Although it was about a single person (n=1, as they say), I found it interesting that that person's PD symptoms came and went, apparently depending on their diet and intake of Fisetin. I searched around online and found supporting studies and theories about Fisetin's ability to reach the brain, although I found no studies that applied Fisetin to PD. That was enough to buy some and try it on myself. Since then, a lot's happened.
Fisetin is fairly inexpensive and readily available at many online supplement providers. All studies that I read about said that it was well-tolerated. But until recently it's not been the subject of very many studies. At least to me it seemed that it was yet another dead-end, so I stopped taking it. But I kept an eye on it and about a year ago I noticed an increase in interest. Here's a list of several of the more interesting developments. About 6 months ago, I began taking Fisetin again, along with my other supplements, exercise, and red-light therapy. I've seen some improvements, but not enough yet to make any other claims. By posting this now, I'm hoping that others will give their opinions and insights. I think the list below shows that there might be enough info to keep it in my supplement list for an extended time. I'm currently taking 100 mg dissolved in EVOO (extra virgin olive oil) since it is fat-soluble. I'm seriously thinking of increasing that.
Unfortunately every single study listed that was not a survey and actually tested fisetin either pretreated or simultaneously treated fisetin while applying the toxicant. These are not valid Parkinson's models because even a simple antioxidant can protect against toxicant insult under this circumstance. A valid Parkinson model requires first applying the toxicant and only applying treatment after alpha synuclein aggregation appears. I did find one study which showed that fisetin reduced the amounts of alpha synuclein aggregation in a yeast model:
Well done JAS9! I started poking around those links and found Dr. Pamela Maher was one of the authors. Which led me to this:
Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper 2020researchgate.net/publicatio...
"My laboratory has shown that the flavonoid fisetin (3,7,30,40 tetrahydroxyflavone) has both
neuroprotective and cognition-enhancing activities [1]. Fisetin was first identified in a screen for compounds that could protect nerve cells from a form of oxidative stress-induced nerve cell death called oxytosis or ferroptosis [2]. Not only does fisetin have direct antioxidant activity but it can also maintain the levels of the major intracellular antioxidant, glutathione (GSH), in the presence of oxidative stress by inducing the transcription factors, Nrf2 and ATF4 [3]. Importantly, administration of fisetin via the diet prevented the loss of cognitive function in mouse models of both familial (APPswe/PS1dE9 (huAPP/PS1) double transgenic AD mice) [4] and sporadic (rapidly aging SAMP8 mice) [5] Alzheimer’s disease (AD). In addition, fisetin has shown efficacy in preclinical models of Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis as well as multiple models of stroke [forreview1]. Importantly, fisetin was found to have robust anti-inflammatory activity both in vitro [6–8] and in vivo [9]. Together, these observations suggest that fisetin has multiple properties
that might make it useful for the treatment of age-related neurological diseases.
Antioxidants 2020,9, 1113; doi:10.3390/antiox9111113 mdpi.com/journal/antioxidants Antioxidants 2020,9, 1113 2 of 18 With aging there is an increase in both iron and copper in the brain and these levels are further increased in AD [10–16] suggesting that they might play a role in the cognitive dysfunction that is the primary characteristic of the disease. For instance, a correlation was found between accelerated cognitive decline and high copper intake [17]. Analysis of the brains of AD patients with magnetic
resonance imaging (MRI) found that damage to the hippocampus, the region of the brain that plays a key role in memory, is associated with iron accumulation [18,19]. Moreover, increases in brain iron levels as determined by MRI were associated with a decrease in cognitive function [19,20]. Importantly, the iron accumulation occurs only in the parts of the brain that are involved in AD [18]. A more recent study which investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD found a strong correlation between high levels of iron in the inferior temporal cortex and cognitive decline while no increase in iron was seen in the cerebellum, a part of the brain not affected by AD [21]. Not only can iron and copper accumulation contribute to increases in oxidative stress and the potentiation of nerve cell death by oxytosis/ferroptosis [22] but recent studies suggest they may also may play roles in cellular senescence, a pro-inflammatory cell fate associated with age-related diseases, including AD [23,24]. Furthermore, iron and copper chelators have shown beneficial effects in animal models of AD [11,25,26] as well as some limited positive results in human AD patients [24,27]. However, these human results are tempered by the neurotoxicity associated with one of these compounds, cliquinol [28,29], as well as questions about its efficacy [30]. Indeed, the cliquinol clinical trials were stopped due to severe neurotoxic effects due to oxidative damage [29].
Metal chelation has been implicated in the beneficial effects of a number of different flavonoids including fisetin [31]. Indeed, fisetin has been reported to bind both iron [31–34] and copper [33,35].
Therefore, in this study it was asked if at least some of the neuroprotective and/or anti-inflammatory properties of fisetin could be due to its ability to modulate the effects of iron and/or copper on cells"
Modern Healthspan and others on YouTube discuss this. You literally need at least 500mg - 1 gram from what I have read.
Here's a video about how Fisetin helps keep "zombie cells cleared out by working as a senolytic that's as powerful as dasatinib and quercitin combined."
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