Fisetin – why is it worth using this health-promoting flavonoid?

Nature is full of many organic compounds that can affect brain health. In order to ensure good brain condition, it is important not only to have a balanced diet and physical activity, but also to consume health-promoting substances of organic origin. One of them is fisetin, whose beneficial properties are worth learning more about.

Fisetin – what is it?

So what is fisetin? The substance is one of the most thoroughly researched flavonoids in the scientific world. Technically speaking, fisetin is a molecule belonging to the flavonol subgroup. Structurally, it resembles the flavonols found in dark chocolate and cocoa.

Chemically, fisetin is also one of the flagship examples of flavonoid polyphenols (natural pigments). As a flavonol, it has antioxidant properties that protect cells from the harmful effects of free radicals. For this reason, the benefits of fisetin are also used in medicine.

Podolian smoketree – what is it?

The Podolian smoketree, known in botany as Cotinus coggygria, is the main source of fisetin. Smoke tree is a popular shrub with high decorative value. Its roots extend from the Mediterranean to distant Asia. It is fisetin that is responsible for the characteristic smell and appearance of smoke tree flowers.

Fisetin – where is it found?

Fisetin is found in small amounts in fruits and vegetables such as:

• Tomatoes
• Onions
• Kiwis
• Apples
• Grapes
• Strawberries

Strawberries definitely have the highest fisetin content among fruits and vegetables, followed by apples. The amount of fisetin in strawberries is about five times higher than in apples, and more than 30 times higher than in kiwis, grapes, tomatoes and onions.

However, the highest concentration of fisetin in nature is found in the flowers of the Podolian wig tree, which has become famous as a true organic treasure trove of this health-promoting compound.

Fisetin – medicinal properties

Like other flavonoids, fisetin offers a wide range of beneficial properties. First and foremost, its effects can be seen in brain health, cognitive function and memory.

The medicinal properties of fisetin include:

• Activates the body's antioxidant mechanisms that protect brain cells from oxidative stress;
• Increases glutathione content in brain cells, promoting detoxification and better cellular energy transfer;
• Supports the growth of new brain cells;
• Stimulates brain circuits and signalling pathways associated with long-term memory function.

Numerous studies examining the effect of fisetin on brain health have confirmed that fisetin is indeed a surprising ‘nootropic’ agent. This term describes substances whose supplementation can improve memory, concentration and promote good brain function.

What is more, fisetin is also a neurotrophic compound. These types of substances promote the survival, differentiation and maintenance of high functionality of brain cells. In other words, fisetin is characterised by the fact that it not only helps brain cells to function ‘better’, but also plays a role in brain plasticity.

Fisetin – potential health benefits

It should be noted that few studies have been conducted on the use of fisetin in humans. Despite this, we know that the substance appears to have a positive effect on:

• Memory improvement – fisetin supplementation increases the number of neural pathways;
• Protection against degenerative brain diseases – fisetin has been shown to regulate many metabolic functions that are associated with declining brain health. Fisetin protects nerve cells from oxidative stress and also reduces the accumulation of harmful chemicals that are associated with the development of Alzheimer's disease and dementia;
• Protects the brain from stroke – fisetin appears to protect every part of the brain that is vulnerable to a lack of adequate blood flow during a stroke. Thanks to its protective abilities, fisetin is one of the few compounds that directly protects the condition of the brain;
• Treats depressive disorders – fisetin is a powerful antidepressant that can help increase serotonin and noradrenaline levels. This action reduces the symptoms of depression and anxiety syndrome, among other things.

Fisetin in the diet – what is worth knowing?

When using fisetin, one should not expect immediate effects. What is more, natural sources of fisetin (apart from the Podolian wig tree) contain relatively low concentrations of the compound compared to dietary supplements.

For this reason, despite including foods containing fisetin in your daily diet, it would be impossible to take advantage of its enormous health potential.

Fisetin and lifespan – does it promote longevity?

After initial digestion, fisetin easily crosses the blood-brain barrier, acting through a very complex set of mechanisms that induce nootropic and neurotrophic effects. Like many other polyphenols, such as resveratrol, fisetin is able to activate sirtuin. The activation of sirtuin, a group of enzyme proteins, contributes to the prolongation of life in many living organisms, including, possibly, humans.

Although there is no direct evidence that sirtuin activation can lead to prolonged life, there is evidence suggesting that, in this context, fisetin appears to prevent many ‘common’ diseases responsible for shortening the lifespan of the human body.

Furthermore, fisetin itself leads to the elimination of damaged or ageing cells, reducing the risk of age-related diseases. This directly delays the effects of ageing. On the other hand, the substance prevents or delays autophagy, i.e. the controlled breakdown of the body's cells.

In addition to the above, fisetin has proven therapeutic effects, supporting long-term memory and stimulating concentration, while protecting neurons and supporting their growth. It is known that the deterioration of brain function directly contributes to a decline in quality of life and, consequently, its length.

Fisetin – how to dose and use?

The average daily requirement for fisetin from food is approximately 0.4 mg. Supplements, on the other hand, contain much higher amounts. Most leaflets and manufacturers' instructions recommend doses of 100 to 500 mg per day.

As fisetin is poorly absorbed by the body, it is recommended to take the substance with a fatty meal. Some supplement manufacturers offer fisetin with added oils and other fats to increase the bioavailability of the compound.

It should be remembered that, as with any dietary supplement, you should consult your doctor before starting supplementation. In addition, you should be aware of the risk of potential side effects, although their existence has not been confirmed by any clinical evidence.

Fisetin and quercetin – an effective combination?

Fisetin and quercetin are health-promoting, natural substances that have a long-term effect on the human body. Both compounds have neuroprotective, anti-inflammatory and antioxidant properties and appear to support a healthy balance of biochemical processes in the body.

As antioxidants, they act preventively against oxidative stress (free radicals in the body's cells), which is associated with various neurodegenerative diseases.

Bibliography

‘A computational study on the reaction between fisetin and 2,2-diphenyl-1-picrylhydrazyl (DPPH)’ – E. N Maciel et al., Journal of Molecular Modelling, Springer, 2019.

‘Antioxidant properties of the flavonoid fisetin: An updated review of in vivo and in vitro studies’ – A. Farsad Naeimi, M. Alizadeh, scientific journal Trends in Food Science & Technology, Elsevier, 2017.

‘Dietary flavonoid fisetin: A novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management’ – V. M. Adhami et al., scientific journal Biochemical Pharmacology, Elsevier, 2012.

Electrochemical and Density Functional Theory Study on the Reactivity of Fisetin and Its Radicals: Implications on in Vitro Antioxidant Activity – Z. S. Markovic et al., scientific journal The Journal of Physical Chemistry, ACS Publications, 2009.

‘Fisetin as a caloric restriction mimetic protects rat brain against ageing induced oxidative stress, apoptosis and neurodegeneration’ – S. Singh et al., scientific journal Life Sciences, Elsevier, 2018.

‘Fisetin is a senotherapeutic that extends health and lifespan’ – M. J. Yousefzadeh et al., scientific journal The Lancet, Elsevier, 2018.

Fisetin: A Dietary Antioxidant for Health Promotion – N. Khan et al., scientific journal Antioxidants & Redox Signalling, Mary Ann Liebert, 2013.

‘Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory’ – P. Maher, Tatsuhiro Akaishi, K. Abe, PNAS scientific journal, National Academy of Sciences, 2006.

‘Study of the Complexation of Fisetin with Cyclodextrins’ – M. R. Guzo et al., scientific journal The Journal of Physical Chemistry, ACS Publications, 2006.