What would you get done enjoying an extra ten years of perfect health?
Travel the world?
Write that book you’ve dreamed of?
Become the best in the world at your hobby?
Senolytic “zombie” cells suck up energy, waste the body’s precious resources, and initiate a cascade of infecting other cells.
The more of these we remove, the longer our healthspan.
A potent senolytic zombie cell-killing supplement called fisetin does exactly that.
If you’re interested in slowing and reversing the aging process, you may have heard of it. New research has world-renowned longevity researchers like Dr. David Sinclair taking fisetin daily.
He’s not alone. The scientific community has deemed fisetin one of the most promising anti-aging molecules. And best of all, it’s easier than ever to get.
But not all products are the same, and there are a few things you should know before buying fisetin supplements.
Today’s post is an ultimate guide to this anti-aging molecule. In case you’re in a hurry, this article starts with the criteria I use to look for to determine quality, then the best fisetin supplements for your unique situation. Next, we’ll cover a basic introduction to this special compound, the latest scientific research, how to best use it to maximize absorption.
Let’s dig in.
Maximum Absorption & Potency Fisetin Supplements
Your ideal product depends on all kinds of factors.
But overall, some products are far better than others.
Here are some of the factors I consider when evaluating the best quality fisetin supplements:
- Form — topicals give the best skin, pain, and muscle benefits, while powders, gels, and capsules are better for full-body effects
- Bioavailability — normal fisetin is poorly absorbed, but liposomal gels and other technologies increase the body’s ability to use this nutrient
- Additives — manufacturers often add all kinds of unnecessary and unhealthy ingredients to cut costs and make their products last longer
- Safety — credible products should be produced in FDA-inspected, cGMP-certified facilities, and readily display a certificate of analysis (CoA) showing that their fisetin passed third-party purity and safety testing
- Cost — we want the lower end of average, because products considerably cheaper than normal indicate lack of quality control standards
Unless you’re just seeking the gut health benefits, you’ll need maximum absorption. Polyphenol supplements like fisetin usually get excreted before they can exert their powerful effects. As discussed below, lipo fisetin provides the best potency-to-dollar value. The other bioavailability-enhancing techniques are less proven.
You can buy each of these fisetin products online. I recommend avoiding supplements on Amazon, as they’re often counterfeit, contaminated with heavy metals, and sometimes contains zero active ingredient.
Best Overall: Do Not Age PURE Fisetin
Fisetin Dose: 400mg
Servings: 60 or 366
Other Ingredients: Cellulose
Certifications: No Artificial Ingredients, Wheat, Gluten, Yeast, Soy, Corn, Milk, Preservatives
Price: $76.50 – $450.00 (using code URBAN)
Another hot longevity supplements vendor, Do Not Age offers many of the products recommended by Dr. David Sinclair and other famous researchers. The company is based out of the UK, making them a good and speedy option for those outside the USA. If you have an arsenal of anti-aging supplements, their subscription feature works around your desired schedule to save you time and money. When stock runs low, they prioritize your orders.
After third-party testing, manufacturers often store their supplements in hot, sunny, and moist environments. By the time they reach your door, the harsh conditions have oxidized and degraded the active ingredient to the point of uselessness. Do Not Age manufactures to GMP and ISO9001 standards and guarantees the quality of their products all the way to your doorstep.
Each capsule contains 400mg of fisetin, considerably stronger than most supplements. Their fisetin comes in two sizes: 60 or 366 capsules. And with no other ingredients (just the capsule), this is truly pure fisetin.
If you’re looking for additive-free fisetin or live outside the USA, Do Not Age’s Pure Fisetin is a great choice.
Use the exclusive Do Not Age code URBAN for 10% off
Best Budget: Life Extension Bio-Fisetin
Other Ingredients: Cellulose, Silica, Vegetable Stearate, Soluble Fiber, Sunflower Lecithin
Certifications: Gluten-Free, non-GMO, Vegetarian
Life Extension is one of the oldest and most trusted names in supplements. They have an entire Science Team dedicated to reviewing the current literature, as well as the newest pre-prints that the general public cannot access. As a result, they make some of the best formulations. Since they buy raw ingredients in massive quantities, Life Extension can pass the savings on to us.
What makes their product unique, is the combination of fisetin with special galactomannan compounds from fenugreek seeds. They claim that this proprietary phytoestrogen-free 44.5mg blend increases fisetin’s bioavailability by 25-fold. If true, that’d make the meager 8mg dose equivalent to 200mg of pure fisetin. Since Life Extension’s fenugreek seed research is unavailable to the public, we must blindly trust the design of their study.
At just over $11 for 30 doses, Bio-Fisetin is by far the most affordable. Likely due to the shelf-stabilizing fillers like vegetable stearate and silica (which I’m not a fan of). Others don’t seem to mind, because on their website alone, their fisetin has accumulated a 4.8-star rating over 133 reviews. It’s also easy to find and commonly stocked in large grocers.
If you trust Life Extension’s internal bioavailability research and want the most affordable fisetin supplement, this is one to consider.
Renue by Science LIPO Fisetin
Fisetin Dose: 75 mg Liposomal Fisetin
Other Ingredients: Water, Xanthan Gum, Guar Gum, Citric Acid, Dextrose, Phospholipids, Potassium Sorbate, Propylene Glycol, Sodium Citrate, Monk Fruit Extract, Vitamin E, Citrus Burst,
Certifications: FDA-Approved & cGMP Certified Facility, Non-GMO, No Artificial Color or Flavors, Vegan
Renue by Science produces potent, maximum-absorption longevity supplements using their proprietary liposomal encapsulation technology.
Renue’s lipo fisetin should also be a good choice. Produced without heat, pressure, and using pharmaceutical-grade ingredients for the best bioavailability of any product. After passing four rounds of rigorous internal testing, Renue transparently displays the results of third-party testing (CoA) on the product’s page, so you know exactly what you’re getting.
Their customer service is friendly and knowledgeable about longevity supplements. I use this as a core component in my safe and effective senescent cell clearing protocol.
If you want the high-quality and third-party verified pure liposomal fisetin, pick Renue.
What is Fisetin?
Fisetin is a plant pigment that colors many fruits and vegetables and helps protect them from predators. It belongs to the flavonoid group of polyphenols and was discovered by a chemist back in 1891. Fisetin recently gained attention as scientists uncover wide-ranging its role in a wide array of health benefits.
Structurally, the molecule is nearly identical to another popular longevity supplement called quercetin. The two share many of the same mechanisms.
You can do several things to get greater potency out of your supplement.
How to take fisetin for the best effects
So how should you actually use fisetin?
As with other senolytics, I don’t recommend long-term daily fisetin use. This is because the body responds best to pulses of autophagy and cellular repair.
Don’t expect to see instant results. Though clinical trials show results beginning in as little as seven days, the benefits of fisetin accrue over a longer timeframe.
Despite myriad health benefits, the body metabolizes and excretes fisetin too quickly. Studies show fisetin’s half-life is around 3.1 hours in mice.
You can increase fisetin absorption in multiple ways, including:
- Taking it with a fatty meal
- Black pepper extract
- Fenugreek seeds
- Using liposomal fisetin products
While you can take it on an empty stomach, since it’s fat-soluble, you can easily increase bioavailability by taking it with a meal.
BioPerine is a patented black pepper extract that inhibits enzymes and pathways that break down a wide variety of molecules and drugs. Supplement manufacturers claim to achieve 30% higher bioavailability with black pepper extract. Since it’s non-specific and interferes with healthy metabolism (of other supplements, drugs, etc), I avoid black pepper extract.
Fenugreek and its seeds contain special compounds called galactomannans. Life Extension’s Bio-Fisetin uses the fenugreek fiber coating to protect the fisetin from digestion. Resulting in supposedly 25X greater bioavailability. The study used to validate their claim was not published to the public, so we cannot verify their claim.
Last, is the most powerful supplement absorption technology called Liposomes. Essentially, tiny droplets of fat encapsulate the supplement and drastically improve absorption, more than any other method. Using liposomal fisetin supplements is the best way to maximize bioavailability.
Taking normal fisetin during fasts may improve gut health, but won’t have the same systemic effects due to low bioavailability. Unless the fisetin product is liposomal, or contains either black pepper extract or fenugreek galactomannans.
Scientists are still uncovering exactly how this molecule works, but they’ve made a few striking discoveries.
How fisetin works
Fisetin appears to work via several distinct mechanisms of action:
- Antioxidant defense boost
- Cellular energy balance shift
- Inflammatory pathway blocking
- Gut microbiome modulation
First, fisetin improves antioxidant defenses by scavenging free radicals, upregulating endogenous antioxidant (glutathione) production, and protecting neurons from oxidative stress.
Next, fisetin powerfully activates AMPK, inhibits mTOR, and increases cellular senescence (cleaning “zombie cells”).
Inflammation is widely considered the root of all disease. Fisetin inhibits inflammation through several pathways, including NF-κB. It shows anti-hyperlipidemic, anti-inflammatory, and neurotrophic properties.
Newer research suggests that, like most poorly absorbed longevity compounds, many of fisetin’s core healthspan-increasing benefits may come from altering the gut microbiome.
Foods that naturally contain fisetin
Certain pigmented produce naturally contains fisetin, albeit in minuscule amounts.
Don’t let that fool you. When packaged in whole foods, fisetin is likely more bioavailable and requires a lower dose.
A study quantified the dose of fisetin in fruits, vegetables, and other foods:
|Fruit or Vegetable
Some companies (like Novusetin) report especially high concentrations in the Japanese fruit wax tree.
As you can see, strawberries contain the most fisetin by a landslide. Even then, there’s slightly under 2mg of fisetin within one strawberry. You’d need to consume hundreds of strawberries to get the same amount as one pill. As a plant defense compound, unfortunately, the fisetin content of produce depends heavily on the growing environment and soil quality.
Though current research hasn’t found serious adverse effects from supplementation, your safest option is to get fisetin from whole foods.
Scientific Health Benefits of Fisetin
Hundreds of papers show how fisetin improves human health with remarkable safety.
As of March 2022, PubMed contains nearly 950 papers investigating this molecule. I’ve read through and summarized some of the most interesting and important findings.
Health and longevity benefits of fisetin include:
- Reproductive lifespan extension in S. cerevisiae by 55%
- Lifespan extension
- Healthspan extension, and the median and maximum lifespan of mice
- Nootropic and cognitive health improvement via increased BDNF
- Long-term memory improvements
- Learning enhancement
- Resilience against frailty
- Serotonin levels increase
- Noradrenaline production increase
- Skin health improvements
- Tans skin by increasing melanin production
- AMPK, mitophagy, and autophagy activator
- CNS function improvements
- TBI/concussion protection
- Allergy improvement
- Glutathione production increase
- Chronic stress reduction in mice
- Anti-inflammatory, anti-oxidant, anti-tumorigenic, anti-invasive, anti-angiogenic, anti-diabetic, neuroprotective, and cardioprotective
- Pain reduction (back & arthritic) in those with heightened sensitivity
- Muscle soreness post-workout (DOMS) reduction
- Immune system modulation
- Anti-depressant like mood improvements
- Mental clarity improvements (anecdotal)
- Neuroinflammation reduction
- Neurodegenerative disease protection
- Neurotoxin (aluminum chloride) protection
- Blood flow and blood pressure improvements
- Alcohol breakdown accelerated and liver damage reduced
- Weight loss via reversing weight gain
- Diabetes symptoms improve
- Fat cell prevention
- Sun-induced skin damage prevention
This is not an exhaustive list, but rather an introduction to fisetin’s wide-ranging benefits and uses.
Fisetin Compared to Other Popular Longevity Supplements
Antioxidants once garnered the prominent spot in any longevity supplement protocol.
Today, much of the buzz around polyphenols and flavanols has faded. Top stacks include multiple ingredients, one of which, research suggests should include fisetin.
A great longevity stack would include several of the ingredients discussed below:
Now, let’s compare and contrast some of these longevity supplements.
Fisetin vs NMN
Compared to NMN, fisetin is a better senolytic and AMPK activator but regulates fewer cellular functions and is less essential.
NMN is the most popular NAD+ booster which the body requires as cellular energy. We’d die without NAD. The body naturally produces and recycles it, but levels decline as we age. Research from Harvard’s Dr. David Sinclair and others suggest restoring to proper levels may slow the aging process. Though the two work in very different ways, according to the current data, NMN is more important than fisetin for longevity and lifespan.
Fisetin is not a dietary requirement, but rather a powerful senolytic and non-essential nutrient that we likely got more of before the advent of chemical farming. I think that a well-formulated stack combines NMN with fisetin.
Fisetin vs Spermidine
Compared to fisetin, spermidine supplements activate more anti-aging pathways (6 of the 9), and better improves skin and gut health.
Spermidine is a polyamine well known and studied for its profound ability to activate the process of cellular cleaning (autophagy and mitophagy). It seems to stop and even reverse hair loss, improve skin complexion, help heal the gut, protect the heart and brain against disease, and even plays a minor role in cognition. Few foods in the Western diet contain appreciable amounts of spermidine.
It’s better absorbed than fisetin, and due to its necessity for optimal health, researchers are urging policymakers to reclassify it as an essential nutrient. Backed by thousands of studies, spermidine deserves a spot in your senolytic stack. This is one of the most exciting anti-aging molecules in the last decade.
Fisetin vs Resveratrol
While resveratrol is the most researched polyphenol, fisetin holds considerably more promise and effectiveness to improve human health.
Resveratrol is the antioxidant found in grapes and wine that led many journalists to wrongly ascribe healthy properties to alcohol. In reality, you can buy better alcohol alternatives that still make you feel great.
As I looked into the top resveratrol supplements, I found a breathtaking number of studies conducted on this molecule. The benefits seemed almost too good to be true. Many of which scientists struggled to replicate. Fisetin is the better version of resveratrol, with more uses and fewer side effects. After discovering fisetin, I stopped taking resveratrol.
Fisetin vs Apigenin
Apigenin and fisetin are structurally similar flavonoids with a wide range of benefits and great safety profiles. Both greatly inhibit inflammation. Fisetin is better known for enhancing healthspan, while apigenin doubles as a NAD booster.
You get appreciable amounts of apigenin from parsley. I add it to my NAD boosting smoothie since apigenin is well-known to inhibit a NAD-degrading enzyme called CD38. It has accumulated more research than fisetin but exerts many of the same effects.
Due to the substantial overlap yet subtle differences, I believe that the two flavonoids have a synergistic effect. I include both in my diet/supplement routine.
Fisetin vs Quercetin
Fisetin and quercetin are plant flavonoids found in produce. Quercetin has a much larger body of research, but fisetin is nearly twice as effective at killing senescent cells and extending healthspan.
Both fisetin and quercetin suffer from low bioavailability. Multiple non-comparative studies have shown that fisetin has better life extension properties than quercetin. Virtually all research comparing fisetin and quercetin has focused on the senolytic properties and pharmacological potential.
Killing “zombie cells” is one important component of life extension. But I think Dr. Sauna Kauffman’s approach of consuming low doses of many related molecules will yield the best results.
Should You Supplement High-Quality Fisetin?
With dozens of longevity-enhancing ingredients and hundreds of products, you may be wondering if fisetin is worth taking.
It’s an antioxidant polyphenol swiss-army knife.
Current research indicates fisetin has serious potential for:
- Extending lifespan and healthspan
- Improving cognition, memory, and learning
- Natural pain relief
- Boosting glutathione levels
- Reducing inflammation
- Protection against various diseases
The glaring issue with most supplements is that you rapidly metabolize and excrete them.
To enjoy all the benefits of fisetin, first, you must absorb it. You can do this by either eating hundreds of strawberries per day, or with high-quality products.
Liposomal technology is the modern solution to oral fisetin’s low bioavailability.
Every time I run my special senescent cell clearing protocol, I include lipo fisetin to maximize the effects without relying on harsh, immunosuppressive pharmaceuticals.
But I’m curious… do you use fisetin products? Let me know your experience in the comments below!