Named Bioactive Compounds · Compound
Neohesperidin
Moderate Evidenceflavonoid
Hermetica Superfood Encyclopedia
Neohesperidin is a flavanone glycoside derived from citrus peels that exhibits anti-inflammatory and antioxidant properties. It works primarily by modulating inflammatory cytokine production and enhancing antioxidant enzyme activity.
Neohesperidin is a flavanone glycoside primarily sourced from the immature fruits and peel of Citrus aurantium L. (bitter orange). It serves as the precursor to neohesperidin dihydrochalcone (NHDC), a synthetic sweetener produced through hydrogenation of neohesperidin.
No human clinical trials were identified in the available research. All evidence comes from preclinical animal studies including mouse sepsis-associated lung injury models (PMC12939339) and rat colitis experiments using 40-80 mg/kg doses over 7-12 weeks.
No human dosage data available. Animal studies used: NHDC at 100 mg/kg in mice (intraperitoneal), neohesperidin at 40-80 mg/kg daily in rats (oral). Consult a healthcare provider before starting any new supplement.
Neohesperidin (chemical formula C₂₈H₃₄O₁₅, MW 612.58 g/mol) is a flavanone glycoside — specifically a neohesperidoside — found predominantly in bitter citrus species. It is not a macronutrient source and provides negligible calories, protein, fat, or fiber when consumed in typical supplemental or dietary amounts. Key details: • **Primary bioactive compound:** Neohesperidin itself, a flavanone-7-O-neohesperidoside consisting of the aglycone hesperetin linked to a neohesperidose (rhamnose-α-1,2-glucose) disaccharide at the 7-position. • **Natural concentrations:** Found at approximately 100–500 mg/L in Seville (bitter) orange juice (Citrus aurantium), 50–250 mg/kg in dried bitter orange peel, and lower amounts in grapefruit (Citrus paradisi). Negligible in sweet orange varieties. • **Derivative of note:** Neohesperidin dihydrochalcone (NHDC), a semi-synthetic sweetener (~1,500× sweeter than sucrose) derived by catalytic hydrogenation, is approved as a food additive (E959) in the EU at levels up to 50 mg/kg in certain food categories. • **Micronutrient content:** As a purified compound, neohesperidin contains no significant vitamins or minerals. When consumed as part of whole citrus peel extracts, co-occurring compounds include naringin, hesperidin, vitamin C, potassium, calcium, and dietary fiber (pectin). • **Key bioactive functional groups:** The phenolic hydroxyl groups on the B-ring (3′-OH, 4′-OCH₃) are primarily responsible for antioxidant radical-scavenging activity; the sugar moiety influences solubility and absorption kinetics. • **Bioavailability notes:** Oral bioavailability of intact neohesperidin is low (~5–10% estimated from animal pharmacokinetic studies). The neohesperidose sugar is cleaved by colonic microbiota (primarily by α-rhamnosidases and β-glucosidases), releasing the aglycone hesperetin, which is better absorbed in the colon. Peak plasma hesperetin metabolites (glucuronidated and sulfated conjugates) appear 4–7 hours post-ingestion, reflecting colonic metabolism. Absorption is enhanced when co-administered with lipids or in the presence of piperine. Hepatic phase II metabolism yields hesperetin-7-O-glucuronide and hesperetin-3′-O-sulfate as the major circulating metabolites. Renal clearance is the primary excretion route with a plasma half-life of approximately 2–5 hours for metabolites. • **Solubility:** Moderately soluble in water (~1 mg/mL at 25°C), more soluble in hot water and ethanol; solubility is pH-dependent (increased at alkaline pH).
Neohesperidin reduces inflammatory cytokine production including TNF-α, IL-1β, and IL-6 through NF-κB pathway inhibition. It enhances antioxidant defense by upregulating catalase, superoxide dismutase (SOD), and glutathione (GSH) levels. The compound also modulates gut microbiota composition, potentially supporting intestinal barrier function.
Current research on neohesperidin is limited to animal studies, primarily in rodent models. Colitis studies in rats (n=8 per group) demonstrated significant reductions in inflammatory markers TNF-α, IL-1β, and IL-6. Mouse studies on lung injury (n=6 per group) showed increased antioxidant enzyme activity. Human clinical trials are lacking, limiting the translation of these findings to therapeutic applications.
Safety data for neohesperidin supplementation in humans is limited due to lack of clinical trials. No specific drug interactions have been documented, though potential interactions with anti-inflammatory medications may exist. Pregnant and breastfeeding women should avoid supplementation due to insufficient safety data. Individuals with citrus allergies should exercise caution as neohesperidin is derived from citrus sources.
