The effects of Rutivite on the circulation
In a clinical experiment Rutivite was shown to have interesting and promising effects on small blood vessels in the body. Plant products containing rutin and other flavonoids have for long been used in the treatment of circulatory problems, and are known for example to be an essential factor with vitamins C in the prevention of scurvy. Rutivite, made from buckwheat leaf, in one such remedy whose use has been associated with relief in some congestive conditions like varicose veins, venous congestion and capillary damage from a number of causes.
In a clinical study at the Centre for Complementary Health Studies at the University of Exeter, thirty-seven subjects with symptoms of poor venous circulation were recruited. Using the mild provocation of a suction cup applied to the lower leg and monitoring changes in local circulatory activity with laser Doppler flowmetry it was found that compared to healthy subjects these sufferers manifested sluggish recovery after the suction cup was applied. After Rutivite treatment the response of their capillary circulation moved significantly towards that seen in healthy subjects. There was an increase in general circulatory activity, with both an increase in blood flow and greater pulsatile activity. A number of likely mechanisms for these changes could be deduced. These reinforce the view that Rutivite has valuable potential for treating problems of poor or damaged capillary circulation.
Further long-term follow-up observations to pursue these leads will be conducted.
Simon Y. Mills MA, FNIMH. Centre for Complementary Health Studies, University of Exeter.
Extracts of the 1993 Controlled clinical observations of the effects of Rutivite on the microcirculation are shown below.
Summary
Thirty-seven subjects suffering the symptoms of venous insufficiency were entered into a controlled clinical study to determine the impact on their microcirculation of Rutivite, a popular natural treatment for this condition that contains high levels of plant flavonoids commonly encountered in the normal diet. Using a mild provocation of a suction cup applied to the lower leg and monitoring changes in local circulatory activity with laser Doppler flowmetry it was possible to identify three characteristics of vascular responses that differentiated sufferers of venous insufficiency from healthy controls. After establishing baseline levels for these characteristics the subjects took Rutivite for a total of six weeks. Twenty-four subjects satisfactorily completed all stages of the study. In this sample it was possible to demonstrate statistically significant benefits in vascular reactivity and vasomotor activity. In a smaller subgroup [n=9] with oedematous symptoms, there was also a significant benefit on vascular resolution after suction. The desirability of further investigating the pharmacological effects of nutritional flavonoids is emphasised.
Introduction
Flavonoids, a group of phenolic constituents found widely in plants, including most fruits and vegetables, have been found to possess a number of anti-inflammatory effects, including, especially for rutin and others from the flavonol subgroup, effects on the microvasculature [Lewis]. However their bioavailability in the natural form has been widely questioned. Buckwheat, a plant rich in flavonols, has for many years had a popular reputation for efficacy in the treatment of circulatory problems. This reputation has not been confirmed scientifically although buckwheat, especially as the proprietary product Rutivite, remains a widely-available retail health product. As many people are drawn to use it, and personal impressions of its effects are often good, it is appropriate to see if there is any basis for such use.
The immediate difficulty was in finding a way of observing any impact on the microcirculation in a non-invasive way. The subjects who use such remedies are not hospitalised, nor are they often seriously ill. What was required was a technique for monitoring modest changes in physiological function that is also reliable and applicable to common health problems. The current project began with a protracted series of observations to establish clear and reliable baseline measurements of microcirculatory dysfunction.
As a test model the behaviour of the capillary circulation in the legs in chronic venous insufficiency was eventually considered suitable on two counts. First there are microcirculatory dysfunctions, which are known to be at least partly responsible for the symptoms of this condition. These include faulty capillary membranes which flavonoids might be expected to correct. Second, buckwheat has a reputation in helping the subjective symptoms of varicosed veins and venous congestion: this would point to a possible effect on common microcirculatory problem.
This study set out to observe the response of the microvasculature exposed to a mild stress, in the form of a suction cup applied to the skin of the lower leg. Compared to healthy individuals those with symptomats of chronic venous insufficiency take longer to recover from, and in other ways respond differently to, such an intervention. The difference is most likely to be due to the state of health of the capillary circulation, a condition theoretically accessible to treatment by the constituents of buckwheat. The behaviour was monitored with laser Doppler flowmetry.
The Treatment
Buckwheat
The formulation of the treatment was as proprietary tablets Rutivite, made up of buckwheat herb powder, maize starch, lactose, seaweed extract, calcium carbonate, gum karaya, magnesium stearate. They may be swallowed or dissolved in water.
Buckwheat, Fagopyrum esculentum Moench., of the family Polygonaceae, is a plant grown primarily for its seeds which are used for animal and human food. The leaves have been used popularly for circulatory problems and by herbal practitioners as a remedy for hypertension, varicosed veins, petechiae due to capillary fragility, retinal haemorrhage, purpura, and chilblains [British Herbal Pharmacopoeia 1983].
This application has been linked to its most well-known constituent, rutin, which it contains at levels of up to 6.4%. Samples of Rutivite
to be used for this trial were prescribed at a daily dose of 2280 mg of dried buckwheat which yields a total of 120 mg of rutin. The daily dose of pure rutin recommended in pharmacopoeias and other references is between 30 and 300 mg. Other constituents in the whole plant, including related flavonoids, may have similar pharmacological activity.
Rutin
Rutin, quercetin-3-rutoside, is a flavonoid glycoside with quercetin as an aglycone and rhamnose and glucose as sugar moieties. It is very widely distributed in the plant kingdom. It has been reported to decrease capillary permeability and fragility, being an essential constituent of anti-scorbitic factor with ascorbic acid or vitamin C [it was initially referred to as vitamin P after its discovery by Szent-Gyorgy in 1936]. It is official in many pharmacopoeias and is widely sold as a health supplement, sometimes in association with Vitamin C.
In experiments it has been shown to increase survival times of rats fed a thrombogenic diet, and in other animals to reduce oedema, reduce cholesterol-induced atheroma, and inhibit the carcinogenic action of benzo[a]pyrene [Leung]. Like ascorbic acid it is an oxygen radical scavenger and has been shown to reduce the mutagenicity of dusts and asbestos [Korkina et al] and other stressors [Deschner et al., Negre-Salvayre et a1., Steele et a1., Teofili et al].
Commercial products with a similar structure, hydroxyethylrutosides, or oxerutins, are marketed under the name of Paroven for the treatment of chronic venous insufficiency. There are a number of reports demonstrating positive effects on capillary permeability [Blumberg et al., Burnand, Wismer], on venous insufficiency [Fitzgerald, Halborg-Sorenson], venous hypertension [Belcaro et al. 1989, Prerovsky et al., Rose] and the subjective symptoms of varicosed veins [Bergstein, Pulvertaft 1979 and 1983]. Other researchers have reported an improvement in oxygen perfusion of tissues surrounding varicosed veins [McEwan and McArdle], including in tissues of those suffering lipodermatosclerosis [Bishop et al.].
The development of synthetic rutosides has followed the finding that natural rutin is poorly absorbed. However rutin is now known to be rapidly metabolised by bacteria in the intestine, via quercetin, to 3,4-dihydroxyphenylacetic acid [3,4-DPA], a small phenolic compound that is also easily absorbed and is likely to have appreciable pharmacological activity [Goldin].
Toxicology
Regular searches of Toxline, Excerpta Medica and Chemical Abstracts databases confirmed that there are no published accounts of adverse reports following the ingestion of buckwheat leaf. There are also no adverse drug reactions reported to the National Poisons Unit.
Occasional dermatological irritation from contact with buckwheat plant has been reported [Johnson] and a haptenic substance have been isolated from the plant [Yagi et al]. There is no suggestion of immunological challenge on oral ingestion, and such an event is unlikely.
There have been reports that rutin content in wines is associated with their in vitro mutagenicity [Rueff et a1]. However rutin's contribution to the mutagenicity of wine has since been challenged [Jurado et al]. Other reports have rutin being converted to excreted mutagenic metabolites when fed at levels of 2000 mg/kg body weight to Sprague-Dawley rats [Crebelli et al], with indications that certain oral streptococci, S. milleri, found also in humans, might be responsible [shillitoe et al.]. However in the first report no mutagenicity was found in the rat's plasma, and in the second, no conversion was established in body fluids. Other investigations [Habs et a1., Hirono et al., Morino et a1.] showed no evidence of carcinogencity in administering rutin to experimental animals even at doses as high as 500 mg/kg body weight, and an in vitro lack of genotoxicity has also been found [Popp and Schimmer]. Rutin was found to be an inactive constituent in the anti-fertility activity of Ruta graveolens [Gandhi et all]. Rutin is a common constituent of the vegetable and fruit component of the diet. It was concluded therefore that at the low therapeutic dosages of rutin provided here [less than 2 mg/kg] there was likely to be no appreciable health risk.
Methods
The objectives of the study were to observe the effects of Rutivite on the response of the microvasculature after mild provocation of the cutaneous microcirculation in the lower limb in patients with chronic venous insufficiency. Treatment effect was assessed by change in a three parameters taken from laser Doppler flowmetry readings, referred to as vascular reactivity, vascular resolution and vasomotor activity.
Subjects were recruited with symptoms of chronic venous insufficiency: leg pain especially on standing, often with ankle swelling, oedema, varicose veins, schema, pigmentation and/or lipodermatosclerosis. Prior prescription or use of elasticated stockings was also inclusion criteria. The presentation and the sample population accorded well with that likely to seek health-food treatments for circulatory conditions.
All the subjects eventually assessed also satisfied diagnostic criteria for venous hypertension. In most cases however it was not possible to confirm the existence of previous thrombotic incidences.
Subjects with symptomatic arterial disease, heart failure, neoplasms, scleroderma, and connective tissue disease, with active venous ulceration, with a prescription of antithrombotics, insulin, digoxin, diuretics or other cardiovascular drugs, or with liver, kidney or neurological disease were excluded from the study. Subjects also needed to be ambulatory, to be capable of giving their fully informed consent, and could not be pregnant.
For an initial 6-week period each subject attended for 3 visits at 3-week intervals, to provide a measure of baseline readings with the laser Doppler flowmeter and to familiarise them with the routine. A proportion of subjects were withdrawn from the trial during this phase. At the third visit after 6 weeks subjects were provided with the treatment tablets. The treatment itself lasted for 6 weeks. Other medication was maintained with the request that the subject notify the Investigator if there was any change.
The temperature of the study rooms was kept at 22C during the trial and 30 minutes of acclimatisation was allowed before measurements were taken. For at least the last 15 minutes of this the subject was asked to lie supine on a treatment table with a laser Doppler probe attached with a lightly adhesive ring at a marked spot on an area of healthy skin about 2 cm from the malleolar prominence on the antero-medial aspect of the ankle. To ensure that measurements were taken from the same area at each visit, each case card included a map of the ankle Fitly the location of the probe drawn in. At the end of the 15 minutes a baseline reading was taken and the probe then removed. A small plastic chamber of 2.5 cm internal diameter attached to an Albert Waeschle electric Mini-Aspirator providing a negative vacuum pressure of between 55-60mm Hg was attached. The suction cup was placed so that the marked spot was midway between its centre and circumference, and the aspirator was switched on for 3 minutes. As soon as it was switched off the laser Doppler probe was replaced on exactly the previous spot, so that some of the wheal was still visible at one side. Recording proceeded for up to 90 minutes, or until circulatory activity had returned to normal stable levels. Visible healing time was also recorded.
Subject compliance was assessed in the initial week familiarisation phase. Poor prospects were withdrawn from the study. At the end of the 6 week treatment subjects were asked to return unused tablets to the Practice Manager and these were counted: in an ideal compliance there should be 82 tablets remaining. Compliance was considered adequate if less than 120 tablets remained.
Each subject was recalled for further observation 6 weeks after the completion of the trial.
Conclusion
It has been demonstrated that Rutivite, containing high levels of rutin and other flavonols, leads to a significant improvement in the responsiveness of the microcirculation in those suffering venous insufficiency, as manifested by the degree of vascular reactivity and vasomotor activity after mild physical stress to the tissues. These observations are consistent with the explanation that Rutivite stimulates and dilates collateral or shunt circulation. Although not significantly influencing measures reflecting the degree of oedema for the group as a whole, there was evidence of such an effect in those with the worst symptoms initially.
Further long-term follow-up observations on subjects choosing to continue with Rutivite will be conducted to provide further indications of long-term changes in the degree of vascular resolution and in subjective symptoms. It is clear that the full impact of nutritional flavonoids on the circulation deserves further scrutiny.
