Named Bioactive Compounds · Compound
Didymin (7-O-rutinoside of naringenin)
Moderate Evidenceflavonoid4 PubMed Studies
Hermetica Superfood Encyclopedia
Didymin is a citrus flavanone glycoside — the 7-O-rutinoside of naringenin — found naturally in citrus fruits including lemons and oranges. Preclinical research suggests it may inhibit TRPM3 ion channels and exhibit antioxidant activity, though no human clinical trials have been completed.
Didymin is a flavanone glycoside (7-O-rutinoside of isosakuranetin) with molecular formula C27H32O14, naturally occurring in various Citrus species including sweet orange, blood orange, mandarin, grapefruit, lemons, and limes. It is typically extracted from fruit peels or juices using solvent-based methods, followed by chromatographic purification or precipitation techniques.
No human clinical trials, RCTs, or meta-analyses specifically on didymin were identified in the available sources. Research is limited to in vitro, animal, or phytochemical studies on Citrus flavanone glycosides, with no PubMed PMIDs for didymin-specific human trials provided.
No clinically studied dosage ranges, forms, or standardization details for didymin are available, as human trials are lacking. Consult a healthcare provider before starting any new supplement.
Didymin (also known as isosakuranetin-7-O-rutinoside) is a flavanone glycoside with molecular formula C₂₈H₃₄O₁₄ and molecular weight ~594.56 g/mol. It is not a macronutrient source and provides negligible calories, protein, fat, fiber, or carbohydrates at physiologically relevant doses. **Bioactive compound identity:** It is the 7-O-rutinoside (rhamnosyl-glucoside) conjugate of isosakuranetin (4'-methyl-naringenin), structurally analogous to hesperidin (hesperetin-7-O-rutinoside) and narirutin (naringenin-7-O-rutinoside). Note: Some literature incorrectly identifies didymin as the 7-O-rutinoside of naringenin; the aglycone is specifically isosakuranetin (4'-O-methylnaringenin), distinguishing it from narirutin. **Natural concentrations:** Found in Citrus fruits, particularly in sweet oranges (Citrus sinensis) at approximately 0.5–5 mg/100 mL juice, bergamot (Citrus bergamia) at higher concentrations (~10–50 mg/100 mL juice), and in smaller amounts in lemons, mandarins, and grapefruits. Concentrations vary significantly with cultivar, maturity, and tissue (peel > juice). **Key bioactive properties (preclinical only):** Exhibits antioxidant activity (ORAC and DPPH scavenging, though weaker than aglycone isosakuranetin), anti-inflammatory effects (suppression of NF-κB pathway in cell models), and anticancer activity in vitro (apoptosis induction reported in neuroblastoma SH-SY5Y cells, lung cancer A549 and H460 cells, and leukemia cell lines at concentrations of ~10–100 µM). Reported to modulate Ras/MAPK and PI3K/Akt signaling pathways in cell culture. **Bioavailability notes:** Like other flavanone rutinosides (e.g., hesperidin), didymin's rutinoside bond is not cleaved by small intestinal enzymes and requires colonic microbiota (α-rhamnosidase and β-glucosidase) for hydrolysis to the aglycone isosakuranetin. This results in delayed absorption (Tmax typically 4–8 hours post-ingestion, extrapolated from hesperidin pharmacokinetics). The aglycone undergoes extensive phase II metabolism (glucuronidation, sulfation) in enterocytes and liver. Estimated oral bioavailability is very low (<5% as intact compound), with circulating metabolites (glucuronides and sulfates of isosakuranetin) being the predominant plasma forms. No established RDA, adequate intake, or tolerable upper intake level exists. No vitamins or minerals are contributed at supplemental doses.
Didymin, as the 7-O-rutinoside of naringenin, is structurally related to isosakuranetin and may inhibit transient receptor potential melastatin 3 (TRPM3) channels, which are calcium-permeable cation channels implicated in pain signaling and inflammation. The rutinosyl sugar moiety at the C-7 position influences its bioavailability and may modulate its binding affinity relative to its aglycone naringenin, potentially affecting NF-κB pathway suppression and reactive oxygen species scavenging. These mechanisms remain theoretical extrapolations from structurally related citrus flavanones and have not been confirmed for didymin specifically in peer-reviewed mechanistic studies.
No human clinical trials have been conducted specifically on didymin as an isolated compound, making its evidence base absent at the clinical level. Available data consists primarily of in vitro cell-based studies and structural comparisons to better-researched flavanones such as naringenin and hesperidin. Extrapolation from naringenin research — which includes small human trials of 20–100 participants examining cardiovascular and anti-inflammatory markers — suggests a plausible but unconfirmed benefit profile. Until dedicated pharmacokinetic and interventional studies are conducted on didymin, any claimed health benefits remain speculative.
No dedicated human safety studies exist for isolated didymin; however, its presence as a minor constituent in commonly consumed citrus fruits suggests a low acute toxicity profile by dietary association. Structurally related citrus flavanones like naringenin are known to inhibit CYP3A4 and CYP1A2 enzymes, raising the theoretical concern that didymin could similarly affect the metabolism of drugs such as statins, calcium channel blockers, and certain immunosuppressants. Pregnant or breastfeeding individuals should avoid supplemental doses of isolated didymin due to a complete absence of safety data in these populations. Drug interaction risk remains theoretical but warrants caution, particularly with narrow-therapeutic-index medications metabolized by cytochrome P450 pathways.
