Efficacy and safety of Cortex Eucommiae (Eucommia ulmoides Oliver) extract in subjects with mild osteoarthritis: Study protocol for a 12-week, multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Osteoarthritis (OA) is a major degenerative disease that affects the elderly. The global prevalence of OA is increasing annually. However, current treatments are unable to halt the progress of OA. At present, pharmacological treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors control the pain; however, there may be side effects to these medications. We hypothesized that Cortex Eucommiae (CE; Eucommia ulmoides Oliver) extract, which is used as a dietary supplement, may slow down or prevent OA. METHODS: This is a protocol for a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of CE extract in subjects with mild OA. One-hundred subjects with mild OA will be recruited and randomly divided in a 1:1 ratio into 2 groups. One group will receive CE extract for 12 weeks and the other group will receive placebo for 12 weeks. Outcomes will be evaluated by using the visual analog scale (VAS), Korean-Western Ontario and McMaster Universities index (K-WOMAC), Korean-Short Form health survey-36 score (KSF-36), and laboratory test results. DISCUSSION: This clinical trial is expected to provide evidence of the efficacy and safety of CE extract as a treatment for mild OA. TRIAL REGISTRATION: Clinical Trials.gov NCT03744611, registered on November 12, 2018, at https://clinicaltrials.gov/ct2/show/NCT03744611.

The effects of Jerusalem artichoke and fermented soybean powder mixture supplementation on blood glucose and oxidative stress in subjects with prediabetes or newly diagnosed type 2 diabetes.

BACKGROUND/OBJECTIVES: The objective of this study was to evaluate the effect of supplementation with a Jerusalem artichoke and fermented soybean powder mixture on blood glucose and oxidative stress levels. SUBJECTS/METHODS: This randomized, double-blinded, placebo-controlled study was conducted on 60 subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes. The subjects were randomly assigned to either a group that ingested 40 g of a Jerusalem artichoke and fermented soybean powder mixture (19.45 g each) daily or a group that received a placebo for 12 weeks. Paired t-test and independent t-test were performed for comparisons within groups and between groups, respectively. RESULTS: Supplementation with the Jerusalem artichoke and fermented soybean powder mixture reduced the levels of fasting glucose (p < 0.001) and FFAs (p = 0.034), glucose at 60 min (p = 0.004), glucose (p = 0.006) areas under the response curve (AUC), homeostasis model assessment-insulin resistance (p = 0.018), and the urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) level (p = 0.028). The changes (Δ) in urinary 8-epi-PGF2α, glucose at 60 min, 120 min, and AUC, FFAs at 0 min and AUC were significantly different between the two groups. In addition, Δ glucose at 120 min (r = 0.472, p = 0.027) and the Δ glucose AUC (r = 0.572, p = 0.005) were positively correlated with △ plasma malondialdehyde in the test group. CONCLUSIONS: The consumption of a Jerusalem artichoke and fermented soybean powder mixture for 12 weeks was effective for reducing postprandial glucose and oxidative stress level, particularly 8-epi-PGF2α, in subjects with IFG, IGT, or newly diagnosed type 2 diabetes.

Supplementation of fermented Maillard-reactive whey protein enhances immunity by increasing NK cell activity.

OBJECTIVE: The objective of this study was to investigate the impact of supplementation with fermented Maillard-reactive whey protein (F-MRP) on natural killer (NK) cell activity, circulating cytokines, and serum protein levels. METHODS: A randomized, double-blind, placebo-controlled study was conducted on a sample of 80 participants without diabetes or obesity. Over an 8-week study period, the F-MRP group consumed 6 g of powder containing 4.2 g of F-MRP each day, whereas the placebo group consumed the same amount of maltodextrin. For each participant, NK cell activity was evaluated based on the ratio of effector cells (E; peripheral blood mononuclear cells, PBMCs) to target cells (T; K562 cells) at E : T ratios of 10 : 1, 5 : 1, 2.5 : 1, and 1.25 : 1. RESULTS: Body mass index (BMI) and NK cell activity under all assay conditions were significantly increased in the F-MRP group at the 8-week follow-up visit compared with the values at the baseline, whereas the placebo group showed significant reductions in NK cell activity (at an E : T ratio of 5 : 1), serum albumin, and pre-albumin at the 8-week follow-up visit compared with the values at the baseline. When comparing the changes between the placebo and F-MRP groups, the increases in NK cell activity under all assay conditions and serum interleukin (IL)-12 in the F-MRP group were greater than those in the placebo group after adjusting for baseline values. There were also significant differences in pre-albumin and insulin-like growth factor (IGF)-1 between the two groups; the change in (Δ) IL-12 was positively correlated with both Δpre-albumin (r = 0.435, P = 0.006) and ΔNK cell activity at an E : T ratio of 10 : 1 (r = 0.571, P < 0.001) in the F-MRP group. CONCLUSION: Daily consumption of F-MRP enhanced NK cell function, which was positively associated with ΔIL-12. Moreover, ΔIL-12 was positively correlated with Δpre-albumin.

Associations among oxidative stress, Lp-PLA2 activity and arterial stiffness according to blood pressure status at a 3.5-year follow-up in subjects with prehypertension.

BACKGROUND AND AIMS: We aimed to determine changes in oxidative stress, lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and arterial stiffness in subjects with persistent prehypertensive symptoms during a 3.5-year follow-up period. METHODS: We divided 254 subjects with prehypertension according to their blood pressure (BP) status at 3.5 years of follow-up into three groups: reversed normotensive, persistent prehypertensive and developed hypertensive group. BP, serum lipid profile, oxidized LDL (ox-LDL), Lp-PLA2 activity and brachial-ankle pulse wave velocity (ba-PWV) were measured at baseline and the 3.5-year follow-up. RESULTS: The reversed normotensive group showed a significant reduction in average BP (14.7/10.1 mmHg), whereas the developed hypertensive group showed a significant increase in average BP (15.2/11.5 mmHg). The persistent prehypertensive group showed increases in serum lipid profiles, circulating levels of Lp-PLA2 activity, ox-LDL and arterial stiffness as measured by ba-PWV at 3.5 years. The persistent prehypertensive and developed hypertensive groups showed greater increases in ox-LDL than the reversed normotensive group. The developed hypertensive group showed greater increases in Lp-PLA2, 8-epi-PGF2α, and ba-PWV than those observed in the reversed normotensive and persistent prehypertensive groups. In all subjects, changes (Δ) in systolic blood pressure (SBP) positively correlated with Δ Lp-PLA2, Δ ox-LDL, Δ urinary 8-epi-PGF2α and Δ ba-PWV. CONCLUSIONS: This study indicates that in persistent prehypertension, increased ox-LDL hydrolysis by Lp-PLA2 enhances arterial stiffness without an age-related increase in BP.

Effect of Immune-Enhancing Enteral Nutrition Enriched with or without Beta-Glucan on Immunomodulation in Critically Ill Patients.

We investigated whether high-protein enteral nutrition with immune-modulating nutrients (IMHP) enriched with ß-glucan stimulates immune function in critically ill patients. In a randomized double-blind placebo-controlled study, 30 patients consumed one of three types of enteral nutrition: a control or IMHP with and without ß-glucan. The IMHP with ß-glucan group showed increases in natural killer (NK) cell activities relative to the baseline, and greater increases were observed in NK cell activities relative to the control group after adjusting for age and gender. The IMHP groups with and without ß-glucan had greater increases in serum prealbumin and decreases in high-sensitivity C-reactive protein (hs-CRP) than the control group. The control group had a greater decrease in peripheral blood mononuclear cell (PBMC) interleukin (IL)-12 production than the IMHP with and without ß-glucan groups. In all patients, the change (Δ) in hs-CRP was correlated with Δ prealbumin and Δ PBMC IL-12, which were correlated with ΔNK cell activity and Δ prealbumin. This study showed beneficial effects of a combination treatment of ß-glucan and IMHP on NK cell activity. Additionally, strong correlations among changes in NK cell activity, PBMC IL-12, and hs-CRP suggested that ß-glucan could be an attractive candidate for stimulating protective immunity without enhanced inflammation (ClinicalTrials.gov: NCT02569203).

Beneficial effect of xylose consumption on postprandial hyperglycemia in Korean: a randomized double-blind, crossover design.

BACKGROUND: Previous studies have reported that xylose selectively inhibited the activity of sucrase. Xylose supplementation may have a beneficial effect on the postprandial glycemic response. However, no studies have investigated patients with IFG or the effectivity of a dose of D-xylose less than 10 % (w/w). METHODS: The present study determined the effect of xylose consumption on postprandial hyperglycemia in normal (n = 25) and hyperglycemic subjects (n = 50). Subjects in this double-blind crossover design study were randomly assigned to consume a sucrose drink (Control, sucrose 50 g + deionized water 100 g) or a sucrose drink additionally containing 5 g (Test 1, sucrose:xylose = 10:1), 3.33 g (Test 2, sucrose:xylose = 15:1), or 2.5 g (Test 3, sucrose:xylose = 20:1) of D-xylose separated by a one-week interval. RESULTS: Normal subjects in all test groups exhibited a significant decrease in serum glucose levels 15 min and 30 min after consuming the xylose-containing drinks compared to the control group. Significantly lower serum levels of insulin were observed at 15 min and 30 min after consuming the xylose-containing drinks compared to the control group. The test 1 group also exhibited a significantly lower insulin area under the curve than the control group. Hyperglycemic subjects (n = 50) in all test groups exhibited a significant decrease in serum glucose levels at 30 min compared to the control group. However, the test 1 group exhibited a significant increase in serum glucose levels at 120 min compared to the control group. Glucose-related markers did not significantly differ in each group. CONCLUSION: Xylose supplementation may exert a beneficial effect on postprandial glycemic responses in subjects with normal glucose levels and prediabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02654301 . Registered 12 January 2016.

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein A-V levels in non-diabetic subjects with hypertriglyceridemia.

OBJECTIVE: Previous studies have indicated that supplementation with probiotics might improve lipid metabolism. The objective of the study was to evaluate the effect of supplementation with probiotic strains Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 on triglyceride (TG) and apolipoprotein A-V (apo A-V) levels. METHODS: A randomized, double-blinded, placebo-controlled study was conducted with 128 non-diabetic subjects with hypertriglyceridemia. Over a 12-week test period, the probiotic group consumed 2 g/day of a powdered supplement containing L. curvatus HY7601 and L. plantarum KY1032, whereas the placebo group consumed a powder lacking probiotics. RESULTS: After the treatment, the probiotic group showed an 18.3% (P < 0.001) reduction in TGs and increases of 21.1% (P = 0.001) and 15.6% (P < 0.001) in the apo A-V and LDL particle size, respectively. The probiotic group had a significant reduction in TGs (P = 0.040) and increases in the plasma apo A-V (P = 0.003) and LDL particle size (P < 0.001) compared with the placebo group. In the probiotic group, the reduction in the TG levels was negatively correlated with changes in the apo A-V and baseline TGs, regardless of the APOA5 -1131T > C genotype. CONCLUSION: The consumption of two probiotic strains for 12 weeks reduced TGs and increased the apo A-V and LDL particle size in hypertriglyceridemic subjects. This effect was more pronounced in subjects with higher levels of fasting TGs regardless of their APOA5 -1131T > C genotype.

Circulating Lp-PLA2 activity correlates with oxidative stress and cytokines in overweight/obese postmenopausal women not using hormone replacement therapy.

Controversy remains regarding whether there is an association between circulating lipoprotein-associated phospholipase A2 (Lp-PLA2), cytokines, and oxidative stress in healthy postmenopausal women. We investigated the influence of age on Lp-PLA2 activity in postmenopausal women not using hormone therapy and the relationship of Lp-PLA2 enzyme activity to serum cytokine levels and oxidative stress indices. Normal weight (n = 1284) and overweight/obese (n = 707) postmenopausal women not using hormone therapy were categorized into five age groups: 50-54, 55-59, 60-64, 65-69, and 70-89 years. Overweight-obese women showed higher plasma Lp-PLA2 activity, urinary 8-epi-prostaglandin F2α (8-epi-PGF2α), serum interleukin (IL)-6, and smaller LDL particles than normal-weight women after adjusting for age, years postmenopause, smoking, drinking, blood pressure, glucose, insulin, lipid profiles, BMI, and waist circumference. Overweight/obese women 70-89 years old showed higher Lp-PLA2 activity than those aged 50-54 years, whereas no significant difference in Lp-PLA2 activity existed across normal-weight female age groups. Overweight/obese women aged ≥ 65 years showed higher Lp-PLA2, oxidized LDL (ox-LDL), IL-6, and 8-epi-PGF2α than age-matched normal-weight controls. Overweight/obese women aged ≥ 70 years had higher ox-LDL levels than those aged 50-59, and overweight/obese women aged 65-89 showed higher IL-6 and 8-epi-PGF2α. There were strong positive correlations between Lp-PLA2 and ox-LDL (r = 0.385, P < 0.001), Lp-PLA2 and IL-6 (r = 0.293, P < 0.001), and ox-LDL and IL-6 (r = 0.303, P < 0.001) in overweight/obese women; however, these relationships were weak in normal-weight women. These results suggest that aging and obesity-related oxidative and inflammatory mediators are associated with Lp-PLA2 activity in overweight/obese postmenopausal women not using hormone therapy.

The effects of chitosan oligosaccharide (GO2KA1) supplementation on glucose control in subjects with prediabetes.

We aimed to evaluate the effect of chitosan oligosaccharide (GO2KA1) supplementation on glucose control in subjects with prediabetes. This study was a randomized, double-blind, placebo-controlled clinical trial. Subjects with prediabetes were randomly assigned to the GO2KA1 intervention group or the placebo group for 12 weeks. We assessed the serum levels of glucose, insulin, and C-peptide by a 2 hour value in the 75 g oral glucose tolerance test (OGTT), HbA1c, pro-inflammatory cytokines, and plasma adiponectin at baseline and after the 12 week intervention. The treatment group showed a significant decrease in the serum glucose level at 30 min (p = 0.013) and at 60 min (p = 0.028). The change of the serum glucose level at 60 min was significant in the treatment group compared with the placebo group (p = 0.030). Also, the plasma level of HbA1c (p = 0.023) and the pro-inflammatory cytokines (IL-6 and TNF-α) were reduced and plasma adiponectin was increased in the GO2KA1 intervention group after the 12 week treatment. However, the placebo group did not show any significant changes in these biomarkers. In subjects with prediabetes, 12 week supplement with GO2KA1 may help control postprandial glucose compared with control.

Korean red ginseng improves glucose control in subjects with impaired fasting glucose, impaired glucose tolerance, or newly diagnosed type 2 diabetes mellitus.

This study was designed to evaluate the effect of Korean red ginseng (KRG) supplementation on glucose control in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo-controlled (5 g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose-related biomarkers, including serum and whole blood levels of glucose, insulin, and C-peptide, were measured by 2-h oral glucose tolerance tests (OGTTs) at baseline and after the 12-week intervention. After the intervention, the test group showed a significant decrease in serum levels of glucose at 30 min (-22.24±10.77 mg/dL) and whole blood levels of glucose at 30 min (-17.52±5.22 mg/dL). In addition, the test group tended to have lower whole blood levels of glucose at 0 min and glucose area under curve (AUC). However, the placebo group did not show any changes in blood glucose-related indices. The changes (difference from baseline) in serum glucose levels at 30 min, whole blood glucose levels at 60 min, and glucose AUC during OGTTs in the test group exhibited a tendency toward a decrease from those in the placebo group. There were significant decreases or trends toward a decrease in both serum insulin and C-peptide concentrations at most time intervals in the test group. In conclusion, KRG supplementation (5 g/day) may be beneficial for controlling serum and whole blood glucose levels compared with placebo among patients with IFG, IGT, or T2DM.