Myricetin

• Antioxidant
• Anti-inflammatory
• Anti-cancer
• Neuroprotective

• Anti-diabetic
• Cardioprotective
• Antimicrobial
• Hepatoprotective
• Anti-allergic
• Anti-viral

Myricetin exerts its diverse biological effects through multiple molecular mechanisms and signaling pathways. As a potent antioxidant, myricetin directly scavenges reactive oxygen species (ROS) and reactive nitrogen species (RNS), including superoxide anions, hydroxyl radicals, hydrogen peroxide, and peroxynitrite. This direct scavenging activity is primarily attributed to the hydroxyl groups in its structure, particularly the catechol moiety in the B-ring and the 3-hydroxyl group in the C-ring, which donate hydrogen atoms to neutralize free radicals. Notably, myricetin possesses six hydroxyl groups, more than many other flavonoids, which contributes to its exceptionally strong antioxidant capacity.

Beyond direct scavenging, myricetin enhances the endogenous antioxidant defense system by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Upon activation, Nrf2 translocates to the nucleus and binds to antioxidant response elements (AREs), promoting the expression of antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Myricetin also exhibits metal-chelating properties, binding transition metals like iron and copper that can catalyze oxidative reactions, thereby preventing lipid peroxidation and oxidative damage to cellular components. The anti-inflammatory effects of myricetin are mediated through multiple pathways.

It potently inhibits the nuclear factor-kappa B (NF-κB) signaling pathway, a master regulator of inflammatory responses. Myricetin blocks the phosphorylation and degradation of inhibitor of kappa B (IκB), preventing NF-κB translocation to the nucleus and subsequent transcription of pro-inflammatory genes. Additionally, myricetin inhibits the mitogen-activated protein kinase (MAPK) pathways, including p38 MAPK, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK), which are involved in inflammatory signal transduction. These actions result in decreased production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8).

Myricetin also inhibits the activity of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), reducing the production of prostaglandins and excessive nitric oxide associated with inflammation. Furthermore, myricetin modulates the activity of phospholipase A2 (PLA2), decreasing the release of arachidonic acid and subsequent production of inflammatory mediators. In the context of cancer prevention and treatment, myricetin demonstrates multiple mechanisms. It induces cell cycle arrest by modulating the expression of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors such as p21 and p27.

Myricetin triggers apoptosis (programmed cell death) in cancer cells through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways, involving activation of caspases and regulation of Bcl-2 family proteins. It inhibits cancer cell proliferation by suppressing various signaling pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt, MAPK/ERK, and Janus kinase/signal transducer and activator of transcription (JAK/STAT). Myricetin also inhibits angiogenesis (formation of new blood vessels) by downregulating vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs), thereby limiting tumor growth and metastasis. Furthermore, myricetin exhibits epigenetic effects by inhibiting DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), potentially reversing aberrant epigenetic modifications associated with cancer.

Myricetin has demonstrated significant neuroprotective effects through several mechanisms. It protects neurons from oxidative stress-induced damage through its potent antioxidant properties. Myricetin reduces neuroinflammation by inhibiting microglial activation and the release of pro-inflammatory mediators in the central nervous system. It also modulates various neurotransmitter systems, including cholinergic, dopaminergic, and glutamatergic pathways, potentially improving cognitive function.

Additionally, myricetin inhibits the aggregation of amyloid-beta peptides and tau protein, which are implicated in Alzheimer’s disease pathogenesis, and promotes the expression of neurotrophic factors such as brain-derived neurotrophic factor (BDNF), supporting neuronal survival and plasticity. Recent research has shown that myricetin can suppress traumatic brain injury-induced inflammatory responses via the EGFR/AKT/STAT pathway. In metabolic regulation, myricetin influences glucose metabolism through several mechanisms. It enhances insulin sensitivity by activating the insulin receptor substrate-1 (IRS-1) and PI3K/Akt signaling pathway, promoting glucose uptake in peripheral tissues.

Myricetin inhibits alpha-glucosidase and alpha-amylase, enzymes involved in carbohydrate digestion, thereby slowing glucose absorption. It also protects pancreatic beta cells from oxidative stress-induced damage and stimulates insulin secretion. Additionally, myricetin activates AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, which promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis. Myricetin has demonstrated antimicrobial properties through multiple mechanisms.

It disrupts bacterial cell membranes, inhibits bacterial DNA gyrase and topoisomerase IV, and interferes with bacterial quorum sensing. Against viruses, myricetin inhibits viral enzymes such as reverse transcriptase, protease, and helicase, and prevents viral attachment and entry into host cells. Recent studies have shown that myricetin can inhibit the main protease (Mpro) of SARS-CoV-2, suggesting potential antiviral activity against COVID-19. The cardioprotective effects of myricetin involve improving endothelial function by enhancing nitric oxide (NO) production through activation of endothelial nitric oxide synthase (eNOS).

Myricetin reduces platelet aggregation and thrombus formation by inhibiting thromboxane A2 (TXA2) production and modulating calcium signaling in platelets. It also prevents cardiac hypertrophy and fibrosis by inhibiting transforming growth factor-beta (TGF-β) signaling and reducing the production of extracellular matrix proteins. Additionally, myricetin protects cardiomyocytes from oxidative stress-induced damage through its antioxidant properties and by maintaining mitochondrial function.

The optimal therapeutic dosage of myricetin is not firmly established due to limited clinical trials

specifically using isolated myricetin. Based on available research and extrapolation from studies on myricetin-rich foods and extracts, dosages typically range from 10 mg to 100 mg per day. For general health maintenance and antioxidant support, lower doses of 10-30 mg daily may be sufficient. Higher doses are typically used for specific therapeutic purposes and should be guided by healthcare professionals.

General Timing: Myricetin is typically taken with meals to enhance absorption and reduce potential gastrointestinal side effects. For twice-daily dosing, morning and evening administration with food is recommended.

Specific Considerations: For conditions involving inflammatory responses, consistent daily timing helps maintain stable blood levels. For neuroprotective benefits, some research suggests that evening administration may be beneficial, though clinical evidence is limited.

Tablets Capsules: Most common form, typically available in 10 mg, 25 mg, and occasionally 50 mg strengths.

Powder: Allows for flexible dosing but has a bitter taste. Typically mixed with juice or smoothies to mask flavor.

Combination Products: Often combined with other flavonoids (quercetin, rutin) or antioxidants. Dosages vary by formulation.

For those new to myricetin supplementation, starting with a lower dose (10-20 mg daily) for the first week and gradually increasing to the target therapeutic dose can help minimize potential digestive discomfort or other side effects.

Estimated Intake: The average dietary intake of myricetin from food sources is estimated to be 2-6 mg per day in Western diets, with higher intakes (up to 10-15 mg daily) in diets rich in berries, tea, and certain vegetables.

Food Equivalents: A serving (100g) of fresh cranberries contains approximately 6.8 mg of myricetin, black currants contain 4.3 mg, and a cup of brewed black tea provides about 0.5-1.6 mg.

It’s important to note that optimal dosing guidelines for myricetin are still evolving as research continues. Many recommendations are based on preclinical studies, limited clinical trials, and extrapolation from studies on myricetin-rich foods rather than isolated supplements. The bioavailability of myricetin is relatively low, which may necessitate higher doses or enhanced formulations for therapeutic effects.

Myricetin has poor oral bioavailability (approximately 1-3%) due to its low water solubility, limited intestinal absorption, and extensive first-pass metabolism. The planar structure and multiple hydroxyl groups (six in total, more than many other flavonoids) contribute to its limited absorption in the small intestine.

Intestinal Metabolism: In the intestine, myricetin undergoes extensive metabolism by intestinal microflora and intestinal enzymes. Bacterial metabolism includes dehydroxylation, demethylation, and ring cleavage reactions. Intestinal enzymes primarily catalyze phase II conjugation reactions, including glucuronidation and sulfation.

Hepatic Metabolism: After absorption, myricetin undergoes further metabolism in the liver, primarily through phase II conjugation reactions. The main metabolic pathways include glucuronidation (mediated by UDP-glucuronosyltransferases), sulfation (mediated by sulfotransferases), and methylation (mediated by catechol-O-methyltransferases).

Primary Metabolites: Myricetin-3-O-glucuronide, Myricetin-4′-O-glucuronide, Myricetin-3′-O-glucuronide, Myricetin-3-O-sulfate, Myricetin-4′-O-sulfate, 3′-O-Methylmyricetin (laricitrin), 4′-O-Methylmyricetin, Various mixed conjugates (glucuronide-sulfates)

Peak Plasma Time: For standard myricetin, peak plasma concentrations of metabolites occur approximately 1.5-3 hours after oral administration, reflecting rapid metabolism. The parent compound is typically detected at very low concentrations in plasma.

Half Life: The elimination half-life of myricetin metabolites ranges from 2-4 hours for the parent compound to 8-12 hours for various metabolites, with considerable individual variation.

Protein Binding: Approximately 95-99% of circulating myricetin and its metabolites are bound to plasma proteins, primarily albumin.

Blood Brain Barrier: Myricetin can cross the blood-brain barrier to a limited extent, with brain concentrations typically reaching 2-5% of plasma levels. Enhanced delivery systems like liposomes or nanoparticles may improve CNS penetration.

Target Tissues: After absorption, myricetin and its metabolites distribute to various tissues, with higher concentrations observed in the liver, kidneys, and intestines. Lower concentrations are found in the brain, heart, and skeletal muscle.

Accumulation: Limited evidence of significant tissue accumulation with regular dosing, though some metabolites may have longer residence times in specific tissues.

Myricetin and its metabolites undergo enterohepatic circulation, where conjugated metabolites are excreted in bile, deconjugated by intestinal bacteria, and reabsorbed. This process extends the presence of active compounds in the body.

For optimal absorption, myricetin should be taken with meals, preferably those containing some fat content. Dividing the daily dose into two administrations (morning and evening with meals) may help maintain more consistent blood levels of active metabolites. Consistency in timing from day to day helps maintain stable therapeutic effects.

Myricetin generally has lower bioavailability compared to quercetin and kaempferol, primarily due to its higher number of hydroxyl groups (six versus five and four, respectively), which reduces its lipophilicity. Its absorption profile is similar to other flavonols but with some unique metabolic pathways that may contribute to its specific biological activities.

Myricetin has a generally favorable safety profile based on available research, though long-term human studies using isolated myricetin supplements are limited. As a naturally occurring flavonoid present in many foods, myricetin is generally recognized as safe for most individuals

when consumed in dietary amounts. Supplemental forms at higher doses warrant some caution, particularly due to potential interactions with certain medications and limited clinical safety data. The presence of six hydroxyl groups in myricetin’s structure, more than many other flavonoids, may contribute to both its potent antioxidant properties and potential pro-oxidant effects at high doses.

• Known hypersensitivity to myricetin or other flavonoids
• Bleeding disorders (use with caution due to potential antiplatelet effects)
• Scheduled surgery (discontinue at least 2 weeks before due to potential anticoagulant effects)
• Pregnancy and lactation (insufficient safety data, use only if clearly needed and under medical supervision)
• Hormone-sensitive conditions (due to potential estrogenic effects)
• Severe liver or kidney disease (use with caution due to limited elimination data)

Pregnancy: Category C – Animal reproduction studies have shown adverse effects on the fetus, and there are no adequate well-controlled studies in humans. Use only if potential benefit justifies potential risk to the fetus.

Lactation: Limited data available. It is unknown if myricetin is excreted in human milk. Use caution and consider risk-benefit ratio.

Pediatric: Safety and efficacy not established in children. Not recommended for supplemental use in pediatric populations.

Geriatric: No specific dose adjustments required, but start at lower doses and monitor for side effects due to potential decreased renal/hepatic function and increased likelihood of drug interactions.

Renal Impairment: Use with caution in moderate to severe renal impairment. Consider reduced dosing.

Hepatic Impairment: Use with caution in moderate to severe hepatic impairment. Consider reduced dosing.

Acute Toxicity: Myricetin has low acute toxicity. Animal studies show LD50 values greater than 2,000 mg/kg body weight, indicating a wide margin of safety.

Chronic Toxicity: Long-term studies in humans are limited. Animal studies have not identified significant toxicity concerns at therapeutic doses. Monitoring liver function with long-term use may be prudent.

Genotoxicity: Available studies do not indicate significant genotoxic potential at therapeutic doses. Some in vitro studies suggest potential DNA-damaging effects at very high concentrations, but these are not likely to be relevant at typical supplemental doses.

Carcinogenicity: No evidence of carcinogenic potential in available studies. Some research suggests potential anti-cancer properties.

No official upper limit has been established. Based on available research, doses up to 100 mg daily appear to be well-tolerated in most individuals. Doses above 150 mg daily have not been well studied and are not recommended without medical supervision due to potential for increased risk of side effects, drug interactions, and theoretical pro-oxidant effects at very high doses.

For long-term use (>3 months), consider periodic monitoring of liver function, complete blood count, and blood pressure, particularly at higher doses.

Limited data on overdose. Expected symptoms may include gastrointestinal disturbances, hypotension, and potential liver stress. Supportive care is the primary management approach.

Compared to other flavonoids, myricetin appears to have a similar safety profile to quercetin and kaempferol, though its higher number of hydroxyl groups may theoretically contribute to both enhanced antioxidant activity and potential pro-oxidant effects at very high doses. Direct comparative safety studies are limited.

Classification: Dietary Supplement

Approval Status: Not approved as a drug in the United States. Marketed as a dietary supplement under DSHEA (Dietary Supplement Health and Education Act) regulations.

Permitted Claims: Structure/function claims related to antioxidant support, inflammatory response, and cellular health are permitted with appropriate disclaimer. Disease claims (such as treating neurodegenerative diseases, cancer, or inflammatory conditions) are not allowed without drug approval.

Restrictions: Must comply with dietary supplement GMP (Good Manufacturing Practices) regulations. Cannot be marketed with claims to treat, cure, or prevent specific diseases.

Increasing Scrutiny: Growing regulatory attention to quality control and standardization of botanical supplements, including myricetin-containing products.

Evidence Requirements: Increasing emphasis on clinical evidence to support health claims, with regulatory bodies requiring more robust scientific substantiation.

Safety Monitoring: Enhanced post-market surveillance systems for dietary supplements in many jurisdictions, potentially affecting myricetin products.

United States: Must include standard supplement facts panel, appropriate structure/function claim disclaimers, and cannot make disease claims.

European Union: Must comply with food supplement labeling regulations, including ingredient listing, recommended daily dose, warning statements, and no unauthorized health claims.

General Requirements: Most jurisdictions require batch/lot numbers, expiration dates, storage conditions, and manufacturer information.

Clinical Trials: Several registered clinical trials investigating myricetin-rich extracts for various conditions, including neurodegenerative disorders, metabolic conditions, and viral infections. Most are small-scale or early-phase studies.

Investigational New Drug: Some myricetin derivatives or formulations may be under investigation as potential pharmaceutical agents, though most remain in preclinical or early clinical stages.

Enhanced Formulations: Novel delivery systems for myricetin (liposomal, nanoparticle, etc.) may face additional regulatory scrutiny as they could alter the absorption, distribution, metabolism, and excretion profiles.

Combination Products: Products combining myricetin with other bioactives may face more complex regulatory pathways, particularly if synergistic effects are claimed.

Personalized Nutrition: Emerging regulatory frameworks for personalized nutrition may impact how myricetin supplements are recommended and marketed based on individual genetic or metabolic profiles.

Status: Myricetin as a pure compound does not have Generally Recognized as Safe (GRAS) status for use as a food additive in the United States.

Food Sources: Natural food sources of myricetin (berries, vegetables, tea) are generally recognized as safe for consumption.

Compound Patents: As a naturally occurring compound, myricetin itself is not patentable. However, various patents exist for specific formulations, delivery systems, and synthetic derivatives of myricetin.

Application Patents: Patents exist for specific applications of myricetin in areas such as neurodegenerative disease treatment, cancer therapy, and antiviral applications.

Formulation Patents: Several patents cover enhanced bioavailability formulations of myricetin, including liposomal, nanoparticle, and phytosomal delivery systems.

2024-07-10

High

Myricetin supplements tend to be relatively expensive compared to many other dietary supplements.

This is due to the complex extraction and purification processes required, limited commercial sources, and relatively low market volume. Pure myricetin supplements are less common than other flavonoids like quercetin, which contributes to their higher price point. The presence of six hydroxyl groups in myricetin’s structure (more than many other flavonoids) may also contribute to more complex extraction and stabilization processes, potentially increasing production costs.

Standard Myricetin: $45-90 USD for 30-60 mg daily dose, $1.50-3.00 USD per day for standard formulations, Basic myricetin supplements are relatively expensive and may have limited bioavailability. Quality can vary significantly in this price range.

Enhanced Bioavailability Formulations: $75-130 USD for 30-60 mg daily dose, $2.50-4.30 USD per day, Liposomal, phytosomal, or nanoparticle formulations command premium prices but may offer improved absorption and efficacy.

Combination Products: $55-95 USD for products combining myricetin with other flavonoids or antioxidants, $1.80-3.20 USD per day, Products combining myricetin with complementary compounds like quercetin, resveratrol, or EGCG may offer better value through synergistic effects.

Myricetin-rich Extracts: $30-65 USD for extracts standardized to contain myricetin, $1.00-2.20 USD per day, Plant extracts rich in myricetin (e.g., cranberry extracts, tea extracts) are generally less expensive than isolated myricetin but contain lower concentrations and other compounds.

Regional Variations: Prices vary significantly by country and region. European and Japanese products tend to be more expensive than those manufactured in the United States or India.

Vs Other Flavonoids: Myricetin is typically more expensive than common flavonoids like quercetin (60-120% higher) and rutin (120-180% higher), comparable to or slightly more expensive than resveratrol, and less expensive than some specialized flavonoids like fisetin.

Vs Other Supplements: Myricetin is highly priced compared to many other dietary supplements. It is typically more expensive than basic supplements like vitamin C or B vitamins, significantly more expensive than mid-range supplements like CoQ10 or alpha-lipoic acid, and comparable to premium supplements like NMN or certain medicinal mushroom extracts.

Vs Dietary Sources: Obtaining therapeutic amounts of myricetin from food sources is significantly more cost-effective than supplements. For example, 100g of fresh cranberries (approximately $2-4) provides about 6.8 mg of myricetin, making the cost per mg much lower than supplements.

Dietary Approach: Increasing consumption of myricetin-rich foods (cranberries, black currants, tea) is the most cost-effective way to increase myricetin intake. This approach provides additional health benefits from other nutrients and compounds in these foods.

Supplement Selection: If supplementation is desired, combination products that include myricetin along with complementary compounds may offer better value than isolated myricetin supplements.

Dosing Strategies: Starting with lower doses (10-30 mg daily) and titrating up based on response may optimize cost-effectiveness. For some conditions, intermittent dosing or cycling may provide benefits while reducing costs.

Purchasing Tips: Bulk purchases may reduce per-dose cost, Subscription services often offer 10-20% discounts, Look for sales or promotional discounts from reputable suppliers, Consider combination products if you would otherwise purchase multiple supplements separately

When evaluating cost-efficiency, consider the potential long-term savings from preventing progression of certain conditions or reducing the need for more expensive interventions. These indirect savings may outweigh the direct costs of myricetin supplementation in some cases, though evidence for such outcomes is currently limited.

Limited Production: Relatively small market demand for isolated myricetin supplements leads to limited production volume and higher costs compared to more mainstream supplements.

Extraction Complexity: The complex extraction and purification processes required to isolate myricetin from plant sources contribute to higher production costs. The presence of six hydroxyl groups in myricetin’s structure may require more sophisticated extraction and stabilization methods.

Research Investment: Ongoing research and development costs for enhanced formulations and delivery systems are reflected in higher retail prices.

Antioxidant Capacity: While myricetin has exceptionally strong antioxidant capacity due to its six hydroxyl groups (more than many other flavonoids), the cost per unit of antioxidant activity is relatively high compared to other antioxidants like vitamin C or mixed tocopherols.

Anti-inflammatory Effects: The cost per unit of anti-inflammatory effect is relatively high compared to other natural anti-inflammatories like curcumin or omega-3 fatty acids, though direct comparisons are limited by differences in mechanisms and bioavailability.

Standard myricetin supplements typically have a shelf life of 2-3 years when stored properly. The actual stability can vary based on formulation, packaging, and storage conditions. Due to its six hydroxyl groups (more than many other flavonoids), myricetin may be more susceptible to oxidative degradation than some other flavonoids.

Temperature: Store at room temperature (15-25°C or 59-77°F). Avoid exposure to temperatures above 30°C (86°F), as higher temperatures can accelerate degradation through oxidation and other chemical reactions.

Humidity: Keep in a dry place with relative humidity below 60%. Myricetin can absorb moisture, which may lead to hydrolysis and degradation.

Light: Protect from direct light, especially sunlight and UV radiation, which can cause photodegradation. Myricetin is particularly susceptible to photodegradation due to its flavonoid structure with conjugated double bonds and multiple hydroxyl groups.

Container: Keep in the original container, preferably in opaque or amber bottles with tight-fitting lids. Blister packs provide good protection against moisture and light.

Special Considerations: Some formulations may include stabilizers such as vitamin C, vitamin E, or other antioxidants to extend shelf life by protecting against oxidation. Nitrogen-flushed packaging may also help prevent oxidative degradation.

Tablets: Generally stable with shelf life of 2-3 years. Film-coated tablets offer better protection against moisture and oxidation. Inclusion of antioxidants like vitamin C or vitamin E can enhance stability.

Capsules: Moderately stable with shelf life of 2-3 years. Vegetable capsules may be more susceptible to moisture than gelatin capsules. Oxygen absorbers in packaging can improve stability.

Powders: Less stable than solid dosage forms, with shelf life typically 1-2 years due to increased surface area exposed to environmental factors. Should be stored with desiccants.

Liquid Extracts: Least stable form with shelf life of 6-12 months. Often contain preservatives and antioxidants to extend stability. Glycerin-based extracts tend to be more stable than alcohol-based ones.

Liposomal Formulations: Moderate stability with shelf life of 1-2 years. The phospholipid encapsulation provides some protection against degradation but introduces potential for lipid oxidation.

Cooking Effects: Myricetin in foods is moderately stable during cooking, with losses of 20-60% depending on cooking method and duration. Steaming and microwaving result in lower losses compared to boiling and frying.

Processing Effects: Food processing methods like freezing, drying, and fermentation can affect myricetin content, with varying degrees of loss depending on specific conditions.

Compared to other flavonoids, myricetin may be somewhat less stable due to its six hydroxyl groups (more than many other flavonoids), which make it more susceptible to oxidation. However, this same structural feature contributes to its exceptionally strong antioxidant capacity.

Synthesis Methods

Natural Sources

Quality Considerations

Sustainability

Market Trends

Dietary Intake Estimates

Ancient Medicine: While myricetin itself was not identified until the 20th century, plants rich in myricetin have been used in traditional medicine systems for centuries. Myrica cerifera (bayberry), from which myricetin derives its name, has been used in Native American and traditional Chinese medicine for various ailments including fever, diarrhea, and skin conditions.

Folk Remedies: Cranberries and other berries rich in myricetin have long histories of medicinal use in various cultures for urinary tract infections, digestive issues, and as general tonics. Tea, another significant source of myricetin, has been consumed for thousands of years for its health-promoting properties.

Initial Discovery: Myricetin was first isolated in the early 20th century from the bark of Myrica nagi (now classified as Myrica esculenta), a plant in the Myricaceae family. It was later found to be widely distributed in the plant kingdom.

Structural Elucidation: The complete chemical structure of myricetin was elucidated in the 1940s through chemical analysis. Its classification as a flavonol with a specific hydroxylation pattern (3,3′,4′,5,5′,7-hexahydroxyflavone) was established through chemical degradation studies and later confirmed by spectroscopic methods.

Early Research: Initial scientific interest in myricetin was primarily in the context of plant pigmentation, taxonomy, and phytochemistry. Its biological activities began to be investigated more thoroughly in the mid-20th century.

1950s-1970s: Early research focused on the chemical properties and botanical distribution of myricetin. Limited studies began to explore its potential biological activities, particularly its antioxidant properties.

1980s-1990s: Increased research into the biological activities of flavonoids in general, with growing interest in myricetin’s antioxidant and anti-inflammatory properties. Studies began to elucidate its mechanisms of action at the molecular level.

2000s-2010s: Significant expansion of research into myricetin’s therapeutic potential, with studies exploring its effects on cancer, inflammation, neurodegenerative diseases, and metabolic conditions. Mechanisms of action were more thoroughly characterized, and epidemiological studies began to associate dietary myricetin intake with health outcomes.

2010s-Present: Growing interest in myricetin’s potential applications for neurodegenerative disorders, viral infections (including recent studies on SARS-CoV-2), and as an adjunctive therapy in cancer treatment. Increased focus on improving bioavailability and developing novel delivery systems. Expansion of clinical research, though still limited compared to preclinical studies.

Early Products: Initial commercial products containing myricetin were primarily plant extracts rather than isolated myricetin. These included cranberry extracts, tea extracts, and various berry concentrates, which were marketed for various health benefits.

Supplement Formulations: Isolated myricetin supplements began to appear in the market in the early 2000s, initially at relatively low doses and often combined with other flavonoids. More recently, higher-dose formulations and enhanced bioavailability products have been developed, though they remain less common than other flavonoid supplements like quercetin.

Specialized Formulations: Development of specialized formulations targeting specific conditions, particularly neurodegenerative and inflammatory disorders. These often combine myricetin with complementary compounds for enhanced efficacy.

Pharmaceutical Interest: Growing pharmaceutical interest in myricetin as a lead compound for drug development, particularly for anti-inflammatory, neuroprotective, and anticancer applications. Several derivatives and analogs are under investigation.

Regional Variations: Plants rich in myricetin, such as cranberries, black currants, and tea, have significant cultural importance in many regions. Cranberries have been important in Native American culture and cuisine, while tea ceremonies in East Asian countries inadvertently promote myricetin consumption.

Modern Perception: In contemporary wellness culture, myricetin is increasingly recognized as a beneficial flavonoid, though it has not yet achieved the widespread recognition of some other flavonoids like quercetin or resveratrol.

Early 20th century: First isolation of myricetin from Myrica nagi, 1940s: Elucidation of myricetin’s complete chemical structure, 1990s: Identification of key molecular mechanisms underlying myricetin’s antioxidant and anti-inflammatory effects, 2000s: Discovery of myricetin’s potential neuroprotective properties and mechanisms, 2010s: Epidemiological studies linking dietary myricetin intake with reduced risk of various chronic diseases, 2020s: Studies identifying myricetin as a potential inhibitor of SARS-CoV-2 main protease, expanding interest in its antiviral applications, 2020s: Research demonstrating myricetin’s ability to suppress traumatic brain injury-induced inflammatory responses via the EGFR/AKT/STAT pathway

Early Sources: Initially obtained through extraction from specific medicinal plants, primarily for research purposes rather than commercial production.

Modern Sources: Commercial production now relies primarily on extraction from myricetin-rich plants like cranberries, black currants, and tea leaves, which offer higher yields and more economical processing.

Extraction Methods: Early extraction methods used simple solvent extraction with alcohol or water. More sophisticated methods using selective solvents and purification techniques developed over time.

Synthetic Approaches: While total chemical synthesis of myricetin has been achieved, it has not been commercially viable compared to extraction from natural sources.

Early Focus: Initial research focused primarily on myricetin’s chemical properties, botanical distribution, and basic biological activities.

Expanding Applications: Research gradually expanded to include more diverse potential applications, from cancer prevention to neurodegenerative disorders and viral infections.

Mechanistic Understanding: Over time, studies have provided increasingly detailed insights into myricetin’s molecular mechanisms of action, including its effects on various signaling pathways and cellular processes.

Clinical Translation: Despite extensive preclinical research, clinical studies specifically on myricetin remain limited, with most human evidence coming from epidemiological studies of dietary intake rather than interventional trials.

The name ‘myricetin’ is derived from the genus Myrica, specifically Myrica nagi (now classified as Myrica esculenta), the plant from which it was first isolated. The suffix ‘-etin’ is common in flavonoid nomenclature.

Myricetin has moderate evidence supporting its biological activities, particularly its antioxidant and anti-inflammatory effects, which are well-established in preclinical studies. Clinical evidence for specific therapeutic applications is limited, with most research consisting of in vitro and animal studies. Human studies primarily focus on epidemiological associations between myricetin intake from dietary sources and health outcomes, rather than interventional trials using isolated myricetin supplements. The quality of available clinical evidence is limited by small sample sizes, short durations, and often the use of myricetin-rich extracts rather than isolated myricetin.

Myricetin’s unique structure with six hydroxyl groups (more than many other flavonoids) contributes to its exceptionally strong antioxidant capacity, which is well-documented in laboratory studies.

Clinical trial evaluating myricetin-rich extract for neurodegenerative disorders (NCT04782181), Study of myricetin supplementation for metabolic syndrome (ISRCTN15483459), Investigation of myricetin for viral respiratory infections (NCT04523389)

Well-designed clinical trials using isolated myricetin supplements, Long-term safety and efficacy data beyond 6 months of treatment, Optimal dosing strategies for different conditions, Comparative effectiveness studies against standard treatments for inflammatory and neurodegenerative conditions, Studies on enhanced bioavailability formulations and their clinical outcomes, Research on potential synergistic effects with other flavonoids and antioxidants

Development and clinical testing of enhanced bioavailability formulations, Larger, well-designed clinical trials for specific conditions, particularly neurodegenerative and inflammatory disorders, Investigation of optimal dosing regimens and treatment durations, Exploration of synergistic combinations with other bioactive compounds, Long-term safety studies, particularly in special populations

Most of the human evidence for myricetin’s health benefits comes from epidemiological studies of dietary intake rather than interventional studies using supplements. This distinction is important, as dietary myricetin is consumed alongside other bioactive compounds that may contribute to observed health effects. The limited clinical evidence specifically for myricetin supplements represents a significant research gap.