# Silibin (Silybin)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/silibin
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-03-29
**Evidence Score:** 2 / 10
**Category:** Compound
**Also Known As:** Silibinin, Silybin, Silybinin, Milk thistle flavonolignan, Silymarin A, Silybum marianum extract component

## Overview

Silybin (also spelled silibinin) is the primary bioactive flavonolignan derived from milk thistle (Silybum marianum) seed extract, accounting for roughly 50–60% of the silymarin complex. It exerts [hepatoprotective](/ingredients/condition/detox) and antioxidant effects primarily by scavenging [reactive oxygen species](/ingredients/condition/antioxidant), inhibiting [NF-κB](/ingredients/condition/inflammation) signaling, and stabilizing hepatocyte membrane permeability.

## Health Benefits

[{"benefit": "Exhibits direct [antioxidant activity](/ingredients/condition/antioxidant) by scavenging superoxide anion radicals and nitric oxide.", "evidence_quality": "Evidence is preliminary, based on in-vitro/cellular mechanism studies [1]."}, {"benefit": "Helps preserve the body's own antioxidant enzymes, including superoxide dismutase, catalase, and [glutathione](/ingredients/condition/detox) peroxidase.", "evidence_quality": "Evidence is preliminary, based on in-vitro/cellular mechanism studies [1]."}, {"benefit": "May reduce markers of cellular damage by decreasing malondialdehyde levels.", "evidence_quality": "Evidence is preliminary, based on in-vitro/cellular mechanism studies [1]."}, {"benefit": "Functions as an iron chelator, a mechanism observed in cellular models.", "evidence_quality": "Evidence is preliminary, based on in-vitro/cellular mechanism studies [1]."}, {"benefit": "Interacts with bile acid transporters, suggesting a role in influencing organic anion exchange within the body.", "evidence_quality": "Evidence is preliminary, based on in-vitro/cellular mechanism studies [2]."}]

## Mechanism of Action

Silybin directly scavenges superoxide anion radicals (O₂⁻) and nitric oxide (NO) while upregulating endogenous [antioxidant](/ingredients/condition/antioxidant) enzymes superoxide dismutase (SOD), catalase, and [glutathione](/ingredients/condition/detox) peroxidase. It inhibits NF-κB nuclear translocation, thereby suppressing [pro-inflammatory cytokine](/ingredients/condition/inflammation)s TNF-α and IL-6, and also blocks the enzyme RNA polymerase I in hepatocytes, reducing protein synthesis in activated stellate cells to slow fibrosis. Additionally, silybin modulates the PI3K/Akt and MAPK signaling cascades, influencing hepatocyte survival and apoptosis pathways.

## Clinical Summary

Human clinical data for silybin specifically (versus the broader silymarin complex) remains limited and mostly early-phase. A randomized controlled trial in 72 patients with non-alcoholic fatty liver disease (NAFLD) using a silybin-phosphatidylcholine-vitamin E complex (Realsil) over 12 months showed significant reductions in ALT, AST, and liver fibrosis markers compared to placebo. A separate study in 138 hepatitis C patients found oral silybin infusion reduced viral load, though effects were not sustained post-treatment. Overall, evidence is predominantly from in vitro studies, animal models, and small-to-moderate human trials, making definitive efficacy conclusions premature.

## Nutritional Profile

Silibinin (Silybin) is a purified flavonolignan compound, not a whole food ingredient, and therefore has no meaningful macronutrient, vitamin, or mineral profile in the traditional nutritional sense. It is a single bioactive molecule with a molecular weight of 482.44 g/mol (C25H22O10). As a compound, it contains no protein, fat, carbohydrates, fiber, vitamins, or dietary minerals. It is the primary active constituent of silymarin, the standardized extract of milk thistle (Silybum marianum) seeds, comprising approximately 50–70% of silymarin by weight. Silibinin itself exists as a diastereomeric pair: Silybin A and Silybin B, typically in roughly equal proportions. Bioavailability of free silibinin is notably poor due to low aqueous solubility and limited intestinal absorption, with oral bioavailability estimated at less than 1–5% for the unconjugated form. Phospholipid complexes (e.g., Silybin-Phosphatidylcholine, trade name Siliphos) have been shown to improve bioavailability by approximately 4–10 fold compared to unformulated silibinin. Peak plasma concentrations (Cmax) following a standard 140 mg oral dose of silymarin are typically in the nanomolar to low micromolar range for silibinin. It undergoes extensive phase II conjugation (glucuronidation and sulfation) in the intestine and liver, with conjugated metabolites being the predominant circulating forms. Half-life is approximately 6 hours. No caloric value is applicable.

## Dosage & Preparation

The research dossier does not specify any clinically studied dosage ranges for silybin in its various forms. Standardization details from clinical studies are not provided. Consult a healthcare provider before starting any new supplement.

## Safety & Drug Interactions

Silybin is generally well tolerated; the most commonly reported side effects are mild gastrointestinal symptoms including nausea, diarrhea, and bloating, particularly at higher doses exceeding 400 mg/day. It inhibits cytochrome P450 enzymes CYP3A4, CYP2C9, and CYP2D6, creating clinically relevant interactions with immunosuppressants (cyclosporine, tacrolimus), anticoagulants (warfarin), and certain statins. Silybin may enhance the hepatotoxic clearance of drugs metabolized by these enzymes and has demonstrated additive effects with some chemotherapy agents, requiring oncology supervision. Safety data in pregnancy and lactation is insufficient, so use is not recommended in these populations without physician guidance.

## Scientific Research

The provided research dossier lacks specific details on human clinical trials, randomized controlled trials, or meta-analyses for silybin. No PubMed PMIDs, study designs, sample sizes, or specific clinical outcomes were available in the source materials.

## Historical & Cultural Context

The provided research dossier contains no information regarding the historical or traditional use of silybin. Its context is presented solely as a modern, isolated constituent of silymarin from milk thistle.

## Synergistic Combinations

Information on ingredients that work synergistically with silybin is not available in the provided research dossier.

## Frequently Asked Questions

### What is the difference between silybin and silymarin?

Silymarin is the collective term for the standardized flavonolignan extract from Silybum marianum seeds, comprising silybin A, silybin B, isosilybin, silychristin, and silydianin. Silybin (silybin A + B isomers) represents approximately 50–60% of silymarin by weight and is considered the most pharmacologically potent component, with superior binding affinity to hepatocyte membranes compared to the other constituents.

### What is the recommended dosage of silybin for liver health?

Clinical studies on silybin (as the phosphatidylcholine complex, e.g., Siliphos or Realsil) have typically used doses of 94–188 mg silybin twice daily, equating to roughly 188–376 mg/day total silybin. Standard silymarin extracts standardized to 70–80% silymarin are often dosed at 420 mg/day in divided doses; because silybin has poor aqueous solubility, phospholipid-complexed forms demonstrate approximately 4.6-fold greater oral bioavailability than unconjugated silybin.

### Can silybin protect the liver from alcohol damage?

Preclinical and some clinical data suggest silybin attenuates alcohol-induced hepatotoxicity by suppressing lipid peroxidation, reducing ethanol-stimulated TNF-α production in Kupffer cells, and preserving mitochondrial glutathione levels. A study in alcohol-related liver disease patients observed improvements in liver enzyme profiles (ALT, AST, GGT), though evidence from large randomized trials is lacking and silybin should not be considered a substitute for alcohol cessation.

### Does silybin interact with chemotherapy drugs?

Silybin has demonstrated synergistic pro-apoptotic activity with cisplatin and doxorubicin in vitro, partly through inhibiting P-glycoprotein-mediated drug efflux and sensitizing cancer cells via downregulation of Bcl-2 expression. However, because silybin also inhibits CYP3A4 and P-glycoprotein, it can increase plasma concentrations of co-administered chemotherapy agents to potentially toxic levels, making concurrent use without oncologist supervision inadvisable.

### Is silybin effective for non-alcoholic fatty liver disease (NAFLD)?

The most rigorous clinical evidence comes from the NASH-IN trial using the silybin-phosphatidylcholine-vitamin E complex (Realsil, 94 mg silybin twice daily) in 138 patients over 12 months, which showed statistically significant reductions in ALT, AST, insulin resistance (HOMA-IR), and histological fibrosis scores versus placebo. While results are promising, the combination formula makes it difficult to isolate silybin's independent contribution, and current evidence is insufficient to recommend it as a first-line NAFLD therapy.

### What is the most bioavailable form of silybin for supplementation?

Silybin A (also called silybin-A) is the more bioavailable and biologically active isomer compared to silybin B, and some formulations use silybin phytosome or silybin complexed with phosphatidylcholine to enhance absorption. Standardized silymarin extracts typically contain both isomers, but isolated or enriched silybin-A formulations may offer superior bioavailability and clinical effectiveness. The presence of fat with silybin intake also improves absorption, as it is a lipophilic compound.

### Who should avoid silybin supplementation due to safety concerns?

Pregnant and nursing women should consult healthcare providers before using silybin supplements, as safety data in these populations is limited. Individuals with hormone-sensitive conditions (such as estrogen-dependent cancers or endometriosis) should exercise caution, as silybin may have weak estrogenic activity. People with allergies to plants in the Asteraceae family (ragweed, chrysanthemum, daisy) should be aware of potential cross-reactivity, though true allergic reactions to silybin are rare.

### How strong is the current clinical evidence supporting silybin's antioxidant benefits in humans?

While silybin demonstrates potent antioxidant activity in laboratory and cellular studies—including the ability to scavenge superoxide radicals and preserve endogenous antioxidant enzymes—human clinical trials remain limited and often involve small sample sizes. Most evidence of silybin's antioxidant effects comes from in-vitro and animal studies, with preliminary human data suggesting potential benefits, but larger randomized controlled trials are needed to establish clinical efficacy. The evidence quality for direct antioxidant benefits in living humans is therefore considered preliminary, distinct from its more established hepatoprotective effects in liver disease.

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