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.

Scientific Evidence

Tradition/Theory

The below uses are based on tradition or scientific theories. 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 health care professional.

• Antihistamine, anti-inflammatory, antimicrobial, antioxidant (helps protect against damage caused by chemicals known as free radicals), antiviral, aphthous ulcers (canker sores), arthritis (adjuvant), bleeding gums, bone density improvement, cancer prevention, chemopreventive (prevention of disease), cholesterol levels, diabetic retinopathy (eye disease), edema (swelling), endometriosis (growth of endometrial tissue outside the uterus), energy metabolism (stimulant), diabetic complications (slow emptying of the bowel), gastrointestinal disorders (diabetic gastroparesis), heart conditions, heart disease (prevention), high blood pressure, hot flashes, immune system function, nosebleeds, paralysis (caused by poliomyelitis), premature birth prevention, premenstrual syndrome (PMS), skin pigmentation disorders, uterine fibroids (noncancerous tumors in the uterus), varicose veins (in the bladder), weight loss, wound healing.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

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.

Children (under 18 years old)

• There is no proven safe or effective dose for hesperidin in children.

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.

Allergies

• Avoid with known allergy or hypersensitivity to hesperidin or to foods and supplements that contain hesperidin, such as citrus fruits.

Side Effects and Warnings

• Hesperidin may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

• Hesperidin may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or those taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.

• Hesperidin may cause low blood pressure. Caution is advised in patients taking agents that lower blood pressure.

• Hesperidin may interfere with the way the body processes certain drugs, herbs, or supplements using the liver's cytochrome P450 enzyme system. As a result, the levels of these agents may change in the blood and may cause increased or decreased effects or potentially serious adverse reactions. Patients taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

• Drowsiness or sedation may occur. Use caution if taking sedatives, CNS depressants, or if driving or operating heavy machinery.

• Use with caution in patients with musculoskeletal disorders or in those taking muscle relaxants.

• Use with caution in patients prone to headaches.

• Use with caution in patients with gastrointestinal disorders or in those taking antacids or agents to treat nausea and vomiting.

• Use with caution in patients taking antiseizure agents.

• Use with caution in patients taking agents that affect the cardiovascular system such as beta-blockers and calcium channel blockers.

• Avoid in patients with a known allergy/hypersensitivity to hesperidin, and hesperidin containing foods and supplements, such as citrus.

• Avoid in pregnant or breastfeeding women.

Pregnancy and Breastfeeding

• Hesperidin is not recommended in pregnant or breastfeeding women, due to a lack of available scientific evidence.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. 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.

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.

Interactions with Herbs and Dietary Supplements

• Hesperidin may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

• Hesperidin may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

• Hesperidin may cause low blood pressure. Caution is advised in patients taking herbs or supplements that lower blood pressure.

• Hesperidin may increase the amount of drowsiness caused by some herbs or supplements such as CNS depressants or sedatives.

• Hesperidin may interfere with the way the body processes certain herbs or supplements using the liver's cytochrome P450 enzyme system. As a result, the levels of other herbs or supplements may change in the blood. It may also alter the effects that other herbs or supplements potentially may have on the P450 system.

• Hesperidin may also interact with antacids, antianxiety herbs and supplements, antibacterials, anticancer herbs and supplements, antihistamines, anti-inflammatory herbs and supplements, antiseizure agents, antivirals, calcium, cholesterol-lowering herbs and supplements, herbs and supplements regulated by P-glycoprotein, herbs and supplements that affect the cardiovascular system, herbs and supplements that affect the gastrointestinal system, herbs and supplements that affect the nervous system, herbs and supplements that may damage the kidney, herbs and supplements that may damage the liver, herbs and supplements that protect against the harmful effects of radiation, herbs and supplements used to treat conditions of the teeth and gums, herbs and supplements used to treat osteoporosis, nicotine, padimate O (sunscreen agent), painkillers, Ruscus aculeatus, valerian, vanadyl, and vitamin C.

Author Information

• 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).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Aguilar Peralta GR, Arévalo Gardoqui J, Llamas Macías 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.View Abstract

2. 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.View Abstract

3. 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.View Abstract

4. 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.View Abstract

5. Garg A, Garg S, Zaneveld LJ, et al. Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother Res 2001;15(8):655-69.View Abstract

6. 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.View Abstract

7. 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.View Abstract

8. 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.View Abstract

9. Kalpana KB, Srinivasan M, Menon VP. Evaluation of antioxidant activity of hesperidin and its protective effect on H2O2 induced oxidative damage on pBR322 DNA and RBC cellular membrane. Mol Cell Biochem 2009;323(1-2):21-9.View Abstract

10. 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.View Abstract

11. 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.View Abstract

12. 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.View Abstract

13. 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.View Abstract

14. 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.View Abstract

15. 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.View Abstract