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Diosmin/Hesperidin En Español (Spanish Version) Approach to the Patient | Common Uses | Mechanism of Action | Dosage | Safety Issues | Drug Interactions | References Alternate Names/Supplement Forms: • Citrus Bioflavonoids Approach to the Patient A fixed micronized combination of the citrus bioflavonoids diosmin (90%) and hesperidin (10%) is widely used in Europe to treat diseases of the blood vessels and lymphatic system. The strongest evidence supports its use in hemorrhoids. The combination also appears to have benefit in chronic venous insufficiency and venous stasis ulcers. Extensive safety evaluations have found diosmin/hesperidin free from toxicological risk. Patients interested in trying this treatment may have trouble finding it; at the time of publication, diosmin/hesperidin is difficult to obtain in the U.S. Reportedly, this may change soon. Common Uses Hemorrhoids [+3] Chronic Venous Insufficiency /Stasis Ulcers [+3X] Capillary Fragility [+2] Lymphedema [-1] (Higher numbers indicate stronger evidence; X modifier indicates contradictory results. See the Introduction for details of the rating scale.) Hemorrhoids +3 A 2-month, double-blind, placebo-controlled trial of 120 individuals with recurrent hemorrhoid flare-ups found that treatment with combined diosmin and hesperidin significantly reduced the frequency and severity of hemorrhoidal exacerbations. 1 Another double-blind, placebo-controlled trial of 100 individuals found that the same bioflavonoid preparation relieved symptoms once an exacerbation of hemorrhoid pain had begun. 2 Benefits of diosmin/hesperidin were also seen in a 90-day, double-blind trial of 100 individuals with bleeding hemorrhoids.3 In another trial, this bioflavonoid combination was found to compare favorably with rubber band ligation.4 However, in a trial where both treated and placebo groups received soluble fiber, intergroup differences were small.5 Two studies claimed to find that diosmin/hesperidin reduces pain after hemorrhoid surgery. 13,14 Unfortunately, the researchers failed to provide their control groups with a placebo, and therefore the results are unreliable. Chronic Venous Insufficiency/Stasis Ulcers +3X A fixed micronized combination of the citrus bioflavonoids diosmin and hesperidin is widely used in Europe for Page 1 of 4 Copyright © 2010 EBSCO Publishing. All rights reserved. the treatment of various venous conditions, and there is meaningful (if not altogether consistent) supporting evidence for this use. A 2-month, double-blind, placebo-controlled trial of 200 individuals with severe chronic venous insufficiency found that treatment with diosmin/hesperidin significantly improved symptoms as compared to placebo. 11 Another double-blind, placebo-controlled trial of diosmin/hesperidin enrolled 101 individuals with relatively mild chronic venous insufficiency. 12 The results showed little difference between the two groups; the authors theorize that diosmin/hesperidin might be generally more effective in more severe forms of the condition. A 2-month, double-blind, placebo-controlled trial involving 107 individuals with nonhealing venous stasis ulcers found that diosmin/hesperidin significantly improved rate of healing. 6 One study supposedly showed that the supplement oxyrutin is more effective than diosmin/hesperidin for chronic venous insufficiency, but this was an open study with nonrandomized participants, and therefore shows little to nothing.15 Capillary Fragility +2 A double-blind, placebo-controlled trial of 96 individuals with fragile capillaries (resulting in such symptoms as easy bruising and frequent epistaxis) found that a combination of diosmin and hesperidin decreased tendency toward capillary rupture.7 Lymphedema -1 A double-blind trial that followed 94 individuals with upper limb lymphedema following breast cancer therapy found no significant difference between groups. 8 However, clinical evidence of benefit was reported in the most severely affected subgroup. Mechanism of Action Like oxerutins, diosmin/hesperidin appears to increase venous tone and normalize capillary permeability. Dosage A typical dosage of micronized diosmin/hesperidin is 500 mg twice daily. See the Appendix for U.S. brand names of clinically tested products. Safety Issues Micronized diosmin/hesperidin has undergone extensive safety evaluation, and appears to be essentially free from toxicological risk.9 Maximum safe dosages in individuals with severe hepatic or renal disease are not known. Safety in Young Children and Pregnant or Lactating Women Page 2 of 4 Copyright © 2010 EBSCO Publishing. All rights reserved. Maximum safe dosages for pregnant or lactating women, or young children, have not been established. However, diosmin/hesperidin has been used in clinical trials of pregnant women, with no apparent harm. 10 Drug Interactions There are no known drug interactions.9 References [ + ] 1. Godeberge P. Daflon 500 mg in the treatment of hemorrhoidal disease: a demonstrated efficacy in comparison with placebo. Angiology. 1994;45:574-578. 2. Cospite M. Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids. Angiology. 1994;45:566-573. 3. Misra MC, Parshad R. Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids. Br J Surg. 2000;87:868-872. 4. Ho YH, Tan M, Seow-Choen F. Micronized purified flavonidic fraction compared favorably with rubber band ligation and fiber alone in the management of bleeding hemorrhoids: randomized controlled trial. Dis Colon Rectum. 2000;43:66-69. 5. Thanapongsathorn W, Vajrabukka T. Clinical trial of oral diosmin (Daflon®) in the treatment of hemorrhoids. Dis Colon Rectum. 1992;35:1085-1088. 6. Guilhou JJ, Dereure O, Marzin L, et al. Efficacy of Daflon 500 mg in venous leg ulcer healing: a double-blind, randomized, controlled versus placebo trial in 107 patients. Angiology. 1997;48:77-85. 7. Galley P, Thiollet M. A double-blind, placebo-controlled trial of a new veno-active flavonoid fraction (S 5682) in the treatment of symptomatic capillary fragility. Int Angiol. 1993;12:69-72. 8. Pecking AP, Fevrier B, Wargon C, et al. Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to conventional therapy of breast cancer). Angiology. 1997;48:93-98. 9. Meyer OC. Safety and security of Daflon 500 mg in venous insufficiency and in hemorrhoidal disease. Angiology. 1994;45:579-584. 10. Buckshee K, Takkar D, Aggarwal N. Micronized flavonoid therapy in internal hemorrhoids of pregnancy. Int J Gynaecol Obstet. 1997;57:145-151. 11. Laurent R, Gilly R, Frileux C. Clinical evaluation of a venotropic drug in man. Example of Daflon 500 mg. Int Angiol 1988;7:39-43 12. Danielsson G, Jungbeck C, Peterson K, et al. A randomised controlled trial of micronised purified flavonoid fraction vs placebo in patients with chronic venous disease. Eur J Vasc Endovasc Surg. 2002;23:73–76. 13. La Torre F, Nicolai AP. Clinical use of micronized purified flavonoid fraction for treatment of symptoms after hemorrhoidectomy: results of a randomized, controlled, clinical trial. Dis Colon Rectum. 2004 Mar 25 [Epub ahead of print] 14. Colak T, Akca T, Dirlik M, et al. Micronized flavonoids in pain control after hemorrhoidectomy: a prospective randomized controlled study. Surg Today. 2003;33:828-32. Page 3 of 4 Copyright © 2010 EBSCO Publishing. All rights reserved. 15. Cesarone MR, Belcaro G, Pellegrini L, et al. HR, 0-(Beta-hydroxyethyl)-rutosides, in comparison with diosmin+hesperidin in chronic venous insufficiency and venous microangiopathy: an independent, prospective, comparative registry study. Angiology. 2005;56:1-8. Last reviewed May 2005 by EBSCO CAM Review Board Page 4 of 4 Copyright © 2010 EBSCO Publishing. All rights reserved.