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Hesperidin: Health Benefits, Side Effects, Uses, Dose & Precautions

Hesperidin

Other Name(s):

Bioflavonoid, Bioflavonoid Complex, Bioflavonoid Concentrate, Bioflavonoid Extract, Bioflavonoïde, Bioflavonoïde d'Agrume, Bioflavonoïdes d'Agrumes, Citrus Bioflavones, Citrus Bioflavonoid, Citrus Bioflavonoids, Citrus Bioflavonoid Extract, Citrus Flavones, Citrus Flavonoids, Complexe de Bioflavonoïdes, Concentré de Bioflavonoïdes, Extrait de Bioflavonoïdes, Extrait de Bioflavonoïdes d'Agrumes, Flavonoid, Flavonoïde, Hesperidin Methyl Chalcone, Hesperidina, Hespéridine, Trimethylhesperidin-chalcon.

Overview

Hesperidin is a plant chemical that is classified as a “bioflavonoid.” It is found primarily in citrus fruits. People use it as medicine.

Hesperidin alone, or in combination with other citrus bioflavonoids (diosmin, for example), is most often used for blood vessel conditions such as hemorrhoids, varicose veins, and poor circulation (venous stasis). It is also used to treat lymphedema, a condition involving fluid retention that can be a complication of breast cancer surgery.

How does work?

Hesperidin may help blood vessels function better. It may also reduce inflammation.

Uses

Possibly Effective for...

  • Poor circulation in the legs (chronic venous insufficiency, CVI). Taking a particular product (Cyclo 3 Fort) containing hesperidin methyl chalcone, butcher's broom, and vitamin C by mouth seems to relieve the symptoms of poor circulation in the legs. Also, taking a specific product (Daflon 500, Les Laboratoires Servier) containing hesperidin and diosmin by mouth for 2-6 months seems to improve CVI symptoms, although taking the drug Venoruton might be more effective for treating this condition.
  • Hemorrhoids. Some research suggests that taking a specific product (Daflon 500, Les Laboratoires Servier) containing hesperidin and diosmin by mouth for up to 3 months improves symptoms of anal hemorrhoids. It may also prevent hemorrhoids from coming back after they have healed.
  • Leg ulcers from poor circulation (venous stasis ulcers). Taking a specific product (Daflon 500, Les Laboratoires Servier) containing hesperidin and diosmin by mouth for 2 months seems to improve the healing of small venous stasis ulcers when used along with compression dressings.

Insufficient Evidence to Rate Effectiveness for...

  • Diabetes. Early research suggests that taking one tablet of a specific product (Daflon 500, Les Laboratoires Servier) containing hesperidin and diosmin by mouth for 45 days decreases blood sugar levels and improves blood sugar control in women with type 2 diabetes.
  • Swelling of the arms (lymphedema). Early research suggests that taking a specific product (Cyclo 3 Fort) containing butcher's broom root extract, hesperidin methyl chalcone, and vitamin C by mouth for 90 days reduces swelling in the upper arm and forearm, and improves mobility and heaviness, in women with swelling of the arm after breast cancer treatment. However, other research shows that taking a specific product (Daflon 500, Les Laboratoires Servier) containing hesperidin and diosmin by mouth does not reduce arm swelling in women following breast cancer surgery.
  • Rheumatoid arthritis (RA). Early research suggests that drinking a beverage containing alpha-glucosyl hesperidin for 12 weeks improves symptoms of RA.
  • Varicose veins.
  • Other conditions.
More evidence is needed to rate the effectiveness of hesperidin for these uses.

SLIDESHOW

How to Get Rid of Hemorrhoids: Types, Causes and Treatments See Slideshow

Side Effects

Hesperidin is POSSIBLY SAFE for most people when taken by mouth for up to 6 months. The safety of using it for a longer period of time is unknown. Side effects include stomach pain and upset, diarrhea, and headache.

Precautions

Pregnancy and breast-feeding: Hesperidin is POSSIBLY SAFE for pregnant or breast-feeding women when taken by mouth with diosmin.

Bleeding disorder: Hesperidin might slow blood clotting and increase the risk of bleeding. In theory, hesperidin might make bleeding disorders worse.

Low blood pressure: Hesperidin might lower blood pressure. In theory, taking hesperidin might make blood pressure become too low in people who already have low blood pressure.

Surgery: Hesperidin might prolong bleeding. There is concern that hesperidin might increase the risk of bleeding during and after surgical procedures. Stop taking hesperidin at least 2 weeks before a scheduled surgery.

Interactions


CeliprololInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Hesperidin may reduce how much celiprolol the body absorbs. This might decrease how well celiprolol works. Do not take hesperidin with celiprolol.


DiltiazemInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Hesperidin may reduce how much diltiazem the body absorbs. This might decrease how well diltiazem works. Do not take diltiazem with hesperidin.


Medications for high blood pressure (Antihypertensive drugs)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Hesperidin might decrease blood pressure. Taking hesperidin along with medications used to lower high blood pressure might cause your blood pressure to go too low.

Some medications for high blood pressure include nifedipine (Adalat, Procardia), verapamil (Calan, Isoptin, Verelan), diltiazem (Cardizem), isradipine (DynaCirc), felodipine (Plendil), amlodipine (Norvasc), and others.


Medications moved by pumps in cells (P-Glycoprotein Substrates)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Some medications are moved by pumps in cells. Hesperidin might make these pumps less active and increase the amount of some medications that get absorbed by the body. This might increase the amount of some medications in the body, which could lead to more side effects. But there is not enough information to know if this is a big concern.

Some medications that are moved by these pumps include etoposide, paclitaxel, vinblastine, vincristine, vindesine, ketoconazole, itraconazole, amprenavir, indinavir, nelfinavir, saquinavir, cimetidine, ranitidine, diltiazem, verapamil, corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, and others.


Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Hesperidin might slow blood clotting. Taking hesperidin along with medications that also slow clotting might increase the chances of bruising and bleeding.

Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.


Sedative medications (Benzodiazepines)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Hesperidin might cause sleepiness and drowsiness. Drugs that cause sleepiness and drowsiness are called sedatives. Taking hesperidin along with sedative medications might cause too much sleepiness.

Some of these sedative medications include alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), midazolam (Versed), temazepam (Restoril), triazolam (Halcion), and others.


Sedative medications (CNS depressants)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Hesperidin might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking hesperidin along with sedative medications might cause too much sleepiness. Taking hesperidin along with sedative medications used in surgery might cause prolonged sedation.

Some sedative medications include pentobarbital (Nembutal), phenobarbital (Luminal), secobarbital (Seconal), thiopental (Pentothal), fentanyl (Duragesic, Sublimaze), morphine, propofol (Diprivan), and others.


VerapamilInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Hesperidin may increase how much verapamil the body absorbs. This might increase the effects and side effects of verapamil. Do not take verapamil with hesperidin.

Dosing

The following doses have been studied in scientific research:

BY MOUTH:

  • For the treatment of hemorrhoids inside the anus: 150 mg of hesperidin plus 1350 mg of diosmin twice daily for 4 days, followed by 100 mg of hesperidin and 900 mg of diosmin twice daily for 3 days.
  • For preventing the return of hemorrhoids inside the anus: 50 mg of hesperidin plus 450 mg of diosmin twice daily for 3 months.
  • For the treatment of leg ulcers caused by poor blood circulation (venous stasis ulcers): a combination of 100 mg of hesperidin and 900 mg of diosmin daily for up to 2 months.

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, and Insufficient Evidence to Rate (detailed description of each of the ratings).

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Habauzit, V., Nielsen, I. L., Gil-Izquierdo, A., Trzeciakiewicz, A., Morand, C., Chee, W., Barron, D., Lebecque, P., Davicco, M. J., Williamson, G., Offord, E., Coxam, V., and Horcajada, M. N. Increased bioavailability of hesperetin-7-glucoside compared with hesperidin results in more efficient prevention of bone loss in adult ovariectomised rats. Br.J.Nutr. 2009;102(7):976-984. View abstract.

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Horcajada, M. N., Habauzit, V., Trzeciakiewicz, A., Morand, C., Gil-Izquierdo, A., Mardon, J., Lebecque, P., Davicco, M. J., Chee, W. S., Coxam, V., and Offord, E. Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats. J.Appl.Physiol 2008;104(3):648-654. View abstract.

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Juteau, N., Bakri, F., Pomies, J. P., Foulon, C., Rigaudy, P., Pillion, G., Lange, G., Genre, O., and Cron, J. P. The human saphenous vein in pharmacology: effect of a new micronized flavonoidic fraction (Daflon 500 mg) on norepinephrine induced contraction. Int Angiol. 1995;14(3 Suppl 1):8-13. View abstract.

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Koseki, T., Mese, Y., Nishibori, N., Masaki, K., Fujii, T., Handa, T., Yamane, Y., Shiono, Y., Murayama, T., and Iefuji, H. Characterization of an alpha-L-rhamnosidase from Aspergillus kawachii and its gene. Appl.Microbiol.Biotechnol. 2008;80(6):1007-1013. View abstract.

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Lay, H. L., Chen, C. C., Huang, S. C., Cham, T. M., Wu, T. S., and Lin, I. H. Simultaneous analysis of nine components in patch preparations of Ru-Yi-Jin-Huang-San by high-performance liquid chromatography. J.Nat.Med. 2010;64(2):194-202. View abstract.

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Lee, K. H., Yeh, M. H., Kao, S. T., Hung, C. M., Liu, C. J., Huang, Y. Y., and Yeh, C. C. 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. 4-15-2010;194(1-2):42-49. View abstract.

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Lee, S., Khoo, C. S., Pearson, J. L., Hennell, J. R., and Bensoussan, A. Liquid chromatographic determination of narirutin and hesperidin in Zhi Ke (Citrus aurantium L.) in the form of the raw herb and of the dried aqueous extract. J.AOAC Int. 2009;92(3):789-796. View abstract.

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Li, K., Yuan, J., and Su, W. Determination of liquiritin, naringin, hesperidin, thymol, imperatorin, honokiol, isoimperatorin, and magnolol in the traditional Chinese medicinal preparation Huoxiang-zhengqi liquid using high-performance liquid chromatography. Yakugaku Zasshi 2006;126(11):1185-1190. View abstract.

Li, R., Cai, L., Xie, X. F., Yang, F., and Li, J. Hesperidin suppresses adjuvant arthritis in rats by inhibiting synoviocyte activity. Phytother.Res. 2010;24 Suppl 1:S71-S76. View abstract.

Li, R., Li, J., Cai, L., Hu, C. M., and Zhang, L. Suppression of adjuvant arthritis by hesperidin in rats and its mechanisms. J.Pharm.Pharmacol. 2008;60(2):221-228. View abstract.

Li, Y. M., Li, X. M., Li, G. M., Du, W. C., Zhang, J., Li, W. X., Xu, J., Hu, M., and Zhu, Z. In vivo pharmacokinetics of hesperidin are affected by treatment with glucosidase-like BglA protein isolated from yeasts. J.Agric.Food Chem. 7-23-2008;56(14):5550-5557. View abstract.

Limasset, B., le Doucen, C., Dore, J. C., Ojasoo, T., Damon, M., and Crastes, de Paulet. Effects of flavonoids on the release of reactive oxygen species by stimulated human neutrophils. Multivariate analysis of structure-activity relationships (SAR). Biochem.Pharmacol 10-5-1993;46(7):1257-1271. View abstract.

Liu, L., Xu, D. M., and Cheng, Y. Y. Distinct effects of naringenin and hesperetin on nitric oxide production from endothelial cells. J.Agric.Food Chem. 2-13-2008;56(3):824-829. View abstract.

Liu, R., Meng, F., Liu, Y., Bai, H., and Liu, B. W. [Inhibitory effect of Isorhamnetin and Hesperidin on LDL oxidation induced by Cu2+]. Zhong.Yao Cai. 2007;30(6):677-681. View abstract.

Liu, R., Zhang, J., Liang, M., Zhang, W., Yan, S., and Lin, M. Simultaneous analysis of eight bioactive compounds in Danning tablet by HPLC-ESI-MS and HPLC-UV. J.Pharm.Biomed.Anal. 2-19-2007;43(3):1007-1012. View abstract.

Liu, Y., Li, Y., Liu, S., Li, J., and Yao, S. Monitoring the self-assembly of chitosan/glutaraldehyde/cysteamine/Au-colloid and the binding of human serum albumin with hesperidin. Biomaterials 2004;25(26):5725-5733. View abstract.

Liu, Z. L., Song, Z. Q., and Zhang, L. Comparison of main chemical components in prescription granules and decoction of Fructus aurantii immaturus. Journal of China Pharmacy (China) 2007;18:438-440.

Loscalzo, L. M., Wasowski, C., Paladini, A. C., and Marder, M. Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur.J.Pharmacol. 2-12-2008;580(3):306-313. View abstract.

Lu, Y., Zhang, C., Bucheli, P., and Wei, D. Citrus flavonoids in fruit and traditional Chinese medicinal food ingredients in China. Plant Foods Hum.Nutr 2006;61(2):57-65. View abstract.

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Lyseng-Williamson, K. A. and Perry, C. M. Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs 2003;63(1):71-100. View abstract.

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Maiti, K., Mukherjee, K., Murugan, V., Saha, B. P., and Mukherjee, P. K. Exploring the effect of Hesperetin-HSPC complex--a novel drug delivery system on the in vitro release, therapeutic efficacy and pharmacokinetics. AAPS.PharmSciTech. 2009;10(3):943-950. View abstract.

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Manach, C., Morand, C., Gil-Izquierdo, A., Bouteloup-Demange, C., and Remesy, C. Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice. Eur.J.Clin.Nutr. 2003;57(2):235-242. View abstract.

Mandalari, G., Bennett, R. N., Bisignano, G., Trombetta, D., Saija, A., Faulds, C. B., Gasson, M. J., and Narbad, A. Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia Risso) peel, a byproduct of the essential oil industry. J.Appl.Microbiol. 2007;103(6):2056-2064. View abstract.

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Martinez, M. C., Fernandez, S. P., Loscalzo, L. M., Wasowski, C., Paladini, A. C., Marder, M., Medina, J. H., and Viola, H. Hesperidin, a flavonoid glycoside with sedative effect, decreases brain pERK1/2 levels in mice. Pharmacol.Biochem.Behav. 2009;92(2):291-296. View abstract.

McKay, D. L. and Blumberg, J. B. A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.). Phytother.Res 2006;20(8):619-633. View abstract.

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Miwa, Y., Mitsuzumi, H., Sunayama, T., Yamada, M., Okada, K., Kubota, M., Chaen, H., Mishima, Y., and Kibata, M. Glucosyl hesperidin lowers serum triglyceride level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein metabolic abnormality. J Nutr Sci Vitaminol.(Tokyo) 2005;51(6):460-470. View abstract.

Miwa, Y., Mitsuzumi, H., Yamada, M., Arai, N., Tanabe, F., Okada, K., Kubota, M., Chaen, H., Sunayama, T., and Kibata, M. Suppression of apolipoprotein B secretion from HepG2 cells by glucosyl hesperidin. J Nutr Sci Vitaminol.(Tokyo) 2006;52(3):223-231. View abstract.

Miwa, Y., Yamada, M., Sunayama, T., Mitsuzumi, H., Tsuzaki, Y., Chaen, H., Mishima, Y., and Kibata, M. Effects of glucosyl hesperidin on serum lipids in hyperlipidemic subjects: preferential reduction in elevated serum triglyceride level. J Nutr Sci Vitaminol.(Tokyo) 2004;50(3):211-218. View abstract.

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