Measurement of Saccharin and trans-Resveratrol Metabolites in Urine as Adherence Markers for Small Quantity Lipid-Based Nutrient Supplement Consumption.

Saccharin and trans-resveratrol were incorporated into small quantity lipid-based nutritional supplements (SQ-LNS) to be evaluated as the markers of consumption for nutritional intervention studies. Forty-seven healthy women consumed a single supplement with either 8.6 mg of saccharin or 5 mg of trans-resveratrol, and urine was collected for 4 h. A rapid 11 min method employing multiple reaction monitoring and ultrahigh performance liquid chromatography coupled to a triple quadrupole mass spectrometer was developed to measure saccharin and resveratrol metabolites in urine simultaneously. The linear dynamic range of the method was from 3 to 1000 ng mL-1, with the correlation coefficient of 0.999 and limits of quantification from 15.28 to 53.03 ng mL-1. Sample preparation was simple dilution with an average recovery of 97.8%. Ion suppression was observed with urine concentrations >10%. Mean levels of saccharin and resveratrol-3-O-sulfate in urine were 5.481 ± 4.359 and 3.440 ± 4.160 nmol L-1, respectively. We developed and validated a method to measure saccharin and trans-resveratrol metabolites in urine to objectively corroborate the consumption of SQ-LNS for the first time in nutrition intervention studies.

Urinary Resveratrol Metabolites Output: Differential Associations with Cardiometabolic Markers and Liver Enzymes in House-Dwelling Subjects Featuring Metabolic Syndrome.

Metabolic syndrome (MetS) components are strongly associated with increased risk of non-alcoholic fatty liver disease (NAFLD) development. Several studies have supported that resveratrol is associated with anti-inflammatory and antioxidant effects on health status. The main objective of this study was to assess the putative associations between some urinary resveratrol phase II metabolites, cardiometabolic, and liver markers in individuals diagnosed with MetS. In this cross-sectional study, 266 participants from PREDIMED Plus study (PREvención con DIeta MEDiterránea) were divided into tertiles of total urinary resveratrol phase II metabolites (sum of five resveratrol conjugation metabolites). Urinary resveratrol metabolites were analyzed by ultra- performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS), followed by micro-solid phase extraction (µ-SPE) method. Liver function markers were assessed using serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Moreover, lipid profile was measured by triglycerides, very-low-density lipoprotein cholesterol (VLDL-c), and total cholesterol/high-density lipoprotein ratio (total cholesterol/HDL). Linear regression adjusted models showed that participants with higher total urine resveratrol concentrations exhibited improved lipid and liver markers compared to the lowest tertile. For lipid determinations: log triglycerides (ßT3= -0.15, 95% CI; -0.28, -0.02, p-trend = 0.030), VLDL-c, (ßT3= -4.21, 95% CI; -7.97, -0.46, p-trend = 0.039), total cholesterol/HDL ratio Moreover, (ßT3= -0.35, 95% CI; -0.66, -0.03, p-trend = 0.241). For liver enzymes: log AST (ßT3= -0.12, 95% CI; -0.22, -0.02, p-trend = 0.011, and log GGT (ßT3= -0.24, 95% CI; -0.42, -0.06, p-trend = 0.002). However, there is no difference found on glucose variables between groups. To investigate the risk of elevated serum liver markers, flexible regression models indicated that total urine resveratrol metabolites were associated with a lower risk of higher ALT (169.2 to 1314.3 nmol/g creatinine), AST (599.9 to 893.8 nmol/g creatinine), and GGT levels (169.2 to 893.8 nmol/g creatinine). These results suggested that higher urinary concentrations of some resveratrol metabolites might be associated with better lipid profile and hepatic serum enzymes. Moreover, urinary resveratrol excreted showed a reduced odds ratio for higher liver enzymes, which are linked to NAFLD.

The Oral Bioavailability of Trans-Resveratrol from a Grapevine-Shoot Extract in Healthy Humans is Significantly Increased by Micellar Solubilization.

SCOPE: Grapevine-shoot extract Vineatrol30 contains abundant resveratrol monomers and oligomers with health-promoting potential. However, the oral bioavailability of these compounds in humans is low (˂1-2%). The aim of this study was to improve the oral bioavailability of resveratrol from vineatrol by micellar solubilization. METHODS AND RESULTS: Twelve healthy volunteers (six women, six men) randomly ingested a single dose of 500 mg vineatrol (30 mg trans-resveratrol, 75 mg trans-ε-viniferin) as native powder or liquid micelles. Plasma and urine were collected at baseline and over 24 h after intake. Resveratrol and viniferin were analyzed by HPLC. The area under the plasma concentration-time curve (AUC) and mean maximum plasma trans-resveratrol concentrations were 5.0-fold and 10.6-fold higher, respectively, after micellar supplementation relative to the native powder. However, no detectable amounts of trans-ε-viniferin were found in either plasma or urine. The transepithelial permeability of trans-resveratrol and trans-ε-viniferin across differentiated Caco-2 monolayers was consistent to the absorbed fractions in vivo. CONCLUSION: The oral bioavailability of trans-resveratrol from the grapevine-shoot extract Vineatrol30 was significantly increased using a liquid micellar formulation, without any treatment-related adverse effects, making it a suitable system for improved supplementation of trans-resveratrol.