Wednesday, 6 December 2017
Asian Ginseng Berry Shows Mixed Results in Lowering Blood Glucose in Patients with Diabetes and Pre-Diabetes
HerbalGram Issue: 116 Page: 35-36 by Amy C. Keller, PhD HerbalGram. 2017; American Botanical Council Reviewed: Choi HS, Kim S, Kim MJ, et al. Efficacy and safety of Panax ginseng berry extract on glycemic control: a 12-wk randomized, double-blind, and placebo-controlled clinical trial [published online January 10, 2017]. J Ginseng Res. doi: 10.1016/j.jgr.2017.01.003. Diabetes is prevalent worldwide and often leads to serious health consequences. Although medications exist to treat this condition, alternative and new therapies are needed. Asian ginseng (Panax ginseng, Araliaceae) root preparations have previously been shown to have anti-hyperglycemic activity in clinical trials, but one study has suggested that Asian ginseng berry* may be more effective at decreasing blood glucose levels.1 This randomized, double-blind, placebo-controlled study investigated the impact of ginseng berry (fruit) extract consumption on blood glucose concentrations. Patients were recruited from January 2014 to December 2014 via subway advertisements and at the Dongguk University Ilsan Hospital in Gyeonggi, South Korea. Subjects aged 20-75 years with fasting blood glucose concentrations between 100 and 140 mg/dL were included. (Concentrations in this range meet the criteria for prediabetes or diabetes, according to the American Diabetes Association.2) Those with lipid metabolism problems, inflammation or cardiovascular diseases, allergies to study ingredients, or kidney or liver problems were excluded. Subjects who took insulin injections, therapies to decrease blood glucose concentrations, antipsychotic medication within two months of the study, or corticosteroids within four weeks of the study also were excluded. Both ginseng berry extract capsules and placebo were acquired from Amorepacific Corporation of Gyeonggi, South Korea. The contents of the placebo were not mentioned. Berries were harvested in South Korea and ethanol extracts were made from the deseeded berry pulp and juice. Ginsenoside concentrations were measured with high-performance liquid chromatography, and the extract was standardized to contain 10% of “ginsenoside Re” and a total ginsenoside content of 20%. Capsules contained 250 mg of the standardized berry extract, and patients took a total of 1 g of extract daily for 12 weeks; two capsules were administered each day before breakfast and dinner. Subjects in the placebo group followed the same regimen. Patients were randomly assigned to the ginseng berry extract group or the placebo group and had clinic visits at baseline, six weeks, and 12 weeks. Medical histories of the patients were collected and physical examinations were conducted. Physical parameters were measured and food intake and amount of exercise were assessed. Daily patient logs and unconsumed capsules were used as markers of compliance. The primary outcome measures were changes from baseline in fasting and postprandial blood glucose concentrations. At the beginning and end of the study, subjects fasted overnight and completed a two-hour oral glucose tolerance test (OGTT), in which blood was drawn at 0, 60, and 120 minutes. At both visits, blood collected before the OGTT was used to determine the subjects’ fasting blood glucose levels. Impacts of the treatment on fasting and postprandial insulin, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol concentrations were secondary outcome measures. Serum metabolites were analyzed using ultra-performance liquid chromatography with time-of-flight mass spectrometry and specialized software. Laboratory and physical measurements, as well as reporting of adverse side effects (ASEs), served as tolerance assessments. From a total of 72 patients, six withdrew due to ASEs or personal reasons and another three were not analyzed due to compliance problems. In total, 29 patients in the ginseng berry extract group and 34 in the placebo group were analyzed. Compliance was greater than 70% and everyone who received treatment was included in the safety assessment. No significant differences between groups were observed in demographic parameters at the start of the study. No effects were seen in either group with the OGTT at baseline and the end of the study, and no differences were noted in lipid markers in the ginseng berry extract group; however, in the placebo group, the increase of total cholesterol from baseline to endpoint approached significance (P = .060), and HDL cholesterol concentrations significantly rose (P = .002). Having failed to achieve statistical significance for the primary outcome measures, the authors conducted a post-hoc analysis on a subset of patients with fasting glucose concentrations of 110 mg/dL or higher. In this subgroup, the authors found a small but significant decrease from baseline in fasting glucose for those in the ginseng berry extract group (120.25 ± 10.32 mg/dL vs. 115.81 ± 9.30 mg/dL; P = .035). In this subset of patients, the authors also observed a decrease in blood glucose concentrations from baseline at the 60-minute time point of the OGTT (231.75 ± 37.58 mg/dL vs. 206.94 ± 40.28 mg/dL; P = .006) in the ginseng berry group, but not at the 120-minute time point. These changes were not seen in the placebo group. Using the post-hoc subgroup, the area under the curve of the OGTT (an approximation of the subjects’ glycemic index) for the ginseng berry extract group was significantly less at the end of the study (P = .024), which is indicative of improved glucose tolerance. An analysis of effects between men and women showed a significant decrease from baseline in glucose concentrations at the 60-minute time point of the OGTT in men taking the ginseng berry extract (P = .020). This was not seen in women in the ginseng berry extract group or in men or women in the placebo group. Five ASEs were noted in the ginseng berry extract group, though none were serious, and 11 ASEs, including one serious event, were seen in the placebo group. These were not significantly different between groups. Diastolic blood pressure significantly decreased from baseline in the ginseng berry extract group (P = .010). The authors note significant differences from baseline in the ginseng berry extract group’s hematocrit concentrations (P = .047), as well as lymphocyte count (P = .034). Red blood cell count differences were significant between the groups (P = .042), but the authors state that these differences were not clinically significant. Directionality of these metrics was not mentioned. In the metabolomic analysis, 53 different metabolites were identified, but no significant differences in these were seen between groups. Across the study, there were significantly lower concentrations in the ginseng berry extract group of valine, leucine/isoleucine, glutamine, methionine, xanthine, and phenylpyruvic acid (P < .05 for all). Glycerophosphocholine, linoleoyl carnitine, lysophosphatidylethanolamine, and lysophosphatidylcholine were significantly increased in this group (P < .05 for all). Also in the ginseng berry extract group, significant positive correlations in xanthine, alanine, succinic acid, phenylalanine, creatine, and leucine/isoleucine were seen with fasting blood glucose concentrations (P < .05 for all). Metabolomic changes were not significantly different between groups. This study suggests that for those with higher blood glucose concentrations, Asian ginseng berry extract may be an effective adjuvant anti-hyperglycemic therapy. The extract used here may be well-tolerated. The authors note that the ginsenoside content of Asian ginseng can vary depending on plant part (e.g., berry, root, or leaf). “For this reason,” the authors explain, “each part of the plant may exhibit different pharmacological activities.” Discussed limitations of this trial include the small number of participants, limited severity of elevated glucose concentrations (only a small number of patients were diagnosed with type 2 diabetes), and the lack of follow-up. Future work will ideally target efficacy and safety in multiple populations. The study was supported by the Research and Development (R&D) program of the Ministry of Trade, Industry and Energy/Korea Institute for Advancement of Technology (Establishment of Infrastructure for Anti-aging Industry Support); the Convergence of Conventional Medicine and Traditional Korean Medicine R&D Program funded by the Ministry of Health and Welfare through the Korea Health Industry Development Institute; and Amorepacific Corporation. Two authors are part of the Nutrition and Metabolism Research Group at the Korea Food Research Institute in Gyeonggi, South Korea. The Journal of Ginseng Research is the official, open-access journal of The Korean Society of Ginseng in Seoul, South Korea. —Amy C. Keller, PhD References Dey L, Xie JT, Wang A, Wu J, Maleckar SA, Yuan CS. Anti-hyperglycemic effects of ginseng: comparison between root and berry. Phytomedicine. 2003;10(6-7):600-605. Diagnosing diabetes and learning about prediabetes. American Diabetes Association website. Available at: www.diabetes.org/diabetes-basics/diagnosis. Accessed September 21, 2017.