Note: The following is not medical advice. The author is a biochemist, not a physician, and the sole intent of this fact
sheet is EDUCATION. It is not meant to take the place of medical advice, nor should anyone reading this material stop taking drugs prescribed by their physician. In fact, the best use of this material is in discussion with your physician, as part of a health partnership designed to provide best care. Background Coumadin® (generic name: warfarin) is one of the most widely
prescribed drugs in North America. It impairs the body’s clotting mechanism thereby “thinning” the blood. This in turn reduces risk for
abnormal clots (thrombosis) and subsequent cardiovascular events such as heart attack (blockage of blood vessels leading to the heart) or
thrombotic stroke (blockage of blood vessels leading to the brain). Of course, the clotting mechanism is a necessary and vitally important function of the blood stream, responsible for the fact that when you
cut yourself or get punched in the nose, you do not bleed to death. Less obvious are the unseen clots that stop internal bleeding,
everything from microscopic lesions to gastrointestinal ulcers. (Hemophilia is a disease in which this mechanism is defective.)
The clotting mechanism is an intricate symphony of signaling molecules (“Alert! Leak in sector four!) that cause a rapid series of
biochemical events involving vitamins, enzymes, coenzymes and a variety of cells, most notably platelets, which aggregate or clump
together, sealing the leak. In this process, vitamin K plays critical role, and Coumadin works by interfering with the metabolism of vitamin K.
1. Vitamin K performs many important functions in the human
body besides helping the blood to clot. It is vitally important for moving calcium from the bloodstream to the skeleton, thus
maintaining bone density. Thus not surprisingly, there is evidence that
long-term use of coumadin can increase risk for osteoporosis. Equally disturbing is the fact that calcium that is not taken up by bone can
deposit instead in the blood vessels, leading to hardening of the arteries.i
2. Narrow safety range. As you can imagine, manipulating an
intricate biological system is fraught with danger, as too much coumadin can cause internal bleeding which is usually silent. There
may be external signs, such as easy bruising, but sometimes the first “sign” is hemorrhagic stroke.
At the same time, too little coumadin leaves you vulnerable to
abnormal clotting, which can cause heart attacks and thrombotic stroke. Thus the prescribing physician will want to monitor clotting
time at regular intervals - from every two weeks to once a month. This test is known as the International Normalized Ratio (INR).
Warfarin is the second most common drug – after insulin – responsible for emergency room visits for adverse drug events.
The ideal target INR range will vary from person to person depending on a variety of factors such as age and medical history. Only your physician can determine the appropriate INR range for you, but the most common INR target range for someone on Coumadin is between 2.0 and 4.0. Because of this narrow safety range, doctors can be rather strict about
anything that affects clotting time, such as the use of vitamins, herbs or even vitamin K-containing foods like green leafy vegetables.
And this is where there is widespread confusion. Many people,
including doctors, believe that people on Coumadin should not consume green leafy vegetables. But that is likely to cause a
deficiency of a number of essential nutrients besides vitamin K, including folic acid, a nutrient already scarce in the Standard American Diet. In reality, however, the prescribing information for doctors, the
Physician’s Desk Reference (PDR) and CME (continuing medical education) materials stress the value of green leafy vegetables. They
only caution against making drastic or sudden changes in the consumption of these important foods.
Likewise, there is no prohibition against the use of herbs or vitamins; only that if you make changes in your use of herbs or vitamins, you
should keep your doctor informed. Your doctor will then look carefully at your next INR and adjust your Coumadin dose accordingly.
3. Acute vs long-term therapy
If all of that monitoring and worry sounds burdensome, remember that none of these issues would be serious if Coumadin was used for its
original purpose, which was short-term anticoagulant therapy, Coumadin is quite valuable after heart surgery or in patients with
cardiovascular disease. These are usually hospitalized patients where diet is controlled and blood tests are frequent.
Today, however, the drug is prescribed for anyone with CVD risk
factors, with no careful monitoring and no thought of finding a more suitable alternative. This illustrates a common problem in conventional heath care: it’s easy to put patients on a drug and very difficult to get
them off. Here is the warning that FDA requires to be placed on all packages of Coumadin (warfarin):
WARNING: BLEEDING RISK
Warfarin sodium can cause major or fatal bleeding. Bleeding is more likely to occur during the starting period and with a higher dose (resulting in a higher INR). Risk factors for bleeding include high intensity of anticoagulation (INR > 4.0), age ≥ 65, highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, malignancy, trauma, renal insufficiency, concomitant drugs (seend long duration of warfarin therapy. Regular monitoring of INR should be performed on all treated patients. Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shorter duration of therapy. Patients should be instructed about prevention measures to minimize risk of bleeding and to report immediately to physicians signs and symptoms of bleeding (see PRECAUTIONS:
I find it humorous that anticoagulant drug therapy is often placed in
the category of “disease prevention,” as if people have blood clotting problems due to a deficiency of Coumadin. In truth, people have blood
clotting problems primarily due to diet and lifestyle behaviors. So the discussion with your doctor needs to begin with assurances that you
are a motivated patient, interested in preventing CVD and willing to make diet and lifestyle changes.
You will also need reliable evidence for the efficacy of alternative or
complimentary therapy. The good news is that in the arena of blood clotting (and thickness or viscosity) the medical literature is abundant.
Remember that there are two issues here: the tendency of blood
platelets to clump (known as platelet aggregation) and blood viscosity or thickness. Diet and nutritional supplements can have a remarkably
beneficial effect on both factors. Just eating less meat and more fish has been shown to help normalize blood clotting and viscosity, as well as reduce risk for fatal
arrhythmias.ii,iii Drug companies that make blood thinners acknowledge that these measures should be tried first, but that is rarely done in clinical practice.
Importantly, the utilization of fish or fish oil been shown to be effective
in controlled scientific studies published in peer-reviewed medical journals. A systematic review of 14 randomized clinical trials reported
that omega-3 fatty acid supplementation produced a clinically significant reduction in overall mortality in patients with coronary heart
disease.iv This landmark review followed on the heels of other important studies demonstrating the value of omega 3 fatty acids in
men and women in a wide age range.v,vi,vii It is estimated that Coumadin is responsible for thousands of deaths each year?viii Omega 3 fatty acids, on the other hand, have an
enormous safety window because they have been part of the human diet since the beginning of time. In addition to prevention, omega 3 fatty acids from fish have also been shown to be effective in the
treatment of blood clotting disorders.ix,x,xi What’s more, they have, in my opinion, a mechanism of action that is superior to drugs. That is
because fish oil does not interfere with vitamin K, but reduces risk for abnormal clots by restoring balance to the various clotting factors, including triglycerides, platelets, thrombin and fibrinogen.xii,xiii Summary: I am always amazed that people, in general, know the viscosity of the
oil in their car’s engine, but they do not know anything about the blood that is flowing through their arteries and veins. In fact, I believe that
whole blood viscosity testing will be the next breakthrough in preventive medicine. Some forward-thinking doctors are already
performing these tests and the practice will be common in the next 5 years. In the meantime, here are research-proven steps that you can
take to improve your cardiovascular health: 1. Eat a highly varied natural foods diet with about 70% of calories coming from plants.
2. Eat a wide variety of proteins – not just red meat. These should include beans, nuts and seeds and two or three servings of fish each
week. 3. If you do not like fish, or have been advised not to eat fish
(pregnant women are sometimes asked to limit fish intake to avoid ingesting mercury) you can take fish oil capsules. Just make sure they
are certified to be free of lead and mercury. 4. Ask your doctor about whole blood viscosity testing. At the very
least, have your prothrombin time (INR) measured at your annual physical. If your doctor prescribes Coumadin, make sure you test at least once a month.
5. Maintain ideal weight, normal cholesterol and triglyceride levels. 6. Enjoy regular exercise. For heart health, intensity is not as
important as duration and consistency. For most people, brisk walking is sufficient.
7. Discuss with your doctor research regarding the cardiovascular benefits of CoQ10, fish oil, B vitamins and resveratrol. These studies
can be found by searching the National Library of Medicine, public access site:
References iVitamin K: the coagulation vitamin that became omnipotent.2007
Vitamin K, discovered in the 1930s, functions as cofactor for the posttranslational carboxylation of glutamate residues. Gammacarboxy
glutamic acid (Gla)-residues were first identified in prothrombin and coagulation factors in the 1970s; subsequently, extra-hepatic Gla
proteins were described, including osteocalcin and matrix Gla protein (MGP). Impairment of the function of osteocalcin and MGP due to
incomplete carboxylation results in an increased risk for developing osteoporosis and vascular calcification, respectively, and is an
unexpected side effect of treatment with oral anticoagulants. It is conceivable that other side effects, possible involving growth-arrest-
specific gene 6 (Gas6) protein will be identified in forthcoming years. In healthy individuals, substantial fractions of osteocalcin and MGP
circulate as incompletely carboxylated species, indicating that the majority of these individuals is subclinically vitamin K-deficient. Potential new application areas for vitamin K are therefore its use in
dietary supplements and functional foods for healthy individuals to prevent bone and vascular disease, as well as for patients on oral
anticoagulant treatment to offer them protection against coumarin-induced side effects and to reduce diet-induced fluctuations in their
INR values. ii Breslow JL. n-3 fatty acids and cardiovascular disease. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1477S-1482S. Review. iii Cuevas AM, Germain AM. Diet and endothelial function. Biol Res. 2004;37(2):225-30. Review.
iv Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC. Effect of different antilipidemic agents and diets on mortality: a systematic
review. Arch Intern Med 2005; 165:725-30. v Vanschoonbeek K, de Maat MP, Heemskerk JW. Fish oil consumption and reduction of arterial disease. J Nutr. 2003 Mar;133(3):657-60. Review.
viFish oil consumption and reduction of arterial disease.2003 Mar;133(3):657-60. vii Taddei S, Ghiadoni L, Virdis A, Versari D, Salvetti A. Mechanisms of endothelial dysfunction: clinical significance and
preventive non-pharmacological therapeutic strategies. Curr Pharm Des. 2003;9(29):2385-402. Review.
viii Runciman WB, Roughead EE, Semple SJ, Adams RJ. Adverse drug events and medication errors. International Journal for Quality in Health Care 15:i49-i59 (2003).
ixInfluence polyunsaturated fatty acids omega-3
on coagulation and fibrinolysis systems in patients with NIDDM. Klin Med (Mosk). 2002;80(2):40-3. xEffects of nutritional factors on haemostasis. Hamostaseologie. 2005 Feb;25(1):13-7. xiOmega-3 fatty acids: their role in the prevention and treatment of atherosclerosis related risk factors and complications.2003 May;57(4):305-14. xii Variable hypocoagulant effect
of fish oil intake in humans: modulation of fibrinogen level and thrombin generation.2004
Sep;24(9):1734-40. xiiiDietary n-3 polyunsaturated fatty acids and coronary heart disease-related mortality: mechanism of action.
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