Life Extension Magazine®

Citrus rind containing diosmin used in phlebotonics supplement

Reducing Varicose Veins with Phlebotonics

Unsightly varicose veins are indicative of venous insufficiency, a serious circulatory problem where blood pools in the lower extremities. For years, diosmin, a natural extract of citrus rinds, has been used as a prescription drug in Europe. It is now available in the US as a dietary supplement for the relief of chronic venous insufficiency and the related restless leg syndrome.

Scientifically reviewed by: Dr. Heidi Yanoti, DC, in August 2023. Written 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


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.


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