Diosmin is a flavonoid glycoside derived from citrus that strengthens vein walls, improves circulation, reduces inflammation, and supports lymphatic drainage, making it particularly effective for treating venous insufficiency and hemorrhoids.
Alternative Names: Diosmetin 7-O-rutinoside, 3′,5,7-Trihydroxy-4′-methoxyflavone 7-rutinoside, Barosmin, Citrus Flavonoid, Flavonoid Glycoside
Categories: Flavonoid, Flavone Glycoside, Phytochemical
Primary Longevity Benefits
- Vascular health
- Venous circulation
- Anti-inflammatory
- Antioxidant
Secondary Benefits
- Hemorrhoid relief
- Varicose vein treatment
- Lymphatic drainage
- Edema reduction
- Capillary protection
- Wound healing
Mechanism of Action
Diosmin exerts its therapeutic effects through multiple mechanisms primarily targeting vascular health and inflammatory pathways. As a phlebotonic agent, diosmin increases venous tone by prolonging the vasoconstrictor effect of noradrenaline on the vein wall, resulting in improved venous return and reduced venous stasis. It enhances lymphatic drainage by increasing lymph flow and lymph node output, which helps reduce edema and improve microcirculation. At the microcirculatory level, diosmin decreases capillary hyperpermeability and strengthens capillary resistance by protecting the microvascular endothelium and reducing inflammatory mediator-induced damage.
Its anti-inflammatory properties stem from inhibiting various pro-inflammatory enzymes and mediators, including phospholipase A2, cyclooxygenase, and lipoxygenase, thereby reducing prostaglandin E2 and thromboxane A2 production. Diosmin also inhibits the expression of endothelial adhesion molecules like ICAM-1 and VCAM-1, which prevents leukocyte adhesion, activation, and migration into tissues. As an antioxidant, diosmin scavenges reactive oxygen species (ROS) and enhances the activity of endogenous antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. It inhibits lipid peroxidation and protects cellular membranes from oxidative damage.
Diosmin modulates inflammatory signaling pathways by suppressing nuclear factor-kappa B (NF-κB) activation, which regulates the expression of various pro-inflammatory genes. In the context of venous insufficiency, diosmin reduces the expression of endothelin-1, a potent vasoconstrictor, while increasing nitric oxide production, which promotes vasodilation and improves blood flow. It inhibits platelet aggregation and reduces blood viscosity, thereby improving microcirculation and preventing microthrombi formation. Diosmin also demonstrates protective effects on the vascular endothelium by preserving the integrity of the glycocalyx layer and reducing endothelial cell damage.
In hemorrhoidal disease, diosmin decreases vascular hyperpermeability, reduces inflammation, and improves venous tone in the hemorrhoidal plexus. Recent research suggests that diosmin may also have anti-cancer properties through inhibition of cell proliferation, induction of apoptosis, and suppression of angiogenesis by modulating various signaling pathways including PI3K/Akt, MAPK, and Wnt/β-catenin. Additionally, diosmin has shown potential anti-diabetic effects by enhancing insulin sensitivity, improving glucose metabolism, and protecting pancreatic β-cells from oxidative stress-induced damage.
Optimal Dosage
Disclaimer: The following dosage information is for educational purposes only. Always consult with a healthcare provider before starting any supplement regimen, especially if you have pre-existing health conditions, are pregnant or nursing, or are taking medications.
The typical therapeutic dosage of diosmin ranges from 500 mg to 2,000 mg per day, with most clinical studies using 600-1,000 mg daily. For micronized purified flavonoid fraction (MPFF), which contains 90% diosmin and 10% hesperidin, the standard dose is 1,000 mg per day (500 mg twice daily).
By Condition
| Condition | Dosage | Notes |
|---|---|---|
| Chronic venous insufficiency | 600-1,000 mg daily, typically divided into two doses | Treatment duration of 2-3 months is common, with maintenance therapy of 500-600 mg daily thereafter. May be cycled with 2-3 months on, 1 month off. |
| Acute hemorrhoid episodes | 3,000 mg daily for the first 4 days, followed by 2,000 mg daily for 3 days, then 1,000 mg daily for maintenance | Higher initial dosing helps manage acute symptoms more effectively. Often used in combination with topical treatments. |
| Lymphedema | 1,000-2,000 mg daily | Often used as adjunctive therapy alongside compression therapy and physical treatments. |
| Venous leg ulcers | 1,000 mg daily | Used as adjunctive therapy alongside standard wound care. Treatment duration typically 2-6 months. |
| Varicose veins | 500-1,000 mg daily | May help manage symptoms but not a replacement for medical procedures when indicated. |
| Post-thrombotic syndrome | 1,000 mg daily | Used as adjunctive therapy alongside anticoagulants when indicated. |
By Age Group
| Age Group | Dosage | Notes |
|---|---|---|
| Adults (18-65 years) | 500-2,000 mg daily depending on condition | Standard dosing applies to most healthy adults. |
| Elderly (>65 years) | 500-1,000 mg daily | Lower doses may be appropriate initially; monitor for side effects and drug interactions. |
| Children and adolescents (<18 years) | Not well established | Limited research on safety and efficacy in pediatric populations. Use only under medical supervision. |
| Pregnant women | Use only under medical supervision | Limited safety data available; benefit-risk assessment should be performed by healthcare provider. |
Bioavailability
Absorption Rate
Standard diosmin has relatively poor oral bioavailability (approximately 5-10%) due to its low water solubility and limited intestinal absorption. Micronized diosmin (particle size <2 μm) has significantly improved bioavailability, estimated to be 3-5 times higher than standard diosmin.
Metabolism
After oral administration, diosmin is partially metabolized by intestinal microflora to its aglycone form, diosmetin, which is then absorbed into the bloodstream. Diosmetin undergoes further metabolism in the liver through glucuronidation and sulfation. The primary metabolites include diosmetin glucuronides and sulfates, which are excreted primarily in urine.
Pharmacokinetics
Peak Plasma Time: For standard diosmin, peak plasma concentrations occur approximately 5-6 hours after oral administration. Micronized diosmin reaches peak plasma levels more quickly, typically within 2-3 hours.
Half Life: The elimination half-life of diosmin and its metabolites ranges from 11-14 hours, allowing for once or twice daily dosing.
Protein Binding: Approximately 25-30% of circulating diosmin and its metabolites are bound to plasma proteins.
Enhancement Methods
| Method | Description |
|---|---|
| Micronization | Reducing particle size to <2 μm significantly improves dissolution rate and intestinal absorption, increasing bioavailability by 3-5 times compared to standard diosmin. |
| Phytosomal formulation | Complexing diosmin with phospholipids creates a more lipophilic compound that can more easily cross cell membranes, potentially improving bioavailability by 2-3 times. |
| Liposomal delivery | Encapsulating diosmin in liposomes can protect it from degradation in the GI tract and enhance cellular uptake. |
| Co-administration with piperine | Black pepper extract containing piperine may inhibit intestinal and hepatic enzymes that metabolize diosmin, potentially increasing its bioavailability. |
| Combination with hesperidin | The standard MPFF formulation (90% diosmin, 10% hesperidin) may have synergistic effects and improved clinical outcomes compared to diosmin alone. |
| Taking with fatty meals | Consumption with a moderate-fat meal may enhance absorption due to increased bile secretion and prolonged intestinal transit time. |
Timing Recommendations
For optimal absorption, diosmin should be taken with meals, preferably with breakfast and dinner if using a twice-daily regimen. Taking with food helps improve absorption and may reduce potential gastrointestinal side effects. For acute hemorrhoid treatment with the higher initial dose (3,000 mg daily), dividing into three doses with meals is recommended.
Safety Profile
Safety Rating
Overview
Diosmin has a favorable safety profile with minimal reported adverse effects in clinical studies. It has been used therapeutically for several decades with a good safety record, particularly in the form of micronized purified flavonoid fraction (MPFF). Clinical trials have demonstrated safety at doses up to 2,000 mg daily for extended periods.
Side Effects
| Severity | Effects |
|---|---|
| Mild (common) | Array |
| Moderate (uncommon) | Array |
| Severe (rare) | Array |
Contraindications
- Known hypersensitivity to diosmin or other flavonoids
- Severe renal impairment (use with caution)
- Severe hepatic impairment (use with caution)
- Pregnancy and lactation (insufficient safety data, use only if clearly needed and under medical supervision)
Drug Interactions
| Drug Class | Medications | Interaction | Severity | Evidence Level |
|---|---|---|---|---|
| Anticoagulants/Antiplatelets | Array | Theoretical risk of enhanced anticoagulant effect due to diosmin’s mild antiplatelet properties. Monitor for increased bleeding risk with concurrent use. | Moderate | Limited – primarily theoretical |
| Cytochrome P450 substrates | Array | Limited evidence suggests diosmin may weakly inhibit certain CYP enzymes, potentially affecting metabolism of other drugs. Clinical significance appears minimal. | Low | Limited |
| Diuretics | Array | Potential additive effect on reducing edema. Generally considered beneficial rather than adverse. | Low | Limited |
Special Populations
Pregnancy: Category C – Animal reproduction studies have not demonstrated fetal risk, but there are no adequate well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus.
Lactation: Limited data available. Small amounts may be excreted in breast milk. Use caution and consider risk-benefit ratio.
Pediatric: Safety and efficacy not established in children. Limited clinical data available for pediatric use.
Geriatric: No specific dose adjustments required, but start at lower doses and monitor for side effects due to potential decreased renal/hepatic function.
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.
Upper Limit
Clinical studies have used doses up to 3,000 mg daily for short periods (acute hemorrhoid treatment) and 2,000 mg daily for extended periods without significant adverse effects. No established upper limit, but doses above 2,000 mg daily are rarely necessary for most conditions and may increase risk of gastrointestinal side effects.
Regulatory Status
Fda Status
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 vascular health and circulation are permitted with appropriate disclaimer. Disease claims (such as treating chronic venous insufficiency or hemorrhoids) 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.
International Status
European Union
- Medicinal Product in many EU countries
- Approved as a prescription or over-the-counter medication in several EU countries, particularly for chronic venous insufficiency and hemorrhoidal disease.
- France, Spain, Italy, and Portugal have long-standing approvals for diosmin-containing medications.
- Daflon 500 mg (micronized purified flavonoid fraction) is registered as a medication in numerous EU countries.
United Kingdom
- Licensed Medicine and Food Supplement (depending on formulation and claims)
- Some diosmin products are licensed as medicines for specific indications, while others are marketed as food supplements.
- Daflon and similar MPFF products are available as licensed medicines.
Canada
- Natural Health Product (NHP)
- Regulated under the Natural Health Products Regulations. Several diosmin products have received Natural Product Numbers (NPNs) from Health Canada.
- Approved claims may include ‘Helps relieve symptoms associated with mild to moderate chronic venous insufficiency’ when specific criteria are met.
Australia
- Listed Medicine on the Australian Register of Therapeutic Goods (ARTG)
- Several diosmin products are listed on the ARTG as complementary medicines.
- Low-level claims related to circulation and vascular health may be permitted with supporting evidence.
Japan
- Quasi-drug or Functional Food (depending on formulation)
- Some diosmin products are approved as quasi-drugs for specific health applications.
Brazil
- Registered Medication
- Diosmin products are registered and widely prescribed as medications for venous insufficiency and hemorrhoidal disease.
Russia
- Registered Pharmaceutical
- Diosmin products are registered as pharmaceuticals and commonly prescribed for venous conditions.
Clinical Guidelines
Vascular Disease
- International Union of Phlebology
- Recommends micronized purified flavonoid fraction (MPFF) for the treatment of chronic venous disease with Grade 1B evidence (strong recommendation, moderate-quality evidence).
Hemorrhoidal Disease
- European Society of Coloproctology
- Acknowledges flavonoids including diosmin as an option for symptomatic relief in hemorrhoidal disease, particularly for bleeding and acute symptoms.
Regulatory Trends
Harmonization Efforts: Ongoing efforts to harmonize regulatory approaches to botanical products including diosmin across different regions, particularly within the EU.
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 and botanical medicines in many jurisdictions.
Labeling Requirements
United States: Must include standard supplement facts panel, appropriate structure/function claim disclaimers, and cannot make disease claims.
European Union: Medicinal products must include approved indications, dosage information, and safety warnings. Food supplements must comply with food labeling regulations and health claim restrictions.
General Requirements: Most jurisdictions require batch/lot numbers, expiration dates, storage conditions, and manufacturer information.
Last Updated
2024-07-10
Synergistic Compounds
Antagonistic Compounds
Cost Efficiency
Relative Cost
Medium
Cost Overview
Diosmin supplements vary in cost depending on formulation, purity, and brand. Micronized formulations and pharmaceutical-grade products typically command higher prices than standard diosmin supplements. Generic versions of micronized purified flavonoid fraction (MPFF) are generally less expensive than branded versions (e.g., Daflon).
Price Ranges
Standard Diosmin: $15-30 USD for 500-1000 mg daily dose, $0.50-1.00 USD per day for standard formulations, Standard (non-micronized) diosmin is less expensive but also less bioavailable, potentially reducing therapeutic efficacy.
Micronized Diosmin: $25-45 USD for 500-1000 mg daily dose, $0.80-1.50 USD per day for micronized formulations, The improved bioavailability of micronized formulations may justify the higher cost through enhanced efficacy.
Branded Mpff: $35-60 USD for 1000 mg daily dose (Daflon or equivalent), $1.15-2.00 USD per day, Branded products often have more extensive clinical research supporting their efficacy but may not offer significant advantages over generic MPFF formulations.
Regional Variations: Prices vary significantly by country. In European countries where diosmin is prescribed as a medication, costs may be partially covered by health insurance. In countries like France, Spain, and Brazil, generic MPFF products are widely available at lower costs.
Cost Comparison
Vs Other Supplements: Diosmin is moderately priced compared to other vascular health supplements. It is typically more expensive than basic supplements like vitamin C or horse chestnut extract, but less expensive than specialized formulations like liposomal glutathione or high-quality CoQ10.
Vs Pharmaceuticals: For venous insufficiency and hemorrhoids, diosmin is generally less expensive than prescription medications like pentoxifylline or surgical interventions, making it a cost-effective first-line or adjunctive therapy.
Value Analysis
Chronic Venous Insufficiency
- High
- Multiple clinical studies support efficacy for symptom relief. When compared to the costs of untreated progression (including lost productivity, additional medications, and potential surgical interventions), diosmin therapy represents good value.
- A 2010 pharmacoeconomic analysis found that MPFF treatment was cost-effective for chronic venous disease management compared to no treatment, with an acceptable cost per quality-adjusted life year (QALY).
Hemorrhoidal Disease
- Medium to High
- Effective for symptom management and may reduce the need for more expensive interventions in mild to moderate cases. For severe hemorrhoids requiring surgery, diosmin is best viewed as an adjunctive therapy.
- Studies suggest that MPFF treatment can reduce bleeding and pain, potentially delaying or avoiding surgical intervention in some patients.
Preventive Use
- Low to Medium
- Insufficient evidence to support cost-effectiveness for primary prevention in healthy individuals without symptoms of venous disease.
- May be reasonable for individuals with strong risk factors for venous disease, but routine use in healthy populations is not supported by current evidence.
Maximizing Value
Formulation Selection: Micronized formulations offer better bioavailability and are likely to provide better value despite higher initial cost. MPFF (90% diosmin, 10% hesperidin) has the strongest evidence base for efficacy.
Dosing Strategies: For chronic conditions, using the recommended therapeutic dose during initial treatment (typically 1000 mg daily for 2-3 months), then reducing to a maintenance dose (500-600 mg daily) may optimize cost-effectiveness.
Purchasing Tips: Generic MPFF formulations often provide similar benefits to branded products at lower cost, Bulk purchases may reduce per-dose cost, Prescription versions may be partially covered by insurance in some countries, Look for sales or subscription discounts from reputable suppliers
Long Term Considerations
When evaluating cost-efficiency, consider the potential long-term savings from preventing progression of venous disease, which can lead to costly complications such as venous ulcers, deep vein thrombosis, or surgical interventions. These indirect savings may significantly outweigh the direct costs of diosmin supplementation.
Stability Information
Shelf Life
Standard diosmin supplements typically have a shelf life of 2-3 years when stored properly. Micronized formulations may have slightly shorter shelf lives of 1.5-2.5 years due to the increased surface area of particles, which can make them more susceptible to degradation.
Storage Recommendations
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.
Humidity: Keep in a dry place with relative humidity below 60%. Diosmin can absorb moisture, which may lead to degradation and clumping.
Light: Protect from direct light, especially sunlight and UV radiation, which can cause photodegradation of flavonoids including diosmin.
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 or be packaged in specialized containers to extend shelf life.
Degradation Factors
| Factor | Details |
|---|---|
| Oxidation | Diosmin, like other flavonoids, is susceptible to oxidation, particularly in the presence of oxygen, heat, and light. Oxidation can reduce potency and potentially form degradation products with altered biological activity. |
| Hydrolysis | In the presence of moisture, especially under acidic or basic conditions, diosmin can undergo hydrolysis of its glycosidic bond, converting it to its aglycone form (diosmetin) and rutinose. |
| Photodegradation | Exposure to UV light and sunlight can cause structural changes in diosmin molecules, leading to loss of therapeutic activity. |
| Microbial contamination | While not directly causing chemical degradation, microbial growth in improperly stored supplements can lead to decomposition of active ingredients and formation of potentially harmful metabolites. |
| Temperature fluctuations | Repeated cycling between different temperatures can accelerate degradation through multiple mechanisms, including moisture condensation and structural stress. |
Stability Testing
Methods
- Accelerated stability testing at elevated temperatures and humidity
- Real-time stability testing under recommended storage conditions
- Photostability testing under controlled light exposure
- HPLC analysis to monitor degradation products and potency over time
Key Indicators
- Appearance changes (color, texture)
- Dissolution rate alterations
- Formation of degradation products
- Loss of potency
- pH changes in liquid formulations
Formulation Stability
Tablets: Generally stable with shelf life of 2-3 years. Film-coated tablets offer better protection against moisture and oxidation.
Capsules: Moderately stable with shelf life of 1.5-2.5 years. Vegetable capsules may be more susceptible to moisture than gelatin capsules.
Powders: Less stable than solid dosage forms, with shelf life typically 1-2 years due to increased surface area exposed to environmental factors.
Liquid Extracts: Least stable form with shelf life of 6 months to 1 year. Often contain preservatives and antioxidants to extend stability.
Reconstitution Stability
Not applicable for most diosmin products, as they are typically provided in ready-to-use forms. For any powder formulations requiring reconstitution, the resulting solution should be used promptly as stability in solution is limited.
Sourcing
Synthesis Methods
| Method | Details |
|---|---|
| Hesperidin conversion | The primary commercial method for diosmin production is the oxidation of hesperidin, which is abundant in citrus peels and a by-product of the citrus juice industry. This semi-synthetic process involves the dehydrogenation of hesperidin to form diosmin. |
| Micronization | After synthesis or extraction, diosmin is often subjected to micronization, a process that reduces particle size to less than 2 micrometers. This significantly improves its bioavailability and therapeutic efficacy. Micronized purified flavonoid fraction (MPFF) is produced through this process. |
| Total chemical synthesis | Complete chemical synthesis of diosmin is possible but generally not economically viable for commercial production compared to hesperidin conversion. |
Natural Sources
| Source | Details |
|---|---|
| Citrus fruits | Diosmin is found naturally in the peels and pulp of various citrus fruits, particularly sweet oranges (Citrus sinensis), lemons (Citrus limon), and grapefruits (Citrus paradisi). However, the concentration is relatively low, making direct extraction for commercial purposes inefficient. |
| Rutaceae family plants | Various plants in the Rutaceae family contain diosmin, including Ruta graveolens (common rue) and Citrus species. |
| Scrophulariaceae family plants | Some plants in the Scrophulariaceae family contain diosmin, including certain Verbascum species. |
| Lamiaceae family plants | Several plants in the mint family (Lamiaceae) contain diosmin, including Mentha species (mints) and Rosmarinus officinalis (rosemary). |
Quality Considerations
- Micronization level: Particle size significantly affects bioavailability. High-quality products should specify micronized diosmin with particle size <2 μm.
- Purity: Look for products with at least 95% purity for standard diosmin supplements.
- Standardization: For MPFF products, verify standardization to 90% diosmin and 10% hesperidin.
- Third-party testing: Quality products should be tested by independent laboratories for purity, potency, and contaminants.
- Manufacturing standards: Look for products manufactured in facilities that follow Good Manufacturing Practices (GMP).
- Heavy metals: Can be present if sourced from plants grown in contaminated soil.
- Pesticide residues: May be present if citrus sources are not organically grown.
- Solvent residues: May remain from extraction processes if quality control is inadequate.
- USP (United States Pharmacopeia) verification
- NSF International certification
- GMP (Good Manufacturing Practices) certification
- ISO 9001 certification for quality management systems
Sustainability
- The production of diosmin through hesperidin conversion has a relatively low environmental impact, as it utilizes citrus by-products that would otherwise be waste. This represents a sustainable approach to supplement production.
- No significant ethical concerns are associated with diosmin production, as it does not involve endangered species or controversial harvesting practices.
Historical Usage
Traditional Uses
Ancient Medicine: While diosmin itself was not identified until the 20th century, citrus fruits and plants containing diosmin have been used in traditional medicine systems for centuries. Citrus peels, rich in flavonoids including diosmin precursors, were used in traditional Chinese medicine and Mediterranean folk medicine for various circulatory and inflammatory conditions.
Folk Remedies: Plants from the Rutaceae family containing diosmin, such as rue (Ruta graveolens), were traditionally used in European folk medicine for vascular conditions, including varicose veins and hemorrhoids. These applications align with the modern therapeutic uses of isolated diosmin.
Discovery And Development
Isolation: Diosmin was first isolated and identified in 1925 from the plant Scrophularia nodosa. Its chemical structure was fully elucidated in the 1940s.
Early Research: Initial scientific interest in diosmin began in the 1960s, with early studies focusing on its effects on vascular permeability and inflammation.
Commercial Development: The first medicinal preparations containing diosmin became available in Europe in the 1970s. The development of micronized diosmin in the 1980s significantly improved its bioavailability and clinical efficacy, leading to the introduction of Daflon 500 mg (micronized purified flavonoid fraction) in 1987.
Evolution Of Medical Use
1970s-1980s: Initial clinical use focused primarily on symptoms of venous insufficiency, with limited scientific evidence supporting its efficacy.
1990s: Increased clinical research established diosmin’s efficacy for chronic venous insufficiency and hemorrhoidal disease. The RELIEF study (Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids) in 1997 provided significant evidence for its use in chronic venous disease.
2000s: Expanded research into mechanisms of action and potential applications beyond vascular conditions, including anti-inflammatory, antioxidant, and potential anti-cancer effects.
2010s-Present: Growing interest in diosmin’s potential applications for metabolic disorders, neurodegenerative conditions, and as an adjunctive therapy in cancer treatment. Increased focus on formulation improvements to enhance bioavailability.
Cultural Significance
Regional Variations: Diosmin-containing medications have been particularly popular in European countries, especially France, Spain, and Italy, where they are commonly prescribed for venous conditions. In contrast, awareness and use in North America have been more limited until recently.
Integration With Conventional Medicine: In many European countries, diosmin preparations are prescribed by physicians and may be partially covered by health insurance for specific indications. In other regions, they are primarily used as dietary supplements.
Historical Formulations
Early Preparations: Initial diosmin products were simple extracts or non-micronized formulations with limited bioavailability.
Micronized Formulations: The development of micronization technology in the 1980s revolutionized diosmin therapy by significantly improving absorption and efficacy.
Combination Products: Historical development of combination products, particularly the micronized purified flavonoid fraction (90% diosmin, 10% hesperidin), which has become the standard formulation for clinical use in many countries.
Notable Milestones
1925: First isolation of diosmin from plant material, 1969: First clinical studies on vascular effects, 1987: Introduction of Daflon 500 mg (MPFF) in Europe, 1997: Completion of the RELIEF study, establishing strong evidence for chronic venous disease treatment, 2005: Inclusion in various clinical practice guidelines for chronic venous disease management, 2010s: Expansion of research into novel therapeutic applications
Scientific Evidence
Evidence Rating
Summary
Diosmin has moderate to strong evidence supporting its use for chronic venous insufficiency and hemorrhoidal disease, with numerous clinical trials demonstrating efficacy. Evidence for other applications such as lymphedema, diabetic microvascular complications, and anti-cancer effects is emerging but less robust. Most research has been conducted using micronized purified flavonoid fraction (MPFF) containing 90% diosmin and 10% hesperidin.
Key Studies
Meta Analyses
Ongoing Trials
Clinical trial evaluating diosmin in combination with standard therapy for diabetic retinopathy (NCT04009668), Study of diosmin for radiation-induced skin toxicity in breast cancer patients (NCT03691844), Investigation of diosmin for post-thrombotic syndrome prevention (ISRCTN14648186)
Research Gaps
Long-term safety and efficacy data beyond 12 months of treatment, Comparative effectiveness studies against other treatments for venous disease, Optimal dosing strategies for different conditions, Mechanisms of action in emerging applications such as neuroprotection and cancer prevention, Effects on specific biomarkers of inflammation and oxidative stress in various conditions
Disclaimer: The information provided is for educational purposes only and is not intended as medical advice. Always consult with a healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications.