Warfarin

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Warfarin

Interactions with Vitamins

Bromelain

In theory, bromelain might enhance the action of anticoagulants. This theoretical concern has not been substantiated by human research, however.

Coenzyme Q10 (CoQ10) is structurally similar to vitamin K and may affect blood coagulation. Four case reports describe possible interference by CoQ10 with warfarin activity. It remains unknown how common or rare this interaction is. Those taking warfarin should only take CoQ10 with the guidance of their doctor.

Minerals

Iron, magnesium, and zinc may bind with warfarin, potentially decreasing their absorption and activity. People on warfarin therapy should take warfarin and iron/magnesium/zinc-containing products at least two hours apart.

Papain

Papain, an enzyme extract of papaya, was associated with increased warfarin activity in one patient. Persons taking warfarin should avoid papain supplements until further information about this potential interaction becomes available.

Vitamin C

Although case reports have suggested that vitamin C might increase the activity of anticoagulants in a potentially dangerous way, this interaction has not been confirmed in research studies. In fact, a possible interference by vitamin C with the effect of anticoagulants has also been reported. A 52-year-old woman maintained on 7.5 mg of warfarin per day had a shortening of the blood clotting time which was not corrected by increasing warfarin up to 20 mg per day. Further questioning revealed she had begun taking an unspecified amount of vitamin C each morning. After stopping vitamin C, the blood clotting time returned to desired levels. Based on this and other case reports, people taking warfarin should consult with their physician before taking vitamin C supplements.

Vitamin D

In 1975, a single letter to the Journal of the American Medical Association suggested that vitamin D increases the activity of anticoagulants and that this interaction could prove dangerous. However, there have been no other reports of such an interaction, even though tens of millions of people are taking multivitamins that contain vitamin D. Most doctors typically do not tell patients taking anticoagulant medications to avoid vitamin D.

Vitamin E

An isolated case was reported in 1974 of vitamin E (up to 1,200 IU per day) being associated with increased anticoagulation (blood thinning) in a patient treated with warfarin. A study of 12 people undergoing warfarin therapy found that additional vitamin E (100 IU or 400 IU per day) did not induce a clinical bleeding state. Moreover, a double-blind trial found that supplementation with vitamin E in amounts up to 1,200 IU per day had no effect on warfarin activity. It now appears safe for people taking warfarin to supplement vitamin E despite information to the contrary often provided by doctors about this purported interaction. These warnings are based on the isolated case report from 1974.

Vitamin K

Warfarin slows blood clotting by interfering with vitamin K activity. Since vitamin K reverses the anticoagulant effects of warfarin, people taking warfarin should avoid vitamin K-containing supplements unless specifically directed otherwise by their prescribing doctor. Some vegetables (broccoli, Brussels sprouts, kale, parsley, spinach, and others) are high in vitamin K. Eating large quantities or making sudden changes in the amounts eaten of these vegetables can interfere with the effectiveness and safety of warfarin therapy. The greener the plant, the higher the vitamin K content. Other significant dietary sources of vitamin K include soybean oil, olive oil, cottonseed oil, and canola oil.

Vitamin K supplementation can be used, however, to counteract an overdose of warfarin. In addition, controlled and continuous supplementation with vitamin K (100 to 150 mcg per day) has been used effectively to reduce the fluctuations in dosage requirement that occur in some people taking warfarin or related drugs that have the same action as warfarin. Such treatment requires a doctor's supervision.

Interactions with Herbs

Asian ginseng�(Panax ginseng)

Asian ginseng was associated with a decrease in warfarin activity in a case report. However, in a clinical trial, no interaction was seen between Asian ginseng and warfarin. An animal study also found no significant interaction between warfarin and pure ginseng extract. Nevertheless, persons taking warfarin should consult with a physician knowledgeable about botanical medicines if they are considering taking Asian ginseng or eleuthero/Siberian ginseng (Eleutherococcus senticosus). A 1999 animal study did not reveal any significant interaction between warfarin and pure ginseng extract.

American ginseng

In a study of healthy human volunteers, supplementing with American ginseng reduced warfarin's anticoagulant effect, apparently by stimulating the body to accelerate the metabolism of warfarin. People taking warfarin should not take American ginseng, unless supervised by a doctor.

Cranberry

There have been at least five case reports suggesting that cranberry juice increases the activity of warfarin, possibly by inhibiting the breakdown of warfarin in the body. Because of this potential interaction, people taking warfarin should avoid, or limit the intake of, cranberry juice. The U.K. Medicines Authority has advised people taking warfarin to avoid cranberry juice.

Dan shen (Salvia miltiorrhiza)

Dan shen, a Chinese herb, was associated with increased warfarin activity in several cases. Dan shen should only be used under close medical supervision by people taking warfarin. Sage�(Salvia officinalis), a plant relative of dan shen found in the West, is not associated with interactions involving warfarin.

Devil�s claw�(Harpagophytum procumbens)

Devil�s claw was associated with purpura (bleeding under the skin) in a patient treated with warfarin. However, key details in this case�including other medications taken and the amounts and duration of warfarin and devil�s claw taken�were not reported, making it impossible to evaluate this reported interaction. Until more is known, people taking warfarin should avoid taking devil�s claw.

Dong quai�(Angelica sinensis)

A 46-year-old woman taking warfarin experienced increased strength of the anticoagulant properties of the drug after starting to use dong quai for menopause. The daily amount of dong quai was 1,130�2,260 mg per day. Her bleeding tendency returned to normal after discontinuing the dong quai. While little is known about the potential interaction of dong quai and warfarin, women should discuss the use of the herb with a healthcare professional if they are taking an anticoagulant drug and wish to use dong quai.

Feverfew�(Tanacetum parthenium)

Although there are no documented cases of feverfew interacting with warfarin in humans, feverfew has been shown to interfere with certain aspects of blood clotting in test tube studies.

Garlic�(Allium sativum)

Garlic has been shown to help prevent atherosclerosis (hardening of the arteries), perhaps by reducing the ability of platelets to stick together. This can result in an increase in the tendency toward bleeding. Standardized extracts have, on rare occasions, been associated with bleeding in people. Garlic extracts have also been associated with two human cases of increased warfarin activity. The extracts were not definitively shown to be the cause of the problem. People taking warfarin should consult with a doctor before taking products containing standardized extracts of garlic or eating more than one clove of garlic daily.

Ginger�(Zingiber officinale)

Ginger has been shown to reduce platelet stickiness in test tubes. Although there are no reports of interactions with anticoagulant drugs, people should consult a healthcare professional if they are taking an anticoagulant and wish to use ginger.

Ginkgo

Ginkgo extracts may reduce the ability of platelets to stick together, possibly increasing the tendency toward bleeding. Standardized extracts of ginkgo have been associated with two cases of spontaneous bleeding, although the ginkgo extracts were not definitively shown to be the cause of the problem. There are two case reports of people taking warfarin in whom bleeding occurred after the addition of ginkgo. People taking warfarin should consult with a physician knowledgeable about botanical medicines if they are considering taking ginkgo.

Goji berry

There is one reported case of increased bleeding tendency in a woman taking warfarin who also drank 3 to 4 glasses per day of goji berry tea.

Grapefruit seed extract

In case reports, ingestion of grapefruit seed extract interfered with the effect of warfarin. This inhibitory effect appeared to be due to benzethonium chloride, a synthetic preservative that is added to most grapefruit seed extract products.

Green tea�(Camellia sinensis)

One man taking warfarin and one-half to one gallon of green tea per day developed signs based on laboratory testing suggesting his blood was too thick because the green tea was blocking the effect of warfarin. Removal of the green tea caused normalization of his blood tests. Those taking green tea and warfarin together should have their blood monitored regularly to avert any problems and should consult with a doctor, healthcare practitioner and/or pharmacist before taking any medication.

Herbs containing coumarin derivatives

Although there are no specific studies demonstrating interactions with anticoagulants, the following herbs contain coumarin-like substances that may interact with warfarin and may cause bleeding. These herbs include angelica root, arnica flower, anise, asafoetida, celery, chamomile, corn silk, fenugreek, horse chestnut, licorice root, lovage root, parsley, passion flower herb, quassia, red clover, rue, sweet clover, and sweet woodruff. Dong quai contains at least six coumarin derivatives, which may account for the interaction noted above. People should consult a healthcare professional if they are taking an anticoagulant and wish to use one of these herbs.

Lycium barbarum

There is one case report in which ingestion of a Chinese herbal tea made from Lycium barbarum appeared to interfere with the effect of warfarin.

Maitake

In a case report, ingestion of a maitake extract appeared to enhance the effect of warfarin in an elderly man. Although a cause-effect relation was not demonstrated, people taking warfarin should not take maitake without medical supervision.

Quinine (Cinchona species)

Quinine, a chemical found in cinchona bark and available as a drug product, has been reported to increase warfarin activity. People should read labels for quinine/cinchona content. People taking warfarin should avoid quinine-containing products.

Quilinggao

There is one published case report in which the Chinese herbal product quilinggao increased the action of warfarin and apparently contributed to a bleeding episode. There are many different brands of quilinggao, and the composition varies between manufacturers. Individuals taking warfarin should not take quilinggao.

Reishi (Ganoderma lucidum)

As it may increase bleeding time, reishi is not recommended for those taking anticoagulant (blood-thinning) medications.

St. John�s wort�(Hypericum perforatum)

According to a preliminary report, volunteers taking 900 mg per day of St. John�s wort were given a single dose of an anticoagulant similar in action to warfarin. There was a significant drop in the amount of the drug measured in the blood. Seven case studies reported to the Medical Products Agency in Sweden also found a decrease in the anticoagulant activity of warfarin when St. John�s wort was taken at the same time. This may have occurred because certain chemicals found in St. John�s wort activate liver enzymes that are involved in the elimination of some drugs. People taking warfarin should consult with their doctor before taking St. John�s wort.

Interactions with Foods & Other Compounds

Alcohol

Alcohol use, especially long-term heavy drinking, can decrease the effectiveness of warfarin. People taking warfarin are cautioned to avoid alcohol.

Food

Some vegetables (broccoli, Brussels sprouts, kale, parsley, spinach, and others) are high in vitamin K. Eating large quantities or making sudden changes in the amounts eaten of these vegetables, interferes with the effectiveness and safety of warfarin therapy. Eating charbroiled food may decrease warfarin activity, while eating cooked onions may increase warfarin activity.Soy foods have been reported both to increase and to decrease warfarin activity. The significance of these last three interactions remains unclear.

Preliminary evidence suggests that frequent consumption of mangoes may interfere with the effect of warfarin.

There is one preliminary report in which a high-protein, low-carbohydrate diet appeared to interfere with the effect of warfarin in two people. While additional research is needed to confirm that observation, people taking warfarin should consult their doctor before making large changes in the amount of protein they eat.

Olestra

The FDA-approved fat substitute, olestra, interferes with fat absorption, including the absorption of fat-soluble vitamins. Vitamin K, a fat-soluble vitamin, is added to olestra to offset this adverse effect. Since vitamin K interferes with the activity of warfarin, eating snacks containing olestra may also interfere with the drug�s activity. The impact of eating snacks containing olestra has not been evaluated in people taking warfarin. However, until more is known, it makes sense for people taking warfarin to avoid olestra-containing foods.

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