Fisetin is a flavanoid found most abundantly in strawberries. It is currently being investigated as a dietary supplement that can boost memory performance and help patients with Alzheimer’s disease.
But the benefits of this natural compound do not stop there. It has displayed anticarcinogenic, antioxidant, neurotrophic and anti-inflammatory properties both in vivo and in vitro, however, its mechanisms of action are still being explored.
As Khan concluded in 2013, identifying molecular targets will be the next forward in deriving medical applications from this promising phytochemical.
Since then studies conducted with different cancer cells have shown fisetin can induce apoptosis, but if administered in quantities larger than one would or could consume through dietary sources, its inhibition of DNA topoisomerase (demonstrated in vivo) could have positive or adverse effects on carcinogenesis depending on the patient and the type of cancer.



- Flavonol antioxidant for healthy aging
- Promotes brain cell health
- Maintain mitochondrial function & glutathione
Benefits of Fisetin
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Fisetin shows more promise as a longevity agent since ingestion is thought to mimic caloric restriction, which to date is the only proven method of extending maximum mammalian lifespan.
It has extended the lifespans of yeast, fruit flies and c. elegans (a worm), but it is not sure if it will do the same for humans.
Most pertinent here, and far less ambiguous based on the numerous studies supporting it, is its usefulness as a nootropic and neuroprotectant.
There are no longitudinal studies available and precious few case reports, but it appears to be safe even when taken in unnatural amounts.
Fisetin Supplements for Memory
As a neurotrophic factor its brain benefits are quite clear and fairly certain. Neurotrophic factors promote “the differentiation, survival, and functional maintenance of nerve cells.” This means they have immense therapeutic potential.
The majority of known neurotrophic factors are, predictably, proteins made by the body. At the moment the medical usefulness of these endogenous proteins is limited.
Pamela Maher, citing earlier experiments by Ishigi, mentions fisetin not only promotes nerve cell differentiation, but protects “nerve cells from oxidative stress-induced death.” Oxidative death is one of the many factors associated with cognitive decline, stroke, Alzheimer’s and Parkinson’s.
Maher hypothesized that fisetin would enhance long term memory in mice thanks to its activation of ERK in the hippocampus, which, through a cascade of biochemical events, activates CREB (cAMP responsive element binding protein), which is instrumental in the formation of long term memories. It does not have any measurable effect on short term memory.
Dr. Maher also showed fisetin increases intracellular glutathione and reduces inflammation by inhibiting the production of lipid peroxides. It looks like an excellent candidate for delaying neuro-senescence. This and its influence on memory storage could make it a welcome addition to many nootropic stacks.
Preventing Oxidative Stress on the Brain
On average the brain accounts for 2% of a person’s weight, yet it consumes 20% of the oxygen taken in through respiration. As one can imagine, this exposes the brain to a great deal of possible oxidative damage.
Glutathione helps dispose of peroxides and aids in shielding cells from free radicals. Chronic alcohol consumption, for instance, does damage to the brain partially by reducing glutathione and raising lipid peroxide levels.
Although meta-analyses have found no relationship between drinking alcohol and dementia. According to Anstey, it may even deter dementia. Nevertheless, excessive drinking graphically illustrates what glutathione, among other things, can do to the brain and cognition.
Microglia are the primary line of defense in the brain and spinal cord. They are necessary to fight off infections and maintain brain health by removing debris (plaque, dead or damaged cells, foreign matter, etc), but prolonged overactivation of their immune functions, and the resulting cytokine overproduction and inflammation, has been implicated in the development of a modicum of degenerative disorders, including Alzheimer’s.
Microglia overexpressing interleukin-1 are commonly found in Alzheimer’s patients. To make matters worse, when microglia encounter the beta-amyloid deposits characteristic of the disease, they are prompted to make cytokines and neurotoxic proteins, thus contributing to further inflammation. Fisetin “inhibited the gene expression of TNF-alpha, interleukin (IL)-1beta, cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS).”
Additional Longevity-Boosting Effects
Fisetin and resveratrol have been explored as a means of slowing the progress of Huntington’s disease for this reason. These effects are all potentially beneficial to a healthy person who wants to keep their mind, but not as much to someone with Alzheimer’s since these are not the primary culprits.
However, fisetin has also been shown, along with the flavonoids quercetin, luteolin, and myricetin, to inhibit beta-amyloid aggregation in vitro. This is exciting, to say the least.
It is not yet known how much of a protective effect can come from common foodstuffs, but based on the amounts used in animal and in vivo studies, one can say it is not negligible. Fisetin relieves allergic reactions by inhibiting cytokine production. Kaempferol and quercetin do this as well, but not to the same extent.
There are already many potent allergy medications on the market, so flavonoids will likely never occupy this niche. This quality is of most interest to those looking at fisetin as a way of improving their general health.
Fisetin will likely become a popular study aid. There are only so many people who can cram a semester’s worth of material into their heads the night before the big test. Such cramming may take three or four. Jesting aside, improving one’s retention a week before finals does not sound like a terrible idea.
If you are happy with your long term memory and have no need to improve it and do not have disposable income, there is no need to try it. If one of these is not the case, then perhaps you ought to consider conducting your own experiment with Fisetin supplements… starting with a small dose, of course.
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Article last updated on: June 18th, 2018 by Nootriment