Other Common Names

DRUGS REDUCING BLOOD CLOTTING TENDENCY - ANTI-COAGULANT DRUGS

Enoxaparin (Lovenox®)

Heparin

Warfarin (Coumadin®, Panwarfin®, Warfilone®)

Uses

These drugs are designed to inhibit the formation of the fibrous protein matrix that serves as the infrastructure

of blood clots.  Anticoagulants are used to treat blood clots in the veins (thrombosis) or blood clots in the lungs

(pulmonary embolism).  They are also used for people with atrial fibrillation and in the prevention of strokes.

Coumadin inhibits vitamin K metabolism as a mechanism of action for thinning the blood and

preventing/breaking clots (vitamin K is a clotting factor).

Depletions

Vitamin D

Heparin may interfere with vitamin D metabolism (Aarskog D, Aksens L, Markestad TK, et al. Heparin induced

inhibition of 1,25-dihydroxyvitamin D formation. Am J Obstet Gynecol 1984;148:1141–42).  Osteoporosis has

been reported in subjects taking high dose heparin for several months (Majerus PW, Broze GJ Jr, Miletich JP,

Tollefsen DM. Anticoagulant, thrombolytic, and antiplatelet drugs. In Goodman and Gilman’s The

Pharmacological Basis of Therapeutics, 9th ed. New York: McGraw-Hill 1996, 1346), and osteopenia has been

 reported in women receiving heparin therapy during pregnancy (Haram K, Hervig T, Thordarson H, Aksnes L.

Osteopenia caused by heparin treatment in pregnancy. Acta Obstet Gynecol Scand 1993;72:674–75).

Interactions

Nutrient Interactions

Vitamin E, vitamin C, vitamin D, fish oil, garlic, ginkgo biloba, dong quai, bilberry, astragalus, capsaicin,

fenugreek, vitamin K, feverfew, dan shen, papaya, angelica, enzymes, Siberian or Asian ginseng, alfalfa, green

tea, St. John's wort, buchu, chamomile, ginger, Irish moss, kelp, lungwort, pau’d’arco, prickly ash, wintergreen,

yarrow, horse chestnut, red clover, coenzyme Q10, alcohol

Nutrient Interactions which Potentiate the Drug

Some researchers believe that vitamin E in amounts up to 1200 IU per day is completely safe for patients on

the drug (Am J Cardiol 1996;77:545-46); caution dictates that it would be wise to consult a physician about

combining the two.  One of the reasons the eskimos have a lower risk for heart disease is thought to be the

blood thinning action of fish oil (the thinning may increase risk for stroke, however).  Large amounts of fish oil

should not be combined with anticoagulant drugs.  Although the interaction is uncertain and not proven, vitamin

 C in large amounts (over 5 grams/day) could possibly interfere with the action of blood thinning medications. 

Vitamin C, like vitamin E, exhibits some effect on lowering levels of thromboxane A2 (thromboxane increases

clotting). An isolated letter to JAMA suggested that vitamin D may potentiate anticoagulants, however, this does

not appear to be common (JAMA 1975;232:19 (letter)).

Vitamin E
Vitamin E thins the blood and should not be given (in amounts > 400 IU) at the same time as blood thinning

drugs, or it could increase bleeding time.  Amounts of 400 IU or less have not been reported to cause a

problem (Graedon).

Omega-3 fatty acids

One of the reasons the eskimos have a lower risk for heart disease is thought to be the blood thinning action of

 fish oil (the thinning may increase risk for stroke, however).  Fish oil and flaxseed oil are excellent sources of

omega-3 fatty acids. Diets rich in these compounds induce the accumulation of omega-3 fats on platelet

membranes. This effect results in the production of thromboxane A3, which inhibits platelet aggregation. The

overall effect may increase clotting time.  Large amounts of fish oil should not be combined with anticoagulant

drugs.

Vitamin C

Although the interaction is uncertain and not proven, vitamin C in large amounts (over 5 grams/day) could

possibly interfere with the action of blood thinning medications.  Vitamin C, like vitamin E, exhibits some effect

on lowering levels of thromboxane A2 (thromboxane increases clotting).

Enzymes

It has been theorized that bromelain may potentiate warfarin activity, but no substantial research has supported

 this claim.  The fibrinolytic activity of bromelain may have an additive effect that enhances the activity of

anti-coagulant drugs (Potential Herb-Drug Interactions, Facts and Comparisons: The Review of Natural

Products. St. Louis: Wolters Kluwer Company, 2001, Appendix).  Papain has also been linked to increasing

warfarin activity in one patient.  High amounts of enzymes should be viewed with caution for people taking

blood thinning drugs (Drug Safety 1997;17(5):342-56).

Papaya

According to the PDR for Herbal Medicines, papaya extract may increase the international normalized ratio

(INR) levels when used in combination with warfarin.  It should be noted that an increase in hemorrhaging

tendency cannot be ruled out when using papaya in combination with blood thinners or when taken with

existing coagulation disorders (Medical Economics Company, PDR for Herbal Medicines, Montvale, NJ, 1998,

Interaction with Herbs

Several herbs also possess anticoagulant properties.  It is a good idea to avoid potentiations by not combining

 significant amounts of these herbs with blood thinning medications.

Herbs with coagulant or anticoagulant constituents

Warfarin is a derivative of the coumarin family of botanical constituents. Therefore, plants containing significant

quantities of these compounds are contraindicated for concurrent use. Examples are alfalfa, red clover,

chamomile, celery, and ginkgo biloba. These plants can antagonize or enhance the effect of anti-coagulant

Botanicals that inhibit platelet aggregation

These plants may potentiate the effects of anti-coagulant drugs. An example is garlic.

Plants whose constituents inhibit thromboxane synthesis

Thromoboxanes are compounds generated within platelets from the fatty acids found on platelet membranes.

If dietary fat intake is predominantly omega-6 fatty acids, then thromboxane A2 is generated, causing platelets

to aggregate (clump together). Botanicals that inhibit thromboxane formation may reduce platelet aggregation.

This effect can increase clotting time. An example of this type of plant is ginger.

Plants with high levels of salicylates

Examples include meadowsweet and poplar. These plants may enhance the effects of anticoagulant drugs.
Garlic

The amount of garlic considered is important.  For instance, a few milligrams of garlic in a synergistic formula

should not interact with blood thinning drugs.  However, a standard dose of 500 mg of garlic as a single herb

would definitely be contraindicated with the drugs.  Garlic does have documented antiplatelet activity

(Neurosurg 1990;26:880-82).

Feverfew

Tentative in vitro research may show the possibility that feverfew may interact with antithrombotic medications

such as warfarin and aspirin.  It is believed that the mechanism of action is the inhibition of arachidonic acid,

the prostaglandin precursor involved in the clotting mechanism (Medical Economics Company, PDR for Herbal

 Medicines, Montvale, NJ, 1998, p. 1172).

Siberian or Asian Ginseng

Recent research suggests that high amounts of ginseng may have a potential interaction with warfarin activity

which increases bleeding (Am J Health-Syst Pharm 1997;54:692-93).

Ginkgo Biloba

Standardized extracts of ginkgo have been associated with increased bleeding.  Caution should be used (New

Eng J Med 1997;336:1108). Ginkgo biloba has also demonstrated antiplatelet activity; reported cases of

interactions are rare, however, again, caution dictates that it would be wise to consult a physician about

combining the two.

Dan Shen

Dan shen is a Chinese herbal preparation which can increase bleeding time in people on Coumadin (J Intern

Med 1997;241:337-39;) and should be used only under close medical supervision.  Salvia (sage), which is

related to Dan Shen, has not shown negative side effects when combined with Coumadin.

Angelica

Angelica is a Chinese herb shown to be useful in many female disorders.  Angelica has been shown to

potentially increase the risk of bleeding when taken in combination with warfarin or heparin (Fetrow, C,

PharmD, et. Al, Complementary & Alternative Medicines, Springhouse Corporation, Springhouse, PA, p. 32).

Alfalfa

Empirical evidence suggests that alfalfa may reduce warfarin activity due to the extremely high vitamin K

content found in alfalfa (Saxe, TG, Am Fam Pract 35(5):135-42, 1987).

Green tea

One reported case involved a man drinking 1 to 1-1/2 gallons of green tea daily while on warfarin.  Test results

showed hypercoagulability problems because the green tea was blocking warfarin activity (Ann Pharmacother

1999;33:426–8).  Blood tests normalized once the green tea was removed.

St. John’s Wort

Several case studies have shown decreased warfarin activity in patients taking St. John’s Wort concurrently

(Lancet 2000;355:575–7).  Since St. John’s Wort activates liver enzymes (cytochrome P450 isoenzymes), it is

believed that this is the mechanism by which this interaction occurs.

Interactions which Reduce the Effectiveness of the Drugs

Vitamin K
Blood thinners such as Coumadin inhibit vitamin K metabolism as a mechanism of action (vitamin K is a

clotting factor), so supplementation could interfere with the effectiveness of these drugs.  It is recommended

that people on these drugs not ingest excess amounts of vitamin K-rich foods (see vitamin K in the vitamins,

minerals and nutrients section).  Although vitamin K-rich foods (Brussel sprouts, broccoli, cabbage, spinach,

kale, parsley, etc) do not have to be totally avoided, caution is advised not to go overboard (J Am Dietet Assoc,

Avocado

There are case reports of foods such as avocado interfering with the effectiveness of warfarin (Lancet

1991;337:914).

Coenzyme Q10

Coenzyme Q10 has been observed in Sweden to reduce the effectiveness of Coumadin and change bleeding

time in patients on Coumadin (the blood became more prone to clotting).  Coenzyme Q10 is structurally similar

 to vitamin K and may be the reason why it effects warfarin activity (Lancet 1994;344:1372-73; Ugeskr Laeger

1998;160:3226–7).

Alcohol

The combined effect of the two drugs can increase or decrease the effect of the anticoagulant and should not

be taken together.  Alcohol can alter the response to heparin.

Digitalis or foxglove

Digitalis, or foxglove, is a cardiac glycoside and can reduce the action of heparin.  Digitalis-containing

substances should only be used under the supervision of a doctor.

Notes

Other Herbs

Some herbs possess anticoagulant properties to a lesser extent, and even though case reports have not been

documented about specific interactions, it would be wise to exhibit caution with these nutrients in relation to

these drugs. These include dong quai, bilberry, astragalus, capsaicin, and fenugreek.  Nutrients such as

bromelain have a theoretical ability to interact with Coumadin, with no reported case studies.  Numerous other

herbs have been reported to increase the anticoagulant effect and should not be used with blood thinning

drugs unless closely supervised by a physician.  These herbs include:  buchu, chamomile, ginger, Irish moss,

kelp, lungwort, pau’d’arco, prickly ash, wintergreen, yarrow, horse chestnut and red clover.  Horse chestnut

(which has been used in the treatment of varicose veins, hemorrhoids, prostate enlargement and fever)

contains esculin, a hydroxycoumarin, which may increase the risk of bleeding.  Red clover, a powerful herb

used for the blood and skin also contains coumarin and coumarin-like compounds and should not be taken in

combination with anticoagulants (Fetrow, C, PharmD, et. Al, Complementary & Alternative Medicines,

Springhouse Corporation, Springhouse, PA.).

Heparin therapy may cause abnormally high potassium levels (Threlkeld DS, ed. Blood Modifiers,

Anticoagulants, Heparin. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons,

June 1997).

The statements above have not been evaluated by the FDA.  The nutritional suggestions and research provided are not intended to diagnose, treat, cure or prevent disease and should not be used as a substitute for sound medical advice.  Please see your health care professional in all matters pertaining to your physical health.  The Professional Description, Professional Notes, Patient Instructions, and items marked with an astrisk (*) are provided by the practitioner and are the sole responsibility of the practitioner.Copyright © 1998-2002 Standard in Natural Solutions, LLC.