Clinical Briefs

With Comments from Russell H. Greenfield, MD

Ginseng and Warfarin

Source: Yuan CS, et al. Brief communication: American ginseng reduces warfarin’s effect in healthy patients. Ann Intern Med 2004;141:23-27.

Goal: To evaluate whether American ginseng interacts with warfarin.

Design: Randomized, double-blind, placebo-controlled study completed over four weeks.

Subjects: Twenty healthy subjects (nine men and 11 nonpregnant women, 10 Caucasians) each paid $250 at study’s end.

Methods: After initial screening, subjects received oral warfarin 5 mg daily for the first three days of week 1. During the second week, participants were randomly selected to receive either 2 g of American ginseng orally, or placebo, daily for three consecutive weeks. During the first three days of the last week of the study, all subjects were again given 5 mg warfarin daily. Participants recorded their food intake and filled out a questionnaire each week. Blood was drawn for International Normalized Ratio (INR) and plasma warfarin levels on days 1, 3, 4, 5, and 7 of the first and last week of the study. The primary endpoint was change in peak INR from week 1 to week 4.

Results: A small, but statistically significant, reduction in peak INR occurred in those subjects using American ginseng as compared to the placebo group. Lower results were likewise obtained in the ginseng group for INR area under the curve (AUC), peak plasma warfarin level, and warfarin AUC. Peak INR was correlated with peak plasma warfarin level.

Conclusion: American ginseng lessens the anticoagulant effect of warfarin.

Study strengths: All subjects completed the trial; close follow-up and laboratory evaluation; standardized dose of ginseng.

Study weaknesses: Small sample size; lack of generalizability (subjects were all healthy, while patients receiving warfarin generally are not); atypical dosing schedule.

Of note: Ginseng is one of the best-selling herbs in the country, but three different plants with varied medicinal activities are commonly sold as ginseng: Panax ginseng (Asian ginseng), Panax quinquefolius (American ginseng), and Eleutherococcus senticosus (known as Eleuthero or Siberian ginseng, although not technically a ginseng); ginseng is classified as an adaptogen or a restorative tonic that balances bodily functions; subjects maintained a consistent dietary intake of vitamin K throughout the study and did not use other medications; all ginseng used in the study came from the same lot with an acceptable ginsenoside content (5.19%); 12 subjects were randomized to receive ginseng, while eight ingested the placebo; the researchers used a dose of American ginseng at the high end of the recommended range.

We knew that: Approximately 16% of people in the United States using prescription drugs are also using botanicals, meaning that upwards of 15 million people are at risk for herb-drug interactions; warfarin acts by impairing production of vitamin K-dependent coagulation factors in the liver; ginsenosides (triterpenoid saponins) appear to be the major active constituents of ginseng.

Clinical import: As the authors point out, warfarin possesses a narrow therapeutic index and its use is associated with risk of bleeding. Taking additional agents that may lessen warfarin’s anticoagulant activity may place patients at risk in the opposite fashion, by leaving them with an INR in the sub-therapeutic range. One published report cites decreased anticoagulant activity in a patient previously stabilized on warfarin therapy after using Asian ginseng, and now we have suggestion of American ginseng use potentially causing the same problem, albeit in healthy subjects using an unusual dosing schedule. That stated, the effect of American ginseng on the INR noted in this study is clinically very small (the decrease in peak INR with ginseng compared to placebo at study’s end was 0.19). Still, it is prudent to inquire about botanical medicine use, including use of American ginseng, in patients taking warfarin, especially those with whom there is difficulty maintaining a therapeutic INR.

What to do with this article: Keep a copy of the abstract on your computer.

Dr. Greenfield, Medical Director, Carolinas Integrative Health Carolinas HealthCare System Charlotte, NC, is Executive Editor of Alternative Medicine Alert.