Ingested diosmin becomes diosmetin through Phase I metabolism through the intestinal wall, and then is either glucuronidated (primarily), sulfated, or methylated through Phase II metabolism in the liver. Serum analysis on healthy individuals demonstrates negligible presence of the aglycone in plasma, and low sustained levels of the diosmetin conjugates (primarily glucuronides) in plasma, with t max of 2.3 hrs and t 1/2 ranging from 8-70 hrs. Stachulski and Meng (2013) and Tranoy et al. (2014) note that most glucuronides are rapidly eliminated by the kidneys, posing an apparent limitation to their efficacy. Glucuronidation further reduces bioavailability to the intracellular compartment as the glucuronide moiety imparts a hydrophilicity that prevents cellular uptake. Yet to our knowledge 1) no quantitative bioavailability assays of diosmetin have taken place in non-plasma compartments such as extracellular fluid and tissue in humans; 2) tissue distribution studies of flavonoids in animal models are few. More in vivo distribution data to support therapeutic insights into polyphenols would be valuable.