Interactions with Dietary Supplements
Bromelain
In theory, bromelain might enhance the action of anticoagulants. This theoretical concern has
not been substantiated by human research, however.1
Coenzyme
Q10
Coenzyme Q10 (CoQ10) is structurally similar to
vitamin K and may affect blood coagulation.2 Four case reports describe
possible interference by CoQ10 with warfarin activity.3 4 5
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.6 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.7 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.8 In fact, a possible interference by vitamin C with the effect of
anticoagulants has also been reported.9 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.10 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.11 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.12
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.13 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,14 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 quantities15 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.16 Other significant dietary sources of
vitamin K include soybean oil, olive oil,
cottonseed oil, and canola oil.17
Vitamin K supplementation can be used, however, to counteract an overdose of
warfarin.18 In addition, controlled and continuous supplementation with vitamin K
(100 mcg per day) has been used effectively to reduce the fluctuations in dosage requirement
that occur in some people taking warfarin.19 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.20 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.21
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.22 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.23 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.24 25 26 27 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.28 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.29 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.30 31 32
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.33 This can result in an increase in the tendency toward
bleeding.34 Standardized extracts have, on rare occasions, been associated with
bleeding in people.35 Garlic extracts have also been associated with two human
cases of increased warfarin activity.36 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.37
Ginkgo
biloba
Ginkgo extracts may reduce the ability of platelets to stick together, possibly increasing the
tendency toward bleeding.38 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.39 40 There are two case reports of
people taking warfarin in whom bleeding occurred after the addition of ginkgo.41
42 People taking warfarin should consult with a physician knowledgeable about
botanical medicines if they are considering taking ginkgo.
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.43 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.44 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.45
Quinine
(Cinchona species)
Quinine, a chemical found in cinchona bark and available as a drug product, has been reported
to increase warfarin activity.46 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.47 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.48
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.49 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.50 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.51 52 People
taking warfarin should consult with their doctor before taking St. John’s wort.
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