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Life Extension Magazine

Life Extension Magazine May 2012
As We See It

Reducing Dangerous Varicose Veins with Phlebotonics

By Sarah Clachar
Reducing Dangerous Varicose Veins with Phlebotonics

Unsightly and painful varicose veins, which often mar attractive legs, are more than a cosmetic nuisance. Worming over calves and the lower thigh, these swollen blood vessels hint at more serious circulatory problems.

Varicose veins are a visible sign of chronic venous insufficiency (CVI) which affects more women than men.

Chronic venous insufficiency is marked not only by varicose veins but also by painful ulcers, achy and heavy legs, tingling sensations, cramps, skin pigmentation, itchy and hot feet, and edema.1,2 Restless leg syndrome (RLS) also shows up as a secondary dysfunction associated with chronic venous disease.3,4

Along with the aches and disfiguration, chronic venous disease also brings enormous expense. In the US alone, CVI is behind the loss of an approximately 2 million working days and accounts for an estimated $3 billion in health care costs.5

Surgery, vein stripping, and compression stockings or bandages have all been used with some degree of success to help with the symptoms of chronic venous disease. But nothing has come close to the inexpensive and effective treatment found in taking 600 mg diosmin once a day.6,7

Diosmin is prescribed as a standard pharmaceutical intervention in Europe for chronic venous disease as well as hemorrhoids. Identified in 1925, diosmin is derived from the flavonoid, hesperidin, found in citrus rinds.8

In 2009, Life Extension Magazine® reported that diosmin is the only oral therapy that has been shown to work for chronic venous disease.

Recent studies continue to strengthen the case for diosmin as a treatment for chronic venous disease.

An Alternative Treatment That Works

Surgical remedies are expensive. Compressive bandages are tedious to apply and change. Even worse, they can damage tissue around ulcers that are slowly trying to heal.

For these reasons, doctors are increasingly looking at phlebotonics as a proven effective and safe way to treat chronic venous insufficiency. 9-11 Phlebotonics are drugs or nutrients indicated for improving vein health.

Of the various phlebotonics, diosmin has been singled out as especially useful in countering chronic venous disease. The authors of one review of research published in the journal Current Vascular Pharmacology concluded that, “Although numerous pharmacological agents have been proposed and studied, [diosmin] has demonstrated the greatest clinical benefits in patients with venous disease.”8

Diosmin reduces the sensation of pain, swelling, tension, and heaviness in the legs associated with chronic venous disease.12-15 When it comes to strengthening the tone of distended, weak varicose veins, diosmin helps increase vascular tone at the peripheral sympathetic nerve terminals.16 In one study done on an isolated rat vein, diosmin increased the strength of contractions from 26.3% of the maximum response possible to 78.9%.17

Diosmin has also demonstrated the ability to reduce the size of “cankles,” the lay term used to describe how calves and ankles start to merge into one swollen mass.10,18

In 2010, a team of Czech researchers published the results from a 27-center study involving 215 patients. Within two months of starting a diosmin regimen, participants were pleasantly surprised to see their ankle and calf circumferences shrink by more than half a centimeter. Overall leg volume decreased by an average of 78 cubic centimeters.14

When asked about overall quality of life improvement and satisfaction with the treatment, 93.5% of participating physicians responded that they considered diosmin treatment to be good to excellent. When the patients were queried, 91% responded that they were satisfied or very satisfied and 82% decided to continue using the diosmin after the study finished.14 In addition to working alone, diosmin can also complement other treatments for chronic venous disease. Taken before and after varicose vein surgery, it can decrease the pain and subcutaneous bleeding associated with surgery.13 It’s also proven a useful aid to treating ulcers with compressive bandages.8

Restless Leg Syndrome and Diosmin

Restless Leg Syndrome and Diosmin

Few cures have emerged for the primary form of restless leg syndrome (RLS). RLS is characterized by an overwhelming urge to move one’s legs due to uncomfortable sensations such as creeping, crawling, pulling, itching, tingling, burning, aching, or electric shock type pain.19 Restless leg syndrome may be categorized as either primary which means that the cause is of unknown origin (idiopathic) or as secondary which means that the symptoms are due to some other condition such as chronic venous disease, nerve damage, pregnancy, anemia, and rheumatoid arthritis.19 Researchers have attributed it to being a sleep disorder, mood disorder, problem associated with kidney disease, and a central nervous system disorder. However, none of these hypothetical causes have led to much relief.5 On the contrary; many of the pharmacological treatments prescribed for restless leg syndrome have made the problem worse with the patient incurring additional side effects.20

One form of restless leg syndrome seems to be a secondary development of venous diseases. In a 2007 study published in Phlebology, researchers found that 36% of patients suffering from chronic venous disease also had restless leg syndrome. In comparison, the control population only had 19% occurrence of restless leg syndrome. Interestingly, when the control participants who showed positive for restless leg syndrome were studied more closely, researchers discovered 91% of them had mild indications of venous problems.5

In contrast to the poor track record treatment for primary restless leg syndrome has, treating secondary restless leg syndrome offers much more promise. Data also shows that by alleviating the symptoms of chronic venous disease, secondary restless leg syndrome will be eliminated as well.14,21 In one study, participants with restless leg syndrome who received medical treatment for chronic venous disease reported a 36% increase in quality of sleep and a 67% decrease in severity of symptoms. 22 In a 2010 study, not only did chronic venous disease sufferers experience relief from venous problems by using diosmin but researchers also documented a 60% decline in restless leg syndrome.14

Pharmaceutical inhibitors of the enzyme, catechol-O-methyl transferase (COMT) have been used to help ease symptoms of restless leg syndrome.23 But they can also have severe side effects. For example, the COMT inhibitor, tolcapone (Tasmar®), has been withdrawn from use in several countries (excluding the US) because it can increase liver problems by as much as 100%.24

Diosmin has been shown to effectively inhibit the enzyme COMT,25 but with few or no side effects.9 Diosmin enjoys an excellent record of safety and tolerability.9

Additionally, the symptoms of secondary restless leg syndrome—tingling and crawling sensations in the legs—may be caused by the flow of edema fluid in the legs when a patient reclines at night and elevates their legs. Researchers have observed that restless leg syndrome seems to cause the most discomfort and involuntary leg movement at night and wanes in the morning when the swelling has dissipated.20 Because of this, diosmin’s demonstrated role in relieving edema explains why it may help in relieving restless leg syndrome as well.

What You Need to Know: Diosmin - Head to Toe Benefits
Diosmin - Head to Toe Benefits
  • Varicose and spider veins are indications of deeper circulatory problems known as chronic venous insufficiency (CVI). Heredity and sex factor into developing CVI as well as extensive time spent sitting or standing.

  • Diosmin has been used therapeutically for 30 years and considered by some experts to be the most effective therapy of CVI. It is prescribed in Europe as a treatment for CVI and hemorrhoids.

  • Diosmin may also bring relief to people suffering from secondary Restless Leg Syndrome (RLS) caused by CVI.

  • Some data indicates the possibility of dangerous interactions between blood thinners, like warfarin, and diosmin.

  • Preliminary data shows that diosmin may provide answers for people struggling with diabetes, neurological problems like Alzheimer’s, melanoma and colon cancer, lymphedema and chromosomal damage associated with radiation treatment and women’s reproductive health problems.

Diabetes and Diosmin

Research on rats has demonstrated that diosmin may help with the management of diabetes. In one study, 100 mg/kg body weight diosmin for 45 days reduced blood glucose levels and reduced hemoglobin glycolization.26 The researchers also noted that diosmin worked in a dose dependent manner.

Diosmin and Brain Health

Preliminary studies indicate that diosmin may play a role in preventing neurological diseases like Alzheimer’s and autism.

In a study conducted on mice, researchers found that orally-administered diosmin reduced the number of soluble and insoluble beta-amyloid plaques by 37 and 46% respectively.27 Diosmin along with another closely related compound, luteolin, may inhibit an enzyme implicated in the development of beta-amyloid plaques known as glycogen synthase kinase 3, and has been linked to several disorders of the central nervous system.27

Autism researchers have also observed that diosmin and luteolin seem to block the cytokine, Interleukin-6 (IL-6). IL-6 released during pregnancy has been linked to causing fetal brain development problems connected to autism. The researchers hope that this discovery may play an important role in the prevention of autism during pregnancy.28

What Causes Chronic Venous Insufficiency?
What Causes Chronic Venous Insufficiency

Each pump of the heart pushes the blood around the body. This pump works well for the outgoing blood coursing through the arteries. But by the time blood hits the return trip through the veins, much of the propulsion generated by the heart is gone. To add to the challenge, blood traveling up the legs to return to the heart has to fight gravity as well.

Your body has special mechanisms to aid in this fight. When you walk—with each step—the pressure on your foot and the contraction of your calf muscle pushes the blood upward. Additionally, each pump of your heart pushing blood outward also creates a small vacuum that pulls blood in.

With these three mechanisms, your body can move blood back to the heart. But they also depend heavily on a special feature in your physiology that keeps the blood from seeping back when the pressure is off.

Veins in the leg come equipped with flap-like, one-way valves. When the leg muscles relax after blood moves up through the vein, the flap closes off the vein below.

This helps reduce venous pressure in the lower legs. A normal healthy leg will start with about 90 mm Hg of venous pressure. With each step this pressure decreases to as low as 10 mm Hg.

However, without the valve system working, pressure doesn’t dissipate. The blood seeps back down the leg and builds up pressure in the lower veins, keeping a steady venous pressure of about 90 mm Hg.37

This increased pressure, in turn, weakens the valves farther down, adding to the problem. Engorged with blood, the veins’ walls weaken, turning them into varicose and spider veins.

Eventually, blood seeps out through the weakened vein walls and pools in the calves. The build-up of lymph fluid and blood causes swelling and discoloration. In the worst cases, painful, stubborn ulcers develop.

Height,38 heredity,39 obesity,38 and lifestyle all play a role in the risk for chronic venous insufficiency. Standing or sitting for long periods of time is associated with developing chronic venous insufficiency since it prevents the calf muscles from helping the blood return to the heart.40

Sex may also be a risk factor although some data shows little difference between men and women in their risk for chronic venous insufficiency.41,42 However, there may be a twist to this. Women may develop chronic venous insufficiency as much as six years earlier than men on average. And this earlier development of chronic venous insufficiency may contribute to the greater severity in symptoms women experience.39

Diosmin as Part of Cancer Therapy and Recovery from Treatment

Diosmin may help on two fronts when it comes to treating cancer.

Diosmin itself may work synergistically with other treatments in directly fighting cancer. In vitro studies demonstrated that while the benefit did not come directly from diosmin, its metabolite diosmetin, effectively killed colon cancer cells and inhibited several breast cancer cell lines.29 Diosmetin is produced by your body when it metabolizes diosmin.

Diosmin also seems to augment the effectiveness of Interferon-alpha (IFN-alpha) in the treatment of melanoma. IFN-alpha is one of the most effective treatments for skin cancer. But it’s also very expensive with numerous side effects. However, when combined with diosmin, lower doses of IFN-alpha proved to be just as effective as the standard doses.30

As an added benefit, diosmin may help counter the debilitating side effects of radiation treatment.

One small-scale human study shows diosmin may bring relief to breast cancer patients suffering from secondary swelling (lymphodema) caused by radiation treatment. In women suffering from severe lymphodema, diosmin increased lymphatic migration speed by six times greater than the control group.31 Similarly, one study on rats has shown a similar promise for helping people dealing with proctitis, a painful inflammation of the rectum often incurred through radiation treatment. When diosmin was administered, the rats displayed less inflammation and glandular distortion than the controls showed.32

Finally, diosmin has been shown to protect lymphocytes against genetic damage caused by radiation exposure. Human blood samples were exposed to 150 cGy of cobalt-60 gamma rays. Within an hour, the samples from people who took diosmin before the samples were taken showed 40% less micronuclei than the control samples. The presence of micronuclei usually indicates some level of chromosomal damage.33

Diosmin For Women’s Health

Diosmin For Womens Health

A couple of studies conducted in the late 1990s demonstrated that diosmin relieved the symptoms of pre-menstrual syndrome.34,35 Very little research has been done to follow up on how diosmin may help women with reproductive health issues.

However, in 2008, a group of Bulgarian physicians reported that they rely on the anti-inflammatory properties of diosmin to help reduce uterine contractions in pregnant women at risk for premature delivery. The reporting physicians theorize that diosmin reduces the chance of preterm delivery by blocking the production of prostaglandins and leukotrienes, signal molecules associated with spurring contractions.36

Summary

Sufferers of chronic venous insufficiency may find relief in the natural substance, diosmin.

Diosmin has been shown to improve the tone and health of veins, reduce swelling in the calves and ankles, reduce pain and fatigue in the legs, and even alleviate the symptoms of restless leg syndrome. Many health experts consider diosmin to be the only effective treatment for many of the symptoms associated with lower circulatory problems. In addition, preliminary research indicates diosmin may also help combat diabetes and certain cancers, reduce the risk of neurological diseases, help with women’s reproductive health problems, and prevent swelling (lymphodema) and chromosomal damage associated with radiation treatment.

However, diosmin may be contraindicated if you are taking warfarin or other anticoagulants. If you take any blood thinning medication, please check with your physician before using diosmin.43

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

References

1. Bergan JJ, Schmid-Schönbein GW, Smith PD, Nicolaides AN, Boisseau MR, Eklof B Chronic venous disease N Engl J Med. 2006;355:488-98.

2. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000203.htm. Accessed February 16, 2012.

3. Kanter AH. The effect of sclerotherapy on restless legs syndrome. Dermatol Surg. 1995 Apr; 21:328-32.

4. Available at http://morrisonvein.com/Files/RLS_Information.pdf. Accessed February 28, 2012.

5. McDonagh, B, King T, Guptan RC. Restless legs syndrome in patients with chronic venous disorders: an untold story. Phlebology. 2007;22(4):156-63.

6. Milic DJ. Prevalence and socioeconomic data in chronic venous disease: how useful are they in planning appropriate management? Medicographia. 2011;33:253-8.

7. Carpentier PH, Mathieu M. Evaluation of clinical efficacy of a venotonic drug: Lessons of a therapeutic trial with hemisynthesis diosmin in “heavy legs syndrome.” J Mal Vasc. 1998;23(2):106-12.

8.. Diosmin Monograph. Alt Medicine Review. 2004;9(3):308-11.

9. Gohel MS, Davies AH. Pharmacological agents in the treatment of venous disease: an update of the available evidence. Curr Vasc Pharmacol. 2009 Jul;7(3):303-8.

10. Martinez, MJ, Bonfill, X, Moreno, RM, Vargas, E, Capella, D. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2005;(3):CD003229.

11. Ramelet AA, Boisseau MR, Allegra C et al. Veno-active drugs in the management of chronic venous disease. An international consensus statement: current medical position, prospective views and final resolution. Clin Hemorheol Microcirc. 2005;33(4):309-19.

12. Tsukanov luT, Tsukanov Alu. Results of administering Phlebodia 600 in fertile women with orthostasis-dependent phlebopathy. Angiol Sosud Khir. 2007;13(3):107-12.

13. Pokrovsky Av, Saveljev VS, Kirienko AI et al. Surgical correction of varicose vein disease under micronized diosmin protection (results of the Russian multicenter controlled trial DEFANS). Angiol Sosud Khir 2007;13(2):47-55.

14. Navratilova Z. Efficacy of a 6-month treatment with Daflon 500 mg* in patients with venous edema (Efficacy of Daflon 500 mg* in Edema Treatment. EDET). Phlebolymphology. 2010;17(3)137-42.

15. Maksimović ZV, Maksimović M, Jadranin D, Kuzmanović I, Andonović O. Medicamentous treatment of chronic venous insufficiency using semisynthetic diosmin--a prospective study. Acta Chir Iugosl. 2008;55(4):53-9.

16. Sher E, Codignola A, Biancardi E, Cova D, Clementi F. Amine uptake inhibition by diosmin and diosmetin in human neuronal and neuroendocrine cell lines. Pharmacol Res. 1992 Dec;26(4):395-402.

17. Savineau JP, Marthan R Diosmin-induced increase in sensitivity to Ca2+ of the smooth muscle contractile apparatus in the rat isolated femoral vein. Br J Pharmacol. 1994 Apr;111(4):978-80.

18. Tsukanov luT, Tsukanov Alu, Bazhenov VN. The effect of oral contraceptives on the orthostatic diameter of lower limb major veins and its correction. Angiol Sosud Khir. 2008;14(1):75-7.

19. Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/rls/. Accessed February 21, 2012.

20. Demanet E, Verstraeten, ME. The efficacy of diosmin in restless legs syndrome. Stragen corporation. Unpublished white paper. Stragen Pharma S.A. 2002: 5.

21. Trenkwalder C, Paulus W. Restless legs syndrome: pathophysiology, clinical presentation and management. Nat Rev Neurol. 2010;6(6):337-46.

22. Tison F, Crochard A, Leger D, Bouee S et al. Epidemiology of restless legs syndrome in French adults: A nationwide survey: The INSTANT Study. Neurology. 2005;65(2):239-46.

23. Allen RP, Connor JR, Hyland K, Earley CJ. Abnormally increased CSF 3-Ortho-methyldopa (3-OMD) in untreated restless legs syndrome (RLS) patients indicates more severe disease and possibly abnormally increased dopamine synthesis. Sleep Med. 2009 Jan;10(1):123-8.

24. Watkins P. COMT inhibitors and liver toxicity. Neurology. 2000;55(11 Suppl 4):S51-2; discussion S53-6.

25. Boudet, C, Peyrin L. Comparative effect of tropolone and diosmin on venous COMT and sympathetic activity in rat. Arch Int Pharmacodyn Ther. 1986 Oct;283(2):312-20.

26. Pari L, Srinivasan S, et al. Antihyperglycemic effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Biomed Pharmacother. 2010 Sep;64(7):477-81.

27. Rezai-Zadeh K, Shytle RD, Bai Y, Tian J. Hou H et al. Flavonoid-mediated presenilin-1 phosphorylation reduces Azheimer’s disease beta-amyloid production. J Cell Mol Med. 2009 March; 13(3): 574-88.

28. Parker-Athill E, Luo D, Bailey A et al. Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism. J Neuroimmunol. 2009 Dec 10;217 (1-2):20-7.

29. Androutsopoulos VP, Mahale S, Arroo RR, Potter G. Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation. Oncol Rep. 2009 Jun;21(6):1525-8.

30. Alvarez N, Vicente V, Martinez C. Synergistic effect of diosmin and interferon-alpha on metastatic pulmonary melanoma. Cancer Biother Radiopharm. 2009 Jun;24(3):347-52.

31. Pecking AP, Fevrier B, Wargon C, Pillion G. Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to conventional therapy of breast cancer). Angiology. 1997 Jan;48(1):93-8.

32. Sezer A, Usta U, Kocak Z, Yagci MA. The effect of a flavonoid fractions diosmin + hesperidin on radiation-induced acute proctitis in a rat model. J Cancer Res Ther. 2011 Apr-Jun;7(2):152-6.

33. Hosseinimehr SJ, Ahmadi A, Mahmoudzadeh A, Mohamadifar S. Radioprotective effects of Daflon against genotoxicity induced by gamma irradiation in human cultured lymphocytes. Environ Mol Mutagen. 2009 Dec;50(9):749-52.

34. Meggiorini ML, Cascialli GL, Luciani S, Nusiner MP, Pozzi V. Randomized study of the use of synthetic diosmin in premenstrual and vascular dysplastic mastodynia. Minerva Ginecol. 1990 Oct;42(10):421-5.

35. Serfaty D, Magneron AC. Premenstrual syndrome in France: epidemiology and therapeutic effectiveness of 1000 mg of micronized purified flavonoid fraction in 1473 gynecological patients. Contracept Fertil Sex. 1997 Jan;25(1):85-90.

36. Milchey N, Batashki I, Markova D, Dimitrova E. Using phlebodia in pregnant women during preterm delivery. Akush Ginekol (Sofiia). 2008;47(5):7-9.

37. Coleridge Smith PD. The microcirculation in venous hypertension. Vasc Med. 1997;2:203-13.

38. Svestkova S, Pospisilova A. Risk factors of chronic venous disease inception. Scripta Medica, BRNO. 2008;82(2):111-21.

39. Fiebig, A, Krusche, P, Wolf , A, Krawczak, M, Timm, B. Heritability of chronic venous disease. Human Genetics. doi: 10.1007/s00439-010-0812-9.

40. Sudoł-Szopińska I, Bogdan A, Szopiński T, Panorska AK, Kołodziejczak M. Prevalence of chronic venous disorders among employees working in prolonged sitting and standing postures. Int J Occup Saf Ergon. 2011;17(2):165-73.

41. Evans CJ, Fowkes FGR, Ruckley CV, Lee AJ. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study. J Epidemiol Community Health. 1999;53:149-53.

42. Brand FN, Dannenberg AL, Abbott RD, Kannel WB. The epidemiology of varicose veins: the Framingham Study. Am J Prev Med. 1988;4:96-101.

43. Kumar RM, Van Gompel JJ, Bower R, Rabinstein AA. Spontaneous intraventricular hemorrhage associated with prolonged diosmin therapy. Neurocrit Care. 2011 Jun;14(3):438-40.