Flavonoids Keep the Blood Flowing.....

A major age-related disorder yields to natural plant chemicals

Remember when you were in junior high school and there was a long, ominous rope hanging from the ceiling of the gym? And you got a knot in the pit of your stomach when your gym teacher told you to shinny up it as fast as you could? That may have been the day when the concept of gravity really hit home, as you realized how difficult it was (and still is) to climb vertically against the gravitational pull of the earth. This is probably pretty much how red blood cells feel when they try to get from your feet and legs back up to your heart - it's a long, hard haul that they have ahead of them.

Getting to your feet in the first place was easy, of course. The blood was under pressure from the pumping of your heart and was traveling with the force of gravity. The return route is challenging, however. There are no pumps in your feet or legs to supply a force that can propel your blood upward against the force of gravity, but your body is nothing if not resourceful, and it relies on your leg muscles to do most of the work. As the muscles contract, they squeeze the veins and force the blood upward to your heart. What prevents the blood from being forced back down is a series of one-way valves inside the veins; when functioning properly, these valves permit blood flow only in the right direction.

There is a lot of pressure (literally) on your veins, and if they don't hold up to it adequately, a host of ills can come your way. For example, individuals with poor venous (vein) health may suffer from swelling of the legs and ankles, varicose veins, and hemorrhoids (see the sidebars for more on these conditions), or the potentially more serious disease called chronic venous insufficiency (CVI).

Tips for Improving Your Venous Tone

Loss of venous tone can develop or be aggravated by standing for long periods. As a result, blood may begin to accumulate in the leg veins and give rise to varicose veins. The word varicose stems from the Greek word meaning "twisted," which aptly describes the appearance of these bulging, unsightly veins. Because deep veins are surrounded by muscle tissue, they are not prone to varicosity; only veins on the surface become varicose. However, deep veins can still become distended, a condition that allows fluid to seep into the tissues and promote swelling. Swelling is typically greatest in the lower legs and ankles, which are farthest from the heart and thus under the greatest pressure.

If you have "bad genes," you may not be able to avoid edema, varicose veins, or hemorrhoids. But there are several steps you can take to make these conditions less troublesome. Here are some helpful suggestions:

  • Exercise regularly to strengthen thigh and calf muscles. Muscle contraction in the legs promotes good circulation and helps maintain good venous tone.
  • Try wearing compression stockings. Stockings with graduated compression (more pressure at the feet and ankles, and less at the calves) appear to be the most effective.
  • If you are a desk worker, take frequent breaks to walk around and stimulate circulation in your legs. Try not to sit with your legs crossed, as this impedes circulation and may place additional pressure on the veins.
  • Elevate your legs above your heart at least once a day for 10-15 minutes.
  • To lessen the risk of hemorrhoids, make sure that you eat a diet high in fiber to avoid constipation and straining.

Horrible Hemorrhoids

You may not immediately see the relationship between varicose veins and hemorrhoids; but in reality, hemorrhoids are just varicose veins of the anus. The veins in this region are subject to considerable pressure during the passage of stools, especially if there is straining. If the veins become sufficiently weakened by poor venous tone or excessive pressure, they may become varicose. What starts as an embarrassing but perhaps only annoying condition can eventually spiral out of control, to the point of agony and, possibly, the need for surgery.

Because flavonoids are so beneficial in improving venous health, is it at all surprising that these wonderful molecules are also effective at relieving hemorrhoids? Research conducted last year demonstrated that the administration of micronized flavonoids stops acute bleeding of internal hemorrhoids and also prevents relapse of the bleeding.1Importantly, 80% of the patients treated with flavonoids stopped bleeding within three days of the initial dose, versus only 38% of the control group.

A separate study demonstrated that anal discomfort, pain, swelling, discharge, and prolapse (the condition in which hemorrhoids protrude through the anal opening) all decreased in response to flavonoid treatment, when measured against the control group.2 Flavonoids to the rescue!

  1. Misra MC, Parshad R. Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal hemorrhoids. Brit J Surg2000;87:868-72.
  2. Godeberge P. Daflon 500 mg in the treatment of hemorrhoidal disease. A demonstrated efficacy in comparison with placebo. Angiology 1994;45:574-8.


But there is relief for the afflicted, and a means of prevention for those at risk. It comes in the form of citrus fruits, of all things. Oranges, in particular, are rich in a compound called hesperidin, which is a flavonoid, a type of plant chemical that is receiving much positive press these days in terms of promoting better health. A combination of hesperidin with another citrus flavonoid called diosmin has significantly improved the symptoms of CVI in clinical trials.

Chronic venous insufficiency is a common disease in Western societies. As the name implies, it is a condition in which certain veins (notably those of the legs) become increasingly unable to maintain normal, healthy function. Circulation in individuals with CVI becomes sluggish, and leg tissues may not receive adequate nourishment from the blood, causing localized tissue death. One manifestation of this dire situation is an open skin lesion called a venous ulcer.

One study demonstrated that the 
beneficial effects of flavonoids are
ongoing for at least six months; 
they may well go on indefinitely.

But what causes this deterioration in venous function? It can be traced to two factors in the circulatory system: weakness in the walls of the veins, which can cause them to become distended, and damage to the one-way valves, which can prevent them from closing completely. If the valves fail, blood can backflow and begin to pool up, placing greater pressure on the vein walls. The vein then swells (if this occurs at the skin surface, the result is a varicose vein), the walls are stretched, and plasma - the watery portion of your blood - seeps out into the surrounding tissue, causing edema (swelling).

Normal open valve 
Normal closed valve
Leaky valve


The early stages of CVI are often difficult to diagnose and may occur with no apparent symptoms. As the disease progresses, however, symptoms such as edema in the lower legs and ankles, tenderness or heaviness in the calves, discoloration of the skin, varicose veins, and venous ulcers may occur. These symptoms tend to worsen with prolonged sitting or standing and can impair one's ability to work and enjoy life. The greatest danger by far, however, is blood clots in the deep veins (deep-vein thrombosis), which can break loose, travel to the lungs, and cause sudden death by pulmonary embolism.

Before we get too melodramatic, though, let's consider the beneficial effects of the flavonoids diosmin and hesperidin, which have been used with great success to protect against the ravages of poor venous health.

Most of the research on diosmin and hesperidin has been conducted in Europe, where these nutrients together have been known for several years as micronized purified flavonoid fraction (MPFF).

A number of studies have demonstrated that MPFF improves circulation by improving venous health. Blood flows through the veins more smoothly, without collecting in the lower extremities, and swelling is thus reduced. In a recent review of chronic venous insufficiency published in the journal Angiology, Dr. Albert Ramelet claims that MPFF, owing to its wide-ranging effects, is the method of choice in treating both the early and advanced stages of CVI.1 MPFF improves venous tone and elasticity of the circulatory system, protects the microcirculation (small veins and capillaries), and improves drainage of the lymphatic system. All this helps to reduce edema in the legs and ankles, as measured by a decrease in the leg circumference at both the calf and the ankle.2

Since edema is one of the most frequent complaints of patients with CVI, and one that can cause considerable discomfort, its alleviation through flavonoid treatment is welcome relief. The reductions can be impressive. For example, following treatment with MPFF twice daily (for a total of 900 mg of diosmin and 100 mg of hesperidin per day) for six weeks, patients with edema showed a decrease in the volume of fluid in their legs by an average of 392 ml (equivalent to 13 fl oz, or about 1 1/2 cups).3Additional research has confirmed these results, and one study demonstrated that the beneficial effects of flavonoids are ongoing for at least six months (the duration of the trial); they may well go on indefinitely.4

One of the consequences of CVI is that small veins and capillaries become more permeable to fluid. The resulting leakage of plasma through the vein walls causes edema. At the same time, some leukocytes (white blood cells) may also migrate from the blood to the tissues. This can provoke an inflammatory response and may lead to further damage to the tissues and the vein walls.5 Flavonoids bind up molecules that leukocytes require to initiate and maintain an inflammatory response, and in this way they may diminish the inflammation.

One clinical trial that enlisted 36 French patients with CVI demonstrated that MPFF (500 mg twice daily for two months) dramatically improved skin disorders caused by inflammatory reactions, as well as eczema caused by the pooling of blood in the veins.6

Eighty-eight percent of the MPFF-treated patients showed significant improvement or complete resolution of skin disorders during the two-month time frame, compared with only 21% in the control group.

Additional complications of CVI are skin ulceration and delayed wound healing. Thus it is encouraging to discover that the diosmin/hesperidin combination improves the rate and completeness of wound healing and also accelerates the healing of venous ulcers. One recent study revealed that wound healing is greatly improved following administration of MPFF twice daily for two months. Venous ulcers were completely healed in 32% of the MPFF-treated group, compared with only 13% of the control group.7

A separate study demonstrated that flavonoids are especially beneficial in healing small ulcers of less than 3 cm (1.2 in.) in diameter. A daily dose of 1000 mg of MPFF (in addition to standard compression therapy, which consists of wearing tight elastic stockings) healed these small ulcers in 71% of the patients, versus a 50% healing rate when compression therapy alone was used. Larger ulcers (36 cm, or 1.22.4 in.) healed much better in the treated group as well (60% vs. 32%).8

Additional research indicates that other ingredients also aid in reducing the problems associated with poor venous tone. For example, an extract of horse chestnut seed appears to reduce the seepage of fluid from capillaries in the lower legs, and thus reduces the risk of edema. Importantly, treatment with either horse chestnut extract or troxerutin (another flavonoid) reduced the clinical symptoms of CVI patients participating in clinical trials.9 Finally, an extract of gotu kola (Centella asiatica)enhances microcirculation and reduces venous hypertension and edema. Specifically, gotu kola extract appears to stimulate remodeling of the vein wall to improve venous tone in patients with CVI.10

Diosmin and hesperidin in the 9:1 ratio have been proven to ease the symptoms of chronic venous insufficiency in numerous clinical trials.

Not only are flavonoids an effective treatment for CVI and the complications associated with this disease, they are also very safe to use. The combination of diosmin/hesperidin has an excellent safety record, as demonstrated by its use in clinical trials, as well as from toxicology studies.


  1. Ramelet AA. Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency. Angiology 2001;52(Suppl 1):S49-56.
  2. Struckman JR. Clinical efficacy of micronized purified flavonoid fraction: an overview. J Vasc Res 1999;36(Suppl 1):37-41.
  3. Blume J, Langenbahn H, de Champvallins M. Quantification of edema using the volumeter technique; therapeutic application of Daflon 500 mg in chronic venous insufficiency. Phlebology 1992;7(Suppl 2):37-40.
  4. Jantet G. RELIEF study: first consolidated European data. Angiology2000;51:31-7.
  5. Bergan JJ, Schmid-Schonbein GW, Takase S. Therapeutic approach to chronic venous insufficiency and its complications: place of Daflon 500 mg. Angiology2001;52(Suppl 1):S43-7.
  6. Boineau Geniaux D. Activité thérapeutique de Daflon 500 mg sur les troubles trophiques de l’insuffisance veineuse. Angiologie 1988;73(Suppl):20-3.
  7. Guilhou JJ, Dereure O, Marzin L, et al. Efficacy of Daflon 500 mg in venous ulcer healing: a double-blind, randomized, controlled versus placebo trial in 107 patients. Angiology 1997;48:77-85.
  8. Glinski W, Chodynicka B, Roszkiewica J, et al. The beneficial augmentative effects of micronised purified flavonoid fraction (MPFF) on the healing of leg ulcers: an open, multicenter, controlled, randomized study. Phlebology1999;14:151-7.
  9. Rehn D, Unkauf M, Klein P, Jost V, Lucker PW. Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency. Arzneim Forsch Drug Res 1996;46:483-7.
  10. Incandela L, Cesarone MR, Cacchio M, et al. Total triterpenic fraction of Centella asiatica in chronic venous insufficiency and in high-perfusion microangiopathy. Angiology 2001;52(Suppl 2):S9-13.