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Rutin (C27H30O16)

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Also listed as: Oxerutin, Troxerutin
Related terms
Background
Evidencetable
Tradition
Dosing
Safety
Interactions
Attribution
Bibliography

Related Terms
  • Alpha-glycosylrutin, ascorutin, benzopyrone, Birutan Forte, buckwheat (Fagopyrum esculentum), dihydroxyethylrutoside, eldrin, Ercevit fort, ergot compound, essaven, flavanoid, Fleboside, Globulariacitrin, Globularicitrin, glucopyranoside, HR, hydrolytic enzymes (HE), hydroxyethyl rutoside, hydroxyethylrutosiden, ilixanthin, melin, myrticalorin, myrticolorin, myticolorin, osyritrin, oxyritin, oxerutin, paliuroside, Paroven® (UK, S. Africa, Australasia), paveron 75, phlebolan-spray, phlebotropic drugs, phytomelin, Q1, quercetin, quercetin rutinoside, Relvene® (France), rexiluven (DRA 363, Sandoven), ritmilen, rutabion, rutin trihydrate, rutinic acid, rutinion acid, rutosid, rutoside, rutozyd, sandoven, sophorin, tanrutin, tetrahydroxyethyl-quercitin, tetrahydroxyethylrutoside, tri-(hyroxyethyl)-rutin, trihydroxyethylrutoside ("varemoid"), trioxyethylrutin, troxerutin (CAS 7085-55-4), trypsin, Venoruton® (most of Continental Europe), Venoruton 1000®, Venoruton Forte®, vicalin, violaquercitrin, vitamin P.

Background
  • Rutin is a yellow crystalline flavonol glycoside (C27H30O16) that occurs in various plants (rue, tobacco, buckwheat, etc.). Upon hydrolysis (a chemical reaction that uses water to break down a compound), rutin yields quercetin and rutinose.
  • Rutin is used in many countries as a vasoprotectant and is an ingredient in numerous multivitamin preparations and herbal remedies. The rutosides are naturally occurring flavonoids that have documented effects on capillary permeability and edema (swelling) and have been used for the treatment of disorders of the venous and microcirculatory systems.
  • There is some evidence for the use of rutin for chronic venous insufficiency, edema, hemorrhoids, microangiopathy (disease of small blood vessels), varicosis and venous disorders. Well presented clinical trials are required in these fields before solid recommendations can be made.
  • Formulations, mainly consisting of the trihydroxyethyl derivative of rutin, are used in Europe, Mexico and other Latin American countries for the treatment of such venous disorders as varicose veins and hemorrhoids. The generic name for these formulations is troxerutin. Troxerutin has been widely used in Europe since the mid-1960s.

Evidence Table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *


Overall, the results suggest a benefit for O-(beta-hydroxyethyl)-rutosides in chronic venous insufficiency. Additional study is needed to confirm these findings.
B


Overall, the results suggest a benefit for various rutin compounds in reducing edema and flight edema. Better-designed studies are needed to confirm these results.
B


Preliminary evidence suggests that o-(beta-hydroxyethyl) rutosides and trihydroxyethylrutosides may be safe and effective treatments for hemorrhoids. Studies investigating the effect of rutin in different populations, as well as efficacy on third or fourth degree hemorrhoids are warranted in future studies.
C


One clinical trial supported the use of O-(beta-hydroxyethyl)-rutosides for reduction of symptoms associated with Meniere's syndrome. Additional study is warranted in this area.
C


Overall, the results suggest a benefit for O-(beta-hydroxyethyl)-rutosides in microangiopathy (disease of the small blood vessels). Better-designed clinical trials in this field are required before a firm recommendation can be made.
C


One well designed clinical trial has been conducted in the area of retinal vein occlusion. Further well designed studies are required in this field before a firm recommendation can be made.
C


Preliminary evidence does not suggest that tri-(hydroxyethyl)-rutin offer benefits to retinopathy patients. Well-designed studies in this field are required before a firm recommendation can be made.
C


One well designed study suggests that O-[beta-hydroxyethyl]-rutosides may offer benefit in terms of schizophrenia. More studies are required in this area before a strong recommendation can be made.
C


In one clinical trial, O-(beta-hydroxyethyl)-rutoside offered benefit in terms of skin irritation to individuals with breast cancer undergoing radiation treatment. Additional study is needed in this area
C


Superficial vein thrombosis (SVT) is a common complication of varicose veins. One clinical trial suggests that Venoruton®, in combination with elastic compression or thrombectomy, offers benefit as compared to these treatments alone. Additional study is needed in this area.
C


Rutin, in combination with compression, appears to have benefit over compression alone in the treatment of varicose leg ulcers. However, results are conflicting. Additional study is needed in this area.
C


Overall, the evidence suggests a benefit of troxerutin or O-(beta-hydroxyethyl) rutoside for varicosis. Well-designed clinical trials are required before a firm recommendation can be made.
C


Overall, the results suggest a benefit of hydroxyethylrutosides for venous hypertension (high blood pressure). Additional study is needed in this area.
C
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)


Tradition / Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

  • Anticoagulant (dicoumarin damage), antioxidant, arrhythmia (cardiac rhythm abnormalities), atherosclerosis (arterial insufficiency), blood circulation (hemodynamic effects), brain injuries (cerebral function disorders), breast disease (mastopathy), common cold, coronary heart disease (CHD), deafness (sudden), dental procedures, eye diseases (euthyroid endocrine ophthalmopathy), gastric ulcer, Grave's disease (orbitopathy), immunomodulation, inflammation (oral, radiogenic sialadenitis and mucositis), mucositis, multiple sclerosis, musculoskeletal conditions (orthopedics), neck pain (cervical syndrome), nutritional deficiencies (trophic complications), osteoarthritis, pain, platelet aggregation (inhibition), post-operative pain, recovery after surgery (recovery from hemorrhoidectomy), sepsis, surgical uses, trauma.

Dosing

Adults (18 years and older)

  • There are various preparations of rutin used in clinical trials, including capsules, sachets and injections. Various dosages of hydroxyethylrutosides (HR) have been used, including 500 milligrams twice per day and 250-300 milligrams three to four times per day for 28 days. The most commonly used dose by mouth is 1-2 grams of rutin per day in divided doses for four weeks. However, up to 3,500 milligrams has been studied in clinical trials. Rutin has also been taken as trihydroxyethylrutosides (troxerutin) and oxerutin. Brand name products studied include Venoruton® and Paroven®.
  • Venoruton® 1 gram three times daily is a commonly used dose in combination with elastic compression for eight weeks to treat superficial vein thrombosis or flight edema.
  • Troxerutin is typically taken in higher doses of 3,500-7,000 milligrams per day in divided doses for up to four months. To treat venous insufficiency in premenstrual and pregnant women, 4 grams daily troxerutin has been given for four months.
  • One 300-milligram tablet of trihydroxyethylrutosides twice daily for up to four weeks has been used for hemorrhoids. However, 500-4,000 milligrams HR given by mouth twice daily in the treatment of first-, second-, or third-degree hemorrhoids is more commonly used.
  • For schizophrenia, 3 grams per day of a mixture of O-[beta-hydroxyethyl]-rutosides (Paroven®/Venoruton®) for three months has been used.
  • A single injection of 1,000 milligrams HR followed by 500 milligrams three times per day by mouth for four weeks has been used for chronic venous insufficiency. Injections should only be given under the supervision of a qualified healthcare professional, including a pharmacist.

Children (under 18 years old)

  • There is no proven safe or effective dose of rutin in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in individuals with a known allergy or hypersensitivity to O-(beta-hydroxyethyl)-rutosides or plants that rutin is commonly found in, such as rue, tobacco or buckwheat. One case of leg dermatitis was noted in an elderly patient while taking O-(beta-hydroxyethyl)-rutosides.

Side Effects and Warnings

  • Rutins, oxerutins and troxerutins have been used effectively and safely in several clinical and equivalence trials. Numerous reports have reported no adverse side effects with rutin treatment. Laboratory findings were noted as unchanged. Few adverse effects have been reported, most of which were mild or transient. Rutin is possibly unsafe when taken in very high doses for long periods of time.
  • Adverse effects reported while taking O-(beta-hydroxyethyl)-rutosides have included monocytosis, eosinophilia (increased white blood cell count), deep vein thrombosis, superficial thrombophlebitis, skin rash, hair loss, gastritis (stomach inflammation), vomiting, diarrhea, constipation, dry mouth, abdominal pain, headache, acute brain syndrome, dizziness, sleeping problems, tiredness, swelling, muscle stiffness, and upper respiratory tract infection.
  • Use cautiously in elderly patients; most adverse effects have been reported in elderly populations.
  • Use cautiously in individuals with skin conditions; dermatitis has been noted with use.

Pregnancy and Breastfeeding

  • Rutin supplements have been safely used during pregnancy to treat venous insufficiency, hemorrhoids, and varicose veins. Consult with a qualified healthcare professional, including a pharmacist, before taking rutin to make sure that the benefits of rutin supplementation outweigh the risks in each individual. Rutin is not recommended in breastfeeding women due to a lack of available scientific evidence.

Interactions

Interactions with Drugs

  • Rutin is often used in combination with coumarin. Caution is advised in patients with bleeding disorders or taking drugs that my increase the risk of bleeding. Dosing adjustments may be necessary.
  • Phlogenzym® tablets (a combination product containing rutin) have been used with antibiotics. In theory, rutin should be safe to combine with antibiotics.
  • Theoretically, rutin may have additive effects when used in combination with benzopyrones, anti-edema drugs, Wobenzym® (contains rutin), Dicynone® or Reparil®.
  • Intramuscular administration of the fixed combination of troxerutin and carbazochrome has been well-tolerated in improving hemorrhoidal and post-surgical symptoms during the five days following surgery. Injections should only be given under the supervision of a qualified healthcare professional, including a pharmacist.
  • Theoretically, rutin may have additive effects when used in combination with diuretics. Caution is advised.
  • Taking hydroxyethylrutoside by mouth may counteract docetaxel-fluid retention.
  • N-acetylcysteine (NAC) in combination with rutin may reduce ethane and MDA concentrations, and increase GSH; this combination may be efficient in protecting the lungs of patients with adult respiratory distress syndrome.
  • High doses of O-(beta-hydroxyethyl)-rutosides may counteract the unwanted activity of birth control pills on venous function.
  • Theoretically, rutin may competitively inhibit action of quinolone antibiotics, which are used in the treatment of malaria.

Interactions with Herbs and Dietary Supplements

  • Oxerutins may have an additive effect when used concomitantly with horse chestnut extract.
  • Rutosid enzyme is often used in combination with bromelain and trypsin. Based on early evidence, troxerutin appears safe for use with Gingko bilobo for the treatment of hemorrhoids.
  • N-acetylcysteine (NAC) in combination with rutin may reduce ethane and MDA concentrations and increase GSH; this combination may be efficient in protecting the lungs of patients with adult respiratory distress syndrome.
  • Rutin supplements may have an additive effect with quercetin supplements, as quercetin is a flavonoid yielded from rutin.
  • Theoretically, rutin may increase absorption of vitamin C. Rutin is found in buckwheat herb tea and thus may have an additive effect when taken concomitantly.

Attribution
  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Akhtar NM, Naseer R, Farooqi AZ, et al. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee--a double-blind prospective randomized study. Clin Rheumatol 2004;23(5):410-415.
  2. Basile M, Gidaro S, Pacella M, et al. Parenteral troxerutin and carbazochrome combination in the treatment of post-hemorrhoidectomy status: a randomized, double-blind, placebo-controlled, phase IV study. Curr Med Res Opin 2001;17(4):256-261.
  3. Baumhackl U, Kappos L, Radue EW, et al. A randomized, double-blind, placebo-controlled study of oral hydrolytic enzymes in relapsing multiple sclerosis. Mult Scler 2005;11(2):166-168.
  4. Belcaro G, Cesarone MR, Bavera P, et al. HR (Venoruton1000, Paroven, 0-[beta-hydroxyethyl]-rutosides) vs. Daflon 500 in chronic venous disease and microangiopathy: an independent prospective, controlled, randomized trial. J Cardiovasc Pharmacol Ther 2002;7(3):139-145.
  5. Cesarone MR, Belcaro G, Pellegrini L, et al. HR, 0-(beta-hydroxyethyl)-rutosides; (Venoruton): rapid relief of signs/symptoms in chronic venous insufficiency and microangiopathy: a prospective, controlled study. Angiology 2005;56(2):165-172.
  6. Cesarone MR, Belcaro G, Ricci A, et al. Prevention of edema and flight microangiopathy with Venoruton (HR), (0-[beta-hydroxyethyl]-rutosides) in patients with varicose veins. Angiology 2005;56(3):289-293.
  7. Cesarone MR, Incandela L, DeSanctis MT, et al. Variations in plasma free radicals in patients with venous hypertension with HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides): a clinical, prospective, placebo-controlled, randomized trial. J Cardiovasc Pharmacol Ther 2002;7 Suppl 1:S25-S28.
  8. Grotz KA, Wustenberg P, Kohnen R, et al. Prophylaxis of radiogenic sialadenitis and mucositis by coumarin/troxerutine in patients with head and neck cancer--a prospective,randomized, placebo-controlled, double-blind study. Br J Oral Maxillofac Surg 2001;39(1):34-39.
  9. 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.
  10. Petruzzellis V, Troccoli T, Candiani C, et al. Oxerutins (Venoruton): efficacy in chronic venous insufficiency--a double-blind, randomized, controlled study. Angiology 2002;53(3):257-263.
  11. Rammer E, Friedrich F. [Enzyme therapy in treatment of mastopathy. A randomized double-blind clinical study]. Wien Klin Wochenschr 1996;108(6):180-183.
  12. Sumboonnanonda K, Lertsithichai P. Clinical study of the Ginko biloba--Troxerutin-Heptaminol Hce in the treatment of acute hemorrhoidal attacks. J Med Assoc Thai 2004;87(2):137-142.
  13. Tilscher H, Keusch R, Neumann K. [Results of a double-blind, randomized comparative study of Wobenzym-placebo in patients with cervical syndrome]. Wien Med Wochenschr 1996;146(5):91-95.
  14. Tilwe GH, Beria S, Turakhia NH, et al. Efficacy and tolerability of oral enzyme therapy as compared to diclofenac in active osteoarthrosis of knee joint: an open randomized controlled clinical trial. J Assoc Physicians India 2001;49:617-621.
  15. Turner RB, Fowler SL, Berg K. Treatment of the common cold with troxerutin. APMIS 2004;112(9):605-611.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.


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