Hesperitin benefit and side effects
November 24 2015 by
Ray Sahelian, M.D.

Hesperitin is one of the Citrus bioflavonoids. I have also seen it spelled hesperetin.

A high-vegetable diet with various fruits and vegetables daily including on average one glass of orange juice, one-half orange and one-half mandarin provides 130 mg of hesperetin and 30 mg of naringenin.

Benefits of Hesperitin flavonoid research
Hesperitin has antioxidant and anti-inflammatory properties. Hesperidin can also act as a vasodilator, which may be useful in Hypertension.

Crit Rev Food Sci Nutr. 2015. Health-promoting Effects of the Citrus Flavanone Hesperidin. Preclinical studies and clinical trials demonstrated therapeutical effects of hesperidin and its aglycone hesperetin in various diseases, such as neurological disorders, psychiatric disorders and cardiovascular diseases and others, due to its anti-inflammatory, antioxidant, lipid-lowering and insulin-sensitizing properties.

Cell Biochem Funct. 2013. Letter to editor: hesperetin and its anti-neoplastic effects in systemic malignancies. Comment on Hesperetin impairs glucose uptake and inhibits proliferation of breast cancer cells.

Hesperetin or Hesperitin study
Structure-activity relationship (SAR) between some natural flavonoids and ocular blood flow in the rabbit.
J Ocul Pharmacol Ther. 2004.
Flavonoids with two to five hydroxy groups, with or without sugar, and/or methoxy groups were studied on their effects to affect ocular blood flow. METHODS: Colored microsphere technique was used to determine the ocular blood flow in rabbit eyes. Flavonoids with three free hydroxy (OH) groups seemed to produce the optimal effects in increasing ocular blood flow (naringenin and hesperitin, Pfalts and Bauer, Waterbury, CT). Whether the OH groups are below three (naringenin, hesperitin, Pfalts and Bauer, Waterbury, CT) or above four (Quercetin, Pfalts and Bauer, Waterbury, CT), they produced no effects on the ocular blood flow. When OH groups are four (rutin, Aldrich, Milwaukee, WI), it produced mixed effects on ocular blood flow. The attachment of rutinose and/or methoxy group in the structure did not affect the ocular blood flow one way or the other. CONCLUSION: The ocular blood flow is increased significantly by the number of OH group in the molecule, with three the best to increase the ocular blood flow.

Comparative study of the vasorelaxant activity, superoxide-scavenging ability and cyclic nucleotide phosphodiesterase-inhibitory effects of hesperetin and hesperidin.
Naunyn Schmiedebergs Arch Pharmacol. 2004;
This study investigated the vasorelaxant activity, superoxide radicals (O2(*-))-scavenging capacity and cyclic nucleotide phosphodiesterase (PDE)-inhibitory effects of hesperidin and hesperetin, two flavonoids mainly isolated from citrus fruits. Hesperetin concentration-dependently relaxed the isometric contractions induced by noradrenaline (NA, 1 microM) or by a high extracellular KCl concentration in intact rat isolated thoracic aorta rings. However, hesperetin (10 microM-0.3 mM) did not affect the contractile response induced by okadaic acid (OA, 1 microM). Mechanical removal of endothelium and/or pretreatment of aorta rings with glibenclamide (GB, 10 microM), tetraethylammonium or nifedipine did not significantly modify the vasorelaxant effects of this flavonoid. Hesperetin (10 microM-0.1 mM) did not affect the basal uptake of (45)Ca but decreased the influx of (45)Ca(2+) induced by NA and KCl in endothelium-containing and endothelium-denuded rat aorta. Hesperetin (10 microM-0.1 mM) did not scavenge O2(*-) generated by the phenazine methosulfate (PMS)-reduced beta-nicotinamide adenine dinucleotide (NADH) system. Hesperetin (0.1 mM) significantly reversed the inhibitory effects of NA (1 microM) and high KCl (60 mM) on cyclic nucleotide (cAMP and cGMP) production in cultured rat aortic myocytes. Hesperetin preferentially inhibited calmodulin (CaM)-activated PDE1 and PDE4 isolated from bovine aorta with IC(50) values of about 74 microM and 70 microM respectively. In contrast, the 7-rhamnoglucoside of hesperetin, hesperidin (10 microM-0.1 mM), was inactive in practically all experiments, although it inhibited basal and cGMP-activated PDE2 isolated from platelets. These results suggest that the vasorelaxant effects of hesperetin are basically due to the inhibition of PDE1 and PDE4 activities.

Interaction between flavonoids and the blood-brain barrier: in vitro studies.
J Neurochem. 2003.
There is considerable current interest in the neuroprotective effects of flavonoids. This study focuses on the potential for dietary flavonoids, and their known physiologically relevant metabolites, to enter the brain endothelium and cross the blood-brain barrier (BBB) using well-established in vitro models (brain endothelial cell lines and ECV304 monolayers co-cultured with C6 glioma cells). We report that the citrus flavonoids, hesperetin, naringenin and their relevant in vivo metabolites, as well as the dietary anthocyanins and in vivo forms, cyanidin-3-rutinoside and pelargonidin-3-glucoside, are taken up by two brain endothelial cell lines from mouse (b.END5) and rat (RBE4). In both cell types, uptake of hesperetin and naringenin was greatest, increasing significantly with time and as a function of concentration. In support of these observations we report for the first time high apparent permeability (Papp) of the citrus flavonoids, hesperetin and naringenin, across the in vitro BBB model (apical to basolateral) relative to their more polar glucuronidated conjugates, as well as those of epicatechin and its in vivo metabolites, the dietary anthocyanins and to specific phenolic acids derived from colonic biotransformation of flavonoids. The results demonstrate that flavonoids and some metabolites are able to traverse the BBB, and that the potential for permeation is consistent with compound lipophilicity.

Flavanone absorption after naringin, hesperidin, and citrus administration.
Clin Pharmacol Ther. 1996.
Disposition of citrus flavonoids was evaluated after single oral doses of pure compounds (500 mg naringin and 500 mg hesperidin) and after multiple doses of combined grapefruit juice and orange juice and of once-daily grapefruit. Cumulative urinary recovery indicated low bioavailability ( < 25%) of naringin and hesperidin. The aglycones naringenin and hesperitin were detected in urine and plasma by positive chemical ionization-collisionally activated dissociation tandem mass spectrometry (PCI-CAD MS/MS). After juice administration, PCI-CAD MS/MS detected naringenin, hesperitin, and four related flavanones, tentatively identified as monomethoxy and dimethoxy derivatives. These methoxyflavanones appear to be absorbed from juice. Absorbed citrus flavanones may undergo glucuronidation before urinary excretion.

Can a flavonoid supplement be taken the same day as ahcc mushroom extract, serrapeptase enzyme, coq10 or saw palmetto?
   As long as the dosages are not excessive, this should be okay.