Summary Following consecutive 12-wk administration of tablets containing 0, 200 or 400 mg grape seed extract (calculated as proanthocyanidin) to 61 healthy subjects with LDL cholesterol (LDL-C) levels of 100 to 180 mg/dL, effects of such treatment compared to administration of placebo tablets on malondialdehyde-modified LDL (MDA-LDL), representing one oxidized type of LDL, were investigated by a single blind method. MDA-LDL level in the 200 mg (calculated as proanthocyanidin) group was significantly ( p ϭ 0.008) reduced compared to the basal level, 12 wk after the start of administration. In the 400 mg (calculated as proanthocyanidin) group, a significant decrease in MDA-LDL level compared to the basal level was found 6 and 12 wk after the start of administration (6 wk: p ϭ 0.015, 12 wk: p ϭ 0.009). Subjects with high levels of MDA-LDL/ApoB (MDA-LDL/ApoB Ն 100 mU/mL) in the 200 mg group showed significantly ( p ϭ 0.011) reduced MDA-LDL levels at 12 wk after the start of administration. In the 400 mg group, significant decreases in MDA-LDL level compared to the basal level were seen 6 and 12 wk after the start of administration (6 wk: p ϭ 0.001, 12 wk: p Ͻ 0.001); and at week 6, significantly ( p ϭ 0.048) lower values were observed compared to those in patients who took placebo tablets (0 mg proanthocyanidin). In subjects demonstrating the least body weight changes during the test period (less than ± 1.0 kg) in the 400 mg group, there was an increasing trend ( p ϭ 0.088) in adiponectin levels 12 wk after the start of treatment. These results suggested that tablets containing grape seed extract exerted reducing effects on oxidized LDL, and might be useful in preventing lifestylerelated diseases such as arteriosclerosis.

The ingestion of Lactobacillus plantarum OLL2712 (OLL2712) cells improved glucose metabolism by suppressing chronic inflammation in mouse models and in a preliminary clinical study. We aimed to clarify the effect of OLL2712 on glucose metabolism and chronic inflammation for healthy adults. Prediabetic adults (n = 130, age range: 20–64 years) were randomly assigned to either the placebo or OLL2712 groups (n = 65 each) and were administered conventional yogurt or yogurt containing more than 5 × 109 heat-treated OLL2712 cells, respectively, daily for 12 weeks. Reduced HbA1c levels after 12 weeks of treatment were observed in both groups compared to those at baseline; however, the 12-week reduction of HbA1c levels was significantly greater in the OLL2712 group than in the placebo group. Increased chronic inflammation marker levels and insulin-resistant index (HOMA-IR) occurred in the placebo group but not in the OLL2712 group. Fasting blood glucose (FBG) levels did not change significantly in both groups; however, in subgroup analyses including participants with higher FBG levels, FBG levels were significantly reduced only in the OLL2712 group compared to baseline. These results suggest that OLL2712 cell ingestion can reduce HbA1c levels and can prevent the aggravation of chronic inflammation and insulin resistance.

Background Chronic inflammation and insulin resistance are factors that are related to obesity. We have suggested that the administration of heat-treated Lactobacillus plantarum OLL2712 (OLL2712) cells can improve glucose and lipid metabolism by suppressing chronic inflammation in mouse models and a pilot clinical study. Objective The aim of this study was to investigate whether ingesting OLL2712 cells can reduce body fat accumulation and improve metabolic risk factors, in overweight, healthy adults. Methods This study was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at a single center in Japan. The study participants included 100 overweight (BMI range, ≥25 to < 30 kg/m2) adults aged 20–64 y. They were randomly assigned to either the placebo or OLL2712 group (n = 50 each) and were administered conventional yogurt or yogurt containing more than 5 × 109 heat-treated OLL2712 cells, respectively, daily for 12 wk. The primary outcome was the 12-wk change in the abdominal fat area, as assessed by computed tomography, and the secondary outcomes were glucose and lipid metabolism-related parameters and chronic inflammation markers, which were analyzed using a linear mixed model. Results The 12-wk change of abdominal fat area (difference: 8.5 cm2; 95% CI: 0.3, 16.6 cm2; P = 0.040) and fasting plasma glucose (difference: 3.2 mg/dL; 95% CI: 0.8, 5.6 mg/dL; P = 0.021) were significantly less in the OLL2712 group than the placebo group. The overall trend of serum interleukin-6 was significantly decreased in the OLL2712 group compared with baseline and the placebo group. Conclusions The ingestion of heat-treated OLL2712 cells reduces body fat accumulation and the deterioration of glycemic control and chronic inflammation, in overweight, healthy adults. We hypothesize that OLL2712 cells may prevent obesity by regulating chronic inflammation. This trial was registered at UMIN Clinical Trials Registry as UMIN000027709.

PurposeThe purpose of this study was to test the efficacy of arginine, alanine, and phenylalanine mixture (A-mix) ingestion at 1,500 mg/day in combination with the promotion of physical activity for abdominal fat reduction in overweight adults.MethodsA placebo-controlled, double-blind, parallel-group, randomized trial for 12 weeks combined with a 4-week follow-up period was conducted at a single center in Minato-ku, Tokyo, Japan, between December 2016 and May 2017. Data were analyzed between June and August 2017. The study participants were 200 overweight adults within the age range of 20–64 years. The participants were randomly assigned to the A-mix group (n=100) or a placebo group (n=100) and were administered 500 mL of test beverage containing 1,500 or 0 mg of A-mix, respectively, for 12 weeks. All participants maintained a physically active lifestyle between week 0 and week 12 through monthly sessions of physical activity. The primary outcomes were the 12-week changes in the abdominal total, subcutaneous, and visceral fat areas, as assessed by computed tomography.ResultsOf the 200 enrolled participants, 199 (99%) accomplished the 12-week intervention and 4-week follow-up period. The per-protocol-based analysis for 194 participants demonstrated that the abdominal total fat area decreased significantly in the A-mix group compared with that in the placebo group (difference, 10.0 cm2; 95% confidence interval [CI]: 0.4–19.6 cm2; P=0.041). Comparable outcomes were obtained for the abdominal subcutaneous fat area (difference, 7.4 cm2; 95% CI: 0.1–14.7 cm2; P=0.047). No study-related unfavorable events occurred.ConclusionA-mix supplementation in combination with physical activity promotion facilitated abdominal fat reduction in overweight adults.

A double-blind, placebo-controlled study was carried out to determine the effective dosage of a vegetable and fruit juice mix, enriched with free plant sterol (sterol VFJ), on serum concentrations of cholesterol and safety assessment was made for normocholesterolemic and mildly hypercholesterolemic Japanese subjects as high dosage (HG: 1.6 g sterol/day), low dosage (LG: 0.8 g sterol/day) and placebo control groups (CG). All subjects were continuously monitored during a 12-week treatment period and serum cholesterol were measured. Throughout the experiment, the subjects were allowed to engage in normal daily activities. It is noteworthy that total cholesterol (T-C) and LDL-cholesterol (LDL-C) in LG and HG decreased significantly at 4, 8 and 12 weeks (LG: p <0.05; HG: p <0.01) compared to the baseline (0 weeks). The degree of change in T-C (DT-C) and LDL-C (DLDL-C) in HG and LG compared to CG was significant at 4, 8 and 12 weeks (LG: p < 0.05; HG: p < 0.01). Stratified analysis indicated T-C and LDL-C in LG and HG of high T-C (T-C 220 mg/dL) subjects (CG: n = 32; LG: n = 31; HG: n = 36) decreased significantly at 4, 8 and 12 weeks compared to the baseline (LG: p < 0.01; HG: p < 0.05). DT-C and DLDL-C in HG and LG compared CG significantly decreased at 8 and 12 weeks (LG: p <0.05; HG: p < 0.05). But in normal T-C (T-C< 220 mg/dL) subjects (CG: n = 19; LG: n = 19; HG: n = 18), T-C and LDL-C were significantly changed at some point during the period of treatment though not at 12 weeks. Sterol VFJ is thus shown less effective for diminishing serum lipid in normal and healthy subjects. Safety assessment data indicated significant change in some parameters, but which in all cases was within the normal range. No time-dependent or dosage-dependent change could be detected. From the present findings, sterol VFJ would appear a safe and effective beverage for improving serum lipid concentrations in normocholesterolemic and mildly hypercholesterolemic subjects.