Resveratrol bioavailability studies

While consumption of products rich in resveratrol appears to be beneficial for the reasons discussed above, little is known about resveratrol bioavailability in humans and animals. Emilia et al. (1999) developed an analytical method to measure stilbene present in blood. Resveratrol administered orally to rats was detected in plasma. Excellent HPLC-based separation of tram-resveratrol from other compounds in the blood was achieved, allowing a rapid analysis of the sample for absorption, distribution, and metabolism studies. 

Various studies have focused on the metabolism of piceid, the glucoside of resveratrol. These studies are of great interest due to the higher amount of piceid compared to resveratrol in food. Therefore, bioavailability studies of this compound are required. In vitro studies have already observed the absorption of piceid in the enterocytes, but in vivo studies in animal models are still scarce. 

Absorption of trans-resveratrol and other related compounds in rats was investigated [36]. Male Wistar rats (350 g) were used in a bioavailability study of [ H]trans-resveratrol administered by gavage together with (+ )-catechin, quercetin, and unlabeled trans-resveratrol in matrices of 10% ethanol, V8 vegetable homogenate mixture, and white grape juice. Whole blood, blood serum, urine, feces, and tissue... 

There is an extensive amount of literature on the in vitro activities of resveratrol. Bertelli et al. [1996] were the first to study the bioavailability of resveratrol in rats. They assessed analysis of plasma and tissues from rats that were administered red wine in a single dose or a regular dose for 15 day. Results indicated that resveratrol is quickly absorbed with a maximum peak at 1 h in plasma as well as in liver and kidney, although in the heart it peak at 2 h. Values obtained after regular consumption of red wine were higher than without the regular consumption in the different organs studies, in particular in the liver. The kidney seemed to be the main route of excretion (Table 13.2) [Bertelli et al., 1996]. 

Studies that investigate the bioavailability of resveratrol in humans are scarce. Moreover, the research in this area is quite recent. It has been summarized in Table 13.5. The experimental approaches have been improved with the use of new analytical techniques such as mass spectrometry to identify and quantify metabolites present in very low concentrations. Resveratrol and its metabolites have been measured in several biofluids plasma or serum, urine, LDL, and feces. 

Zamora-Ros et al [2006] carried out the first work that assessed the bioavailability of resveratrol (provided by different wines) in a regular intervention during 28 day. The analyses were performed by LC-MS/MS. In the first study, 10 healthy males were recruited to consume 300 mL/day of sparkling wine (1.19 mg resveratrol/1). After 28 day of supplementation, urinary trans-and m-resveratrol-3-O-glucuronides were 75 and 38 nmol/g creatinine, respectively. In the second study, 10 healthy females were selected to consume 200 mL of white wine (1.99 mg resveratrol/L) or 200 mL of red wine (12.8 mg resveratrol/L) in a crossover clinical trial. Likewise after 28 days only resveratrol metabolites were detected in morning urine, trans- (205 and 473 nmol/g creatinine) and ra-resveratrol-3-O-glucuronidcs (58 and 140 nmol/g creatinine) were found after white and red wine intake, respectively. Those studies showed that urinary excretion was dose dependent. Furthermore, slight amounts of resveratrol metabolites were also detected at baseline periods. No free resveratrol or piceid were detected in any of the studies. 

A study in animals found that pretreatment with oral ciclosporin had no effect on the pharmacokinetics of alcohol or acetaldehyde. This suggests that any difference in the alcohol consumption of patients taking ciclosporin is unlikely to have a pharmacokinetic basis. The mechanism by which red wine exerts its effect is not known. White wine does not appear to affect ciclosporin pharmacokinetics," so the interaction is not believed to be an effect of alcohol. Antioxidants in red wine such as resveratrol may inactivate the cytochrome P450 isoenzyme CYP3A4 and this would also be expected to increase ciclosporin levels. The solubility of ciclosporin is decreased in red wine and it is possible that substances in red wine bind ciclosporin in the gastrointestinal tract and reduce its bioavailability. Another study by the same authors suggested that ciclosporin absorption is possibly impaired by P-glycoprotein induction. ... 

The plant polyphenol trani-resveratrol (3, 5, 4 -trihydroxystilbene), mainly found in grape, peanut, and other few plants, displays a wide range of biological effects. Numerous in vitro studies have described various biological effects of resveratrol. In order to provide more information regarding absorption, metabolism, and bioavailability of resveratrol, different research approaches... 

Holbnan PCH (1997) Bioavailability of flavonoids. Eur J Clin Nutr 5LS66-S69 Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y (2004) Role of resveratrol in prevention and therapy of cancer preclinical and clinical studies. Anticancer Research 24(5A) 2783-2840... 

Numerous studies on animals and humans have shown resveratrol s low bioavailability. Once it is absorbed, at least 70% of the ingested resveratrol is readily metabolized to form mainly glucuronide and sulfate derivatives. Since the in vivo concentration of individual metabolites from ingested resveratrol can be much higher than that of resveratrol itself, further studies on the activity of its metabolites become necessary. 

To validate a nutritional biomarker, all criteria mentioned in the previous section have to been fulfilled. In summary, a good biomarker should be analyzable with robust methodology, bioavailable, specific, and sensitive (Spencer et al, 2008). First, extensive knowledge about wine composition was essential for selecting the possible target compounds that are present only in wines. After exhaustive studies on minor molecules in wine composition, mostly based on the polyphenol profile, resveratrol appeared as an optimal candidate (Lamuela-Raventos et al, 1995 Burns et al, 2002). Once it was preselected as a possible biomarker of wine consumption, the criteria had to be fulfilled. 

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