Rutin supplement health benefit by Ray Sahelian, M.D.
February 6 2014

Quercetin is a flavonoid with a wide range of biological activities. It mainly occurs in plants as glycosides, such as rutin (quercetin rutinoside) in tea. Quercetin and rutin are used in many countries as medications for blood vessel protection and are ingredients of numerous multivitamin preparations and herbal remedies. Rutin is also called rutoside.

Food Sources
Rutin is found in buckwheat seed, fruits and fruit rinds, especially citrus fruits (orange, grapefruit, lemon, lime) and berries such as mulberry.

Benefits
Rutin inhibits platelet aggregation, making the blood thinner and improve circulation.
Has anti-inflammatory activity.
Rutin inhibits aldose reductase activity. Aldose reductase is an enzyme normally present in the eye and elsewhere in the body. It helps change glucose (sugar - glucose) into a sugar alcohol called sorbitol. Too much sorbitol trapped in eye and nerve cells can damage these cells, leading to retinopathy and neuropathy. Substances that prevent or slow the action of aldose reductase are being studied as a way to prevent or delay these complications of diabetes. Aldose reductase is the first enzyme in the sorbitol pathway. This pathway is responsible for the conversion of glucose to sorbitol, and of galactose to galactitol. Under conditions of hyperglycemia, sorbitol accumulation occurs. Aldose reductase inhibitors prevent the accumulation of intracellular sorbitol.

Rutin has been evaluated in the following conditions:
Inflammatory bowel disease, see natural ways to treat this medical condition
Has been tested as a treatment for varicose veins
In tardive dyskenisia as a result of antipsychotic medication use

Antioxidant benefit
In vitro catabolism of rutin by human faecal bacteria and the antioxidant capacity of its catabolites.
Free Radic Biol Med. 2009. Division of Ecology and Evolutionary Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
The role of colonic microflora in the breakdown of quercetin-3-O-rutinoside rutin was investigated. An in vitro fermentation model was used and i) 28 micromoles of rutin and ii) 55 micromoles of quercetin plus 18 x 10(6) dpm [4-(14)C]quercetin (60 nmoles) were incubated with fresh faecal samples from three human volunteers, in the presence and absence of glucose. The accumulation of quercetin during in vitro fermentation demonstrated that deglycosylation is the initial step in the breakdown of rutin. The subsequent degradation of quercetin was dependent upon inter-individual composition of the bacterial microflora and was directed predominantly towards the production of either hydroxyphenylacetic acid derivatives or hydroxybenzoic acids. Possible catabolic pathways for these conversions are proposed. The presence of glucose as a carbon source stimulated the growth and the production of bacterial microflora responsible for both the deglycosylation of rutin and the catabolism of quercetin. 3,4-Dihydroxyphenylacetic acid accumulated in large amounts in the faecal samples and was found to possess significant reducing power and free radical scavenging activity. This catabolite may play a key role in the overall antioxidant capacity of the colonic lumen following the ingestion of quercetin-rich foods.

Cancer, neuroblastoma
Scientific World Journal. December 2013. Anti-Tumor Effect of Rutin on Human Neuroblastoma Cell Lines through Inducing G2/M Cell Cycle Arrest and Promoting Apoptosis.

Rutin and cholesterol
Effects of rutin on lipid profile in hypercholesterolaemic rats.
Basic Clin Pharmacol Toxicol. 2009; Ziaee A, Zamansoltani F, Nassiri-Asl M, Abbasi E. Department of Endocrinology, Qazvin University of Medical Sciences, Qazvin, Iran.
Rutin (3, 3', 4', 5, 7-pentahydrohyflavone-3-rhamnoglucoside) is a flavonoid of the flavonol type. Rutin is found in many plants and is also an important dietary constituent of food and plant-based beverages. Rutin has several pharmacological properties including antioxidant and cardioprotective activities. Also, it was identified that rutin is the major low-density lipoprotein (LDL) antioxidant compound of mulberry in an in vitro study. The effects of rutin were tested by using it as a supplement in a high-cholesterol diet. Our results indicate that rutin in combination with lovastatin showed improvement in lowering cholesterol levels in an animal model.

Rutin for dyskinesia
Protective effect of rutin, a polyphenolic flavonoid against haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes.
Fundam Clin Pharmacol. 2007. Centre with Potential for Excellence in Biomedical Sciences, Panjab University, Chandigarh , India.
The occurrence and irreversibility of tardive dyskinesia, a motor disorder of the orofacial region, resulting from chronic neuroleptic treatment has been considered a major clinical issue in the treatment of schizophrenia. Several animal studies have demonstrated an enhancement of oxidative damage and increased glutamatergic transmission after chronic administration of neuroleptics. The present study investigated the effect of rutin, an antioxidant in haloperidol-induced orofacial dyskinesia. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements, tongue protrusions and facial jerking in rats, which were significantly inhibited by rutin. Haloperidol also induced oxidative damage in all regions of brain which was prevented by rutin, especially in the subcortical region containing striatum. The findings of the present study suggested the involvement of free radicals in the development of neuroleptic-induced orofacial dyskinesia, a putative model of TD, and rutin as a possible therapeutic option to treat this hyperkinetic movement disorder.

Rutin and blood vessel health
5-Year control and treatment of edema and increased capillary filtration in venous hypertension and diabetic microangiopathy using O-(beta-hydroxyethyl)-rutosides: a prospective comparative clinical registry.
Angiology. 2008 Feb-Mar. Department of Biomedical Sciences, Chieti-Pescara University, and the San Valentino Vascular Screening Project, Italy.
This independent prospective controlled trial evaluates the efficacy of O-(beta-hydroxyethyl)-rutosides during 5 years of administration against signs and symptoms and further degeneration of microcirculatory disturbances. Patients having a severe degree of chronic venous insufficiency (CVI) and venous microangiopathy and completing at least 5 years of treatment are included. The following 4 groups are considered: group A (patients with CVI but without diabetes mellitus, receiving 1500 mg/d of O-(beta-hydroxyethyl)-rutosides), group B (patients with CVI and diabetes mellitus, receiving 2 g/d of O-(beta-hydroxyethyl)-rutosides), group C (control subjects receiving no pharmacologic or compression treatment), and group D (patients using elastic compression stockings only). No adverse effects or intolerance is noted, with good compliance (>85%). In group A, there is a statistically significant decrease in the CFR during 5 years of follow-up. In group B, the decrease in the CFR is greater than that in group A. Reductions in edema, swelling, and the CFR during 5 years are notable, and values approach normal levels. During 5 years, O-(beta-hydroxyethyl)-rutosides is effective in treating venous edema and hypertension and in preventing deterioration of the distal venous system.
   Dr Sahelian says: Could rutin be of benefit is those with easy bruising?

Testimonial, benefit for bruising
I am a 72 year old male and have been suffering for years this ugly and unsightly condition of constant bruising on my arms, many times even spontaneous, without bumping into anything. I tried many things, nothing worked, until I tried one tablet of rutin daily with 2 Vitamin C x 500 mg tablets. After a month of this treatment, my bruising has totally STOPPED. I am cured of this disease. I beg you to please publish this testimony on your website to the benefit of millions of elderly people that may be suffering from this condition and don't know what to do about it. I understand that not all individuals react the same way to a treatment, but I'm sure that my experience will be helpful to many. I used Country Life Labs rutin, 500 mg daily, 100 tabs per bottle. As a curious detail, after I reported to my doctor how I was able to get rid of the bruising and blood spots on the arms, he then remembered that in Cuba, in the 50's, a product was for sale that combined Rutin and Vitamin C in one tablet. The name of the product in those days was "Rutascorbin". My doctor said he just forgot about that, after so many years.

Glaucoma
Perhaps rutin can be of help in reducing intraocular pressure in patients with glaucoma.
J Ocul Pharmacol Ther. 2012. Oral administration of forskolin and rutin contributes to intraocular pressure control in primary open angle glaucoma patients under maximum tolerated medical therapy.

Kidney disease, not helpful
J Agric Food Chem. July 2013. Rutin (quercetin rutinoside) induced protein-energy malnutrition in chronic kidney disease, but quercetin acted beneficially in a rat study.

Rutin side effects, safety, risk
Can you tell me if rutin side effects are known? I am 65, have high cholesterol, taking LIpitor and one aspirin a day, otherwise in good health.
   A 5 year long study using rutin did not show it to have any serious side effects. However, it is difficult to know what interactions rutin supplements would have with Lipitor and aspirin. Much is still not known about its long term use and its interactions with medications.

Rutin allergy?
Q. I was tested for allergies today by AllergiCare. They told me I'm allergic to rutin and several other substances including tetracycline, grape sugar and table salt. I had never heard of rutin before, so I've been researching it for the past several hours. I stumbled upon an article of yours in which you demonstrate a high level of understanding about rutin. I'd greatly appreciate any insight you may have on what the effects of an allergy to rutin might be. It seems to be a substance found in many foods that has many antioxidant and other benefits. What happens if my body is having a histamine response to rutin? Any ideas you may have on this would be greatly appreciated.
   A. I have not studied rutin allergy in detail but I think it is not common. Allergy testing is quite controversial and it may be a good idea to have a completely different doctor and laboratory retest for allergies to either confirm or question the initial results provided by AllergiCare. Most studies show rutin to inhibit allergies.

I was perusing your site regarding rutin allergy. You said you had not seen any. I definitely have it that results in rashes usually on my lower leg. It developed from taking rutin tablets. It returns if I eat large quantities of blueberries and now orange juice. I have to eat these products in moderation or else the rashes develop which do not respond well to antihistamines. Even triamcinolone cream is of only modest benefit. The product I was taking is Nature's Plus Rutin 500mg (from Sophora japonica leaf) made by Natural Organics Laboratories, Amityville NY.

Rutin Research studies
Partial reversal by rutin and quercetin of impaired cardiac function in streptozotocin-induced diabetic rats.
Can J Physiol Pharmacol. 2005.
The present investigation was carried out to evaluate the effects of the cyclodextrin complexes quercetin and rutin on left ventricle dysfunction in streptozotocin-induced diabetic rats. Echocardiography and biochemical and histological studies were carried out under normal control, diabetic untreated, normal and diabetic vehicle (β-cyclodextrin, p.o.), quercetin, and rutin treated normal and diabetic animals at varying time intervals (1 and 12 weeks). The increase in the serum triglycerides and cholesterol levels was attenuated in the cyclo dextrin complexes of rutin-treated animals significantly more than in the quercetin-treated and diabetic vehicle-treated animals.  Results from the present investigation demonstrated that rutin has a cardioprotective activity, and we conclude that the observed cardioprotection with rutin may be due to its aldose reductase inhibitory activity, as the enhanced aldose reductase pathway is implicated in the development of left ventricle dysfunction by several studies.

Effect of rutin on total antioxidant status of rats exposed to cigarette smoke.
Pharmacol Rep. 2005 Jan-Feb;57(1):84-9.
Exposure to tobacco smoke impairs the antioxidant defense mechanisms. In female Wistar rats fed on regular rodent chow and supplemented with a flavonoid rutin, Trolox Equivalent Antioxidant Capacity (TEAC) was measured as an ABTS-radical cation reduction power in plasma, lungs, liver, brain and kidneys. Exposure to smoke reduced the TEAC values in the liver, brain and kidneys and enhanced antioxidant potential in lungs in comparison to control animals. In plasma no change of TEAC value was observed. Supplementation with rutin increased antioxidant status of plasma, but TEAC was reduced in kidneys, brain and liver of smoke-exposed animals when compared to the matched controls. In lung no change in TEAC was found. The results suggest a complex pattern of influence of tobacco smoke on blood and tissue antioxidant mechanisms. The enrichment of diet with non-nutrient antioxidant rutin did not result in direct improvement of tissue TEAC with the exception of blood plasma.

Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin).
Carcinogenesis. 2005 Apr 14;
Diets rich in bioactive phytochemicals are associated with reduced risk of certain cancers, notably, colon cancer. Herbal supplements have not been directly tested as sources of bioactive cancer preventives. Hence, this study compares the ability of four herbal flavonoids (quercetin, curcumin, rutin, and silymarin) and one whole herb mixture (ginseng powder) to suppress aberrant crypt foci in an azoxymethane-induced rat colon cancer model. Taken together, the results of this study suggest that these herbal supplements may exert significant and potentially beneficial effects on decreasing the amount of precancerous lesions and inducing apoptosis in the large intestine.

Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice: attenuation of pro-inflammatory gene expression.
Biochem Pharmacol. 2005 Feb 1;69(3):395-406.
Oxidative stress has been shown to play a pivotal role in the onset of inflammatory bowel disease and carcinogenesis. We evaluated the effects of two dietary anti-oxidants, rutin and its aglycone quercetin, on dextran sulfate sodium (DSS)-induced experimental colitis in mice. Female ICR mice were fed a diet containing 0.1% rutin or 0.1% quercetin for 2 weeks, and given 5% DSS in drinking water during the second week to induce colitis.  Our results suggest that rutin may be useful for the prevention and treatment of inflammatory bowel disease and colorectal carcinogenesis via attenuation of pro-inflammatory cytokine production.

Inhibitory effect of quercetin, rutin and puerarin on HDL oxidation induced by Cu2+
Sichuan Da Xue Xue Bao Yi Xue Ban. 2004 Nov;35(6):836-8.
To evaluate the inhibitory effect of quercetin, rutin and puerarin on the HDL oxidation induced by Cu2+ and to investigate their action on the prevention and cure of atherosclerosis. The serum HDL of healthy human was isolated by the one step density gradient ultracentrifugation. The HDL oxidation was induced by Cu2+ in vitro for different time, quercetin and rutin at 5 micromol/L were added ahead, respectively. The above findings suggested that quercetin and rutin inhibit oxidation of HDL significantly, but puerarin has less antioxidative function.

Effect of hesperidin and rutin on oxidative modification of high density lipoprotein in vitro
Zhong Xi Yi Jie He Xue Bao. 2004 Mar;2(2):115-6, 119.
To study the effect of hesperidin and rutin on oxidative modification of high density lipoprotein (HDL) in vitro. HDL was isolated from healthy human plasma by sequential ultracentrifugation, and was oxidized by copper ions.The inhibitory effects of hesperidin and rutin on HDL oxidative modification were valued by the formation of malondialdehyde (MDA). Hesperidin and rutin significantly inhibited copper-induced oxidation of HDL in a dose-dependent manner. Both hesperidin and rutin can prevent HDL from copper-induced oxidative modification in vitro. This result suggests that they might have antiatherogenic effect.

Mechanisms involved in the antiplatelet activity of rutin, a glycoside of the flavonol quercetin, in human platelets.
J Agric Food Chem. 2004.
The aim of this study was to systematically examine the inhibitory mechanisms of rutin, a well-known flavonoid in platelet aggregation. In this study, rutin concentration-dependently inhibited platelet aggregation in human platelets stimulated by agonists (i.e., collagen). Rutin did not significantly interfere with the binding of FITC-triflavin to the glycoprotein IIb/IIIa complex in human platelets. Rutin markedly inhibited intracellular Ca(2+) mobilization and thromboxane A(2) formation in human platelets stimulated by collagen. Rapid phosphorylation of a platelet protein of M(r) 47000 (P47), a marker of protein kinase C activation, was triggered by collagen (1 microg/mL). This phosphorylation was markedly inhibited by rutin. On the other hand, rutin did not significantly increase the formations of cyclic AMP and nitric oxide/cyclic GMP in platelets. In conclusion, these results indicate that the antiplatelet activity of rutin may involve the following pathways: rutin inhibited the activation of phospholipase C, followed by inhibition of protein kinase C activity and thromboxane A(2) formation, thereby leading to inhibition of the phosphorylation of P47 and intracellular Ca(2+) mobilization, finally resulting in inhibition of platelet aggregation.

The modulating effects of quercetin and rutin on the mitomycin C induced DNA damage.
Toxicol Lett. 2004 Jun 15;151(1):143-9.
The present study was carried out to investigate the modulating effects of the two flavonoids quercetin and rutin on the mutagenic anticancer drug mitomycin C by single cell gel electrophoresis (Comet assay) in human lymphocytes. Lymphocytes were incubated with different concentrations of quercetin and rutin, with or without mitomycin C, and DNA damage was evaluated. In human lymphocytes quercetin and rutin displayed protective effects on DNA damage induced by mitomycin C, in a concentration-dependent manner.

Synergistic inhibition of low-density lipoprotein oxidation by rutin, gamma-terpinene, and ascorbic acid.
Phytomedicine. 2004.
Low-density lipoprotein (LDL) oxidation may play a significant role in atherogenesis. Flavonoids are well-known for their excellent antioxidative capacity in various model systems, therefore we examined the behaviour of rutin, a quercetin-3-rutinosid, in the copper-mediated LDL oxidation. Rutin alone has been shown to protect LDL against oxidation. Furthermore we investigated the combination of rutin with a hydrophilic (ascorbate) and a lipophilic antioxidant (gamma-terpinene) in copper-mediated LDL oxidation. In both cases we found a synergistic effect on lag phase prolongation. To elucidate whether this effect mainly depends on the copper chelating ability of rutin we examined its reaction in more detail. Although inhibiting the oxidation of alpha-linolenic acid in the "rose bengal system" no direct influence of a copper-rutin-complex was determined. We conclude that a redox active copper-rutin-complex is still able to initiate the LDL oxidation but may prevent copper from a reaction at the binding sites of apoB-100. The synergistic effect in preventing LDL oxidation is due to this trapping of copper in a complex in the case of ascorbate. The synergistic action of rutin and gamma-terpinene can be explained by different distribution of rutin and gamma-terpinene in, and around the LDL-particle, respectively.

Protective effects of N-acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome.
Shock. 2000.
This study investigates the effects of N-acetylcysteine (NAC) and rutin on the lung oxidative burden of patients with early adult respiratory distress syndrome (ARDS). The protection was evaluated by measuring expired ethane and malondialdehyde (MDA), and oxidized (GSSG) and reduced glutathione (GSH) in the epithelial lining fluid of 36 patients who developed ARDS less than 24 hours before enrollment in the study. The patients were randomly assigned to 3 groups, receiving 250 mL 5% dextrose in water (group 1), NAC 50 mg/kg body weight in 5% dextrose (group 2), and NAC 50 mg/kg + rutin 5 mg/kg in 5% dextrose (group 3). Ethane and MDA concentrations were significantly reduced in the treatment groups after day 6. GSH was 30% increased in the treatment groups. No significant variations were observed in the control group until day 9. The trial confirms that NAC and rutin are efficient in protecting the lungs of patients with ARDS.

Questions
Q. I suffer from abnormally high pressure in my eyes. At this point, the nerves are not damaged but I am at risk. I understand that Rutin supplement in very good to lower the eye pressure. Is that true?
   A. We have not come across any human trials regarding the use of rutin supplements for glaucoma or high pressure in the eye.

Q. Recently I have been exposed for a very long time to a (possible) carcinogen. This is why I have been looking for a long time for an effective chemopreventive agent. This is why I use Rutin 500 mg a day from Solvay. Recently I have discovered that the supplement might not contain 500 mg of pure Rutin, but actually partially quercetin and partially rutin, because when I soluate the supplement in water I get some green (unsoluable) residue that looks like pure quercetin. But some of it is soluable. Recently I have changed my dose into 1000 mg a day, worried that 500 mg might not be enough for me, but I am also worried if this dosage may also pose a health risk, such as causing bleeding (GI bleeding for example). Do you think that using rutin might pose a dangerous health risk?
   A. There is no human research with using rutin by itself or with quercetin for prolonged periods, so we don't know. We prefer people take breaks and also there are many other options you and your doctor can read on the cancer web page.

Q. Can 5-htp be taken the same day as a rutin supplement?
   A. Probably, we don't see any major interaction when dosages are kept low.

Q. I am a 50 yr old woman with multiple medical issues. Within the last year, I developed a case of Schamberg's Purpura on my feet and ankles and it is traveling up my shins. I have seen my dermatologist who said there is nothing to do but wear support hose. I tried that and it doesn't really help. He said no one knows for sure what causes Schamberg's purpura. I did some research and found that it can be a number of things from water retention, which I have had, to an allergic response. I finally found two different remedies. One is the use of a gout medication called colchicine. Since I am on several medications, my doctor was not interested in me taking another powerful medication so that was out. The other remedy I found was an O-T-C remedy using the bioflavonoid, rutin, and Vit C. According to the research, a patient is to take rutin 500 mg and Vit C 500 mg twice a day. It can take up to 4-6 months to go away, but it is supposed to work. I have been taking rutin and vitamin C for two months. The purpura seems to be lightening and going away. However, that may have happened anyway. I believe mine is an allergic response to something, given that I've noticed a pattern to it. I notice that I get red bumps that itch just before it gets worse and then gets better. They recommend using cortisone cream for the itching which I do. I wondered if you've heard anything about this? BTW- the rutin can be purchased at the natural health food stores as a supplement or you can get it in a product called Venastat. This product is found at local drugstores and is used to help the leg pain of poor circulation by improving circulation. I've noticed that my legs don't hurt like they used to when I am on them a lot. This Venastat product is also supposed to be useful for spider veins. I have a number of them and I am waiting to see if it works. I know that when using natural supplements it can take several months to see or feel a difference. Great and informative site!

It seems like the supplement sources for both Rutin and Quercetin are often from the Dimorphandra mollis plant. Rutin is a glycoside of Quercetin. Since I don't have a very extensive scientific background, is this saying that Rutin actually contains Quercetin (like Lactose is made up of galactose and glucose)? So would Rutin supplements (from Dimorphandra mollis extract) be a source of Quercetin? If so, what percentage of Rutin is Quercetin? Could a person take 500 mg of Rutin and in essence be taking a Quercetin supplement?
   Rutin is quercetin plus a glycoside. When rutin is ingested as a supplement, it is possible that the glycoside is cleaved and quercetin remains. However, we don't have a full understanding of what percentage of rutin is changed to quercetin in the body when a rutin supplement is taken. Since we have not seen any clinical trials regarding the effects of taking a rutin supplement versus a quercetin supplement, we don't know what clinical differences there would be between the two.

I was diagnosed with type 1 diabetes 2 years ago, and now I also have background retinopathy. A naturopath suggested I take rutin and vitamin C, but I read on the internet that it the evidence suggests that it canít help with this. I bruise terribly easily, due to having taken a large amount of steroids for my allergic asthma, and I notice that since taking the rutin, the bruising has improved. Do you think the it can help the background retinopathy also?
   I am not aware of such studies yet as a treatment for retinopathy.