Blood Clot Prevention: A Nutrition and Natural-Health Reference
1. Definition and Overview
Thrombosis is a main cause of death globally, representing the most common underlying pathology in major cardiovascular events, including acute coronary syndrome, stroke, myocardial infarction, pulmonary embolism, and venous thromboembolism. It occurs when a blood clot, or thrombus, forms within arterial or venous blood vessels due to an imbalance between pro- and anti-coagulant factors, leading to disrupted blood flow.
Hemostasis facilitates a series of enzymatic activations that lead to the formation of a clot with platelets and fibrin polymer. This clot seals the injured area, controls and prevents further bleeding while the tissue regeneration process takes place. When this same process occurs pathologically inside an intact vessel, the result is a thrombus that can obstruct blood flow and cause tissue damage.
Venous thromboembolism (VTE) is a condition that arises when a blood clot forms in a vein due to a disruption in hemostasis. It is a multifactorial chronic disease resulting from the interaction between acquired and hereditary risk factors. Acquired risk factors for VTE include modifiable factors like obesity, pregnancy, hormonal therapy, and immobilization, and non-modifiable factors such as advanced age.
2. Body Systems Involved
2.1 The Coagulation Cascade
The coagulation cascade, or secondary hemostasis, is a series of steps in response to bleeding caused by tissue injury, where each step activates the next and ultimately produces a blood clot. The term hemostasis is derived from "hem-" (blood) and "-stasis" (to stop), and therefore hemostasis is the process by which bleeding stops.
First, primary hemostasis forms an unstable platelet plug at the site of injury. Then, the coagulation cascade (secondary hemostasis) is activated to stabilize the plug, stop blood flow, and provide time for tissue repair.
The coagulation cascade has a common pathway that bridges the intrinsic and extrinsic pathways. Activated factor 10 with its cofactor (factor 5) in conjunction with calcium, tissue, and platelet phospholipids, converts prothrombin to thrombin. Thrombin breaks circulating fibrinogen to fibrin and activates factor 13, which crosslinks fibrin leading to a stable clot. The third stage in the clotting process is the termination of clot formation and the antithrombin control mechanism, which are designed to prevent and mediate the extent of clot formation, thereby preventing processes that can lead to thrombosis, vascular inflammation, and tissue damage.
2.2 Regulatory (Anti-Coagulant) Mechanisms
To prevent over-coagulation, which causes widespread thrombosis, there are certain processes to keep the coagulation cascade in balance. As thrombin acts as a procoagulant, it also acts as negative feedback by activating plasminogen to plasmin and stimulating the production of antithrombin. Plasmin acts directly on the fibrin mesh and breaks it down. Antithrombin decreases the production of thrombin from prothrombin and decreases the amount of activated factor X. Proteins C and S also act to prevent coagulation, mainly by inactivating factors V and VIII.
2.3 The Fibrinolytic System
The fibrinolytic system is a parallel system which is activated along with the coagulation cascade and serves to limit the size of the clot. Fibrinolysis is an enzymatic process that dissolves the fibrin clot into fibrin degradation products (FDPs) by plasmin originating from fibrin-bound plasminogen in the liver.
2.4 Clinical Manifestations
Deep vein thrombosis (DVT) is a blood clot that most often forms in the deep veins of the lower extremities or pelvis, but sometimes in the arm or other veins. A DVT can develop when blood flow slows, the vein wall is injured, or the blood becomes more likely to clot. Major risk factors include surgery, trauma, cancer, long periods of immobility, and serious medical illnesses.
Pulmonary embolism (PE) is a condition that occurs when part of a blood clot that forms in a deep vein breaks loose, travels to the lungs, and blocks blood flow in the pulmonary arteries. Blood clots starting in the thigh are more likely to travel to the lungs than blood clots in the lower leg or other parts of the body.
3. Contributing and Associated Risk Factors
3.1 Virchow's Triad
The pathophysiology of venous thrombosis has been famously described by Rudolf Virchow, known as the triad of Virchow, which includes stasis, endothelial injury, and hypercoagulability. Venous thrombosis can be superficial venous thrombosis or deep venous thrombosis (DVT). This triad remains the foundational conceptual framework for understanding thrombotic risk.
3.2 Exogenous (Environmental/Acquired) Risk Factors
Major risk factors for thrombosis, other than age, include exogenous factors such as surgery, hospitalization, immobility, trauma, pregnancy and the puerperium, and hormone use, and endogenous factors such as cancer, obesity, and inherited and acquired disorders of hypercoagulation.
All surgeries, especially major orthopedic and neurovascular surgeries, are associated with a significantly higher risk of DVTs and pulmonary embolism. Prolonged surgical times and post-surgical immobilization times are further associated with increased risk for DVTs.
Immobilization associated with prolonged travel, by air or ground, increases the risk of DVTs by 2 to 4 fold.
3.3 Obesity
Obesity is associated with an increased risk of VTE. The higher the body mass index, or BMI, the higher the risk. Obesity appears to be associated with an increased risk for VTE. A meta-analysis of 1 cohort and 8 case-control studies involving a total of 8,125 patients with VTE and 23,272 control patients indicated that the likelihood of first spontaneous VTE among people who were obese was more than twice that of individuals with a normal BMI (odds ratio = 2.33; 95% CI, 1.68–3.24). However, the OR reduced to 1.84 (95% CI, 1.55–2.18) after excluding three studies that had no adequate controls or BMI measurements.
3.4 Smoking
In a meta-analysis of 32 observational studies involving 3,966,184 participants and 35,151 events, current, ever, and former smoking was associated with risk of venous thromboembolism.
3.5 Hormonal and Genetic Factors
Oral contraceptives or estrogen treatment for menopause symptoms may increase the blood's tendency to clot by affecting clotting proteins. Family history of VTE, especially in a first-degree relative (parent, sibling, child), is also a recognized risk factor.
Over the past 20 years several gene variants have been identified as risk factors for venous thrombosis. These conditions are often referred to as "thrombophilic disorders," "thrombophilias," or "hypercoagulable syndromes."
3.6 Hyperhomocysteinemia
Elevated levels of homocysteine (Hcy) are associated with an increased risk for thrombosis. The association of hyperhomocysteinemia with thrombosis has triggered debate in the medical literature. While meta-analyses and prospective studies have found associations between moderate homocysteine elevations with recurrent thromboembolic events, other studies have disputed this relationship. Some nutritional deficiencies, such as folate or vitamin B12, can raise homocysteine levels.
3.7 Physical Inactivity
Low physical activity (PA) levels are associated with a higher risk of VTE, which has been shown for bed rest and a sedentary lifestyle. Two reviews concluded that higher PA level showed lower VTE risk versus low PA level. However, the relationship is not linear: one large longitudinal study of French women found that traditional cardiovascular risk factors, including physical activity, were not associated with the overall risk of thrombosis after adjustment for BMI, suggesting that confounding by obesity is an important consideration.
4. Dietary Factors and Patterns
4.1 General Role of Diet
An increased prothrombotic state is a major risk factor for the development of heart attacks, strokes, and venous thromboembolism. Platelet activation and aggregation play an important role in determining a prothrombotic state. Although pharmaceutical agents such as aspirin, heparin, and warfarin are able to reduce prothrombotic tendency, long-term drug treatment may produce a variety of side effects, including bleeding. Diet is generally recognized to be significantly involved in modifying the individual risk for the development of thrombotic diseases.
A review of the literature examining the effect of different plant-based diets (vegan, lacto-vegetarian, lacto-ovo-vegetarian, pescatarian, and flexitarian) and dietary patterns (Mediterranean, Nordic, Portfolio, and DASH) on specific thrombotic risk factors (fibrinogen, platelets, factor VII, fibrinolysis) demonstrated that a one-size-fits-all conclusion cannot be drawn, and that the potential antithrombotic effect of different plant-based diets depends on the nutrient composition, the content of active antithrombotic dietary components, the relative absence of prothrombotic dietary factors, as well as the degree of total caloric restriction.
4.2 Mediterranean Dietary Pattern
Many researchers have associated the Mediterranean diet with improvements in blood lipid profile (especially LDL cholesterol and triglycerides), decreased oxidation of lipids, and decreased risk of thrombosis (i.e., fibrinogen levels), all changes meaning improvement in endothelial function.
In participants of the PREDIMED (PREvención con DIeta MEDiterránea) study, a Mediterranean diet enriched with extra-virgin olive oil or nuts was assessed for effects on platelet count and cardiovascular outcomes. Accruing evidence from observational studies and randomized controlled trials such as PREDIMED indicates that following a Mediterranean diet reduces the risk of developing cardiovascular outcomes. It is believed that the Mediterranean diet exerts these benefits via improving glucose and lipid metabolism, enhancing endothelial function, and decreasing oxidative stress and low-grade inflammation.
Following a Mediterranean diet has been associated with improvements in atherothrombosis biomarkers, platelet function, and platelet count, as well as with decreases in the circulating levels of pro-thrombotic microvesicles.
4.3 Homocysteine, Folate, and B Vitamins
Although high homocysteine levels are associated with increased risk of blood clots, lowering homocysteine with folic acid and B vitamins does not reduce the frequency of venous blood clots. This suggests that simply targeting homocysteine through diet or supplements may not be effective for blood clot prevention.
5. Nutrients Studied in Relation to Blood Clot Prevention
5.1 Omega-3 Polyunsaturated Fatty Acids (PUFAs)
Diets rich in omega-3 polyunsaturated fatty acids (PUFAs), such as those found in fish like salmon, have been shown to prolong bleeding and clotting times, suggesting a potential benefit in reducing clot formation. These diets lead to the incorporation of omega-3 PUFAs into platelet phospholipids, which may alter platelet and hemostatic function.
Scientific Evidence: A meta-analysis of randomized controlled trials identified using PubMed, Embase, and the Cochrane Library included fifteen studies. In comparison to placebo, omega-3 PUFA supplementation significantly reduced adenosine diphosphate-induced platelet aggregation (SMD = −1.23; 95% CI −2.24 to −0.23, p = 0.02) and platelet aggregation units determined using the VerifyNow® rapid platelet-function assay (SMD = −6.78; 95% CI −12.58 to −0.98, p = 0.02).
In a study of 40 healthy subjects and 16 patients with a history of cardiovascular disease, omega-3 PUFA supplementation significantly reduced ADP-induced and adrenaline-induced platelet aggregation in healthy subjects. Omega-3 PUFA also reduced P-selectin expression on platelets and platelet-monocyte aggregates after ADP activation. There were fewer changes in platelet aggregation and activation found in subjects with CVD.
The Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT) demonstrated that daily intake of 2 × 2 g icosapent ethyl (IPE), a highly purified ethyl ester of EPA, reduced cardiovascular events by 25% compared with placebo in statin-treated high-cardiovascular-risk patients.
Limitations: The effect of omega-3 fatty acids on platelet aggregation and coagulation is highly unclear. Studies both support and refute the impacts of omega-3 fatty acids on prolonged bleeding time and platelet inhibition as well as their purported positive effects on cardiovascular disease. In one well-powered study on healthy volunteers, no effects of high doses of omega-3 fatty acids after 10 days of intake could be demonstrated, either on coagulation or platelet function.
5.2 Vitamin K
Warfarin acts by inhibiting epoxide reductase, a critical component in coagulation factor production because it helps recycle vitamin K. Without vitamin K, more coagulation factors cannot be produced by the liver. Vitamin K is therefore essential to the hepatic synthesis of coagulation factors II, VII, IX, and X, and of the anticoagulant proteins C and S. Consistent dietary intake of vitamin K is important for maintaining stable coagulation function.
5.3 Flavonoids and Polyphenols
Flavonoids, at concentrations mainly between 2 and 300 μM, are capable of regulating platelet aggregation, blood coagulation, fibrinolysis, and nitric oxide production due to their action on multiple receptors and enzymes. Most of the studies have been carried out through in vitro and in silico models.
Flavonoids are capable of regulating platelet aggregation, blood coagulation, fibrinolysis, and nitric oxide production due to their action on multiple receptors and enzymes; however, most studies have been carried out through in vitro and in silico models, and limited studies have reported the in vivo and clinical effect of flavonoids.
From all phenolic standards tested, flavonoids and especially a mixture of flavonoids (catechin + quercetin) showed higher in vitro antioxidant capacity and anti-inflammatory and antiplatelet efficacy, followed by polyphenols and then simple phenolics. A combined vitamin C and flavonoid supplement showed the most potent antioxidant capacity, but also the strongest anti-inflammatory and antiplatelet activities, suggesting synergy from the co-presence of flavonoids and vitamin C.
5.4 Vitamin C
Accumulating evidence suggests that vitamin C modulates platelet function and endothelial integrity, contributing to antithrombotic activity. Vitamin C (ascorbic acid), a well-known antioxidant, demonstrates anti-inflammatory, antithrombotic, immune-modulatory, and endothelial-protective activities across various experimental and clinical disease models. Evidence is largely from in vitro and experimental models; large-scale clinical trials specifically on thrombosis outcomes are limited.
5.5 Vitamin E
Antioxidant agents such as vitamin C, vitamin E, resveratrol, astaxanthin, and coenzyme Q provide additional vascular protection but can interfere with hemostasis, metabolism, or redox-sensitive pathways. Studies on vitamin E in patients on anticoagulant therapy suggest caution: patients who experienced bleeding events showed a significant difference in cholesterol-adjusted vitamin E levels compared with those who did not bleed, with higher vitamin E levels found in patients who bled. Overall evidence for vitamin E's role in thrombosis prevention specifically is preliminary and mixed.
6. Herbs and Natural Ingredients
6.1 Garlic (Allium sativum)
Traditional Use: Garlic has been used medicinally for millennia across Mediterranean, Egyptian, Chinese, and Indian (Ayurvedic) traditions. Traditional preparations included raw cloves, garlic-infused oil, and decoctions, applied for circulatory support, wound healing, and general vitality.
Scientific Evidence: Various clinical trials and meta-analyses have shown a positive impact of garlic in cardiovascular disease prevention, especially its effects on lipid levels; however, some contradictory results are also reported. Similarly, its effects on hypertension control and platelet function are mild with limited data availability. The possible reason for these inconsistent results is the difference in preparations with diverse composition, variations in sulphur content present in different garlic preparations used, and methodological variations.
A PubMed search and review of the literature found that garlic supplementation is strongly associated with surgical bleeding independent of anticoagulants. Evidence for garlic's antiplatelet effects is based on in vitro and some human studies, but clinical trial results remain inconsistent due to heterogeneity in preparations.
6.2 Ginger (Zingiber officinale)
Traditional Use: Ginger has a long history of use in Ayurvedic and Traditional Chinese Medicine (TCM) for circulatory stimulation, reducing blood stagnation, and as a warming herb. It was traditionally prepared as fresh root juice, dried powder, or decoction.
Scientific Evidence: Based on laboratory research, ginger is thought to inhibit thromboxane synthetase and decrease platelet aggregation. However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials. In one case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen. A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months. However, research in healthy people suggests that ginger has no effect on INR or the pharmacokinetics or pharmacodynamics of warfarin.
Overall evidence for bleeding risk associated with ginger supplementation is conflicting.
6.3 Turmeric / Curcumin (Curcuma longa)
Traditional Use: Turmeric has been central to Ayurvedic and TCM practice for over 2,500 years, used as an anti-inflammatory and circulatory herb. It was consumed as a food spice and prepared as a root paste, milk decoction, or powder.
Scientific Evidence: In vitro, turmeric has been shown to have antiplatelet effects. However, results from human research are inconsistent. Turmeric has reportedly increased the international normalized ratio (INR) in a patient using the vitamin K antagonist fluindione. However, use of a whole food supplement containing turmeric powder for 6 months does not influence INR in men taking warfarin. Also, combining curcumin 500 mg with aspirin 100 mg does not appear to increase antiplatelet effects or bleeding risk.
A review of Chinese herbal medicines and drug interactions found that among the major consequences were increased bleeding risks due to the additive anticoagulant or antiplatelet effects, specifically including turmeric. Evidence in humans for curcumin as an independent antithrombotic agent remains preliminary and inconsistent.
6.4 Ginkgo Biloba
Traditional Use: The leaves and seeds of Ginkgo biloba have been used in Chinese medicine for hundreds of years to support circulation, memory, and respiratory conditions. Traditional preparations included decoctions of leaves and seeds.
Scientific Evidence: Ginkgo may decrease platelet aggregation, and many case reports have suggested increased bleeding risk, as verified by a systematic review. The increased bleeding risk posed by ginkgo may therefore be of great concern in persons taking anticoagulants such as warfarin. A statistical analysis using a large clinical data repository suggests that taking ginkgo concurrently with warfarin significantly increases patients' risk of a bleeding adverse event (hazard ratio = 1.38; 95% CI: 1.20 to 1.58, p <.001).
Ginkgo biloba is a widely used herbal product that could potentially have a severe interaction with warfarin. However, the literature provides conflicting evidence on the presence and severity of the interaction.
6.5 Nattokinase
Traditional Use: Nattokinase is an enzyme found in natto, a traditional Japanese food produced by fermenting soybeans with the bacterium Bacillus subtilis. Natto has been consumed in Japan for over 1,000 years and was traditionally associated with cardiovascular longevity in Japanese dietary culture.
Scientific Evidence: Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, lipid-lowering, antiplatelet, and neuroprotective effects.
In 1987, Sumi et al. discovered that natto contained a potent fibrinolytic enzyme called nattokinase. Since then, a considerable amount of research confirmed that NK is an alkaline protease of 275 amino acid residues with a molecular weight of approximately 28 kDa, and is responsible for many favourable effects on cardiovascular health.
Nattokinase is capable of inhibiting platelet aggregation by blocking the formation of thromboxane and inactivating the type 1 plasminogen activator inhibitory factor. Recently, it was proposed that nattokinase can attenuate oxidative stress and the inflammatory process in in vitro and animal models. However, there are no studies in dyslipidemic patients evaluating these data. Clinical evidence in humans remains limited; larger randomized controlled trials are needed to establish efficacy and safety.
6.6 Resveratrol
Traditional Use: Resveratrol, a stilbene polyphenol, occurs naturally in grapes, red wine, and certain berries. Its use is not associated with a specific traditional medical system, though grape and wine consumption have been part of Mediterranean folk medicine and diet for centuries.
Scientific Evidence: Resveratrol might improve cardiovascular health by affecting the gene expression of platelet aggregating factors. Antioxidant agents such as resveratrol provide additional vascular protection but can interfere with hemostasis, metabolism, or redox-sensitive pathways. Most studies to date have been preclinical (in vitro or animal models); robust human clinical trial evidence specifically on resveratrol and thrombosis prevention is lacking.
6.7 Green Tea Catechins
Traditional Use: Green tea (Camellia sinensis) has been consumed in China, Japan, and across Asia for over 2,000 years. Traditional and folk medical systems used green tea for its stimulating, detoxifying, and cardiovascular-supporting properties.
Scientific Evidence: Green tea catechins exert antithrombotic effects through the inhibition of thromboxane A2 (TXA2) formation by modulating arachidonic acid liberation and TXA2 synthase. Most evidence is from in vitro and animal studies. Human clinical trials specifically on catechins and thrombosis endpoints are limited and preliminary.
6.8 Danshen (Salvia miltiorrhiza), Dong Quai (Angelica sinensis), and Licorice (Glycyrrhiza spp.)
Traditional Use: These herbs occupy a central role in Traditional Chinese Medicine (TCM) for circulation, blood nourishment, and gynecological conditions. Danshen is used for "blood stasis" conditions; Dong Quai is a foundational blood tonic; licorice functions as a harmonizing herb in many TCM formulas.
Scientific Evidence: A structured review found that 90 single-entity Chinese herbal medicines contributed to 306 documented drug-herb interactions. A total of 194 (63.4%) interactions were verified for their evidence describing possible mechanisms and severity; 155 interactions (79.9%) were attributable to pharmacodynamic interactions, and almost all were rated as moderate to severe. The major consequences were increased bleeding risks due to the additive anticoagulant or antiplatelet effects of the herbs, specifically danshen, dong quai, ginger, ginkgo, licorice, and turmeric. These findings are based on documented interactions and case evidence rather than prospective clinical trials on thrombosis prevention.
6.9 Flaxseed and Grape Seed Extract
Scientific Evidence: Randomized controlled trials have shown that flaxseed oil decreases platelet aggregation, and grape seed extract increases platelet closure time in humans. These represent relatively specific mechanistic findings; long-term clinical outcome data for thrombosis prevention are not yet established.
7. Dietary and Lifestyle Factors
7.1 Overall Dietary Composition
Diet plays a significant role in the prevention of blood clots, with certain foods and nutrients influencing blood coagulability. Dietary intervention has proven effective in lowering serum lipid levels, which are otherwise essential elements in the pathogenesis of cardiovascular disease. Likewise, certain dietary components have been proven effective in decreasing platelet activation through various mechanisms and therefore may contribute to attenuating the future risk of thrombotic events.
Evidence from in vitro, ex vivo, and clinical studies underscores the importance of integrating dietary strategies into preventive and therapeutic approaches for managing thrombosis and cardiovascular health.
7.2 Mediterranean Dietary Pattern — Summary of Evidence
Mediterranean diet interventions promote the consumption of fruits, vegetables, pulses, nuts, and fish; the use of virgin olive oil as the main culinary fat; a decrease in the intake of ultra-processed foods and animal fats; and the substitution of red and processed meats for poultry. Despite the relatively large number of studies included in systematic reviews, there is still some uncertainty regarding the effects of a Mediterranean-style diet on clinical endpoints and CVD risk factors for both primary and secondary prevention.
7.3 Oxidative Stress and Dietary Antioxidants
Oxidative stress is a condition characterized by an imbalance between excessive production and inadequate clearance of reactive oxygen species (ROS), leading to disruption of the cellular redox balance — a mechanism linked to endothelial injury and platelet activation in thrombosis. A diet rich in antioxidant-containing foods (fruits, vegetables, whole grains) is considered relevant to maintaining vascular endothelial health, though translation from in vitro antioxidant activity to confirmed clinical endpoints requires further investigation.
7.4 Physical Activity
The inverse association between physical activity and arterial thrombotic disease is well established. Evidence on the association between physical activity and venous thromboembolism is divergent. Low physical activity levels are associated with a higher risk of VTE, which has been shown for bed rest and a sedentary lifestyle, and two reviews concluded that higher PA level showed lower VTE risk versus low PA level.
7.5 Nutraceuticals — General Evidential Caution
Several nutraceuticals demonstrate potential cardiovascular benefits through lipid-lowering, antithrombotic, and vascular protective mechanisms. Omega-3 fatty acids, berberine, garlic, and nattokinase exert favorable metabolic and vascular effects, yet their clinical efficacy depends on formulation, dosage, and patient characteristics, and may be limited by bleeding risk or drug interactions.
In selected patients, such as those with statin intolerance or seeking integrative approaches, certain supplements may provide incremental benefit, though routine use for CVD prevention is not supported by high-quality evidence. Nutraceuticals should not replace proven therapies.
Some supplements promoted for anti-atherosclerotic effects also possess antiplatelet activity and may increase bleeding risk, particularly in patients receiving anticoagulant or antiplatelet drugs. Examples include omega-3 fatty acids, garlic, ginkgo biloba, ginseng, curcumin, vitamin E, ginger, green tea extract, and high-dose fish oil. Caution is advised in patients on anticoagulation or undergoing surgery.
Further research is needed to better understand long-term effects and personalize these interventions for optimizing patient outcomes.
References
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