Citrus bioflavonoids as dietary supplements

• DEFINITION: Natural substance used as a dietary supplement for specific health benefits.
• PRINCIPAL PROPOSED USES: Chronic venous insufficiency, hemorrhoids
• OTHER PROPOSED USES: Easy bruising, hypertension, leg ulcers, lymphedema following breast cancer surgery, nosebleeds

Overview

Citrus fruits are well known for providing ample amounts of vitamin C, but they also supply bioflavonoids, substances that are not required for life but that may improve health. The major bioflavonoids found in citrus fruits are diosmin, hesperidin, rutin, naringin, tangeretin, diosmetin, narirutin, neohesperidin, nobiletin, and quercetin. The first five bioflavonoids listed here are discussed in this article.

Citrus bioflavonoids and related substances are widely used in Europe to treat diseases of the blood vessels and lymph system, diseases including hemorrhoids, chronic venous insufficiency, leg ulcers, easy bruising, nosebleeds, and lymphedema following breast cancer surgery. These compounds are thought to work by strengthening the walls of blood vessels. Bioflavonoids are also often said to act as antioxidants; however, while they do have antioxidant activity in the test tube, additional evidence is necessary to understand their ability to act as antioxidants in humans.

Requirements and Sources

Citrus fruits contain citrus bioflavonoids in varying proportions. Even different brands of citrus juice may vary widely in their bioflavonoid concentrations and composition. For use as a supplement, bioflavonoids are extracted either from citrus fruits or from other plant sources, such as buckwheat.

Therapeutic Dosages

A typical dosage of citrus bioflavonoids is 500 milligrams twice daily. The most-studied citrus bioflavonoid treatment is a special micronized (finely ground) combination of diosmin (90 percent) and hesperidin (10 percent).

Therapeutic Uses

Double-blind trials suggest (but do not prove conclusively) that a micronized combination preparation of diosmin and hesperidin may be helpful for hemorrhoids. Diosmin, hesperidin, and the bioflavonoid rutin may also be helpful for chronic venous insufficiency, a condition in which the veins in the legs begin to weaken. One double-blind trial found diosmin and hesperidin also to be helpful for persons who develop bruises or nosebleeds easily.

Citrus bioflavonoids have also been tried, with some success, for treating lymphedema (arm swelling) following breast cancer surgery. One should not use bioflavonoid combinations containing tangeretin if taking tamoxifen for breast cancer.

In addition, preliminary evidence suggests that citrus bioflavonoids may help reduce cholesterol levels, control inflammation, benefit people with diabetes, reduce allergic reactions, and prevent cancer. “Sweetie fruit,” a bioflavonoid-rich hybrid of grapefruit and pomelo, has shown some promise for the treatment of high blood pressure.

Scientific Evidence

Hemorrhoids. A two-month, double-blind, placebo-controlled trial of 120 persons with recurrent hemorrhoid flare-ups found that treatment with combined diosmin and hesperidin significantly reduced the frequency and severity of hemorrhoid attacks. Another double-blind, placebo-controlled trial of one hundred persons had positive results with the same bioflavonoids in relieving symptoms once a flare-up of hemorrhoid pain had begun. A ninety-day, double-blind trial of one hundred persons with bleeding hemorrhoids also found significant benefits for both the treatment of acute attacks and the prevention of new ones. Finally, this bioflavonoid combination was found to compare favorably with the surgical treatment of hemorrhoids. However, less impressive results were seen in a double-blind, placebo-controlled study in which all participants were given a fiber laxative with either combined diosmin and hesperidin or placebo.

Two studies claimed to find that diosmin-hesperidin reduces pain after hemorrhoid surgery. These studies, though, show little to nothing, as the researchers failed to use a placebo group and simply compared treated participants to untreated participants. Overall, the evidence remains incomplete, though promising.

Chronic venous insufficiency. A two-month, double-blind, placebo-controlled trial of two hundred people with relatively severe chronic venous insufficiency found that treatment with diosmin-hesperidin significantly improved symptoms compared with placebo. Another double-blind, placebo-controlled trial of diosmin-hesperidin enrolled 101 people with relatively mild chronic venous insufficiency. The results showed little difference between the two groups; the authors theorize that diosmin-hesperidin might be more effective in severe chronic venous insufficiency.

A two-month, double-blind, placebo-controlled trial evaluated the effects of diosmin-hesperidin in 107 people with nonhealing leg ulcers (sores) caused by venous insufficiency or other conditions. The results indicated that treatment significantly improved the rate of healing. Also, a three-month, double-blind, placebo-controlled trial of sixty-seven persons evaluated buckwheat tea (a good source of rutin) for chronic venous insufficiency. The results showed less leg swelling in the treated group. One study reportedly showed that the supplement oxerutin is more effective than diosmin-hesperidin for chronic venous insufficiency, but the study was too poorly designed to provide meaningful results.

Easy bruising. Some people bruise particularly easily because of fragile capillaries. A six-week, double-blind, placebo-controlled study of ninety-six people with this condition found that combined diosmin and hesperidin decreased symptoms of capillary fragility, such as bruising and nosebleeds. Two rather poorly designed studies from the 1960s found benefits with a combination of vitamin C and citrus bioflavonoids for decreasing bruising in college athletes.

Lymphedema. Breast cancer surgery sometimes causes persistent swelling of the arm (lymphedema) caused by damage to lymph vessels. Citrus bioflavonoids and other natural supplements have shown promise for this condition. In a three-month, double-blind study, fifty-seven women with lymphedema received either placebo or combination therapy consisting of the modified citrus bioflavonoid trimethyl hesperidin chalcone plus the bioflavonoid-rich herb butcher’s broom. The results indicated that the use of the bioflavonoid combination resulted in significantly less swelling.

Cancer. In a review of twelve studies involving more than five thousand cases, researchers found that people who consumed the highest amounts of flavonoids in their diets had a lower risk of lung cancer than those who consumed less. The significance of these results is weakened because none of the studies were controlled trials and because the most favorable among them did not account for the quantity of fruits, vegetables, or vitamins in the participants’ diets.

Anaerobic capacity. One randomized, double-blind, placebo-controlled, parallel clinical study found that citrus bioflavonoids improved anaerobic capacity and increased peak power of individuals partaking in high-intensity exercise. Further research is required to fully understand and confirm these results.

Safety Issues

Extensive investigations of diosmin and hesperidin have found them to be essentially nontoxic and free of drug interactions. The combination has been given to fifty pregnant women in a research study without apparent harm to women or fetuses.

Some evidence suggests that the bioflavonoid naringin may interact with medications in the calcium channel blocker family, increasing blood levels of the drug. This may necessitate a reduction in drug dosage.

The citrus bioflavonoid tangeretin may reduce the effectiveness of tamoxifen, a drug used to treat breast cancer. One highly preliminary study suggests that some citrus bioflavonoids in the diet of pregnant women might increase the risk of infant leukemia; hesperidin did not produce this effect, and diosmin was not tested.

Important Interactions

The use of the bioflavonoid naringin may necessitate a reduction in medication dose for those who take calcium channel blockers. Persons taking tamoxifen for breast cancer should avoid citrus fruits and juices and the citrus bioflavonoid tangeretin.

Bibliography

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