Lucy Dey

Brief communication: American ginseng reduces warfarin's effect in healthy patients: a randomized, controlled Trial.

Context Consuming ginseng, a commonly used herbal dietary supplement, has been associated with a decrease in warfarins anticoagulant effect in at least 1 case report. Contribution Healthy volunteers took warfarin with and without concurrently taking ginseng. Ginseng consumption lowered the international normalized ratio and decreased plasma warfarin levels. Cautions Patients and physicians should be aware that ginseng is among many substances that can interfere with warfarins anticoagulant effect. The Editors The beneficial effects of several commonly used botanicals have been documented (1), but data on the safety of these herbs are limited. At least 16% of people using prescription medication concurrently take herbal supplements. An estimated 15 million Americans are at risk for herbdrug interactions (2). Advocated for almost every purpose, including maintaining general health, combating fatigue, and improving immune function (3), ginseng is one of the best-selling herbs in the United States (4). Herbs such as ginseng may interact with medications that have a narrow therapeutic index, such as warfarin, a commonly used oral anticoagulant (5, 6). A widely cited case report showed a substantial decrease in the anticoagulant effect of warfarin after ginseng consumption in a patient who was previously maintained with stable warfarin therapy (7). We conducted a randomized, double-blind, placebo-controlled trial to evaluate the potential interactions between American ginseng and warfarin. Methods Patients Nine men and 11 nonpregnant women (who were paid

Anti-hyperglycemic effects of ginseng: Comparison between root and berry

250 after trial completion) were enrolled in this study. Patients were screened with a medical history, physical examination, 12-lead resting electrocardiography, complete blood and platelet counts, international normalized ratio (INR) (the prothrombin time testcontrol ratio) (8), blood chemistry tests, and urinalysis. Patients agreed to abstain from tobacco products for at least 2 weeks before and during the study, abstain from alcohol and other medications during the study, and limit caffeine-containing products for 48 hours before and during the study. Protocol The institutional review board approved this 4-week study conducted at the University of Chicago Medical Center, Chicago, Illinois. All patients provided written, informed consent. Patients received oral warfarin, 5 mg daily, for the first 3 consecutive days during week 1. Beginning in week 2, patients were randomly assigned to receive either oral American ginseng, 1.0 g, or placebo, twice daily, for 3 consecutive weeks. During week 4, all patients again received oral warfarin, 5 mg daily, for the first 3 consecutive days (Appendix Figure). Ginseng or placebo assignment was determined by a table of random numbers with blocks of 8 (4 ginseng and 4 placebo assignments per block), from which sealed, opaque envelopes were prepared and opened sequentially as patients were enrolled in the study. A biostatistician who did not acquire data prepared the assignments. Patients and investigators were blinded to the treatment groups. Patients were instructed to eat a balanced diet to maintain a consistent amount of vitamin K and to avoid drastic changes in dietary habits. The daily intake of vitamin Kcontaining foods was recorded 1 week before the study to obtain the baseline value and to adjust the diet if vitamin K intake was high. Patients recorded their daily diet throughout the study period, completed a written weekly questionnaire, and were asked to report any adverse events. Blood samples were obtained at the same time (0.5 hour) on days 1, 3, 4, 5, and 7 of weeks 1 and 4 to measure INR and plasma warfarin levels (detection limit, 0.1 g/mL). Study Drugs Warfarin (3-(-acetonylbenzyl)-4-hydroxycoumarin or Coumadin, DuPont Pharmaceuticals, Wilmington, Delaware) is a racemic mixture composed of equal amounts of 2 optical isomers. In our laboratory, we ground the root of American ginseng (Panax quinquefolius, Wisconsin Ginseng Board, Wausau, Wisconsin) from 1 lot into a fine powder and placed 0.5 g in nontransparent capsules. Using a high-performance liquid chromatography method, we found that the total ginsenoside content was 5.19%. The constituent split was as follows: ginsenoside Rb1, 1.93%; Rb2, 0.20%; Rc, 0.61%; Rd, 0.42%; Re, 1.68%; and Rg1, 0.35%. We prepared identical placebo capsules that contained cornstarch powder. Statistical Analysis The primary end point of this study was the change in peak INR (week 4 week 1). Additional analysis end points were change in INR area under the curve (AUC) (week 4 week 1), defined as the area under the INR versus time curve; change in peak plasma warfarin level; change in warfarin AUC (week 4 week 1), defined as the area under the plasma warfarin level versus time curve; and weekly vitamin K intake. The AUC was calculated on the basis of the trapezoidal rule by using measurements for days 1 through 7. We compared changes in peak INR, INR AUC, peak plasma warfarin level, and warfarin AUC between the ginseng and placebo groups by using the Wilcoxon rank-sum test. We calculated the difference in median changes between the 2 groups and corresponding 95% CIs according to the method described by Hollander and Wolfe (9), which is based on consideration of all pairwise differences between the 2 sets of observations. We calculated the Spearman rank correlation coefficients to examine the correlation between the change in peak INR and change in peak plasma warfarin levels. Repeated-measures analysis of variance (ANOVA) models were used to test differences in vitamin K intake between the groups and over time. A P value less than 0.05 was considered statistically significant. Stata, version 8 (Stata Corp., College Station, Texas), and Minitab, version 13 (Minitab, Inc., State College, Pennsylvania), were used for statistical analysis. Role of the Funding Sources The funding sources had no role in the collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Results Data from all 20 patients (12 patients in the ginseng group and 8 patients in the placebo group) were used in the analysis. For the 6 men and 6 women in the ginseng group (7 patients were white, 3 patients were black, 1 patient was Hispanic, and 1 patient was Asian), the mean age and body weight (SD) were 30.2 7.2 years and 69.220.6 kg, respectively. For the 3 men and 5 women in the placebo group (3 patients were white, 2 patients were black, 2 patients were Hispanic, and 1 patient was Asian), the mean age and body weight (SD) were 24.3 4.0 years and 62.09.1 kg, respectively (Appendix Table). In both groups, INR generally reached peak levels on day 4 after 3 consecutive days of warfarin administration. The Figure shows changes in individual peak INR, INR AUC, peak plasma warfarin level, and warfarin AUC from weeks 1 to 4. The modest reduction in INR magnitude in the ginseng group was statistically significant compared with the change in the placebo group (P= 0.0012). Changes in INR AUC, peak plasma warfarin level, and warfarin AUC were also statistically significantly greater in the ginseng group. The Table summarizes results for the primary and secondary end points. Figure. Changes in individual peak international normalized ratio ( INR ), INR area under the curve ( AUC ), peak plasma warfarin level, and warfarin AUC in weeks 1 and 4 in American ginseng or placebo groups. A. P B. P C. P D. P Appendix Figure. Study flow chart showing American ginseng and placebo dosing and blood sample collection. Table. Changes in Peak International Normalized Ratio, International Normalized Ratio Area under the Curve, Peak Plasma Warfarin Level, and Warfarin Area under the Curve between Weeks 1 and 4 in American Ginseng and Placebo Groups Appendix Table. Patient Information For both peak warfarin level and AUC, the changes in the placebo group were not statistically significant and therefore probably reflected random variation in the small sample size. The Spearman rank correlation coefficient between changes in peak INR values and changes in peak warfarin levels was 0.72 (P< 0.001). One patient (patient 18) in the ginseng group had a high baseline INR (1.32) on day 1 compared with that in the other patients (mean INR [SD], 0.94 0.04). For this patient, peak INR after warfarin administration on day 4 was 5.16. After ginseng administration, the peak INR was 2.75 and the corresponding AUC decreased from 17.46 to 11.1. The patients peak plasma warfarin level also decreased from 1.6 g/mL during week 1 to 0.9 g/mL in week 4. If this patient is excluded from the analysis, the results remain statistically significant. No unusual medical or drug history or diet was noted for this patient. For weeks 1, 2, 3, and 4, average daily vitamin K intake (SD) for the ginseng group was 32.3 5.2 g/d, 42.6 7.6 g/d, 41.9 8.6 g/d, and 34.0 5.5 g/d, respectively. The average daily vitamin K intake (SD) for the placebo group for weeks 1, 2, 3, and 4 was 36.4 11.2 g/d, 32.0 8.4 g/d, 39.5 8.7 g/d, and 38.6 11.4 g/d, respectively. Vitamin K intake did not statistically significantly differ between the 2 groups (P> 0.2) or over time (P> 0.2). No adverse effects of clinical importance occurred in this study. Discussion Among the several different species of ginseng, the major active components are ginsenosides, which are a diverse group of steroidal saponins (3). Ginseng may promote bleeding in surgical patients (6). Ginsenosides prolonged both thrombin time and activated partial thromboplastin time in rats (10) and inhibited platelet aggregation in vitro in human platelets (11). In our healthy patients, however, ginseng reduced the anticoagulant effect of warfarin. We selected the commonly consumed American ginseng and a dose at the high end of the recommended range (12). Warfarin indirectly interferes with blood clotting by depressing the hepatic synthesis of vitamin Kdependent coagulation factors. The atte

Ginseng berry reduces blood glucose and body weight in db/db mice

Previous studies demonstrated that both ginseng root and ginseng berry possess anti-diabetic activity. However, a direct comparison between the root and the berry under the same experimental conditions has not been conducted. In the present study, we compared anti-hyperglycemic effect between Panax ginseng root and Panax ginseng berry in ob/ob mice, which exhibit profound obesity and hyperglycemia that phenotypically resemble human type-2 diabetes. We observed that ob/ob mice had high baseline glucose levels (195 mg/dl). Ginseng root extract (150 mg/kg body wt.) and ginseng berry extract (150 mg/kg body wt.) significantly decreased fasting blood glucose to 143 +/- 9.3 mg/dl and 150 +/- 9.5 mg/dl on day 5, respectively (both P < 0.01 compared with the vehicle). On day 12, although fasting blood glucose level did not continue to decrease in the root group (155 +/- 12.7 mg/dl), the berry group became normoglycemic (129 +/- 7.3 mg/dl; P < 0.01). We further evaluated glucose tolerance using the intraperitoneal glucose tolerance test. On day 0, basal hyperglycemia was exacerbated by intraperitoneal glucose load, and failed to return to baseline after 120 min. After 12 days of treatment with ginseng root extract (150 mg/kg body wt.), the area under the curve (AUC) showed some decrease (9.6%). However, after 12 days of treatment with ginseng berry extract (150 mg/kg body wt.), overall glucose exposure improved significantly, and the AUC decreased 31.0% (P < 0.01). In addition, we observed that body weight did not change significantly after ginseng root extract (150 mg/kg body wt.) treatment, but the same concentration of ginseng berry extract significantly decreased body weight (P < 0.01). These data suggest that, compared to ginseng root, ginseng berry exhibits more potent anti-hyperglycemic activity, and only ginseng berry shows marked anti-obesity effects in ob/ob mice.

Anti-diabetic effects of Gymnema yunnanense extract

In this study, we observed anti-diabetic and anti-obesity effects of Panax ginseng berry in adult C57BL/Ks db/db mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract at 150 mg/kg body wt. for 12 consecutive days. On Day 5, the extract-treated db/db mice had significantly lower fasting blood glucose levels as compared to vehicle-treated mice (180.5+/-10.2 mg/dl vs. 226.0+/-15.3 mg/dl, P < 0.01). On day 12, the extract-treated db/db mice were normoglycemic (134.3+/-7.3 mg/dl) as compared to vehicle-treated mice (254.8+/-24.1 mg/dl; P < 0.01). Fasting blood glucose levels of lean mice did not decrease significantly after treatment with extract. After 12 days of treatment with the extract, glucose tolerance increased significantly, and overall blood glucose exposure calculated as area under the curve (AUC) decreased 53.4% (P < 0.01) in db/db mice. Furthermore, db/db mice treated with extract (150 mg/kg body wt.) showed weight loss from 51.0+/-1.9 g on Day 0, to 46.6+/-1.7 g on Day 5, and to 45.2+/-1.4 g on Day 12 (P < 0.05 and P < 0.01 compared to Day 0, respectively). The body weight of lean littermates also decreased at the same dose of extract. These data suggest that Panax ginseng berry extract may have therapeutic value in treating diabetic and obese patients.

Alternative Therapies for Male and Female Sexual Dysfunction

In this study, we evaluated anti-hyperglycemic effect and body weight reduction activity of Gymnema yunnanense extract in obese ob/ob and diabetic db/db mice. Animals received daily intraperitoneal injections of the extract 100 mg/kg for 12 days. On Day 5, the extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to vehicle-treated mice (161+/-14.5mg/dl versus 238+/-21.5mg/dl, P<0.01). On Day 12, the extract-treated ob/ob mice had normal fasting blood glucose levels, compared with vehicle-treated mice (119+/-3.3mg/dl versus 240+/-12.9 mg/dl, P<0.01). Glucose tolerance improved significantly. This was demonstrated by overall glucose excursion calculated as area under the curve (AUC) during the 2h intraperitoneal glucose tolerance test (IPGTT), which decreased by approximately 22% (P<0.01) compared to vehicle-treated ob/ob mice. In addition, extract-treated ob/ob mice lost weight significantly from 51.7+/-1.9 g on Day 0 to 45.7+/-1.2g on Day 12 (P<0.05 compared to vehicle-treated mice). In db/db mice, after treatment with same dose of the extract, fasting blood glucose levels also decreased significantly from Day 0 of 247+/-13.9 mg/dl to Day 5 of 172+/-7.5mg/dl and to Day 12 of 190+/-2.7 mg/dl (both P<0.01 compared to vehicle-treated group from Day 0 of 239+/-12.1mg/dl to Day 5 of 230+/-8.5mg/dl and Day 12 of 247+/-18.9 mg/dl, respectively). After 12 days of extract treatment, body weight in db/db mice reduced from 61.8+/-1.4 g on Day 0 to 59.8+/-1.1g on Day 12 (P<0.05). Our results support an in vivo anti-hyperglycemic and body weight reduction activity of G. yunnanense extract that may prove to be of clinical importance in improving the management of type 2 diabetes.

Transcutaneous Electrical Acupoint Stimulation Potentiates Analgesic Effect of Morphine

Sexual dysfunction is prevalent in both men and women. Although new pharmaceutical agents have been identified for male erectile problems, sexual desire and orgasm disorders, individuals with sexual dysfunction often seek alternative therapies, including traditional Chinese medicine. This article reviews currently used alternative therapies, such as herbal medications, L-arginine, acupuncture, biofeedback and others. Potential herb-drug interactions are also presented.

Analgesic Effects of Different Acupoint Stimulation Frequencies in Humans

Pain is the major complaint of patients who choose acupuncture treatment. Transcutaneous electrical acupoint stimulation (TEAS) provides a safe, standardized technique without needle insertion. TEAS can be tested with the cold‐pressor test, a simple, reliable, and widely used model in humans for the induction of tonic pain. In this controlled study, the effects of TEAS on cold‐pressor‐induced pain were evaluated in 20 healthy human subjects. Electrical stimulation electrodes were applied to He‐Gu (LI 4) and Nui‐Guan (P 6) acupoints. The effects of saline plus no TEAS, 15‐minute TEAS alone, 0.05 mg/kg morphine alone, and 15‐minute TEAS plus morphine were assessed. Pain score ratings were evaluated at four time points from 30 to 170 seconds during the cold‐pressor test. The authors observed analgesic effects in both TEAS‐alone and morphine‐alone sessions, and pain score rating reductions were statistically significant compared to unstimulated control (both p < 0.01). The degree of TEAS analgesia combined with 0.05 mg/kg morphine was significantly higher than TEAS alone (p < 0.01). The results support the efficacy of TEAS analgesia and suggest that combination of TEAS with low‐dose morphine can achieve better pain control in a variety of clinical settings.

Antidiabetic Effects of Panax ginseng Berry Extract and the Identification of an Effective Component

Transcutaneous electrical acupoint stimulation (TEAS) provides a convenient and standardized technique for pain treatment. The cold-pressor test is a simple and reliable model in humans for the induction of tonic pain. In this controlled study, the effects of TEAS on cold pressor-induced pain were evaluated in 22 healthy human subjects. Electrical stimulation at 4 Hz and 32 Hz was applied to He-Gu (LI 4) and Nui-Guan (P 6) acupoints for 15 minutes. Pain score ratings were evaluated at four time points from 30-170 seconds during the cold-pressor test. We observed an analgesic effect at both 4 Hz and 32 Hz of stimulation, and pain score rating reductions were statistically significant compared to control (p < 0.01). Our data support the efficacy of TEAS analgesia. However, there was no significant difference between pain scores at 4 Hz and 32 Hz stimulation.