What You Should Know About Your Diet and Warfarin

What is warfarin?
Warfarin is a medication that helps thin your blood to decrease your bodys chance of forming harmful
clots. Unwanted blood clots may cause strokes, heart attacks, or other potentially harmful events such as
clots in the legs (deep vein thrombosis) or lungs (pulmonary embolism).

How does warfarin work?

There are proteins in your blood to help form clots. These proteins are made by your liver with the help
of vitamin K. Warfarin works by blocking the effects of vitamin K, making it harder for your body to form
clots. In order to make sure the amount of warfarin youre taking is right for you, your healthcare
professional will test your blood periodically. The blood test checks your protime (PT) or international
normalized ratio (INR) to measure how long it takes for your blood to clot. If your PT/INR is outside your
target range, your warfarin dose will need to be adjusted.

How does your diet affect warfarin?

Since vitamin K and warfarin work against each other, the amount of vitamin K in your diet can change
warfarins effects. It is important to keep your dietary intake of vitamin K consistent. Foods such as green
leafy vegetables and certain oils have higher contents of vitamin K. (See the next page for a chart of vitamin
K content in selected foods). If you DECREASE your intake of vitamin K (eat fewer foods containing
vitamin K) your dose of warfarin may need to be lowered to prevent bleeding. If you INCREASE your
intake of vitamin K, your dose of warfarin may need to be increased to prevent blood clots. A MAJOR
change in your vitamin K intake can affect your PT/INR, but normal daily variation in the foods you eat is
okay. You DONT have to avoid foods that are high in vitamin K, just keep your diet consistent. You
should let your healthcare professional know if there is going to be a major change in your diet, so your
PT/INR can be closely monitored.
Many people are on special diets, such as the Atkins or South Beach diets, to lose weight. These diets
are high protein diets and can also affect the way warfarin works in your body. Once you take a dose of
warfarin, some of it binds to protein in your bloodstream. While warfarin is attached to this protein, it has
no effect on your body. Its thought that high protein diets can increase the amount of proteins in your body
and cause more warfarin to be bound to protein. This causes a DECREASE in warfarin available to prevent
clots, so your warfarin dose may need to be increased. Always check with your healthcare professional
before starting any special diets, so your PT/INR can be closely monitored.
Certain foods can also affect how your liver clears warfarin from your body, causing warfarin levels to
increase or decrease. Examples include alcohol, cranberry products (e.g., juice, supplements), and possibly
grapefruit or grapefruit juice. Too much alcohol, cranberry products, or grapefruit products can
INCREASE warfarins effect and increase your risk of bleeding. Avoid or limit your intake of alcohol,
cranberry products, and grapefruit or grapefruit juice. Make sure your healthcare professional knows if your
diet contains any of these products, so your PT/INR can be closely monitored.

Other things to remember when taking warfarin

In addition to foods, many prescription and over-the-counter drugs, including vitamins and herbal
supplements, can affect your warfarin level. You should not start, stop, or change doses of any drugs or
supplements without first talking with your healthcare professional. Try to keep a healthy, well-balanced
diet and keep your vitamin K intake consistent. Take your warfarin dose around the same time each day. If
you miss a dose, take it as soon as you remember. If it is almost time for the next dose, skip the missed dose
and continue your regular dosing schedule. Dont double up doses without checking with your healthcare
professional. Tell your healthcare professional immediately if you have unusual bleeding or bruising, black
or bloody stools, blood in the urine, or stomach pain.

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 Vitamin K Content of Selected Foods*
Note: This is NOT a list of foods to avoid. This list provides information on the vitamin K
content of certain foods.
Vitamin K Content
Foods Low Moderate High
Vegetables
Green beans Asparagus Broccoli
Carrots Avocado Brussels sprouts
Cauliflower Red Cabbage Cabbage
Celery Green peas Collard greens
Corn Endive (raw)
Cucumber (peel removed) Pickle (dill) Kale (raw leaf)
Eggplant Lettuce (iceberg) Lettuce (bib, red leaf)
Mushrooms Mustard greens (raw)
Onions Parsley
Green pepper Spinach
Potato Turnip greens (raw)
Pumpkin Watercress (raw)
Sauerkraut (canned) Swiss chard
Tomato
Fruits
Apple
Banana
Blueberries
Grapes
Orange
Meats
Beef
Chicken
Pork
Tuna
Turkey
Fats and Oils
Corn oil Margarine Mayonnaise
Peanut oil Olive oil Canola oil
Safflower oil Soybean oil
Sesame oil
Sunflower oil
Dairy Products
Butter
Cheese (cheddar)
Eggs
Sour cream
Yogurt
Beverages
Coffee
Cola
Fruit juices
Milk
Tea (black) Tea (green)**
* Adapted with permission from Clotcare Online Resource at www.clotcare.com. (Accessed April 20, 2005).
** There is some controversy as to whether brewing green tea alters the vitamin K content and/or whether green tea
may alter the effect of warfarin by some other mechanism.

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Detail-Document #210507
This Detail-Document accompanies the related article published in

PHARMACISTS LETTER / PRESCRIBERS LETTER
May 2005 ~ Volume 21 ~ Number 210507

Warfarin-Food Interactions
Lead author: Wan-Chih Tom, Pharm.D.

Background diets have an induction phase, where patients are

The interaction between warfarin and vitamin to eliminate almost all carbohydrates from their
K-containing foods is well documented. Patients diet for at least two weeks.3,4 Anticoagulation
on warfarin therapy are instructed to report any clinicians are seeing more INR fluctuations in
significant changes in their dietary vitamin K patients who are on high-protein, low-
intake in order to maintain a therapeutic carbohydrate diets. There are two case reports of
international normalized ratio (INR). However, decreased INR after initiation of high-protein,
possible interactions between warfarin and high low-carbohydrate diets, requiring warfarin dosage
protein diets, foods with antiplatelet effects, or to be increased by 20% to 30% to achieve
foods that affect the cytochrome P450 enzyme therapeutic INR.5
system are not as well documented. Warfarin is a medication that is highly protein
Warfarin is a racemic mixture of R-warfarin bound.1 The decreased INR in patients following
and S-warfarin enantiomers.1 Warfarin is initiation of a high-protein, low-carbohydrate diet
predominately metabolized by the cytochrome may be related to the effect of protein intake on
P450 enzyme system.1 The two warfarin albumin level.5 An increase in albumin level
enantiomers have different therapeutic potency appears to occur within ten days of initiating a
and are metabolized by different CYP450 high-protein, low-carbohydrate diet.5 The increase
isoenzymes. S-warfarin is the most potent of the in albumin level causes an increase in warfarin
two enatiomers.1,2 S-warfarin is primarily a binding to albumin, making less free warfarin
substrate for CYP2C9 and secondarily CYP3A4.2 available for anticoagulant effect.5 Some experts
R-warfarin is primarily a substrate for CYP1A2, suggest that a high-protein, low-carbohydrate diet
secondarily CYP3A4, and slightly CYP2C19.2 may also have an affect on warfarins metabolism
Foods that induce these isoenzymes can decrease via the cytochrome P450 system.
warfarin effect and foods that inhibit these Because of the potentially significant decrease
isoenzymes can potentiate warfarin effect.2 The in INR level, patients are at high risk of
significance of the interaction will depend on developing thromboembolism shortly after
which isoenzyme(s) the food affects and how starting the diet. Advise patients to consult their
much of the implicated food is consumed. anticoagulation clinician prior to starting a high-
Theoretically, foods such as cranberry juice, protein, low-carbohydrate diet in order to ensure
grapefruit juice, mango fruit, charbroiled foods, close monitoring of INR level [Evidence level D;
alcohol, and caffeine can affect warfarin Anecdotal evidence].5
metabolism via the CYP450 enzyme system and
potentially alter warfarin effects. Cranberry Juice
In 2003, the England-based Committee on
High Protein Diets Safety of Medicine (CSM) issued a warning about
In the last few years, the popularity of high the possible interaction between cranberry juice
protein, low carbohydrate diets, such as the Atkins and warfarin based on five case reports of such
diet and South Beach diet has soared in the U.S. interactions.6 The potential interaction is
Patients get on these diets in hopes of shedding suspected to be due to flavonoids found in
extra pounds. The diets instruct patients to cranberry. It is theorized that the flavonoids in
increase dietary intake of protein and decrease cranberry might inhibit CYP2C9 metabolism of
intake of carbohydrate-containing foods. Both warfarin, and therefore, increase INR.7,8 Another
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 (Detail-Document #210507: Page 4 of 8)

theoretical mechanism of interaction is the alcohol levels competes for protein binding sites,
antiplatelet effect of the cranberry constituent, making more active warfarin available for clinical
salicylic acid.8 Cranberry juice contains activity.12 Acute alcohol consumption can
approximately 7 mg of salicylic acid per liter. decrease warfarin metabolism and increase
Drinking three 250 mL servings of cranberry juice warfarin effect, whereas chronic alcohol
daily for two weeks increases serum salicylate consumption can induce warfarin metabolism and
levels.8 Theoretically, the salicylic acid in decrease warfarin effect.12 Due to the increased
cranberry could potentiate warfarins risk of bleeding with acute alcohol consumption,
anticoagulant effect. It is not known how patients should be advised to avoid or limit
different cranberry products affect warfarin alcohol consumption while on warfarin [Evidence
metabolism or if this interaction can be avoided level D; Anecdotal evidence].12
by separating doses or limiting cranberry product
consumption. For now, advise warfarin patients to Mango Fruit
avoid or limit cranberry product consumption. There are at least thirteen cases of increased
Closely monitor warfarin patients who are INR associated with mango fruit consumption
consuming cranberry products concurrently reported.13 The subjects ingested anywhere from
[Evidence level D; Anecdotal evidence].9 one to six mangos daily for two days to a month.
The average increase in INR was 38%. It is
Grapefruit Juice theorized that mango fruit inhibits CYP2C19;
Grapefruit juice contains flavonoids that can therefore, inhibit R-warfarin metabolism and
inhibit CYP3A4, CYP2C9, CYP2C19, and increase INR.13 Advise patients to limit
CYP1A2 isoenzymes.2,10 The effect of grapefruit consumption of mangos while on warfarin therapy
juice on drugs is difficult to predict because the [Evidence level D; Anecdotal evidence].13
amount of flavonoids may vary from product to
product and the uptake of these flavonoids may Caffeine and Charbroiled Foods
also vary among individuals.10 Theoretically, Caffeine and charbroiled foods both have an
grapefruit juice and the fruit itself might increase effect on the CYP450 enzyme system and
warfarin effect by competing with both R- theoretically can affect warfarin metabolism;
warfarin and S-warfarin metabolism. There is one however, there are no case reports or evidence to
case report of significantly increased INR support such interactions. Caffeine is a substrate
associated with consumption of 50 ounces of for CYP1A2 and theoretically may compete with
grapefruit juice daily.10 But a small clinical trial R-warfarin for metabolism.2 The hydrocarbons of
found that consumption of 24 ounces of grapefruit charbroiled food can induce CYP1A2, therefore
juice daily for one week had no effect on INR in a can theoretically increase R-warfarin metabolism
group of men on warfarin therapy.10 Given the and decrease warfarin effect.2 Due to the lack of
inconsistent findings and lack of clinical research, evidence of these interactions, the best advice
the best advice now is to advise warfarin patients right now is to tell warfarin patients to keep their
to avoid or limit grapefruit juice consumption to caffeine consumption consistent and limit
24 ounces or less a day [Evidence level D; consumption of charbroiled foods [Evidence D,
Anecdotal evidence].10 Monitor INR closely if a Anecdotal evidence].2
large amount of grapefruit juice or grapefruit
consumption and warfarin use occur Garlic
concomitantly [Evidence level D; Anecdotal Garlic can inhibit platelet aggregation and
evidence].10 theoretically can potentiate the effects of
warfarin.14 There are case reports of excessive
Alcohol garlic or garlic supplement consumption
Interactions between alcohol and warfarin have associated with altered platelet aggregation and
been reported. There are two possible prolonged bleeding.15 In addition, there are two
mechanisms of interaction with alcohol: alteration anecdotal reports of increased INR in patients
of protein binding and inhibition or induction of previously stabilized on warfarin when they took
CYP2C9 isoenzyme.11 An increase in blood garlic products.15 Patients taking warfarin should

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 (Detail-Document #210507: Page 5 of 8)

be advised to avoid garlic supplements [Evidence expected [Evidence level D; Anecdotal

level D; Anecdotal evidence].15 They should also evidence].19
be advised that regular consumption of foods
containing small amounts of garlic is unlikely to Soy
have an effect on warfarin efficacy [Evidence Soybeans contain vitamin K and may also
level D, Anecdotal evidence].15 Monitor INR inhibit platelet aggregation.20 Different soy
closely if excessive garlic consumption and preparations have varying amounts of vitamin K
warfarin occurs concomitantly [Evidence level D, content. There is a case report where a patients
Anecdotal evidence].15 INR decreased significantly after consuming soy
milk daily for four weeks.20 However, the vitamin
Ginger K content of soy milk is so low that there are
Ginger is thought to inhibit thromboxane probably other mechanisms for the interaction
synthetase and decrease platelet aggregation.16 between warfarin and soy milk. Its been
Theoretically, excessive consumption of ginger theorized that soy can also decrease the absorption
might increase the risk of bleeding. There is a case of warfarin, but the exact mechanism of
report of increased INR when ginger supplements interaction is unknown.20,21 Advise patients to
were used concomitantly with phenprocoumon, a limit consumption of soy products and monitor
coumarin derivative.17 Regular consumption of INR closely if consumption of soy products and
food containing ginger is unlikely to pose a warfarin occurs concurrently [Evidence level D;
problem in patients taking warfarin. However, Anecdotal evidence].21
ginger supplements contain much more ginger
than regularly found in food and might have the
Conclusion
potential of increasing bleeding risk in patients
Most of the available information on these
taking warfarin. Patients taking warfarin and
potential drug-food interactions is based on in
ginger supplements concomitantly should be
vitro data or case reports. Without well-designed
advised to watch for symptoms of unusual
clinical trials, it is difficult to prove a definitive
bleeding or bruising and their INR should be
cause and effect relationship between these foods
monitored closely [Evidence level D; Anecdotal
and warfarin.
evidence].15
Drug-food interactions with warfarin can
Green Tea potentially lead to hemorrhage or
There are constituents in green tea that seem to thromboembolism. Therefore, it is important that
have antiplatelet effects and theoretically might healthcare professionals are aware of the potential
increase the effect of warfarin.18 However, there implications of these drug-food interactions with
are no reports of green tea increasing the effect of warfarin. Patients should be aware that changes
warfarin in patients to date. Excessive in dietary habits can sometimes affect warfarin
consumption of green tea has been reported to efficacy and should be advised to consult their
antagonize the effects of warfarin in a patient healthcare professional prior to making major
previously stable on warfarin therapy.19 The changes in their diet.
interaction has been attributed to the vitamin K1 In addition to foods, a number of dietary
content or possibly other constituents in green supplements may also affect warfarins efficacy.
tea.18,19 The amount of vitamin K1 content or other (See the chart on the next page for a list of
constituents vary greatly among different green selected dietary supplements that may increase or
tea products depending on their sources and decrease warfarin effectiveness). For more details
processing; therefore, its difficult to determine on interactions between warfarin and dietary
how much green tea consumption would have an supplements, please refer to Natural Medicines
effect on warfarin. Patients should be advised that Comprehensive Database at http://www.natural
excessive consumption of green tea might database.com. If you see a possible interaction
decrease the effectiveness of warfarin. Close between certain foods/supplements and warfarin,
monitoring is warranted if concomitant use of use the online reporting form at
large amounts of green tea and warfarin is https://www.accessdata.fda.gov/scripts/medwatch/
to submit a report to the FDA.
More. . .
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 (Detail-Document #210507: Page 6 of 8)

Potential Interactions of Dietary Supplements with Warfarina

Potential Increase in Risk of Bleeding
Acetyl-L-carnitine Fish oil Mate
Arnica Flaxseed, Flaxseed oil Melatonin
Alcohol, acute use Fo-ti Mesoglycan
Bishops weed Forskolin Milk thistle
Black tea Forsythia N-acetyl glucosamine
Bladderwrack Gamma-linolenic acid Nattokinase
Boldo Garlic Oolong tea
Borage seed oil Ginger Pantethine
Burdock Ginkgo Papaya
Caffeine Ginseng, Siberian Peppermint oil
Chondroitin sulfate Glucosamine Propionyl-L-carnitine
Cod liver oil Grapefruit, Grapefruit juice Red clover
Coltsfoot Guarana Reishi mushroom
Cranberry, cranberry juice Guggul Resveratrol
Danshen Holy basil Saw palmetto
Devils claw Honeysuckle Sea buckthorn
Dong quai Horse chestnut Tiratricol
Epimedium Ipriflavone Turmeric
Eucalyptus oil Jiaogulan Vinpocetine
Evening primrose oil Kava Vitamin A
Fenugreek L-carnitine Vitamin E
Feverfew Lycium Willow bark
Wintergreen
Possible Decrease in Warfarins Effects
Acerola
Alcohol, chronic use
Alfalfa
Cherokee rosehip
Chlorella
Coenzyme Q10
Corn silk
EDTA
Ginseng, American
Ginseng, Panax
Green tea
Limonene
Rose hip
Smartweed
Soy
Spinach
St. Johns wort
Stinging nettle
Vitamin C
Vitamin K
Watercress
a
Adapted from Natural Medicines Comprehensive Database at www.naturaldatabase.com. (Accessed 4/21/05).
More. . .
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 (Detail-Document #210507: Page 7 of 8)

8. Jellin JM, Gregory, PJ, Batz F, et al. Cranberry

Users of this document are cautioned to use their own Monograph. Therapeutic Research Faculty.
professional judgment and consult any other necessary Natural Medicines Comprehensive Database.
or appropriate sources prior to making clinical http://www.naturaldatabase.com. (Accessed April
judgments based on the content of this document. Our 11, 2005).
editors have researched the information with input 9. Suvarna R, Pirmohamed M, Henderson L.
Possible interaction between warfarin and
from experts, government agencies, and national cranberry juice. BMJ 2003;327:1454.
organizations. Information and Internet links in this 10. Jellin JM, Gregory, PJ, Batz F, et al. Grapefruit
article were current as of the date of publication. Monograph. Therapeutic Research Faculty.
Natural Medicines Comprehensive Database.
Levels of Evidence http://www.naturaldatabase.com. (Accessed April
In accordance with the trend towards Evidence-Based 11, 2005).
Medicine, we are citing the LEVEL OF EVIDENCE 11. Jellin JM, Gregory, PJ, Batz F, et al. Beer
Monograph. Therapeutic Research Faculty.
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Adapted from Siwek J, et al. How to write an evidence-based garlic, ginger, ginkgo, or ginseng: nature of the
clinical review article. Am Fam Physician 2002;65:251-8. evidence. Ann Pharmacother 2000;34:1478-82.
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Cite this Detail-Document as follows: Warfarin-food interactions. Pharmacists Letter/Prescribers Letter

2005;21(5):210507.

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