Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women,,

Abstract

A single-dose administration of purified unconjugated isoflavones at amounts that exceed normal dietary intakes had minimal clinical toxicity in healthy postmenopausal women. The pharmacokinetic data suggest that chronic dosing at 12-24-h intervals would not lead to progressive accumulation of these isoflavones.

Modulation of gene methylation by genistein or lycopene in breast cancer cells

“…In human feeding studies, consumption of high-soy diets for 10 weeks yielded plasma levels of genistein of 700 nM with large interindividual variation [Wiseman et al, 2004]. Dietary supplementation with a purified genistein-daidzein-glycitein ''bullet'' that delivers genistein amounts 3-to 4-fold greater than a soy-rich Japanese diets yielded plasma genistein levels in humans up to 27 lM, with minimal reported DNA toxicity [Bloedon et al, 2002;Miltyk et al, 2003]. In our recent review of the potential genotoxic effects of genistein we note that DNA damaging and other potentially adverse effects were primarily induced by high genistein concentrations in the 25-200 lM dose range, therefore we have used a low 3.125 lM concentration of genistein that we show here to be nontoxic to MCF-7 and MDA-MB-468 breast cancer cells.…”

Genistein, a natural product from soy, is a potent inhibitor of transthyretin amyloidosis

“…A significant, but not insurmountable, issue is that the oral bioavailabilities of genistein and genistin are modest, with in vivo plasma concentrations of genistein Ϸ0.1-8 M at a dose of 16 mg͞kg of body weight (12,13,57). Liu and Hu's (58) study using Caco-2 cells and perfused rat intestinal models shows that genistein is efficiently absorbed into the intestine, but extensive first-pass metabolism results in formation of 7-OH-glucuronic acid as the major metabolite.…”

“…The half-life of genistein in plasma was determined to be 3.2 h for men and 3.8 h for women. These appealing pharmacokinetics suggest that a slow-release formula could be useful (12,13).…”

“…Genistein is being evaluated in preliminary trials for treatment of breast, prostate, and uterine cancers (6,7), as well as for osteoporosis (8), cardiovascular disease (9), and treatment of menopausal symptoms (10). Toxicity studies reveal that this isoflavone does not appear to cause adverse health effects, even at the relatively high concentrations used (11)(12)(13). The isoflavone daidzein (3), lacking the hydroxyl group at the 5 position of genistein, is also found in soy foods, but no chemoprotective effects have been attributed to it.…”

“…The benefits of using such a nutraceutical are many; it is possible that some patients may benefit simply from increasing their intake of soy products or adding a soy-based supplement to their diets, but further research is needed. The wealth of toxicity information on genistein suggests that it is safe for human consumption, even at the high concentrations used for cancer trials (11)(12)(13). This compound, however, is known to target multiple pathways (7,50) and, as such, must be used cautiously.…”