Trial reportDrug metabolism and disposition: the biological fate of chemicals2014
The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity.
Trial report in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- The Effects and Safety of Silymarin on β-thalassemia in Children and Adolescents: A Systematic Review based on Clinical Trial Studies.Reviews on recent clinical trials · 2024Pooled it
- Effect of Low-Furanocoumarin Hybrid Grapefruit Juice Consumption on Midazolam Pharmacokinetics.Journal of clinical pharmacology · 2017Trial
- Herbal Medicines and Drugs Interactions: Cytochrome P450 Responsibility.Current medicinal chemistry · 2026Review
- Brain Metastatic Lung Cancer Patients: A Multitarget Therapeutic-Supportive Strategy with Anti-STAT3 Silibinin.NeuroSci · 2025Article
- Natural Products That Protect Against Acetaminophen Hepatotoxicity: A Call for Increased Rigor in Preclinical Studies of Dietary Supplements.Journal of dietary supplements · 2025Review
- Milk Thistle (Current medicinal chemistry · 2025Review
- Silybin A fromTheranostics · 2025Article
- Silymarin Protects against Acute Liver Injury Induced by Acetaminophen by Downregulating the Expression and Activity of the CYP2E1 Enzyme.Molecules (Basel, Switzerland) · 2022Article
- A review of therapeutic potentials of milk thistle (Iranian journal of basic medical sciences · 2022Review
- HDI Highlighter, The First Intelligent Tool to Screen the Literature on Herb-Drug Interactions.Clinical pharmacokinetics · 2022Review
- Herb-Drug Interaction in Inflammatory Diseases: Review of Phytomedicine and Herbal Supplements.Journal of clinical medicine · 2022Review
- Enzyme Activity of Natural Products on Cytochrome P450.Molecules (Basel, Switzerland) · 2022Review
- Herb-Drug Interactions: Worlds Intersect with the Patient at the Center.Medicines (Basel, Switzerland) · 2021Review
- No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women.Journal of agricultural and food chemistry · 2020Article
- Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance.Life (Basel, Switzerland) · 2020Review
- Flavolignans from Silymarin as Nrf2 Bioactivators and Their Therapeutic Applications.Biomedicines · 2020Review
- Transcriptome profiling reveals Silibinin dose-dependent response network in non-small lung cancer cells.PeerJ · 2020Article
- Metabolism, Transport and Drug-Drug Interactions of Silymarin.Molecules (Basel, Switzerland) · 2019Review
- Herb-drug interactions: a novel algorithm-assisted information system for pharmacokinetic drug interactions with herbal supplements in cancer treatment.European journal of clinical pharmacology · 2019Article
- Interaction between phytotherapy and oral anticancer agents: prospective study and literature review.Medical oncology (Northwood, London, England) · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Milk thistle (Silybum marianum) extracts are widely used as a complementary and alternative treatment of various hepatic conditions and a host of other diseases/disorders. The active constituents of milk thistle supplements are believed to be the flavonolignans contained within the extracts. In vitro studies have suggested that some milk thistle components may significantly inhibit specific cytochrome P450 (P450) enzymes. However, determining the potential for clinically significant drug interactions with milk thistle products has been complicated by inconsistencies between in vitro and in vivo study results. The aim of the present study was to determine the effect of a standardized milk thistle supplement on major P450 drug-metabolizing enzymes after a 14-day exposure period. CYP1A2, CYP2C9, CYP2D6, and CYP3A4/5 activities were measured by simultaneously administering the four probe drugs, caffeine, tolbutamide, dextromethorphan, and midazolam, to nine healthy volunteers before and after exposure to a standardized milk thistle extract given thrice daily for 14 days. The three most abundant falvonolignans found in plasma, following exposure to milk thistle extracts, were silybin A, silybin B, and isosilybin B. The concentrations of these three major constituents were individually measured in study subjects as potential perpetrators. The peak concentrations and areas under the time-concentration curves of the four probe drugs were determined with the milk thistle administration. Exposure to milk thistle extract produced no significant influence on CYP1A2, CYP2C9, CYP2D6, or CYP3A4/5 activities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.