Natural Sources of Rutin: Buckwheat seed, Eucalyptus leaves, fruits and fruit rinds, especially citrus fruits and rinds (orange, grapefruit, lemon, lime).

Forms:
Standardized rutin extracts used in antioxidant products and multivitamin and mineral supplements.

Therapeutic Uses:
– Allergies

– Anti-aging

– Anti-inflammatory

– Antioxidant

– Bleeding (recurrent)

– Bruises

– Cancer

– Capillary Fragility

– Cellular Regeneration

– Chronic Venous Insufficiency

– Circulatory Disorders

– Cramps (legs)

– Diabetic Complications

– Free Radical Related Diseases

– Hay Fever

– Hemorrhoids

– High Blood Pressure

– Hypertension

– Immune System

– Leg Vein Health

– Lower LDL Cholesterol

– Menopausal Symptoms

– Nocturnal Leg Cramps

– Pain (lower extremities)

– Prevention of abnormal growths

– Skin Conditions

– Vascular Disorders

– Venous Hypertension

– Venous Insufficiency

– Wounds

Overview:

Rutin, a bioflavonoid, is a water-soluble antioxidant that is widely distributed in the plant kingdom. It is often found together with vitamin C in fruits and potentates vitamin C activity within the body. Rutin is particularly concentrated in buckwheat. In 1942, researchers at the U.S. Department of Agriculture postulated the important physiological effect of rutin on capillary blood vessels. The USDA also discovered that buckwheat was an economical source for isolating rutin and developed manufacturing procedures. Bioflavonoids, in general, are essential for the processing of vitamin C within the body, the maintenance of capillary walls and the fortification of collagen, the intercellular “cement” of the body. A deficiency of rutin in the diet has been linked with abnormal capillary leakiness as well as pain in the extremities causing aches, weakness and night leg cramps. Supplemental rutin has been shown to reduce edema or excess swelling in the legs due to fluid retention. Like other bioflavonoids, rutin works best when given with vitamin C and other bioflavonoids. Rutin and other flavonoids are widely used for the treatment of chronic venous insufficiency (CVI). In clinical trials, rutin has demonstrated its activity by improving venous tone and vein elasticity. Randomized, double-blind, placebo-controlled clinical studies have shown an improvement in signs and symptoms related to chronic venous insufficiency including heavy legs, edema, paresthesia and cramps. Additionally, a randomized double-blind, placebo-controlled clinical study has shown that treatment with rutin for 2 weeks improved body temperature and was effective in controlling chronic venous hypertension, without side effect, and with good tolerability. Clinical research also shows that rutin can prevent the progression of micro-angiopathy to clinical stages and can prevent neuropathy. This is of particular importance for diabetic patients. Studies show that rutin is also effective treating hemorrhoids and reducing plasma free radicals both locally and systemically.

Chemistry:
Rutin is a polyphenolic compound classified as a bioflavonoid that is widely distributed in the plant kingdom. Rutin is found especially concentrated in buckwheat seeds, eucalyptus leaves and citrus rinds as a non-bitter tasting flavonoid glycoside (rutoside), together with other flavonoids. Bioflavonoids are often found together with vitamin C in fruits. Buckwheats are considered the most useful sources of rutin in food. Therefore, the development of buckwheat varieties that have high rutin content in seed is of interest to growers and manufacturers of buckwheat rutin products. As for the seed rutin content, researchers have already reported the varietal difference in two cultivated buckwheat species, common buckwheat (Fagopyrum esculentum) and tartary buckwheat (F. tataricum). Research on genetic variation within varieties and strains has shown that it is possible to produce crops with high (33 mg) and low (13 mg) ruitn content relatively easily by individual selection.

Suggested Amount:
The recommended daily dose of rutin ranges from between 1000mg to over 3000mg daily, depending upon the severity of the condition being treated. Significant healing of blood vessels with rutin can occur within only two weeks, although it is best to use flavonoids in therapeutic dosages for several months and then continue with maintenance dosages thereafter to produce and maintain the best results.

Drug Interactions:
Rutin and other bioflavonoids tend to reduce blood platelet stickiness in a beneficial way and therefore may reduce the dosage required for blood thinners.

Contraindications:
Bioflavonoids, including rutin, tend to reduce blood platelet stickiness and therefore individuals taking blood thinners should consult with their physician prior to commencing supplementation.

Side Effects:
No signs of toxicity have been observed with the normal intake of rutin or other flavonoids.

References:

Cesarone MR, Incandela L, DeSanctis MT, Belcaro G, Dugall M, Acerbi G. 2002. 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 Jan; 7 Suppl 1: S25-8.

Cesarone MR, Incandela L, DeSanctis MT, Belcaro G, Griffin M, Ippolito E, Acerbi G. 2002. Treatment of edema and increased capillary filtration in venous hypertension with HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides): a clinical, prospective, placebo-controlled, randomized, dose-ranging trial. J Cardiovasc Pharmacol Ther 2002 Jan; 7 Suppl 1: S21-4.

Incandela L, Cesarone MR, DeSanctis MT, Belcaro G, Dugall M, Acerbi G. 2002. 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 Jan; 7 Suppl 1: S11-5.

Petruzzellis V, Troccoli T, Candiani C, Guarisco R, Lospalluti M, Belcaro G, Dugall M. 2002. Oxerutins (Venoruton): efficacy in chronic venous insufficiency–a double-blind, randomized, controlled study. Angiology 2002 May-Jun; 53(3): 257-63.

Titapant V, Indrasukhsri B, Lekprasert V, Boonnuch W. 2001. Trihydroxyethylrutosides in the treatment of hemorrhoids of pregnancy: a double-blind placebo-controlled trial. J Med Assoc Thai 2001 Oct; 84(10): 1395-400.

Additional Information:

Rutin as a Component of ‘Vitamin P’:

Citrus bioflavonoids were first identified by Albert Szent-Gyorgyi in 1936, winner of The Nobel Prize for the discovery of vitamin C. He reported that citrus bioflavonoids strengthened blood vessel walls and prevented capillary permeability in ways that vitamin C did not. Indeed, he called these bioflavonoids ‘vitamin P’ after the Permeability factor because they prevented the permeability of capillaries. It was in the course of isolating vitamin C that he came across the bioflavonoids. Certain vitamin C deficiency symptoms, such as easy bruising and bleeding gums, were found in early studies to be relieved by crude vitamin C extract but not by purified vitamin C. Bioflavonoids were found to be the essential component in correcting this bruising tendency and improving the permeability and integrity of capillary walls. It so happened that Szent-Gyorgyi had a friend with bleeding gums and thought this condition might have something to do with a vitamin C deficiency. He gave the man some raw, impure vitamin C, and sure enough the bleeding gums cleared up. Later on, confronted by a recurrence of bleeding gums, he decided to try again; this time with pure vitamin C. He expected to observe an even more dramatic result but it did not occur. The man’s gums went right on bleeding. Szent-Gyorgyi re-examined his earlier preparation and decided that the effective impurity was bioflavonoids. He then tried these by themselves, and reported that they worked. He named these substances “vitamin P.” Bioflavonoids thus first came into use as protectors of capillaries, the tiniest blood vessels in the body. Later studies disputed his findings because a deficiency state could not be identified and so these compounds (including rutin) never actually attained full vitamin status. This is because there are over 4,000 different flavonoids with different properties and biological activities. Later studies done by Dr. Jacques Masquelier of France found that certain bioflavonoids called oligomeric proanthocyanidins (concentrated in grape seeds, grape skins, red wine, pine bark and many tree leaves) are the most effective components of the ‘vitamin P’ mixture that Szent-Gyorgyi spoke of. Rutin also has significant ‘vitamin P’ activity.

Flavonoids also serve as enzyme inhibitors. They block the enzymes that produce estrogen, thus reducing the risk of estrogen-induced cancers. And by blocking the enzyme cyclooxygenase, which breaks down prostaglandins, they reduce platelet stickiness and aggregation. For diabetic complications (neuropathy, microangiopathy, etc.), hemorrhoids, varicose veins, and other conditions in which capillaries and smaller blood vessels become weak, flavonoids such as rutin can help. Significant healing of blood vessels with rutin can occur within only two weeks, although it is best to use flavonoids in therapeutic dosages for several months and then continue with maintenance dosages thereafter to produce and maintain the best results. Flavonoids also strengthen collagen, the most abundant protein in the body. Collagen literally holds the body together. Intertwined strands of collagen make up soft tissues, tendons, ligaments, and bones. Flavonoids with ‘vitamin P’ activity provide structural support for collagen by helping to repair damaged cross-links within collagen structures and prevents tissues from sagging. Collagen also promotes wound and burn healing by helping form connective tissue in scarred areas.

Positive Clinical Findings:

Petruzzellis V, Troccoli T, Candiani C, Guarisco R, Lospalluti M, Belcaro G, Dugall M. 2002. Oxerutins (Venoruton): efficacy in chronic venous insufficiency–a double-blind, randomized, controlled study. Angiology 2002 May-Jun; 53(3): 257-63.

The aim of this study was to confirm the clinical efficacy of oxerutins by evaluation of venous parietal tone and microvascular perfusion in a double-blind, randomized, placebo-controlled study. The study included 60 patients. Venous tone was evaluated by air-plethysmography (APG) in patients with venous insufficiency (CVI). Forty patients were treated with oxerutins and 20 with placebo for 4 weeks. The dose of the first 2 weeks was higher than that of the following 2 weeks. The age range was between 18 and 65 years. Randomized patients received treatment (oxerutins or placebo) according to the grade of CVI. Patients with grade I CVI received 2 g/day in the first 2 weeks of treatment and 1 g/day in the following weeks. Patients with grade II CVI received 3 g/day in the first 2 weeks and 2 g/day in the following 2 weeks. Visits were scheduled at baseline time (visit 1), at 2 weeks (visit 2) and at 4 weeks (visit 3). They were assessed with the following: (1) APG; (2) light reflection rheography (LRR); (3) capillaroscopy; (4) liquid crystals thermography. CVI signs/symptoms–heavy legs, edema, paresthesia, and cramps–were evaluated following a 4-point rating scale (0 = no symptom; 3 = severe symptoms). At visit 3 a final opinion on efficacy was provided by both patients and investigators, based on a 4-point scale (none, fairly good, good, excellent). The two groups were homogeneous for age, sex, and clinical distribution. The changes in venous capacity, were significant (p<0.01) in the oxerutins group at visits 2 and 3; values in the placebo group remained unchanged. The changes in LRR were significant in the treatment group at visits 2 (p<0.05) and 3 (p<0.01); values in the placebo group remained unchanged. Changes in temperature were significant in the oxerutins group at visits 2 (p<0.05) and 3 (p<0.01); changes in the placebo group were not significant at the end of the study. Capillaroscopy showed an improvement in patients treated with oxerutins. The results of the analysis of signs/symptoms favored active treatment. The overall effects of oxerutins were significantly better than the effects of placebo. Considering both noninvasive tests and clinical evaluation, oxerutins is effective in controlling chronic venous hypertension, without side effect, and with good tolerability. Cesarone MR, Incandela L, DeSanctis MT, Belcaro G, Dugall M, Acerbi G. 2002. 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 Jan; 7 Suppl 1: S25-8. The aim of this study was to demonstrate whether HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides), was effective in improving levels of plasma free radicals (PFRs) in patients with chronic venous insufficiency (CVI) and venous microangiopathy. Patients were randomized into the treatment group, which received oral HR (1g sachets, twice daily, for 4 weeks), and a placebo group, which received comparable placebo. Below-knee Sigvaris stockings were used during the study. PFRs were measured with the D-Rom test at the finger and at a vein of the leg in an area of CVI. The mean age of included subjects was 46 years (SD 11) in the treatment group (20 patients; 6 females) and 46.4 (SD 8) in the placebo group (20 patients; 7 females). There were no differences between placebo and treatment groups at inclusion in age and sex distribution and in parameters indicating venous hypertension. The decrease of PFRs levels in the treatment group was significant, both at the finger and in the distal blood taken in areas of CVI. There there were no significant changes in the control group. In areas of venous hypertension, PFRs values were on average higher than at the finger (systemic) level (P < 0.05). In parallel with the progressive decrease in PFRs associated with treatment, the analogue score was significantly decreased at 2 (P < 0.05) and 4 weeks (P < 0.02) in the HR group. No changes were observed in the placebo group. No adverse effects were observed. In conclusion, HR treatment is effective in decreasing both the systemic and local values of PFRs and therefore may have a positive effect on the evolution of CVI. Cesarone MR, Incandela L, DeSanctis MT, Belcaro G, Griffin M, Ippolito E, Acerbi G. 2002. Treatment of edema and increased capillary filtration in venous hypertension with HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides): a clinical, prospective, placebo-controlled, randomized, dose-ranging trial. J Cardiovasc Pharmacol Ther 2002 Jan; 7 Suppl 1: S21-4. The variation of capillary filtration rate (CFR) and ankle edema (AE) were evaluated in three groups of patients with venous hypertension with ambulatory venous pressure > 42 mmHg and in healthy subjects before and after treatment for four weeks with HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (30 patients) was treated with HR 500 mg tid; group B (30 patients) was treated with 1 g tid; group C (30 patients) was treated with placebo; group D (10 healthy subjects) was treated with HR 1 g/day in a randomised study. CFR was assessed by venous occlusion plethysmography. Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. RESULTS: There were no significant differences for sex and age distribution among the groups; no significant differences were found for ambulatory venous pressure and refilling time and parameters of venous hypertension among groups. There was a significant difference between normal subjects and patients. There were no drop-outs and observed intolerance. In group A, there was a significant decrease of CFR (P < 0.01) after treatment. In group B (2 g/day), the decrease was greater than that in group A (P < 0.05). In group C (placebo) there was no significant difference before or after treatment. The variations in analogue score was higher with the higher dosage. The score of group A fell from 7.8 (SD 1.3) to 4 (1). Group B’s score fell from 7.9 (2) to 3.1 (1.2). In group C (placebo) there was no change. The decrease in the score in the groups of patients was correlated with the variation in edema and CFR. CONCLUSION: HR is effective in venous edema and hypertension. Its effects are dose-related. Incandela L, Cesarone MR, DeSanctis MT, Belcaro G, Dugall M, Acerbi G. 2002. 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 Jan; 7 Suppl 1: S11-5. This study was planned to demonstrate in a prospective, placebo-controlled, randomized study, whether HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides), is effective in improving the microcirculation in subjects with diabetic microangiopathy and neuropathy. Patients with severe diabetic microangiopathy, neuropathy and edema, patients with microangiopathy, without neuropathy, and 20 healthy subjects were included. Microangiopathy was defined by laser Doppler flowmetry and capillary filtration (rate of ankle swelling (RAS)). Inclusion criteria were: increase in resting flux (RF) and RAS, a decrease in venoarteriolar response (VAR), and alterations in flux increase with temperature. The 2 groups of patients and the control group were randomized in a treatment sub-group which received HR (1 g, twice daily for 6 months); those in the placebo group received similar treatment. RESULTS: Groups were comparable; there were no drop-outs. There were no differences in the treatment and placebo groups at inclusion. Treatment was well tolerated; no adverse effects were reported. No variations were observed in healthy subjects at 6 months. In both groups of patients, significant decreases (P < 0.05) in RF and RAS were observed in the active treatment groups. The decrease in RAS was associated with a decrease in edema (P < 0.05) in both treatment groups. The decrease in RF and the increase in VAR were associated with a proportional decrease in RAS (P < 0.05). In patients without neuropathy, the variations in RF, VAR, and RAS were larger (P < 0.05) at 6 months. The variations in healthy subjects were limited and not significant. CONCLUSION: The decrease in capillary filtration and edema with HR is associated with symptomatic improvement. The action on edema is beneficial for the evolution of neuropathy. The effects of HR on flux, RAS, and edema are important in early stages of microangiopathy to avoid progression to clinical stages. Titapant V, Indrasukhsri B, Lekprasert V, Boonnuch W. 2001. Trihydroxyethylrutosides in the treatment of hemorrhoids of pregnancy: a double-blind placebo-controlled trial. J Med Assoc Thai 2001 Oct; 84(10): 1395-400. The safety and efficacy of Trihydroxyethylrutosides (HR) in the treatment of 53 patients with 1st-2nd degree hemorrhoids of pregnancy (16th-34th week) was investigated in a double-blind randomised, placebo controlled trial. The dosage of Trihydroxyethylrutosides was 1 tablet of 300 milligrams twice daily for the first 2 weeks. If the treatment was successful, the treatment was stopped. If the clinical signs or symptoms still persisted, the treatment was continued for another two weeks using the same dosage and re-evaluated at the end of the fourth week after initial treatment. The parameters for efficacy were symptoms (pain, bleeding, exudation and pruritus) and the objective signs on proctoscopy (bleeding, inflammation and dilatation of the hemorrhoidal venous plexus). The study revealed improvement of symptoms in the study group which was better than in the control group after 2 weeks of treatment but the clinical signs were not different. After a further 2 weeks of treatment, the result showed improvement of both clinical signs and symptoms in this study. Only one mild transient side effect was reported in the HR group and there were no drug-related problems in the pregnancies, delivery or the babies.