Efficacy and Safety of Panax ginseng Sprout Extract in Subjective Memory Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Sprout ginseng extract (ThinkGIN™) manufactured through a smart farm system has been shown to improve memory in preclinical studies. This study conducted a 12-week randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of ThinkGIN™ for improving memory in subjective memory impairment (SMI). Subjects aged 55 to 75 years with SMI participated in this study. A total of 80 subjects who met the inclusion/exclusion criteria were assigned to the ThinkGIN™ group (n = 40, 450 mg ThinkGIN™/day) or a placebo group (n = 40). Efficacy and safety evaluations were conducted before intervention and at 12 weeks after intervention. As a result of 12 weeks of ThinkGIN™ intake, significant differences in SVLT, RCFT, MoCA-K, PSQI-K, and AChE were observed between the two groups. Safety evaluation (AEs, laboratory tests, vital signs, and electrocardiogram) revealed that ThinkGIN™ was safe with no clinically significant changes. Therefore, ThinkGIN™ has the potential to be used as a functional food to improve memory.

Anti-obesity effect of Neoagaro-oligosaccharides with overweight and obese subjects: a 16-week, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: This trial aimed to evaluate the anti-obesity effects and safety of Neoagaro-oligosaccharides (NAOs) in humans in a 16 week, randomized, double-blind, placebo-controlled clinical trial. METHODS: One hundred overweight or obese subjects with a body mass index of 23 to 34.9 kg/m2 and a percent body fat of > 25% for males or > 30% for females were enrolled. NAOs or placebo products were administered at 3 g (twice a day, four capsules once) each for 16 weeks. Efficacy and safety biomarkers were measured before and after intervention. RESULTS: After 16 weeks of intervention, the group administered with NAOs had statistically significant decreases in visceral fat area and visceral-subcutaneous fat area ratio compared to the placebo group. The NAOs group suppressed the increase in weight and BMI compared to the placebo group, which was significant between groups. High-density lipoprotein- cholesterol was increased in the group administered with NAOs, which showed a significant trend compared to the placebo group. Clinical changes were not observed for any safety biomarkers. CONCLUSIONS: These results suggest that NAOs have a beneficial effect on obesity. Thus, NAOs could be used as an anti-obesity supplement without side effects. TRIAL REGISTRATION: cris.nih.go.kr: (KCT0006640, 07/10/2021).

Efficacy and Safety of Omija (Schisandra chinensis) Extract Mixture on the Improvement of Hyperglycemia: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

A previous animal study demonstrated that the administration of Omija extract and soybean mixture (OSM) improved glycemic control in the type 2 diabetes model. In this study, we conducted a 12-week, randomized, double-blinded, and placebo-controlled clinical trial to determine the effects of OSM in humans with hyperglycemia. Participants with fasting plasma concentrations of 100-140 mg/dL were enrolled (n = 80) and administered either OSM or placebo products for 12 weeks. The outcomes included measurements of efficacy (fasting plasma glucose (FPG), postprandial glucose (PPG), fasting plasma insulin (FPI), postprandial insulin (PPI), hemoglobin A1c (HbA1c), C-peptide, fructosamine, and lipid parameters) and safety at baseline and at 12 weeks. After the intervention, the OSM group showed significantly decreased levels of FPG, PPG (30, 60 min), PPI (60 min), insulin area under the curve (AUC), fructosamine, and low-density-lipoprotein (LDL) cholesterol compared to the placebo group. No clinically significant changes in any safety parameter were observed. Therefore, it is hypothesized that OSM supplementation is an effective and safe functional food supplement for humans with hyperglycemia.

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.

Efficacy and Safety of Aronia, Red Ginseng, Shiitake Mushroom, and Nattokinase Mixture on Insulin Resistance in Prediabetic Adults: A Randomized, Double-Blinded, Placebo-Controlled Trial.

We determined whether oral consumption of Aronia, red ginseng, shiitake mushroom, and nattokinase mixture (3.4: 4.1: 2.4: 0.1 w/w; AGM) improved glucose metabolism and insulin resistance in prediabetic adults in a 12-week randomized, double-blinded clinical trial. Participants with fasting serum glucose concentrations of 100-140 mg/dL were recruited and randomly assigned to an AGM or placebo group. Participants of the AGM group (n = 40) were given an AGM granule containing 4 g of freeze-dried Aronia, red ginseng, shiitake mushroom, and nattokinase (3.4: 4.1: 2.4: 0.1 w/w) twice daily for 12 weeks, and the placebo group participants (n = 40) were provided with corn starch granules identical in appearance, weight, and flavor for 12 weeks. Serum glucose and insulin concentrations were measured during oral-glucose tolerance tests (OGTT) after administering 75 g of glucose in a fasted state. HOMA-IR, liver damage, and inflammation indices were determined, and safety parameters and adverse reactions were assessed. As determined by OGTT, serum glucose concentrations were not significantly different between the AGM and placebo groups after the intervention. However, changes in serum insulin concentrations in the fasted state and Homeostatic model assessment-insulin resistance (HOMA-IR) index after the intervention were significantly lower in the AGM group than in the placebo group (-3.07 ± 7.06 vs. 0.05 ± 6.12, p = 0.043 for serum insulin; -0.85 ± 2.14 vs. 0.07 ± 1.92, p = 0.049 for HOMA-IR). Serum adiponectin concentrations were reduced by intervention in the placebo group but not in the AGM group. Changes in liver damage indexes, including serum activities of the γ-glutamyl transferase, alanine aminotransferase, and aspartate aminotransferase, were lower in the AGM group and significantly reduced in the AGM group more than in the placebo group (p < 0.05). Changes in serum high sensitive-C-reactive protein concentrations in AGM and placebo groups were significantly different (-0.12 ± 0.81 vs. 0.51 ± 1.95, p = 0.06). In conclusion, AGM possibly improves insulin sensitivity and ß-cell function and reduces liver damage and inflammation in prediabetic adults.

Efficacy and Safety of Sesame Oil Cake Extract on Memory Function Improvement: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Pilot Study.

The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer's disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid ß (Aß) proteins and urine 8-OHdG (8-hydroxy-2'-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-ß (1-40) and amyloid-ß (1-42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma ß-amyloid levels of older adults with memory impairment.

Effects of Porphyra tenera Supplementation on the Immune System: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

OBJECTIVE: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. METHODS: Subjects who met the inclusion criteria (3 × 103 ≤ peripheral blood leukocyte level ≥ 8 × 103 cells/µL) were recruited for this study. Enrolled subjects (n = 120) were randomly assigned to either the PTE group (n = 60) and were given 2.5 g/day of PTE (as PTE) in capsule form or the placebo group (n = 60) and were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed based on measuring natural killer (NK) cell activity, cytokines level, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. RESULTS: Compared with baseline, NK cell activity (%) increased for all effector cell-to-target cell ratios in the PTE group after 8 weeks; however, changes were not observed in the placebo group (p < 0.10). Subgroup analysis of 101 subjects without URI showed that NK cell activity in the PTE group tended to increase for all effector cell/target cell (E:T) ratios (E:T = 12.5:1 p = 0.068; E:T = 25:1 p = 0.036; E:T = 50:1 p = 0.081) compared with the placebo group. A significant difference between the two groups was observed for the E:T = 25:1 ratio, which increased from 20.3 ± 12.0% at baseline to 23.2 ± 12.4% after 8 weeks in the PTE group (p = 0.036). A significant difference was not observed in cytokine between the two groups. CONCLUSION: PTE supplementation appears to enhance immune function by improving NK cell activity without adverse effects in healthy adults.

A 12-week, randomized, double-blind study to evaluate the efficacy and safety of liver function after using fermented ginseng powder (GBCK25).

BACKGROUND: Recently, clinical research has suggested that red ginseng components play a role in liver protection and combating fatigue. However, fermented ginseng has not been analyzed for liver-protective or anti-fatigue effects. OBJECTIVE: This study evaluates the positive effects of fermented ginseng powder (GBCK25) on liver function. METHODS: Ninety participants with elevated alanine aminotransferase levels (35 ≤ ALT ≤1 05 IU/L) were randomized to one of three groups. The participants were treated with GBCK25 tablets at a dose of 500 mg/day (high dose), 125 mg/day (low dose), or placebo group daily for 12 weeks. The primary outcomes included changes in ALT and gamma-glutamyl transferase (GGT) levels. The secondary outcomes included changes in aspartate amino-transferase (AST), high-sensitivity C-reactive protein (hs-CRP), multidimensional fatigue scale, lipid profile, and antioxidant markers. RESULTS: In male subjects, after 12 weeks of low-dose GBCK25 (125 mg) supplementation, the GGT (P = 0.036) and hs-CRP (P = 0.021) levels decreased significantly more than those in the placebo group. High-dose GBCK25 (500 mg) supplementation significantly decreased the fatigue score compared with the placebo group. There were no clinically significant differences between the groups when studying any safety parameter. CONCLUSION: Our results suggest that GBCK25 supplementation has beneficial effects on liver function. TRIAL REGISTRATION: This study was registered at Clinical Trials.gov (NCT03260543).

The effects of steamed ginger ethanolic extract on weight and body fat loss: a randomized, double-blind, placebo-controlled clinical trial.

Steamed ginger ethanolic extract (SGE) is a product with a high 6-shogaol contents and is thought to be more potent than other ginger products. We conducted a 12-week, randomized, double-blind, placebo-controlled clinical trial to determine the effects of SGE on weight and body fat loss. Eighty healthy obese participants were recruited and randomly divided into the SGE and placebo groups. The outcome measures comprised indicators of efficacy (body weight, body mass index, body composition, and blood markers) and safety. Following the supplementation period, mean body weight, body mass index, and body fat level were significantly lower in the SGE group than in the placebo group. No clinically significant changes were observed for any safety parameter. These results suggest that SGE is a potent anti-obesity agent that does not cause significant side effects. Therefore, SGE supplementation combined with lifestyle modification could be effective in the management of body weight and fat mass.

Silk peptide treatment potentiates natural killer cell activity in vitro and induces natural killer cell maturation and activation in mouse splenocytes.

Context: Silk peptide from cocoons of silkworm (Bombyx mori L., Bombycidae) has been employed as a biomedical material and exhibits various bioactivities, including immune-modulating activity. Objective: We analyzed whether silk peptide exerts direct modulating effects on NK cells using an NK cell line in vitro and ex vivo splenocytes. We also attempted to delineate the mechanism underlying the modulation. Material and methods: In vitro activity of silk peptide on NK cells was determined by measurement of cytolytic activity against K562 cells at an effector-to-target ratio of 5:1 after incubation of NK-92MI cells with silk peptide (0-2000 µg/mL) for 48 and 72 h. Ex vivo activity of silk peptide on mouse splenic NK cells was determined similarly by using YAC-1 cells. Results: Treatment of NK-92MI NK cells with silk peptide (500-2000 µg/mL) significantly increased cytolytic activity on target cells by 2- to 4-fold. The same concentrations (500-2000 µg/mL) of silk peptide treatment also significantly enhanced the cytolytic activity of splenic NK cells against YAC-1 cells. Silk peptide treatment of IL-2-stimulated splenocytes induced enhanced expression of Th1, 2 and 17 cytokines including TNF-α, IFN-γ, IL-6, IL-4 and IL-17. Finally, ex vivo treatment with silk peptide on mouse splenocytes significantly enhanced the degree of NK cell maturation in a dose-dependent manner from 3.49 to 23.79%. Discussion and conclusions: These findings suggest that silk peptide stimulates NK cells, thereby influencing systemic immune functions and improving natural immunity. Thus, silk peptide could be useful as a complementary therapy in cancer patients.

Supplementation with extract of Gynostemma pentaphyllum leaves reduces anxiety in healthy subjects with chronic psychological stress: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: The ethanol extract of Gynostemma pentaphyllum Makino leaves (EGP) has been reported recently to have anxiolytic effects on chronically stressed mice models. PURPOSE: We aimed to investigate the efficacy and safety of EGP on anxiety level in healthy Korean subjects under chronic stressful conditions. STUDY DESIGN: Double-blind, placebo-controlled trial. METHODS: This study was conducted with 72 healthy adults who had perceived chronic stress and anxiety with a score on the State-Trait Anxiety Inventory (STAI) from 40 to 60. Participants were randomly assigned to receive either EGP (200 mg, twice a day, N = 36) or placebo (N = 36). All participants were exposed to repetitive loads of stress by performing the serial subtraction task for 5 min every second day during the 8-week intervention. Primary outcome of Trait-STAI and secondary outcomes of State-STAI, total score of STAI, Hamilton Anxiety Inventory (HAM-A), Beck Anxiety Inventory (BAI), blood norepinephrine and adrenocorticotropic hormone (ACTH), salivary cortisol and alpha-amylase, cardiovascular autonomic nervous system (ANS) functional test, and heart rate variability (HRV) test were measured before and after intervention. RESULTS: After the 8-week intervention, the EGP significantly lowered the score of the Trait Anxiety Scale of the STAI (T-STAI) by 16.8% compared to the placebo (p = 0.041). The total score on the STAI decreased by 17.8% in the EGP group and tended to improve compared with that of the placebo group (p = 0.067). There were no significant differences in the changes in score of S-STAI, HAM-A, BAI, and other parameters from baseline between the two groups. There was no causal relationship between the ingestion of EGP and adverse drug reactions. CONCLUSION: We found that supplementation with EGP reduced "anxiety proneness" in subjects under chronic psychological stress, as shown by a decrease in the score of T-STAI and the tendency for decrease in the total score of STAI. This result suggests that EGP supplementation can be used as a regimen to safely reduce stress and anxiety; however, more studies are needed to establish the long-term safety and effectiveness.

Oral Administration of Silk Peptide Enhances the Maturation and Cytolytic Activity of Natural Killer Cells.

Silk peptide, the hydrolysate of silk protein derived from cocoons, has been employed as a biomedical material and is believed to be safe for human use. Silk peptide display various bioactivities, including anti-inflammatory, immune-regulatory, anti-tumor, anti-viral, and anti-bacterial. Although earlier investigations demonstrated that silk peptide stimulates macrophages and the production of pro-inflammatory cytokines, its effect on natural killer (NK) cell function has not yet been explored. In this study, we initially confirmed that silk peptide enhances NK cell activity in vitro and ex vivo. To assess the modulatory activity of silk peptide on NK cells, mice were fed various amounts of a silk peptide-supplemented diet for 2 months and the effects on immune stimulation, including NK cell activation, were evaluated. Oral administration of silk peptide significantly enhanced the proliferation of mitogen- or IL-2-stimulated splenocytes. In addition, oral silk peptide treatment enhanced the frequency and degree of maturation of NK cells in splenocytes. The same treatment also significantly enhanced the target cell cytolytic activity of NK cells, which was determined by cell surface CD107a expression and intracellular interferon-γ expression. Finally, oral administration of silk peptide stimulated T helper 1-type cytokine expression from splenic lymphocytes. Collectively, our results suggest that silk peptide potentiates NK cell activity in vivo and could be used as a compound for immune-modulating anti-tumor treatment.

Randomized, double-blind, placebo-controlled trial of Ficus carica paste for the management of functional constipation.

BACKGROUND AND OBJECTIVES: Constipation affects up to 20% of the world's population. The aim of this study was to investigate whether supplementation with Ficus carica paste could be used to treat constipation in Korean subjects with functional constipation. METHODS AND STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled trial. Subjects with functional constipation were orally supplemented with either F. carica paste (n=40) or placebo (n=40) for 8 weeks. We measured the efficacy and safety of F. carica paste. Primary outcomes (colon transit time) and secondary outcomes (questionnaire related to defecation) were compared before and after the 8-week intervention period. RESULTS: F. carica paste supplementation was associated with a significant reduction in colon transit time and a significant improvement in stool type and abdominal discomfort compared with the placebo. Blood parameters and clinical findings for organ toxicity remained within normal ranges. CONCLUSION: These results suggest that F. carica paste may have beneficial effects in subjects suffering from constipation.