IngredientsNote on nomenclature: The ingredient commonly rendered as enocitrin in some commercial and lay contexts is the same compound as eriocitrin — the two spellings reflect variant transliterations and trade-context usage of the same molecule. All scientific literature and regulatory databases record the compound under the name eriocitrin, and that spelling is used throughout this article.
Eriocitrin is a flavanone-7-O-glycoside formed between the flavanone eriodictyol and the disaccharide rutinose. Its full systematic name is (S)-eriodictyol-7-rutinoside, where rutinose (L-rhamnosyl-D-glucose) is bound with eriodictyol (C₁₅H₁₂O₆; also called 3′,4′,5,7-tetrahydroxyflavanone) belonging to flavanones, a group of flavonoids. It is also catalogued under the synonyms CAS number 13463-28-0, with synonyms Eriodictioside and Eriodictyol 7-O-rutinoside.
Eriocitrin is colloquially called a "lemon flavonoid" or a "citrus flavonoid," one of the plant pigments that bring color to fruit and flowers. Within the broader flavonoid classification, the main flavonoid subgroups are flavones, flavonols, flavanones, flavononols, flavan-3-ols, anthocyanins, isoflavones, and chalcones, and eriocitrin belongs specifically to the flavanone subclass.
Eriocitrin is commonly found in lemons and other citrus fruits. The distribution of eriocitrin in citrus fruits was found to be especially abundant in lemons and limes; however, it was scarcely found in other citrus fruits. Eriocitrin is present in citrus fruits, and is especially contained in lemon and lime in a large amount; it is also present in oranges. More specifically, the citrus fruits used as raw material sources include fruits of flavorful acid citruses such as lemon (Citrus limon), lime (Citrus aurantifolia), Citrus depressa, Citrus sudachi, Citrus junos, bitter orange (Citrus aurantium), grapefruit (Citrus paradisi), navel orange, Valencia orange, and pomelo (Citrus maxima).
In the lemon fruit, eriocitrin is primarily distributed in the peel (about 1,500 ppm), composed of the albedo (mesocarp), flavedo (epicarp), and pulp vesicles; it is also significantly present in the juice (about 200 ppm) but was not detected in the seed. Two varieties of lemon — Eureka and Lisbon — were found to have almost the same eriocitrin content. Hesperidin and eriocitrin are much more abundant in the albedo than in the flavedo and pulp.
Beyond citrus, eriocitrin also predominates (38% in one study) in peppermint infusions. It has also been identified in fennel: among compounds isolated for the first time in fennel was eriodictyol-7-O-rutinoside (eriocitrin), along with several caffeoylquinic acid and kaempferol derivatives.
The purified eriocitrin is readily soluble in water, methanol, and ethanol. A water solution of 0.05% eriocitrin is weakly acidic (pH 4.2), and eriocitrin was found to be stable even at high temperature (121 °C, 15 min) in acidic solution (pH 3.5). This relatively high water solubility is chemically significant in comparison with some other citrus flavanones: the higher solubility of (lemon) eriocitrin versus (orange) hesperidin may yield more bioavailable metabolites than hesperidin.
While the specific compound "eriocitrin" was not isolated and named until modern times, citrus fruits rich in this bioactive molecule have been valued for centuries in traditional medicinal practices. Citrus peels and juices were used in folk remedies to combat scurvy, boost immunity, and promote digestive health. The beneficial effects attributed to these remedies can be largely credited to the presence of flavonoids like eriocitrin, which exhibit potent antioxidant and anti-inflammatory properties.
Human beings have consumed lemon (Citrus limon) and lime (Citrus aurantifolia or Citrus latifolia) for thousands of years. Among the variety of citrus families, lemon and lime originated from the hybridization of citron with primitive papeda, making them similar from the nutritional and organoleptic standpoints.
Ancient healers often utilized citrus extracts in combination with other botanicals. Citrus peel was commonly blended with ginger, honey, or licorice root to create soothing teas for respiratory ailments and to relieve cold symptoms.
It is important to note that no traditional medical system explicitly isolated or identified eriocitrin as a discrete therapeutic compound; historical use was always as part of whole-fruit or peel preparations. The scientific isolation and characterization of eriocitrin as a distinct antioxidative molecule is a modern development. An antioxidant was isolated from the peel and juice of lemon fruit (Citrus limon BURM. f.) and identified as eriocitrin (eriodictyol 7-rutinoside), with that antioxidant identity confirmed by HPLC, ¹H-NMR and ¹³C-NMR analyses and first published in 1997.
Eriocitrin has the structural name eriodictyol-7-rutinoside, and it is a flavonoid glycoside in which rutinose (disaccharide: glucose and rhamnose) is bound to eriodictyol belonging to a flavanone of flavonoid compounds. The aglycone, eriodictyol, is itself a bioactive flavanone: eriodictyol is the parent aglycone of eriocitrin.
The commercially studied eriocitrin-rich supplement Eriomin (Ingredients by Nature, USA) is a blend, not a pure isolate. The composition of Eriomin is 70% eriocitrin, 5% hesperidin, 4% naringin, 1% didymin, and 20% fiber material from epidermis and periderm cell-wall (including suberin, cutin, lignin, pectin, and cellulose). A dose of 200 mg of active ingredients per capsule is equal to 140 mg of eriocitrin plus 10 mg of hesperidin plus 8 mg of naringin plus 2 mg of didymin. This multi-flavanone composition means that some effects attributed to eriocitrin in clinical studies using Eriomin may involve synergistic contributions from its companion flavanones.
Eriocitrin is a flavonoid originally isolated from lemon peel that has antioxidant and enzyme inhibitory activity. It inhibits lipid peroxidation in a cell-free assay when used at a concentration of 10 µM and enhances the effect of α-tocopherol on lipid peroxidation. It also decreases thiobarbituric acid reactive substances (TBARS) in rat plasma when administered at a dose of 75 µmol/kg, indicating a reduction in lipid peroxidation.
A key aspect of eriocitrin's antioxidant activity relates to its structural features: the ortho-hydroxyl groups on the B ring of eriocitrin indicate antioxidant potential. It has been suggested that eriocitrin metabolites, eriodictyol and 3,4-dihydroxyhydrocinnamic acid, might scavenge free radicals and reactive oxygen species, resulting in suppression of lipid peroxidation.
Nitric oxide (NO), IL-1β, IL-6, IL-8, TNF-α, NF-κB, MPO, MAPK, and MMP-9 secretion are reduced by eriocitrin, inhibiting cell apoptosis and the production of pro-inflammatory cytokines, while eriocitrin increases the content of IL-10, Nrf2, DUSP14, HO-1, and NQO1. A key upstream signaling node is the dual-specificity phosphatase DUSP14: eriocitrin enhances Nrf2 and suppresses NF-κB by increasing DUSP14 activation, thereby reducing the inflammatory cytokines IL-1β, TNF-α, and IL-6.
Polyphenols including eriocitrin can potentially reduce postprandial hyperglycemia by inhibiting glucose uptake and its release from the intestine to the liver, stimulating insulin secretion by the pancreas, and increasing glucose uptake by muscles and adipocytes. These events can occur through direct action on intestinal cells, stimulating the production of the incretin hormone glucagon-like peptide-1 (GLP-1), which in turn increases insulin secretion, and also through an indirect action on the microbiota in the distal intestine. The transformation of polyphenols by resident gut bacteria increases their bioavailability and the production of short-chain fatty acids, which have favorable metabolic effects to reduce hepatic glucose secretion.
Eriocitrin is also an inhibitor of monoamine oxidase A (MAO-A) and MAO-B, with IC₅₀ values of 86.5 and 164 µM, respectively, for human recombinant receptors. Additionally, eriocitrin and apigenin have been identified as new potent inhibitors of human carbonic anhydrase VA isozyme.
In preclinical cell-line studies, several mechanisms of antitumor activity have been characterized. Eriocitrin inhibits the proliferation of HepG2 and Huh7 liver cells through the intrinsic apoptosis pathway and cell cycle arrest; it promotes intrinsic apoptosis in MCF-7 breast cancer cells through JAK2/STAT3/Src inhibition and reactive oxygen species (ROS)-dependent JNK/p38 MAPK stimulation; and it has been reported to trigger ferroptosis in A549 and H1299 lung adenocarcinoma cells, thereby circumventing cancer cell resistance to apoptosis.
Dietary intervention with eriocitrin significantly alters the beta diversity of the gut microbiota; probiotics such as Lachnospiraceae_UCG_006 were significantly enriched, and the production of butyrate, valerate, and hexanoate was increased. Eriocitrin can increase the content of all short-chain fatty acids (SCFAs) in the colon of mice, with butyrate, valerate, and hexanoate showing the most amplification. Butyrate plays an important role in maintaining intestinal barrier stability and can also prevent and treat diet-induced obesity.
Various samples (plasma, urine, and organs) were collected at different intervals (0–24 h) for pharmacokinetic studies and examination of the allocation of orally given eriocitrin in rats using HPLC-PDA-MS. The eriocitrin metabolites homoeriodictyol-7-O-glucuronide and homoeriodictyol were found extensively distributed in rat urine and tissues, while plasma metabolites showed a half-life between 3 and 3.2 h, with an overall bioavailability of eriocitrin remaining less than 1%.
Pharmacokinetic studies have shown that multiple metabolites of eriocitrin were found in blood, feces, urine, and various organs of rats after dietary intervention. Eriocitrin can be metabolized into eriodictyol first, and then undergo phase II metabolism such as glucuronidation, sulfation, and methylation, thereby producing hesperetin, homoeriodictyol, eriodictyol-O-glucuronide, and other compounds.
An earlier study identified the products of eriocitrin metabolized by intestinal bacteria derived from the human gut in vitro, finding that eriocitrin can be metabolized to eriodictyol by gut bacteria such as Bacteroides, Bifidobacterium, and Enterobacter.
A total of 136 flavonoids were found in colon contents of mice supplemented with eriocitrin, including eriocitrin and its six metabolites: eriodictyol, homoeriodictyol, hesperetin, eriodictyol-3′-O-glucoside, hesperetin-7-O-glucoside, and eriodictyol-7-O-(6″-O-galloyl) glucoside.
Results from a pharmacokinetic study indicated that eriocitrin metabolites are associated with blood glucose support, cardiovascular support, and improved antioxidant capacity. Researchers found that seven of nine metabolites were detected in various organs, including liver, pancreas, kidneys, spleen, and blood plasma. The in vivo concentrations and distributions of the eriocitrin metabolites, found in high amounts in the pancreas, connect with the ingredient's ability to improve blood glucose levels.
A human pharmacokinetic comparison between lemon (eriocitrin) and orange (hesperidin) flavanones has been published: a randomized-crossover human pharmacokinetic study (n = 16) compared the bioavailability and metabolism of flavanones from lemon and orange extracts and postprandial changes in oxidative, inflammatory, and metabolic markers after a high-fat, high-sugar meal. The human metabolism of lemon eriocitrin was noted to be poorly characterized prior to this study, but researchers hypothesized that the higher solubility of eriocitrin compared with hesperidin might yield more bioavailable metabolites.
This is the area with the strongest available human clinical evidence for eriocitrin.
Crossover randomized controlled trial (RCT): A double-blind, randomized, placebo-controlled, crossover study evaluated the efficacy of Eriomin® in reducing hyperglycemia and improving diabetes-related biomarkers in individuals with hyperglycemia above 110 mg/dL (mean 123 ± 18 mg/dL). Subjects (n = 30), divided into two groups (Eriomin or placebo), received a dose of 200 mg/d of the designated supplement for 12 weeks and, after a washout period of 2 weeks, switched to the other supplement in the following 12 weeks. Treatment with 200 mg/d of Eriomin significantly decreased blood glucose (−5%), homeostasis model assessment of insulin resistance (HOMA-IR; −11%), glucagon (−13%), interleukin-6 (−14%), TNF-α (−20%), and alkaline phosphatase (−13%), but increased GLP-1 by 17% (P ≤ .05). The authors concluded that intervention with Eriomin benefited glycemic control of prediabetic and diabetic patients with higher blood glucose levels by increasing GLP-1 and decreasing systemic inflammation.
Dose-response RCT in prediabetes: The effectiveness of eriocitrin in managing hyperglycemia and reversal of prediabetes was demonstrated in a double-blind randomized controlled study, which evaluated the potential effectiveness of different doses of Eriomin on hyperglycemia and insulin resistance associated with other metabolic biomarkers in prediabetic individuals. Short-term intervention with Eriomin, at doses of 200, 400, or 800 mg/day, benefited glycemic control, reduced systemic inflammation and oxidative stress, and reversed the prediabetic condition in 24% of the evaluated patients.
All volunteers had insulin resistance at the beginning, during, and at the end of the experiment (HOMA-IR ≥ 2.71), but there was a reduction of −8% after intervention with 200 mg of Eriomin (p=0.037), −7% with 400 mg (p=0.043), and −6% with 800 mg (p=0.042). These results were mainly due to the reduction of blood glucose, because no significant changes were detected in insulin levels. Regarding blood lipids, there was no reduction in total cholesterol, LDL-cholesterol, HDL-cholesterol, or triglycerides during and at the end of the experimental period, although the patients did not present high levels of these parameters.
Evidence strength: Human clinical evidence exists at the RCT level, but studies are limited by small sample sizes (n = 30 in the crossover trial), the use of a multi-flavanone blend (not pure eriocitrin), short duration (12 weeks), single-center Brazilian populations, and the absence of replication by independent research groups. Large-scale, long-term clinical trials in diverse human populations are limited.
Animal studies: Eriocitrin decreases thiobarbituric acid reactive substances (TBARS) in rat plasma when administered at a dose of 75 µmol/kg, indicating a reduction in lipid peroxidation. Eriocitrin prevents acute exercise-induced increases in TBARS, Nε-(hexanoyl)lysine (HEL), o,o-dityrosine (DT), and nitrotyrosine (NT) in rat liver when administered at a dose of 600 mg/kg prior to exercise.
Eriocitrin may play an important role in the control of the change in glutathione redox status in rat liver during exercise, and these findings showed that eriocitrin was effective in the prevention of oxidative damages caused by acute exercise-induced oxidative stress.
In vitro: The antioxidative activity of eriocitrin in the linoleic acid autoxidation system was found to be equal to that of α-tocopherol, and it was enhanced when used in combination with it.
Evidence strength: Robust in vitro and animal data; human clinical data on antioxidant endpoints are exploratory and embedded within glycemic studies.
Animal studies: Mice were fed a high-fat diet for 28 days to induce obesity, followed by supplementation of eriocitrin (10, 25, 100 mg/kg body weight) for the same period. Mice given eriocitrin (25 mg/kg) showed significantly reduced blood serum glucose and blood and liver triacylglycerols, and improved insulin, total cholesterol, resistance, and lipid peroxidation levels.
Dietary eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis. Previous studies have demonstrated that eriocitrin has obvious lipid-lowering effects on both high-fat and high-cholesterol fed rats.
Evidence strength: Animal studies consistently show lipid-lowering and hepatoprotective effects at various doses. The human RCT did not show significant changes in blood lipids, possibly because participants' baseline lipid levels were not elevated, meaning no clear clinical human evidence for lipid-lowering exists yet.
Animal and in vitro studies: Eriocitrin has been shown to have anti-inflammatory effects in both in vitro and in vivo studies. In a rat model of cerebral ischemia-reperfusion, male Sprague-Dawley rats were randomly divided into groups including I/R + eriocitrin 8 mg/kg, 16 mg/kg, and 32 mg/kg groups. Different doses of eriocitrin were administered once daily for 7 days before middle cerebral artery occlusion (MCAO).
In a rodent periodontal disease model: researchers studied whether a diet supplemented with eriocitrin and the flavanone eriodictyol could reduce the inflammatory response in mice with lipopolysaccharide-induced periodontal disease. Periodontitis is an inflammatory oral disease.
Human clinical signal: The Eriomin crossover trial found significant reductions in IL-6 (−14%) and TNF-α (−20%) in humans at 200 mg/d, providing human-level evidence for systemic anti-inflammatory activity in a prediabetic population.
Evidence strength: Anti-inflammatory mechanisms are well-characterized in preclinical models with mechanistic clarity (NF-κB/Nrf2/DUSP14 axis). Human data comes indirectly from the glycemic trials. No dedicated human anti-inflammatory trial has been published to date.
Ischemia-reperfusion (IR)-induced acute kidney injury (AKI) is accompanied by increased inflammatory response and oxidative stress. Eriocitrin is a flavonoid mainly derived from lemon or citrate juice that exhibits various pharmacological effects and is known to have antioxidant and anti-steatotic benefits. In one study, the cell line OGD/R and a rat model of AKI were treated with eriocitrin at different doses (60, 30, 10 mg/kg). Eriocitrin protected IR-induced AKI by attenuating oxidative stress and inflammation via elevating DUSP14.
Severe inflammation and oxidative stress are characteristics of sepsis-associated kidney injury. Eriocitrin has shown promise in suppressing sepsis-associated kidney injury and LPS-induced periodontal disease.
Evidence strength: Preclinical (animal and cell-line) only. No human kidney-protection trials have been published.
Eriocitrin is a flavanone-7-O-glycoside with antioxidant, anti-inflammatory, anticancer, and anti-allergic properties. When compared to other antioxidants, eriocitrin was more effective in scavenging free radicals associated with diabetes mellitus and other chronic illnesses. Several studies have shown that eriocitrin stimulates apoptosis in nucleated cells; in HL-60 cells, eriocitrin causes caspase-dependent apoptosis characterized by DNA fragmentation and chromatin condensation.
Eriocitrin has been reported to trigger ferroptosis in A549 and H1299 lung adenocarcinoma cells, thereby circumventing cancer cell resistance to apoptosis. Eriocitrin suppressed the proliferation of human hepatocellular carcinoma cells.
Evidence strength: All anticancer evidence is from cell-line studies (in vitro) with no animal tumor models or human data reported. These are mechanistic findings only and cannot be extrapolated to clinical anticancer use.
In an animal model of cerebral ischemia-reperfusion injury, in vitro experiments of OxyHb-induced BV2 cells revealed that eriocitrin promoted Nrf2 while markedly suppressing NF-κB by increasing DUSP14 activation, thereby reducing concentrations of inflammatory cytokines. Moreover, eriocitrin decreased MDA while evidently increasing SOD and GSH-px.
Evidence strength: Animal and cell-line data only. No human neuroprotection studies exist.
Eriocitrin suppresses muscle atrophy by reducing oxidative stress in the skeletal muscles of mice. Eriocitrin has been included in a recent review evaluating the anti-sarcopenic potential of selected flavonoids based on preclinical findings and mechanistic insights.
Evidence strength: Preclinical only.
Preclinical work has examined eriocitrin's potential role in modulating angiogenesis pathways. Laboratory studies indicate that eriocitrin may modulate endothelial function and angiogenesis pathways (e.g., VEGFR2-PI3K-AKT-mTOR). These findings are preclinical and should be treated as mechanistic clues, not clinical claims.
The following dosages are cited only as reported in the research literature and do not constitute recommended dosing.
The supplement is currently being evaluated in a registered clinical trial: participants, who are adults with pre-diabetes, will receive 200 mg/d of eriocitrin, with assessments including anthropometric measures, and biochemical parameters (lipid and glucose profile, inflammatory parameters, endothelial markers, liver function, renal function).
Eriocitrin is marketed as a dietary supplement, usually in conjunction with B and C vitamins and other substances, but there is no established medical use or FDA-approved application of the compound.
Comparing the body weight, liver, and spleen index of mice in the eriocitrin group and the control group, no observed difference was found between the groups (p > 0.05). Indicating that 100 mg·kg⁻¹·d⁻¹ eriocitrin in diet had no appreciable toxic effect on mice.
A significant preclinical safety finding relates to potential hemolytic activity at pharmacological concentrations used in anticancer studies. Eriocitrin caused significant, concentration-dependent hemolysis in erythrocytes at 20–100 µM. Eriocitrin also significantly increased the percentage of eryptotic cells characterized by calcium elevation and oxidative stress. In whole blood, eriocitrin significantly elevated MCV and ESR, with no appreciable effects on other peripheral blood cells. These findings were observed at concentrations used in anticancer research and may not be relevant to dietary supplementation doses, but they represent a documented safety signal warranting further investigation.
Eriocitrin is an inhibitor of monoamine oxidase A (MAO-A) and MAO-B (IC₅₀s = 86.5 and 164 µM, respectively, for human recombinant receptors). The clinical relevance of MAO inhibition at dietary supplement doses has not been established, but this pharmacological property is of theoretical significance for interactions with serotonergic or adrenergic medications, or tyramine-containing foods, at sufficiently high doses.
The documented ability of eriocitrin to increase GLP-1 levels and reduce blood glucose and insulin resistance raises the theoretical possibility of additive hypoglycemic effects when used alongside antidiabetic medications (insulin secretagogues, GLP-1 receptor agonists, or insulin itself). The human trials have involved prediabetic individuals not currently on hypoglycemic agents; safety in medicated diabetic populations has not been systematically evaluated.
The plasma metabolites of eriocitrin showed a half-life between 3 and 3.2 hours, with overall bioavailability of eriocitrin remaining less than 1%. This very low oral bioavailability of the parent compound means that biological activity is substantially mediated by gut microbial metabolites, introducing inter-individual variability based on microbiome composition.
More in-depth studies are recommended to explore eriocitrin for clinical trials. The existing human RCTs are small (n = 30) and of short duration (12 weeks), providing limited power to detect adverse effects. No dedicated human safety or toxicology studies have been published.
Eriocitrin is available in several forms:
Eriocitrin has shown antioxidant, anticancer, and anti-allergic properties, and the pharmacokinetic and pharmacological mechanisms of action of eriocitrin have been studied in vivo. The overall body of evidence can be summarized by area:
Health conditions that Enocitrin may help support.
Body systems that Enocitrin may help support.
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