A Health Supplement Dosed Incorrectly

A supplement with promising anti-aging results* is dosed too low by all supplement companies.  This review article by Life Extension (LE), contains lots of good information and citations about a fisetin.  

Source: https://www.lifeextension.com/magazine/2021/2/fisetin-senolytic-benefits

Fisetin is a promising senolytic that is found in low concentrations in strawberries.  It would be necessary to eat several pounds of strawberries to achieve an effective dose.  Life Exention (LE) is a reputable supplement company dedicated to anti-aging support.  However, even LE failed to select the right dose for their supplement.

The study cited in the review above showed effects in mice at 60 to 100mg/kg body weight per day (Yousefzadeh et al, 2018).  For humans, this would be more than 4 to 6 grams of Fisetin. Using a standard mouse to human conversion factor for effective dose, that would still be more than 325-550mg of Fisetin.  

Assuming the LE supplement is 25x as bioavailable (as claimed), it would still need to be dosed at 13-22mg (1 pill is only 8mg, so 2-3 pills/day). BUT: Yousefzadeh et al already dosed Fisetin in phospholipids (liposomes), so it is not clear that the LE supplement really is more bioavailable or if it would be the same. If it isn’t more available, a consumer would need to take 40 to 70 pills per day to match the dose in the mouse study. 

Although there are unknowns in translating animal doses to humans and determining bioavailability, in this case LE has human pharmacokinetics from the Akay study (Krishnakumar et al, 2022). That study used 192mg of Fisetin per dose, and measured peak plasma concentrations (Fig.5) around 250ng/mL. The LE supplement dose of 8mg is less than 5% of the tested dose, and is probably equivalent to the unformulated (ie insoluble) Fisetin in that study. 

So, in conclusion, LE developed a more bioavailable Fisetin. But they then dosed it to be as equally ineffective as non-bioavailable Fisetin.

References

Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018 Oct;36:18-28.

Krishnakumar IM, Jaja-Chimedza A, Joseph A, Balakrishnan A, Maliakel B, Swick A. Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study. J Nutr Sci. 2022 Sep 9;11:e74. doi: 10.1017/jns.2022.72. PMID: 36304817; PMCID: PMC9574875.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574875/

*However, recent results from mouse study did not find any benefit:  Harrison, D.E., Strong, R., Reifsnyder, P. et al. Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used. GeroScience (2023).  https://link.springer.com/article/10.1007/s11357-023-01011-0