Efficacy of plant-derived dietary supplements in improving overall menopausal symptoms in women: An updated systematic review and meta-analysis.

This updated systematic review and meta-analysis aims to confirm the effectiveness of plant-based supplements in improving overall menopausal symptoms and vasomotor symptoms. A systematic review of the literature was conducted by searching the PubMed/MEDLINE, Web of Science, EMBASE, and CENTRAL databases up to June 2022. Randomized placebo-controlled clinical trials that evaluated the effects of dietary supplements on menopausal symptoms were included. Outcome measures included daily hot flash frequency, Kupperman's index, Menopause Rating Scale, and Greene Climacteric Scale. Pooled data were analyzed using a fixed-effects model and expressed as a weighted mean difference with a 95% confidence interval for continuous outcomes. For qualitative assessment, 67 studies were selected. For quantitative assessment, 54 reports were obtained from 61 studies. The study participants were peri- or postmenopausal women aged 38-85, most of whom experienced hot flashes as a menopausal symptom. The investigational products included 28 soy-derived, 6 red clover-derived, and 28 other plant-derived supplements. Qualitative assessment revealed that approximately 76% of the studies were generally of fair or good quality, whereas 24% were of low quality. Meta-analysis results indicated significant improvements in all questionnaire scores, including hot flash frequency, in the dietary supplement group compared with the placebo group. Comprehensive evaluation using different questionnaire tools showed that the various plant-derived dietary supplements can significantly alleviate menopausal symptoms. However, further rigorous studies are needed to determine the association of plant-derived dietary supplements with menopausal health because of the general suboptimal quality and heterogeneous nature of current evidence.

Lycium chinense Miller fruit extract lowers liver enzyme levels in subjects with mild hepatic dysfunction: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: In our previous study, we showed that Lycium chinense Miller fruit extract (LFE) exerted hepatoprotective effects in mice. In the current study, we examined the effect of LFE on liver enzyme levels in subjects with mild hepatic dysfunction. METHODS: A total of 90 subjects, aged 19 to 70 years old, with abnormal alanine aminotransferase (ALT) levels, were randomly placed into either an LFE (n = 45) treatment group or a placebo group (n = 45). During the 12-week clinical trial, subjects in each group received either LFE or placebo capsules, and were instructed to take four tablets per day (1760 mg/day). The primary outcome of the study was the changes of ALT and γ-glutamyltransferase (GGT) levels in each subject. The safety of LFE supplementation was assessed and adverse events were recorded. RESULTS: LFE supplementation for 12 weeks resulted in a significant reduction of ALT (P = 0.0498) and GGT (P = 0.0368) levels in comparison to the placebo. No clinically significant changes were observed in any safety parameters. CONCLUSION: These results suggest that LFE can be applied to subjects with mild hepatic dysfunction with no possible side effects. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service (CRIS) as no. KCT0003985.

Effect of Ginseng Extracts on the Improvement of Osteopathic and Arthritis Symptoms in Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Ginsenosides are active compounds that are beneficial to bone metabolism and have anti-osteoporosis properties. However, very few clinical investigations have investigated the effect of ginseng extract (GE) on bone metabolism. This study aims to determine the effect of GE on improving bone metabolism and arthritis symptoms in postmenopausal women with osteopenia. A 12-week randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 90 subjects were randomly divided into a placebo group, GE 1 g group, and GE 3 g group for 12 weeks based on the random 1:1:1 assignment to these three groups. The primary outcome is represented by bone metabolism indices consisting of serum osteocalcin (OC), urine deoxypyridinoline (DPD), and DPD/OC measurements. Secondary outcomes were serum CTX, NTX, Ca, P, BsALP, P1NP, OC/CTX ratio, and WOMAC index. The GE 3 g group had a significantly increased serum OC concentration. Similarly, the GE 3 g group showed a significant decrease in the DPD/OC ratio, representing bone resorption and bone formation. Moreover, among all the groups, the GE 3 g group demonstrated appreciable improvements in the WOMAC index scores. In women with osteopenia, intake of 3 g of GE per day over 12 weeks notably improved the knee arthritis symptoms with improvements in the OC concentration and ratios of bone formation indices like DPD/OC.

Effect of processed aloe vera gel on immunogenicity in inactivated quadrivalent influenza vaccine and upper respiratory tract infection in healthy adults: A randomized double-blind placebo-controlled trial.

BACKGROUND: Aloe vera is a functional food with various pharmacological functions, including an immune-modulating effect. Until now, A. vera has never been studied as an adjuvant in influenza vaccine, and its effects on upper respiratory tract infection (URI) are unknown. PURPOSE: The objective of our study was to investigate the effect of processed A. vera gel (PAG) on immunogenicity of quadrivalent inactivated influenza vaccine and URI in healthy adults. STUDY DESIGN: A randomized, double-blind, placebo-controlled clinical trial was performed. METHODS: This study was conducted in 100 healthy adults at a single center from September 2017 to May 2018. Subjects were randomly divided into a PAG group (n = 50) and a placebo group (n = 50). The enrolled subjects were instructed to ingest the study drug for 8 weeks. The participants received a single dose of quadrivalent inactivated influenza vaccine after taking the study drug for the first 4 weeks of the study. The primary endpoint was seroprotection rate against at least one viral strain at 4 weeks post-vaccination. Other outcomes were seroprotection rate at 24 weeks post-vaccination, seroconversion rate, geometric mean fold increase (GMFI) at 4 and 24 weeks post-vaccination, seroprotection rate ratio and geometric mean titer ratio (GMTR) at 4 weeks post-vaccination between PAG and placebo groups, and incidence, severity, and duration of URI. RESULTS: The European Committee for proprietary medicinal products (CPMP) evaluation criteria were met at least one in the PAG and placebo groups for all strains. However, there was no significant difference in the seroprotection rate at 4 weeks post-vaccination against all strains in both PAG and placebo groups. Among secondary endpoints, the GMFI at 4 weeks post-vaccination for the A/H3N2 was significantly higher in the PAG than in placebo group. The GMTR as adjuvant effect was 1.382 (95% CI, 1.014-1.1883). Kaplan-Meier curve analysis showed a reduction in incidence of URI (p = 0.035), and a generalized estimating equation model identified a decrease in repeated URI events (odds ratio 0.57; 95% CI, 0.39-0.83; p = 0.003) in the PAG group. CONCLUSIONS: Oral intake of PAG did not show a significant increase in seroprotection rate from an immunogenicity perspective. However, it reduced the number of URI episodes. A well-designed further study is needed on the effect of PAG's antibody response against A/H3N2 in the future.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Assessing the Effects of Angelica Gigas Nakai Extract on Blood Triglycerides.

Angelica gigas Nakai, Korean dang-gui, has long been widely used in traditional treatment methods. There have been a number of studies of the health effects of A. gigas and related compounds, but studies addressing effects on blood triglycerides (TG) are lacking. To investigate the effects of A. gigas Nakai extract (AGNE) on TG in Korean subjects, we carried out a 12-week, randomized, double-blind, placebo-controlled clinical trial. Subjects who met the inclusion criterion (130 mg/dL ≤ fasting blood TG ≤ 200 mg/dL) were recruited for this study. One hundred subjects were assigned to the AGNE group (n = 50) or the placebo group (n = 50), who were given 1 g/day of AGNE (as a gigas Nakai extract 200 mg/d) in capsules and the control group for 12 weeks. Outcomes were efficacy TG, lipid profiles, atherogenic index, and safety parameters were assessed initially for a baseline measurement and after 12 weeks. After 12 weeks of supplementation, TG and very low-density lipoprotein cholesterol (VLDL-C) concentration and TG/HDL-C ratio in the AGNE group were significantly reduced compared to the placebo group (p < 05). No significant changes in any safety parameter were observed. These results suggest that the ingestion of AGNE may improve TG and be useful to manage or prevent hypertriglyceridemia.

Epigallocatechin-3-Gallate-Rich Green Tea Extract Ameliorates Fatty Liver and Weight Gain in Mice Fed a High Fat Diet by Activating the Sirtuin 1 and AMP Activating Protein Kinase Pathway.

The prevalence of metabolic diseases has risen globally in parallel with the obesity epidemic over the past few decades. Green tea has been reported to have metabolically beneficial effects on obesity; however, the mechanism by which green tea regulates lipid metabolism is not clearly understood. Male c57BL/6 mice were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with various doses of epigallocatechin gallate-rich green tea extract (GTE) for 12 weeks. GTE supplementation reduced body weight gain, prevented hepatic fat accumulation, decreased hypertriglyceridemia, and improved hyperglycemia and insulin resistance in HFD-fed mice. The underlying mechanisms of these beneficial effects of GTE might involve the upregulation of sirtuin 1 and AMP activated protein kinase (AMPK) and the downregulation of enzymes related to de novo lipogenesis. Consistent with the in vivo findings, GTE increased the expression and activity of sirtuin 1, enhanced the binding of sirtuin 1 to liver kinase B1 (LKB1) and subsequent deacetylation of LKB1, and reduced triglyceride accumulation in HepG2 cells. These results suggest the possible therapeutic potential of dietary epigallocatechin gallate-rich GTE supplementation for preventing the development and progression of hepatic steatosis and obesity.

Angelica gigas Ameliorates Hyperglycemia and Hepatic Steatosis in C57BL/KsJ-db/db Mice via Activation of AMP-Activated Protein Kinase Signaling Pathway.

The prevention and management of type 2 diabetes mellitus has become a major global public health challenge. Decursin, an active compound of Angelica gigas Nakai roots, was recently reported to have a glucose-lowering activity. However, the antidiabetic effect of Angelica gigas Nakai extract (AGNE) has not yet been investigated. We evaluated the effects of AGNE on glucose homeostasis in type 2 diabetic mice and investigated the underlying mechanism by which AGNE acts. Male C57BL/KsJ-db/db mice were treated with either AGNE (10 mg/kg, 20 mg/kg, and 40 mg/kg) or metformin (100 mg/kg) for 8 weeks. AGNE supplementation (20 and 40 mg/kg) significantly decreased fasting glucose and insulin levels, decreased the areas under the curve of glucose in oral glucose tolerance and insulin tolerance tests, and improved homeostatic model assessment-insulin resistant (HOMA-IR) scores. AGNE also ameliorated hepatic steatosis, hyperlipidemia, and hypercholesterolemia. Mechanistic studies suggested that the glucose-lowering effect of AGNE was mediated by the activation of AMP activated protein kinase, Akt, and glycogen synthase kinase-3[Formula: see text]. AGNE can potentially improve hyperglycemia and hepatic steatosis in patients with type 2 diabetes.

Anti-obesity effects of Yerba Mate (Ilex Paraguariensis): a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Obesity is a major health problem. A food field research that has recently aroused considerable interest is the potential of natural products to counteract obesity. Yerba Mate may be helpful in reducing body weight and fat. The aim of this study was to investigate the efficacy and safety of Yerba Mate supplementation in Korean subjects with obesity. METHODS: A randomized, double-blind, placebo-controlled trial was conducted. Subjects with obesity (body mass index (BMI) ≥ 25 but < 35 kg/m(2) and waist-hip ratio (WHR) ≥ 0.90 for men and ≥ 0.85 for women) were given oral supplements of Yerba Mate capsules (n = 15) or placebos (n = 15) for 12 weeks. Subjects take three capsules per each meal, total three times in a day (3 g/day). Measured outcomes were efficacy (abdominal fat distribution, anthropometric parameters and blood lipid profiles) and safety (adverse events, laboratory test results and vital signs). RESULTS: During 12 weeks of Yerba Mate supplementation, decreases in body fat mass (P = 0.036) and percent body fat (P = 0.030) compared to the placebo group were statistically significant. WHR was significantly decreased (P = 0.004) in the Yerba Mate group compared to the placebo group. No clinically significant changes in any safety parameters were observed. CONCLUSIONS: Yerba Mate supplementation decreased body fat mass, percent body fat and WHR. Yerba Mate was a potent anti-obesity reagent that did not produce significant adverse effects. These results suggested that Yerba Mate supplementation may be effective for treating obese individuals. TRIAL REGISTRATION: ClinicalTrials.gov: (NCT01778257).

Postprandial glucose-lowering effects of fermented red ginseng in subjects with impaired fasting glucose or type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Red ginseng is prepared by steaming raw ginseng, a process believed to increase the pharmacological efficacy. Further bioconversion of red ginseng through fermentation is known to increase its intestinal absorption and bioactivity, and bioconversion diminishes the toxicity of red ginseng's metabolite. This study was conducted to investigate the effects of daily supplementation with fermented red ginseng (FRG) on glycemic status in subjects with impaired fasting glucose or type 2 diabetes. METHODS: This study was a four-week long, randomized, double-blind, placebo-controlled trial. Forty-two subjects with impaired fasting glucose or type 2 diabetes were randomly allocated to two groups assigned to consume either the placebo or fermented red ginseng (FRG) three times per day for four weeks. Fasting and postprandial glucose profiles during meal tolerance tests were assessed before and after the intervention. RESULTS: FRG supplementation led to a significant reduction in postprandial glucose levels and led to an increase in postprandial insulin levels compared to the placebo group. There was a consistently significant improvement in the glucose area under the curve (AUC) in the FRG group. However, fasting glucose, insulin, and lipid profiles were not different from the placebo group. CONCLUSION: Daily supplementation with FRG lowered postprandial glucose levels in subjects with impaired fasting glucose or type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01826409.

Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The effects of actiponin was investigated, a heat-processed Gynostemma pentaphyllum extract, on body weight, fat loss, and metabolic markers of Korean participants in a 12-week, randomized, double-blind, placebo-controlled clinical trial. DESIGN AND METHODS: Obese participants (BMI ≥ 25 kg m(-2) and WHR ≥ 0.90 for male or WHR ≥ 0.85 for female) who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 80 subjects were randomly divided into actiponin (n = 40, 450 mg day(-1) ) and placebo (n = 40) groups. Outcomes included measurement of efficacy (abdominal fat distribution, anthropometric parameters, and blood lipid profiles) and safety (adverse events, laboratory test results, electrocardiogram data, and vital signs). RESULTS: During 12-week of actiponin supplementation, total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (P = 0.044, P < 0.05, P < 0.0001, P < 0.0001, and P < 0.05, respectively) in the actiponin group compared to the placebo group. No clinically significant changes in any safety parameter were observed. CONCLUSION: Our study revealed that actiponin is a potent antiobesity reagent that does not produce any significant adverse effects. These results suggest that actiponin supplementation may be effective for treating obese individuals.

Meta-analysis of Complementary and Alternative Intervention on Menstrual Distress.

PURPOSE: This study was to analyze the effect size of complementary and alternative intervention studies in reference to dysmenorrhea and menstrual distress. METHODS: In order to conduct a meta-analysis, a total of 393 studies were retrieved from the database. Twenty-eight studies that were published from March 2001 to February 2011 were selected. RESULTS: Intervention studies included seven studies on aromatherapy, five on auriculotherapy, three on each Koryo-Sooji-Chim and moxibustion, two on each heat therapy and magnetic therapy and six on other therapy. The effect size of the intervention studies on dysmenorrhea and menstrual distress was greater than 0.48 for Koryo-Sooji-Chim, moxibustion, aromatherapy, auriculotherapy and other therapy. CONCLUSION: This study suggests that drug free therapy can reduce the levels of menstrual distress, despite the small number of intervention studies and randomized controlled trials.

A placebo-controlled trial of Korean red ginseng extract for preventing influenza-like illness in healthy adults.

BACKGROUND: Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults. METHODS/DESIGN: We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale. DISCUSSION: This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence. TRIAL REGISTRATION: NCT01478009.

Improved cognitive performance following supplementation with a mixed-grain diet in high school students: a randomized controlled trial.

OBJECTIVE: Adolescence is a stage of rapid growth, when rich nutritional supplementation is important. Maintaining optimal cognitive functioning is critical in high school students, who are under considerable academic pressure. The objectives of this study were to identify the effects of a 9-wk randomly assigned diet of mixed grains versus a regular diet on cognitive performance and on levels of plasma brain-derived neurotrophic factor (BDNF) and S100B, a calcium-binding protein produced by astroglial cells, in healthy high school students (grades 10 and 11). METHODS: In this 9-wk, single-blind, controlled study, subjects were randomly allocated to either a mixed-grain or a regular diet. Cognitive assessments and measurements of plasma BDNF and S100B levels were performed at baseline and after the 9-wk intake of a mixed-grain or regular diet. Computerized neuropsychological tests and self-rating scales were used for the cognitive assessments. RESULTS: Significant improvements in some neuropsychological tests were found after 9 wk in both the mixed-grain and the regular-diet groups, but the changes from baseline between the two groups were not significantly different. Significant impairments on the AX-continuous performance test were observed at the endpoint in the regular-diet group, and the changes from baseline between the two groups were also significantly different for this test. A significant difference in changes in BDNF levels was observed between the two groups. CONCLUSIONS: These results suggest that intake of mixed grains for 9 wk is beneficial for cognitive performance and plasma BDNF levels in high school students. These beneficial effects seem to be related to the prevention of cognitive deterioration in a mental-fatigue test with the mixed-grain diet, rather than cognitive enhancement per se.

Effects of Ficus carica paste on constipation induced by a high-protein feed and movement restriction in beagles.

Constipation is one of the most common functional digestive complaints worldwide. We investigated the laxative effects of figs (Ficus carica L) in a beagle model of constipation induced by high protein diet and movement restriction. The experiments were consecutively conducted over 9 weeks divided into 3 periods of 3 weeks each. All 15 beagles were subjected to a non-treatment (control) period, a constipation induction period, and a fig paste treatment period. We administered fig paste (12 g/kg daily, by gavage) for 3 weeks following a 3-week period of constipation induction in dogs. Segmental colonic transit time (CTT) was measured by counting radiopaque markers (Kolomark) using a radiograph performed every 6 h after feeding Kolomark capsules, until capsules were no longer observed. Fig paste significantly increased fecal quantity in constipated dogs, and segmental CTT was also reduced following fig paste administration. There were no significant differences in feed intake, water intake, body weight, or blood test results, between the constipation and fig paste administration periods. Our results demonstrate that fig is an effective treatment for constipation in beagles. Specifically, stool weight increased and segmental CTT decreased. Fig pastes may be useful as a complementary medicine in humans suffering from chronic constipation.