Crocetin

Crocetin (C₂₀H₂₄O₄, molecular weight 328.4 g/mol) is a naturally occurring apocarotenoid dicarboxylic acid, not a conventional nutrient with macronutrient or micronutrient content. It is the aglycone (sugar-free) form of crocin, the primary pigment of saffron (Crocus sativus L.) stigmas and gardenia (Gardenia jasminoides) fruit. Key bioactive characteristics: (1) Structure — a 20-carbon conjugated polyene chain with seven trans-double bonds and terminal carboxylic acid groups, classifying it as a diapocarotenoid; (2) Natural concentration — saffron stigmas contain approximately 6–16% crocins (by dry weight), which upon hydrolysis yield crocetin; gardenia fruit yields comparable crocin levels; (3) Bioavailability — crocetin is significantly more bioavailable than its parent glycoside crocin due to its smaller molecular size and moderate lipophilicity (log P ~2.3); oral administration in humans shows rapid absorption with peak plasma concentrations (Cmax) typically reached within 1–2 hours; in a pharmacokinetic study, oral crocetin at 22.5 mg achieved a Cmax of approximately 100–200 ng/mL; it is absorbed via passive transcellular diffusion across intestinal epithelium; (4) Key bioactive properties — potent antioxidant activity (quenches singlet oxygen and scavenges free radicals owing to its extended conjugated double-bond system), anti-inflammatory activity (inhibits NF-κB signaling and reduces TNF-α, IL-6 production), and carotenoid-like photoprotective properties; (5) Typical supplemental/research doses — 7.5 mg to 22.5 mg per day in human clinical trials (e.g., the cardiac recovery trial used doses in this range); (6) No appreciable vitamin, mineral, fiber, or protein content as it is a single purified phytochemical compound; (7) Stability notes — crocetin is sensitive to light, heat, and oxidation due to its polyene chain; formulations often require protection from UV exposure and may use microencapsulation to enhance stability; (8) Metabolism — undergoes glucuronidation in the liver, with mono- and di-glucuronide conjugates identified as primary metabolites in human plasma; elimination half-life is approximately 6–7 hours.