Meta Information
ID:fisetin-liposomal
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/dietary/high-fat-meal
Target name:
Fat-Containing Meal
Severity:
major
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Fisetin is a lipophilic (fat-soluble) polyphenol with very poor water solubility, leading to low oral bioavailability. Co-administration with fats or oils significantly enhances its absorption from the gastrointestinal tract.
Actionable advice:
Fisetin should be taken during or immediately after a meal containing healthy fats like olive oil, avocado, or nuts to ensure absorption.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
141-fold higher bioavailability than when treated with free fisetin
Label source:
Action type:
separate
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Fisetin exhibits antiplatelet activity and inhibits CYP2C9, the primary enzyme metabolizing warfarin. This combination can significantly increase the risk of serious bleeding events.
Actionable advice:
Fisetin should not be taken with any anticoagulant (e.g., warfarin, apixaban) or antiplatelet (e.g., aspirin, clopidogrel) medication unless approved and closely monitored by a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CYP2C9, a polymorphic enzyme, is likely to be the principal form of human liver CYP450 that modulates the in vivo anticoagulant activity of warfarin.
Label source:
Action type:
avoid
Target id:
/class/cyp3a4-substrates
Target name:
CYP3A4 Substrates
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Fisetin is a moderate inhibitor of the CYP3A4 enzyme, which is responsible for metabolizing approximately 50% of clinical drugs. This can increase the plasma concentration and risk of side effects from medications like certain statins, calcium channel blockers, and benzodiazepines.
Actionable advice:
It is a good idea to consult a pharmacist or physician to review the medication list for potential CYP3A4 interactions before starting fisetin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
However, strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir)
may increase the plasma concentrations of amlodipine to a greater extent.
Label source:
Action type:
informational_none
Target id:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Fisetin's inhibition of CYP3A4 can dangerously increase levels of immunosuppressants like tacrolimus and cyclosporine, which have a narrow therapeutic window, leading to a high risk of toxicity. [class-derived from: quercetin (flavonol class)]
Actionable advice:
Fisetin should not be taken during calcineurin inhibitor immunosuppressant therapy following an organ transplant.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Exact phrase from label:
pomegranate juice contains quercetin, which inhibits CYP3A4
Label source:
Action type:
avoid
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Fisetin may lower blood glucose levels through various mechanisms. When combined with insulin or oral hypoglycemic agents, this can lead to an additive effect and increase the risk of hypoglycemia (dangerously low blood sugar).
Actionable advice:
If you have diabetes, monitor your blood glucose levels closely when starting fisetin and consult your doctor, as medication adjustments may be necessary.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Metformin hydrochloride may increase the risk of hypoglycemia when combined with insulin and/or an insulin secretagogue.
Label source:
Action type:
monitor
Target id:
/procedure/surgery
Target name:
Surgery
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
336
Hours after target:
72
Description:
Due to its antiplatelet effects, fisetin can impair blood clotting and increase the risk of excessive bleeding during and after surgical procedures.
Actionable advice:
Fisetin should be discontinued at least 2 weeks prior to any scheduled surgery and should not be resumed until cleared by a surgeon.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
fisetin, butein, and sulfuretin were identified as effective inhibitors of platelet aggregation by collagen, thrombin, and adenosine-5'-diphosphate.
Label source:
PubMed: Journal of medicinal food (2015)
Source url:
Exact phrase from label:
The inhibitory effects of five flavonoids on the aggregation and secretion of platelets were studied. These flavonoids inhibited markedly platelet aggregation and ATP release of rabbit platelets induced by arachidonic acid or collagen, and slightly those by platelet-activating factor.
Label source:
PubMed: Thrombosis research (1991)
Source url:
Exact phrase from label:
we found that both RVS and fisetin could inhibit the coagulation of human peripheral blood cells.
Label source:
PubMed: Journal of medicinal food (2016)
Action type:
avoid
Target id:
/class/chemotherapy-radiation
Target name:
Cytotoxic Cancer Therapies (Chemotherapy & Radiation)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
As a potent antioxidant, fisetin could theoretically interfere with the pro-oxidant mechanisms of action of many chemotherapeutic agents and radiation therapy, potentially reducing their efficacy.
Actionable advice:
Fisetin and other potent antioxidant supplements should be strictly avoided during active cancer treatment unless specifically directed by an oncologist.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Some patients received post-operative radiation therapy in addition to surgery.
Label source:
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There is no safety data on the use of fisetin supplements during pregnancy. Due to unknown effects on fetal development, it is contraindicated.
Actionable advice:
Fisetin supplements should not be taken during pregnancy or when trying to conceive.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
NatMed Pro Monograph: Quercetin
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known whether fisetin or its metabolites are excreted into breast milk or what their effects might be on a nursing infant. Therefore, its use should be avoided.
Actionable advice:
Fisetin supplements should not be taken while breastfeeding.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
NatMed Pro Monograph: Quercetin
Action type:
avoid
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Fisetin may exert mild vasodilatory and blood pressure-lowering effects. This could be additive with prescribed antihypertensive drugs, potentially increasing the risk of hypotension (dizziness, lightheadedness).
Actionable advice:
It is a good idea to check blood pressure when initiating fisetin alongside medication to lower blood pressure.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Fisetin significantly relaxed fluoride-, thromboxane A2- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis.
Label source:
PubMed: Biomolecules & therapeutics (2016)
Source url:
Exact phrase from label:
The flavonoids are proved to have cardiovascular benefits based on a plethora of animal experiments over the last decade. Thus, the flavonoids or flavonoid-rich plant extracts endowed with anti-hypertension activities and probable mechanisms were reviewed.
Label source:
PubMed: Pharmacological research (2021)
Source url:
Exact phrase from label:
Fisetin, a biologically active flavonoid, and telmisartan, the highly selective competitive AT1 receptor antagonist, recently exhibited potent anti-inflammatory and immunomodulatory activities.
Label source:
PubMed: Pharmacological reports : PR (2019)
Action type:
monitor
Target id:
/intervention/quercetin
Target name:
Quercetin
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Fisetin and quercetin are structurally similar flavonoids with overlapping biological activities, including senolytic and anti-inflammatory effects. Taking them together may result in additive or synergistic benefits.
Actionable advice:
Consider that taking fisetin and quercetin together may enhance effects but also amplify shared side effects or drug interactions.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In the present study, high-throughput virtual screening was performed to evaluate the interaction between 4,4'-DPE and six aforementioned aging regulators, further validating its role as a natural senotherapeutic along with squalene and some well-known anti-aging botanicals (quercetin, curcumin, resveratrol, metformin, and fisetin).
Label source:
PubMed: Computational exploration of squalene analog 4,4'diapophytofluene as a potential anti-aging phytotherapeutic. (PMID 41671944)
Action type:
informational_none
Target id:
/dietary/hot-foods-beverages
Target name:
Hot Foods or Beverages
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Liposomal fisetin relies on a heat-sensitive phospholipid bilayer to protect and deliver its payload. Stirring it into a hot beverage (coffee, tea, soup) can melt or rupture the liposomes, destroying the enhanced-absorption advantage that is the entire point of the liposomal form.
Actionable advice:
Liposomal fisetin should not be added to hot drinks or food. It should be taken with cool or room-temperature liquid to keep the liposomes intact.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Mechanism / liposome thermal stability
Exact phrase from label:
Phospholipid liposomal delivery systems are thermally labile and lose bilayer integrity when exposed to hot liquids, negating the absorption advantage of the liposomal format.
Label source:
Mechanistic inference
Action type:
avoid
Derived From
fisetin
Provenance Note
Interactions duplicated from 'fisetin'. Liposomal formulation; same interactions.