Natural Approach to Guard Against Deep Vein ThrombosisJanuary 2017
By Michael Downey
Long periods spent sitting—behind a desk, in a car, on a long flight, or on a couch—increase the risk of deep vein thrombosis (DVT), a blood clot that forms mainly in a deep vein in the leg, which can lead to a pulmonary embolism, a condition that is often fatal.1,2
Practically anyone can be at risk, and the statistics are frightening. According to the American College of Cardiology, those who sit more than four hours a day have a 48% increased risk of mortality from blood clots that originate in the veins.3
Through a series of well-designed studies, scientists investigating certain natural extracts found that they can block these blood clots from forming and can help break down small clots before they grow.4-7 They also found that these extracts safely restore the natural anti-clotting and clot-reversal processes, making a dangerous clot less likely to form and quicker to resolve if it does.7-10
When tested on humans in a placebo-controlled study, those taking a dual plant extract experienced zero cases of deep vein thrombosis compared to 5.4% afflicted in the control group.6
Veins have valves, which work with the natural pumping action of the leg muscles to prevent backflow of blood into the lower limbs. With age those valves tend to leak. In people who don’t move around much, blood tends to pool in their legs.
According to the Centers for Disease Control and Prevention (CDC), as many as 900,000 Americans could be affected by venous thromboembolisms (blood clots) every year.11 Compare that to epidemics like all forms of cancer, which kill about 570,000 Americans annually.
As sedentary lifestyles become common, the threat of deep vein thrombosis continues to grow and claim an ever larger number of lives.
Research conducted by the American College of Cardiology found that individuals that spent four hours or more a day sitting compared to those who spent less than 2 hours had an approximate 125% increase in risk of cardiovascular events. This association was independent of traditional risk factors like smoking, hypertension, physical activity, and body mass index.3 Some even consider sitting to be the new smoking!12
How Deadly Venous Thromboembolism Occurs
A deep vein thrombosis can occur quickly, often at first with no warning symptoms. But when this clot breaks apart, symptoms occur with a deadly vengeance. Large pieces of the clot travel silently through the circulatory system and eventually block blood flow into the lungs. This sudden event produces a pulmonary embolism, a blockage that can severely reduce, and even entirely stop, critical blood flow to the lungs—an event that is commonly fatal within minutes.
About 30% of those with a venous thromboembolism will die within one month, and about 25% of those fatalities will occur as sudden death. And about 33% of survivors have a recurrence within 10 years.11 Venous thromboembolisms are estimated to kill up to 100,000 Americans annually.11
Lifestyle changes can reduce the risk, such as quitting smoking, regularly exercising, and eating a healthy diet, but these are often insufficient to prevent a deadly catastrophe. Anticlotting drugs involve a risk of undesired bleeding, 13,14 and compression stockings have shown limited effectiveness.15,16 The reason that these approaches provide limited protection is that with physical pooling of blood, natural clot-breakdown systems slowly lose pace with the body’s clot-forming systems.17,18
Clearly, a new defensive strategy is needed.
A natural, dual plant extract formula has been studied based on its ability to simultaneously inhibit venous clot formation and promote venous wall elasticity.
Combating Deep Vein Thrombosis
After searching for natural, deep vein thrombosis-inhibiting interventions, scientists identified two ingredients that demonstrated powerful preventive effects:
- Nattokinase, an enzyme extracted from soybeans fermented with the bacterium Bacillus natto, and
- French maritime pine bark, a natural extract rich in polyphenols.
Nattokinase was shown in studies to break down fibrin—long, strand-like molecules that make up the main protein found in clots—and its precursor, fibrinogen, both of which are involved in red blood cell-induced clot formation.8,19,20 Nattokinase decreased levels of other factors in the blood-clotting cascade, while raising levels of factors that prevent clotting. Specifically, nattokinase reduces the activity of two proteins (factor VIII and factor VII) that can produce unwanted clotting when elevated. No adverse effects or undesirable bleeding were reported.4
French maritime pine bark extract was demonstrated to reduce platelet aggregation, while increasing the activity of a blood flow-boosting enzyme that generates nitric oxide in blood vessels. Nitric oxide plays a critical role in regulating vascular function, which reduces thrombotic risks.
Nattokinase and pine bark extract were shown to work together to prevent clots as well as to improve the microcirculation of the legs.9,21
French maritime pine bark extract was also found to inhibit the action of “protein-melting” matrix metalloproteinase enzymes. These enzymes would otherwise degrade elastic proteins in the blood vessel walls, making them stiff and reducing blood flow.10,22
Given these observations, scientists recognized that these two extracts could result in significant prevention of deep vein thrombosis by:4,7-10,19-22
- Inhibiting unwanted clot formation within veins,
- Improving microcirculation in the veins of the legs, and
- Promoting elasticity of vessel walls.
- Inducing breakdown of fibrin clots.
Now let’s look at a more detailed evaluation of these ingredients.
Nattokinase Breaks Down Blood Clots
Before designing human trials, scientists conducted animal studies that clearly demonstrated the beneficial effects of nattokinase.
Studies in dogs showed that nattokinase produces a mild—but steady—increase in the rate of fibrin degradation in the blood. This effect works to prevent clots and to reduce the size and toughness of any existing ones.8
When nattokinase was given to dogs with experimentally-induced blood clots, researchers were literally able to watch the clots break down in real time using a type of X-ray technology called angiography.8
Then, in spontaneously hypertensive rats—a standard model for studies of high blood pressure in humans—nattokinase was demonstrated to break down fibrinogen (the precursor to fibrin) in the blood. And by a related mechanism, nattokinase reduced blood pressure, potentially by preventing conversion of the hormone angiotensin into its active, blood pressure-boosting form.23
A human study evaluating the effects of nattokinase found that it improves markers of coagulation. For this study, researchers recruited volunteers comprised of healthy individuals, cardiovascular disease patients, and dialysis patients. On a daily basis for two months, subjects took two capsules of nattokinase, each containing 2,000 fibrinolytic units.4
The researchers found that all three groups demonstrated significant decreases in procoagulation factors VII and VIII, and fibrinogen compared to baseline, suggesting that nattokinase works equally well in individuals with normal and impaired endothelial and coagulation function.4
No adverse effects were seen in this study,4 and safety tests completed on nattokinase confirmed its low-risk status.20
Preventing Venous Thromboses with French Maritime Pine Bark Extract
Scientists also conducted human studies on French maritime pine bark extract’s effects on the risks of venous thrombosis.
First, they enlisted 198 people at risk for deep or superficial venous thromboses during flights ranging from seven to 12 hours, with an average flight time of 8.25 hours.5 Test subjects were randomly assigned to either the control or test group. The test group took two capsules, each containing 100 mg of French maritime pine bark extract, two to three hours preflight, two more capsules six hours into the flight, and one capsule the day after. The controls took placebos at the same intervals. All subjects underwent ultrasound scans of their leg veins within 90 minutes before and after their flights to detect clots.
The French maritime pine bark extract-treated group showed no blood clots for an event rate of 0.0%. But the placebo group showed four superficial venous thromboses and one deep venous thrombosis, equivalent to an event rate of 5.15%. No adverse events were observed.5 This study presented evidence to support that French maritime pine bark extract can prevent dangerous blood clots during prolonged sitting.5
Guarding against Lower Leg Fluid Accumulation
The same scientific team conducted a similar study to evaluate ankle swelling during long-haul air flights.24 Aside from being uncomfortable, ankle swelling is an excellent indicator of poor blood return up the veins of the legs, making it a great way to assess the risk of deep vein thrombosis.
The team enlisted 169 volunteers at risk of deep vein thrombosis due to remaining seated during a long flight. The same dose of 200 mg of French maritime pine bark extract was given at the same intervals as in the earlier study. Using standard measurements, edema (swelling) was measured before and after flights, as well as the rate of swelling.
Compared to preflight levels, the edema score in placebo subjects was increased by 58.3%. The edema score in the French maritime pine bark extract-supplemented volunteers increased only 17.9%. This dramatic decrease in edema score represented a significantly reduced thrombotic risk.24 Similarly, the ankle swelling rate was increased during the flight by a mean of 91% in controls, while the French maritime pine bark extract recipients showed only a 36% increased ankle swelling rate, a much safer rate.24
These studies showed the capacity of French maritime pine bark extract to reduce the risk of deep vein thrombosis without any of the side effects of anticlotting drugs. However, the question remained as to whether this extract was superior to compression stockings, which are known to be safe but not necessarily effective in reducing post-thrombotic syndrome. Post-thrombotic syndrome is a common complication of an otherwise localized deep vein thrombosis, in which blood pools in the affected leg because it cannot return to the heart—causing skin swelling, thinning, and discoloration and sometimes, painful, infection-prone leg ulcers.
To settle this issue, scientists conducted a study comparing French maritime pine bark extract to compression stockings in their ability to prevent post-thrombotic syndrome.25 In this study, 156 patients who had experienced a single, major episode of deep vein thrombosis were divided into three groups. For 12 months, one group used the compression stockings, the second group took 50 mg of French maritime pine bark extract three times daily, and the third group used both the stockings and the same daily French maritime pine bark extract regimen.25 The researchers measured edema score, ankle circumference, and volume of the previously deep-vein thrombosis-afflicted leg compared with the other leg.
These confirmatory findings indicate that this novel dual-extract formula helps prevent deep vein thrombosis.
Their findings soundly confirmed the superior effectiveness of French maritime pine bark extract:25
- In the compression stocking-only group, two new deep vein thrombosis cases occurred in the first six months, compared with no new deep vein thrombosis cases in either of the pine bark extract groups.
- After the first six months, French maritime pine bark extract alone proved significantly more effective than compression stockings alone for relieving symptoms of edema (while the combination of both was better still).
- Leg volume and ankle circumference measurements showed French maritime pine bark extract-plus-stockings to be superior to stockings alone.
- In the microcirculation (blood flow in the tiniest vessels), French maritime pine bark extract—but not compression stockings—enhanced blood flow, raised oxygen levels in circulating blood, and decreased carbon dioxide levels, demonstrating improved function.
Human Clinical Trial Combining Nattokinase and French Maritime Pine Bark Extract
Scientists set out to test a formulation combining nattokinase and French maritime pine bark extract in a randomized, placebo-controlled human trial.6 All 204 passengers on a New York-to-London flight were instructed in deep vein thrombosis-prevention techniques: isometric exercises, standing and moving for five to ten minutes, and keeping hydrated. Passengers were randomly assigned to receive either capsules of placebo or capsules of the proprietary blend of nattokinase and French maritime pine bark extract. All subjects took the blend two hours predeparture and again six hours later. Ultrasound scans were done before and after the flight to detect clots.
Passengers taking the supplement had zero deep vein thrombosis cases. However, five of the control passengers developed a deep vein thrombosis, and two others developed superficial clots, for a total of seven events—a 5.4% DVT rate among controls, compared to a 0.0% rate among the test subjects.6 The scientists also measured leg swelling, which was equal between the two groups preflight. Edema increased by 12% in the controls. But edema decreased by 15% in the supplemented passengers.6
These findings confirm that this novel dual-extract formula helps prevent deep vein thrombosis in individuals who spend long periods sitting and reduces the risk of sudden death from a resultant pulmonary embolism. No adverse side effects were reported.
Deep vein thrombosis is a serious risk for anyone who spends long periods sitting and can lead to a deadly pulmonary embolism.
The two novel ingredients described in this article were shown to protect against venous thrombosis.
These extracts inhibit unwanted venous clot formation, improve leg microcirculation, and promote vessel-wall elasticity.
In a placebo-controlled human trial, these two nutrients prevented deep vein thrombosis in all volunteers who supplemented with it and decreased leg swelling.
While the medical establishment provides no safe or practical solutions, these two agents are available to augment the effects of taking frequent breaks from any kind of prolonged sitting.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Available at: http://www.medicinenet.com/deep_vein_thrombosis/article.htm. Accessed September 19, 2016.
- Available at: http://emedicine.medscape.com/article/1911303-overview. Accessed September 19, 2016.
- Stamatakis E, Hamer M, Dunstan DW. Screen-based entertainment time, all-cause mortality, and cardiovascular events: population-based study with ongoing mortality and hospital events follow-up. J Am Coll Cardiol. 2011;57(3):292-9.
- Hsia CH, Shen MC, Lin JS, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009;29(3):190-6.
- Belcaro G, Cesarone MR, Rohdewald P, et al. Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol. Clin Appl Thromb Hemost. 2004;10(4):373-7.
- Cesarone MR, Belcaro G, Nicolaides AN, et al. Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial. Angiology. 2003;54(5):531-9.
- Kurosawa Y, Nirengi S, Homma T, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.
- Sumi H, Hamada H, Nakanishi K, et al. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol. 1990;84(3):139-43.
- Golanski J, Muchova J, Golanski R, et al. Does pycnogenol intensify the efficacy of acetylsalicylic acid in the inhibition of platelet function? In vitro experience. Postepy Hig Med Dosw (Online). 2006;60:316-21.
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- Available at: http://www.cdc.gov/ncbddd/dvt/data.html. Accessed September 20, 2016.
- Available at: http://www.huffingtonpost.com/the-active-times/sitting-is-the-new-smokin_b_5890006.html. Accessed September 22, 2016.
- Hass B, Pooley J, Harrington AE, et al. Treatment of venous thromboembolism - effects of different therapeutic strategies on bleeding and recurrence rates and considerations for future anticoagulant management. Thromb J. 2012;10(1):24.
- King DA, Pow RE, Dickison DM, et al. Apixaban versus enoxaparin in the prevention of venous thromboembolism following total knee arthroplasty: a single-centre, single-surgeon, retrospective analysis. Intern Med J. 2016;46(9):1030-7.
- Skervin AL, Thapar A, Franchini AJ, et al. Systematic Review and Meta-Analysis of Utility of Graduated Compression Stockings in Prevention of Post-Thrombotic Syndrome. Eur J Vasc Endovasc Surg. 2016;51(6):838-45.
- Jin YW, Ye H, Li FY, et al. Compression Stockings for Prevention of Postthrombotic Syndrome: A Systematic Review and Meta-Analysis. Vasc Endovascular Surg. 2016;50(5):328-34.
- Favaloro EJ, Franchini M, Lippi G. Aging hemostasis: changes to laboratory markers of hemostasis as we age - a narrative review. Semin Thromb Hemost. 2014;40(6):621-33.
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- Ero MP, Ng CM, Mihailovski T, et al. A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose. Altern Ther Health Med. 2013;19(3):16-9.
- Lampe BJ, English JC. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food Chem Toxicol. 2016;88:87-99.
- Fitzpatrick DF, Bing B, Rohdewald P. Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol. 1998;32(4):509-15.
- Grimm T, Chovanova Z, Muchova J, et al. Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol). J Inflamm (Lond). 2006;3:1.
- Fujita M, Ohnishi K, Takaoka S, et al. Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats. Biol Pharm Bull. 2011;34(11):1696-701.
- Cesarone MR, Belcaro G, Rohdewald P, et al. Prevention of edema in long flights with Pycnogenol. Clin Appl Thromb Hemost. 2005;11(3):289-94.
- Errichi BM, Belcaro G, Hosoi M, et al. Prevention of post thrombotic syndrome with Pycnogenol(R) in a twelve month study. Panminerva Med. 2011;53(3 Suppl 1):21-7.
- Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(4 Suppl):S495-501.
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- Shirakawa T, Iso H, Yamagishi K, et al. Watching Television and Risk of Mortality From Pulmonary Embolism Among Japanese Men and Women: The JACC Study (Japan Collaborative Cohort). Circulation. 2016;134(4):355-7.