Anticoagulants and Herbal-Nutritional Supplements

Fed by the insatiable needs of the New-Age must-feel-good self-medicating generation, the past decade has seen an explosion in the commerce and popularity of alternative therapies and countless over-the-counter supplements and herbal products. Its use in the older patient population has brought consequent concerns on potential interactions with their often already complicated regimens of prescription drugs. Conflating the problem, patients are often hesitant to inform their physicians of their use of supplements and herbal products ­  their use of herbals and supplements often misguided and misinformed by the grapevine of word-of-mouth and cybermongers. Physicians, on the other hand, are often unable to provide the necessary guidance and information that will assist patients in maneuvering through the maze of alternative and supplementary therapies. In patients on anticoagulant therapy, this information becomes critically important. Patients should be encouraged to inform their health care providers of their use of herbals and supplements and this information should be reviewed and regularly up-dated on subsequent follow-up visits.
SUPPLEMENTS AND HERBALS
THAT DECREASE ANTICOAGULANT EFFECT OF WARFARIN
Coenzyme Q 10
A provitamin found in all tissues of the body with increased concentrations in the heart, liver, and pancreas. Essential for certain metabolic reactions, its cardiac use stems from its antioxidant effects, stabilization of the NaK-ATPase and its effects on calcium channels. It has been used for congestive heart failure, angina, ventricular arrhythmias.
Anticoagulant effect: The decrease in INR ­ which can be significant ­ may be due to its structural similarity to vitamin K2 (menaquinone) which may be antagonistic to warfarin effects.
Ginseng
The mechanism for its interaction with warfarin is not known, but possibly, it may be warfarin antagonism from an active ingredient, gensenosides.
Green Tea
Recently hyped and promoted for its anticancer, cardioprotective and positive cognitive and gastrointestinal effects, dried green tea leaves contain a significant amount of vitamin K - one of the highest among foodstuff - that is antagonistic to warfarin.
Other herbals and supplements
Vitamin C may attenuate the effect of warfarin. Foods containing vitamin K, a natural antagonist of warfarin, can weaken its effect. Besides green tea, dark green leafy vegetables - spinach, collard greens, broccoli, and brussels sprouts - are rich in vitamin K. Cabbage and raw forms of vegetables like endives, green scallions, green mustard, green turnips and watercress have high vitamin K1 content. Patients should maintain a constant consumption of these foods to minimize a yo-yo effect on the INR. Of the oils, canola and soybean have a higher content of vitamin K1 compared to peanut, safflower, sesame and sunflower oils. Nutritional supplements like Ensure and Isocal also contain vitamin K. Verbana officinalis, juniper and passionflower contain vitamin K and can decrease the anticoagulant effect of warfarin. St. John's wort, goldenseal, and yarrow have been reported to decrease the effects of coumadin.
SUPPLEMENTS AND HERBALS
THAT INCREASE ANTICOAGULANT EFFECT OF WARFARIN
Garlic
Isolated reports have suggested that garlic may decrease platelet aggregation; thus, combined use with anticoagulants may increase the risk of bleeding.
Ginger
Ginger (zingiber officinale) may decrease thromboxane production and prolong bleeding time. Therefore, it should be used with caution by patients receiving anticoagulant therapy.
Feverfew
Feverfew (Tanacetum parthenium), used in the treatment of migraines, fever and menstrual problems, appears to inhibit platelet activity and should be used with caution by patients receiving anticoagulant therapy.
Ginkgo biloba
Ginkgo is promoted to treat Alzheimer's disease and dementia, improve memory and cognitive function, cerebral and peripheral blood flow, tinnitus and vertigo. Ginkgo therapy has been associated with decreased platelet aggregation and spontaneous bleeding, and should be used with caution by patients receiving anticoagulants, vitamin E, aspirin, NSAIDs and other drugs or herbal supplements with antiplatelet or anticoagulant effects.
Grape seed
Grape seed extract may have antiplatelet effects. If a patient is having elective surgery, it may be prudent to stop the supplement 2 to 3 days before surgery. Monitor PT and INR.
Kava
Kava has been used for the treatment of anxiety and insomnia. The pharmacologic actions are believed to be due to compounds called kavalactones found in its roots. A specific kavalactone, kawain, appears to decrease thromboxane 2 production and inhibit cyclo-oxygenase, indicating that kava may have significant inhibitory effect on platelet aggregation.
Papain
An extract of enzymes from papaya, papain (carica papaya) has been used for a variety of a ailments: diarrhea, edema, symptoms of herpes zoster and psoriasis. Few reports have been made of a significant increase in INR which resolved on discontinuance of papain use.
Danshen
Also known as tan seng, danshen from the root of
Salvia miltiorrhiza, has been promoted to reduce blood pressure, promote myocardial contractility and coronary vasodilation, improve the microcirculation. Its anticoagulant effect is through the suppression of thromboxane production and inhibition of platelet aggregation, protecting against myocardial ischemia. It is widely used alone or in combination with other herbs and a common ingredient in many cardiotonic herbal preparations. Patients taking it may not be aware of its effects on anticoagulant medications. It is available in tablet and in nebulizer forms, and in China, incorporated into some brands of cigarettes. The extract of danshen root, as well as its other forms, may also increase the absorption and reduce the elimination half-life of warfarin.
Dong quai
Dong quai (Angelica sinensis) contains coumarin derivatives that promote vasodilation and uterine stimulation, as well as antiinflammatory, antipyretic, antispasmodic and estrogen-like effects. It has been primarily promoted for the management of menstrual and menopausal symptoms. Its antithrombotic effect is through inhibition of platelet aggregation and activation.
Other herbals and supplements
Avoid herbal teas containing tonka beans, melilot (sweet clover), or sweet woodruff since these products contain natural coumarin derivatives. Other herbal products contain coumarin derivations that may cause an increase in INR: alfalfa, anise, arnica, artemesia, asa foetida, bogbean, bromelains, capsicum, celery, chamomile, fenugreek, horse chestnut, licorice, parsley, passionflower, prickly ash, quassia, and red clover. Some herbals may increase the risk of bleeding from inhibition of platelet aggregation, for example: cassio, clove, feverfew, ginger, onion and tumeric. Meadowsweet, poplar and willow bark contain salicylate derivatives that may also increase the risk of bleeding.
Vitamin E has a weak antiplatelet effect and in doses above 800 mg/d may potentiate the action of warfarin. Chondroitin sulfate may have a mild blood-thinning effect and should probably not be taken by patients using anticoagulants. Chamomile contains a coumarin ingredient; it is unknown whether it affects coagulation or if there is significant interaction between chamomile and warfarin; monitoring is indicated. Other supplements that may reinforce warfarin effect are: ganoderma japonicum, papaw, salvia miltorrhiza, devil's claw, quinine, and horse-chestnut.
 
Physicians who suspect serious interactions of drugs such as warfarin with any herbal products are encouraged to report them through the FDA Medwatch system Web site at http://www.fda.gov or to call (800) FDA-1088 or fax (800) FDA-0178.

SOURCES
Consultation and Comments: Danshen, another herb patients don't tell their physicians about: Consultant, May 2004
Herbal Therapeutics (Kava): Top 12 Remedies-R.W. Watkins, Md, Emergency Medicine April 2002 (www.emedmag.com)
Warfarin has multiple drug interactions: Barbara S,. Wiggins, PharmD, Today in Cardiology, May 2002
Smolinske SC. Dietary supplement-drug interactions. J Am Med Womens Assoc. 1999;54:191-192.
Fugh-Berman A. Herb-drug interactions. Lancet. 2000;355:134-138.
Interactions between warfarin and nutritional supplements: PATIENT CARE / Aug 15, 2000 <www.patientcareonline.com>
Professional Guide to Complementary & Alternative Therapies. Springhouse. 2001