53 replies to this topic

[Sunshine1]

Studies showed that Fisetin, a natural flavonoid in strawberries, dramatically improved LTP, although it would require almost 10 lbs. of strawberries to achieve the lab results. I recently cam across Fisetin from Japan that is extracted from the smoketree, and was wondering if anyone else has tried it yet?

[bgwithadd]

What were your results? And what does LTP stand for?

[mystery]

What were your results? And what does LTP stand for?

LTP = Long Term Potentiation, which I think means forming memories and/or learning. It seems to be similar to the concept of neuro plasticity.

Edited by mystery, 22 August 2008 - 05:44 AM.

[bgwithadd]

Hmm, that is very interesting. I wonder how many things that would help.

[tjcbs]

Any sources? (I'm in the US)

[Sunshine1]

Any sources? (I'm in the US)

Here's the research report on Fisetin -

Lead author Pamela Maher, Ph.D., a researcher in the Cellular Neurobiology Laboratory at the Salk Institute. Maher hit upon the beneficial effects of fisetin when she screened a collection of flavonoids, substances with anti-oxidant activities found in many plants, for their neuroprotective abilities in tissue culture models of neurodegenerative disease.

Maher found that some of those compounds, including fisetin, induced differentiation or maturation of neural cells. Maher explains, “That suggested to us that these compounds might be particularly beneficial, since they might not only protect neural cells from dying but might be able to promote new connections between nerve cells.”

Interestingly the signaling pathway activated by fisetin in neural differentiation also played a role in memory formation, a process neuroscientists call “long-term potentiation” or LTP. LTP allows memories to be stored in the brain by strengthening connections between neurons. “We wanted to find out whether we could detect any effects of fisetin on long-term potentiation and the formation of memories in animals,” Maher recalls.

Since the hippocampus plays an important role in establishing new memories, Maher, and co-authors Tatsuhiro Akaishi and Kazuho Abe, both at Musashino University in Tokyo, Japan, extended the study and found that fisetin activates the same signaling pathway in rat hippocampal tissues and also induces LTP.

Next, they tested fisetin’s effects in a so-called object discrimination test in mice. The mice get to explore two objects for a certain amount of time. The next day, one of the objects is replaced with a novel one. If the mice remember the object from the day before, they spend less time exploring the old one and instead turn their attention to the novel object. Indeed, mice administered a single dose of fisetin could better recall familiar objects. In fact, fisetin worked almost as well as rolipram, a substance known to enhance memory.

Memory loss caused by neurodegenerative disease occurs due to loss of neurons, a situation very different from that of healthy mice. Thus the ultimate goal is to stop neuronal loss. Nevertheless, memory-enhancing drugs can improve Alzheimer’s disease symptoms.

The observations that fisetin protects and promotes survival of cultured neurons and boosts memory in healthy mice make it a promising candidate for further studies. Notes Maher, “This is the first time that the function of a defined natural product has been characterized at the molecular level in the central nervous system and also shown to enhance both LTP in vitro and long-term memory in vivo.”

[tjcbs]

No I mean to purchase.

[tjcbs]

Here is pricing info from vitaspace.com. Anyone know what an active dose would be?

Fisetin 50% Powder Extract,
50 grams = $100.00 IN STOCK
100 grams = $200.00 IN STOCK
250 grams = $400.00 IN STOCK
1 kg = $1200.00 (This size is not in stock. Lead time = 4 weeks.)

[lynx]

The research on Fisetin really excites me, because unlike other flavonoids, Fisetin enhances neuronal function and growth through a largely non-ERK pathway. FISETIN increases proteasome activity, which is probably the single most important factor in succesful aging.

The flavonoid fisetin promotes nerve cell survival from trophic factor withdrawal by enhancement of proteasome activity.
Maher P.

The Salk Institute for Biological Studies, Cellular Neurobiology, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA. pmaher@salk.edu

To explore the possibility that specific flavonoids can substitute for neurotrophic factors, we examined the ability of the flavonol fisetin and several related flavonoids to support the survival of low density, serum-free cultures of rat cortical neurons. Normally these cells die within 24h in the absence of trophic factors but in the presence of fisetin and several related flavonoids the cells survive and produce long neurites. While the survival-promoting effect of several of the fisetin-related flavonoids was partially dependent on ERK activation, the effect of fisetin was not. Fisetin can enhance glutathione synthesis but the survival-promoting effect of fisetin was also not dependent on glutathione. However, proteasome inhibitors almost completely blocked the ability of fisetin to promote survival. Consistent with this observation, fisetin increased proteasome activity. Together these results demonstrate a new activity for fisetin and tie this activity to its neurotrophic effects.

[luv2increase]

Here is pricing info from vitaspace.com. Anyone know what an active dose would be?

I second this question. Can someone figure out what the ~ dosage would be in humans?


Thanks much! I'm going to add this to my stack. Make this addition # 2,344

[Thales]

"As shown in Fig. 5, three doses of fisetin were tested in the object-recognition task, and significant effects were seen at both 10 and 25 mg/kg. Higher doses were not tested."
http://www.pubmedcen...i?artid=1637622

Can anyone take a guess at a reasonable does for humans based on this?

[tjcbs]

Does anyone know how much fisetin is contained on average in say a pound of strawberries?

[Thales]

The flavanoid content of strawberries(with the exception of fisetin...)
http://www.nal.usda....Flav/Flav02.pdf

Can we assume the fisetin content in strawberries is something similar to that of the other flavonals?

[luv2increase]

Can we assume the fisetin content in strawberries is something similar to that of the other flavonals?

from http://content.karge...oduktNr=224161:

Recently, it has been reported that fisetin is found in strawberries (160 mg/kg) and apples (27 mg/kg) [33].

One site said that you would have to eat 10lbs of strawberries a day. This would equate to 10/2.2 = 4.54kg * 160mg = 726.4mg daily of fisetin


I don't know if the site talking about 10lbs was correct or not. The link above will only let you view it one time.


Concluding from the 50% powder source above, you are looking at around $100 a month!!!! It better had be worth it. One thing is for sure though, not many things have been shown to improve long-term memory. Most of the nootropics we talk about when dealing with memory only really help the short-term memory.

Who wants to be a tester?

Edited by luv2increase, 03 September 2008 - 07:37 AM.

[Thales]

What if I turn red?

[luv2increase]

What if I turn red?

What do you mean?

[Thales]

What if I turn red?

What do you mean?

It was a bad joke... I'm just concerned about potential health issues. Would it be as safe as eating 10lbs of strawberries?

[hamishm00]

What if I turn red?

What do you mean?

It was a bad joke... I'm just concerned about potential health issues. Would it be as safe as eating 10lbs of strawberries?

It didn't kill the mice, or turn them red (allegedly), so I suspect we humans can handle it.

Could you compare other supplements to the actions (LTP or otherwise) of Fisetin?

[brotherx]

What if I turn red?

then take a picture and upload it - we'll make it then sticky - with a warning - fisetin and associated health risks.

[Thales]

http://jn.nutrition....t/135/3/525.pdf

"In summary, we found that quercetin and fisetin were readily taken up into H4IIE cells and protected against H2O2-induced cytotoxicity, DNA strand breaks, and apoptosis at concentrations of 10–25
mol/L; however, these compounds themselves induced cytotoxicity, DNA strand breaks, oligonucleosomal DNA fragmentation and caspase activation at concentrations between 50 and 250
mol/L."

"More data on the pharmacokinetics of quercetin in humans are also available. Both the aglycone and the glucosides can enter the body via the small intestine, whereas other conjugates can be taken up only after hydrolysis by colonic bacteria (37,38). One study with 4 doses (250 mg)/day of quercetin administered as capsules resulted in plasma concentrations of 1.5
mol/L (39); however, later studies using quercetin glucosides yielded relatively higher plasma concentrations, i.e.,7
mol/L after quercetin- 4-O-glucoside equivalent to 100 mg quercetin (40), 4.5 mol/L after 150 mg quercetin 4-glucoside, and 5
mol/L after 150 mg quercetin 3-glucoside (41). When administered in onions (a plant source that contains quercetin as glucosides) the following plasma concentrations of total quercetin as related to dose were reported: 0.05
mol/L after 15 mg (42), 0.63 mol/L after 68–94 mg (43), 7.65
mol/L after 100 mg (40), and 4
mol/L after 300 mg (44). Half-lives between 10 and 30 h were reported (40,41,45), suggesting that continuous daily intake will result in a steady-state concentration. All kinetic variables measured in humans were measured in plasma, and no information on flavonoid concentrations in different tissues is available. In some studies, no free quercetin was found in blood samples [e.g., (43)], whereas in others, free quercetin was detected (46). Isorhamnetin is the only phase I metabolite described (40). It is unclear at present whether the metabolites still possess pharmacologic activity. Data suggest that flavonoids can be deglucuronidated at the site of action, e.g., in endothelial cells (47,48). In contrast to quercetin, data on fisetin plasma concentrations in humans are lacking, probably because it is minimally present in the diet. Fisetin, like quercetin, is methylated in human liver (49). Taken together, the data on quercetin pharmacokinetics in humans suggest that a dietary supplement of 1–2 g of quercetin, an a mount proposed by supplement makers, may result in plasma concentrations exceeding 10
mol/L but probably not exceeding 50 mol/L if taken properly."

So maybe we shouldn't test it until we find out what it would take to exceed 50 mol/L.

[neogenic]

Actually, since both 10 and 25mg/kg showed significance it'd be 750-1875mg for 75kg person and 1000-2500...THEN adjust using the skin surface measurement (of which some debate, but is FDA tested and reference for big pharma) of about 6. 125mg-313mg for a 75kg person and 167mg-417mg of the fisetin.
http://www.pubmedcen...e...igure&id=F5
Using this table, there is a linear increase in cognitive effect with an exponential increase...aka diminishing returns with increasing doses. 25mg is not a dramatic difference between 10mg. To maybe top out...who knows...it could be further exponential of like 100mg/kg...and then you could run in to the down sides such as the mentioned DNA damage.

10mg/kg seems like a financially feasible and smart dose to experiment with. Buth either way study dosing in human terms would be about 100-500mg qd.

[Thales]

Actually, since both 10 and 25mg/kg showed significance it'd be 750-1875mg for 75kg person and 1000-2500...THEN adjust using the skin surface measurement (of which some debate, but is FDA tested and reference for big pharma) of about 6. 125mg-313mg for a 75kg person and 167mg-417mg of the fisetin.
http://www.pubmedcen...e...igure&id=F5
Using this table, there is a linear increase in cognitive effect with an exponential increase...aka diminishing returns with increasing doses. 25mg is not a dramatic difference between 10mg. To maybe top out...who knows...it could be further exponential of like 100mg/kg...and then you could run in to the down sides such as the mentioned DNA damage.

10mg/kg seems like a financially feasible and smart dose to experiment with. Buth either way study dosing in human terms would be about 100-500mg qd.

I'm not sure if I understood you correctly. If we just need between 167-417mg of fisetin then does it follow that 1 kg of strawberrys should contain an active dose(given it contains 160 mg/kg)?

Edited by Thales, 05 September 2008 - 09:10 PM.

[neogenic]

Actually, since both 10 and 25mg/kg showed significance it'd be 750-1875mg for 75kg person and 1000-2500...THEN adjust using the skin surface measurement (of which some debate, but is FDA tested and reference for big pharma) of about 6. 125mg-313mg for a 75kg person and 167mg-417mg of the fisetin.
http://www.pubmedcen...e...igure&id=F5
Using this table, there is a linear increase in cognitive effect with an exponential increase...aka diminishing returns with increasing doses. 25mg is not a dramatic difference between 10mg. To maybe top out...who knows...it could be further exponential of like 100mg/kg...and then you could run in to the down sides such as the mentioned DNA damage.

10mg/kg seems like a financially feasible and smart dose to experiment with. Buth either way study dosing in human terms would be about 100-500mg qd.

I'm not sure if I understood you correctly. If we just need between 167-417mg of fisetin then does it follow that 1 kg of strawberrys should contain an active dose(given it contains 160 mg/kg)?

Forget strawberries...its irrelevant. Just think of fisetin. The study used 0mg (control) 5mg, 10mg, and 25mg/kg of fisetin in rodents. As described in the aforementioned diagram from the study I linked 10 and 25mg/kg showed significance. The rodent to human ratio for metabolism used by these studies and is not always accurate, but a starting place is 5-7:1 depending on the species. So 6:1. We divide those number by 6. Next the average person is 75-100kg. I gave ranges using the low and high dose and the low and high weight.

The math is straightforward. If you were using a 50% powder (and not strawberries...) you'd have to double the dose recommendation to get the desired fisetin. As you described strawberries are not a strong source and it would be pointless to get 160mg (active)/1,000,000mg(strawberries)...so that source is moot and the supplement is logical.

Edited by neogenic, 05 September 2008 - 10:57 PM.

[Thales]

Thank you for simplifying that a bit for me. And I unfortunately was thinking of 1 lbs (which wouldn’t be unrealistic) instead of 1 kg, so thats why I brought up strawberries again...

Edited by Thales, 06 September 2008 - 01:58 AM.

[neogenic]

That's fine so is anyone going to buy this and post thoughts? Its reasonable at the doses I described and the prices given.

[MrSpud]

Anybody know anything about Fisetin? Is it a legit nootropic? Any info on specific effects, dosage, side effects?

[maxwatt]

Anybody know anything about Fisetin? Is it a legit nootropic? Any info on specific effects, dosage, side effects?

Fisetin was one of the compounds that Sinclair found stimulated SIRT1 in his lab's screening for SIRT1 activators. However a later paper, where the researchers developed an assay that did not rely on the fluorophoine in the original assay, found fisetin activated Sirt1 almost as strongly as resveratrol, which is not very strongly at all: a 30 to 40% increase over baseline. That paper is discussed HERE. Fiestin shares some of resveratrol's properties as an anti-inflammatory and apoptic agent against cancer but it's not as thoroughly studied. I've seen no strong nootropic claims made for either substance, though anecdotal reports have suggested as much for resveratrol.

[MrSpud]

I just found a patent about fisetin called "Methods of Using Flavonoids to Enhance Memory" at http://www.salk.edu/...S28021096A1.pdf

In it it says this about dosage

Edited by MrSpud, 22 January 2011 - 04:19 PM.

[APBT]

I've seen no strong nootropic claims made for either substance, though anecdotal reports have suggested as much for resveratrol.

Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory
http://www.ncbi.nlm....les/PMC1637622/

Fisetin in Strawberries, like Blueberries And Red Wine, Offer Memory Health Benefits
http://memoryzine.co...ealth-benefits/

Natural Chemical Found In Strawberries Boosts Memory In Healthy Mice
http://www.scienceda...61017164401.htm

Google Scholar
http://scholar.googl...s=1&oi=scholart

[maxwatt]

Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory
http://www.ncbi.nlm....les/PMC1637622/

Fisetin in Strawberries, like Blueberries And Red Wine, Offer Memory Health Benefits
http://memoryzine.co...ealth-benefits/

Natural Chemical Found In Strawberries Boosts Memory In Healthy Mice
http://www.scienceda...61017164401.htm

Google Scholar
http://scholar.googl...s=1&oi=scholart

Suggestive paper, but I am not holding my breath waiting for human studies. What oral dose would give a serum concentration similar to the in vitro concentration seen in the slices of rat brain?