✓ Medically Reviewed and Fact-Checked by Dr. Jesse Ropat, PharmD, RPh, B.Sc.
For years, health experts have searched for ways to slow the process of degenerative aging. Fisetin, a plant extract, might be a possible solution. Research suggests the benefits of fisetin might encourage healthy aging and even contribute to a longer lifespan.
Today, we’re diving into those potential benefits and the best fisetin supplements on the market. For years, health experts have searched for ways to slow the process of degenerative aging.
Fisetin, a plant extract, might be a possible solution. Research suggests the benefits of fisetin might encourage healthy aging and even contribute to a longer lifespan. Today, we’re diving into those potential benefits and the best fisetin supplements on the market.
Fisetin is a flavonoid (this just describes the chemical structure of the compound) found in some fruits like strawberries and apples – see the end of this article for more examples of foods with Fisetin. Compared to other flavonoids, fisetin has profound senolytic qualities, which are at the forefront of current anti-aging research.
Senolytics is the study of compounds that selectively kill off cells that are no longer dividing but are instead damage neighboring healthy cells, like one moldy peach in an otherwise fresh bowl of fruit.
Based on these senolytic contents, fisetin might have the ability to slow the aging process. While more human studies are needed, what research we do have on fisetin is promising, enough so that Dr. David Sinclair, professor of genetics and leading longevity scientist, admits to using this supplement daily.
More evidence that #coronavirus accelerates aging. @ScienceMagazine mouse study shows FISETIN, a molecule in fruits that kills off senescent cells, dramatically reduces covid symptoms & extends lifespan. Been taking fisetin for 2 years https://t.co/5ixX1z7iJR #healthylifestyle pic.twitter.com/790T59oPrP
— David Sinclair (@davidasinclair) June 9, 2021
Fisetin offers health benefits that might contribute to greater longevity, cancer prevention, and brain health.
Normally, old or dysfunctional cells die off so that new ones can take their place. As we age, however, some of these cells become senescent. This means that they fail to divide and perform as expected but also fail to die, pumping out toxins and inflaming the body.
Senescence is an anti-cancer mechanism our bodies developed to prevent cells replicating with damaged DNA – this process also contributes to aging and age-related diseases. Fisetin acts as a senolytic activator, which means it can kill senescent cells and make room for healthy ones. This is important because early research has suggested that clearing senescent cells might improve brain function. In one study, mice who received fisetin lived 2.5 months longer than average, even when treatment started late in their lifespan.
Fisetin can likely prevent aging in other ways too. One review suggests that fisetin can play a role in fighting disease by reducing age-inducing inflammation and quenching oxidative stress molecules.
Fisetin might even mimic the effects of a restrictive caloric diet which may help the body reduce inflammation and fight infection. A restrictive diet was shown to increase lifespan by approximately 30% on average, and this was largely mimicked by other flavonols, including Fisetin. Not only does it help reduce inflammation by these pesky senescent cells, but it seems to effectively target only those cells, and not our healthy ones.
Now that we have some background on Fisetin, let’s take a look at our top picks for supplementation. See below for how we picked these excellent products.
*Note: We do have affiliate links throughout this article, which means we receive a commission if you purchase from any of our links. This supports our mission to bring complicated health and fitness info in an entertaining package. And it keeps us from putting up annoying things like banner ads. Those suck.
Best Overall: Renue LIPO Fisetin capsules
Best Bulk: PureBulk Fisetin
Best Combination: Renue ACTIVATOR
Renue LIP Fisetin is a potent supplement, containing 150 mg of fisetin in a liposomal capsule. Liposomes are a special lipid that surround active ingredients, like fisetin, so that they can survive the harsh environment of our digestion system, and therefore make it into the bloodstream. In a word, it enhances bioavailability. Renue LIPO Fisetin is suitable for vegans and contains 90 servings per bottle.
Are pills not your jam? Renue offers an alternative way to take fisetin with their Fisetin LIPO Gel. To use, just place two pumps under your tongue for fast absorption. Like the capsule, it’s vegan-friendly and contains liposomes. Each bottle contains 75 servings of 75 mg of fisetin.
Double Wood Supplements offers a potent and cost-effective option for your fisetin needs. Each bottle contains 60 servings, and each serving contains 100 mg of fisetin extracted from smoke tree stems. It’s vegan, gluten free, soy free, and manufactured in the USA.
Life Extension Bio-Fisetin is both an affordable and effective option. It’s made with fibers derived from fenugreek seeds. These fibers might increase their bioavailability by preserving fisetin through the digestive process, keeping fisetin in the body for longer. It’s also gluten-free and vegetarian. Each bottle contains 30 vegetarian capsules, and each serving contains 45 mg of fisetin.
Each serving of Doctor’s Best contains Novusetin, which is a naturally sourced flavanol containing fisetin. It’s vegan, gluten free, and soy free. Each bottle contains 30×100 mg softgel capsules.
PureBulk Fisetin gives you options. You can pick the kind (powder or capsule) and quantity of fisetin you want. Plus, both of the fisetin options are free of soy, dairy, gluten, and added sugars. If you prefer to buy in bulk, this one’s a great option.
This product is included as an honorable mention as it’s not pure Fisetin. Not only does it contain high quality Fisetin, but also contains other senolytic compounds which have shown great promise over the past several years. These include: Spermidine, and Quercetin. All of these three super compounds are contained within lipid nanoparticles to ensure optimal drug delivery and absorption. With Renue’s superior formulation, quality control, and customer service, you can’t go wrong with this combination.
Although we ranked these supplements, we want you to decide on the best product for you. Here’s what we took into consideration when ranking these fisetin products.
The supplement industry isn’t FDA-regulated, which can make finding a reputable supplement challenging.
That’s why we only select companies that adhere to Good Manufacturing Practice (GMP) regulations and have their products third-party tested.
The average dose of fisetin given in clinical research has been around 100 mg, so we looked for products with similar doses. We also made sure the products we selected were free of any junk you don’t need, like additives and preservatives.
You shouldn’t have to spend a fortune to live a healthy life. That’s why we selected high-quality products that won’t hurt your wallet.
There is one protocol from the Mayo Clinic that is quite common, and has become known as the Fisetin Mayo Protocol. This protocol recommends Fisetin be taken for 3 consecutive days out of each month. The dose used in the protocol was 20mg/kg/day, so multiply your weight in kilograms by 20 and this gives you the recommended daily amount for those 3 days.
It’s possible to take Fisetin daily, but typically at a lower dose (roughly 1/10th or less of the Mayo dosing).
As fisetin’s effectiveness as a supplement has only recently been explored, researchers have not yet determined its long-term effects. However, existing research indicates that fisetin is a safe supplement with no side effects, even in high doses.
Fisetin has no known side effects or medication interactions, so it might be okay to take if you have liver disease. In fact, animal studies suggest that fisetin might help treat ALD (alcoholic liver disease) by preventing oxidative stress. However, you should speak with a health professional before trying this supplement.
Fisetin acts on many molecular pathways. This anti-aging supplement targets oxidative stress pathways, inflammatory mediators, and key cancer enzymes.
Fisetin is a glutathione transferase inhibitor, which has been shown to sensitize cancer cells to chemotherapy. Other studies also demonstrate that Fisetin, alone or in combination, can also assist in the treatment of solid tumors.
The way in which it does this is complex, as demonstrated by the diagram below. However, Fisetin induces apoptosis (cell death) in tumor cells by inhibiting many key oxidative pathways, including the COX2 pathway, and the Wnt pathway. Its action here activates the caspase-3 cascade, which eventually leads to cellular death in these cancer cells.
These pathways also impact other key biological functions, including cognitive health and longevity.
Sirtuin genes in animals play a key role in life-span extension and longevity. NMN is a great way to stimulate these genes to produce their valuable proteins, since these sirtuins require NAD for their activity. NAD levels decline with obesity, age, and our body is always using up our stores, making replenishing these supplies of the utmost importance. NMN is a precursor to NAD and is a key component of Dr. David Sinclair’s anti-aging stack. He reports that taking 1g of NMN over about 2 weeks will on average double your serum NAD levels. This molecule works synergistically with fisetin, and both of these workhorses can be used successfully in your supplement routine.
See our article outlining the best NMN supplements to see which one is right for you.
Like Fisetin, resveratrol has been shown to increase lifespan, suppress tumor proliferation, and enhance brain health by protecting against and slowing neurodegeneration. Interestingly, just like Fisetin, Resveratrol also seems to mimic calorie restriction as described above.
One downside is that resveratrol has a much lower bioavailability and is metabolized rather quickly. However, at higher concentrations, Resveratrol exhibits complete senolytic activity, and its activity may be increased further in combination with NMN supplementation.
Dr. David Sinclair recommends supplements like Resveratrol to be taken either every other day, or on a cyclical basis, to reap the greatest rewards. He typically takes 1g of Resveratrol every other day.
Another flavonoid, apigenin, is isolated from plants (parsley and chamomile). This compound has highly anti-inflammatory, antioxidant, and anti-cancer properties that we are just now beginning to understand. Just like Fisetin, it acts upon a myriad of biological pathways to produce these effects. It may also aid in reducing the negative effects of obesity, as was shown in mice models.
Spermidine is known as an autophagy inducer. This means the cells that have accumulated as we age need to be cleaned out and removed, and replaced with healthier cells. We find spermidine in foods like wheat germ, soybeans, aged cheese, mushroom, peas, and apples, among others. Data has shown spermidine to be a potent molecule for age-related pathologies. In mice and humans, we see cardio-protective effects, and greatly aids our cellular homeostasis by preventing inflammation and acting as an antioxidant. Not only that, but it may promote neuroprotection, and the maintenance of our immune system health by removing all the toxic debris left behind as we age.
These two compounds act hand-in-hand through different mechanisms to aid in anti-aging and longevity.
Fisetin and Quercetin are both flavonoids, and both exhibit antioxidant and anti-inflammatory properties, suggesting benefit in preventing heart disease and anti-cancer activity. However, the bulk of evidence suggests that fisetin has higher senolytic abilities than quercetin and may be a better choice in your longevity supplement stack.
Coenzyme Q10 (CoQ10) or ubiquinol (the oxidized form of ubiquinone) is quite different from fisetin. CoQ10 plays a key role in the electron transport chain in the mitochondria. CoQ10 deficiency is associated with diseases such as neurodegenerative disorders, diabetes, cancer, fibrosis, and cardiovascular diseases, so maintaining our levels of CoQ10 may synergistically pair with fisetin to improve these health outcomes.
Our in-house Pharmacist, Dr. Jesse Ropat, has extensive research in the area of curcumin, and curcumin-like analogues as it pertains to anti-cancer activity. See his article in Nature here. Curcumin plays a role as a potent senolytic, through its activity in a variety of oxidative pathways and longevity-modulating pathways.
If you’re a runner like Dr. Jesse, you may be interested to know that after a 6-week curcumin supplementation, runners had improved antioxidant and aerobic capacity, along with an increase in SIRT3. SIRT3 is a key protein responsible for inhibiting the production of oxidative molecules that cause all of the negative consequences we’ve been discussing throughout this article. Not only that, but SIRT3 stimulates the expression of antioxidant enzymes, further promoting oxidative balance in our body.
While they are very different compounds, Curcumin may also synergistically pair with fisetin to both boost NAD+ and prevent the negative consequences of aging, and combining the two may very well be what your supplement stack is missing.
Hypothesized model of supplementing NAD+ precursors with other NAD+ enhancing genoprotectors.