Reasonable Rascal
07-16-04, 20:21
Ginseng Reduces Warfarin Efficacy
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
July 6, 2004 — American ginseng, a widely used herbal supplement, inhibits the anticoagulant effect of warfarin, according to the results of a randomized trial published in the July 6 issue of the Annals of Internal Medicine.
"Warfarin has a narrow therapeutic index, which means precise dosing is crucial," lead author Chun-Su Yuan, MD, PhD, from the University of Chicago in Illinois, says in a news release. "A substance, such as ginseng, that alters warfarin's effects, even slightly, can have significant consequences."
In this double-blind, four-week trial, 20 healthy volunteers received warfarin, 5 mg, daily for three days during week one and week four. Beginning in week two, 12 subjects took 2 g of powdered ginseng in capsules, while the other eight volunteers received placebo capsules.
After two weeks, daily doses of ginseng significantly reduced the blood levels and the anticoagulant effects of warfarin. Peak international normalized ratio (INR) decreased after two weeks of ginseng compared with placebo (difference, -0.19; 95% confidence interval, -0.36 to -0.07; P = .001).
Compared with the placebo group, the ginseng group had significantly reduced INR area under the curve (AUC), peak plasma warfarin level, and warfarin AUC. Peak INR was positively correlated with peak plasma warfarin level.
The main study limitation is possible lack of generalizability to patients taking therapeutic doses of warfarin because this study was done in young, healthy subjects.
"Whether ginseng interferes with other hepatically metabolized drugs remains to be evaluated," the authors write. "When prescribing warfarin, physicians should ask patients about ginseng use."
The National Institutes of Health and the Tang Center for Herbal Medicine Research funded this study.
Ann Intern Med. 2004;141:23-27
Clinical Context
At least 16% of people using prescription medication in the U.S. concurrently take herbal supplements. An estimated 15 million Americans are at risk of herb-drug interactions according to a study by Kaufman and colleagues reported in the January 2002 issue of JAMA. Ginseng is one of the most commonly used herbals. Both case reports and animal studies have suggested that ginseng may reduce the anticoagulant effect of warfarin. However, a report by Ang-Lee and colleagues published in the July 2001 issue of JAMA suggests that ginseng may promote bleeding in surgical patients. Ginsenosides were shown in rats to prolong prothrombin time and activated thromboplastin time in a study by Park and colleagues in the November 1996 issue of the Biological and Pharmaceutical Bulletin.
The authors of this four-week blinded, randomized controlled study used healthy, young volunteer subjects not receiving therapeutic doses of warfarin and who were paid U.S. $250 to determine the drug-herb interaction between ginseng and warfarin. This is the first randomized study on a ginseng-drug interaction.
Study Highlights
· 9 men and 11 nonpregnant women were screened with medical history, physical examination, electrocardiogram, chemistry, urinanalysis, and INR and randomized to receive either 2.0 g of American ginseng (n = 12) or identical-looking placebo (n = 8) as capsules for two weeks.
· The ginseng preparation used was ground root of America ginseng (Panax quinquefolias, Wisconsin ginseng Board) in a fine powder with 0.5 g per capsule. Total ginsenoside content was 5.19% by liquid chromatography.
· Patients maintained a consistent intake of dietary vitamin K, recorded daily diet, completed a weekly questionnaire, and reported any adverse events. They abstained from smoking, alcohol, and other medications during the study.
· The week prior to and the week after ginseng or placebo intake, patients were given 5 mg of oral warfarin daily for 3 consecutive days.
· Patients and investigators were blinded to assignment.
· Primary outcome was change in peak INR between week 4 and week 1.
Secondary outcomes were AUC (week 4 to week 1), change in peak warfarin level, change in warfarin AUC, and weekly vitamin K intake.
· Blood tests were performed on days 1, 3, 4, 5, and 7 of weeks 1 and 4.
· In the ginseng group, the 6 men and 6 women had a mean age of 30 years and mean body weight of 69 kg. In the placebo group, the 3 men and 5 women had a mean age of 24 years and mean body weight of 62 kg. Half the volunteers were white.
· In both groups, INR reached peak levels on day 4 after 3 consecutive days of warfarin.
· There was a modest but significant decrease in INR in the ginseng group compared with placebo (-0.19; P = .001).
· INR AUC was reduced by 0.43 in the ginseng compared with the placebo group (P = .02).
· The difference in peak plasma warfarin level was -0.20 μg/mL between the ginseng and placebo groups (P = .03).
· Daily vitamin K intake did not differ between the two groups over time.
· No adverse clinical effects were reported by volunteers.
· Peak INR and peak plasma warfarin level were positively correlated.
Pearls for Practice
· American ginseng reduces the anticoagulant effect of warfarin in health young subjects.
· When prescribing warfarin, physicians should ask patients about ginseng use.
Medscape Medical News 2004
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
July 6, 2004 — American ginseng, a widely used herbal supplement, inhibits the anticoagulant effect of warfarin, according to the results of a randomized trial published in the July 6 issue of the Annals of Internal Medicine.
"Warfarin has a narrow therapeutic index, which means precise dosing is crucial," lead author Chun-Su Yuan, MD, PhD, from the University of Chicago in Illinois, says in a news release. "A substance, such as ginseng, that alters warfarin's effects, even slightly, can have significant consequences."
In this double-blind, four-week trial, 20 healthy volunteers received warfarin, 5 mg, daily for three days during week one and week four. Beginning in week two, 12 subjects took 2 g of powdered ginseng in capsules, while the other eight volunteers received placebo capsules.
After two weeks, daily doses of ginseng significantly reduced the blood levels and the anticoagulant effects of warfarin. Peak international normalized ratio (INR) decreased after two weeks of ginseng compared with placebo (difference, -0.19; 95% confidence interval, -0.36 to -0.07; P = .001).
Compared with the placebo group, the ginseng group had significantly reduced INR area under the curve (AUC), peak plasma warfarin level, and warfarin AUC. Peak INR was positively correlated with peak plasma warfarin level.
The main study limitation is possible lack of generalizability to patients taking therapeutic doses of warfarin because this study was done in young, healthy subjects.
"Whether ginseng interferes with other hepatically metabolized drugs remains to be evaluated," the authors write. "When prescribing warfarin, physicians should ask patients about ginseng use."
The National Institutes of Health and the Tang Center for Herbal Medicine Research funded this study.
Ann Intern Med. 2004;141:23-27
Clinical Context
At least 16% of people using prescription medication in the U.S. concurrently take herbal supplements. An estimated 15 million Americans are at risk of herb-drug interactions according to a study by Kaufman and colleagues reported in the January 2002 issue of JAMA. Ginseng is one of the most commonly used herbals. Both case reports and animal studies have suggested that ginseng may reduce the anticoagulant effect of warfarin. However, a report by Ang-Lee and colleagues published in the July 2001 issue of JAMA suggests that ginseng may promote bleeding in surgical patients. Ginsenosides were shown in rats to prolong prothrombin time and activated thromboplastin time in a study by Park and colleagues in the November 1996 issue of the Biological and Pharmaceutical Bulletin.
The authors of this four-week blinded, randomized controlled study used healthy, young volunteer subjects not receiving therapeutic doses of warfarin and who were paid U.S. $250 to determine the drug-herb interaction between ginseng and warfarin. This is the first randomized study on a ginseng-drug interaction.
Study Highlights
· 9 men and 11 nonpregnant women were screened with medical history, physical examination, electrocardiogram, chemistry, urinanalysis, and INR and randomized to receive either 2.0 g of American ginseng (n = 12) or identical-looking placebo (n = 8) as capsules for two weeks.
· The ginseng preparation used was ground root of America ginseng (Panax quinquefolias, Wisconsin ginseng Board) in a fine powder with 0.5 g per capsule. Total ginsenoside content was 5.19% by liquid chromatography.
· Patients maintained a consistent intake of dietary vitamin K, recorded daily diet, completed a weekly questionnaire, and reported any adverse events. They abstained from smoking, alcohol, and other medications during the study.
· The week prior to and the week after ginseng or placebo intake, patients were given 5 mg of oral warfarin daily for 3 consecutive days.
· Patients and investigators were blinded to assignment.
· Primary outcome was change in peak INR between week 4 and week 1.
Secondary outcomes were AUC (week 4 to week 1), change in peak warfarin level, change in warfarin AUC, and weekly vitamin K intake.
· Blood tests were performed on days 1, 3, 4, 5, and 7 of weeks 1 and 4.
· In the ginseng group, the 6 men and 6 women had a mean age of 30 years and mean body weight of 69 kg. In the placebo group, the 3 men and 5 women had a mean age of 24 years and mean body weight of 62 kg. Half the volunteers were white.
· In both groups, INR reached peak levels on day 4 after 3 consecutive days of warfarin.
· There was a modest but significant decrease in INR in the ginseng group compared with placebo (-0.19; P = .001).
· INR AUC was reduced by 0.43 in the ginseng compared with the placebo group (P = .02).
· The difference in peak plasma warfarin level was -0.20 μg/mL between the ginseng and placebo groups (P = .03).
· Daily vitamin K intake did not differ between the two groups over time.
· No adverse clinical effects were reported by volunteers.
· Peak INR and peak plasma warfarin level were positively correlated.
Pearls for Practice
· American ginseng reduces the anticoagulant effect of warfarin in health young subjects.
· When prescribing warfarin, physicians should ask patients about ginseng use.
Medscape Medical News 2004