Safety Profile
Information not yet available for this ingredient profile.
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
MPFF (Micronized Purified Flavonoid Fraction) is a pharmaceutical-grade citrus bioflavonoid complex containing approximately 90% diosmin and 10% hesperidin. It is the active principle of Daflon® 500 mg, a registered prescription drug in France and widely used in Europe for chronic venous insufficiency and hemorrhoidal disease. Its clinical safety is among the best documented of any vascular supplement: landmark RCTs (including Lancet 1994), Cochrane reviews, and decades of post-marketing surveillance show an excellent tolerability profile. Adverse effects are limited to mild, transient GI symptoms. No clinically relevant drug interactions have been identified. It is considered safe for use during pregnancy for hemorrhoidal disease in the second and third trimesters based on European clinical data.
Biological and Chemical Classification
- Scientific Name
- Citrus aurantium
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Main clinical benefit observed: Botanical
- Evidence consistency: High consistency across studies (100%)
- No significant safety signals identified in the reviewed literature.
The available scientific evidence for MPFF indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 10/40 |
| Evidence consistency | 20/20 |
| Safety signals | 0/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 10 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 16 ივნ 2026, 01:59
Evidence Distribution
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Observational / other LOW evidence YELLOWIntegrated morphological, pomological, biochemical, and ISSR-based assessment of genetic diversity in wild sour orange (Citrus aurantium L.) genotypes from the Hassa district… ↗Tunu00e7 Y. Integrated morphological, pomological, biochemical, and ISSR-based assessment of genetic diversity in wild sour orange (Citrus aurantium L.) genotypes from the Hassa district of Hatay, Tu00fcrkiye.. Biol Res. 2026. PMID:42289725.PMID 42289725 ↗Journal Biol ResYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42289725/
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Observational / other LOW evidence YELLOWCitrus aurantium honey-mediated gut homeostasis and anti-inflammation via Thorl/Nprl2-TORC1 signaling: Network pharmacology and Drosophila validation. ↗Wan W et al.. Citrus aurantium honey-mediated gut homeostasis and anti-inflammation via Thorl/Nprl2-TORC1 signaling: Network pharmacology and Drosophila validation.. Animal Model Exp Med. 2026. PMID:42226584.PMID 42226584 ↗Journal Animal Model Exp MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42226584/
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Observational / other LOW evidence YELLOWIntegration of network pharmacology, deep learning, and molecular biology reveals the efficacy of Citrus aurantium L. var. amara Engl. blossom extract in… ↗Ni Q et al.. Integration of network pharmacology, deep learning, and molecular biology reveals the efficacy of Citrus aurantium L. var. amara Engl. blossom extract in ameliorating diabetic osteoporosis.. J Ethnopharmacol. 2026. PMID:42217588.PMID 42217588 ↗Journal J EthnopharmacolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42217588/
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Observational / other LOW evidence YELLOWRadiation-induced in vivo biochemical disruptions, acetylcholinesterase inhibition and synergistic radiosensitivity of (60)Co-u03b3 radiation integrated with Citrus aurantium nanoemulsions against Sitophilus oryzae (L.)… ↗Senevirathne WHKE et al.. Radiation-induced in vivo biochemical disruptions, acetylcholinesterase inhibition and synergistic radiosensitivity of (60)Co-u03b3 radiation integrated with Citrus aurantium nanoemulsions against Sitophilus oryzae (L.) and Tribolium castaneum (Herbst).. Appl Radiat Isot. 2026. PMID:42217440.PMID 42217440 ↗Journal Appl Radiat IsotYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42217440/
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Observational / other LOW evidence YELLOWComposition analysis, QSAR, molecular docking, molecular dynamics simulation and ADMET profiles of Citrus aurantium fruit essential oil compounds as inhibitors of NF-u03baB… ↗Ogunleye FA et al.. Composition analysis, QSAR, molecular docking, molecular dynamics simulation and ADMET profiles of Citrus aurantium fruit essential oil compounds as inhibitors of NF-u03baB and MAPK in brain injury.. Comput Biol Chem. 2026. PMID:42208171.PMID 42208171 ↗Journal Comput Biol ChemYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42208171/
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Observational / other LOW evidence YELLOWTangeretin, a bioactive polymethoxyflavone from immature Citrus aurantium L. fruit, ameliorates experimental colitis by targeting the macrophage u03b22 integrin Mac-1. ↗Zhu J et al.. Tangeretin, a bioactive polymethoxyflavone from immature Citrus aurantium L. fruit, ameliorates experimental colitis by targeting the macrophage u03b22 integrin Mac-1.. J Ethnopharmacol. 2026. PMID:42202920.PMID 42202920 ↗Journal J EthnopharmacolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42202920/
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Observational / other LOW evidence YELLOWExogenous ascorbic acid enhances drought tolerance in sour orange through integrated physiological and antioxidant mechanisms. ↗Mijani Z et al.. Exogenous ascorbic acid enhances drought tolerance in sour orange through integrated physiological and antioxidant mechanisms.. BMC Plant Biol. 2026. PMID:42157095.PMID 42157095 ↗Journal BMC Plant BiolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42157095/
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Observational / other LOW evidence YELLOWUnexplained Supraventricular Tachycardia and Myocardial Injury After Bitter Orange Supplement Use in a Young Woman. ↗Plaitis A et al.. Unexplained Supraventricular Tachycardia and Myocardial Injury After Bitter Orange Supplement Use in a Young Woman.. JACC Case Rep. 2026. PMID:42132724.PMID 42132724 ↗Journal JACC Case RepYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42132724/
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Observational / other LOW evidence YELLOWChemical composition and insecticidal activity of essential oils from Citrus limon, Citrus aurantium, and Citrus margarita against Musca domestica. ↗Elmaidomy AH et al.. Chemical composition and insecticidal activity of essential oils from Citrus limon, Citrus aurantium, and Citrus margarita against Musca domestica.. Sci Rep. 2026. PMID:42010347.PMID 42010347 ↗Journal Sci RepYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42010347/
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Observational / other LOW evidence YELLOWThe Antimicrobial and Antibiofilm Potential of Citrus Aurantium and Artemisia Annua Essential Oils Nanoemulsions. ↗Mahmoud O et al.. The Antimicrobial and Antibiofilm Potential of Citrus Aurantium and Artemisia Annua Essential Oils Nanoemulsions.. Arch Razi Inst. 2025. PMID:42058245.PMID 42058245 ↗Journal Arch Razi InstYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/42058245/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for MPFF. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a low safety concern under normal conditions of use.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the Low classification for MPFF
A score of 1.5 places this ingredient in the Low band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.