Flavonoids for Varicose Veins, Hemorrhoids, and Wound Healing

Accelerated Wound Healing with Flavonoids

t's your body's largest organ, but one that you probably rarely think of as an organ. It's your skin - protector, savior, and vanquisher of hostile foreign agents. Your skin helps to stop harmful things from getting into your body, while preventing the loss of essential fluids. Think about it: your skin is what distinguishes and separates you from the rest of the world. And when something penetrates this formidable yet delicate barrier, trouble may soon follow, likely in the form of an infection. We all suffer wounds, of course - superficial or deep cuts, scrapes, bruises, perhaps ulcers - but thanks to a superb wound-healing mechanism, we are usually none the worse for the wear.

The healing of a wounded area is most effective and rapid in individuals who are nutritionally sound. That's because virtually every nutrient is involved in the healing process, which relies on a number of different tissues and hence a number of different cell types with specific nutrient needs. But what nutrients are most important? Well, anything that enhances the immune system will likely help. In addition, recent research indicates that certain plant compounds called flavonoids are especially effective in accelerating wound healing.

The outer surface of your skin, called the stratum corneum (corneum means horny) is mostly dead and is composed of about ten to twenty layers of cells that are extremely tough, owing to their high content of keratin, a very resilient protein. (To give you an idea of how tough keratin is, it's the principal component of hair, nails, claws, hooves, beaks, feathers, and, yes, horns.) Under the stratum corneum is the basal cell layer of living cells; together these two layers constitute the epidermis. New epidermal cells are constantly being produced in the basal cell layer, and as they migrate upward, they toughen up, die, and eventually fall off. These cells, by the way, become the primary component of household dust . . . fascinating, huh?

You can think of your skin as a pop-up dispenser that never goes empty - it constantly produces new cells that sacrifice themselves to prevent injury to those below. It generally takes a few weeks for dead cells to be pushed all the way to the surface and cast off. This slow journey is important, however, because, for the entire time that they are still part of the epidermis, these cells protect you against minor abrasions, infections, solar ultraviolet radiation, and dehydration.

The deeper layer of the skin, called the dermis, contains a lot of connective tissue, is rich with nerve endings and blood vessels, and gives your skin tensile strength that makes it resistant to tearing. All the cells of the dermis are alive and are well armed against hostile elements (germs, free radicals, toxic chemicals, etc.) that are constantly trying to penetrate your skin. In particular, these cells are richly supplied with antioxidants to help prevent aging, disease, and other disorders of the skin. (See the article on lycopene in this issue.)

All in all, the skin does a wonderful job not only of holding us together and making us look attractive to the opposite sex, but of protecting us from many of life's little slings and arrows. Among its most important functions are:

  • Preventing dehydration and loss of internal fluids
  • Regulating body temperature
  • Limiting the penetration of UV radiation
  • Absorbing the impact of surface abrasions and scratches so as to protect the underlying tissues
  • Acting as a "disinfectant," with an acidic pH to limit bacterial growth

As you can see, your skin is pretty important. That's why your body sees to it that you have an effective mechanism by which to repair wounds. Whenever the integrity of your skin is breached, bad things can get in, and good things can get out. So your body responds by quickly repairing the damage in superficial wounds. The first step is the formation of a blood clot to prevent excessive loss of blood. As the clot dries, it becomes a hard, unsightly scab. The really exciting activities in wound healing occur underneath the scab, where living tissue is being repaired.

To accomplish this, the body's immune system, circulatory system, and specialized cells called fibroblasts join forces. The circulatory system is especially important, as it provides a number of "activating factors" - molecules that provide instructions for muscle repair and new blood-vessel growth and that organize the growth and formation of new skin cells in the wounded area. But not all wounds heal quickly, and this process gets less efficient as we age. Indeed, children excel at this recuperative process and heal quickly, whereas the elderly typically require a long time to heal. A number of other factors work against adults in the wound-healing process, including smoking, obesity, stress, and diabetes.

Is there any way to beef up our wound-repair process? Fortunately, many studies indicate that there is, and the answer is found in flavonoids.

Flavonoids are members of a large class of colorful plant pigments with potent antioxidant properties. They provide a broad spectrum of well-documented benefits in cases of heart disease, cancer, vision disorders, allergies, viral infections, and more - and they have no known toxicities, adverse reactions, or other side effects. Certain flavonoids, notably diosmin and hesperidin, have been used routinely in Europe for many years to treat varicose veins, hemorrhoids, and the edema (swelling) that often accompanies chronic venous insufficiency - the weakening and deterioration of vein function that causes varicosity and hemorrhoids in the first place. (Hemorrhoids, by the way, are just a special category of varicose veins.)

Now these flavonoids are being used to accelerate wound repair as well. Two separate European studies indicate that oral application of flavonoids to patients with leg ulcers (a common complication of chronic venous insufficiency) greatly increases the healing rate. The European formulation used is called micronized purified flavonoid fraction (MPFF) and consists of diosmin and hesperidin in a 9:1 ratio. The typical daily dose is 900 mg of diosmin and 100 mg of hesperidin.

When this formulation was given for two months to a group of individuals (average age 71) who were suffering from leg ulcers, their ulcers healed faster and to a greater degree than those of a control group that received a placebo instead.1 Specifically, 32% of the patients in the treated group had ulcers that healed completely, while only 14% of those in the control group had wounds that healed during the same time.

A larger, randomized study recently completed in Poland underscores the role that flavonoids play in the wound-repair process.2 In this study, patients with chronic venous insufficiency and associated leg ulcers received standard compression therapy (tight elastic stockings), either alone or in combination with MPFF treatment. Consistent with previous results, those patients who received the flavonoids were much more likely to have completely healed ulcers than those who received compression therapy alone. Not surprisingly, smaller ulcers healed better than larger ones. These studies further demonstrated that conventional treatment, such as compression therapy, is greatly aided by the supplemental use of flavonoids to accelerate wound healing.

Another recent study demonstrates that infected wounds heal more quickly if treated with flavonoids.3 This study, performed on guinea pigs, showed that either topical or oral application of diosmin/hesperidin (in the standard 9:1 ratio) was effective in accelerating the healing of infected wounds but had no effect on the rate of healing for clean wounds. The researchers suggest that flavonoids such as diosmin and hesperidin may have antibacterial properties.

Diosmin and hesperidin have many other beneficial properties where wound healing is concerned.4 For example, they help to regulate microcirculation in the vicinity of the wound, which prevents blood and lymph from pooling in the wounded area. (Lymph is the watery yellowish fluid that circulates throughout the body carrying infection-fighting white blood cells to wherever they are needed.) As a result, swelling is reduced, and a continuous supply of fresh red and white blood cells to the damaged area is ensured. In addition, these flavonoids are thought to have anti-inflammatory properties and to regulate lymphatic drainage.

On a molecular level, flavonoids have been shown to inhibit the synthesis of prostaglandins (potent, hormone-like substances that perform many functions throughout the body), a feature that likely contributes to their anti-inflammatory effect.5 The combination of all these properties at the site of a wound is important in creating an environment that favors tissue repair.

Yet another important feature of diosmin and hesperidin is that they improve venous tone and elasticity. Put simply, they improve the overall health of veins and make them stronger. Not surprisingly, this reduces the risk of varicose veins and hemorrhoids, because good venous tone reduces the likelihood of stagnant blood accumulating in the veins. Such stagnation occurs when the one-way valves that generally prevent the backflow of blood become impaired. The buildup of pressure in the pooled blood causes the vein to bulge and twist, and - presto! - a varicose vein appears.

Varicose veins occur most commonly in the legs, because that is where the downward force of gravity on the blood as it returns to the heart (in this case, a long uphill journey) is most pronounced. And varicose veins occur most commonly at the legs' surface, because these surface veins do not have surrounding layers of muscle tissue to keep them uniformly compressed from all sides. Finally, as we have seen, when varicose veins occur in the anus (which is actually a canal about 10 cm long, leading to the rectum), they're called hemorrhoids.

Fortunately, the same mixture of diosmin and hesperidin that accelerates wound healing also protects against varicose veins and hemorrhoids. In a study comprised of 120 patients with hemorrhoids, half were treated daily with 900 mg of diosmin and 100 mg of hesperidin for two months, while the other half received placebo for the same period.6 In the treated group, there were fewer hemorrhoid attacks (40% vs. 70% in the control group), the attacks were of shorter duration (2.6 days vs. 4.6 days), and they were less severe. On a severity scale of 1 to 3, the attacks in the treated group averaged 1.1, while those in the control group averaged 1.6. It seems a safe bet that the individuals who did not receive flavonoid supplementation were pretty envious of those who did.

We all suffer minor wounds, and chances are that we will also experience venous insufficiency, varicose veins, or hemorrhoids, especially as we get older. A healthy immune system, good venous tone, and sound nutrition reduce the chances, however, and they improve our ability to cope with these afflictions when they do occur. A diet rich in flavonoids such as diosmin and hesperidin is a good strategy for success. Sweet oranges are a good source of hesperidin, for example.7


  1. Guilhou JJ, Fevrier F, Debure C, et al. Benefit of a 2-month treatment with a micronized, purified flavonoidic fraction on venous ulcer healing. A randomized, double-blind, controlled versus placebo trial. Int J Microcirc Clin Exp 1997;17 Suppl 1: 21-6.
  2. Glinski W, Chodynicka B, Roszkiewicz J, et al. Effectiveness of a micronized purified flavonoid fraction (MPFF) in the healing process of lower limb ulcers. Minerva Cardioangiol 2001;49:107-14.
  3. Hasanoglu A, Cengiz A, Suleyman O, Kali K, Senol M, Ertas E. Efficacy of micronized flavonoid fraction in healing of clean and infected wounds. Intl J Angiol 2001;10:41-4.
  4. Struckmann JR, Nicolaides AN. Flavonoids. A review of the pharmacology and therapeutic efficacy of Dalon 500 mg in patients with chronic venous insufficiency and related disorders. Angiology 1994;45:419-28.
  5. Manthey JA. Biological properties of flavonoids pertaining to inflammation. Microcirc 2000;7:S29-34.
  6. Godeberge P. Daflon 500 mg in the treatment of hemorrhoidal disease: a demonstrated efficacy in comparison with placebo. Angiology 1994;45:574-8.
  7. Arriaga FJ, Rumbero A. Naringin, hesperidin, and neohesperidin content in juices from thirteen citrus spp. Fitotherapia 1990;61:31-6.

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