- The Rejuvenation Now Risk-Benefit Analysis of Fisetin as a Senolytic Therapy
- For Dementia Patients
- Fisetin: The Flavonoid That Slows Aging and Protects the Brain
- Benefits of fisetin
- Fisetin slows down aging…a lot
- Fisetin protects you from stress and inflammation
- Fisetin may fight cancer cells
- Foods that contain fisetin
- Fisetin Benefits & Side Effects
- Benefits of Fisetin
- Regulates Blood Sugar
- May Help Fight Cancer
- Heart Health
- Skin Health
- Cognitive Health
- Fisetin in Foods
- Side Effects of Fisetin
- The Bottom Line
- How Quercetin Is Used to Help Allergies and High Blood Pressure
The Rejuvenation Now Risk-Benefit Analysis of Fisetin as a Senolytic Therapy
The Forever Healthy Foundation's Rejuvenation Now program is engaged in the production of detailed analyses of risk and reward for presently available treatments that may act to slow or reverse aging.
I think this is helpful, as a great deal of information exists, but is very scattered, and there is far too much uninformed hype out there. Putting all of the facts together in one place, coupled to a sober assessment of what those facts mean, is a good use of resources.
This is particularly true given that senolytic therapies presently exist, and, to the degree to which these treatments successfully clear senescent cells with minimal side-effects, should be expected to produce sizable benefits to health for all old people who use them.
Those old people just need to be told, so that they can make an informed choice about their own health.
One of the potential senolytic therapies of interest is a cheap and readily available supplement, fisetin. This is interesting because animal data shows it to be about as good as the dasatinib plus quercetin combination.
One might ask how a supplement can be readily available for years, and yet no-one noticed that if you take the whole bottle at once, it significantly reverses inflammatory age-related conditions. Perhaps that is in fact the case, but as the analysis from the Forever Healthy Foundation notes, we just don't know.
Human trials are ongoing, and we might expect initial publications from the research groups involved over the next year. This will clarify whether or not fisetin happens to be unusually effective in mice only.
In a sense, either outcome would be surprising. The important parts of the biochemistry of senescent cells, when it comes to the operation of senolytic drugs, are essentially the same between mice and humans.
The dasatinib and quercetin combination has been shown to work in humans much as it does in mice when it comes to destroying these cells.
Yet fisetin has been readily available and widely used as a supplement for a while, without the sort of attendant murmuring one might expect given the sizable benefits it should produce if it is as senolytic in humans as it is in mice.
We shall see what the story is when the clinical trial data for fisetin emerges. Meanwhile, many more self-experimenters are using fisetin than are using the far more proven dasatinib and quercetin combination, given that fisetin is much more easily obtained.
Fisetin Senolytic Therapy Risk-Benefit Analysis
Senolytics are agents that selectively induce apoptosis of senescent cells. Fisetin is a flavonoid polyphenol found in many types of fruits and vegetables that is believed to act as a senolytic in addition to its numerous other known benefits.
Although natural senolytics are less potent, compared to the targeted senolytics, they have lower toxicity and are thus, ly to be more readily translatable to clinical medicine.
This risk-benefit analysis focuses on the risks and benefits of using fisetin as a senolytic rather than its more common use as a supplement.
There are currently three phase 2 clinical trials underway and the first data is expected to be reported in about a year. The data from the phase 1 trials has not been published.
All trials are being conducted by the same investigators at the Mayo clinic using the same treatment protocol. Only two papers directly related to the use of fisetin as a senolytic were identified, neither of which were conducted in humans.
The other 5 studies included in the table relate to pharmacokinetics, risk, and lifespan extension.
To the best of our knowledge, there haven't been any studies published on the pharmacokinetics of fisetin in humans.
Only one animal study on fisetin has reported any form of toxicity from fisetin use and the authors concluded that the elevations in ALT/AST levels (indications of liver toxicity) were in large part due to the vehicle used to administer the fisetin (DMSO).
However, the fisetin + vehicle group showed significantly higher elevations than the vehicle alone group indicating that high doses of fisetin may additionally burden the liver because of its poor bioavailability.
At a lower dose (112 mg/kg), fisetin didn't significantly increase apoptosis or lead to liver toxicity. Intermittent dosing and use of a form of fisetin with increased bioavailability are ly to mitigate the risk of liver toxicity.
Fisetin has been shown to decrease senescent cell biomarkers as well as the numbers of senescent cells in a variety of tissues, including ex vivo, human adipose tissue as well as in vivo, in mice.
The primary risk mitigation strategy is to wait to commence therapy until clinical trial data has been published that describes the possible benefits and adverse effects. At the current time, the only form and dose that has been tested in phase 1 clinical trials is the so-called “Mayo Protocol”.
The Mayo Protocol consists of taking 20 mg/kg of oral fisetin on two consecutive days and repeating the same dose, one month later.
Preclinical data suggests that fisetin may improve cognition or protect against Alzheimer’s disease, but there is no data suggesting that it will be effective in humans. Our search identified:
• 0 meta-analyses or systematic reviews• 0 human clinical trials or observational studies
• Fewer than 10 preclinical studies suggesting a benefit to cognition or protection from Alzheimer's disease
Data from preclinical studies suggest that fisetin might strengthen the connections between brain cells and enhance memory in healthy rodents . Studies in animal models of Alzheimer's disease suggest fisetin may also lower levels of phosphorylated tau and aggregated beta-amyloid (i.e.
, the tangles and plaques common in patients with Alzheimer's) [2-4], lower levels of neuroinflammation , and prevent the development of memory deficits . Some studies also suggest that fisetin might be protective against stroke, which may lead to dementia .
Despite this promising preclinical data, no studies have tested fisetin in humans.
For Dementia Patients
No studies have examined fisetin in Alzheimer's patients, but some preclinical evidence (see above) suggests it could theoretically have a protective effect.
Fisetin consumed in the diet is safe, and fisetin supplements are commercially available with no reports that we could find for safety concerns or reported side effects.
However, there is currently no scientific research in humans on whether supplemental doses of fisetin are safe, especially in the long term.
Although fisetin is being researched as a potential treatment to protect from cancer, possible carcinogenic effects have been identified and the effects in humans have not been determined [10-13].
NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.
No studies have examined the correct dosing of fisetin in human beings. It is estimated that a person would have to eat 37 strawberries every day to reach the doses used in animal studies. Fisetin is currently available over-the-counter as a supplement, generally in 100 mg tablets.
- Maher P, Akaishi T, Abe K (2006) Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proceedings of the National Academy of Sciences of the United States of America 103, 16568-16573.
- Kim H, Park BS, Lee KG et al.
(2005) Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. Journal of agricultural and food chemistry 53, 8537-8541.
- Ushikubo H, Watanabe S, Tanimoto Y et al. (2012) 3,3',4',5,5'-Pentahydroxyflavone is a potent inhibitor of amyloid beta fibril formation. Neuroscience letters 513, 51-56.
- Kim S, Choi KJ, Cho SJ et al. (2016) Fisetin stimulates autophagic degradation of phosphorylated tau via the activation of TFEB and Nrf2 transcription factors. Sci Rep 6, 24933.
- Chuang JY, Chang PC, Shen YC et al. (2014) Regulatory effects of fisetin on microglial activation. Molecules 19, 8820-8839.
- Cho N, Lee KY, Huh J et al.
(2013) Cognitive-enhancing effects of Rhus verniciflua bark extract and its active flavonoids with neuroprotective and anti-inflammatory activities. Food Chem Toxicol 58, 355-361.
- Currais A, Prior M, Dargusch R et al. (2014) Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice.
Aging cell 13, 379-390.
- Ahmad A, Ali T, Park HY et al. (2016) Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice. Mol Neurobiol.
- Maher P (2015) How fisetin reduces the impact of age and disease on CNS function. Front Biosci (Schol Ed) 7, 58-82.
- Lopez-Lazaro M, Willmore E, Austin CA (2010) The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells. Mutat Res 696, 41-47.
- Lim DY, Park JH (2009) Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin.
Am J Physiol Gastrointest Liver Physiol 296, G1060-1068.
- Bothiraja C, Yojana BD, Pawar AP et al. (2014) Fisetin-loaded nanocochleates: formulation, characterisation, in vitro anticancer testing, bioavailability and biodistribution study. Expert opinion on drug delivery 11, 17-29.
- Strick R, Strissel PL, Borgers S et al.
(2000) Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proceedings of the National Academy of Sciences of the United States of America 97, 4790-4795.
Fisetin: The Flavonoid That Slows Aging and Protects the Brain
- Fisetin is a special antioxidant found in strawberries, apples, persimmons, onions, and other plants, that’s particularly good for slowing down aging.
- Recent research found that eating fisetin regularly increases lifespan by about 10% and improves quality of life in aging mice. There are clinical trials going on right now to find out whether fisetin can slow down aging in humans.
- Fisetin also protects you from future inflammation and gets rid of existing inflammation. Low inflammation means your cells can run at full power and you can recover faster.
- Fisetin shows a lot of promise at fighting cancer, too. It prevents cancer cells from spreading and destroys them. Fisetin seems particularly good at destroying breast cancer cells.
- Strawberries are a rich source of fisetin. You can also get some fisetin from cucumbers and onions. Check out the recipes below for ideas about fitting more fisetin into your diet; it might help you live a longer, better life.
Have you heard of the flavonoid fisetin? It’s a plant chemical, found most abundantly in strawberries, with promising health benefits.
Anti-aging scientists have been researching fisetin and its benefits for a while. They expected it to perform as well as other antioxidants do at decreasing inflammation and making cells more efficient.
However, a couple recent studies have found that fisetin is much more powerful than anyone expected, in a couple different ways.
Let’s take a look at the benefits of fisetin, and why you definitely want to supplement your diet with fisetin.
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Benefits of fisetin
- Improves brain health and memory
- Slows down aging
- Shows anti-cancer abilities
- Protects against stress and inflammation
- May protect against stroke and Alzheimer’s
- May improve symptoms of depression
Fisetin slows down aging…a lot
One of the main reasons you age is senescence — your cells stop dividing as they get older. When cells no longer divide, they become mostly useless, start to accumulate in your body, and trigger inflammation, gradually impairing your cellular function and increasing your risk of age-related disease.
Senescence isn’t pretty, which is why anti-aging researchers are on the hunt for senolytics, compounds that delay or reverse aging by destroying old, damaged cells.
New research has found that fisetin is a particularly powerful senolytic. Scientists fed aging mice either normal diets or fisetin-rich diets and watched for signs of aging. The mice that ate fisetin daily lived about 10% longer and their bodies worked better, even at a very old age.
A 10% increase in longevity means living to 110 instead of 100. That’s a big deal. If you plan to live to 180, Bulletproof founder Dave Asprey, hacks this can move the needle a lot.
There’s a clinical trial going on right now that will shed light on how well fisetin slows down aging in humans. In the meantime, it can’t hurt to eat foods rich in fisetin, or even take a fisetin supplement. For a therapeutic dose, supplements are the way to go.
Studies suggest that a dose of 50mg to 150mg per day can be beneficial, though more research is needed.
Fisetin protects you from stress and inflammation
Fisetin protects your cells from stress-related damage so they can run at full power. Fisetin regulates inflammatory pathways and deactivates several major inflammatory compounds. It also helps you make more glutathione, the most powerful anti-inflammatory substance in your body.
In other words, fisetin both prevents future inflammation and boosts your body’s ability to deal with existing inflammation. Low inflammation means your cells can make more energy and you look better, feel better, and recover faster.
Related: Why Reducing Stress Will Protect Your Telomeres and Help You Live Longer
Fisetin may fight cancer cells
Among fisetin’s benefits, a few studies have found that fisetin keeps cancer cells from multiplying and spreading. Fisetin seems particularly good at destroying breast cancer cells.
Foods that contain fisetin
You can get fisetin from a few different foods.
- Strawberries are particularly rich in fisetin. This strawberries and cream smoothie is a great way to get some strawberries, as well as a bunch of quality fats. Strawberries are pretty low in sugar, but you probably don’t want to eat a whole carton of them in one sitting.
- Cucumbers and onions both have a moderate amount of fisetin. You can combine them in this easy Bulletproof pickle recipe to get a nice boost of fisetin. Just be sure you aren’t sensitive to onions — some people don’t tolerate them.
- Grapes and persimmons also have fisetin. They’re both high in sugar, so save them for an occasional treat, or skip them entirely and stick with strawberries when you want some fruit.
Related: Superfoods That Destroy Inflammation in Your Brain
One last thought: Fisetin is one of many polyphenols, antioxidants that often have unique benefits. There are a lot of different polyphenols, and it’s worth your time to include as many of them in your diet as possible, from foods coffee, green tea, blueberries, chocolate, and more. Check out this article for a deeper look at what different polyphenols do for you and where to get them.
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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 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 (x, x).
This compound can help relieve inflammatory conditions, reduce oxidative stress and regulate the growth of our heart cells (x).
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 (x).
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 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 (x).
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 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 (x).
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 (x).
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 (x, x, x).
Fisetin supplementation also appears to help increase insulin secretion in diabetic rats (x).
May Help Fight Cancer
Fisetin may fight cancer from multiple different angles. As an antioxidant, fisetin, 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 (x).
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 (x).
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.
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 (x).
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 (x).
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 Parkinson’s or Alzheimer’s (x). 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 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 (x).
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 cancer and Alzheimer’s. Fisetin can help our skin retain its youth.
It also fights off oxidative damage from sun exposure.
By: Lulu Wong
How Quercetin Is Used to Help Allergies and High Blood Pressure
Betsie Van Der Meer/Taxi/Getty Images
Quercetin is a chemical found naturally in a number of foods including apples, onions, teas, berries, and red wine. This flavonoid is also found in some herbs such as ginkgo biloba and St. John's wort.
Quercetin acts as an antioxidant, neutralizing free radicals—the chemical by-products that harm cell membranes and damage DNA. Available as a dietary supplement, quercetin also possesses antihistamine and anti-inflammatory properties.
In alternative medicine, quercetin is said to help with the following conditions:
- Cardiovascular disease
So far, results to support the benefits of quercetin are mixed—with some conditions examined only in test tubes or on animals. Here's how the research shakes out:
Quercetin is thought to prevent the release of histamine—an inflammatory chemical involved in allergic symptoms such as sneezing and itching—from certain immune cells. Although lab experiments suggest that quercetin may help fight allergic conditions allergic rhinitis, most have been performed in vitro or in animals. Researchers recommend further studies on humans to prove a correlation.
A 2016 review of randomized controlled trials found quercetin significantly reduced both systolic and diastolic blood pressure, particularly in diabetics who were given at least 500 milligrams per day. It's still unclear the precise dosage and duration to see the most benefits.
Quercetin may be no better than a placebo when it comes to enhancing athletic performance, according to a 2011 review of 11 previous studies. All studies showed a boost in exercise endurance via VO2 max—oxygen consumption during physical activity—when people ingested quercetin but the effect was minimal.
Another study found a more impressive link. A 2013 study analyzing 60 male students who've participated in athletics for at least three years saw improved lean body mass, total body water, basal metabolic rate, and total energy expenditure after taking quercetin.
Studies on cell cultures have shown that quercetin may help slow the growth of some types of cancer cells.
Some in vitro and animal-based research indicates that quercetin may protect against certain types of cancer, such as leukemia and lung cancer.
For example, a 2010 study looked at the relationship between quercetin intake and lung cancer risk in 38 non-tumor lung tissues and found an inverse correlation—the higher the intake of quercetin, the lower the risk.
However, since there is currently a lack of human studies on quercetin's cancer-fighting effects, it's too soon to tell whether quercetin might play a significant role in cancer prevention.
Quercetin is generally well-tolerated when used in appropriate amounts. Some have reported tingling in the arms and legs, as well as upset stomach and headaches when taking quercetin orally. Very high doses—greater than 1 gram per day—might cause kidney damage.
Supplements haven't been tested for safety and due to the fact that dietary supplements are largely unregulated, the content of some products may differ from what is specified on the product label.
Also keep in mind that the safety of supplements in pregnant women, nursing mothers, children, and those with medical conditions or who are taking medications—particularly antibiotics—has not been established.
Under the care of medical supervision, quercetin has been safely used in amounts up to 1,000 mg twice daily for 12 weeks. There is not enough evidence to know if it is safe for long-term use.
The appropriate dose for you may depend on factors including your age, gender, and medical history. Speak to your healthcare provider to get personalized advice if you choose to take this supplement.
Food sources of quercetin include teas, onions, apples, buckwheat, and pau d'arco. When taking quercetin in supplement form, it may be beneficial to choose a product that also contains papain and/or bromelain. These are plant-derived enzymes (fruit extracts) shown to increase the intestine's absorption of quercetin.
Due to the lack of supporting research, it's too soon to recommend quercetin for any health purpose. If you're considering using it, consult your primary care provider first. Self-treating a condition and avoiding or delaying standard care may have serious consequences.
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