ArticleDrug metabolism and disposition: the biological fate of chemicals2013
An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review.Advances in therapy · 2020Pooled it
- Trial
- Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study.Clinical therapeutics · 2018Trial
- The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity.Drug metabolism and disposition: the biological fate of chemicals · 2014Trial
- Milk Thistle Treatment for Children and Adults with Trichotillomania: A Double-Blind, Placebo-Controlled, Crossover Negative Study.Journal of clinical psychopharmacologyTrial
- Shikonin Ameliorates Alcohol-Associated Liver Disease by Reducing Oxidative Stress, Apoptosis, and Inflammation.Food science & nutrition · 2025Article
- Isosilybin B: a potential novel therapeutic agent with hepatoprotective, anticancer and antifibrotic properties.Discover oncology · 2025Article
- Novel Micellar Formulation of Silymarin (Milk Thistle) with Enhanced Bioavailability in a Double-Blind, Randomized, Crossover Human Trial.Pharmaceutics · 2025Article
- Pharmaceutical technological trends containing flavonoids: a patent review.Future medicinal chemistry · 2025Review
- Silybin Cocrystals with Improved Solubility and Bioavailability.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Study on the preparation of stabilizer-free silymarin nanocrystals and its oral absorption mechanisms.International journal of pharmaceutics: X · 2024Article
- Silymarin: Unveiling its pharmacological spectrum and therapeutic potential in liver diseases-A comprehensive narrative review.Food science & nutrition · 2024Review
- Authentication of milk thistle commercial products using UHPLC-QTOF-ESI + MS metabolomics and DNA metabarcoding.BMC complementary medicine and therapies · 2023Article
- Myricitrin: A promising herbal therapy for periodontitis in immunosuppressed status.The Saudi dental journal · 2023Article
- Detecting and Profiling of Milk Thistle Metabolites in Food Supplements: A Safety-Oriented Approach by Advanced Analytics.Metabolites · 2023Review
- Synthesis, characterization and hepatoprotective effect of silymarin phytosome nanoparticles on ethanol-induced hepatotoxicity in rats.BioImpacts : BI · 2023Article
- Design and optimization of silymarin loaded in lyophilized fast melt tablets to attenuate lung toxicity inducedDrug delivery · 2022Article
- Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Chirality Matters: Biological Activity of Optically Pure Silybin and Its Congeners.International journal of molecular sciences · 2021Review
- Valuable Hepatoprotective Plants - How Can We Optimize Waste Free Uses of Such Highly Versatile Resources?Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Milk thistle (Silybum marianum) extracts, one of the most widely used dietary supplements, contain a mixture of six major flavonolignans (silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin) and other components. However, the pharmacokinetics of the free individual flavonolignans have been only partially investigated in humans. Furthermore, antioxidant effects of the extract, which may underlie the basis of many therapeutic effects, have not been thoroughly assessed. The present study evaluated the pharmacokinetics of the six major flavonolignans in healthy volunteers receiving single doses of either one (175 mg), two (350 mg), or three (525 mg) milk thistle capsule(s) on three separate study visits. Additionally, the steady-state pharmacokinetic parameters were determined after the subjects were administered one capsule three times daily for 28 consecutive days. Our results demonstrated that all six flavonolignans were rapidly absorbed and eliminated. In order of abundance, the exposure to free flavonolignans was greatest for silybin A followed by silybin B, isosilybin B, isosilybin A, silychristin, and silydianin. The systemic exposure to these compounds appeared linear and dose proportional. The disposition of flavonolignans was stereoselective, as evidenced by the apparent clearance of silybin B, which was significantly greater than silybin A, whereas the apparent clearance of isosilybin B was significantly lower than isosilybin A. The concentrations of urinary 8-epi-prostaglandin F2α, a commonly used biomarker of oxidative status in humans, were considerably decreased in study subjects after a 28-day exposure to the extract (1.3 ± 0.9 versus 0.8 ± 0.9 ng/mg creatinine) but failed to reach statistical significance (P = 0.076).
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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.