Flavonoids Promote Stronger, Healthier Veins Diosmin and hesperidin fight weak veins, venous ulcers, and hemorrhoids By Dr. Edward R. Rosick or those of us who advocate the benefits of preventive and holistic medicine, living in America means that we have great choices in nutritional supplements. For marketing purposes, most supplement formulators, manufacturers, and sellers tend to emphasize the importance of their products in maintaining the health of the more glamorous parts of the human body—the brain, the heart, the genitals. But there is another important bodily system—the venous system—that often gets short shrift, even by holistically minded physicians. How Veins Work, and How They Fail The venous system returns oxygen-poor blood to the heart after it has delivered its life-sustaining cargo of oxygen and other nutrients, via the arteries, to all the body’s cells. The heart then pumps the blood through the lungs, where it picks up more oxygen. It then returns to the heart, which pumps it out through the arteries once again. If problems arise anywhere in this closed circuit—be it in the thick-walled arteries, the thin-walled veins, or the gossamer-walled capillaries that connect them—the results can be catastrophic. After blood passes through the capillaries, which deliver nutrients to the cells and receive waste products from them, its pressure is greatly reduced. Although the heart generates some venous blood pressure, it’s no longer strong and rhythmic, like arterial blood pressure, and it’s insufficient to push blood—against the force of gravity—from the legs back up to the heart. That job is performed mainly by the muscles surrounding the veins of the legs, whose rhythmic contractions gently push the blood “uphill.” This process is facilitated by a series of one-way valves in the leg veins that prevent the blood from flowing back down. As we grow older, however, and especially if we don’t stay physically fit through exercise, the vein walls can lose their tone and become weak. As a result, the one-way valves begin to fail, allowing blood to backflow. This exerts undue pressure on the capillaries, particularly in the ankles. The capillaries, being permeable, then begin to leak fluid into the surrounding tissues, which swell as a result. CVI Can Lead to Venous Ulcers and Thrombosis The condition of weakened veins, called chronic venous insufficiency (CVI), is thought to affect at least 7 million people in the United States. In addition to ankle and leg edema (swelling), CVI can produce generalized leg pain, and it often (but by no means always) leads to varicose veins, those unsightly, twisted bulges in surface veins caused by the pooling of blood at weak spots. A serious consequence of advanced CVI is venous ulcers, which are open sores on the skin, usually on the ankles. They are thought to result from tissue damage caused by excessive leakage of fluid from the capillaries, including protein molecules, to which the capillary walls are normally impermeable. Over half a million Americans are believed to suffer from venous ulcers. They are most commonly seen in the elderly, although about 72% of the people who get them have their first one by the time they’re 60, and 22% by the time they’re 40. Venous ulcers are resistant to treatment and very slow to heal. They cause pain and impaired mobility in the vast majority of people who have them and are thought to cost the U.S. healthcare system about 2.5 billion dollars a year.1 The most dangerous consequence of CVI is deep-vein thrombosis, the formation of blood clots deep inside the leg, where they can’t be seen or felt. Such clots tend to form where circulation is severely impaired and the blood stagnates. If a clot breaks free and finds its way to a lung, it can cause a pulmonary embolism, which can be almost instantly fatal. Hemorrhoids—A Pain in the Butt A condition often, but not necessarily, associated with CVI is hemorrhoids, which are actually varicose veins of the anus. They may be the butt of jokes, but anyone who has had them knows they’re no laughing matter—they can be intensely painful. Hemorrhoids, which afflict about three-fourths of U.S. adults at least once in their lives, have been plaguing people for thousands of years. In the 1300s, an English surgeon named Ardene is said to have said, “The common people call them piles, the aristocracy call them hemorrhoids, the French call them figs—what does it matter, so long as you can cure them?”2 Treatment Can Be Low-Tech or High-Tech A common treatment for CVI is compression stockings, which help push the blood in impaired leg veins back toward the heart. Although they can help alleviate the common symptoms of CVI, they do nothing to correct the underlying problem. Compression stockings are also used in the treatment of venous ulcers, along with traditional wound-care treatments, such as debridement (removal of dead tissue) and topical antibiotics. Unfortunately, the healing rate for venous ulcers by conventional methods is at best 50–60%, with recurrence as high as 72%.1 Unsightly varicose veins are often treated by surgery or by the use of sclerotherapy. In this procedure, a caustic solution is injected into the varicose vein, destroying it and causing the blood to find its way into healthier veins. In the majority of cases, however, the problem recurs within 5 years. There can also be deleterious side effects, including allergic reactions to the sclerosing agent, scarring, and blood clots. Since hemorrhoids are also varicose veins, the same types of treatment are used for them—and a few more besides. A low-tech but effective treatment is rubber-band ligation, which kills the hemorrhoids, causing them to fall off. Additional treatments include photocoagulation (the use of infrared radiation to destroy the hemorrhoids) and cryotherapy, (the use of liquid nitrogen to destroy them by freezing). While these high-tech treatments offer some degree of initial success, they must often be repeated to provide lasting results. Flavonoids Give New Life to Your Veins For anyone with CVI or hemorrhoids, the kinds of treatments just described are none too appealing. Fortunately, there are safe, reliable, natural supplements that can both prevent and treat these conditions. Two such agents are the chemical compounds diosmin and hesperidin. Both are flavonoids, plant pigments that give colors to flowers, fruits, and vegetables. Diosmin and hesperidin in combination are used throughout much of the world as a prescription drug treatment for CVI and related disorders, and there’s a plethora of scientific studies supporting their use. A recent review paper in the journal Drugs (see the sidebar regarding this journal) affirms the safety and efficacy of these flavonoids in the form of a widely used formulation that is commonly called micronized purified flavonoid fraction (MPFF); it consists of 90% diosmin and 10% hesperidin.3 Following are some examples, as cited in the Drugs paper, of how this formulation can be a potent weapon in the fight to maintain venous health. Quality Is Where You Find It Most medical journals contain peer-reviewed papers written by academic researchers with advanced degrees (usually M.D., D.O., or Ph.D.) and are published, typically, under the auspices of a professional medical or scientific society. Not all medical journals fit that description, however, and it’s important to know when one is dealing with a different kind of journal. The accompanying article is based on a 30-page review paper in the journal Drugs, which is published by New Zealand-based Adis International Ltd., a healthcare marketing and communications firm whose business consists, in part, of producing high-level reports that are paid for by client firms. The authors of the report in question are staff members of Adis, and the client firm is unidentified. Does this mean that the paper is tainted? Not necessarily. Honesty can prevail over bias, and the review appears to be professional, comprehensive, and meticulous. It was written by two authors who are scientifically knowledgeable and familiar with the subject matter, even though there is no indication that they have advanced degrees in medicine or science. They are, however, skilled reporters of the existing literature on MPFF, and they cited 111 research papers from numerous respected medical journals in the fields of angiology, pharmacology, vascular surgery, etc. It all adds up to a credible case that diosmin and hesperidin are excellent nutrients with well-established safety and efficacy—claims that we have made previously in Life Enhancement based on our own analyses of original research papers in the field. [See, e.g., Get Relief from Varicose Veins and Hemorrhoids (June 2000), Flavonoids to the Rescue When Hemorrhoids Bleed (November 2000), Accelerated Wound Healing with Flavonoids (July 2001), and Restore and Maintain Healthy Vein Function with Flavonoids (December 2001).] Flavonoids Have Multiple Actions and Benefits MPFF has been shown in multiple studies to be safe and effective. Reported side effects (such as abdominal pain and nausea) are rare, and typically mild and transient. The efficacy of this substance in helping to prevent and treat problems in the venous system has been demonstrated in both short-term studies and studies lasting a year. The flavonoids are thought to act in multiple ways, such as increasing venous tone, improving lymphatic drainage, and reducing capillary hyperpermeability. Two randomized, double-blind, placebo-controlled trials have shown that 500 mg of MPFF taken twice daily for 2 months can significantly decrease ankle and calf circumference and improve many of the other symptoms of CVI. Another study examined the effect of different dosage schedules. In a placebo-controlled, double-blind trial of 308 CVI patients, MPFF was given either as two 500-mg tablets in the morning or as one tablet in the morning and one at night. During the 2-month treatment period, there was significant improvement in CVI symptoms in both groups: as measured by ankle and calf circumference, leg edema resolved in 28–43% of the 263 patients who had that symptom at the beginning of the study, with the greater degree of improvement found in the group of patients who received both tablets in the morning. Flavonoids Give RELIEF from Vein Problems One of the most extensive MPFF studies was the RELIEF Study (Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids in chronic venous insufficiency), carried out in the late 1990s in 23 countries on 3174 patients with mild to moderately severe CVI. The patients were given two 500-mg MPFF tablets daily for 6 months. The results showed major improvements in symptoms such as leg edema, pain, and cramps. In another long-term study, this one for one year, researchers looked at the effects of two 500-mg tablets daily in 170 patients with CVI. As in the RELIEF study, there were major reductions in the patients’ symptoms, including functional discomfort, cramps, and leg edema in the evening. Flavonoids Help Heal Venous Ulcers MPFF has been shown to be of great benefit in patients with venous ulcers. In a placebo-controlled, double-blind, 2-month trial with 105 patients, two 500-mg tablets given daily together with standard ulcer management (compression stockings plus local treatment) accelerated the healing of venous ulcers. In fact, with ulcers of 10 cm or less in diameter, this combined treatment completely healed the ulcers in 19% more patients than standard management with a placebo or than standard management alone. In a randomized, nonblinded, 6-month study of 140 patients with venous ulcers, those taking 500 mg of MPFF twice daily together with standard ulcer management had significantly greater healing of their ulcers (3–6 cm in diameter) than those receiving standard management alone (60% vs. 32%). In the same study, patients with ulcers less than 3 cm in diameter had a 71% complete healing rate with the flavonoid treatment vs. 50% without it. Even Hemorrhoids Yield to Flavonoids Several randomized, placebo-controlled, double blind studies have shown that MPFF can improve both acute and chronic cases of hemorrhoids. In one such study of 100 patients, a tapering dose (three 500-mg tablets twice daily for 4 days, then two tablets twice daily for 3 days) gave significant improvements in bleeding, anal discomfort, and pain. In another, longer study (60 days) of 120 patients with hemorrhoids, 500-mg tablets taken twice daily significantly reduced the risk of acute hemorrhoidal symptoms when compared to placebo. Flavonoids—First Line of Defense With all the scientific research on flavonoids, their benefits should be clear to everyone (even within the skeptical mainstream medical community). Flavonoids should be recommended as a first line of defense for patients in any stage of CVI, and they can be used together with other, more aggressive therapies as well. While it’s certainly important to keep your heart, brain, and other high-profile body parts in excellent working shape, it’s wise to remember that your veins too need attention and the benefits of natural supplements to stay healthy so that you’ll stay happy. References Valencia IC, Faiabella A, Kirsner RS, Eagistein WH. Chronic venous insufficiency and venous leg ulceration. J Am Acad Dermatol 2001;44(3):401-21. Moir MH, Bartolo DC. Hemorrhoids. Gastroenterol Clinics 2001;30(1):183-97. Lyseng-Williamson KA, Perry CM. Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs 2003;63(1):71-100. Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master’s degree in healthcare administration.