Drinkable preparation of Theracurmin exhibits high absorption efficiency--a single-dose, double-blind, 4-way crossover study.

Curcumin has various biological activities including antioxidant and antiinflammatory actions, and alcohol detoxification. However, because of its poor absorption efficiency, it is difficult for orally administered curcumin to reach blood levels sufficient to realize its bioactivities. We have generated capsules and tablets containing Theracurmin, a highly absorptive curcumin. In addition, we recently created a drinkable preparation of Theracurmin. To evaluate the absorption efficiency of this type of curcumin, we performed a single-dose, double-blind, 4-way crossover study. We compared plasma curcumin levels after the administration of Theracurmin beverage and 3 other drinkable types of curcumin sold in Japan. Twenty-four healthy subjects (male/female=13/11, age: 23-32) were administered with these 4 drinkable preparations of curcumin. The area under the blood concentration-time curve at 0-8 h was found to be 1.5 to 4.0-fold higher with Theracurmin than with the other 3 kinds of curcumin beverage. Moreover, maximal plasma curcumin concentrations (0-8 h) of Theracurmin were 1.8 to 3.8 times higher than those of the other 3 curcumin beverages. These data indicate that our newly prepared Theracurmin beverage exhibits a much better absorption efficiency than other kinds of curcumin beverage sold in Japan.

Identifying Glucose Metabolism Status in Nondiabetic Japanese Adults Using Machine Learning Model with Simple Questionnaire.

We aimed to identify the glucose metabolism statuses of nondiabetic Japanese adults using a machine learning model with a questionnaire. In this cross-sectional study, Japanese adults (aged 20-64 years) from Tokyo and surrounding areas were recruited. Participants underwent an oral glucose tolerance test (OGTT) and completed a questionnaire regarding lifestyle and physical characteristics. They were classified into four glycometabolic categories based on the OGTT results: category 1: best glucose metabolism, category 2: low insulin sensitivity, category 3: low insulin secretion, and category 4: combined characteristics of categories 2 and 3. A total of 977 individuals were included; the ratios of participants in categories 1, 2, 3, and 4 were 46%, 21%, 14%, and 19%, respectively. Machine learning models (decision tree, support vector machine, random forest, and XGBoost) were developed for identifying the glycometabolic category using questionnaire responses. Then, the top 10 most important variables in the random forest model were selected, and another random forest model was developed using these variables. Its areas under the receiver operating characteristic curve (AUCs) to classify category 1 and the others, category 2 and the others, category 3 and the others, and category 4 and the others were 0.68 (95% confidence intervals: 0.62-0.75), 0.66 (0.58-0.73), 0.61 (0.51-0.70), and 0.70 (0.62-0.77). For external validation of the model, the same dataset of 452 Japanese adults in Hokkaido was obtained. The AUCs to classify categories 1, 2, 3, and 4 and the others were 0.66 (0.61-0.71), 0.57 (0.51-0.62), 0.60 (0.50-0.69), and 0.64 (0.57-0.71). In conclusion, our model could identify the glucose metabolism status using only 10 factors of lifestyle and physical characteristics. This model may help the larger general population without diabetes to understand their glucose metabolism status and encourage lifestyle improvement to prevent diabetes.

30-minute postload plasma glucose levels during an oral glucose tolerance test predict the risk of future type 2 diabetes: the Hisayama Study.

INTRODUCTION: To investigate the associations of 30 min postload plasma glucose (30 mPG) levels during an oral glucose tolerance test (OGTT) with the risk of future diabetes in a general Japanese population. RESEARCH DESIGN AND METHODS: A total of 2957 Japanese community-dwelling residents without diabetes, aged 40-79 years, participated in the examinations in 2007 and 2008 (participation rate, 77.1%). Among them, 2162 subjects who received 75 g OGTT in a fasting state with measurements of plasma glucose level at 0, 30, and 120 min were followed up for 7 years (2007-2014). Cox's proportional hazards model was used to estimate HRs and their 95% CIs of each index for the development of type 2 diabetes using continuous variables and quartiles with adjustment for traditional risk factors. The influence of 30 mPG on the predictive ability was estimated with Harrell's C-statistics, integrated discrimination improvement (IDI), and the continuous net reclassification index (cNRI). RESULTS: During follow-up, 275 subjects experienced type 2 diabetes. Elevated 30 mPG levels were significantly associated with increased risk of developing diabetes (p<0.01 for trend): the multivariable-adjusted HR was 8.41 (95% CI 4.97 to 14.24) for the highest versus the lowest quartile, and 2.26 (2.04 to 2.52) per 1 SD increase. This association was attenuated but remained significant after further adjustment for fasting and 2-hour postload plasma glucose levels. Incorporation of 30 mPG into the model including traditional risk factors with fasting and 2-hour postload plasma glucose levels for diabetes improved the predictive ability of type 2 diabetes (improvement in Harrell's C-statistics values: from 0.828 to 0.839, p<0.01; IDI: 0.016, p<0.01; cNRI: 0.103, p=0.37). CONCLUSIONS: Elevated 30 mPG levels were associated with increased risk of diabetes, and inclusion of 30 mPG levels significantly improved the predictive ability for future diabetes, suggesting that 30 mPG may be useful for identifying high-risk populations for type 2 diabetes.

Serum Ethylamine Levels as an Indicator of l-Theanine Consumption and the Risk of Type 2 Diabetes in a General Japanese Population: The Hisayama Study.

OBJECTIVE: This study investigated the association between serum ethylamine levels as an indicator of l-theanine consumption and the development of type 2 diabetes in a Japanese community. RESEARCH DESIGN AND METHODS: A total of 2,253 community-dwelling Japanese individuals aged 40-79 years without diabetes were monitored for 7 years. Serum ethylamine levels were divided into quartiles: ≤0.86, 0.87-2.10, 2.11-5.28, and ≥5.29 ng/mL. Kinetic analysis of serum ethylamine concentrations was performed after ingestion of l-theanine-rich green tea products containing 8 mg of l-theanine by 12 healthy volunteers. RESULTS: During follow-up, 282 subjects developed type 2 diabetes. The age- and sex-adjusted cumulative incidence of type 2 diabetes decreased significantly with elevating levels of serum ethylamine (P for trend = 0.04). This association remained unchanged after adjusting for potential confounding factors. The multivariable-adjusted hazard ratio (HR) for type 2 diabetes was significantly lower in the fourth quartile of serum ethylamine than in the first quartile (HR 0.69, 95% CI 0.49-0.98). This trend of decrease in diabetic risk across serum ethylamine levels was more prominent in middle-aged subjects and in subjects with prediabetes, obesity, or insulin resistance. Kinetic analysis estimated that the minimum concentration at the steady state was >5.90 ng/mL in the case of twice-daily ingestion with an interval of 12 h. CONCLUSIONS: Higher serum ethylamine was significantly associated with lower risk of the development of type 2 diabetes in a general Japanese population. The measurement of serum ethylamine concentration would be a useful biomarker for the objective estimation of l-theanine consumption.

The relationships of cardiovascular disease risk factors to flow-mediated dilatation in Japanese subjects free of cardiovascular disease.

We examined the relationship of several cardiovascular disease (CVD) risk factors to flow-mediated vasodilatation of the brachial artery (FMD) and the clustering effect of risk factors on FMD in Japanese subjects free of CVD. In 819 Japanese subjects free of CVD (age 45+/-10 years, 611 men and 208 women), FMD correlated significantly with the Framingham risk points score (FRS) (r=-0.27, p<0.01). FMD was higher in subjects in the 1st tertile of the FRS range than in patients in either the 2nd or 3rd tertiles of the FRS range, but it was similar between the subjects in the 2nd and 3rd tertiles. FMD was found to have a significant independent negative correlation with age (beta=-0.19, p<0.01), gender (beta=-0.024, p<0.01) and smoking habit (beta=-0.08, p=0.02). In subjects >or=50 years of age, the FMD in men with one CVD risk factor, excluding smoking, was similar to that in men with no CVD risk factors. CVD risk factors did not attenuate FMD in women. Thus, in Japanese subjects free of CVD, FMD may be a useful marker of CVD risk, but it may not be a robust marker for endothelial damage related to clusters of CVD risk factors. Age, gender and smoking were independent variables related to the impairment of FMD, which therefore appears to be less applicable in subjects aged 50 or more, and especially in women. (Hypertens Res 2008; 31: 2019-2025).

Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial.

Cooperative effects of isoflavones and exercise on bone and lipid metabolism have been exhibited in estrogen-deficient animals; however, results from clinical trials have not been published. In this study, we determined the effects of isoflavone intake and walking and their interaction on bone and lipid metabolism in postmenopausal women over 24 weeks. The bioavailability and metabolism of isoflavones (daidzein in particular) were also examined to clarify the mechanism of their bone-protective effects in humans. One hundred twenty-eight subjects were randomly assigned to 4 groups: placebo; placebo combined with walking (3 times per week); isoflavone intake (75 mg of isoflavones conjugates per day); and isoflavone combined with walking. The subjects were classified by equol status (producers or nonproducers) as identified using production of equol from daidzein in fecal culture. Bone mineral density (BMD), body composition, and serum concentrations of isoflavones were assessed. Serum high-density lipoprotein cholesterol concentration significantly increased (6.1%, P = .03), and fat mass in the whole body significantly decreased (-4.3%, P = .0003) from the baseline in the combined intervention group. There were no significant differences in BMD between baseline and postintervention in any of the treatment groups. However, the percent changes in BMD in equol producers were -0.53% and +0.13% in the sub-whole body and total hip, respectively. This was significantly different compared with -1.35 and -1.77 for the sub-whole body and total hip, respectively, in nonproducers in the isoflavone group (P = .049 and .040, respectively). The mean serum equol concentration was significantly higher in equol producers than in nonproducers in the isoflavone groups, but not in the placebo group. The combination of isoflavones and exercise exhibited favorable effects on serum lipid and body composition of postmenopausal women. The findings of this study suggest that the preventive effects of isoflavones on bone loss depend on the individual's intestinal flora for equol production.

Effects of docosahexaenoic Acid supplementation on blood pressure, heart rate, and serum lipids in Scottish men with hypertension and hypercholesterolemia.

To investigate the effects of daily supplementation with docosahexaenoic acid (DHA) on coronary heart disease risks in 38 middle-aged men with hypertension and/or hypercholesterolemia in Scotland, a five-week double-blind placebo-controlled dietary supplementation with either 2 g of DHA or active placebo (1 g of olive oil) was conducted. Percent composition of DHA in plasma phospholipids increased significantly in DHA group. Systolic and diastolic blood pressure and heart rate decreased significantly in DHA group, but not in placebo group. High-density lipoprotein cholesterol (HDL-C) increased significantly, and total cholesterol (TC)/HDL-C and non-HDL-C/HDL-C ratios decreased significantly in both groups. There was no change in TC and non-HDL-C. We conclude that 2 g/day of DHA supplementation reduced coronary heart disease risk factor level improving blood pressure, heart rate, and lipid profiles in hypertensive, hypercholesterolemic Scottish men who do not eat fish on a regular basis.

Effects of dietary intake of soy protein and isoflavones on cardiovascular disease risk factors in high risk, middle-aged men in Scotland.

OBJECTIVE: To investigate the effects of soy protein and isoflavones on blood pressure (BP) and cholesterol levels among high risk middle-aged Scottish men. DESIGN: A randomized, double-blind, placebo-controlled, parallel-group dietary intervention study SETTING: Inhabitants on Isles of Lewis and Harris in Scotland SUBJECTS: Sixty-one men with relatively higher BP and/or total cholesterol (TC) levels aged 45 to 59 went through the dietary intervention. INTERVENTION: Diets containing at least 20 g of soy protein and 80 mg of isoflavones were compared to the placebo diets. Intervention period was 5 weeks duration. RESULTS: Significant difference was found in 24-hour urinary isoflavone excretion between the two groups after intervention. Significant reductions from the baselines were observed in systolic BP (SBP) and diastolic BP (DBP), TC and non-high density lipoprotein cholesterol (non-HDL-C) in the soy-containing diet group, but not in the olive oil containing active placebo group. Significant increases in high density lipoprotein cholesterol (HDL-C) were observed in both groups. CONCLUSION: Dietary intakes of soy protein (at least 20 g) and isoflavones (at least 80 mg) for 5 weeks would be effective in reducing CHD risk among high-risk, middle-aged men.

Soybean isoflavones reduce postmenopausal bone resorption in female Japanese immigrants in Brazil: a ten-week study.

OBJECTIVE: Some human studies and animal models of experimental osteoporosis have shown that soy isoflavones may be effective on bone health. In this study, we carried out an intervention study to explore the effects of dietary isoflavone on bone metabolism. METHODS: Forty healthy female postmenopausal Japanese immigrants living in Brazil were divided into two groups: isoflavone-administered (n = 20) or placebo (n = 20). Subjects in the isoflavone-administered group ingested 37.3 mg per day for 10 weeks. The collection of 24-hour urine and the measurement of bone stiffness were performed at 0 and 10 weeks. Urinary excretion of isoflavones and bone resorption markers were analyzed. RESULTS: Urinary isoflavone excretion in the isoflavone-administered group was significantly increased at weeks 3 and 10. Urinary excretion of bone resorption markers was reduced in the isoflavone-administered group, while the placebo group did not show any significant reduction. Differences in levels of urinary isoflavones and bone resorption markers between the two groups were significant. CONCLUSION: This study demonstrated that the bone resorption was associated with the intake of soy isoflavones in postmenopausal women, and continuous dietary intake of isoflavone may inhibit postmenopausal osteoporosis.