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Diosmin (diosmetin 7-O-rutinoside), a
flavone Flavone is an organic compound with the formula . A white solid, flavone is a derivative of chromone with a phenyl (Ph) substituent adjacent to the ether group. The compound is of little direct practical importance, but susbstituted derivatives, t ...
glycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...
of
diosmetin Diosmetin, also known as 5,7,3′-trihydroxy-4′-methoxyflavone, is an ''O''-methylated flavone, a chemical compound that can be found in the Caucasian vetch. It has been found to act as a weak TrkB receptor agonist. Glycosides Diosmetin is t ...
, is manufactured from citrus fruit peels as a phlebotonic non-prescription
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
used to aid treatment of
hemorrhoid Hemorrhoids (or haemorrhoids), also known as piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualified term ''hemo ...
s or chronic venous diseases, mainly of the legs.


Uses

Diosmin is a dietary supplement used to aid treatment of
hemorrhoid Hemorrhoids (or haemorrhoids), also known as piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualified term ''hemo ...
s and venous diseases, i.e.,
chronic venous insufficiency Chronic venous insufficiency (CVI) is a medical condition in which blood pools in the veins, straining the walls of the vein. The most common cause of CVI is superficial venous reflux which is a treatable condition. As functional venous valves are ...
including spider and varicose veins, leg swelling (
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
), stasis dermatitis and
venous ulcer Venous ulcer is defined by the American Venous Forum as "a full-thickness defect of skin, most frequently in the ankle region, that fails to heal spontaneously and is sustained by chronic venous disease, based on venous duplex ultrasound testing." ...
s. The mechanism of action of Diosmin and other phlebotonics is undefined, and clinical evidence of benefit is limited. Diosmin is not recommended for treating the
rectal mucosa The rectum is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the sigmoid colon) at the le ...
, skin irritations, or wounds, and should not be used to treat
dermatitis Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can v ...
,
eczema Dermatitis is inflammation of the Human skin, skin, typically characterized by itchiness, erythema, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become lichenification, thick ...
, or
urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...
. Diosmin is not recommended for use in children or women during
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
. There is moderate-quality evidence that diosmin or other phlebotonics improved leg and ankle swelling and lower leg pain, and low-quality evidence for treating
hemorrhoid Hemorrhoids (or haemorrhoids), also known as piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualified term ''hemo ...
s.


Phlebotonics

Diosmin is included among a small class of agents called " phlebotonics" having heterogeneous composition and consisting partly of
citrus peel Peel, also known as rind or skin, is the outer protective layer of a fruit or vegetable which can be peeled off. The rind is usually the botanical exocarp, but the term exocarp also includes the hard cases of nuts, which are not named peels si ...
extract An extract is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol, oil or water. Extracts may be sold as tinctures, absolutes or in powder form. The aromatic principles of many spices, nuts, h ...
s (
flavonoid Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans. Chemically, flavonoids ...
s, such as
hesperidin Hesperidin is a flavanone glycoside found in citrus fruits. Its aglycone form is called hesperetin. Its name is derived from the word "hesperidium", for fruit produced by citrus trees. Hesperidin was first isolated in 1828 by French chemist M. ...
) and synthetic compounds, which are used to treat
chronic venous insufficiency Chronic venous insufficiency (CVI) is a medical condition in which blood pools in the veins, straining the walls of the vein. The most common cause of CVI is superficial venous reflux which is a treatable condition. As functional venous valves are ...
or
hemorrhoid Hemorrhoids (or haemorrhoids), also known as piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualified term ''hemo ...
s. In 2017, the American Working Group in Chronic Venous Disease recommended use of micronized purified flavonoid fraction (
diosmiplex Diosmin (diosmetin 7-O-rutinoside), a flavone glycoside of diosmetin, is manufactured from citrus fruit peels as a phlebotonic non-prescription dietary supplement used to aid treatment of hemorrhoids or chronic venous diseases, mainly of the ...
) as a
medical food Medical foods are foods that are specially formulated and intended for the dietary management of a disease that has distinctive nutritional needs that cannot be met by normal diet alone. In the United States they were defined in the Food and Drug A ...
for chronic venous disease symptoms and
venous ulcer Venous ulcer is defined by the American Venous Forum as "a full-thickness defect of skin, most frequently in the ankle region, that fails to heal spontaneously and is sustained by chronic venous disease, based on venous duplex ultrasound testing." ...
s, having "beneficial outcomes without serious adverse events", alone or combined with compression therapy, concurring with the previous guidance of the International European Society for Vascular Surgery. The German Dermatological Society indicated that Diosmin may be used with other treatments for symptoms of
chronic venous disease Chronic venous insufficiency (CVI) is a medical condition in which blood pools in the veins, straining the walls of the vein. The most common cause of CVI is superficial venous reflux which is a treatable condition. As functional venous valves are ...
s. The
American Society of Colon and Rectal Surgeons The American Society of Colon and Rectal Surgeons (ASCRS), formerly the American Proctologic Society, is a professional society for surgeons specializing in colorectal surgery. It is one of the oldest surgical societies, having been established in ...
mentions phlebotonics as a possible treatment for symptoms of hemorrhoid grades I to II, as there is only moderate-quality evidence of effectiveness with "expectations of minimal harm", while having no evidence of long-term benefit. French, Indian, Portuguese, and Italian professional societies of
coloproctology Colorectal surgery is a field in medicine dealing with disorders of the rectum, anus, and colon. The field is also known as proctology, but this term is now used infrequently within medicine and is most often employed to identify practices rela ...
issued similar recommendations regarding phlebotonics for hemorrhoids.


Adverse effects

In some 10% of users, diosmin causes mild
gastrointestinal disorders Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the gastrointestinal tract, namely the oesophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestion, the live ...
or skin irritations (hives, itching), stomach pain, nausea, heart
arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
s, or
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
. Preliminary research indicates no evidence of
toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...
. The US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) concluded in 2001 that there was inadequate evidence on which to base an expectation of safety. , the FDA did not revise this position.


Regulatory status

Diosmin is distributed in the U.S. as a dietary supplement called
Daflon Daflon is an oral micronized purified phlebotonic flavonoid fraction containing 90% diosmin and 10% hesperidin. It is manufactured by Laboratoires Servier and often used to treat or manage disorders of the blood vessels. Flavonoids are a type of ph ...
. Diosmin is not approved as a
prescription drug A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
in the United States or Europe. Phlebotonics are not approved in Germany, and are restricted in Spain only for the treatment of chronic venous diseases.


See also

*
Daflon Daflon is an oral micronized purified phlebotonic flavonoid fraction containing 90% diosmin and 10% hesperidin. It is manufactured by Laboratoires Servier and often used to treat or manage disorders of the blood vessels. Flavonoids are a type of ph ...
*
Venalex Venalex is a micronized purified flavonoid fraction containing 90% diosmin and 10% hesperidin Hesperidin is a flavanone glycoside found in citrus fruits. Its aglycone form is called hesperetin. Its name is derived from the word " hesperidiu ...


References

{{flavone Flavone glycosides Dietary supplements Medical food