What effects does Fisetin have?
Due to its molecular structure, Fisetin has the ability to neutralize free radicals. This makes it, similar to other secondary plant compounds, a natural antioxidant. Additionally, the molecule can increase the amount of glutathione, the strongest antioxidant in many organisms.
In addition, it interacts with some inflammatory signaling pathways and has been shown to repeatedly produce anti-inflammatory properties in cell studies .
Where is Fisetin found in foods?
It occurs naturally in a variety of foods. In larger amounts, the substance is found in strawberries, making this fruit one of the best natural sources of this flavonoid. In addition, Fisetin is found in other fruits such as apples and mangoes as well as in vegetables such as tomatoes, onions, and cucumbers .
It is also found in manageable amounts in nuts and seeds as well as in wine and dark chocolate . Some spices, including turmeric and ginger, also contain fisetin.
Since the fisetin content in foods varies, it is important to consume a variety of foods to ensure that you are getting an adequate amount of this beneficial flavonoid. It is also worth noting that fisetin is heat-sensitive, so raw or minimally processed foods tend to have a higher content of this nutrient.
How much fisetin is contained in foods?
Depending on the database, you may get slightly different results to this question.To give you a better overview, we have summarized some of the foods with the highest content of Fisetin. The basis for the table is this study:
| Foods | Fisetin content (µg/g fresh weight) |
| Strawberries | 160 |
| Apples | 26.9 |
| Grapes | 6.2 |
| Onions | 4.8 |
| Cucumbers | 5.2 |
| Tomatoes | 0.8 |
| Kiwis | 2.0 |
| Peaches | 1.9 |
Fisetin, Quercetin, and Luteolin.
The three molecules, Fisetin, Quercetin and Luteolin are all classified as secondary plant substances. To give you a better overview of which fruits and vegetables contain which molecule, we have created another table for you here. The data comes from this study.
| Food | Fisetin (μg/g fresh weight) | Quercetin (μg/g fresh weight) | Luteolin (μg/g fresh weight) |
| Green Bean | not measured | 12.6 | 10.1 |
| Green Pepper | not measured | 14.1 | 14.7 |
| Parsley | not measured | 7.0 | 3.1 |
| Onion | 4.8 | 337.0 | 1.9 |
| Lotus Root | 5.8 | 4.4 | 3.6 |
| Salad | not measured | 4.8 | 5.2 |
| Orange | not measured | 17.5 | 1.0 |
| Persimmon | 10.5 | not measured | 1.4 |
| Strawberry | 160.0 | 6.9 | not measured |
The current state of research
Currently, research on Fisetin is still based on animal studies, but the first studies on humans are already being conducted.We show you in which areas of science Fisetin is being researched:
Alzheimer
The Alzheimer's disease is a serious and chronic brain disorder characterized by the deposition of a substance called Amyloid-Beta and the excessive phosphorylation of proteins called Tau in the brain . This accumulation leads to problems with brain function, particularly with memory and perception.
In a study on mice, researchers investigated the protective effect of Fisetin on the brains of mice, particularly in relation to Alzheimer’s. They used a model of Alzheimer's disease in which the mice were injected with Amyloid-Beta.This injection led to the known memory and synapse problems, as well as inflammation in the brain and degeneration of neurons.
The mice were then treated with Fisetin, which was injected into the body (not directly into the brain). This treatment began one day after the amyloid-beta injection and lasted for two weeks. The researchers found that the molecule significantly reduced the accumulation of amyloid-beta as well as the hyperphosphorylation of tau proteins in the mouse brain. Furthermore, it contributed to the improvement of synaptic function , leading to an enhancement of the memory performance of the mice.
The treatment also activated pathways in the brains of the mice that helped counteract the effects of amyloid-beta.
Inhibition of Inflammatory Factors
To find out what properties Fisetin has, scientists conducted cell culture studies . These are basic research studies to better understand the biochemical relationships between the molecules. It is important to note that these studies only represent a foundation for how molecules are likely to act.
What have the scientists discovered about Fisetin in the cell culture studies? Fisetin interacts in the cell culture studies in several ways: It can reduce the production of pro-inflammatory cytokines and chemokines.Furthermore, Fisetin can inhibit the activity of enzymes involved in inflammatory processes, such as Cyclooxygenase-2 (COX-2) and Lipoxygenase (LOX), which are responsible for the production of inflammatory mediators.
Another mechanism through which Fisetin may exert its anti-inflammatory effect is the modulation of signaling pathways involved in inflammatory responses. Fisetin appears to inhibit the activation of NF-kB (nuclear factor kappa B), an important regulator of the inflammatory response, and modulate the activity of signaling pathway proteins such as MAP kinases and PI3K/Akt, which are involved in inflammatory processes .
Furthermore, Fisetin has shown that it can regulate the activity of inflammatory cells such as macrophages and neutrophils by reducing the release of inflammatory mediators such as nitric oxide (NO) and prostaglandins .
Fisetin & Longevity
In studies with mice, the administration of Fisetin in late life led to a restoration of tissue homeostasis, a reduction of age-related pathologies, and an extension of mean and maximum lifespan.
Even when administered to rodents at the equivalent of 75 human years, Fisetin was able to extend lifespan by 10%. These results are likely attributable to the effect of Fisetin on the Hallmarks of Aging .Not only in mice did researchers demonstrate that Fisetin has a life-extending effect, but also in flies and worms. The life-extending effect in animal studies is likely due to the activation of the Sirtuins . This family of genes, often referred to as longevity genes, is at the center of aging research. Other molecules that also count as Sirtuin activators include z.B. the one researched by David Sinclair Resveratrol.
To help you better understand the molecular background, we will show you using the example of cellular senescence how Fisetin affects longevity in animal studies.
Senescence
Before we introduce you to the molecular interaction of Fisetin, we first explain the concept of senescence and senolysis. Senescence refers, simply put, to old cells that no longer divide and remain in a kind of intermediate state – not really dead, but also not really alive. Hence the nickname "zombie cells".
We find these senescent cells at every stage of life in our body, and under certain circumstances, they can even be beneficial. With age, however, too many of these "zombie cells" probably accumulate, and the body can no longer keep up with the elimination, the senolysis, of these cells. This excess of senescent cells leads to the activation of tissue hormones and signaling molecules, which are summarized under the name SAPS. In particular, studies in animals have shown that the elimination of "zombie cells" led to a longer and healthier life. The molecules that can help the body detect and eliminate such "zombie cells" are called senolytics.
Senolytics – the weapon against "zombie cells"
The senolytic therapy, which aims at the selective removal of senescent cells, has attracted a lot of attention in recent years. Much of it is still theory and has only been tested on animals.
According to this paper , the senolytic potency of Fisetin is higher than that of comparable flavonoids. A study showed that Fisetin could destroy senescent cells in old mice and improve both their health and lifespan.
One of the molecular mechanisms behind the extension of lifespan in animal experiments is presumably the DAF-16-induced stress response and the induced autophagy. The altered autophagy is one of the hallmarks of aging, and a reversal of this could thus be one of the molecular reasons for the effects of Fisetin in longevity research.
Did you know? Autophagy refers to the body's ability to sort out "old cells," as happens during fasting .
Quercesome - 20 times increased bioavailability compared to conventional quercetin powder. Thanks to phospholipids from sunflower and natural vitamin C.
Side effects of fisetin
Fisetin is generally considered well tolerated. As with all dietary supplements, side effects may occur, especially at higher dosages.These include:
- Gastrointestinal complaints: Some people may experience gastrointestinal issues such as stomach pain, nausea, or diarrhea after taking Fisetin dietary supplements .
- Allergic reactions: Although rare, it is possible for individuals to have an allergic reaction to Fisetin. Symptoms of an allergic reaction may include rash, itching, breathing difficulties, and swelling of the face or throat.
- Interactions with medications: Fisetin may potentially interact with certain medications, especially those that affect blood clotting, such as blood thinners (anticoagulants). This could increase the risk of bleeding.
Conclusion
Fisetin is a versatile and exciting molecule from the group of flavonoids. It is being researched for its senolytic properties. Currently, there is mainly basic research on Fisetin, but this will certainly change in the near future.
