Supplementation with a Natural Source of Amino Acids, Sil-Q1 (Silk Peptide), Enhances Natural Killer Cell Activity: A Redesigned Clinical Trial with a Reduced Supplementation Dose and Minimized Seasonal Effects in a Larger Population.

The aim of this study was to re-validate the changes in natural killer (NK) cell cytotoxicity and cytokines related to T cells after Sil-Q1 (SQ; silk peptide) supplementation in a larger pool of Korean adults with minimized daily dose of SQ and controlling seasonal influence compared to the previous study. A total of 130 subjects were randomly assigned (1:1) to consume either 7.5 g of SQ or placebo for 8 weeks. NK cell cytotoxicity and cytokines were measured at T0 (baseline) and T8 (follow-up). Comparing the NK cell cytotoxicity values at T0 and T8 within each group, the cytotoxicity at all effector cell (E) to target cell (T) ratios of 10:1, 5:1, 2.5:1, and 1.25:1 was significantly increased in the SQ group at T8. Additionally, significant differences in the changed value (Δ, subtract baseline values from follow-up values) comparison between the groups at E:T = 10:1, 5:1, and 2.5:1 were found. As a secondary endpoint, the interleukin (IL)-12 level in the SQ group was significantly increased for 8 weeks, and Δ IL-12 in the SQ group was greater than in the placebo group. In conclusion, the present study showed considerable practical implications of SQ supplementation. Thus, SQ is an effective and safe functional food supplement for enhancing immune function.

Potential Mechanisms of Improved Activity of Natural Killer Cells Induced by the Consumption of F-MRP for 8 weeks.

SCOPE: The authors used metabolomics to investigate the nutritional modulatory effect of fermented Maillard-reactive whey protein (F-MRP) on the activity of natural killer (NK) cells. METHODS AND RESULTS: Fifty subjects who had participated in our previous intervention study were included in the present study in the test (n = 20) and placebo groups (n = 30). Additional analyses using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and gas chromatography (GC)-MS were conducted to identify relevant metabolic features. After 8 weeks, the activity of lipoprotein-associated phospholipase A2 (Lp-PLA2) (p = 0.021), levels of interleukin (IL)-1ß (p = 0.001), and activity of NK cells were considerably increased in the test group compared with those in the placebo group. Based on the metabolites discovered by UPLC-MS, ten altered metabolic pathways were observed in the test group after 8 weeks of F-MRP consumption. Specific pathways with most pronounced associations with immune-enhancing effect of F-MRP included aminoacyl-tRNA biosynthesis, glycine/serine/threonine metabolism, arginine/proline metabolism, and sphingolipid metabolism. CONCLUSIONS: The present study demonstrated the effects of 8 weeks of F-MRP supplementation on the metabolic status manifested as changes in the Lp-PLA2 activity, IL-1ß level, and activity of NK cells. Intermediate metabolites of the identified metabolic pathways can be used to confirm the immune-enhancing efficacy of short-term supplementation.

Ginsenoside Mc1 improves liver steatosis and insulin resistance by attenuating ER stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside, a major pharmacologically active ingredient in ginseng, has been known to exhibit beneficial properties such as antioxidant and anti-inflammatory effects. Ginsenoside compound Mc1 is one of the newly identified de-glycosylated ginsenosides. Endoplasmic reticulum (ER) stress has implicated in the development of non-alcoholic fatty liver disease (NAFLD) through apoptosis and lipid accumulation. AIM OF THE STUDY: We aimed to examine the protective effects of Mc1 treatment on ER stress-induced cell death and impaired insulin signaling in HepG2 human hepatoblastoma cells and ER stress-induced liver steatosis and insulin resistance in a diet-induced obesity (DIO) mouse model. MATERIALS AND METHODS: HepG2 cells were treated with palmitate and Mc1 to evaluate the effects of Mc1 on ER stress-induced damage. C57BL/6 mice were fed with a high-fat diet (HFD) for 4 weeks and received an intraperitoneal injection of either vehicle or Mc1 (10 mg/kg/day). The control mice were fed with a chow diet and injected with vehicle for the same period. ER stress, cell death, and degree of steatosis were evaluated in the liver tissues of mice. The effect of Mc1 treatment on glucose metabolism was also determined. RESULTS: Mc1 co-treatment reduced the palmitate-induced ER stress and death of HepG2 cells. The palmitate-induced insulin resistance improved after Mc1 co-treatment. Consistent with the in vitro data, chronic Mc1 supplementation reduced ER stress and apoptotic damage in the liver of obese mice. Mc1 treatment ameliorated glucose intolerance and insulin resistance through the suppression of c-Jun N-terminal kinase (JNK) phosphorylation. In addition, Mc1 treatment reduced obesity-induced lipogenesis and prevented fat accumulation in the liver of DIO mice. CONCLUSIONS: Mc1 exerted protective effects against ER stress-induced apoptotic damage, insulin resistance and lipogenesis in palmitate-treated hepatocytes and in the liver of DIO mice. Therefore, Mc1 supplementation could be a potential therapeutic strategy to prevent NAFLD in patients with obesity and insulin resistance.

The effects of nattokinase supplementation on collagen-epinephrine closure time, prothrombin time and activated partial thromboplastin time in nondiabetic and hypercholesterolemic subjects.

The aim of this study was to investigate whether supplementation with nattokinase, which is considered one of the most active functional ingredients found in natto, alters hemostatic factors. Subjects presenting with hypercholesterolemia (serum cholesterol: 200-280 mg dL-1) were randomly divided into nattokinase and placebo groups (n = 50, respectively). No significant between-group differences were found at baseline in collagen-epinephrine closure time (C-EPI CT), prothrombin time (PT), or activated partial thromboplastin time (aPTT). After 8 weeks of treatment, the nattokinase group exhibited significant increases in C-EPI CT, PT, and aPTT. The nattokinase group showed significantly greater increases in C-EPI CT (P = 0.001) and aPTT (P = 0.016) than the placebo group. Moreover, at 8 weeks, the nattokinase group showed a significantly higher C-EPI CT than the placebo group (P = 0.001). Additionally, a significant correlation between PT and aPTT was observed (r = 0.491, P < 0.001). In conclusion, nattokinase supplementation was associated with prolonged C-EPI CT and aPTT in nondiabetic and borderline-to-moderate hypercholesterolemic subjects.

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.

Effects of weight loss using supplementation with Lactobacillus strains on body fat and medium-chain acylcarnitines in overweight individuals.

Our previous study showed that supplementation with a combination of Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 reduced the body weight, body fat percentage, body fat mass and L1 subcutaneous fat area in overweight subjects. We aimed to evaluate whether the changes in adiposity after supplementation with Lactobacillus strains were associated with metabolic intermediates. A randomized, double-blind, placebo-controlled study was conducted on 66 non-diabetic and overweight individuals. Over a 12-week period, the probiotic group consumed 2 g of probiotic powder, whereas the placebo group consumed the same product without the probiotics. To investigate metabolic alterations, we performed plasma metabolomics using ultra-performance liquid chromatography and mass spectrometry (UPLC-LTQ/Orbitrap MS). Probiotic supplementation significantly increased the levels of octenoylcarnitine (C8:1), tetradecenoylcarnitine (C14:1), decanoylcarnitine (C10) and dodecenoylcarnitine (C12:1) compared with the levels from placebo supplementation. In the probiotic group, the changes in the body weight, body fat percentage, body fat mass and L1 subcutaneous fat area were negatively associated with changes in the levels of C8:1, C14:1, C10 and C12:1 acylcarnitines. In overweight individuals, probiotic-induced weight loss and adiposity reduction from the probiotic supplementation were associated with an increase in medium-chain acylcarnitines.

Influences of body size phenotype on the incidence of gestational diabetes needing prescription; analysis by Korea National Health Insurance (KNHI) claims and the National Health Screening Examination (NHSE) database.

OBJECTIVES: Although growing evidence has emphasized the pivotal role of metabolic status irrespective of body mass index (BMI), there has been no study to examine the association of body size phenotype with development of gestational diabetes that requires treatment with oral hypoglycemic agent or insulin (GDM+T) in primiparas. METHODS: Data from a total of 216,961 women who participated in the National Health Screening Examination (NHSE) between January 2007 and December 2011 and delivered their first babies within two years of the NHSE were analyzed. Body size phenotypes were classified according to body mass index (BMI) and the presence/absence of metabolic syndrome according to the results of the NHSE. GDM+T was identified using the International Classification of Diseases-10th Revision (ICD-10) and prescription codes using Korea National Health Insurance (KNHI) claims. RESULTS: Approximately 0.39% of primiparas developed GDM+T. Compared to metabolically healthy normal weight (MHNW) women, both metabolically unhealthy normal weight (MUNW) and metabolically healthy obese (MHO) women had a significantly increased risk for developing GDM+T (odds ratio, OR: 9.53, 95% confidence interval, CI: 5.64-16.09 and OR: 3.30, 95% CI: 2.56-4.25, respectively). Specifically, MUNW individuals had a significantly higher risk of GDM+T when directly compared to MHO women even after adjusting for other GDM risk factors (OR: 2.92, 95% CI: 1.67-5.10). Furthermore, underweight women with metabolic syndrome showed a significantly increased frequency of GDM+T compared to MHNW subjects (OR: 8.87, 95% CI: 1.19-66.32). CONCLUSIONS: Pre-pregnant metabolic status is critical for development of GDM+T, regardless of their BMI. Therefore, intensive intervention for the components of metabolic syndrome may be helpful for the prevention of GDM+T even in low or normal weight women.

Low vitamin D status is associated with nonalcoholic Fatty liver disease independent of visceral obesity in Korean adults.

OBJECTIVE: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and nonalcoholic fatty liver disease (NAFLD) independent of visceral obesity in Koreans and to examine whether the associations differ according to the presence of diabetes or insulin resistance. RESEARCH DESIGN AND METHODS: A total of 1081 adults were enrolled from a population-based cohort in Ansan city. Serum 25(OH)D concentrations were measured in all subjects. Insulin resistance was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Using computed tomography, NAFLD was diagnosed if the liver attenuation index (LAI, the difference between the mean hepatic and splenic attenuation) was <5 Hounsfield Units. RESULTS: In subjects with diabetes (n = 282), 25(OH)D levels were negatively associated with waist circumference, fasting insulin, HOMA-IR, triglyceride levels, and visceral abdominal fat, and were positively associated with LAI after adjusting for age, sex, season, exercise, and vitamin supplementation. In subjects without diabetes, only triglyceride level was negatively associated with 25(OH)D. The adjusted odds ratio (OR) for NAFLD increased sequentially across decreasing quartiles of 25(OH)D in subjects with diabetes even after adjusting for visceral fat [Q1 vs. Q4; OR for NAFLD 2.5 (95% CI:1.0-6.2)]. In contrast, no significant difference in OR was observed in subjects without diabetes. When we classified non-diabetic subjects by HOMA-IR, an increase in the OR for NAFLD across decreasing quartiles of 25(OH)D was observed in the high HOMA-IR (≥2.5) group [n = 207, Q1 vs. Q4; OR 3.8(1.4-10.3)], but not in the low HOMA-IR (<2.5) group [n = 592, OR 0.8 (0.3-1.9)]. CONCLUSIONS: Low vitamin D status is closely associated with NAFLD, independent of visceral obesity in subjects with diabetes or insulin resistance.