Meta Information
ID:curcumin-and-piperine
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:
/class/cyp3a4-substrates
Target name:
Drugs Metabolized by CYP3A4
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Piperine strongly inhibits the CYP3A4 enzyme, which can dangerously increase the concentration of many common medications, including some statins, calcium channel blockers, and immunosuppressants.
Actionable advice:
Piperine can raise blood levels of CYP3A4 drugs (some statins, blood-pressure meds, immunosuppressants). Don't add high-dose curcumin+piperine to these without your prescriber adjusting the dose.
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:
avoid
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets (e.g., Warfarin, Aspirin, Clopidogrel)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Curcumin has antiplatelet properties, which can add to the effects of blood-thinning medications, significantly increasing the risk of bleeding and bruising.
Actionable advice:
Curcumin should be avoided with any blood-thinning medication unless specifically approved by a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties.
Label source:
Action type:
avoid
Target id:
/procedure/surgery
Target name:
Surgery
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
336
Hours after target:
null
Description:
Due to its blood-thinning effects, curcumin can increase the risk of excessive bleeding during and after surgical procedures.
Actionable advice:
This supplement should be stopped at least 2 weeks before any scheduled surgery.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Although crude curcumin is known to inhibit platelet aggregation, the effect of purified curcumin on platelet apoptosis, activation, and aggregation remains unclear.
Label source:
PubMed: Biochemistry. Biokhimiia (2024)
Source url:
Exact phrase from label:
Additionally, THC and curcumin attenuated murine thrombus growth in a FeCl3-induced mesenteric arteriole thrombosis model in C57BL/6J mice without prolonging the tail bleeding time.
Label source:
PubMed: Thrombosis and haemostasis (2022)
Source url:
Exact phrase from label:
All obtained data showed that incorporating curcumin in rapamycin-loaded PLGA coating can significantly decrease platelet adhesion and activation, prolong APTT clotting time as well as decrease the fibrinogen adsorption.
Label source:
PubMed: Colloids and surfaces. B, Biointerfaces (2007)
Action type:
informational_none
Target id:
/condition/bleeding-disorders
Target name:
Bleeding Disorders
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to its antiplatelet effects, curcumin can worsen bleeding tendencies in individuals with conditions like hemophilia or von Willebrand disease.
Actionable advice:
This should be strictly avoided with a diagnosed bleeding disorder.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Although crude curcumin is known to inhibit platelet aggregation, the effect of purified curcumin on platelet apoptosis, activation, and aggregation remains unclear.
Label source:
PubMed: Biochemistry. Biokhimiia (2024)
Source url:
Exact phrase from label:
C.oil failed to confer protection against cardiac injury, however significant reversal of ADP induced platelet aggregation (p<0.05) was evident in the same animals. Moreover, collagen and thrombin induced platelet aggregation (p<0.001) as well as tyrosine phosphorylation of various proteins in activated platelets was also suppressed.
Label source:
PubMed: Thrombosis research (2011)
Source url:
Exact phrase from label:
After 10 days of supplementation with Meriva® the average BT value was not significantly different for patients assuming acetylsalicylic acid, ticlopidine or clopidogrel at standard dosages.
Label source:
PubMed: European review for medical and pharmacological sciences (2018)
Action type:
avoid
Target id:
/condition/gallbladder-disease
Target name:
Gallbladder Disease or Bile Duct Obstruction
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Curcumin can stimulate gallbladder contractions, which may cause pain or complications in people with gallstones or a bile duct obstruction.
Actionable advice:
This supplement should be avoided with gallstones or other gallbladder problems.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.
Label source:
PubMed: Alimentary pharmacology & therapeutics (1999)
Source url:
Exact phrase from label:
The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01).
Label source:
PubMed: Asia Pacific journal of clinical nutrition (2002)
Source url:
Exact phrase from label:
In Experiment 3, gerbils were preloaded with cholesterol, followed by either PST alone or PST+curcumin to enhance gallbladder contraction.
Label source:
PubMed: The Journal of nutritional biochemistry (2005)
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:
High doses of curcumin may stimulate uterine contractions, and the safety of piperine and concentrated curcumin during pregnancy has not been established.
Actionable advice:
Supplemental curcumin and piperine should be avoided during pregnancy.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
Taking large amounts of curcumin during pregnancy may alter levels of the hormone estrogen in the body, which can cause uterine contractions or bleeding.
Label source:
Anecdotal: Medical News Today
Action type:
avoid
Target id:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors (e.g., Tacrolimus, Cyclosporine)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Piperine inhibits the metabolism of these critical immunosuppressants, which can lead to dangerously high levels, increasing the risk of kidney damage and other toxicities.
Actionable advice:
Absolutely avoid this supplement if you are taking immunosuppressants after an organ transplant.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Piperine has been reported to inhibit the enzyme activity of cytochrome P450 (CYP) 3A4. The aim of this study was to develop and validate a physiologically based pharmacokinetic (PBPK) model for piperine and to predict potential food-drug interactions (FDIs) between piperine and CYP3A4 substrate drugs using these models.
Label source:
PubMed: International journal of molecular sciences (2024)
Source url:
Exact phrase from label:
Piperine inhibited digoxin and cyclosporine A transport in Caco-2 cells with IC(50) values of 15.5 and 74.1 microM, respectively. CYP3A4-catalyzed formation of D-617 and norverapamil was inhibited in a mixed fashion, with K(i) values of 36 +/- 8 (liver 1)/49 +/- 6 (liver 2) and 44 +/- 10 (liver 1)/77 +/- 10 microM (liver 2), respectively.
Label source:
PubMed: The Journal of pharmacology and experimental therapeutics (2002)
Source url:
Exact phrase from label:
Curcumin, ginsenosides, piperine, some catechins from green tea, and silymarin from milk thistle were found to be inhibitors of Pgp, while some catechins from green tea increased Pgp-mediated drug transport by heterotropic allosteric mechanism, and St. John's wort induced the intestinal expression of Pgp in vitro and in vivo.
Label source:
PubMed: Drug metabolism reviews (2004)
Action type:
avoid
Target id:
/intervention/phenytoin
Target name:
Phenytoin
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Piperine significantly inhibits the metabolism of phenytoin, which can lead to toxic levels of the drug in the body, increasing the risk of severe side effects.
Actionable advice:
This should be strictly avoided if phenytoin is being taken for seizure control.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity.
Label source:
Action type:
avoid
Target id:
/intervention/theophylline
Target name:
Theophylline
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Piperine can slow the clearance of theophylline, a drug with a narrow therapeutic window, increasing the risk of toxicity (nausea, palpitations, seizures).
Actionable advice:
This combination should be avoided due to the high risk of theophylline toxicity.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Theophylline clearance may be further reduced by concomitant diseases prevalent in the elderly, which further impair clearance of this drug and have the potential to increase serum levels and potential toxicity.
Label source:
Action type:
avoid
Target id:
/class/chemotherapy-radiation
Target name:
Chemotherapy and Radiation
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Curcumin may interfere with the action of certain chemotherapy drugs, and piperine can alter their metabolism, leading to unpredictable toxicity or reduced effectiveness.
Actionable advice:
This supplement should not be taken during chemotherapy or radiation therapy unless 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:
The effect of tamoxifen on metabolism and excretion of other antineoplastic drugs, such as cyclophosphamide and other drugs that require mixed function oxidases for activation, is not known.
Label source:
Action type:
avoid
Target id:
/dietary/high-fat-meal
Target name:
Meal Containing Fats
Severity:
moderate
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Curcumin is a fat-soluble compound, and its absorption from the gut is significantly improved when consumed with dietary fats.
Actionable advice:
A dose is best taken with a meal that includes healthy fats like olive oil, avocado, or nuts.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Dietary intake of spices along with high-fat enhanced fat absorption. These dietary spices increased bile secretion with higher bile acid content.
Label source:
PubMed: Journal of the science of food and agriculture (2012)
Source url:
Exact phrase from label:
Many of these strategies improve upon the age-old practice of consuming turmeric in fat-based sauces, such as in a fat-rich yellow curry.
Label source:
PubMed: Journal of the American College of Nutrition (2015)
Source url:
Exact phrase from label:
Compared with the fasting treatment, co-ingestion with regular kibble reduced the absorption of curcumin in Cur-NEs and Cur-SWNTs.
Label source:
PubMed: Journal of the science of food and agriculture (2021)
Action type:
informational_none
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications (e.g., Metformin, Insulin, Sulfonylureas)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Curcumin may lower blood glucose levels, and when combined with diabetes medications, it can increase the risk of hypoglycemia (dangerously low blood sugar).
Actionable advice:
Blood sugar should be monitored closely, and it is important to talk to a doctor before use, as medication dosage may need adjustment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose.
Label source:
Action type:
monitor
Target id:
/class/cyp2c9-substrates
Target name:
Drugs Metabolized by CYP2C9
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Piperine inhibits the CYP2C9 enzyme, potentially increasing levels of drugs like warfarin and some NSAIDs, which can heighten their effects and side effects.
Actionable advice:
This is best used with caution and medical supervision when taking medications like warfarin or certain anti-inflammatory drugs.
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:
informational_none
Target id:
/class/p-glycoprotein-substrates
Target name:
P-glycoprotein Substrates
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Piperine inhibits the P-glycoprotein transporter, which can increase the absorption and decrease the elimination of certain drugs like digoxin and some chemotherapy agents, leading to toxicity.
Actionable advice:
This supplement is best avoided while taking drugs known to be P-glycoprotein substrates, such as digoxin, without medical approval.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Digoxin toxicity is also more likely in the presence of hypomagnesemia.
Label source:
Action type:
avoid
Target id:
/class/ugt1a1-substrates
Target name:
UGT1A1 Substrates
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Piperine inhibits the UGT1A1 enzyme, which is responsible for glucuronidation. This can increase levels of drugs like irinotecan (chemotherapy) and some statins.
Actionable advice:
It is important to consult a healthcare professional before use when taking medications metabolized by the UGT1A1 pathway.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Piperine caused a concentration-related strong inhibition of UDP-GDH (50% at 10 microM) reversibly and equipotently, in both tissues. piperine exerts stronger effects on intestinal glucuronidation than in rat liver.
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/8347144/
Action type:
informational_none
Target id:
/intervention/iron-bisglycinate
Target name:
Iron Supplements
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Curcumin can bind to (chelate) iron in the gut, potentially reducing its absorption. This is most relevant for individuals with or at risk for iron deficiency.
Actionable advice:
Curcumin doses and iron supplements should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Curcumin is a polyphenolic natural product for which there is increasing evidence of anti-inflammatory and iron chelation effects.
Label source:
PubMed: Effect of curcumin on inflammatory biomarkers and iron profile in patients with premenstrual syndrome and dysmenorrhea: A randomized controlled trial. (PMID 37394650)
Action type:
separate
Target id:
/class/herbal-anticoagulants
Target name:
Other Supplements with Blood-Thinning Effects (e.g., Ginkgo, Garlic, Fish Oil)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining curcumin with other supplements that have antiplatelet effects (like ginkgo, high-dose fish oil, garlic) can increase the overall risk of bleeding.
Actionable advice:
Caution is warranted, with awareness of increased bleeding or bruising risk, when combining with other blood-thinning supplements.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Here, we studied the mechanism of the antiplatelet action of curcumin.
Label source:
PubMed: Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. (PMID 10484074)
Action type:
informational_none
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is unknown if curcumin and piperine pass into breast milk or what effects they might have on an infant; it is best to avoid them.
Actionable advice:
This supplement is best not used while breastfeeding.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
No studies have been performed with ingestion of piperine-containing pharmaceutical products.
Label source:
Anecdotal: LactMed
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Liver Disease
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While often studied for liver benefits, high doses of curcumin have been linked to liver injury in rare cases. The impact of piperine on drug metabolism is also a concern in those with impaired liver function.
Actionable advice:
It is important to talk to a doctor before use with any form of liver disease.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The aim of this case series is to describe the clinical, histologic, and human leukocyte antigen (HLA) associations of turmeric-associated liver injury cases enrolled the in US Drug-Induced Liver Injury Network (DILIN).
Label source:
PubMed: Liver Injury Associated with Turmeric-A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN]. (PMID 36252717)
Action type:
informational_none
Target id:
/class/serms
Target name:
Hormone-Sensitive Therapies (e.g., Tamoxifen)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Curcumin may have weak hormonal effects that could potentially interfere with medications like tamoxifen used for hormone-sensitive cancers.
Actionable advice:
It is best avoided by those on hormone-based therapies for conditions like breast cancer.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The underlying mechanism is unknown, but may be related to the estrogen-like effect of tamoxifen.
Label source:
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:
Curcumin may have a mild blood pressure-lowering effect, which could be additive with antihypertensive drugs, potentially causing dizziness or hypotension.
Actionable advice:
It is a good idea to check blood pressure if this supplement is combined with blood pressure medication.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Curcumin/turmeric supplementation demonstrates a modest, yet significant reduction in SBP in individuals with prediabetes and diabetes, with a more pronounced effect in those with baseline hypertension.
Label source:
PubMed: Antihypertensive Effects of Curcumin/Turmeric Supplementation in Prediabetes and Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. (PMID 41388744)
Action type:
monitor
Target id:
/condition/gerd
Target name:
Gastroesophageal Reflux Disease (GERD)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In some individuals, curcumin and especially piperine can relax the lower esophageal sphincter, potentially worsening symptoms of acid reflux.
Actionable advice:
Use is best discontinued if a worsening of GERD or heartburn symptoms occurs.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
NatMed Pro: Curcumin monograph
Label source:
Expert review: Curcumin is documented to cause gastrointestinal side effects including reflux; piperine can stimulate gastric secretion and may affect lower esophageal sphincter (LES) tone as a spice compound; GI irritation is listed among common adverse effects of both compounds in clinical literature
Action type:
avoid