ZHICHENG BIO
Fisetin oral exposure: what unformulated 98% powder actually delivers
The human PK arithmetic on fisetin, done in full — and what it means for anyone specifying the raw material.
The short answer
Unformulated 98% fisetin powder does not reach, by oral dosing, the concentrations at which fisetin is active in cell culture — and the gap is two to three orders of magnitude, not a rounding error. In the best available human study, 982 mg of unformulated fisetin produced a plasma Cmax of 9.97 ng/mL, which is 34.8 nM at a molecular weight of 286.24. Published in vitro work in this field typically uses 5–20 µM. Zhicheng Bio publishes this because it changes what a buyer should specify: unformulated 98% powder is the correct starting material for a formulator who intends to build a delivery system around it, and it is not a shortcut to exposure.
- The measured number
- Cmax 9.97 ng/mL from 982 mg unformulated fisetin; AUC0–12 12.67 ng·h/mL; quantifiable for roughly two hours (Tmax 0.88 h, t½ 1.14 h). Randomised double-blind crossover, N = 15 (J Nutr Sci 2022;11:e82, PMID 36304817)
- Converted
- 9.97 ng/mL ÷ 286.24 g/mol = 34.8 nM
- What in vitro work uses
- Typically 5–20 µM — a gap of roughly 144× to 574×
- Below 1,000 mg
- The same authors record that fisetin was not quantifiable at all at doses below 1,000 mg
- A formulated comparison
- A hybrid-hydrogel formulation containing 192 mg — about a fifth of the dose — gave Cmax 238.2 ng/mL and AUC0–12 341.4 ng·h/mL, that is 23.9× and 26.9× higher on a fifth of the dose
- What this does not say
- None of the above is a statement about whether fisetin is beneficial or harmful. It is a statement about how much of it reaches plasma from a powder
Why this number is the one to ask for
Every fisetin supplier will send you an assay figure. Almost none will send you an exposure figure, and the assay is the less decisive of the two. A certificate saying 98% by HPLC tells you what is in the drum. It tells you nothing about what reaches plasma after someone swallows it, and for a flavonol in BCS class IV — poorly soluble and poorly permeable — those two questions have very different answers.
The exposure question has a published answer, and it is not obscure. It sits in a randomised, double-blind crossover trial in 15 healthy volunteers, published in Journal of Nutritional Science in 2022. We link it in full on the fisetin product page rather than paraphrasing it, because a buyer's regulatory team should read the primary source rather than a supplier's summary of it.
The arithmetic, in full
Fisetin has a molecular weight of 286.24 g/mol. A plasma concentration of 9.97 ng/mL therefore corresponds to 34.8 nmol/L. That is the figure to carry forward, and it is worth converting yourself rather than accepting the commonly quoted "about 35 nM" on trust — the conversion is one division and it confirms the number.
Set that against the concentrations used in the cell work that generated interest in this molecule in the first place, which are typically 5–20 µM. Five micromolar is 5,000 nanomolar. The ratio is 144-fold at the low end of the in vitro range and 574-fold at the high end.
The gap does not close at clinically studied doses either. Human trials in this area have used weight-based intermittent dosing, commonly 20 mg/kg, which for a 70 kg adult is 1,400 mg. Extrapolating the measured exposure linearly from 982 mg gives roughly 49.7 nM — still 101- to 403-fold below the in vitro window. A typical retail dose of 100 mg extrapolates to about 3.55 nM, which is below the limit of quantification in the study that produced the source data.
A reviewer's instinct here is to reach for protein binding: plasma is more protein-rich than the 10% serum used in cell culture, so free concentrations differ. That correction runs the wrong way for the optimistic case. Culture medium at 10% serum holds roughly a tenth of the protein of plasma, so correcting to free concentration widens the gap by about another order of magnitude rather than narrowing it. Comparing total concentration to total concentration, as above, is the conservative comparison.
The one argument that could narrow the gap
There is a serious counter-argument, and it deserves stating properly rather than being waved away. Fisetin is heavily conjugated in phase II metabolism, and the sum of the parent compound and its glucuronide and sulfate conjugates is far larger than the parent alone. If those conjugates are hydrolysed back to the aglycone in target tissue, tissue exposure could exceed what plasma parent concentration suggests.
Taken at its upper bound, counting all conjugates, this reaches roughly 975 nM. That is a real improvement on 34.8 nM and it is still 5- to 20-fold short of the in vitro window — and it assumes tissue hydrolysis that has not been demonstrated. The honest position is that this argument reduces the gap without closing it, and that the experiment which would settle it has not been published.
What a buyer should do with this
If you are building a delivery system — solubilisation, cyclodextrin complexation, a lipid or hydrogel carrier — then unformulated 98% powder is exactly what you should be buying, and the exposure gap is the problem you are being paid to solve. The hydrogel comparison above shows the size of the prize: roughly 24-fold more plasma exposure on a fifth of the dose.
If you are filling capsules with neat powder and nothing else, you should know the number above before you commit to a label claim, a clinical programme, or a purchase order. It does not stop the material being saleable. It does determine what you can defensibly say about it, and it is the single most useful thing a supplier can tell you.
Either way, the specification conversation should cover the botanical source and the related-flavonoid profile as well — those are covered in the fisetin purchasing guide.
Frequently asked
Is fisetin bioavailable when taken as unformulated powder?
Measurably, but at low concentrations. A randomised crossover study in 15 volunteers (J Nutr Sci 2022;11:e82) recorded a plasma Cmax of 9.97 ng/mL — about 35 nM — from 982 mg of unformulated fisetin, with the compound quantifiable for roughly two hours. Below a 1,000 mg dose, the authors could not quantify it at all. In vitro work in this field typically uses 5–20 µM, which is 144- to 574-fold higher.
Does a higher purity grade improve fisetin absorption?
No. Purity and absorption are independent. Moving from 90% to 98% assay removes co-extracted flavonoids from the powder; it does not change the solubility or permeability of the fisetin molecule itself. Exposure is changed by formulation, not by assay.
What formulation approaches have published human data?
A hybrid-hydrogel formulation is the one with published human pharmacokinetics: 192 mg in that form gave Cmax 238.2 ng/mL and AUC0–12 341.4 ng·h/mL, against 9.97 ng/mL and 12.67 ng·h/mL from 982 mg of unformulated powder. Cyclodextrin complexation, solid dispersions and lipid systems are widely described for poorly soluble flavonoids generally, but a buyer should ask for data on fisetin specifically rather than on the class.
Why does Zhicheng Bio publish a number that makes its own raw material look weaker?
Because it is public, and because a buyer who discovers it after placing an order is a buyer lost. Zhicheng Bio sells the raw material to formulators, and a formulator needs the exposure figure to design around. Suppliers who imply that neat 98% powder delivers in vitro concentrations are making a claim the primary literature does not support.
This page describes raw-material sourcing and specification. It is not a health claim and not medical advice. Last updated 2026-07-31.