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Caring SunshineIngredientes

silimarina

Condiciones de Salud38
Tabla de contenidos

Otros Nombres

Artichaut sauvageBlessed milk thistleBlessed milkthistleCardo de Santa MaríaCardo di Santa MariaCardo marianoCardo-leiteiroCarduus marianusCarduus marianus L.CCRIS 7096Chardon argentéChardon de Notre-DameChardon marbréChardon-MarieEchte MariendistelÉpine blancheFlavobionFlavonolignan complexFructus SilybiGaidouragathoHarilik maarjaohakasHoly thistleKhar MaryamLady's thistleLait-de-Notre-DameMaarianohdakeMari TiqalMariadistelMarian thistleMariana lactea HillMariana mariana (L.) HillMariatistelMáriatövisMariendistelMarietidselMary thistleMediterranean milk thistleMilk thistleMilk thistle extractMilk thistle flavonolignan complexMilk thistle seed extractNSC 4733Ostropest plamistyOstropestřec mariánskýOur Lady's thistleSaint Mary's thistleScotch thistleSemen Cardui MariaeShawk SennariShook ElgamalShui Fei JiSilybe de MarieSilybonSilybum marianum (L.) Gaertn.Silybum marianum extractSilymarin groupSt Mary's milk thistleSt. Mary thistleTikrasis margainisVariegated thistleWild artichokeРасторопша пятнистаяגדילן מצויマリアアザミ水飞蓟

Sinopsis

Silymarin

1. Identity: Botanical Source, Chemical Name, and Nomenclature

Silymarin is not a single compound but rather a polyphenolic flavonolignan complex extracted from the seeds (technically the fruits) of Silybum marianum (L.) Gaertn., the plant commonly known as milk thistle. Silybum marianum is a flowering plant native to the Mediterranean and is particularly renowned for its longstanding use in liver-related disorders. The plant belongs to the family Asteraceae and its extracts are widely used as dietary supplements due to anti-inflammatory, antitumor, and hepatoprotective effects.

The genus name Silybum was designated by the ancient Greek physician Dioscorides, while the species name marianum derives from Christian legend, in which drops of the Virgin Mary's milk fell upon thistle leaves, leaving distinctive white markings. The plant is also known by a range of common names including cardus marianus, blessed milkthistle, Marian thistle, Mary thistle, Saint Mary's thistle, Mediterranean milk thistle, variegated thistle, and Scotch thistle. This fairly typical thistle has red to purple flowers and shiny pale green leaves with white veins.

The crude commercial product of milk thistle is termed silymarin, a complex of at least 7 flavonolignans and 1 flavonoid that comprises 65% to 80% of milk thistle extract. The main components of lipophilic extracts of milk thistle seeds are flavonoids and flavonolignans including silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, taxifolin, and 2,3-dehydrosilybins. In standardized preparations, the complex includes approximately 70–80 percent silymarin flavonolignans and the remaining 20–30 percent consists of a chemically undefined fraction comprised of polymeric and oxidized polyphenolic compounds.

Silybin is the most abundant and active component of the silymarin complex. Silibinin (INN) is a semipurified fraction derived from silymarin, once thought to be a single compound but now recognized as a 1:1 mixture of two diastereoisomers, silybin A and silybin B. The distinction between silymarin and silibinin is not only important to understanding the historical literature, but thorough characterization and use of chemically defined mixtures in preclinical and clinical studies are essential to the progress of these botanical compounds as human therapeutics.

Most flavonolignans in silymarin are constitutional isomers with the molecular formula C25H22O10. Silymarin belongs to a subclass of plant-based compounds called flavonolignans, which are part of the larger flavonoid family. The seeds contain the highest concentration of silymarin, including its major isomers silybin A and silybin B, along with isosilybin A, isosilybin B, silydianin, silychristin A, silychristin B, and taxifolin.

2. Traditional and Historical Use

Historical records trace the medicinal use of milk thistle back over 2,000 years. Theophrastus (371–287 BC) was the first to mention milk thistle as Pternix, showing its long history of medicinal use. Both Pliny the Elder and Dioscorides described its uses in their works. The Roman naturalist Pliny the Elder, writing in his Naturalis Historia, reportedly recommended the plant for liver ailments.

For centuries, silymarin has been used extensively in traditional medicine throughout Europe and beyond, historically being prescribed for jaundice and a number of hepatobiliary conditions. In cases of food poisoning caused by hepatotoxic fungi, particularly Amanita species, preparations of milk thistle seeds were utilised as an antidotal remedy. Various plant parts were used for a variety of therapeutic purposes in traditional European folk medicine; the aerial parts were advised for uterine disorders, dropsy, and intermittent fevers.

By the 16th century, milk thistle was recognized as an effective remedy for liver and gallbladder disorders. Nicholas Culpeper noted silymarin's effectiveness for treating blockages in the spleen and liver. In medieval times, monks in monastic gardens cultivated it as a staple of their medicinal herb collections, using it to treat everything from jaundice to digestive issues.

Historically, milk thistle fruits were roasted and used as a coffee substitute; flower heads were prepared like artichokes and leaves were used in salads or as a spinach alternative; while in European folk medicine, roots, bark, leaves, and immature fruits were employed to treat gastroenteritis, diarrhea, and dysentery.

Early European colonists brought milk thistle to the Americas, and by the early 20th century, herbalists used it to treat issues related to the kidneys, liver, spleen, and menstruation. Traditional Chinese Medicine incorporated the herb for clearing heat and toxins from the body. Historically, milk thistle was also used to increase breast milk production.

This long history of traditional use laid the groundwork for modern scientific investigation, which began in earnest in the 1960s when German researchers isolated silymarin and started studying its hepatoprotective properties.

From a regulatory standpoint, in 2018, the European Medicines Agency published an assessment report on the oral use of milk thistle fruit and its extracts in EU states, finding that there is a "well-established use" of hepatoprotection approved by 11 countries and a "traditional use" of dyspeptic complaints in 4 countries. The European Medicines Agency (EMA/HMPC) recognises certain milk thistle seed preparations for traditional use in the relief of digestive discomfort, based on long-standing, widespread use across Europe; traditional use recognition is not the same as a clinical disease claim, but it does reflect decades of accepted botanical practice backed by regulatory review.

3. Key Constituents and Active Compounds

The major individual flavonolignans in silymarin have distinct pharmacological profiles. Silymarin, a polyphenolic flavonolignan complex, has long been recognized for its hepatoprotective, antioxidant, anti-inflammatory, and anticancer properties; among its constituents, silybin is the most pharmacologically active and has been extensively studied in both preclinical and clinical settings.

  • Silybin (Silibinin): The major active constituent of silymarin; silibinin itself is a mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio.
  • Isosilybin A and Isosilybin B: Diastereomeric pair also present in significant quantities in the complex.
  • Silychristin A and B: Additional flavonolignans contributing to the overall bioactivity of the complex.
  • Silydianin: A flavonolignan isomer present in the complex.
  • Taxifolin: A flavonoid present in the primary extract of milk thistle, along with the flavonolignans and a number of other constituents.

Fourteen volunteers who consumed an extract of milk thistle were found to absorb and metabolize silychristin, silydianin, silybin, and isosilybin isomers, with 31 metabolites identified in urine, monoglucuronides being the most common excreted form, followed by sulphate-glucuronides and diglucuronides.

4. Mechanisms of Action

4.1 Antioxidant Activity

In the modern era, silymarin exhibits potent antioxidant and anti-inflammatory properties; it stabilises cellular membranes, enhances glutathione levels, scavenges reactive oxygen species (ROS), and modulates inflammatory pathways including NF-κB and Nrf2. Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation, is considered the main driving force of silymarin's antioxidant action.

4.2 Anti-inflammatory Activity

Silymarin activates the Nrf2/ARE pathway, which enhances transcription of phase II enzymes such as heme oxygenase-1, glutathione peroxidase, superoxide dismutase, and catalase, thereby supporting the glutathione pool and limiting reactive oxygen species; in parallel, it suppresses the NF-κB pathway by preventing IκB degradation and nuclear translocation, leading to reduced transcription of pro-inflammatory mediators such as TNF-α, IL-1β, IL-6, COX-2, and iNOS; the convergence of these pathways results in lower oxidative stress, decreased cytokine-driven injury, and protection against apoptosis and necrosis.

4.3 Hepatocellular Mechanisms

Different mechanisms of action of silymarin on hepatocytes include: increasing the regenerative ability of liver cells by enhancing the synthesis of DNA and RNA; altering the structure of the hepatocyte external membrane, preventing entrance of xenobiotics into the cell (as in Amanita mushroom poisoning); scavenging free radicals and increasing cellular glutathione content, leading to inhibition of lipid peroxidation; and modifying the transporters and receptors of cell membranes such as ABC transporters (P-gp), organic anion uptake transporter peptides (OATP), bile salt export pump, and TNF-α-dependent transporters.

Within hepatocytes, silymarin shows a high affinity for membrane-bound and nuclear receptors, including PPAR-α and CAR/PXR, by enhancing the expression of hepatic detoxification enzymes and improving xenobiotic clearance. Its mitochondrial interaction occurs primarily through the stabilisation of mitochondrial membranes and modulation of oxidative phosphorylation, preserving ATP synthesis while preventing cytochrome c leakage and subsequent apoptosis.

4.4 Signalling Pathway Modulation

Mechanistic studies have clarified that silymarin's major bioactive constituents, like silibinin, silydianin, and silychristin, interact with redox-sensitive transcriptional pathways such as Nrf2/ARE and NF-κB, while also influencing metabolic regulators like AMPK and SIRT1. These synergise with receptor-mediated activation of Nrf2 and inhibition of NF-κB, promoting antioxidant defence; moreover, by attenuating MAPK–ERK and PI3K/Akt/mTOR signalling cascades, silymarin reduces oxidative stress, thereby prolonging hepatocellular survival and optimising pharmacokinetic stability through improved metabolic resilience.

4.5 Anti-fibrotic Activity

Existing research reveals that silymarin has potent antioxidant and anti-inflammatory effects, coupled with anti-fibrotic, anti-carcinogenic, neuro-regenerative, and immunomodulatory actions, and has broad therapeutic relevance in both neurological and hepatic disorders.

5. Scientific Evidence by Area of Use

5.1 Liver Disease and Hepatoprotection

The hepatoprotective application of silymarin is the most studied and the one with the longest regulatory history. The hepatoprotective, anti-inflammatory, antioxidant, and anti-fibrotic effects of silymarin have been studied in patients with cirrhosis associated with viral hepatitis, exposure to environmental toxins, alcoholic steatosis, and non-alcoholic steatohepatitis (NASH).

A 2023 systematic review focusing on liver enzyme levels identified 29 studies examining silymarin. Silymarin dosages in these studies ranged from 140 mg to 420 mg, administered for various durations; results revealed that 65.5% of the studies reported reduced liver enzyme levels, 20.7% exhibited no significant change, and 13.8% observed elevated liver enzymes; the review implies a potential advantageous influence of silymarin on liver enzyme levels, but outcome disparities may stem from comorbidities, suboptimal doses, and underlying diseases.

Non-alcoholic steatohepatitis (NASH) / Non-alcoholic fatty liver disease (NAFLD): A trial involving 64 patients with NASH showed substantial reductions in ALT and AST levels after just eight weeks of treatment with 210 mg/day of silymarin. In addition to lowering liver enzyme levels, silymarin has been associated with histological improvements; a double-blind, placebo-controlled trial reported significant reductions in fibrosis scores among patients treated with 700 mg/day of silymarin over 48 weeks, suggesting a potential role in enhancing liver health and slowing NAFLD progression.

A separate randomized, double-blind, placebo-controlled trial conducted in Malaysia enrolled patients with biopsy-proven NASH with a NAFLD Activity Score of 4 or more. Patients were randomized to receive either silymarin 700 mg three times daily or placebo for 48 weeks. An inverse relationship was noted between silymarin use and the progression from fibrosis to cirrhosis.

A US multicenter Phase II trial (the Siliver trial) tested the proprietary standardized preparation Legalon®. Eligible adult patients had liver biopsy showing NASH without cirrhosis; participants were randomized to Legalon® 420 mg, 700 mg, or placebo three times daily for 48 weeks, with the primary endpoint being histological improvement of ≥2 points in NAS; of 116 patients screened, 78 were randomized, with no significant differences in adverse events among the treatment groups.

A systematic review with meta-analysis including six clinical trials showed that silymarin reduced serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in NAFLD patients, but significant variability and methodological differences across available studies prevent the establishment of robust conclusions.

Cirrhosis: A large randomized controlled trial performed in the pre-liver transplantation era indicated that long-term treatment with silymarin may decrease mortality in patients with cirrhosis, mostly in those consuming ethanol.

Hepatitis C: The impact of silymarin on chronic hepatitis B and C has also been investigated; while some studies suggest benefits in improving liver function tests, evidence regarding its direct influence on viral load remains inconclusive. Higher-than-usual-dose silymarin failed to produce a satisfactory anti-hepatitis C virus (HCV) effect in a large randomized controlled trial, possibly because of the poor bioavailability of silymarin, which led to plasma concentrations far below the levels used in in vitro experiments.

Overall liver evidence assessment: There isn't enough high-quality evidence to allow definite conclusions to be reached about the effects of milk thistle on health conditions in people. In most clinical trials, a better definition of endpoints—such as the progression of fibrosis or the reduction of transaminase levels—is needed, and well-designed, double-blind, placebo-controlled studies are still required.

5.2 Amanita Mushroom Poisoning

One of the most clinically established applications of silymarin, particularly its isolated constituent silibinin, is in the treatment of poisoning by Amanita phalloides and related hepatotoxic fungi. Intravenous silibinin (specifically the water-soluble form silibinin-C-2′,3-dihydrogen succinate disodium, trade name Legalon SIL) is approved in Europe for Amanita poisoning. This is distinct from oral silymarin supplementation and represents a formal pharmaceutical application.

5.3 Type 2 Diabetes Mellitus

Results from a small number of studies in people show that milk thistle extracts may help to control blood sugar in people with type 2 diabetes; most of this research was done in Middle Eastern countries, and it is unclear whether the same results would be seen in other parts of the world.

In a systematic review and meta-analysis including five randomized controlled trials and 270 patients, routine silymarin administration was associated with a significant reduction in fasting blood glucose levels (−26.86 mg/dL; 95% CI −35.42–18.30) and HbA1c levels (−1.07; 95% CI −1.73–0.40) and had no effect on lipid profile. Benefits for silymarin on proteinuria and CKD progression are reported in only one small study and are uncertain; being aware of the low quality of the available evidence and elevated heterogeneity of these studies, no recommendation can be made and further studies are needed.

A separate 2021 meta-analysis of seven trials with 350 patients found that silymarin supplementation can decrease fasting blood sugar, hemoglobin A1C, and LDL-cholesterol, but has no effect on total cholesterol or total triglyceride; the available evidence is nonetheless considered insufficient to make firm conclusions.

A triple-blinded randomized controlled clinical trial involving 40 type 2 diabetes patients (25–50 years of age, on stable medication) tested 140 mg of silymarin three times daily for 45 days. Silymarin supplementation led to significant reductions in fasting blood sugar, serum insulin, homeostatic model assessment for insulin resistance, serum triglyceride, and triglyceride-to-HDL cholesterol ratio compared to placebo. However, not all trials have replicated these findings. In one open-label randomized clinical trial, daily consumption of three capsules of 140 mg silymarin for 12 weeks did not show any significant difference on the level of fasting blood sugar or HbA1c.

5.4 Drug-Induced Liver Injury Prevention

Silymarin has been investigated for its ability to prevent liver injury induced by drugs and toxins. A double-blind randomized placebo-controlled trial examined its ability to prevent antituberculosis drug-induced liver injury (DILI). The trial aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug-induced liver injury in patients with tuberculosis, with tuberculosis patients randomly allocated to receive placebo or silymarin.

A small clinical trial (60 patients) also investigated silymarin's renoprotective potential in cisplatin-based chemotherapy. Sixty patients with malignancy as candidates for cisplatin treatment were randomly enrolled in two equal groups; in the case group, silymarin tablet 140 mg twice daily was administered seven days before cisplatin administration together with cisplatin. This study showed that silymarin can decrease cisplatin nephrotoxicity, supporting its use as prophylaxis in various cisplatin-containing chemotherapy regimens.

5.5 Cancer — Preclinical and Preliminary Clinical Evidence

Abundant evidence has proved the chemo-preventive activity of silymarin against cancer both in vitro and in vivo; silymarin has the ability to modulate apoptosis in vitro and survival in vivo by intervention in the expression of cell cycle regulators and proteins related to apoptosis. Silymarin modulates the imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis; it also showed anti-inflammatory as well as anti-metastatic activity.

The protective effects of silymarin and its major active constituent, silibinin, studied in various tissues, suggest a clinical application in cancer patients as an adjunct to established therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity.

With respect to clinical translation, in one study, a high dose of silibinin (13 g daily) was administered to patients prior to prostatectomy, achieving high plasma concentrations, but nevertheless low levels of silibinin were found in prostate tissue; in an attempt to circumvent this, one group used a silymarin-phosphatidylcholine compound administered orally as a daily dose of 2.8 g for 4 weeks prior to surgery, achieving high levels in human breast cancer tissue—an encouraging signal for a Phase II clinical trial.

In oncology, combinations involving curcumin or vincristine have demonstrated preclinical efficacy against NF-κB-mediated resistance; however, clinical validation has not been conducted. Cancer Research UK stated in 2019: "We need a lot more research with reliable clinical trials before we can be sure that milk thistle will play any part in treating or preventing cancers." Overall, evidence from human clinical trials for cancer indications remains very preliminary.

5.6 Neuroprotection

Apart from the hepatoprotective nature, silymarin has recently been reported to be a putative neuroprotective agent against many neurologic diseases including Alzheimer's and Parkinson's diseases, and cerebral ischemia; the underlying neuroprotective mechanism is believed to be due to its capacity to inhibit oxidative stress in the brain, but it also confers additional advantages by influencing pathways such as β-amyloid aggregation, inflammatory mechanisms, cellular apoptotic machinery, and estrogenic receptor mediation.

Neuroprotective evidence in support of silymarin has been documented not only in animal models of neurodegenerative diseases but also in neuronal and non-neuronal cellular models of Alzheimer's disease, cerebral ischemia, and Parkinson's disease. However, reports on the effect of silymarin on other central nervous system disorders where oxidative stress plays a pivotal role, such as Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are lacking. Robust human clinical trials in neurological indications are absent at this time; the available evidence is preclinical.

5.7 Chemotherapy-Associated Complications

A triple-blinded randomized clinical trial evaluated nano-silymarin for the prevention of hand-foot syndrome and neuropathy induced by chemotherapy regimens (XELOX or m-FOLFOX6) in metastatic colorectal cancer. Numerous pre-clinical and clinical studies have examined the effectiveness of silymarin in preventing and treating complications caused by chemotherapeutic agents; however, there is a limited number of well-designed randomized clinical trials on this potential effect of silymarin, and further studies are considered crucial.

6. Dosage Forms and Reported Dosages

6.1 Common Dosage Forms

  • Standardized oral capsules/tablets: Modern supplements typically use a standardized extract of milk thistle containing a specific percentage of silymarin (usually 70–80%) to ensure consistent potency and effectiveness.
  • Phosphatidylcholine (phytosome) complex: Preparations containing phospholipids such as phosphatidylcholine may increase absorption of silymarin and its silybin constituent. Plasma levels of silybin were significantly higher after the administration of silybin–phosphatidylcholine complex capsules compared with that after conventional silymarin tablets.
  • Intravenous formulation: In some European countries, silibinin is available as a water solution containing the dihemisuccinate disodium salt for intravenous injection.
  • Dried fruit / teas: Dosage for the dried fruits is 4–9 g and for the liquid extract 1:1 is 4–9 ml.

6.2 Dosages Reported in Clinical Studies

  • Dosing regimens in studies range from an equivalence of 140 mg of standardized silymarin daily to 900 mg daily.
  • Recommended dosing of silymarin is a range from 70 to 140 milligrams three times per day in various disease conditions.
  • In a triple-blinded diabetes trial, patients received 140 mg of silymarin three times daily (420 mg/day) for 45 days.
  • A trial involving 64 NASH patients used 210 mg/day of silymarin for eight weeks.
  • A double-blind, placebo-controlled fibrosis trial used 700 mg/day of silymarin over 48 weeks.
  • A NASH trial randomized patients to receive either silymarin 700 mg three times daily (2,100 mg/day) or placebo for 48 weeks.
  • A US multicenter Phase II NASH trial randomized participants to Legalon® 420 mg or 700 mg three times daily for 48 weeks.
  • In the cisplatin nephrotoxicity prevention study, silymarin 140 mg twice daily was administered seven days before and during cisplatin administration.
  • Silymarin has been shown to be safe for human consumption at therapeutic doses, even in doses of 700 mg three times daily (2,100 mg/day) for up to 24 weeks.
  • The Health Canada NHP monograph cites a maximum daily therapeutic dose of 600 mg per day of silymarin, with a further recommended maximum single-dose limit of 200 mg.
  • The ESCOP monograph (2009) describes the use of milk thistle fruit for treatment of toxic liver damage and supportive treatment of chronic inflammatory liver conditions, with dosage for the extract corresponding to 165–330 mg silymarin.

7. Pharmacokinetics and Bioavailability

The clinical application of silymarin-based therapies remains limited by poor aqueous solubility, low oral bioavailability, rapid metabolism, and physicochemical instability. Silymarin has oral absorption of only about 23–47% and undergoes quick phase II conjugation, leading to low bioavailability. Silymarin's bioavailability is notably low, averaging about 0.95%, primarily due to poor solubility in water and extensive phase II metabolism.

Orally administered silymarin has a peak concentration (tmax) occurring between 2 and 4 hours and has a half-life of approximately 6 hours; however, only 20–50% of oral silymarin is absorbed from the gastrointestinal tract, where it undergoes extensive enterohepatic circulation. Silymarin undergoes phase I and phase II metabolism, especially phase II conjugation reactions, undergoing multiple conjugation reactions, and is primarily excreted into bile and urine.

After absorption, silymarin undergoes rapid phase II metabolism and is primarily excreted into bile and urine; it exhibits enhanced absorption in patients with hepatitis C and non-alcoholic fatty liver disease. The major efflux transporters of silybin are multidrug resistance-associated protein (MRP2) and breast cancer resistance protein (BCRP).

Clinical trials have shown silymarin is safe at high doses (>1500 mg/day) in humans; however, pharmacokinetic studies over the past three decades related to absorption, distribution, metabolism, and excretion have revealed poor absorption, rapid metabolism, and ultimately poor oral bioavailability. Newer formulation strategies, including phospholipid complexes and nanoparticle-based delivery systems, have been developed to address this limitation. Nanocarriers are a promising solution to silymarin's low solubility and limited bioavailability, aiming to enhance targeted delivery to the central nervous system and hepatic tissue.

8. Safety Considerations and Drug Interactions

8.1 General Safety Profile

Toxicological studies have shown that tolerability of silymarin is suitable, and its adverse effects are mainly limited to negligible allergic reactions, gastrointestinal disorders, headache, nausea, itching, and urticaria. In human and animal studies, silymarin has shown no specific serious side effects; in rare cases, its use has been associated with gastrointestinal symptoms, headaches, confusion, and skin reactions.

Very few side effects from the use of milk thistle or silymarin have been reported; several large studies in patients with liver disorders have found that taking silymarin may rarely have a laxative effect or cause nausea, heartburn, or stomach upset; at high doses, mild allergic reactions have been seen.

8.2 Allergic Reactions

Milk thistle may cause allergic reactions, particularly among people who are allergic to related plants (for example, ragweed, chrysanthemum, marigold, and daisy).

8.3 Drug Interactions

Clinical trial data concluded that silymarin does not pose a clinically relevant risk of drug–drug interaction; although silymarin does inhibit activities of enzymes and transporters concerned with the pharmacokinetics of therapeutic drugs, its concentration within the human body rarely reaches the point that constitutes significant inhibition due to low bioavailability; however, exceptions do exist.

Silymarin has limited effect on the pharmacokinetics of several drugs in vivo, despite decreasing the activity of cytochrome P-450 (CYP) enzymes, UDP-glucuronosyltransferase (UGT) enzyme, and reducing P-glycoprotein (P-gp) transport. In vitro, the enzymes most commonly flagged for potential inhibition include CYP3A4 and CYP2C9, and silymarin may also affect P-glycoprotein transporter function.

Oral administration of silibinin at daily doses up to 1.44 g over a week has been established as safe in clinical studies.

8.4 Product Quality Concerns

Concerns have been raised about poor chemical and microbiological quality of milk thistle dietary supplements sold in the United States and other countries; some products have been found to contain amounts of silymarin substantially different from what's stated on the label, or to be contaminated with pesticides, microorganisms, or mycotoxins.

8.5 Regulatory Status

The U.S. Food and Drug Administration (FDA) has not approved the use of milk thistle as a treatment for cancer or any other medical condition. In the United States, silymarin/milk thistle is sold as a dietary supplement and is not subject to the same pre-market approval requirements as pharmaceutical drugs. As noted, in Europe, intravenous silibinin dihemisuccinate disodium (Legalon SIL) carries specific approval for Amanita phalloides poisoning in several countries.

References

Condiciones de Salud

Condiciones de salud que silimarina puede ayudar a apoyar.

  • AbscesosCientífico

    A published split-face clinical trial in the Journal of Cutaneous Medicine and Surgery (2024) evaluated topical silymarin cream vs. salicylic acid peels in acne vulgaris, demonstrating clinical efficacy for silymarin. Its anti-inflammatory and immunomodulatory mechanisms (TNF-α, IL-1α suppression, COX/LOX inhibition) are well-characterized. It is used in cosmetic and dermatological preparations for acne.

  • HipocondríaCientífico

    Silymarin, a flavonolignan complex from Silybum marianum (milk thistle), has well-documented antioxidant activity supported by human clinical trials and systematic reviews. It scavenges reactive oxygen species (ROS), elevates intracellular glutathione, and upregulates endogenous antioxidant enzymes (SOD, CAT, GPx) via Nrf2 pathway activation. A 2025 meta-analysis of 16 RCTs confirmed significant reductions in oxidative stress markers (MDA, CRP) and increases in antioxidant enzyme activity (SOD, GPx) following silymarin supplementation.

  • Silymarin's immunomodulatory effects—suppression of NF-κB, TNF-α, and T-cell-mediated inflammation—have led to investigation in autoimmune contexts. Documented uses include rheumatoid arthritis and lupus considerations in dermatological and pharmacological literature. Evidence is preliminary and largely mechanistic; controlled human RCTs for specific autoimmune diseases are very limited.

  • Multiple RCTs and meta-analyses demonstrate that silymarin significantly lowers fasting blood glucose and HbA1c in type 2 diabetes patients. A 2021 meta-analysis of 7 RCTs (350 patients) found significant reductions in FBS and HbA1c. A 2024 dose-response meta-analysis of 33 trials (1,943 participants) confirmed a mean FBG reduction of approximately 21.7 mg/dL vs. placebo. Effects appear most robust as adjunctive therapy alongside standard hypoglycemic agents.

  • Silymarin demonstrates osteogenic activity in cell and animal studies, promoting osteoblast differentiation, alkaline phosphatase expression, and osteocalcin production. An in vitro and animal study found silymarin enhanced bone mineral density in tibia-fractured mice. Human clinical trials specifically for bone density are not yet published.

  • Clinical evidence indicates silymarin modestly but significantly reduces total cholesterol, LDL, and triglycerides. A 2024 dose-response meta-analysis of 33 RCTs (1,943 participants) found TC reduced by ~14 mg/dL, LDL by ~17 mg/dL, and TG by ~26 mg/dL vs. placebo. Proposed mechanisms include partial HMG-CoA reductase inhibition, reduced cholesterol absorption, and improved LDL receptor expression. HDL effects are inconsistent.

  • ApendicitisCientífico

    Silymarin, a flavonolignan complex extracted from milk thistle (Silybum marianum), has documented anti-inflammatory activity supported by both mechanistic research and human clinical trials. It suppresses key pro-inflammatory signaling cascades—notably NF-κB, MAPK, and JAK-STAT3—reducing cytokines such as TNF-α, IL-1β, and IL-6 while elevating the anti-inflammatory cytokine IL-10. A 2025 meta-analysis of 11 randomized controlled trials found statistically significant reductions in CRP and oxidative stress markers, though evidence for long-term effects on chronic inflammation remains incomplete.

  • IncontinenciaCientífico

    Silymarin has documented neuroprotective effects in Alzheimer's disease and cognitive impairment models, reducing amyloid-beta deposition and neuroinflammation. Multiple review papers in peer-reviewed journals have catalogued its evidence base for cognitive protection. Evidence is predominantly preclinical (animal and cell models); controlled human trials for cognitive outcomes are very limited.

  • Silymarin, the flavonolignan complex from milk thistle (Silybum marianum), showed positive results in a small randomized, double-blind, placebo-controlled clinical trial in UC patients. It suppresses NF-κB, reduces TNF-α and IL-1β in colonic tissue, and an ongoing registered RCT (NCT06213857) is further evaluating its efficacy in UC.

  • Silymarin has been studied for antidepressant activity in preclinical models and documented in a 2023 Frontiers in Neuroscience systematic review as having potential across psychiatric disorders including depression, operating via antioxidant, anti-inflammatory, and pro-estrogenic pathways. Human RCT data specific to depression diagnosis is very limited.

  • Silymarin has been studied in formulations for atopic dermatitis, with clinical evaluation of organogel formulations documented in the literature. Its mechanisms (NF-κB suppression, TNF-α reduction, antioxidant activity) are relevant to the inflammatory pathophysiology of dermatitis. It is included in cosmetic and therapeutic topical preparations for inflammatory skin conditions.

  • Silymarin, specifically its purified component silibinin (silybin), has documented clinical use as an antidote to Amanita phalloides (death cap mushroom) poisoning. It blocks hepatocellular uptake of amatoxins via competitive inhibition. Intravenous silibinin (Legalon-SIL) has been used in European emergency settings with high survival rates. It also shows hepatoprotection against drug-induced and chemotherapy-related liver toxicity in clinical trials.

  • Silymarin, the active flavonolignan complex from milk thistle, reduces biliary cholesterol saturation and gallstone lithogenicity. A 3-month clinical study in gallstone patients showed significantly improved bile composition. Combined with artichoke and green tea, it reduced biliary sludge in 64% of patients in a 2024 open clinical trial. Ancient physicians used milk thistle for liver and gallbladder diseases.

  • InfecciónCientífico

    Silymarin, the flavonolignan complex from Milk Thistle (Silybum marianum), has been used for centuries for liver and biliary tract diseases (AHRQ/NIH systematic review, NCBI NBK11896). It exhibits choleretic properties, increases bile salt synthesis, reduces biliary cholesterol, and in animal models significantly reduces gallstone formation. A 2025 ScienceDirect study confirmed silymarin restores bile homeostasis and blocks gallstone formation via FXR/BSEP pathway activation.

  • BronquitisCientífico

    Silymarin is the standardized flavonolignan complex from milk thistle with hepatoprotective, Nrf2-activating, and SIRT1-modulating effects. It extends lifespan in C. elegans, protects hepatic function in aging (German Commission E approved), and reduces oxidative stress and inflammation in multiple human RCTs.

  • JuanetesCientífico

    Silymarin shows indirect cardioprotective effects through improvements in lipid profiles, glycemic parameters, and diastolic blood pressure documented in a 2024 meta-analysis of 33 RCTs. Anti-inflammatory and antioxidant actions may reduce LDL oxidation and atherosclerotic risk. Human evidence for direct cardiac outcomes (myocardial infarction, cardiac events) remains limited to cardiometabolic risk factor studies.

  • Silymarin, the flavonolignan complex from milk thistle, inhibits melanogenesis and has antioxidant properties relevant to hyperpigmentation. A scoping review/meta-analysis (2023) identified four clinical studies on silymarin for melasma, confirming it as one of the antioxidants with documented clinical evidence.

  • Olor de piesCientífico

    Silymarin has demonstrated statistically significant improvements in HOMA-IR and fasting insulin in multiple RCTs and a 2025 systematic review and meta-analysis covering 6 studies and 673 participants. A triple-blinded RCT found 25.9% reduction in HOMA-IR and a 6% increase in QUICKI. Effects are consistent across diabetic and non-diabetic obese populations.

  • Silymarin is the standardized flavonolignan complex from milk thistle (Silybum marianum) with documented clinical nephroprotective evidence. Clinical trials demonstrate silymarin protects against cisplatin-induced nephrotoxicity and reduces urinary albumin excretion in diabetic nephropathy patients when added to renin-angiotensin system inhibitors. Its primary mechanisms include Nrf2 activation, glutathione replenishment, and anti-inflammatory activity in renal tissue.

  • Silymarin has the most robust clinical evidence for hepatoprotection. A 2023 systematic review of 29 RCTs (3,846 participants) confirmed its antioxidative, anti-inflammatory, and antifibrotic effects on liver enzymes. It is used in Europe as an adjunct for alcoholic liver disease, drug-induced liver injury, NAFLD, and viral hepatitis. Evidence for chronic HCV is mixed, with one large JAMA RCT showing no significant ALT reduction vs. placebo.

  • EscalofríosCientífico

    Animal and in vitro studies show silymarin improves spatial working memory and reduces anxiety-related behaviors. Preclinical evidence suggests neuroprotective effects relevant to memory via anti-inflammatory and antioxidant CNS mechanisms. Human evidence for memory-specific outcomes is very limited and largely confined to co-administration studies and surrogate biomarker data.

  • GingivitisCientífico

    Silymarin addresses multiple components of metabolic syndrome (hyperglycemia, dyslipidemia, hypertension, insulin resistance) in human and experimental studies. A 2018 PubMed review of human and experimental data concluded silymarin has promising effects on insulin resistance, blood pressure, and lipid profile. The 2024 dose-response meta-analysis (33 trials) confirmed significant reductions in FBG, TG, TC, LDL, diastolic BP, and fasting insulin.

  • BocioCientífico

    Silymarin, the standardized flavonolignan extract of Silybum marianum, is the primary hepatoprotective bioactive studied in mycotoxin-induced liver injury contexts. It is specifically listed in authoritative reviews of chronic aflatoxin exposure mitigation strategies alongside chlorophyllin and is the most studied herbal extract for restoring liver biochemistry and oxidative status in mycotoxin-poisoned animals across multiple species and mycotoxin types.

  • Silymarin has demonstrated neuroprotective effects in preclinical models and is studied in the context of diabetic neuropathy. Clinical evidence includes studies in patients with diabetic nephropathy and neuropathy, and preclinical data showing protection of neuronal integrity via antioxidant and anti-inflammatory pathways. The evidence base is predominantly preclinical; controlled human trials specific to peripheral neuropathy are limited.

  • Silymarin shows osteogenic preclinical evidence relevant to osteoporosis prevention, including enhanced osteoblast differentiation and bone mineral density in animal fracture models. Pro-estrogenic receptor activity provides a mechanistic link to postmenopausal bone loss. Human clinical trials for osteoporosis prevention specifically have not yet been conducted.

  • Duelo y TristezaCientífico

    Silymarin has been investigated for pancreatic protection in the context of its anti-inflammatory and antioxidant properties. Its use in pathological conditions of the pancreas is documented in review literature. It is noted as potentially relevant to pancreatitis via oxidative stress reduction and cytokine suppression, but dedicated large-scale human RCTs for pancreatitis specifically are limited.

  • Silymarin demonstrates neuroprotection in MPTP mouse models of Parkinson's disease, preserving dopaminergic neurons and striatal dopamine levels. Proposed mechanisms include antioxidant, anti-inflammatory, and anti-apoptotic activity in the substantia nigra. Human clinical trial data for Parkinson's disease specifically is not yet established; evidence is currently preclinical.

  • ConjuntivitisCientífico

    The principal active flavonolignan complex from Milk Thistle, silymarin has EU-approved hepatoprotective applications and robust clinical evidence for liver recovery after toxic and viral liver damage. It supports post-illness liver regeneration through antioxidant, anti-inflammatory, and hepatocyte-regenerating mechanisms.

  • Silymarin, the standardized flavonolignan complex from Milk Thistle, has Commission E and ESCOP monograph support for liver protection after viral hepatitis—a direct post-viral recovery indication. Clinical trials confirm it reduces liver enzyme levels and inflammatory markers in viral hepatitis contexts. COVID-19 causes hepatic inflammation in a majority of hospitalized patients, making silymarin directly relevant.

  • Topical silymarin has been investigated in psoriasis. A 2024 trial reported a 38% reduction in PASI scores with silymarin cream (10%) vs. placebo after 8 weeks. Its mechanisms—NF-κB suppression, anti-proliferative effects, cytokine modulation—are directly relevant to psoriasis pathophysiology. Silymarin is listed among dermatological conditions for which it has documented clinical use.

  • Silymarin (from milk thistle) is the active polyphenolic mixture in the pivotal rosacea RCT (Berardesca et al. 2008, n=46, PMID 18254805): topical silymarin plus MSM significantly improved rosacea redness, papules, itching, and hydration (P<0.001) versus placebo. Mechanistically it inhibits NF-κB and reactive oxygen species relevant to rosacea.

  • Costra lácteaCientífico

    Silymarin inhibits UV-induced matrix metalloproteinase (MMP) activity, thereby preserving collagen integrity and reducing photoaging. It scavenges reactive oxygen species, suppresses cyclooxygenase activity, and inhibits tyrosinase to reduce melanin synthesis. Human trial data supports its safety and efficacy at concentrations of 3–10% topically, with documented anti-photoaging activity.

  • Silymarin, the active flavonolignan complex from milk thistle, has preclinical evidence for stimulating collagen synthesis in skin fibroblasts and protecting dermal collagen from UV-induced oxidative degradation. Its antioxidant and anti-inflammatory properties inhibit MMP-mediated collagen breakdown, supporting skin structural integrity.

  • QuistesCientífico

    Silymarin, from milk thistle (Silybum marianum), has documented photoprotective effects with particular evidence for inhibition of UV-induced inflammation, oxidative stress, and photocarcinogenesis. Studies show silymarin inhibits UVB-induced COX-2 expression and production of prostaglandin tumor promoters in skin. Animal studies showed inhibition of UV-induced edema, erythema, and leukocyte infiltration.

  • DebilidadCientífico

    Silymarin, the flavonolignan complex from milk thistle (Silybum marianum), has been shown in RCTs and meta-analyses to reduce triglycerides in NAFLD and T2D patients. The silymarin-berberine combination shows particularly strong TG-lowering in meta-analysis.

  • Silymarin is the standardized flavonolignan extract from milk thistle (Silybum marianum) and is the most extensively studied natural compound for liver protection and detoxification support. A 2023 systematic review of 29 RCTs (n=3,846) found 65.5% of studies reported reduced liver enzyme levels, confirming its hepatoprotective role in whole-body liver cleansing.

  • DifteriaCientífico

    Silymarin promotes wound healing through anti-inflammatory, antioxidant, and pro-regenerative mechanisms. Clinical evidence includes studies in burn patients showing accelerated re-epithelialization with oral silymarin. Topical silymarin has been evaluated in diabetic wound models. Chitosan-pectin films incorporating silymarin show high antioxidant activity in wound dressing applications.

  • AlcoholismoTradicional

    Silybum marianum (milk thistle) has a long-established traditional use as a galactogogue to stimulate milk production. The NIH LactMed database confirms this traditional use but notes no scientifically valid clinical trials support it definitively. A purified silymarin/phosphatidylserine/galega combination product showed some galactogogue activity in one non-randomized study, but quality is insufficient for recommendation.

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