10+ SUPPLEMENTS THAT CAN AFFECT BLOOD CLOTTING

If you have difficulties with bleeding and bruising, you may need to examine your supplements list and lower your intake of hidden anticoagulants. Many nutritional supplements are capable of increasing the risk of internal bleeding and related hospitalization and are often contraindicated for those on blood thinners.

This article aims to explain how anticoagulants work to thin the blood, why anticoagulants may be dangerous in some situations, and which nutritional supplements have potent blood-thinning effects. Anticoagulant additives are also reviewed.

How Anticoagulants Prevent Clotting

For optimal vascular functioning, it is vital for the body to be able to form blood clots through coagulation. The coagulation system refers to a cascade of signaling events that form a blood clot^[1]. Blood clots plug up micro lesions and wounds in blood vessels, preventing blood loss and facilitating repair. The system is regulated by the body’s anticoagulant pathways, which are often enhanced by supplements that thin the blood, as explained briefly below.

The Coagulation Cascade Made Easy. The coagulation cascade is composed of the contact system (intrinsic pathway) and the tissue factor pathway (extrinsic pathway).^[2] These refer to the activity of activation factors. Activation factors are released in response to vascular damage. They undergo a series of transformations in the presence of calcium (Ca2+) and blood platelets before converging at factor Xa and the production of thrombin from prothrombin (the common pathway). Thrombin acts on fibrinogen to create fibrin particles, which combine to produce a blood clot.

Platelets are specialized cells that become activated upon sensing vascular damage and in response to any factors in the coagulation cascade. When activated, they aggregate and tend to plug the wound with red blood cells and various fragmented proteins, such as von Willebrand factor (a clot-forming protein produced by injured vascular cells).^[3] Once fibrin is formed, it binds to the platelet clot and forms a very stable matrix that enhances wound healing.

Anticoagulation Systems. These help to regulate coagulation and prevent non-stop thrombosis. Their constituents are able to prevent coagulation and dissolve clots by acting on various steps of the coagulation cascade. The two main pathways are described below:

• Fibrinolytic (Plasminogen-Plasmin) System. This system comprises of the enzyme plasmin, which dissolves fibrin (fibrinolysis) through protein cleavage. Plasminogen is converted to plasmin by tissue plasminogen activator (TPA). These are secreted by vascular, liver and immune cells in the presence of fibrin, coagulant factors and several other stimuli, including cellular stress, histamine and chemical signals of pain. Inhibitory compounds continuously suppress TPA and plasminogen in favor of potential coagulation. The moment fibrin is formed and creates a clot, it allows for plasminogen to convert and for plasmin to dissolve the fibrin component.^[4] Plasmin additionally inhibits von Willebrand factor and regulates platelet activation.^[5]
• C-Protein S-Thrombomodulin System. This system serves to inhibit blood clot formation and enhance fibrinolysis. It begins with the coagulation cascade, which promotes the release of thrombomodulin from vascular cells. Thrombomodulin is a receptor that binds to thrombin and inactivates it. This interaction suppresses inflammation^[6], contributes towards fibrinolysis (dissolving fibrin) and causes the release of protein C. Together with its cofactor protein S, protein C inactivates coagulation factors and inhibits thrombin release. These effects are enhanced when it binds to the protein C receptor, which also reduces thrombomodulin activity. A large degree of inflammation can inhibit this pathway and promote coagulation.^[7]
• Liver Regulation of Coagulation. The liver releases blood thinners, antithrombin and heparin, in response to factors in the coagulation cascade and thrombin.^[8] Antithrombin and heparin bind to these factors and disable coagulation. They also serve to cleave fibrin and dissolve clots. Lipoprotein A in HDL cholesterol is known to bind to coagulant and anticoagulant factors and send them back to the liver for repurposing or excretion.

Anticoagulants Dissolve Blood Clots Via Inhibiting Coagulation. Anticoagulants thin blood by dissolving blood clots and/or by promoting anticoagulant factors in the body. Common types include fibrinolytics, antiplatelets that block platelet activation and antithrombotics that inhibit thrombin. Other anticoagulants may work via:

• Blocking Inflammation. Anti-inflammatory agents can prevent the coagulation cascade from being triggered by inflammation^[9] and excess Ca2+. Likewise, anticoagulants can often lower and moderate inflammation.
• Vasodilation. These lower the chances of blood clot formation by enhancing blood flow and preventing vascular damage associated with vasoconstriction.
• Vitamin K Depletion. This is another mechanism that inhibits blood clot formation. It works by blocking the production of all coagulant factors and their inhibitors that require vitamin K for their synthesis. Warfarin is a prime example of an anticoagulant that works primarily through depleting vitamin K body reserves, resulting in the inhibition of vitamin K epoxide reductase complex 1 (VKORC1).^[10] Coumarins are natural inhibitors of VKORC1 found in many medicinal herbs.

Are Anticoagulants Dangerous?

Much of the research over the last couple of decades has focused on thrombosis and reducing the risk of excessive blood clotting, as this is substantially associated with vascular stiffness, reduced blood flow, and an increased risk of embolism, cardiovascular disease and heart failure. Anticoagulants have both benefits and risks. Therefore, discussing the anticoagulant activity of nutritional supplements with a doctor is essential.

Blood Thinning Dangers. While not often thought about, bleeding can equally contribute towards cardiovascular disease risk and mortality. Anticoagulants have a broad range of actions that act on the coagulation system, each of which can lead to different side effects. Excessive blood thinning can detract from vascular strength, contribute towards vascular permeability, increase the risk of internal bleeding and slow down or even inhibit wound healing processes. These outcomes are unfavorable for helping a weak heart maintain optimal circulation.

Blood Clots Protect Against Damage and Infection. Aside from their pro-regenerative properties, blood clots serve the extra function of trapping cellular debris and pathogens from spreading in the circulation^[11], which helps to resolve infection and keep inflammation localized. In this sense, extreme blood thinning can make one more susceptible to chronic vascular injury, systemic infections and sepsis.

In line with the above aspects, it is important to maintain a fine balance between blood clotting and thinning, especially if taking blood-thinning medications such as warfarin.

Nutritional Supplements that Unexpectedly Thin Blood

Nutritional supplements, plant extracts and antioxidant-rich foods are often overlooked for their anticoagulant properties. They are frequently admired for their antioxidant and anti-inflammatory benefits that contribute positively towards disease prevention. Bleeding risk associated with supplement use may also be offset by their redeeming qualities, including antimicrobial properties, prebiotic support and their lower potency compared to anticoagulant medications.

The below nutritional supplements act on several parts of the coagulation cascade. They can be a cause for excessive bleeding for those taking anticoagulant medication and may exacerbate symptoms if taken together continuously in large doses.

Vitamin E. Irrespective of being a fat-soluble vitamin, vitamin E has a known reputation for being a blood-thinning supplement. Patients prescribed warfarin and taking supplemental vitamin E simultaneously were more likely to suffer from excessive bleeding^[12] and were advised against Vitamin E supplementation. Studies have not revealed how vitamin E promotes bleeding, yet it likely involves vitamin K depletion and acts in a similar way to warfarin, as supported across animal studies.

The vitamin also appears to reduce levels of plasminogen inhibitors, allowing for an increase in plasmin and fibrinolysis^[13].

Omega-3 Supplements. High doses of omega-3 supplements coupled with a fish-heavy diet may promote extreme blood thinning in some individuals and not others. Omega-3s can inhibit platelet aggregation, thrombin and clot formation^[14], as well as improve vasodilation^[15]. Its anticoagulant potential is frequently overlooked in favour of its lipid-lowering profile and association with a higher HDL to LDL ratio.^[16] This naturally increases the propensity of coagulant products to be swiftly removed from the bloodstream, further enhancing blood clot inhibition. Patients on warfarin are at a much higher risk of suffering from internal bleeding when supplementing with omega-3 fish oil.^[17] The risk may only be noticeable when other blood-thinning supplements are used, when the diet is high in fish, or in those without hypertension.^[18]

Selenium. It is not often acknowledged that selenium is an important trace mineral for regulating coagulation and that deficiency can substantially increase the risk of thrombosis. It is essential for maintaining adequate levels of bodily antioxidant enzymes like glutathione peroxidase, regulating inflammation and enhancing vasodilation. Aside from these effects, selenium directly promotes blood thinning through increasing plasminogen conversion^[19]. It primarily exerts these effects through its interactions with enzymes required to create clotting factors and those that inhibit plasminogen.^[20] Sources claim that selenium inhibits arachidonic acid from forming thromboxane A2^[21], which helps to inhibit platelets and resolve blood clotting. Selenium can increase the efficacy of warfarin, likely due to dislodging it from albumin in the bloodstream, and is contraindicated for patients on blood thinners.

Magnesium is referred to as a natural blood thinning agent due to its potent ability to reduce blood pressure, lower platelet aggregation^[22], decrease inflammation, inhibit fibrin formation^[23] and moderate calcium when present in higher concentrations. Its vasodilatory actions have been shown to help those with hypertension and may increase the chances of fibrinolysis.^[24] While long thought of as purely anticoagulant, research has highlighted magnesium’s role in coagulation as well. Studies suggest that it potentizes coagulant factors, reduces the number of factors required to form a clot and shortens the time it takes.^[25] This is likely to prevent excessive clotting and make coagulation more efficient. When coupled with any of the above supplements, large-dose magnesium has the potential to increase the risk of bleeding in patients on blood-thinning medications.

Others. Very high doses of vitamin D3, vitamin A, vitamin B3 and vitamin C have all been shown to promote blood thinning and negatively interact with some patients on warfarin. Similar results can be seen for Co-Q10 and the amino acid arginine. Caution is advised when contemplating taking one of these nutrients in very high doses. Low doses may be better tolerated for those on conventional blood thinners.

Blood Thinning Plant Extracts

Many supplemental plant extracts are sold for their health-promoting effects[4] [5] ^[26], many of which enhance blood thinning. In a large review of approximately 80 herbal extracts and supplements, 30 of them were shown to interact with prescription medications, with warfarin being one of the most frequently associated.^[27]

These interactions, especially the blood-thinning ones, are attributable to the phytochemical nutrients found across all medicinal plant extracts. Some of the most potent ones are reviewed below.

Licorice Extract is not the same as licorice candy and refers to preparations of the real root.

These are frequently warned about due to their hypertensive effects, which are caused by their interactions with the mineralocorticoid receptors in the adrenal glands.^[28] Licorice is now also noted to inhibit blood clotting in addition to exhibiting anti-inflammatory effects. The combination of elevating blood pressure and promoting anticoagulation dramatically increases the risk of bleeding, as confirmed by case reports of individuals suffering from intracranial hemorrhages after consuming licorice root.^[29]

Grapefruit Seed Extract. Grapefruit as a food is commonly reported to increase bleeding in those on blood thinners. Grapefruit seed extract is one of the most common supplemental forms of grapefruit, known for its superior antimicrobial profile and MAO inhibiting effects. On top of disrupting pathogen membranes in over 900 strains^[30], grapefruit seed extract is acknowledged to be a potent blood-thinning agent at minimal concentrations. It can inhibit both thrombin and blood platelets, directly halting the coagulation cascade in its tracks.^[31] Caution is advised for patients on blood thinners or antidepressants wishing to consume this supplement.

Chamomile has been shown to interact with warfarin as it contains compounds that antagonize vitamin K in a similar fashion^[32]. Studies support these findings, revealing its potent antiplatelet activities^[33], which are complemented by powerful anti-inflammatory effects. Products containing chamomile include topical ointments, teas and supplements, none of which ought to be underestimated for patients on warfarin.

Green Tea Extract. The main constituent of green tea, epigallocatechin-3-gallate (EGCG), is often sold as an extract for general health promotion. While it can prevent thrombin from successfully going on to form blood clots, EGCG’s main blood thinning actions extend towards platelet deactivation^[34], restoration of protein C levels and vasodilation. Similarly to quercetin, it contains tyrosine kinase inhibitory properties that block the action of calcium and blood platelets, preventing them from adding to clots.

Quercetin. In a review, quercetin proved to have one of the highest antithrombotic actions when compared to other flavonoids.^[35] It may additionally inactivate factor Xa and directly inhibit fibrin formation.^[36] Large-dose quercetin is also known to inhibit tyrosine kinase, which may lower platelet activation through several mechanisms.^[37] Quercetin may be a constituent of other antithrombotic herbs and plant extracts, such as chamomile.

Resveratrol is known to regulate platelet activation, reduce calcium’s involvement in coagulation^[38] and promote apoptosis (cell death) in platelets, thereby removing them from blood clots.^[39] It appears to mimic the actions of thrombomodulin, capable of binding to thrombin and neutralizing its effects.^[40] It may not be safe to supplement with resveratrol while on warfarin. Resveratrol is also found in a wide variety of other supplements, including grapefruit seed extract.

Others. Other compounds known to greatly increase the risk of bleeding include ginkgo, ginseng, garlic, ginger, curcumin, salicylates such as willow bark and aspirin, milk thistle, and jasmin. All of these are generally warned against for those on prescribed blood thinning medications and are frequently found in herbal supplemental formulations for reasons other than anticoagulation. Other lesser-known blood-thinning supplements and extracts include feverfew, passion flower, St. John’s wort, dong quai (Chinese herb), lycopene, and taurine.

Anticoagulant Ingredients and Additives

It might come as a surprise that over and above the active ingredients, the inactive ingredients in a supplement may potentiate its anticoagulant (side) effects. These are the binders, fillers, additives and other components that dictate the nutrient’s form.

Frequently understated anticoagulant ingredients include:

Sodium Bicarbonate is commonly used to lower bodily acidity and is a prime ingredient of antacids. It may be able to enhance the effectiveness of other anticoagulants and contribute towards bleeding by interfering with fibrin clot formation.^[41] Those on blood thinners may wish to avoid using large amounts of sodium bicarbonate in baths or supplementally, as well as avoid taking antacids.

Citrate has long been known to have anticoagulant properties that may even be superior to that of administered heparin. Its main mechanism of action would be its ability to bind to serum calcium, preventing activation of the coagulation cascade^[42] and prolonging the time till blood clot formation^[43]. Citrate is found in supplements as an additive, in food as a preservative, and is sometimes added as citric acid or sodium citrate. It is commonly sold as magnesium citrate, which may double up its calcium-inhibiting effects and increase its blood-thinning potential.

Extra Bioflavonoids are sometimes added to supplemental formulas to improve their nutritional value and extend their shelf life. As revealed above, many bioflavonoids are sold separately as plant extracts in very high concentrations. Their presence in low doses may be able to increase the anticoagulant effects of other supplements. This is usually beneficial yet may become problematic if too many are present in a formula or when they are paired with potent blood-thinning plant extracts.

The Difference Between Supplements and Foods

There is a big difference between supplementing any of the above nutrients and getting a steady supply of them from the diet.

Dietary Nutrients Should Not Be Removed. Many of the vitamins and minerals listed above are required in their respective dietary amounts to assist the body with both blood clotting and thinning. This is even true for patients on anticoagulant medications, who should not attempt to completely avoid these nutrients in their diet.

Moderation is Key. Moderating one’s daily intake of teas, herbs and spices can easily negate the associated bleeding risk, especially as the amounts are not high enough to be associated with significant side effects unless consumed in excess (which is usually undesirable and not very cost-effective). It is still important to remember that any amounts are prone to accumulating in the system in the long run, highlighting the benefit of moderate consumption and being consistent.

Blood thinning supplements are not likely to pose a significant risk unless one is taking them with prescription medication, in large quantities and/or taking a wide variety of them on a regular basis. However, if you are using supplements that contain any of the above nutrients or plant extracts in high quantities, being mindful of their interactions with your diet can help.

Plant Extracts vs Nutrient Supplements. It is comparatively easier to consume safe amounts of vitamins and minerals by comparison to plant extracts, as these have clinically proven safe upper limits and are constrained to one essential product. Plant extracts exhibit a broader range of active ingredients with many more effects that increase the likelihood of interacting with other supplements and medications.

Conclusion

The risk of bleeding while on anticoagulants is often dismissed in favor of minimizing thrombosis. Conventional anticoagulants interfere with the coagulation cascade and tend to disable the body’s ability to form clots as well as thin the blood. Natural supplements are becoming increasingly popular as a means of health promotion and disease prevention. However, many of them are capable of increasing the risk of bleeding, especially in those on blood thinners. It is important to weigh the pros and cons of supplements by consulting a doctor before opting to take them and to err on the side of caution. This is especially pertinent to plant extracts that are less standardized than essential vitamins and minerals.[6] [7] [8] 

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