After oral administration of [4-(3)H]EGCg to rats, the radioactivity in blood, major tissues, urine, and feces was measured over time. The radioactivity in blood and most tissues remained low for 4 h postdose, began to increase after 8 h, peaked at 24 h, and then decreased. Major urinary excretion of radioactivity occurred in the 8-24 h period, and the cumulative radioactivity excreted by 72 h was 32.1% of the dose. The radioactivity in the feces was 35.2% of the dose within 72 h postdose. In the case of rats pretreated with antibiotics (antibiotic-pretreated rats), the radioactivity levels of the blood and urine were definitely lower than those in rats not pretreated with antibiotics (normal rats). The radioactivity recovered in the antibiotic-pretreated rat urine was estimated to be only (1)/(100) of that in the normal rat urine. These results clearly demonstrated that the radioactivity detected in the blood and urine of normal rats mostly originated from degradation products of EGCg produced by intestinal bacteria. Furthermore, a main metabolite in the normal rats was purified and identified as 5-(5'-hydroxyphenyl)-gamma-valerolactone 3'-O-beta-glucuronide (M-2). In feces of the normal rats, EGC (40.8% of the fecal radioactivity) and 5-(3',5'-dihydroxyphenyl)-gamma-valerolactone (M-1, 16.8%) were detected. These results suggested that M-1 was absorbed in the body after degradation of EGCg by intestinal bacteria, yielding M-1 with EGC as an intermediate. Furthermore, M-2 was thought to be formed from M-1 in the intestinal mucosa and/or liver, then to enter the systemic circulation, and finally to be excreted in the urine. Taking into account all of the above findings, a possible metabolic route of EGCg orally administered to rats is proposed.

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After intravenous administration of (-)-epicatechin gallate to Wistar male rats, its biliary metabolites were examined. Deconjugated forms of (-)-epicatechin gallate metabolites were prepared by beta-glucuronidase/sulfatase treatment and purified by HPLC. Five compounds were subjected to FAB-MS and NMR analyses. These metabolites were shown to be (-)-epicatechin gallate, 3'-O-methyl-(-)-epicatechin gallate, 4'-O-methyl-(-)-epicatechin gallate, 4' '-O-methyl-(-)-epicatechin gallate, and 3',4' '-di-O-methyl-(-)-epicatechin gallate. After oral administration, five major metabolites excreted in rat urine were purified in their deconjugated forms and their chemical structures identified. They were degradation products from (-)-epicatechin gallate, pyrogallol, 5-(3,4-dihydroxyphenyl)-gamma-valerolactone, 4-hydroxy-5-(3,4-dihydroxyphenyl)valeric acid, 3-(3-hydroxyphenyl)propionic acid, and m-coumaric acid. Time course analysis of the identified (-)-epicatechin gallate metabolites showed that (-)-epicatechin gallate and its conjugate appeared in the plasma with their highest levels 0.5 h after oral administration; their levels rapidly decreased, and then they disappeared by 6 h. The degradation products, mainly in their conjugated forms, emerged at 6 h, peaked at 24 h, and disappeared by 48 h. In urine samples, (-)-epicatechin gallate and its methylated metabolites were hardly detected and the degradation products began to be excreted in the 6-24 h period, peaked in the 24-48 h period, and then began to disappear. The most abundant metabolite in both the plasma and the urine was found to be the conjugated form of pyrogallol. On the basis of these results, a possible metabolic route of (-)-epicatechin gallate orally administered to the rat is proposed.

Objective: Although under-reporting of dietary intake is more common in persons with a high body mass index (BMI), it is not well known whether or not misreporting is selective for different foods (and hence energy and nutrients), particularly in nonWestern populations. We examined misreporting of dietary intake against biomarkers and its relation with BMI in young Japanese women. Design: Cross-sectional study. Subjects: A total of 353 female Japanese dietetic students aged 18-22 years (mean BMI: 21.4 kg/m 2 , mean fat intake: 29.8% of energy). Methods: Misreporting of dietary energy, protein, potassium and sodium (assessed by a self-administered diet history questionnaire) was examined against respective biomarkers (estimated energy expenditure and 24-h urinary excretion). Reporting accuracy was calculated as the ratio of reported intake to that estimated from corresponding biomarkers (complete accuracy: 1.00). Results: Mean reporting accuracy of absolute intake (amount per day) varied considerably (0.86-1.14). Reporting accuracy of absolute intake decreased with increasing BMI (P for trend o0.001). However, no association was observed between reporting accuracy of energy-adjusted values and BMI (P for trend 40.15), indicating that BMI-dependent misreporting was canceled by energy adjustment. This was owing to positive correlation between the reporting accuracy of energy intake and that of absolute intake of the three nutrients (Pearson correlation coefficient: 0.49-0.67, Po0.0001). Conclusions: Although differential misreporting of absolute intake was associated with BMI, differential misreporting of energyadjusted value was not. These findings support the use of energy-adjusted values in the investigation of diet-disease relationships among lean populations with a low-fat intake.

Because a great deal of attention has been focused on the metabolism of (-)-epigallocatechin gallate (EGCg), quantitative analysis of this compound is required. For this purpose we developed a method of chemical synthesis of [4-(3)H]EGCg. Synthesized [4-(3)H]EGCg showed 99.5% radiochemical purity and a specific activity of 13 Ci/mmol. To clarify the excretion route of EGCg, the radioactivity levels of bile and urine were quantified after intravenous administration of [4-(3)H]EGCg to bile-duct-cannulated rats. Results showed that the radioactivity of the bile sample excreted within 48 h accounted for 77.0% of the dose, whereas only 2.0% of the dose was recovered in the urine. The excretion ratio of bile to urine was calculated to be about 97:3. These results clearly showed that bile was the major excretion route of EGCg. Time-course analysis of the radioactivity in blood was also performed to estimate the pharmacokinetic parameters following intravenous administration of [4-(3)H]EGCg. In addition, EGCg metabolites excreted in the bile within 4 h after the intravenous dose of [4-(3)H]EGCg were analyzed by HPLC. The results showed that 4',4"-di-O-methyl-EGCg was present in the conjugated form and made up about 14.7% of the administered radioactivity.

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Background: Animal studies suggest the beneficial effect of hardness of diet on body weight and adiposity. No human studies have examined hardness of diet in relation to obesity. Objective: We examined cross-sectional associations of hardness of the habitual diet with body mass index (BMI; in kg/m 2 ) and waist circumference in free-living humans. Design: Subjects were 454 female Japanese dietetic students aged 18 -22 y. Dietary hardness was assessed as an estimate of masticatory muscle activity for the habitual diet (ie, the difficulty of chewing the food). The consumption of a total of 107 foods was estimated by means of a self-administered, comprehensive diet history questionnaire, and masticatory muscle activity during the ingestion of these foods was estimated according to published equations. Waist circumference was measured at the level of the umbilicus. Results: Mean BMI was 21.4 (95% CI: 21.1, 21.6), and mean waist circumference was 73.6 (72.9, 74.3) cm. Mean dietary hardness was 178 (175, 181) mV ⅐ s/1000 kcal. Dietary hardness was not significantly associated with BMI. However, it was negatively associated with waist circumference (P for trend ҃ 0.005). This association remained after adjustment not only for potential confounding factors (P for trend ҃ 0.028) but also for BMI (P for trend ҃ 0.002). Conclusions: Whereas no association between dietary hardness and BMI was seen, increasing dietary hardness was associated with lower waist circumference even after adjustment for BMI in freeliving young Japanese women. This finding could make innovative contributions to the literature and raise issues for future studies regarding diet and obesity.Am J Clin Nutr 2007;86:206 -13. KEY WORDSHardness of diet, body mass index, waist circumference, Japanese, women, diet history questionnaire, epidemiology

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