ellagitannin and Obesity

The consumption of pomegranate juice (PJ), a rich source of antioxidant polyphenols, has grown tremendously due to its reported health benefits. Pomegranate extracts, which incorporate the major antioxidants found in pomegranates, namely, ellagitannins, have been developed as botanical dietary supplements to provide an alternative convenient form for consuming the bioactive polyphenols found in PJ. Despite the commercial availability of pomegranate extract dietary supplements, there have been no studies evaluating their safety in human subjects. A pomegranate ellagitannin-enriched polyphenol extract (POMx) was prepared for dietary supplement use and evaluated in two pilot clinical studies. Study 1 was designed for safety assessment in 64 overweight individuals with increased waist size. The subjects consumed either one or two POMx capsules per day providing 710 mg (435 mg of gallic acid equivalents, GAEs) or 1420 mg (870 mg of GAEs) of extracts, respectively, and placebo (0 mg of GAEs). Safety laboratory determinations, including complete blood count (CBC), chemistry, and urinalysis, were made at each of three visits. Study 2 was designed for antioxidant activity assessment in 22 overweight subjects by administration of two POMx capsules per day providing 1000 mg (610 mg of GAEs) of extract versus baseline measurements. Measurement of antioxidant activity as evidenced by thiobarbituric acid reactive substances (TBARS) in plasma were measured before and after POMx supplementation. There was evidence of antioxidant activity through a significant reduction in TBARS linked with cardiovascular disease risk. There were no serious adverse events in any subject studied at either site. These studies demonstrate the safety of a pomegranate ellagitannin-enriched polyphenol dietary supplement in humans and provide evidence of antioxidant activity in humans.

Topics: Adult; Aged; Antioxidants; Consumer Product Safety; Dietary Supplements; Dose-Response Relationship, Drug; Female; Flavonoids; Humans; Hydrolyzable Tannins; Lythraceae; Male; Middle Aged; Obesity; Phenols; Polyphenols; Thiobarbituric Acid Reactive Substances; Treatment Outcome

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Biological Transport; Cell Differentiation; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucose; Glucosides; Hydrolyzable Tannins; Hyperglycemia; Insulin; Lipolysis; Mice; Obesity; Plant Extracts; Sapindaceae

Urolithins are microbial metabolites produced after consumption of ellagitannin-containing foods such as pomegranates and walnuts. Parallel to isoflavone-metabolizing phenotypes, ellagitannin-metabolizing phenotypes (urolithin metabotypes A, B and 0; UM-A, UM-B and UM-0, respectively) can vary among individuals depending on their body mass index (BMI), but correlations between urolithin metabotypes (UMs) and cardiometabolic risk (CMR) factors are unexplored. We investigated the association between UMs and CMR factors in individuals with different BMI and health status.. UM was identified using UPLC-ESI-qToF-MS in individuals consuming pomegranate or nuts. The associations between basal CMR factors and the urine urolithin metabolomic signature were explored in 20 healthy normoweight individuals consuming walnuts (30 g/d), 49 healthy overweight-obese individuals ingesting pomegranate extract (450 mg/d) and 25 metabolic syndrome (MetS) patients consuming nuts (15 g-walnuts, 7.5 g-hazelnuts and 7.5 g-almonds/d).. Correlations between CMR factors and urolithins were found in overweight-obese individuals. Urolithin-A (mostly present in UM-A) was positively correlated with apolipoprotein A-I (P ≤ 0.05) and intermediate-HDL-cholesterol (P ≤ 0.05) while urolithin-B and isourolithin-A (characteristic from UM-B) were positively correlated with total-cholesterol, LDL-cholesterol (P ≤ 0.001), apolipoprotein B (P ≤ 0.01), VLDL-cholesterol, IDL-cholesterol, oxidized-LDL and apolipoprotein B:apolipoprotein A-I ratio (P ≤ 0.05). In MetS patients, urolithin-A only correlated inversely with glucose (P ≤ 0.05). Statin-treated MetS patients with UM-A showed a lipid profile similar to that of healthy normoweight individuals while a poor response to lipid-lowering therapy was observed in MB patients.. UMs are potential CMR biomarkers. Overweight-obese individuals with UM-B are at increased risk of cardiometabolic disease, whereas urolithin-A production could protect against CMR factors. Further research is warranted to explore these associations in larger cohorts and whether the effect of lipid-lowering drugs or ellagitannin-consumption on CMR biomarkers depends on individuals' UM.. NCT01916239 (https://clinicaltrials.gov/ct2/show/NCT01916239) and ISRCTN36468613 (http://www.isrctn.com/ISRCTN36468613).

Topics: Adult; Biomarkers; Body Mass Index; Body Weight; Cardiovascular Diseases; Coumarins; Female; Fruit; Gastrointestinal Microbiome; Humans; Hydrolyzable Tannins; Juglans; Lipids; Lythraceae; Male; Metabolic Syndrome; Middle Aged; Nuts; Obesity; Overweight; Plant Extracts; Risk Factors