A combination of pycnogenol, an anticoagulant derived from French Maritime pine, and nattokinase, an enzyme from fermented soybeans, is proving effective for preventing deep vein thrombosis and leg edema during prolonged air travel.
Data from the ongoing LONFLIT-FLITE series of trials indicate that this proprietary combination of plant-based substances can reduce the incidence of deep and superficial thromboses as well as swelling of the lower extremities in high-risk individuals. The fixed combination, available from Aidan Products as Flite Tabs, has shown no adverse effects, and offers significant advantages over compression hose and low molecular weight heparin.
Deep vein thrombosis (DVT) is far more common and more serious than many people realize. The best current estimates suggest that between 4% and 10% of all individuals on flights of 7 hours duration or greater have DVTs or leg edema. While the majority of cases are asymptomatic, DVTs can cause significant discomfort, and are sometimes fatal.
DVT risk increases with the length of flight time. Risk is also increased by age, prior history of DVT or venous insufficiency, cardiovascular disease, obesity, diabetes, renal disease, cancer, oral contraceptives or other hormonal therapies, smoking, and chronic fatigue syndrome.
London’s Heathrow airport reports an average of one death per month associated with DVT, and a nearby hospital recorded 30 DVT-associated passenger deaths over the past 3 years. Similarly, the Narita hospital near Tokyo’s main international airport recorded an average of between 100 and 150 episodes of DVT requiring immediate treatment each year. Between 3% and 5% of individuals admitted to Narita for flight-related DVTs die from complications.
In the US, DVT is the fourth leading cause of stroke, and there are roughly 2,000 deaths attributed to DVTs each year. This is likely an underestimate, since in many cases DVT goes unrecognized as the underlying cause of a stroke death.
Better than Heparin
Julian Kenyon, MD, a British surgeon who now heads the Dove Clinics in the UK, estimated that greater than 10% of the patients in his comprehensive holistic practice are at increased risk for flight-related DVTs. He has been recommending the Flite Tabs formula for more than a year now, and has found it to be convenient, safe and highly effective.
“It is more effective than heparin, which does not reduce leg swelling while Flite Tabs do. Leg swelling is much more than just a nuisance; it is an indicator of poor venous return,” Dr. Kenyon told Holistic Primary Care. He currently recommends the product to all at-risk patients who must travel by air, and this includes short flights. While risk of DVT is lower for flights of fewer than 6 hours, it is still significant, especially if a patient is already at risk. “There’s really no such thing as a safe flight.”
The Flite Tabs formula contains 150 mg of “Pinokinase,” a proprietary combination of pycnogenol and nattokinase. The former is a water extract from the bark of French maritime pine trees that is rich in bioflavonoids including catechin, epicatechin, taxifolin, proanthocyanidins and phenolic fruit acids in very consistent proportions.
Pycnogenol is produced by Natural Health Science/Horphag, and has been well studied in Europe. In angiographic trials it was shown to increase capillary wall resistance, making vessels less permeable. Clinically, this translated into reduced edema both objectively and subjectively in patients with venous insufficiency (Schmidtke I, Schoop W, J Suisse Med Globale 1995; 3(95): 114–115; Petrassi C, et al., Phytomedicine 2000; 7: 383–388).
Nattokinase, the other active constituent of Flite Tabs, is a fibrinolytic enzyme derived from a traditional Japanese fermented soy food called Natto. Oral consumption of nattokinase produces a measurable increase in fibrinolytic activity in plasma (Sumi H, JTTAS 1994; 1: 49; Sumi H, et al., Nihon Shokukakoushi 1996; 43: 139–140).
“Nattokinase is highly fibrinolytic,” said Dr. Kenyon. “If you put a blood clot in a test tube and add nattokinase, it dissolves readily. Pycnogenol also reduces platelet stickiness without increasing bleeding time.” Combined, pycnogenol and nattokinase appear to have a synergistic and highly complementary effect.
Dr. Kenyon was among the investigators in the recently published LONFLIT-FLITE trial (Cesarone MR, et al., Angiology 2003; 54(5): 531–539). The study involved 204 patients at high-risk for DVT and about to take flights of 7–8 hours between New York and London. They were randomized to either placebo or Flite Tabs (two 150-mg capsules two hours before flight time, and two more six hours later).
Subjects had a mean age of 49 years (range = 27–69 years), and all had significant DVT risk factors including prior DVT history, coagulation disorders, obesity, limited joint mobility, large varicose veins, CVD, or history of cancer within the last two years. Subjects taking anticoagulants, antithrombotic drugs or any other cardiovascular drugs were excluded. Both the control and the active treatment groups were told to do mild isometric exercises (standing and moving legs for 5–10 minutes every hour), and to drink 100–150 ml of water every hour.
The investigators used ultrasound scanners to evaluate the femoral, popliteal, tibial and superficial veins within 90 minutes of take-off, and again within 90 minutes of landing. They also measured D-dimer and fibrinogen levels at least 12 hours before and within 4 hours after the flights. Objective measures (ankle circumference, calf volume) and subjective rating of leg edema were combined in a single edema score, calculated prior to and immediately following the flights.
There were a total of seven thrombotic events in the control group: 5 DVTs and 2 SVTs, for a total event rate of 7.6% among the 92 patients. There were no events whatsoever in the Flite Tabs group. Patient dropouts were due largely to missed flight connections or other travel associated problems.
The differences between the two groups were even more marked with regard to leg edema. The post-flight combined edema score for the controls was increased by 12%, whereas the active-treatment group showed a 15% decrease. Among the controls, 89% had a measurable increase in ankle circumference and volume, which was readily apparent and associated with discomfort.
In terms of blood chemistry, the D-dimer and fibrinogen values were within normal ranges both before and after flights in both groups, with no significant differences.
Based on the strength of the LONFLIT findings, Aidan Products is hoping to convince British Airways and other major carriers to stock Flite Tabs on all long-haul flights.
Dr. Kenyon stressed there were no adverse effects, either objective or subjective, associated with Flite Tabs. While it is natural for clinicians to be concerned about giving a potent fibrinolytic agent to patients already on warfarin or other blood-thinning drugs, he has had patients combine the two without ill effect.
CFS Patients, Serious Athletes at Risk
He has identified two patient subgroups at high-risk for DVTs that often go overlooked: high performance athletes and people with chronic fatigue syndrome (CFS). In the former group, the risk is attributed to their characteristically low heart rates. “Many serious athletes have resting heart rates of under 50 beats per minute, which can increase the odds of venous pooling. So you sometimes see very fit young people ending up with DVTs which are sometimes fatal.”
At the other end of the physical activity spectrum, patients with CFS tend to have very sticky blood. “You frequently see a lot of red cell aggregation, with rouleaux (cells stacked together like rolls of coins) which greatly increases risk of DVT.” For both of these groups, Dr. Kenyon routinely recommends Flite Tabs whenever such patients must travel by air.
He has also found the product useful in clinical contexts not involving air travel. “I am using it more and more for patients undergoing surgery. Among the reasons for readmission following any type of surgery, DVT is very common. So, if you give Flite Tabs as soon as possible after surgery, you will reduce the risk of post-surgical DVT.”
Dr. Kenyon is also using the pycnogenol-nattokinase combination in the management of hypertension, particularly among men. He was prompted to do so by a Japanese study of nattokinase showing it to be effective in the control of mild hypertension. “Conventional antihypertensives tend to induce impotence. With Flite Tabs, I can gradually get patients off the conventional drugs.” So far, he has treated 10 hypertensive men in this manner, and he believes this is a topic that is ripe for a full-scale clinical trial.