Myricetol

Myricetol, commonly known as myricetin, is a polyhydroxylated flavonol found in berries, grapes, and herbs that exerts its effects primarily through inhibition of matrix metalloproteinases (MMP-2/MMP-9), viral enzymes, and modulation of oxidative stress pathways. Its broad preclinical activity spans anti-metastatic, antiviral, and neuroprotective mechanisms, though robust human clinical trials remain limited.

Origin & History

Myricetol, also known as Myricetin, is a naturally occurring flavonol derived from various plants, including berries, vegetables, tea, and herbs like Myrica rubra. It is extracted using solvent-based methods, although specific industrial processes are not detailed in the available research.

Historical & Cultural Context

The research does not provide specific information on traditional or historical uses of Myricetol. It is primarily studied for its modern pharmacological potential without an ethnopharmacological context.

Health Benefits

• Exhibits anti-metastatic properties through inhibition of MMP-2/MMP-9 enzymes, though primarily supported by preclinical evidence.
• Shows potential antiviral activity by inhibiting viral enzymes such as HIV reverse transcriptase and SARS-CoV-2 Mpro, based on preclinical studies.
• May promote apoptosis and cell cycle arrest, suggesting anti-cancer potential, but lacks robust clinical trials.
• Demonstrates anti-inflammatory effects by modulating pathways like NF-κB and reducing cytokines such as TNF-α and IL-6, supported by preclinical studies.
• Acts as an antioxidant, scavenging reactive oxygen species, with evidence from in vitro studies.

How It Works

Myricetol inhibits MMP-2 and MMP-9, zinc-dependent endopeptidases critical for extracellular matrix degradation and tumor metastasis, by binding to their catalytic domains and reducing their proteolytic activity. It also competitively inhibits HIV-1 reverse transcriptase and occupies the active site of SARS-CoV-2 main protease (Mpro), blocking viral replication machinery. Additionally, myricetol activates the Nrf2/ARE signaling pathway, upregulating endogenous antioxidant enzymes such as heme oxygenase-1 (HO-1) and superoxide dismutase (SOD), while modulating AMPK pathways relevant to metabolic function.

Scientific Research

The clinical evidence for Myricetol is limited, with few human trials and no comprehensive RCTs or meta-analyses identified in the research. Reviews call for more human trials to validate preclinical findings, but no specific PMIDs are available.

Clinical Summary

The majority of myricetol's evidence derives from in vitro cell culture and rodent models, with few controlled human trials published to date. Preclinical studies demonstrate IC50 values in the low micromolar range (1–20 µM) for MMP inhibition and antiviral enzyme suppression, though translating these concentrations to achievable human plasma levels remains uncertain. A small number of epidemiological studies suggest inverse associations between dietary flavonol intake, including myricetin-rich foods, and risks of certain cancers and cardiovascular events, but causality cannot be established from observational data alone. Overall, the evidence is promising but insufficient to make definitive clinical recommendations without larger, well-designed randomized controlled trials.

Nutritional Profile

Myricetol (also known as Myricetin, CAS 529-44-2) is a polyphenolic flavonoid compound (flavonol subclass), not a macronutrient or conventional food ingredient. Molecular formula: C15H10O8, molecular weight: 318.24 g/mol. It is not a source of protein, fat, or dietary fiber. Caloric contribution is negligible at physiological intake levels. As a pure bioactive compound, its 'nutritional profile' is defined by its polyphenolic structure featuring a 3,5,7,3',4',5'-hexahydroxyflavone backbone, which confers strong antioxidant capacity (ORAC value estimated >1000 μmol TE/g in vitro). Naturally occurring concentrations in food sources: red wine (~0.5–10 mg/L), onions (~0.3–1.2 mg/100g fresh weight), berries such as cranberries and blackcurrants (~0.1–3.5 mg/100g), green tea (~0.2–2 mg/100g dry weight), and walnuts (~0.4–1.1 mg/100g). Bioavailability is notably limited: oral bioavailability is estimated at less than 10% in humans due to extensive first-pass metabolism, poor aqueous solubility (~0.3 mg/mL at physiological pH), and rapid phase II metabolic conjugation (glucuronidation, sulfation, methylation) in the intestinal wall and liver. Gut microbiota play a significant role in its biotransformation to smaller phenolic metabolites such as 3,4-dihydroxybenzoic acid and phloroglucinol derivatives, which may carry residual bioactivity. No established dietary reference intake (DRI) or recommended daily allowance (RDA) exists for myricetin. Plasma half-life following oral administration is approximately 1–3 hours. Nanoformulation and phospholipid complexation have been studied to enhance its bioavailability by up to 3–5 fold in preclinical models.

Preparation & Dosage

No clinically studied dosage ranges are specified due to limited human trials. Preclinical studies have used various doses, but standardized human dosing is not established. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

Quercetin, Resveratrol, Curcumin, Green Tea Extract, Vitamin C

Safety & Interactions

Myricetol is generally considered safe at dietary intake levels found in foods such as berries, red wine, and tea, but high-dose supplementation has not been rigorously evaluated for long-term safety in humans. At supraphysiological doses, in vitro data suggest potential pro-oxidant activity, and caution is warranted. Myricetol may interact with anticoagulant medications such as warfarin by inhibiting CYP1A2 and CYP2C9 enzymes, potentially altering drug metabolism and increasing bleeding risk. Pregnant and breastfeeding women should avoid supplemental doses beyond normal dietary exposure due to insufficient safety data, and individuals on diabetes medications should monitor blood glucose, as myricetin may have additive hypoglycemic effects.