Fisetin

Preclinical data suggests that fisetin may improve cognition or protect against Alzheimer’s disease, but there is no data suggesting that it will be effective in humans. Our search identified:

• 0 meta-analyses or systematic reviews
• 0 human clinical trials or observational studies
• Fewer than 10 preclinical studies suggesting a benefit to cognition or protection from Alzheimer's disease

Data from preclinical studies suggest that fisetin might strengthen the connections between brain cells and enhance memory in healthy rodents [1]. Studies in animal models of Alzheimer's disease suggest fisetin may also lower levels of phosphorylated tau and aggregated beta-amyloid (i.e., the tangles and plaques common in patients with Alzheimer's) [2-4], lower levels of neuroinflammation [5][6], and prevent the development of memory deficits [7][8]. Some studies also suggest that fisetin might be protective against stroke, which may lead to dementia [9]. Despite this promising preclinical data, no studies have tested fisetin in humans.

For Dementia Patients

No studies have examined fisetin in Alzheimer's patients, but some preclinical evidence (see above) suggests it could theoretically have a protective effect.

Fisetin consumed in the diet is safe, and fisetin supplements are commercially available with no reports that we could find for safety concerns or reported side effects. However, there is currently no scientific research in humans on whether supplemental doses of fisetin are safe, especially in the long term. Although fisetin is being researched as a potential treatment to protect from cancer, possible carcinogenic effects have been identified and the effects in humans have not been determined [10-13].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

No studies have examined the correct dosing of fisetin in human beings. It is estimated that a person would have to eat 37 strawberries every day to reach the doses used in animal studies. Fisetin is currently available over-the-counter as a supplement, generally in 100 mg tablets.

Salk Institute press release of treatment of Alzheimer's mouse model with fisetin

Article on fisetin and memory from Consumer Lab

1. Maher P, Akaishi T, Abe K (2006) Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proceedings of the National Academy of Sciences of the United States of America 103, 16568-16573.
2. Kim H, Park BS, Lee KG et al. (2005) Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. Journal of agricultural and food chemistry 53, 8537-8541.
3. Ushikubo H, Watanabe S, Tanimoto Y et al. (2012) 3,3',4',5,5'-Pentahydroxyflavone is a potent inhibitor of amyloid beta fibril formation. Neuroscience letters 513, 51-56.
4. Kim S, Choi KJ, Cho SJ et al. (2016) Fisetin stimulates autophagic degradation of phosphorylated tau via the activation of TFEB and Nrf2 transcription factors. Sci Rep 6, 24933.
5. Chuang JY, Chang PC, Shen YC et al. (2014) Regulatory effects of fisetin on microglial activation. Molecules 19, 8820-8839.
6. Cho N, Lee KY, Huh J et al. (2013) Cognitive-enhancing effects of Rhus verniciflua bark extract and its active flavonoids with neuroprotective and anti-inflammatory activities. Food Chem Toxicol 58, 355-361.
7. Currais A, Prior M, Dargusch R et al. (2014) Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice. Aging cell 13, 379-390.
8. Ahmad A, Ali T, Park HY et al. (2016) Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice. Mol Neurobiol.
9. Maher P (2015) How fisetin reduces the impact of age and disease on CNS function. Front Biosci (Schol Ed) 7, 58-82.
10. Lopez-Lazaro M, Willmore E, Austin CA (2010) The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells. Mutat Res 696, 41-47.
11. Lim DY, Park JH (2009) Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin. Am J Physiol Gastrointest Liver Physiol 296, G1060-1068.
12. Bothiraja C, Yojana BD, Pawar AP et al. (2014) Fisetin-loaded nanocochleates: formulation, characterisation, in vitro anticancer testing, bioavailability and biodistribution study. Expert opinion on drug delivery 11, 17-29.
13. Strick R, Strissel PL, Borgers S et al. (2000) Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proceedings of the National Academy of Sciences of the United States of America 97, 4790-4795.