Hesperidin is an antioxidant flavonoid found in citrus fruit. Its name comes from hesperidium, the Greek-derived botanical name for citrus. Hesperidin is most highly concentrated in the white, inner part of the peel (called the pith), as well as in the membranous material that separates lemons, oranges, and other citrus fruit into sections. For this reason, consuming citrus fruits in their whole form provides more hesperidin than juice, although juice with a high pulp content will provide more hesperidin than pulp-free. And while the pith is slightly bitter, for an extra bit of hesperidin, it’s not a bad idea to run a knife along the inner peel, to eat more of the pith than is typically consumed.

Citrus fruits have long been known to have antioxidant properties. This is usually attributed to the actions of vitamin C, but hesperidin may give citrus an additional antioxidant boost. Nature conveniently packages vitamin C and hesperidin together in some foods, but supplements that contain vitamin C may get a synergistic boost when hesperidin is added.

Vitamin C is also recognized for its crucial role in collagen synthesis, as it donates the hydroxyl groups to form the key structural amino acids, hydroxyproline and hydroxylysine. Healthy collagen is critical for blood vessel integrity. This may be why hesperidin and its metabolites have been shown to help support cardiovascular health and be beneficial for hypertension. Collagen is also a fundamental protein for healthy skin, and aside from hesperidin delivered orally, topical hesperidin has been shown to support skin health in mice by enhancing epidermal permeability barrier homeostasis via stimulating epidermal proliferation and differentiation, as well as increasing protective lipid secretions.

Hesperidin may also improve overall health through both its free radical scavenging capacity and its anti-inflammatory effects. Supplemental hesperidin may reduce markers of chronic inflammation, as well as inhibit the expression of COX-2 normally induced by lipopolysaccharide. Hesperidin has been shown to protect against chemically-induced liver fibrosis in rats. Supplemental hesperidin resulted in decreases in lipid peroxidation, NF-κB and IL-1β in rat models of liver cirrhosis. The kidneys are another organ that may be protected by hesperidin’s antioxidant properties. In a rat model of cisplatin-induced nephrotoxicity, oral administration of hesperidin (200 mg/kg) or rutin, another citrus flavonoid found in the peel and membranous fibers (30 mg/kg) for 14 days, with a single cisplatin dose on the tenth day, attenuated the drug’s toxicity, as indicated by reduced pathological changes to the kidneys and restoration of healthy organ function.

Another area where hesperidin may be beneficial is in neurological health. Citrus bioflavonoids can cross the blood-brain barrier, so they may exert antioxidant and anti-inflammatory effects in the brain. Hesperetin, a metabolite of hesperidin, incudes cellular defense mechanisms against oxidative stress and neurotoxicity. In a rat model of global cerebral ischemia/reperfusion (I/R), supplementation with hesperidin for 10 days (100mg/kg) resulted in significant reversal of the oxidative effects of I/R and inhibited pathological changes indicative of neurodegeneration. The researchers concluded that the beneficial effects of hesperidin were primarily due to its antioxidant and free radical-scavenging properties.

Additional studies lend more evidence to a neuroprotective role for hesperidin. In a mouse model of Alzheimer’s disease, 10 days of supplemental hesperidin (100mg/kg) significantly attenuated deposition of β-amyloid plaques, and reduced expression of amyloid precursor proteins. Improvements in the treated mice’s nesting skills and socialization suggest that the hesperidin-induced changes may have implications for improving non-cognitive behavior in Alzheimer’s patients. Other mouse studies indicate that even without obvious reductions in the buildup of β-amyloid plaques, administration of hesperidin reduced learning and memory deficits, improved locomotor activity, and protected against mitochondrial oxidative stress, the latter of which may be one of the primary underlying factors in Alzheimer’s.

Note: Growing up in the all Sicilian family, we could not drink the juice, we had to eat the oranges cut in quarters and eating the pulp and some pith.  These “old timers” knew where the “gold” was.