Diosmin supplement health benefit
June 17 2015 by Ray Sahelian, M.D.

Diosmin is a flavonoid that can be isolated from various plant sources or derived from the flavonoid hesperidin. It was first introduced used in medical treatment in 1969. It is useful in chronic venous insufficiency, hemorrhoids, lymphedema, and varicose veins. Diosmin also has anti-inflammatory, antioxidant, and anti-cancer properties. Only rare occurrences of side effects have been reported in medical journals as of 2015.

Diabetic neuropathy
J Integr Med. 2014 Jan. Protective effect of diosmin against diabetic neuropathy in experimental rats.

Lung cancer
The effect of the flavonoid diosmin, Grape-Seed extract and red wine on the pulmonary metastatic B16F10 melanoma.
Histol Histopathol. 2005. Pathology Department, Faculty of Medicine, University of Murcia, Espinardo, Spain.
To study the effect of different phenolic compounds and red wine on pulmonary metastatic melanoma. Swiss mice were inoculated with 500000 melanocytes B16F10 and given oral doses of diosmin, grape seed extract (GSE) and red wine. A macroscopic count was made of the metastatic nodules on the lung surface and a microscopic study by image analysis of five sections, calculating the implantation percentage and tumoral growth and invasion indices.  Macroscopically, the group treated with diosmin showed the greatest reduction (52%) in the number of metastatic nodules compared with the control group, which was treated with ethanol, while GSE and red wine caused decreases of 26 and 28%, respectively. Microscopically, there was a decrease in the implantation percentage after the administration of diosmin (79%) and red wine (20%), and an increase of 2% after the administration of GSE, all relative to the ethanol-treated control. As regards the growth index, diosmin produced a reduction of 67% and red wine a reduction of 20%, while GSE again produced an increase (25%). Diosmin originated the greatest reduction in pulmonary metastases, both at the macroscopic and microscopic levels.

Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin.
J Agric Food Chem. 2005. Pathology Department, Faculty of Medicine, University of Murcia, Espinardo, Murcia, Spain.
Melanoma is one of the most frequently metastasizing malignant neoplasias. This study examines an experimental model of pulmonary metastasis and the B16F10 cell subline, highly metastatic in the lung. Antimetastatic effects of the flavonoids tangeretin, rutin, and diosmin were analyzed, and at the same time an analysis of the metastatic activity of ethanol was performed, considered to be necessary because it is used as a vehicle for administering the flavonoids. The greatest reduction in the number of metastatic nodules (52%) was obtained with diosmin. Rutin  and tangeretin treated groups also showed reductions of the same index compared with the ethanol group. It would seem that structural factors would better explain these results and the antimetastatic activity of each flavonoid and the respective metabolites.

Diosmin in Daflon and product DiosVein - press release by Berg imports
There appears to be improvement in microcirculatory disorders experienced by diabetic patients that were treated with Daflon 500mg -a fraction flavonoid, 90% of which is comprised of the supplement Diosmin. Derived from Sweet Orange, Diosmin is the predominant component of the ingredient DiosVein, used for over 30 years as an anti-inflammatory and vascular-protecting agent. A study conducted in France by a research team lead by A. Behar, M.D., treated thirteen diabetic outpatients who had been suffering from a microcirculatory condition anywhere from one to nineteen years and who had abnormal albumin retention. Each study participant took two tablets daily of Daflon 500 mg for the duration of one month. Any treatments that were already in place prior to participation were continued during the study. A test was performed before and at the end of the study to measure albumin retention in the urine. Twelve of the thirteen patients experienced normalization in the levels of albumin. In 10 out of 13 patients, the test was carried out a third time several months after the Daflon 500mg treatment was withdrawn. For patients who had albumin normalization during treatment, results were again abnormal. In a different study, also conducted by Behar, a placebo-controlled trial lasting 30 to 42 days included two equal groups of 20 diabetic patients - one group treated with the flavonoid fraction and one being a placebo group. At the end of treatment, albumin retention significantly decreased in the group treated with the flavonoid fraction in contrast with the placebo group. In 65% of the flavonoid patients, albumin levels normalized, compared to only 25% of patients in the placebo group. This study, along with others testing the flavonoid fraction Daflon 500mg, suggest that this treatment can improve and even normalize capillary filtration of albumin in diabetic patients. DiosVein, made from the supplement Diosmin, provides soothing relief of vein discomfort and rarely interferes with other doctor-prescribed therapies. Recommended by doctors in Europe as an efficacious, natural option, DiosVein has been clinically shown to be effective in strengthening veins and aiding in circulation health. The DiosVein brand of Diosmin has been launched into the U.S. supplement and nutraceutical market. Exclusively available through Berg Imports LLC.

Restless leg syndrome
Q. Is Diosmin 95 used off label to treat restless leg syndrome? It is an ingredient in a cream for varicose veins and one of the claims they make is that it calms the nerves that cause restless leg syndrome.
   I don't know.

Side effects, safety
J Med Case Rep. 2014. Uncommon serum creatine phosphokinase and lactic dehydrogenase increase during diosmin therapy: two case reports. Short-term administration of diosmin is usually considered safe, with only minor side effects (stomach and abdominal pain, diarrhea, dermatological disorders, and headache) occasionally observed. Within a 4-year period, a general practitioner noticed 17 cases of mild, diosmin-induced side effects, two of which showed particular interest. Case 1: A 55-year-old Caucasian woman presented with chronic leg venous insufficiency. She was prescribed diosmin 450 mg twice a day. After 5 days of therapy, she developed pain in the legs (myalgia), and diosmin therapy was suspended. She made a spontaneous attempt of drug rechallenge and her leg pain reappeared. Thus, she underwent blood analysis, which showed elevation of creatine phosphokinase levels. Creatine phosphokinase values normalized only after prolonged discontinuation of the therapy. Case 2: A 79-year-old Caucasian man, who was diagnosed with acute hemorrhoidal syndrome. After 21 days of continuous diosmin treatment, increased levels of serum lactic dehydrogenase were detected. In both cases a comprehensive analysis of all possible causes for enzyme elevation was made. A feasible hypothesis to explain these rare effects could be that exaggerated adrenergic activity occurred on microcirculation, leading to an excessive peripheral vasoconstriction and subsequent ischemic damage. An individual predisposition is strongly suggested. A concurrence of events was probably responsible for the elevation of nonspecific tissue necrosis markers. Physicians and patients must be aware of these rare, but possible, adverse drug reactions.

Review
Chin J Integr Med. 2013 Oct;19. A review on pharmacological and analytical aspects of diosmetin: a concise report. Plants have been used as a source for food material and natural remedies for the treatment of vast range of diseases. Nature provides us remedies for the treatment of various types of disorders ranging from simple ailments to complicated diseases. Plants are known to possess different pharmacological activities due to the presence of various phytoconstituents. Flavonoids are one of the main active phytoconstituents found in fruits, vegetables, wines, tea and cocoa. Flavonoids exhibit various pharmacological activities such as antioxidant, anti-inflammatory, anti-allergic, antibacterial, oestrogenic, cytotoxic antitumoural, hepatoprotective, antithrombotic and antiviral activity. Diosmetin (3', 5, 7-trihydroxy-4'-methoxyflavone), the aglycone part of the flavonoid glycosides diosmin occurs naturally in citrus fruit. Although it is found in herbal medicines and plays an important role in the treatment of various ailments, only limited scientific researches have been conducted.

Emails
Q. Thank you so very much for you report on diosmin and hesperidin. I will continue to read your website. I found you via MSN search engine.

Q. Could you tell me if DiosVein (Diosmin) would interfere with warfarin as I am currently using warfarin but am very interested in DiosVein for my varicose veins.
   A. Most flavonoids have blood thinning potential. We have not seen studies regarding the combination of warfarin (Coumadin) and diosmin, therefore we don't know what interactions there would be. Much would depend on the dosage of the diosmin and the dosage of the warfarin, along with a person's diet and baseline blood clotting status. According to one website, "DiosVein is a branded ingredient containing the supplement diosmin, which has been used for over thirty years as a popular anti-inflammatory and vascular-protecting agent. DiosVein, derived from Sweet Orange and rich in bioflavonoids, is an efficacious, natural option for promoting healthy legs and sound circulation and has been highly recommended by doctors in Europe."

I recently began taking Diosmin 95. I took it for about 5 weeks when I began to have heart palpitations. I've been feeling weak and fatigued as well. Given the information I read about it on your site and from other sources, I'm wondering if these palpitations could be a result of taking Diosmin 95. I know you state there haven't been major side effects as of May 2009. But it seems to make sense that it "could" cause my symptoms, since it is a potent flavonoid which can have blood thinning properties. I stopped taking it for the last two days, and the palpitations have subsided almost to a stop. I'm thinking of trying it again at half the dose, by cutting the pill in half. Could you or your staff please weigh in on this, and let me know your thoughts and advice, or if you've heard of this side effect?
    Since this supplement has not been tested thoroughly, it is possible that this could be a side effect although we will need more confirmation from other users and studies.

I am writing in response to your statement, "No major side effects have been reported in medical journals as of May 2009." I do not question the truthfulness of that statement, but I want to advise you of my own recent experience with Venacura. I am a 58 year old male. My health is good except that I have a 20 year history of stomach ulcers and hiatal hernia problems. I started taking Venacura about 90 days ago for spider veins on my face. I noticed dramatic results within 10 days. The spider veins began to fade. They continued to fade. Side effects. At the same time I began taking Venacura, because of my stomach problems getting pretty painful, I stopped drinking coffee, 3 to 5 large cups per day, and stopped drinking beer, 1 to 4 per day. I also reduced my food intake and began exercising. In this same 90 days, I lost about 10 pounds, my blood pressure went from 140/86 to 110/60. I don't know if the Venacura had anything to do with this. So much for the good news. Here's the bad news. I started getting occasional headaches, every few days, lasting in various intensity for a few minutes to a few hours. Most importantly, I also had some serious vision problems. At first I thought I might be getting AMD. But I did a little research and concluded that was not the case. Here are the symptoms. It starts with a headache. Then, right in the center of my vision, both eyes, there is a small blurry void. The void is kind of like a pebble tossed into a calm pool of water. This small blurry void radiates out and dissipates. While this happens, I am unable to see well enough to read, but otherwise it is not debilitating. The event takes about 5 to 10 minutes, then it's gone as if nothing happened. Seven days ago I stopped taking Venacura. The second day after I discontinued taking Diosmin I had a headache and the vision problem. Since then, no headaches, no vision problems. I will not take Diosmin for another 23 days, then if I have not had the headaches or the vision problems I will resume taking Venacura to see if the headaches and vision problems return. If you want to know what happens, let me know and I will keep you updated.
    Yes, do keep us updated with your experiences with this product. This is what is says on a website: "Diosmin 95, the key ingredient in Venacura has been clinically proven to strengthen the vein walls and vein valves by keeping the neuramediators in your veins more active for a longer period of time. Keeping the neuramediators more active will prevent and reduce the discomfort and appearance of spider veins. The addition of Diosmin95® is recommended and safe for people with both normal veins and those with unhealthy spider veins."
        Since I emailed you, I had two episodes in a single day, 12 days after discontinuing diosmin95. I just got back from seeing my ophthalmologist. He is confident that I am suffering from migraine headaches. He said my retinas are fine. If anything changes that may indicate that diosmin is the problem, I will contact you. Thank you very much for your concern.

Can you tell me if there is a difference between diosmin and diosmin 95 as in Venacura, its very difficult to obtain in the Uk but I can buy Diosmin, will that work against spider veins?
    A search on the internet shows Venacura to contain Diosmin 95. I also have not seen human studies using this substance to treat spider veins.

I was reading the articles on diosmin 95 and Venacura and wanted to know if these are pharmaceutical products or are they made with ingredients from nature.
   As far as I know, they are plant extracts.

I have a family member who was diagnosed with Melanoma, had many lymph nodes removed and now is struggling with severe lymphedema in his leg. He developed a blood clot resulting in a cessation of the massage type therapy that he was undergoing for his lymphedema. He is being treated for his melanoma with one of the newly approved immune therapy agents, Ipilimumab, which was approved in March 2011. I do not see anything in the literature that would suggest that the use of Diosmin with Ipilimumab would create an adverse reaction. Are you aware of any contraindications?
   I have not seen any studies using these two together so it is not easy to predict the interactions.