Citrus flavonoids

Related Terms

Alpha-glucosylhesperidin, bioflavonoids, citrus flavonoids, Dangyooja (Citrus grandis Osbeck), flavanones, flavonoid glycosides, flavonoids, G-hesperidin, glucosyl hesperidin, hesperidin, hesperidin-7-O-rutinoside, hesperidin-7-rhamnoglucoside, hesperidin-7-rutinose, hesperidin-7-rutinoside, hesperidin glycoside, hesperidin methyl chalcone (HMC), hesperidine methylchalcone, Kjool (Citrus unshiu Marcow), micronized purified flavonoid fraction, MPFF, neohesperidin, rhamnoglucosides, trimethyl-hesperidin-chalkon, vitamin P, Yuza (Citrus junos Sieb. ex Tanaka).
Select combination products: 5682 SE, Alvenor?, Ardium?, Arvenum 500?, Capiven?, Daflon? 500mg, Detralex?, Elatec?, Rikkunshito, S 5682, Venotec?, Venitol? (micronized purified flavonoid fraction containing diosmin and flavonoids (hesperidin, isorhoifolin, linarin, disometin)), Cyclo 3 Fort?, Great Legs (Ruscus aculeatus root extract, hesperidin methyl chalcone and ascorbic acid). Diosmin Complex? (diosmin and hesperidin) has been deemed qualitatively and quantitatively identical to other branded diosmin/hesperidin formulations available outside the United States.

Background

Hesperidin is a flavonoid found in citrus fruits such as lemons, oranges, and grapefruits before they ripen. Hesperidin is available as a supplement, both alone and in combination products with other ingredients. Scientific studies of the effects of hesperidin have used these combination products. As a result, conclusions about the effects of hesperidin alone cannot be made based on the available studies.
Hesperidin may have antioxidant and antimicrobial properties. It may have effects on the immune system and help prevent disease. The combination products that contain hesperidin and other ingredients may have beneficial effects on blood vessels.

Evidence Table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *


Combination products containing hesperidin, hesperidin methyl chalcone (HMG), ascorbic acid, diosmin, and other ingredients may improve the symptoms of CVI. Additional research on the effect of hesperidin alone is needed before a firm conclusion may be drawn.

A


Combination products containing hesperidin, hesperidin methyl chalcone (HMG), ascorbic acid, diosmin, and other ingredients may improve the symptoms of CVI. Additional research on the effect of hesperidin alone is needed before a firm conclusion may be drawn.

A


The combination product micronized purified flavonoid fraction (MPFF), which contains hesperidin and the flavonoid diosmin, may improve symptoms of hemorrhoids. Additional research on the effect of hesperidin alone is needed.

 A


The combination product micronized purified flavonoid fraction (MPFF), which contains hesperidin and the flavonoid diosmin, may improve symptoms of hemorrhoids. Additional research on the effect of hesperidin alone is needed.

 A


The combination product micronized purified flavonoid fraction (MPFF), which contains hesperidin and the flavonoid diosmin, may improve symptoms of venous leg ulcers when used together with routine ulcer care. Additional research on the effect of hesperidin alone is needed before a firm conclusion may be drawn.

 B


The combination product micronized purified flavonoid fraction (MPFF), which contains hesperidin and the flavonoid diosmin, may improve symptoms of venous leg ulcers when used together with routine ulcer care. Additional research on the effect of hesperidin alone is needed before a firm conclusion may be drawn.

 B


In early study, a hesperidin derivative was found to improve symptoms of arthritis. Additional research is needed before a conclusion can be made.

 C


In early study, a hesperidin derivative was found to improve symptoms of arthritis. Additional research is needed before a conclusion can be made.

 C


The combination product micronized purified flavonoid fraction (MPFF), which contains hesperidin and the flavonoid diosmin, may improve symptoms of capillary fragility, or easily damaged small blood vessels. Additional research on the effect of hesperidin alone is needed.

 C


The combination product micronized purified flavonoid fraction (MPFF), which contains hesperidin and the flavonoid diosmin, may improve symptoms of capillary fragility, or easily damaged small blood vessels. Additional research on the effect of hesperidin alone is needed.

 C


Micronized purified flavonoid fraction (MPFF), which contains the flavonoid diosmin in addition to hesperidin, may help lower blood sugar in women with type 2 diabetes. Additional research on the effect of hesperidin alone is needed before a firm conclusion may be drawn.

 C


Micronized purified flavonoid fraction (MPFF), which contains the flavonoid diosmin in addition to hesperidin, may help lower blood sugar in women with type 2 diabetes. Additional research on the effect of hesperidin alone is needed before a firm conclusion may be drawn.

 C


A combination product (Cyclo 3 Fort?) containing Ruscus aculeatus root extract, hesperidin methyl chalcone (HMC), and ascorbic acid may help reduce swelling of the arm in women who have been treated for breast cancer. Additional research on the effect of hesperidin alone is needed.
.
 C


A combination product (Cyclo 3 Fort?) containing Ruscus aculeatus root extract, hesperidin methyl chalcone (HMC), and ascorbic acid may help reduce swelling of the arm in women who have been treated for breast cancer. Additional research on the effect of hesperidin alone is needed.
.
 C
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

Dosing

Adults (18 years and older)
There is not enough evidence concerning doses of hesperidin used alone. Most studies describe the use of hesperidin in combination products that also contain other ingredients.
Hesperidin has been taken by mouth in the following forms: Daflon?, a micronized purified flavonoid fraction (one tablet contains 450 milligrams of diosmin plus 50 milligrams of flavonoids expressed as hesperidin); Cyclo 3 Fort? (one tablet contains 150 milligrams of Ruscus aculeatus root extract, 150 milligrams of hesperidin methyl chalcone, and 100 milligrams of ascorbic acid); a preparation containing 16.5 milligrams of an extract of Ruscus aculeatus, 75 milligrams of hesperidin, and 50 milligrams of ascorbic acid; and Detralex? (90% diosmin and 10% flavonoids expressed as hesperidin).
For arthritis, beverages containing 3 grams of a hesperidin derivative have been used every morning for 12 weeks.
For blood vessel disorders (easily damaged capillary blood vessels), one tablet of Daflon? has been used twice daily.
For chronic venous insufficiency, one tablet of Cyclo 3 Fort? has been used twice daily. Two tablets of Daflon? have also been used daily. A preparation containing 16.5 milligrams of an extract of Ruscus aculeatus, 75 milligrams of hesperidin, and 50 milligrams of ascorbic acid, has been taken three times daily for two months.
For type 2 diabetes, one tablet of Daflon? has been used twice daily for 45 days.
For hemorrhoid attacks, six tablets of Daflon? daily for four days, followed by four tablets daily for the next three days, has been used. To prevent repeat bleeding, two tablets of Daflon? has been used daily for 2-3 months. Following surgery to treat hemorrhoids, two tablets of Detralex? has been used three times daily for five days.
For lymphedema, two tablets of Daflon? has been used daily for six months. Cyclo 3 Fort? has been taken for three months.
For venous leg ulcers, two tablets of Daflon? has been used daily together with standard ulcer treatment.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Interactions

Interactions with Drugs
Hesperidin may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
Hesperidin may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin?) or heparin, antiplatelet drugs such as clopidogrel (Plavix?), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin?, Advil?) or naproxen (Naprosyn?, Aleve?).
Hesperidin may cause low blood pressure. Caution is advised in patients taking drugs that lower blood pressure.
Hesperidin may increase the amount of drowsiness caused by some drugs. Examples include benzodiazepines such as lorazepam (Ativan?) or diazepam (Valium?), barbiturates such as phenobarbital, narcotics such as codeine, some antidepressants, CNS depressants, sedatives, and alcohol. Caution is advised while driving or operating machinery.
Hesperidin may interfere with the way the body processes certain drugs using the liver's cytochrome P450 enzyme system. As a result, the levels of these drugs may change in the blood and may cause increased or decreased effects or potentially serious adverse reactions. Patients taking any medication should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
Hesperidin may also interact with antacids, antianxiety agents, antibiotics, anticancer agents, antihistamines, anti-inflammatory agents, antiseizure agents, antiviral agents, beta-blockers, calcium channel blockers, celiprolol, cholesterol-lowering agents, cyclophosphamide, drugs regulated by p-glycoprotein, drugs that affect the cardiovascular system, drugs that affect the gastrointestinal system, drugs that affect the nervous system, drugs that may damage the kidney, drugs that may damage the liver, drugs that protect against the harmful effects of radiation, drugs that treat osteoporosis, drugs used to treat conditions of the teeth and gums, methotrexate, opiate antagonists, and painkillers.

Attribution

This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Aguilar Peralta GR, Ar?valo Gardoqui J, Llamas Mac?as FJ, et al. Clinical and capillaroscopic evaluation in the treatment of chronic venous insufficiency with Ruscus aculeatus, hesperidin methylchalcone and ascorbic acid in venous insufficiency treatment of ambulatory patients. Int Angiol 2007;26(4):378-84.
Chiou CS, Lin JW, Kao PF, et al. Effects of hesperidin on cyclic strain-induced endothelin-1 release in human umbilical vein endothelial cells. Clin Exp Pharmacol Physiol 2008;35(8):938-43.
Demonty I, Lin Y, Zebregs YE, et al. The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women. J Nutr 2010;140(9):1615-20.
Etcheverry SB, Ferrer EG, Naso L, et al. Antioxidant effects of the VO(IV) hesperidin complex and its role in cancer chemoprevention. J Biol Inorg Chem 2008;13(3):435-47.
Garg A, Garg S, Zaneveld LJ, et al. Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother Res 2001;15(8):655-69.
Guex JJ, Enriquez Vega DM, Avril L, et al. Assessment of quality of life in Mexican patients suffering from chronic venous disorder - impact of oral Ruscus aculeatus-hesperidin-methyl-chalcone-ascorbic acid treatment - 'QUALITY Study'. Phlebology 2009;24(4):157-65.
Hosseinimehr SJ, Mahmoudzadeh A, Ahmadi A, et al. Radioprotective effects of hesperidin against genotoxicity induced by gamma-irradiation in human lymphocytes. Mutagenesis 2009;24(3):233-5.
Iriz E, Vural C, Ereren E, et al. Effects of calcium dobesilate and diosmin-hesperidin on apoptosis of venous wall in primary varicose veins. Vasa 2008;37(3):233-40.
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Kim YS, Kim JJ, Cho KH, et al. Biotransformation of ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, hesperidin, poncirin, glycyrrhizin, and baicalin by human fecal microflora and its relation to cytotoxicity against tumor cells. J Microbiol Biotechnol 2008;18(6):1109-14.
Lee CJ, Wilson L, Jordan MA, et al. Hesperidin suppressed proliferations of both human breast cancer and androgen-dependent prostate cancer cells. Phytother Res 2010;24 Suppl 1:S15-9.
Lee KH, Yeh MH, Kao ST, et al. The inhibitory effect of hesperidin on tumor cell invasiveness occurs via suppression of activator protein 1 and nuclear factor-kappaB in human hepatocellular carcinoma cells. Toxicol Lett 2010;194(1-2):42-9.
Nizamutdinova IT, Jeong JJ, Xu GH, et al. Hesperidin, hesperidin methyl chalone and phellopterin from Poncirus trifoliata (Rutaceae) differentially regulate the expression of adhesion molecules in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells. Int Immunopharmacol 2008;8(5):670-8.
Saha RK, Takahashi T, Suzuki T. Glucosyl hesperidin prevents influenza a virus replication in vitro by inhibition of viral sialidase. Biol Pharm Bull 2009;32(7):1188-92.
Yeh MH, Kao ST, Hung CM, et al. Hesperidin inhibited acetaldehyde-induced matrix metalloproteinase-9 gene expression in human hepatocellular carcinoma cells. Toxicol Lett 2009;184(3):204-10.