Concomitant use of tea catechins affects absorption and serum triglyceride-lowering effects of monoglucosyl hesperidin.

The present study investigated whether combined ingestion of green tea catechins (GTC) and monoglucosyl hesperidin (GHES) influences the pharmacokinetic parameters of polyphenols and serum triglycerides (TG). We conducted 2 randomized, controlled trials. Study 1: 8 healthy male subjects participated in a crossover study in which they ingested a test beverage containing GHES (0, 84, 168, or 336 mg GHES) with GTC, or 336 mg GHES without GTC. After ingestion, the pharmacokinetic changes in plasma hesperetin (HEP) and catechins were measured. Study 2: 36 healthy male and female subjects (mean age, 53 ± 2 years; mean BMI, 25.2 ± 0.5 kg m-2) were recruited for a double-blind, placebo-controlled study in which they ingested a test beverage containing 165 mg GHES with 387 mg GTC or a placebo beverage daily for 4 weeks. Fasting serum TG and other lipids and glucose metabolites were analyzed. Study 1 showed that the pharmacokinetics of HEP did not differ significantly between the 336 mg GHES without GTC treatment and the 168 mg GHES with GTC treatment. Study 2 showed that continuous ingestion of 165 mg GHES and 387 mg GTC for 4 weeks significantly decreased fasting serum TG levels compared with baseline values (change in TG, -30 ± 13 mg dl-1, P = 0.040) in the intention-to-treat analysis. In conclusion, our findings suggest that GTC affects the oral bioavailability of GHES, and combined ingestion of low doses of GHES with GTC effectively improves fasting TG levels.

Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients. METHODS: Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors. RESULTS: Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast. CONCLUSION: Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and increased plasma renin activity, which may be a compensatory mechanism for sodium retention, leading to subsequent urine output recovery. CLINICAL TRIAL REGISTRATION: UMIN000019462. FUNDING: Mitsubishi Tanabe Pharma Corporation.

Effect of fragmented Lactobacillus amylovorus CP1563 on lipid metabolism in overweight and mildly obese individuals: a randomized controlled trial.

BACKGROUND: Previously, we showed that fragmented Lactobacillus amylovorus CP1563 (CP1563) functions as a dual agonist of peroxisome proliferator-activated receptor α and γ in vitro and in vivo. OBJECTIVE: Here, we examined the safety and effect of CP1563 ingestion on body fat in obese class I participants in a double-blinded, placebo-controlled, randomized clinical trial (RCT). DESIGN: In the RCT, 200 participants with a body mass index (BMI) of 25-30 kg/m(2) consumed test beverages with or without 200 mg of CP1563 daily for 12 weeks. In total, 197 subjects completed the study without any adverse effects. RESULTS: Body fat percentage, whole body fat, and visceral fat were significantly decreased in the test group compared with the placebo group (p<0.001, p<0.001, and p<0.001, respectively). Triglycerides, total cholesterol, LDL-cholesterol, and diastolic blood pressure showed significant reductions in the test group compared with the placebo group (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). Additionally, significant differences in the changes in blood glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), and uric acid were observed between the two groups (p<0.001, p=0.004, p<0.001, and p<0.001, respectively). Improvements in anthropometric measurements and markers were observed in obese class I subjects in the test group. CONCLUSIONS: Daily consumption of beverages containing fragmented CP1563 for 12 weeks by obese class I subjects improved anthropometric measurements and markers related to lipid and glucose metabolism without any adverse effects. These results suggest that the consumption of foods containing fragmented CP1563 reduces body fat and prevents metabolic syndrome.

Regulatory effect of paraprobiotic Lactobacillus gasseri CP2305 on gut environment and function.

BACKGROUND: Lactobacillus gasseri CP2305 (CP2305) is a strain of Lactobacillus isolated from a stool sample from a healthy adult that showed beneficial effects on health as a paraprobiotic. In a previous study, we demonstrated that CP2305-fermented heat-treated milk modified gut functions more than artificially acidified sour milk. Thus, the regulatory activity of the former beverage was attributed to the inactivated CP2305 cells. OBJECTIVE: The aim of this study was to elucidate the contribution of non-viable paraprobiotic CP2305 cells to regulating human gut functions. We thus conducted a randomized, placebo-controlled, double-blinded parallel group trial. DESIGN: The trial included 118 healthy participants with relatively low or high stool frequencies. The test beverage was prepared by adding 1×10(10) washed, heat-treated, and dried CP2305 cells directly to the placebo beverage. The participants ingested a bottle of the assigned beverage daily for 3 weeks and answered daily questionnaires about defecation and quality of life. Fecal samples were collected and the fecal characteristics, microbial metabolite contents of the feces and composition of fecal microbiota were evaluated. RESULTS: The number of evacuations and the scores for fecal odors were significantly improved in the group that consumed the CP2305-containing beverage compared with those of the group that consumed the placebo (p=0.035 and p=0.040, respectively). Regarding the fecal contents of microbial metabolites, the level of fecal p-cresol was significantly decreased in the CP2305 group relative to that of the placebo group (p=0.013). The Bifidobacterium content of the intestinal microbiota was significantly increased in the CP2305 group relative to that of the placebo group (p<0.008), whereas the content of Clostridium cluster IV was significantly decreased (p<0.003). The parasympathetic nerve activity of the autonomic nervous system became dominant and the total power of autonomic activity was elevated in the CP2305 group (p=0.0401 and p=0.011, respectively). CONCLUSIONS: The continuous ingestion of heat-treated CP2305 cells clearly affected intestinal functionality. This is the first report of sterilized Lactobacillus cells having a significant impact on the environment and functions of the intestinal tract. The observed effects might be due, at least in part, to the brain-gut interaction.

Torsade de pointes associated with the combination of solifenacin and clenbuterol for urinary incontinence.

A 79-year-old woman undergoing medical treatment with solifenacin and clenbuterol for urinary incontinence was admitted to our hospital because of recurrent syncope. Her syncope appeared one month after the doses of clenbuterol were increased. Torsade de pointes (TdP) was evident on her Holter electrocardiogram at the time when she developed syncope. Ultimately, a cardioverter-defibrillator with dual chamber pacing capability was implanted. To our knowledge, this is the first report of TdP associated with the combination of solifenacin and clenbuterol for urinary incontinence. .

Irbesartan, an angiotensin receptor blocker, exhibits metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension.

Irbesartan, an angiotensin II receptor blocker (ARB), acts as a selective PPAR-γ (peroxisome proliferator-activated receptor-γ) modulator, and thus may have anti-inflammatory and antioxidative effects, as well as beneficial effects on glucose and lipid metabolism. We enrolled 118 high-risk hypertensive outpatients, defined as those with the presence of at least one complication such as coronary artery disease, cerebrovascular disease or diabetes, and who were receiving any ARB except for irbesartan (67±10 years, 80% male subjects). After a 4-week control period, all ARBs were switched to an equivalent dose of irbesartan. We evaluated changes in lipid parameters, inflammatory markers and derivatives of reactive oxygen metabolites (d-ROMs) as an oxidative stress index. After 12 weeks of irbesartan, there were significant decreases in triglycerides (138±73 versus 123±65 mg dl(-1), P<0.05), high-sensitivity C-reactive protein (hs-CRP) (2.80±0.53 versus 2.66±0.50, log (ng ml(-1)), P<0.05) and d-ROMs (338±74 versus 305±62 U.CARR, P<0.001). There were significant increases in high-density lipoprotein cholesterol (50±13 versus 52±14 mg dl(-1), P<0.01) and adiponectin (9.4±6.2 versus 16.6±13.4 ng ml(-1), P<0.05). There were no significant changes in systolic and diastolic blood pressure. The change in d-ROMs from baseline to 12 weeks was positively correlated with the change in hs-CRP (R=0.34, P<0.01). Irbesartan appears to exert beneficial effects on oxidative stress, inflammation, lipid metabolism and metabolic syndrome, indicating that it may be useful in high-risk hypertensive patients.