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Thrombosis Prevention

CONSULTING YOUR PHYSICIAN

When over-the-counter supplements, such as aspirin, vitamins, herbs, and oils are used as primary antithrombotic therapy, the risk of undesirable side effects is reduced significantly. However, although over-the-counter medications such as aspirin and natural therapies come with a lower risk of hemorrhaging, they should not be substituted for prescription medication if you are at a high risk for thrombosis. Some common conditions that cause a high risk of thrombosis include atrial fibrillation, valvular replacement, recurrent or chronic deep venous thrombosis, pulmonary embolism, and cancer.

Because appropriate therapeutic dosing is crucial and the associated risks can be life-threatening in all circumstances that require anticoagulation therapy or antiplatelet therapy, your physician must be consulted if you desire to make any substitutions to your medication. Because medications, such as Coumadin and heparin, have very narrow therapeutic ranges, anyone on these medications should have his or her blood tested frequently for prothrombin using the INR as a reference range. Once the effective dose is achieved, blood testing is recommended every 1-2 weeks to monitor the medication blood levels and to avoid overdosing, which could lead to hemorrhaging. In addition to the INR values, template bleeding time should also be closely monitored if any over-the-counter drugs or natural supplements that affect the clotting cascade are added to the regimen. Some of these supplements include vitamin E, ginkgo biloba, CoQ10, garlic, ginseng, green tea, vitamin C, vitamin A, policosanol, Dong Quai, white willow, ipriflavone, and vinpocetine (periwinkle).

NUTRITIONAL SUPPLEMENTS

• Cholesterol-Lowering Supplements
• Natural Platelet Aggregation Inhibitors
• Lowering Homocysteine
• Anti-Inflammatories
• Antioxidants
• Sulfur-Containing Compounds
• Exercise

The nutritional supplements listed below have been scientifically studied specifically for their ability to reduce the risk of thrombosis. The bulk of the research focuses on inhibiting platelet aggregation. The supplements are divided into several broad categories based on their primary actions:

• Cholesterol-lowering supplements
• Natural platelet aggregation inhibitors
• Homocysteine-lowering supplements
• Anti-inflammatories
• Antioxidants
• Sulfur-containing compounds

Note: The supplements in the natural blood thinners category could easily have been put into other categories. Ginkgo and vitamin E, for instance, are very powerful antioxidants. Essential fatty acids are also known for their anti-inflammatory actions. However, their blood-thinning effects are much more important in the prevention of thrombosis.

Other protocols contain further information on specific topics. (For research on supplements that increase fibrinolysis, see the Fibrinogen section of the Cardiovascular Disease protocol.)

Cholesterol-Lowering Supplements

Policosanol
Policosanol is a cholesterol-lowering agent derived from sugar cane wax. In some cases, it can normalize cholesterol, as well as prescription drugs, doing so without side effects.

The efficacy and safety of policosanol has been shown in numerous clinical trials. It has been used by millions of people in other countries. Policosanol can lower LDL cholesterol as much as 20% and raise protective HDL cholesterol by 10%. This compares favorably with some cholesterol-lowering drugs that can cause side effects such as liver dysfunction and muscle atrophy (Mas et al. 1999).

Policosanol works by blocking the synthesis of cholesterol. It may not inhibit the HMG-CoA enzyme like the "statin" cholesterol-lowering drugs. Instead, it may inhibit a different enzyme involved in cholesterol synthesis. However, its exact mechanism is not known. Like statin drugs, policosanol helps stop the formation of atherosclerotic lesions, which was proven in studies using rabbits fed a diet designed to create high cholesterol (Noa et al. 1995).

Policosanol inhibits the formation of clots and may work synergistically with aspirin in this respect. In a comparison of aspirin and policosanol, aspirin was better at reducing one type of platelet aggregation (clumping together of blood cells) and policosanol was better at inhibiting another type. Together, policosanol and aspirin worked better than either one alone (Arruzazabala et al. 1997; Stusser et al. 1998).

An article in the journal Pharmacology Research described a randomized, double-blind, placebo-controlled study of policosanal and aspirin. Participants received either policosanol (20 mg daily), aspirin (100 mg daily), a combination of both, or placebo for 7 days. The effects on platelet aggregation are summarized above (Arruzazabala et al. 1997). A related effect is that significant reductions in the level of thromboxane (a blood vessel-constricting eicosanoid produced by platelets) occur in humans after 2 weeks of policosanol (Carbajal et al. 1998).

The normal dose of policosanol is 10-20 mg taken at bedtime. Cholesterol levels should be measured regularly because both high and low cholesterol levels are considered unhealthy. Consider using aspirin (81 mg daily) in combination with policosanol.

Aged Garlic
Aged garlic has become a well-known, popular supplement for the cardiovascular system. Garlic has been found to increase the synthesis of nitric oxide, a chemical messenger that inhibits platelet aggregation and vasodilates blood vessels (Das et al. 1995; Dirsch et al. 1998; Kim-Park et al. 2000; Kim et al. 2001).

An article in the journal Nutrition described a randomized, double-blind study of aged garlic on normal, healthy individuals. The researchers found that aged garlic inhibited platelet adherence and aggregation. Higher doses (7.2 grams daily) had a more profound effect than lower doses (2.4 grams daily) (Steiner et al. 2001).

The specific effects of aged garlic have been the subject of several studies. Aged garlic has been shown to inhibit platelet aggregation by ADP, epinephrine, and collagen, although one study found that it did not affect ADP-induced aggregation (Steiner et al. 1998; Rahman et al. 2000).

Another study examined the effects of consuming one fresh clove of garlic every day on men. After 26 weeks of garlic consumption, there was an approximate 20% reduction of serum cholesterol and about 80% reduction in serum thromboxane B2, a stable metabolite of thromboxane A2. Recall that thromboxane A2 is a platelet aggregator and vasoconstrictor secreted by platelets (Ali et al. 1990, 1995).

Niacin
Niacin (vitamin B3) causes peripheral vasodilation (flushing) within about 20 minutes. Large doses of niacin (up to 6 grams daily) have been found to lower cholesterol, raise HDL, and lower LDL and VLDL lipids. The safest form of niacin is inositol hexa-nicotinate in the dose of 1600-2400 mg daily. Individuals taking continuous high-dose niacin therapy need to have their blood levels monitored for elevations in liver enzymes and uric acid.

An article in the American Heart Journal described the Arterial Disease Multiple Intervention Trial (ADMIT), a multicenter, randomized, placebo-controlled trial to assess the feasibility of an antioxidant therapy on coagulation. Patients with peripheral artery disease randomly received low-dose Coumadin, niacin, an antioxidant vitamin cocktail, or placebo. Unexpectedly, the niacin treatment resulted in a significant decrease in fibrinogen (Chesney et al. 2000).

Natural Platelet Aggregation Inhibitors

Ginkgo Biloba
Ginkgo biloba extract is made from the leaves of the oldest living tree. Ginkgo biloba has a long history of medicinal use. It has become a very popular herb to help improve memory, particularly in the elderly.

Ginkgo biloba has been shown to inhibit platelet aggregation induced by platelet-activating factor (PAF), but not by oxidative stress (Akiba et al. 1998).

An article in the journal Thrombosis Research described a study of the effects of ginkgo biloba in combination with ticlopidine when used to treat rats with experimentally induced thrombosis. The combination of ginkgo biloba (40 mg/kg daily) and a small dose of ticlopidine (50 mg/kg daily) was shown to be comparable to a large dose of only ticlopidine (200 mg/kg daily). The combination also prolonged bleeding time by 150% and consistently decreased the thrombus weight (Kim et al. 1998).

Essential Fatty Acids
Essential fatty acids are found in healthy oils, such as flax, borage, perilla, and fish oils. Essential fatty acids are termed "essential" because they are necessary for life. Essential fatty acids, including DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid), are known to inhibit platelet aggregation and are included as potential contraindications for use with anticoagulant (warfarin) therapy. The contraindication is actually more of a strong caution to avoid thinning the blood too much. What this means is that if a patient on Coumadin does take fish oil supplements, the TBT test should be done in addition to checking the INR reference range.

Several studies examined the antiplatelet mechanisms of essential fatty acids like EPA and DHA and showed they inhibited collagen- and arachidonic acid-induced platelet aggregation. No effects were seen in thrombin-induced aggregation. The mechanism was related to the ability of these fatty acids to suppress thromboxane A2 formation by inhibiting cyclooxygenase-1 (Ikeda et al. 1998; Akiba et al. 2000).

An Australian study found that omega-3 fatty acids (those rich in alpha-linolenic acid, such as flaxseed and perilla oils) were more effective than omega-6 fatty acids (those rich in linoleic acid, such as sunflower oil) (Allman et al. 1995). This same result was also reported in a German study which found that an omega-3 to omega-6 ratio of 15:1 caused a significant decrease of collagen-induced platelet aggregation (Stroh et al. 1991).

Vitamin E
Vitamin E (tocopherol) is a potent antioxidant that has been shown to increase prostaglandin I2 synthesis, one of the platelet aggregation inhibitors and vasodilators. Vitamin E is depleted by estrogen, birth control pills, and chlorine.

A study found that vitamin E was able to inhibit collagen-induced platelet aggregation at concentrations achievable in blood after supplementation. The researchers also isolated a mechanism by which vitamin E blunts hydrogen peroxide formation, which then mediates arachidonic acid metabolism and phospholipase C activation in platelet aggregation induced by collagen (Pignatelli et al. 1999).

Caution: If vitamin E is used with Coumadin, the template bleeding time test should be done by the physician to guard against risk of hemorrhage.

Vitamin K
Vitamin K plays a unique role in the clotting system by contributing to both coagulation and anticoagulation. Vitamin K is a precursor of coagulation factors II, VII, IX, and X. Vitamin K is also a cofactor for the synthesis of proteins C and S. Protein C is a proteolytic enzyme that acts as an anticoagulant by inactivating clotting factors V and VIII and by increasing production of tissue plasminogen activator.

An article in the journal Lancet recommended that asymptomatic patients on Coumadin should consider low-dose vitamin K if blood-clotting time, as measured by the INR, is 4.5-10.0. The article described a multicenter, double-blind, placebo-controlled, randomized trial in which patients received either a placebo or 1 mg of vitamin K orally. Patients given vitamin K had a more rapid decrease in the INR than those given placebo, and fewer of them had bleeding episodes during the follow-up period. The authors concluded that low-dose vitamin K therapy rapidly lowers INR values in patients taking Coumadin and may be effective in preventing hemorrhage (one of the common side effects of Coumadin therapy) (Crowther et al. 1998, 2000).

Vitamin K counteracts the action of Coumadin and is strictly contraindicated in patients on anticoagulant drug therapy. The Life Extension Foundation recommends the use of 10 mg daily of vitamin K in healthy individuals.

Lowering Homocysteine
Homocysteine has slowly become accepted in conventional medicine as a risk factor for cardiovascular disease. Clinical research has shown that some vitamins (folic acid and vitamins B6 and B12) are very effective at lowering homocysteine levels. It has been proposed that homocysteine activates the blood clotting system by damaging endothelial cells.

An article in Thrombosis Research described a study of 11 persons with high homocysteine levels who had atherosclerosis. After an 8-week treatment with folic acid (5 mg daily, orally), vitamin B6 (300 mg daily, orally), and vitamin B12 (1000 mcg weekly, intramuscularly), homocysteine levels dropped from an average of 20 to 10. Vitamin treatment was also associated with a significant decrease in the markers of thrombin formation, including thrombin-antithrombin III complexes and prothrombin fragment 1+2 concentrations in peripheral venous blood. Bleeding time became prolonged by about 60 seconds (Undas et al. 1999).

The Life Extension Foundation strongly recommends that homocysteine levels be measured. Supplementation with vitamins B6 and B12 and folic acid are recommended to lower homocysteine levels.