In this study, ascorbate (Asc) and glutathione (GSH) concentrations were quantified noninvasively using double-edited 1H MRS at 4 T in the occipital cortex of healthy young [age (mean ± standard deviation) = 20.4 ± 1.4 years] and elderly (age = 76.6 ± 6.1 years) human subjects. Elderly subjects had a lower GSH concentration than younger subjects (p < 0.05). The Asc concentration was not significantly associated with age. Furthermore, the lactate (Lac) concentration was higher in elderly than young subjects. Lower GSH and higher Lac concentrations are indications of defective protection against oxidative damage and impaired mitochondrial respiration. The extent to which the observed concentration differences could be associated with physiological differences and methodological artifacts is discussed. In conclusion, GSH and Asc concentrations were compared noninvasively for the first time in young vs elderly subjects.

Reducing the dietary glycemic load and the glycemic index was proposed as a novel approach to weight reduction. A parallel-design, randomized 12-wk controlled feeding trial with a 24-wk follow-up phase was conducted to test the hypothesis that a hypocaloric diet designed to reduce the glycemic load and the glycemic index would result in greater sustained weight loss than other hypocaloric diets. Obese subjects (n = 29) were randomly assigned to 1 of 3 diets providing 3138 kJ less than estimated energy needs: high glycemic index (HGI), low glycemic index (LGI), or high fat (HF). For the first 12 wk, all food was provided to subjects (feeding phase). Subjects (n = 22) were instructed to follow the assigned diet for 24 additional weeks (free-living phase). Total body weight was obtained and body composition was assessed by skinfold measurements. Insulin sensitivity was assessed by the homeostasis model (HOMA). At 12 wk, weight changes from baseline were significant in all groups but not different among groups (-9.3 +/- 1.3 kg for the HGI diet, -9.9 +/- 1.4 kg for the LGI diet, and -8.4 +/- 1.5 kg for the HF diet). All groups improved in insulin sensitivity at the end of the feeding phase of the study. During the free-living phase, all groups maintained their initial weight loss and their improved insulin sensitivity. Weight loss and improved insulin sensitivity scores were independent of diet composition. In summary, lowering the glycemic load and glycemic index of weight reduction diets does not provide any added benefit to energy restriction in promoting weight loss in obese subjects.

Objective To assess the efficacy of TU-025, keishibukuryogan, a Japanese prescription herbal medicine used for hot flash management, in American women. Methods This randomized, double-blind, placebo-controlled, phase II trial enrolled 178 postmenopausal women, aged 45–58 years, with a Mayo hot flash score greater than 28 per week and who met other inclusion criteria. After a one-week placebo run-in period, participants were randomly assigned to either 12 weeks of placebo, 7.5 g/day or 12.5 g/day. Primary and secondary outcomes were measured by the Mayo Clinic Hot Flash Diary, the Greene Climacteric Index and the Pittsburgh Sleep Quality Index. Results At three months, hot flash scores, climacteric symptoms and sleep quality improved by 34% in the placebo group, 40% in the 7.5 g/day group and 38% in the 12.5 g/day group. (p < 0.001). However, the differences in changes between groups were not statistically significant (p = 0.990). Diarrhea unexpectedly developed in 20% of participants receiving active medication. Conclusions For American women, unlike the clinical experience for Japanese women, TU-025 did not significantly reduce the frequency and severity of hot flash symptoms, improve climacteric symptoms or benefit sleep quality. This study identified several potentially significant methodological factors to be considered in future scientific assessments of traditional Asian medicines.

Purpose The Minnesota Green Tea Trial (MGTT) was a randomized, placebo-controlled, double-blinded trial investigating the effect of daily green tea extract consumption for 12 months on biomarkers of breast cancer risk. Methods Participants were healthy postmenopausal women at high risk of breast cancer due to dense breast tissue with differing catechol-O-methyltransferase (COMT) genotypes. The intervention was a green tea catechin extract containing 843.0 ± 44.0 mg/day epigallocatechin gallate or placebo capsules for one year. Annual digital screening mammograms were obtained at baseline and month 12, and fasting blood and 24-hour urine samples were provided at baseline, months 6, and 12. Primary endpoints included changes in percent mammographic density, circulating endogenous sex hormones and insulin-like growth factor axis proteins; secondary endpoints were changes in urinary estrogens and estrogen metabolites and circulating F2-isoprostanes, a biomarker of oxidative stress. Results The MGTT screened more than 100,000 mammograms and randomized 1075 participants based on treatment (green tea extract vs. placebo), stratified by COMT genotype activity (high COMT vs. low/intermediate COMT genotype activity). 937 women successfully completed the study and 138 dropped out (overall dropout rate= 12.8%). Conclusions In this paper we report the rationale, design, recruitment, participant characteristics, and methods for biomarker and statistical analyses.

Epidemiologic and animal studies suggest a protective role of green tea against breast cancer. However, the underlying mechanism is not understood. We conducted a randomized, double-blinded, placebo-controlled phase II clinical trial to investigate whether supplementation with green tea extract (GTE) modifies mammographic density (MD), as a potential mechanism, involving 1,075 healthy postmenopausal women. Women assigned to the treatment arm consumed daily 4 decaffeinated GTE capsules containing 1,315 mg total catechins, including 843 mg epigallocatechin-3-gallate (EGCG) for 12 months. A computer-assisted method (Madena) was used to assess MD in digital mammograms at baseline and month 12 time points in 932 completers (462 in GTE and 470 in placebo). GTE supplementation for 12 months did not significantly change percent MD (PMD) or absolute MD in all women. In younger women (50-55 years), GTE supplementation significantly reduced PMD by 4.40% as compared with the placebo with a 1.02% PMD increase from pre- to postintervention ( = 0.05), but had no effect in older women ( = 0.07). GTE supplementation did not induce MD change in other subgroups of women stratified by catechol--methyltransferase genotype or level of body mass index. In conclusion, 1-year supplementation with a high dose of EGCG did not have a significant effect on MD measures in all women, but reduced PMD in younger women, an age-dependent effect similar to those of tamoxifen. Further investigation of the potential chemopreventive effect of green tea intake on breast cancer risk in younger women is warranted. .