” mechanism in the form of a protein enzyme called toiposomerase.
Additionally, fisetin can help us fight chemo-resistant cancers. Some studies have found it effective in helping kill resistant colon cancer cells in the lab. It’s possible that this special compound can actually disrupt survival mechanisms cancer cells use to survive through treatments. Though research is scarce, there seems to be interest in using fisetin in combination with traditional therapies to treat a wide variety of cancers.
Heart Health
Fisetin can also help improve your heart health. It improves circulation, reduces cholesterol, and protects our cardiovascular system from oxidative stress. One study found that fisetin helps prevent complications that can develop after a heart attack. It does this by preventing inflammation that results in irregular scar tissue and cardiac muscle growth that can occur after heart attacks. Researchers used fisetin injections for rats that had suffered a heart attack and found that rats that received the injection had better heart health overall. Additionally, rats receiving fisetin had lower rates of developing heart attack related arrhythmias down the line.
Skin Health
You can also see the benefits of fisetin on your skin. Fisetin has been proposed to help improve collagen, reduce UV damage and even treat eczema. Researchers found that mice taking fisetin were able to prevent skin inflammation and damage induced by UV rays. It also helped block the breakdown of collagen, which is the most important substance to keep skin youthful. As an antioxidant, it can also help neutralize oxidative stress that’s always a consequence of any UV light exposure. It also helps our skin form a healthier, stronger barrier against outside contaminants by promoting tighter seals between each skin cell.
Cognitive Health
Fisetin not only helps you feel and look good, but helps you think faster too. If you’re suffering from any mood disorders or having memory problems, it’s time to give fisetin a closer look. This special nutrient found in our everyday berries and vegetables can help us protect ourselves from diseases like Parkinson’s or Alzheimer’s. It does this by directly influencing the hippocampus, which is where our memories are stored. Fisetin helps prevent nerve damage by fighting toxins that can cause degradation. In animal studies, fisetin has even been helpful in reducing the severity of Huntington’s disease.
Fisetin in Foods
You can find fisetin in many different regular foods like nuts, veggies and even wine. However, to get the biggest dose naturally, you’d have to eat a ton of strawberries. Strawberries are one of the best sources of foods with fisetin. It’s got 6 times the level of fisetin found in apples, and 16 times more than that found in persimmons, which are second and third runner-ups in terms of foods with fisetin.
Side Effects of Fisetin
There are no reported adverse effects associated with taking fisetin, however we are still lacking research in its safety. It’s generally thought to be very safe. However, some proposed side effects would include stomach upset, and it may interact with important medications. Always talk to your doctor before taking any new supplement, including fisetin. Pregnant women and children should avoid taking it as well, as there is no proper research to tell if it’s completely safe for them.
The Bottom Line
Fisetin is a small, unique plant nutrient that is a type of flavonoid (antioxidants often found in berries and other fruits and veggies). Fisetin has many unique abilities that promote health. It’s antioxidant powers help us fight cancer and prevent oxidative damage to our skin, heart and nerves. It may help prevent aging as well aging-related diseases like cancer and Alzheimer’s. Fisetin can help our skin retain its youth. It also fights off oxidative damage from sun exposure.
Source
Untitled Document
The amount of fisetin consumed in clinical trials vary greatly, with participants taking doses ranging from 100 milligrams per day to 1,400 milligrams daily. Recommendations on fisetin supplement labels vary as well, with doses ranging from 100–500 milligrams per day.
There isn’t enough research to make an educated recommendation on an appropriate fisetin dosage. Researchers do know that the antioxidant is fat-soluble, so consuming it with fats promotes better absorption. *
In a clinical study of colon cancer patients, 100 mg/day was effective for reducing inflammation.
In an ongoing clinical trial looking at the effects of fisetin on inflammation, bone health, and frailty in the elderly, fisetin will be used at a high dosage of 20 mg/kg for two consecutive days. This would be around 1,400 mg/day for a 155-lbs person.
We don’t recommend taking such a high dosage until the results of this study are published.
Some researchers are doubtful about the benefits of supplemental fisetin since it is poorly absorbed when taken orally.
But there is at least one simple way to, theoretically, increase its absorption: take it with fats. Fisetin is fat-soluble, similar to other flavonoids like quercetin. Fish oil and other oils enhance the bioavailability of quercetin, and they might do the same for fisetin.
Even so, new formulations combining fisetin into small fat-like molecules (liposomes) may be the only effective solution. These greatly improve its absorption and anticancer effects. However, they are not yet commercially available. *
Untitled Document
Keep in mind that the safety profile of fisetin is relatively unknown, given the lack of well-designed clinical studies. The list of side effects below is not a definite one, and you should consult your doctor about other potential side effects, based on your health condition and possible drug or supplement interactions.
Even at high doses, scientists found no evidence of side effects or toxicity in animal studies. Clinical studies, of course, are needed to confirm its safety.
In the lone clinical trial on cancer patients, stomach discomfort was reported in the fisetin group. However, this might not actually be a side effect of fisetin. All patients were receiving chemotherapy and the same stomach complaint was also reported in the placebo group.
Due to the lack of safety data, pregnant women and children should avoid fisetin supplements.
Drug Interactions
Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.
The liver uses the same pathway to process fisetin as it does for the blood-thinning agent warfarin (Coumadin). This can, in theory, increase the effects of warfarin.
Fisetin substantially reduces blood sugar in diabetic animals. The combination with blood sugar-lowering drugs may further reduce sugar levels. *
Note 2: Cellular and molecular alterations induced by low‑dose fisetin in human chronic myeloid leukemia cells
Note 4: The Effects of Fisetin on Reducing Biological Aging: A Pilot Study
Note 1: Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite
Note 3: Pharmacokinetics and Biliary Excretion of Fisetin in Rats
2023-03-15