Health Library

Oxerutins

Supplement Forms/Alternate Names

  • Hydroxyethylrutosides (HERs)
  • Troxerutin

Uses

Principal Proposed Uses

Other Proposed Uses

  • Requirements/Sources
  • Therapeutic Dosages
  • Therapeutic Uses
  • What Is the Scientific Evidence for Oxerutins?
  • Safety Issues
  • References

Oxerutins are a group of chemicals derived from a naturally occurring bioflavonoid called rutin.

This supplement has been widely used in Europe since the mid-1960s, as a treatment for conditions in which blood or lymph vessels leak fluid. Considerable evidence suggests that oxerutins are effective. Unfortunately, it is difficult to find this supplement in North America.

Requirements/Sources

Although they are closely related to a natural flavonoid, oxerutins are not found in food. The only way to take them is in a supplement.

Therapeutic Dosages

For varicose veins/venous insufficiency , oxerutins are usually taken in dosages ranging from 900 mg to 1,200 mg daily. A typical schedule is 1,000 mg daily, taken in two separate doses of 500 mg.

For treating lymphedema and postsurgical edema , a typical dosage is a good deal higher: 3,000 mg daily.

One particular oxerutin called troxerutin may be taken alone (in similar dosages) as a treatment for varicose veins. There is no evidence as yet that rutin itself is effective.

Therapeutic Uses

Varicose means enlarged or distended. A varicose vein is abnormally enlarged, allowing blood to pool and stagnate instead of moving it efficiently toward the heart. Surface veins of the leg are those most vulnerable to becoming varicose. Venous insufficiency is a closely related condition affecting larger veins deep within the leg. In either case, blood pools within the vein and exerts pressure against the vein walls and capillaries, resulting in pain, aching, swelling, and feelings of heaviness and fatigue. In addition, varicose veins present a cosmetic problem: bulging, often ropy, blue or purple lines visible on the skin of the lower legs.

Strong evidence shows that oxerutins can be helpful for venous insufficiency/varicose veins, improving aching, swelling, and fatigue in the legs. 1-15,59,60

Mixed evidence suggests that oxerutins might also be helpful for the leg ulcers that can develop in venous insufficiency. 16-18 There is no evidence as yet that oxerutins can improve the cosmetic appearance of varicose veins.

Oxerutins have also been found effective for treating varicose veins when they occur during pregnancy. 19,20

Hemorrhoids are a special type of varicose vein, and oxerutins may be helpful for treating them as well, although there have been some negative studies. 21,22

Some evidence suggests that oxerutins may be helpful for lymphedema (chronic arm swelling caused by damage to the lymph drainage system) following surgery for breast cancer, 23-25 as well as for edema in the immediate postsurgical period. 26

Preliminary evidence, including small double-blind trials, suggests that oxerutins might also be helpful for reducing lower extremity swelling in people with diabetes. 28,61 In these trials, oxerutin therapy did not affect blood sugar control.

One small double-blind study suggests oxerutins may be helpful for reducing vertigo and other symptoms of Meniere's disease. 27 This use is based on a theory that Meniere’s disease is caused by excessive fluid leaking from capillaries in the inner ear.

What Is the Scientific Evidence for Oxerutins?

Varicose Veins/Venous Insufficiency

About 20 double-blind, placebo-controlled studies, enrolling a total of more than 2,000 participants, have examined oxerutins' effectiveness for treating varicose veins and venous insufficiency. Virtually all found oxerutins significantly more effective than placebo, giving substantial relief from swelling, aching, leg pains, and other uncomfortable symptoms, while causing no significant side effects.

For example, one large double-blind, placebo-controlled study published in 1983 enrolled 660 people with symptoms of venous insufficiency. 29 Three out of four participants were randomly assigned to receive oxerutins (1,000 mg daily) while one out of four was given placebo. After 4 weeks of treatment, those who took oxerutins reported less heaviness, aching, cramps, and "restless leg" or "pins and needles" symptoms than those who took placebo. According to the researchers' calculations, oxerutins had produced significantly better results than placebo. This report has been criticized, however, for omitting key information (such as whether or not any participants also wore support stockings) and for failing to present data in a usable form.

A more recent, better-designed study supported these positive findings. 30 This 12-week, double-blind, placebo-controlled study enrolled 133 women with moderate chronic venous insufficiency. Half received 1,000 mg oxerutins daily, and the rest took a matching placebo. All participants were also fitted with standard compression stockings and wore them for the duration of the study. The researchers measured subjective symptoms, such as aches and pains, as well as objective measures of edema in the leg.

Those who took oxerutins had significantly less lower-leg edema than the placebo group. Furthermore, these results lasted through a 6-week follow-up period, even though participants were no longer taking oxerutins. Compression stockings, on the other hand, produced no lasting benefit after participants stopped wearing them. They gave symptomatic relief while they were worn, but they didn't improve capillary circulation in a lasting way, as oxerutins apparently did.

Regarding aching, sensations of heaviness, and other uncomfortable symptoms, however, there was little difference between the two groups. The authors theorized that the compression stockings gave both groups so much symptomatic relief that it was difficult to demonstrate a separate subjective benefit of oxerutin therapy.

Many other double-blind, placebo-controlled studies have also found benefits with oxerutins for varicose veins and venous insufficiency. 31-40,59,60

As mentioned above, there is some evidence that troxerutin—one of the compounds in the standardized mixture sold as oxerutins—may be effective when taken alone. One study found it more effective than placebo, 41 but another (very small) study found it less effective than the standard oxerutin mixture. 42

Pregnant women are at especially high risk for varicose veins and venous insufficiency. A 1975 study examined 69 pregnant women with varicose leg veins, and found that oxerutins (900 mg daily) were significantly more effective than placebo against pain as well as swelling. 43 A more recent study also found positive results, 44 but because it was neither placebo-controlled nor double-blind its results mean little (other than to suggest that oxerutins are safe in pregnancy).

Skin ulcers sometimes form on the legs of people with varicose veins or venous insufficiency, when capillary circulation has become too impaired to keep the skin healthy. A French study published in 1987 found that oxerutins combined with compression stockings were significantly more helpful for leg ulcers than the stockings alone. 45 Other positive results have been reported as well. 46

However, some experiments found oxerutins to have no benefit in treating or preventing leg ulcers. 47,48 Until more research is done, the most we can say is that oxerutins might be helpful for leg ulcers—especially if combined with compression stockings.

Hemorrhoids

Some evidence suggests that oxerutins might be helpful for hemorrhoids, as well. A double-blind study enrolling 97 pregnant women found oxerutins (1,000 mg daily) significantly better than placebo in reducing the pain, bleeding, and inflammation of hemorrhoids. 49

Lymphedema

Women who have undergone surgery for breast cancer may experience a lasting and troublesome side effect: swelling in the arm caused by damage to the lymph system. Along with the veins, the lymph system is responsible for returning fluid to the heart, but when the system is damaged, fluid can accumulate. Three double-blind, placebo-controlled studies enrolling more than 100 people have examined the effectiveness of oxerutins in this condition. 50,51,52

In one trial, oxerutins worked significantly better than placebo at reducing swelling, discomfort, immobility, and other measures of lymphedema over a 6-month treatment period, with better results appearing each month 53 —suggesting that, for women with this condition, the full effect of oxerutins might take months to realize.

Two smaller studies also found oxerutins to be more effective than placebo, but the researchers were not sure that the improvement was large enough to make a real difference. 54,55

In all of these studies, the dosage used was 3 g daily—about 3 times the typical dosage for venous insufficiency.

Post-surgical Edema

Swelling often occurs in the recovery period following surgery. In one double-blind trial, researchers gave oxerutins or placebo for 5 days to 40 people recovering from minor surgery or other minor injuries, and they found oxerutins significantly helpful in reducing swelling and discomfort. 56

Safety Issues

Oxerutins appear to be safe and well tolerated. In most studies, oxerutins have produced no more side effects than placebo. For example, in a study of 104 elderly people with venous insufficiency, 26 participants taking oxerutins reported adverse events, compared with 25 in the placebo group. 57 The most commonly observed side effects were gastrointestinal symptoms, headaches, and dizziness. 58

Oxerutins have been given to pregnant women in some studies, with no apparent harmful effects. However, their safety for pregnant or nursing women cannot be regarded as absolutely proven. In addition, the safety of oxerutins has not been established for people with severe liver or kidney disease.

References

1
MacLennan WJ, Wilson J, Rattenhuber V, et al. Hydroxyethylrutosides in elderly patients with chronic venous insufficiency: its efficacy and tolerability. Gerontology 1994;40:45-52.
2
Pulvertaft TB. Paroven in the treatment of chronic venous insufficiency. Practitioner. 1979;223:838-841.
3
Pulvertaft TB. General practice treatment of symptoms of venous insufficiency with oxerutins. Results of a 660 patient multicentre study in the UK. Vasa. 1983;12:373-376.
4
Rehn D, Brunnauer H, Diebschlag W, et al. Investigation of the therapeutic equivalence of different galenical preparations of O-(beta-hydroxyethyl)-rutosides following multiple dose peroral administration. Arzneimittelforschung. 1996;46:488-492.
5
Rehn D, Unkauf M, Klein P, et al. Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency. Arzneimittelforschung. 1996;46:483-487.
6
Rehn D, Golden G, Nocker W, et al. Comparison between the efficacy and tolerability of oxerutins and troxerutin in the treatment of patients with chronic venous insufficiency. Arzneimittelforschung. 1993;43:1060-1063.
7
Unkauf M, Rehn D, Klinger J, et al. Investigation of the efficacy of oxerutins compared to placebo in patients with chronic venous insufficiency treated with compression stockings. Arzneimittelforschung. 1996;46:478-482.
8
Boisseau MR, Taccoen A, Garreau C, et al. Fibrinolysis and hemorheology in chronic venous insufficiency: a double blind study of troxerutin efficiency. J Cardiovasc Surg (Torino). 1995;36:369-374.
9
Balmer A, Limoni C. A double blind placebo-controlled clinical trial of Venoruton on the symptoms and signs of chronic venous insufficiency. The importance of patient selection [in German]. Vasa. 1980;9:76-82.
10
Bergqvist D, Hallbk T, Lindblad B, et al. A double-blind trial of O-(beta-Hydroxyethyl)-Rutoside in patients with chronic venous insufficiency. Vasa. 1981;10:253-260.
11
Anderson JH, Geraghty JG, Wilson YT, et al. Paroven and graduated compression hosiery for superficial venous insufficiency. Phlebology. 1990;5:271-276.
12
van Cauwenberge H. Double blind study of the efficacy of O(beta-hydroxyethyl)-rutosides in the treatment of venous conditions [in French]. Med Hyg (Geneve). 1978;36:4175-4177.
13
de Jongste AB, Jonker JJC, Huisman MV, et al. A double blind three center clinical trial on the short-term efficacy of 0-(beta-hydroxyethyl)-rutosides in patients with post-thrombotic syndrome. Thromb Haemost. 1989;62:826-829.
14
Prerovsky I, Roztocil K, Hlavova A, et al. The effect of hydroxyethylrutosides after acute and chronic oral administration in patients with venous diseases. A double-blind study. Angiologica. 1972;9:408-414.
15
Cappelli R, Pecchi S, Oberhausser V, et al. Efficacy of O-(beta-hydroxyethy)-rutosides at high dosages in counteracting the unwanted activity of oral contraceptives on venous function. Int J Clin Pharmacol Res. 1987;7:291-299.
16
Stegmann W, Hubner K, Deichmann B, et al. The efficacy of O-(beta-hydroxyethyl)-rutosides in the treatment of venous leg ulcers [in French]. Phlebologie. 1987;40:149-156.
17
Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs. 1992;44:1013-1032.
18
Wright DD, Franks PJ, Blair SD, et al. Oxerutins in the prevention of recurrence in chronic venous ulceration: randomized controlled trial. Br J Surg (England). 1991;78:1269-1270.
19
Sohn C, Jahnichen C, Bastert G. Effectiveness of beta-hydroxyethylrutoside in patients with varicose veins in pregnancy [in German]. Zentralbl Gynakol. 1995;117:190-197.
20
Bergstein NAM. Clinical study on the efficacy of O-(beta-Hydroxyethyl)Rutoside (HR) in varicosis of pregnancy. J Int Med Res. 1975;3:189-193.
21
Wijayanegara H, Mose JC, Achmad L, et al. A clinical trial of hydroxyethylrutosides in the treatment of hemorrhoids of pregnancy. J Int Med Res. 1992;20:54-60.
22
Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs. 1992;44:1013-1032.
23
Taylor HM, Rose KE, Twycross RG. A double-blind clinical trial of hydroxyethylrutosides in obstructive arm lymphoedema. Phlebologie. 1993;(suppl 1):22-28.
24
Mortimer PS, Badger C, Clarke I, et al. A double-blind, randomized, parallel-group, placebo-controlled trial of O-(beta-Hydroxyethyl)-Rutosides in chronic arm oedema resulting from breast cancer treatment. Phlebologie. 1995;10:51-55.
25
Piller NB, Morgan RG, Casley-Smith JR. A double-blind, cross-over trial of O-(beta-hydroxyethyl)-rutosides (benzo-pyrones) in the treatment of lymphoedema of the arms and legs. Br J Plast Surg. 1988;41:20-27.
26
Fassina A, Rubinacci A. Post-traumatic oedemas. A controlled study into the activity of hydroxyethylrutoside [translated from Italian]. Gazz Med Ital Arch Sci. 1987;146:103-109.
27
Moser M, Ranacher G, Wilmot TJ, et al. A double-blind clinical trial of hydroxyethylrutosides in Meniere's disease. J Laryngol Otol. 1984;98:265-272.
28
Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs. 1992;44:1013-1032.
29
Pulvertaft TB. General practice treatment of symptoms of venous insufficiency with oxerutins. Results of a 660 patient multicentre study in the UK. Vasa. 1983;12:373-376.
30
Unkauf M, Rehn D, Klinger J, et al. Investigation of the efficacy of oxerutins compared to placebo in patients with chronic venous insufficiency treated with compression stockings. Arzneimittelforschung. 1996;46:478-482.
31
MacLennan WJ, Wilson J, Rattenhuber V, et al. Hydroxyethylrutosides in elderly patients with chronic venous insufficiency: its efficacy and tolerability. Gerontology 1994;40:45-52.
32
Rehn D, Brunnauer H, Diebschlag W, et al. Investigation of the therapeutic equivalence of different galenical preparations of O-(beta-hydroxyethyl)-rutosides following multiple dose peroral administration. Arzneimittelforschung. 1996;46:488-492.
33
Rehn D, Unkauf M, Klein P, et al. Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency. Arzneimittelforschung. 1996;46:483-487.
34
Balmer A, Limoni C. A double blind placebo-controlled clinical trial of Venoruton on the symptoms and signs of chronic venous insufficiency. The importance of patient selection [in German]. Vasa. 1980;9:76-82.
35
Bergqvist D, Hallbook T, Lindblad B, et al. A double-blind trial of O-(beta-Hydroxyethyl)-Rutoside in patients with chronic venous insufficiency. Vasa. 1981;10:253-260.
36
Anderson JH, Geraghty JG, Wilson YT, et al. Paroven and graduated compression hosiery for superficial venous insufficiency. Phlebology. 1990;5:271-276.
37
van Cauwenberge H. Double blind study of the efficacy of O(beta-hydroxyethyl)-rutosides in the treatment of venous conditions [in French]. Med Hyg (Geneve). 1978;36:4175-4177.
38
de Jongste AB, Jonker JJC, Huisman MV, et al. A double blind three center clinical trial on the short-term efficacy of 0-(beta-hydroxyethyl)-rutosides in patients with post-thrombotic syndrome. Thromb Haemost. 1989;62:826-829.
39
Prerovsky I, Roztocil K, Hlavova A, et al. The effect of hydroxyethylrutosides after acute and chronic oral administration in patients with venous diseases. A double-blind study. Angiologica. 1972;9:408-414.
40
Cappelli R, Pecchi S, Oberhausser V, et al. Efficacy of O-(beta-hydroxyethy)-rutosides at high dosages in counteracting the unwanted activity of oral contraceptives on venous function. Int J Clin Pharmacol Res. 1987;7:291-299.
41
Boisseau MR, Taccoen A, Garreau C, et al. Fibrinolysis and hemorheology in chronic venous insufficiency: a double blind study of troxerutin efficiency. J Cardiovasc Surg (Torino). 1995;36:369-374.
42
Rehn D, Golden G, Nocker W, et al. Comparison between the efficacy and tolerability of oxerutins and troxerutin in the treatment of patients with chronic venous insufficiency. Arzneimittelforschung. 1993;43:1060-1063.
43
Bergstein NAM. Clinical study on the efficacy of O-(beta-Hydroxyethyl)Rutoside (HR) in varicosis of pregnancy. J Int Med Res. 1975;3:189-193.
44
Sohn C, Jahnichen C, Bastert G. Effectiveness of beta-hydroxyethylrutoside in patients with varicose veins in pregnancy [in German]. Zentralbl Gynakol. 1995;117:190-197.
45
Stegmann W, Hubner K, Deichmann B, et al. The efficacy of O-(beta-hydroxyethyl)-rutosides in the treatment of venous leg ulcers [in French]. Phlebologie. 1987;40:149-156.
46
Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs. 1992;44:1013-1032.
47
Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs. 1992;44:1013-1032.
48
Wright DD, Franks PJ, Blair SD, et al. Oxerutins in the prevention of recurrence in chronic venous ulceration: randomized controlled trial. Br J Surg (England). 1991;78:1269-1270.
49
Wijayanegara H, Mose JC, Achmad L, et al. A clinical trial of hydroxyethylrutosides in the treatment of hemorrhoids of pregnancy. J Int Med Res. 1992;20:54-60.
50
Piller NB, Morgan RG, Casley-Smith JR. A double-blind, cross-over trial of O-(beta-hydroxyethyl)-rutosides (benzo-pyrones) in the treatment of lymphoedema of the arms and legs. Br J Plast Surg. 1988;41:20-27.
51
Taylor HM, Rose KE, Twycross RG. A double-blind clinical trial of hydroxyethylrutosides in obstructive arm lymphoedema. Phlebologie. 1993;(suppl 1):22-28.
52
Mortimer PS, Badger C, Clarke I, et al. A double-blind, randomized, parallel-group, placebo-controlled trial of O-(beta-Hydroxyethyl)-Rutosides in chronic arm oedema resulting from breast cancer treatment. Phlebologie. 1995;10:51-55.
53
Piller NB, Morgan RG, Casley-Smith JR. A double-blind, cross-over trial of O-(beta-hydroxyethyl)-rutosides (benzo-pyrones) in the treatment of lymphoedema of the arms and legs. Br J Plast Surg. 1988;41:20-27.
54
Taylor HM, Rose KE, Twycross RG. A double-blind clinical trial of hydroxyethylrutosides in obstructive arm lymphoedema. Phlebologie. 1993;(suppl 1):22-28.
55
Mortimer PS, Badger C, Clarke I, et al. A double-blind, randomized, parallel-group, placebo-controlled trial of O-(beta-Hydroxyethyl)-Rutosides in chronic arm oedema resulting from breast cancer treatment. Phlebologie. 1995;10:51-55.
56
Fassina A, Rubinacci A. Post-traumatic oedemas. A controlled study into the activity of hydroxyethylrutoside [translated from Italian]. Gazz Med Ital Arch Sci. 1987;146:103-109.
57
MacLennan WJ, Wilson J, Rattenhuber V, et al. Hydroxyethylrutosides in elderly patients with chronic venous insufficiency: its efficacy and tolerability. Gerontology 1994;40:45-52.
58
Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs. 1992;44:1013-1032.
59
Petruzzellis V, Troccoli T, Candiani C, et al. Oxerutins (Venoruton): efficacy in chronic venous insufficiency—a double-blind, randomized, controlled study. Angiology. 2002;53:257-263.
60
Incandela L, Belcaro G, Renton S, et al. HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides) in venous hypertensive microangiopathy: A prospective, placebo-controlled, randomized trial. J Cardiovasc Pharmacol Ther. 2002;7(Suppl 1):S7-S10.
61
Incandela L, Cesarone MR, DeSanctis MT, et al. Treatment of diabetic microangiopathy and edema with HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides): A prospective, placebo-controlled, randomized study. J Cardiovasc Pharmacol Ther. 2002;7(Suppl 1):S11-S15.