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Milk Thistle & Silymarin Benefits + Dosage, Side Effects

Written by Ana Aleksic, MSc (Pharmacy) | Last updated:
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Milk thistle flower

Milk thistle is a popular herb for liver support. Its extract (silymarin) are said to boost detox, lower inflammation, and increase antioxidant defense. People traditionally use milk thistle for digestive and liver and gallbladder issues. Read on to learn more, along with evidence ratings, dosage information, and potential ways to improve the poor bioavailability of milk thistle’s active compound silybin.

What is Milk Thistle (Silymarin)?

Overview

Milk thistle is a relative of dandelion and regular artichoke. Sometimes it’s called “wild artichoke.” This herb is native to Southern Europe, Russia, Asia, and Africa and is now also cultivated throughout the world [1, 2, 3].

The seed-like fruits of the plant are used medicinally. Traditionally, though, the leaves were used in salads and the fruit of the flower roasted as a coffee substitute [1, 2, 3].

Silymarin is a mix of active components that are highly concentrated in a standardized extract of milk thistle seeds [2].

How much do we know?

Milk thistle (Silybum marianum) is a medicinal plant that belongs to a large family of flowering plants (Asteraceae). It has been used traditionally for thousands of years as a “liver elixir” for a variety of diseases to do with liver dysfunction or gallbladder problems. Despite its long-standing use, clinical evidence about its effectiveness for these uses is lacking [4].

It has also been researched for its effects on protecting the liver against snake poison, insect stings, mushroom poisoning, and alcohol abuse. Nonetheless, these uses also lack solid clinical data [1, 2, 5].
In line with this, National Center for Complementary and Alternative Medicine (NCCIH) concluded that little is known about whether milk thistle is effective in people, as only a few well-designed clinical studies have been conducted [6].

Traditional Uses

In the US, milk thistle is among the most popular herbal supplements. It’s also commonly used in other parts of the world, especially in Germany – the largest producer of milk thistle (Madaus). The German Scientific Board recommends its use for indigestion, toxin-induced liver damage, cirrhosis, and liver inflammation [7, 8, 9].

Milk thistle is a good example of traditional plant uses being put to scientific scrutiny. Although over 70 low-quality human studies in total have been published, few high-quality clinical trials have investigated the health benefits of milk thistle.

Despite insufficient evidence from clinical trials, milk thistle extracts and its main active component (silybin) have been regarded as remedies for liver diseases in Europe solely based on their history of traditional use [1, 4].

The European Medicines Agency stated that although clinical evidence is weak, the effectiveness of milk thistle is “plausible” and there is evidence that this herb has been used safely in for at least 30 years [4].

However, the NCCIH points out that the results from clinical trials of milk thistle for liver diseases have been mixed, and two rigorously-designed studies found no benefit [6].

Milk thistle supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

This article will take you through the science behind milk thistle and its health implications.

Bioactive Components (Silybin)

The seed-like milk thistle fruit (achenes) contains the active ingredient silymarin along with other compounds such as [3]:

  • Other flavonoids (taxifolin, quercetin, kaempferol, apigenin, naringin)
  • Oils (linoleic, oleic acid, and palmitic acid)
  • Vitamin E (Tocopherol)
  • Plant sterols (campesterol, stigmasterol, and sitosterol)
  • Some sugars and proteins

Silymarin makes up to 3% of the dry fruit, while fruit extracts can have up to 80% [3].

Silymarin is a complex mixture of flavonoid complexes that includes [3]:

  • The flavonoid Silybin (a flavonolignan), the most active ingredient
  • Other Silybin-like flavonoid complexes (Silybins and isosilybins A and B)

Since silybin is the main active compound of this mixture, most milk thistle supplements are measured by how much of it they contain [10, 1].

Silybin concentrations in various extracts can vary:

  • The highest concentration of silybin in extracts is 50 – 70%
  • Silybin concentrations in common supplements are 20 – 40%

Tip: Don’t get confused when you look at the supplement label. Remember: Milk thistle extracts should be high in silymarin (60 – 80%) and a large part of this silymarin complex should be silybin (at least 20% but aim for those with 50 – 70%)!

Mechanism of Action & Metabolism

Scientists hypothesize that silymarin might act on the biological pathways to [2]:

  • Increase liver regeneration by enhancing the production of DNA and RNA
  • Prevent poisoning from drugs and toxic substances by making the membrane of liver cells less penetrable to them
  • Affect the division of liver viruses such as Hepatitis C
  • Neutralize free radicals and increase levels of the antioxidant glutathione
  • Reduce inflammatory cytokines (TNF-a, INF-b) and raise anti-inflammatory defense (IL-10)

The above-proposed mechanisms remain unproven in humans.

Additionally, silymarin has poor bioavailability. Absorbed silymarin is quickly broken down and transformed into inactive metabolites in the liver. Most of it is eliminated through bile, together with bile acids [1].

The Legend of the “Blessed Virgin Thistle”

The fruits of milk thistle, not to be confused with blessed thistle (Cnicus benedictus), were historically used by mothers for stimulating milk production. Its use was associated with a legend according to which the white veins of the plant’s leaves were a drop of the milk of the mother of Jesus who found shelter in a bower of the plants. Thus, the plant is sometimes called Mary thistle, holy thistle, blessed virgin thistle or Christ’s crown [1].

Have in mind that the use of milk thistle in breastfeeding women might be dangerous. Pregnant and breastfeeding women should avoid this herb due to a lack of safety data.

Snapshot

Proponents

  • Allegedly improves liver health and detox
  • Considered to be a good antioxidant and anti-inflammatory
  • Relatively low risk for short-term side effects

Skeptics

  • Poor bioavailability
  • Bitter taste
  • Few high-quality clinical trials
  • Long-term safety unknown

Purported Health Benefits of Milk Thistle

Possibly Effective for:

1) Diabetes

Some evidence suggests that milk thistle extract might help control blood sugar in people with diabetes when used as an add-on to conventional therapy.

Silymarin (420 mg/day) improved symptoms in 2 studies of 80 people with type 2 diabetes. It reduced fasting blood sugar, insulin, and insulin resistance over 45 days. The extract used in this study is called Livergol by Goldaru Herbal Products Pharmaceutical Company [11, 12].

In another trial of 51 people with type 2 diabetes, 4 months of silymarin (600 mg/day) added to standard therapy reduced both short- and long-term blood sugar markers (fasting blood glucose and HbA1C) [13].

The combination of milk thistle with berberine (Berberol) has also been researched. In one study of 85 people with type 1 diabetes, this combination reduced the insulin doses needed to keep blood sugar in check and also lowered blood fats [14].

In a trial of 60 people with diabetes and alcoholic liver damage, Silymarin (600 mg/day) improved insulin resistance and oxidative stress while reducing the need for insulin injections over 1 year [15].

Metabolic Syndrome

It’s less certain which disease markers milk thistle affects in people with metabolic syndrome. Some evidence suggests the extract improves blood sugar control in people with both diabetes and metabolic syndrome.

In 136 obese people with type 2 diabetes, a combination of berberine and silymarin improved some disease markers after 6 months. It reduced fasting blood glucose and insulin, improved insulin resistance, raised HDL, reduced total, LDL cholesterol, and triglycerides. It also reduced BMI, waist circumference, and belly fat [16].

In 51 people with type 2 diabetes, silymarin (600 mg/day) reduced blood sugar but also lowered total cholesterol, LDL, triglycerides, and liver enzymes (AST and ALT) [13].

In another study of 40 people with type 2 diabetes, Silymarin (420 mg/day) improved insulin resistance, blood triglycerides, and increased the beneficial HDL cholesterol over 45 days. Plus, it reduced the inflammatory marker CRP and increased antioxidants [11, 12].

In 137 people who didn’t tolerate high doses of lipid-lowering statin drugs, silymarin with berberine (~200/1200 mg/day silymarin/berberine) improved blood sugar, insulin, and didn’t worsen blood fats when the drugs were stopped [17].

Scientists are investigating how milk thistle might act in cells. It seems to block Pancreatic Lipase, an enzyme that breaks down fats in the gut and helps absorb them. By blocking this enzyme, milk thistle may theoretically reduce the amount of fat absorbed from the diet. However, this mechanism remains unconfirmed in humans [18].

2) Indigestion (Dyspepsia)

The European monograph mentions heartburn and indigestion as one of the uses of milk thistle [19].

The popular heartburn product Iberogast contains milk thistle along with 8 other herbs. Iberogast improved indigestion, stomach pain, and heartburn in 3 studies. It has been around for 40 years and has a good safety profile [20, 21].

Milk thistle is a mild bitter. Bitter herbs are hypothesized to reduce indigestion by increasing the secretion of stomach acids and digestive enzymes, as well as by activating the vagus nerve. However, it’s unknown if milk thistle alone reduces indigestion since clinical studies are lacking [22].

Insufficient Evidence for:

The following purported benefits are only supported by limited, low-quality clinical studies.

There is insufficient evidence to support the use of milk thistle for any of the below listed uses.

Remember to speak with a doctor before taking milk thistle supplements. Milk thistle should never be used as a replacement for approved medical therapies.

Liver Health: An Overview

Milk thistle has been researched for its liver-protective effects with mixed results. Few proper trials have been conducted. Two rigorously-designed studies found no benefit [6].

A large recent analysis of 17 clinical trials concluded that the effects of silymarin on lowering the liver enzymes ALT and AST (common markers of liver damage) are clinically insignificant [23].

Some scientists are studying whether milk thistle can boost levels of the antioxidant enzyme glutathione, affect inflammation and liver scarring, detox drug and toxins, or help the liver tissue regenerate. However, solid clinical data are lacking to support any of these effects [24, 2].

Fatty Liver Disease

Some evidence suggests that milk thistle extract (silymarin) may improve markers of liver function people with non-alcoholic liver disease (NAFLD). But it’s unclear how relevant these marker changes are to disease outcomes in people with NAFLD.

A combination of Milk thistle’s active compound, Silybin, phosphatidylcholine, and vitamin E over 1 year improved non-alcoholic fatty liver disease (NAFLD) in a clinical trial of 179 people, some of which were also positive for hepatitis C. It reduced liver enzymes, insulin resistance, and liver scarring [25, 26].

However, the active ingredients can reach higher blood levels in people with fatty liver disease only than in those who also have Hepatitis C. After being absorbed, silybin is secreted into the gut with bile. People with Hepatitis C can’t absorb silybin again and “recycle” it, which seems to lower its blood concentration [27].

Some researchers suggested that people with Hepatitis C may need higher doses (2.1 g/day of silybin) to compensate for the liver damage that affects bioavailability. Proper clinical data are lacking to support this practice, though [28].

Hepatitis

Data on the effects of milk thistle extracts in people with hepatitis C or hepatitis B are conflicting. More research is needed to determine the effectiveness and safety of milk thistle in people with hepatitis C or hepatitis B.

An analysis of over 1k people concluded that there is a lack of high-quality data about the effects of milk thistle in patients with alcoholic and/or hepatitis B or C virus liver diseases [29].

For example, milk thistle reduced the chance of death in people with these liver diseases only in low-quality trials, but not in high-quality trials. The authors stressed that large-scale randomized clinical trials on milk thistle are needed [29].

In an observational study of over 1,000 people with hepatitis C, those with the more severe forms of the disease who used silymarin were less likely to experience cirrhosis, but the effect was not clinically significant [30].

In one clinical trial of 36 people with hepatitis C who didn’t respond just to drugs (Peg interferon + ribavirin), IV silybin alone or as an add-on to the anti-Hep C drugs was well-tolerated. The authors claimed that it had an antiviral effect, but the study sample size is too small to draw any conclusions [31].

In another trial of 154 people with Hepatitis C who previously didn’t respond to standard therapy (interferons), oral silymarin (2.1g/day) did not lower liver enzymes or virus activity after 6 months. The silybin content of the extract was unknown in this study [32, 33].

In a low-quality clinical trial of 105 people with acute hepatitis, silymarin (420 mg/day) reduced symptoms, and improved jaundice and bile flow over 4 weeks [34]

In a trial of 37 people with Hepatitis C, silybin combined with phosphatidylcholine reduced high ferritin levels in ~80% of the cases over 12 weeks. How this impacts disease outcomes remains unclear [35, 36].

According to an analysis of almost 400 people with hepatitis C, oral silymarin is not different from placebo. Nonetheless, some scientists are interested in investigating the effects of silybin, the active ingredient, given through a high-dose IV in people with Hepatitis C [37].

Until more research findings become available, the use of milk thistle extracts for hepatitis remains unproven.

Alcoholic Liver Disease

The effectiveness of milk thistle for alcohol-related liver disease is unclear and research findings have been mixed.

In a low-quality observational study of over 600 people, a water-soluble Silymarin extract (420 mg/day) over 11 months lowered high liver enzymes and bilirubin in those with alcoholic liver disease [38].

Silymarin (450 mg/day) didn’t affect liver function in a clinical trial of 60 people with alcoholic liver disease after 6 months. It only increased glutathione and reduced oxidative stress in red blood cells. It’s unclear how these markers could be clinically related to disease outcomes [39].

Mushroom Poisoning

Most mushroom poisonings worldwide are from a species called “death cap.” Milk thistle is the number 1 antidote for death cap poisoning, given as IV silybin (oral silybin doesn’t work). It saved lives in over 90% of 1,500 cases in the US, which is judged to be better than any other antidote. Scientists say it should be given within 48h to prevent severe liver damage and increase survival [40, 41].

Liver Toxicity from Drugs and Toxins

Some scientists believe milk thistle may protect the liver from drugs and toxins, but proper clinical trials are lacking [42].

In animals, silymarin and silybin had a liver-protective effect against damage from alcohol, toxins (carbon tetrachloride and thallium), a chemotherapy drug (cisplatin), Tylenol (acetaminophen), radiation, iron overload, and the poisonous mushroom death cap (Amanita phalloides) [2+, 43].

In a clinical trial of 50 children with leukemia, milk thistle use was linked with potentially reduced liver toxicity after 1 month. The authors said that further trials need to determine how milk thistle affects liver health and chemotherapy side effects in people with leukemia [44].

Milk thistle doesn’t protect the liver from drugs in general. For example, it didn’t protect the liver from anti-tuberculosis drugs in a study of 380 people. On the contrary, it even slightly increased the risk of liver damage [45].

Quality of Life After Liver Transplantation

In a survey of 32 people who received liver transplants, those who used milk thistle and other herbal products had better problem-solving skills, considered the supplement investment worthwhile, and reported better overall health [46].

This does not speak to the benefits of milk thistle but more likely shows that people who tend to actively seek ways to improve their health and well-being feel better.

Antioxidant Effects

The antioxidant benefits of milk thistle remain unclear. Low-quality evidence points to antioxidant effects, but we don’t know how predictable and meaningful these changes are.

In a clinical trial of 40 people with type 2 diabetes, Silymarin (420 mg/day) over 45 days enhanced antioxidant defense and enzymes such as glutathione and SOD. It also reduced the inflammatory marker CRP [47].

In cell culture, scientists are investigating whether milk thistle:

  • Activates the alleged detox hub, Nrf2 [48].
  • Blocks the inflammation pathway called NF-kB [48].
  • Improves mitochondrial health (via Heat Shock Proteins, which are hypothesized to protect cells and tissues under stress) [48].
  • Increases sirtuins, which might help conserve energy, reduce aging and inflammation [48].
  • Neutralizes free radicals, chelating free iron and copper [48].

However, these mechanisms and their health relevance remain unknown in humans.

OCD

We still don’t know whether milk thistle affects symptoms of OCD.

Some scientists hypothesize that it protects the brain, thus explaining why it should be further researched in people with mental health disorders. In one clinical trial of 35 people with OCD, milk thistle extract (600 mg/day) was comparable to an SSRI drug (fluoxetine) in reducing OCD symptoms over 8 weeks. Large-scale trials are lacking [49].

Kidney Health

Evidence is lacking to support the use of milk thistle for kidney health.

In one clinical trial, silymarin (210 mg/day) for 8 weeks in people on dialysis reduced inflammatory cytokines, especially TNF-alpha [2].

Some scientists are also investigating whether it protects the kidneys in animal studies and how it might affect antioxidants in kidney cell studies. In dogs, it reduced kidney damage from an antibiotic (gentamicin) when combined with vitamin E. Clinical trials are needed [2, 50].

Acne

It’s still uncertain whether milk thistle has any acne-soothing effects. In a trial of 14 people, a combination of silymarin (210 mg/day), N-acetylcysteine, and Selenium reduced acne after 8 weeks by 53% [51].

Prostate Health

Proper clinical trials are lacking to rate the effectiveness of milk thistle for prostate health. A mix of silymarin and selenium reduced prostate symptoms in a clinical trial of 55 men. It improved urine flow and reduced bladder fullness [52].

The same combination reduced blood fats that are linked to prostate cancer worsening in men who previously underwent prostate-removal surgery. Further trials are required [53].

Iron Overload

According to one theory that remains to be proven, the active compounds in milk thistle act as iron chelators. It is being researched for binding excessive iron in genetic disorders of iron buildup.

Silybin reduced iron absorption in 10 people with a genetic disorder that causes iron buildup and overload (Hemochromatosis) [54].

Silymarin reduced iron overload (in combination with desferrioxamine) in 49 people with β-thalassemia, one of the most common genetic disorders [55].

According to a large review 74 studies, silybin from milk thistle may reduce high iron and organ damage in people with thalassemia when used as an add-on, but large-scale trials are needed [56].

Chemo and Radiotherapy Side Effects

Large-scale clinical trials have yet to determine the effectiveness and safety of milk thistle creams and oral formulations for reducing chemo and radiotherapy side effects.

Silymarin from milk thistle formulated into a cream (Leviaderm) prevented skin damage from radiotherapy in one trial of over 100 breast cancer patients [57].

Silymarin gel 1% applied on the palms and soles of hands and feet protected from skin damage typically caused by a chemotherapy drug (capecitabine) in 40 people with stomach cancer [58].

In a low-quality trial of people with brain metastases undergoing radiotherapy, a combination of omega-3 fatty acids and milk thistle increased survival and decreased tissue damage from the radiation [59].

In 77 people with cancer undergoing radiotherapy of the head and neck, silybin (420 mg/day) reduced painful mouth inflammation over 6 weeks [60].

However, milk thistle didn’t reduce kidney damage from the chemotherapy drug Cisplatin in one small clinical trial [61].

Lacking Evidence (Animal Research)

No clinical evidence supports the use of milk thistle for any of the conditions listed in this section.

Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

Liver Detox

The liver breaks down and helps eliminate all harmful substances, both from waste products produced in the body and those that enter via food and environment.

Milk thistle is traditionally used to “protect the liver” and facilitate detox, but no clinical trials back up this use. Studies are limited to cells and animals.

Some researchers are investigating whether milk thistle reduces oxidative damage and inflammation in cells. Others wonder if it helps regenerate liver cells, glutathione, and SOD. According to unproven theories, this plant is said to help detoxify the liver from pollutants, environmental toxins, and drugs [62, 63, 64].

Other cellular studies are exploring potentially heart-protective effects of milk thistle against heavy metals like arsenic, environmental pollutants, fluoride, and oxidative stress [65, 66].

Remember that many plants have antioxidant effects in cells. Most of them fail to pass further animal studies or clinical trials due to a lack of bioavailability, safety, or efficacy.

Silybin protected against an algae liver toxin (microcystin) in mice and against a fungal toxin (aflatoxin) in chickens [67, 68].

The exact effects of milk thistle on healthy people who want to detox hasn’t been confirmed.

Some alternative practitioners claim that occasional detoxes may be helpful even in people not exposed to any specific toxins. No solid evidence backs them up, however. In one study of 25 healthy people, a 7-day detox improved wellbeing and liver health. This study was too small and poorly designed to support detox protocols in the general population [69, 70].

Bone Health

The effects of milk thistle on bone health in humans are unknown.

Milk thistle (silymarin) improved bone healing and increased bone mineral density in mice with bone fractures [71].

Some researchers believe that milk thistle may compensate for low estrogen levels after menopause. It prevented bone loss and increased the activity of cells that help mineralize and rebuild bones in postmenopausal mice. One research group is investigating whether it raises the activity of bone-forming cells in dishes [72, 73].

Milk Production

Although milk thistle has been used traditionally by pregnant women to increase milk production, the safety of supplementation in pregnant women is unknown. Pregnant women should not take milk thistle unless directed by a doctor [74, 75].

In only one low-quality study of 50 breastfeeding women with low milk production, milk thistle slightly increased milk production after a month of daily use (420 mg/day) [75, 76].

Red Blood Cells

Scientists are studying the effects of silymarin on free radicals and glutathione in red blood cells [2].

Weight Loss

The effects of milk thistle on weight loss are unknown. Like many natural substances, it had some anti-obesity effects in animals. Many such plants turn out to be ineffective for weight loss in humans.

In one study, milk thistle prevented mice fed a high-fat diet from developing metabolic disease [77].

Researchers are investigating whether silybin stops fat cells from developing and dividing in test tubes. They are also looking at its effects on weight-associated genes, such as SIRT1, PPAR alpha, and Pgc-1alpha in cells and tissues [78, 79].

It’s uncertain if milk thistle can aid in weight loss in humans, though.

Bile Flow

Some research in animals and cells focused on how milk thistle impacts blocked bile flow, suggesting that it might raise the production of bile salts and their secretion into the gut. This mechanism remains undetermined in humans [80, 81].

Hangovers

Some people use milk thistle to reduce hangovers. Clinical studies have not investigated this use. In mice given a lot of alcohol over a short period of time, milk thistle protected the liver from injury and reduced inflammation. We can’t translate these findings to humans [82].

Inflammation

Scientists investigated the effects of silybin on pregnant mice with infections. They hypothesize it reduces inflammation in the brain and preterm births by affecting inflammatory substances (IL-6, IL-8, PGE2), enzymes (COX-2), pathways (TNF-alpha, and loosely-associated genes (MMP9) [83, 84].

Autoimmunity

Another unproven theory suggests that milk thistle may improve autoimmune conditions by reducing the Th17 response. The effects of milk thistle on autoimmunity in humans are unknown.

Scientists wonder if one of the reasons why women are more susceptible to Th17-dominant autoimmune diseases is because of estrogen’s involvement in the healthy immune response. In order to reduce the Th17 inflammatory response, estrogen receptors might need to be activated. Estrogen normally does this, but its levels drastically fall in women after menopause [85].

Early studies suggest that milk thistle might activate estrogen receptors. In a study of healthy people and those with rheumatoid arthritis, silybin increases ER-beta and miR-155. It seems to bind to estrogen receptors in white blood cells, which may reduce the autoimmune response and inflammatory cytokines (IL-17 and TNF-a) [86].

Infections

We don’t know how milk thistle might affect infections in humans.

Its effects against the following microbes are being researched in cell culture or lab animals:

  • Influenza A [87].
  • Methicillin-Resistant Staphylococcus Aureus [88].
  • E.coli and biofilms [89, 90, 91].
  • Blood-flukes (Schistosomiasis) [92].

Brain

No human studies on the effects of milk thistle on brain health in humans exist.

Scientists are exploring whether silybin and milk thistle extracts affect the following pathways in animals and cells:

  • Infection-related brain inflammation [83].
  • Memory loss from oxidative stress (in the brain’s memory hub, the hippocampus) [93].
  • The expression of BDNF, which helps make new brain cells, and of tyrosine receptor kinase B (TrkB), which helps make and strengthen new connections in the brain in response to BDNF [93].
  • Symptoms of Parkinson’s disease and damage from stroke (via NF-kB and microglia) [93, 94].

Some scientists think silymarin may be anti-aging. They posit it might activate hormesis pathways, increasing stress resilience and defense mechanisms similar to adaptogens. They suspect these pathways might be linked to longevity and brain protection. Still, no evidence backs them up. Silymarin extended the lifespan of worms, but its anti-aging effects haven’t been studied in lab animals or humans [95].

Interaction with Anti-Seizure Drugs

SIlymarin reduced liver injury from anti-seizure drugs in a small trial of 55 children with epilepsy [96].

In rats, milk thistle blocks Pgp, a protein that is suspected to stop drugs from being absorbed in the gut or from passing to the brain [97, 98].

Wounds

The effects of milk thistle on wound healing in humans is not known.

Silymarin increases skin regeneration and decreases inflammation in rats with wounds. Silybin sped up wound healing in rats possibly by affecting genes that help the skin rejuvenate. In cellular studies, milk thistle gel increased collagen and the activity of collagen-producing cells (fibroblasts) [99].

Fertility

We don’t know how milk thistle might affect fertility in humans. Milk thistle with rosemary increased semen quality, boosted antioxidant status, fertility, and sexual performance in rabbits [100].

Since milk thistle also has estrogen-like effects, its effects on fertility in men would need to be studied well in humans. Phytoestrogens that over-activate estrogen receptors usually reduce libido in men and increase the risk of erectile dysfunction [101].

Some researchers have suggested that milk thistle should be studied for increasing the chances of successful In vitro fertilization, but proper studies are lacking [2].

Cancer Research

Milk thistle has not been shown to treat or prevent cancer or reduce the side effects of cancer treatment. Large-scale, properly-designed studies are needed.

In one clinical trial, 60 people with benign polyps in the colon (which often develop into colon cancer) took a herbal blend with milk thistle, a flaxseed antioxidant, and oat fiber for 2 months before colonoscopy. The combination increased estrogen receptors in the colon, which is hypothesized to be beneficial [102].

A combination of Milk thistle (Silymarin) and selenium reduced markers of prostate cancer worsening (LDL and total cholesterol) in 19 men who previously had their prostate removed [103].

Milk thistle has low bioavailability, but standardized extracts might reach the blood. In 12 women with breast cancer, a combination of silybin and phosphatidylcholine (2.8 g/day) for 4 weeks before surgery seemed to build up in the breast cancer tissue more than in healthy tissue [104].

In one study, high doses (up to 13 g/day) of a special milk thistle formulation (Silybin-phytosome) over 4 weeks were safe in 13 people with prostate cancer [105].

Milk thistle is also being researched for preventing skin damage in animal studies [106].

Animal research is also investigating the effects of silybin on prostate cancer and breast tumors. [107, 108, 109, 110].

Limitations and Caveats

Although there is a fair amount of clinical data, most trials were low-quality. More research is needed to determine the effects of milk thistle on various disease states in humans.

Bioavailability was a big issue in many studies, especially in cases of disease when high levels of the active compounds need to reach the blood. Intravenous silybin was used at times, which is very different from taking oral supplements.

Many studies were only done in animals or in cells. Their findings can’t be extrapolated to humans.

Forms of Supplementation & Dosage

Safety & Dosage

Milk thistle is considered to be safe when used properly.

Standardized milk thistle extracts should contain 70 – 80% Silymarin. Ideally, the silybin content should also be mentioned and account for ~40% (the higher the better).

  • The typical silymarin dosage used in most studies was ~420 mg/day divided into 2 or 3 doses.
  • In people with liver disease, the typical dosage was higher, around 1.3 g/day of the standardized for 6 – 8 weeks (divided into 3 doses during the day). For maintenance, the dose was reduced to 280 mg/day [2].
  • Silymarin doses up to 2.1 g per day were used in people with viral hepatitis, especially in those with chronic hepatitis C infection. Even so, IV silybin showed better results than oral extracts in people with serious liver damage [111].
  • Very high doses of the silybin IV solution are used for mushroom poisoning.

Milk thistle appears to be safely used daily for in doses up to 420 mg daily for up to 4 years. In cancer patients, the highest safe dose was about 13 g/day short-term [112].

Milk thistle is available in many forms as a supplement. Milk thistle supplements, including silymarin extracts, include all the following:

  • Capsules
  • Tablets
  • Tinctures
  • Intravenous solutions

Milk thistle has a bitter taste, which you will notice if you take it as a tincture. This allegedly helps if you’re taking it for indigestion but can be unpleasant otherwise.

Some people consider that taking organic milk thistle has additional benefits. Organically-grown plants sometimes have higher concentrations of bioactive compounds, but this has not been confirmed for milk thistle. It’s more important to make sure the supplement you decide to buy is standardized to the active ingredients.

What’s the best time to take milk thistle?

In clinical trials, daily milk thistle doses were usually divided into 3, which can be spread out evenly during the day. Milk thistle has poor bioavailability, though, but taking it with some oils or fats is a potential way to slightly increase its absorption.

Bioavailability Issues & Potential Ways to Overcome Them

Silybin, the main active component in the standardized milk thistle extract Silymarin, has poor bioavailability. Only around 20 – 50% of it gets absorbed from the gut.

Scientists think this is because silybin can’t dissolve in water, which makes up most of the stomach and gut fluids. Stomach acid can also degrade it, so it may not even reach the gut.

There are some potential ways to overcome its bioavailability issues, but none have been adequately researched in humans. Some theoretical and experimental approaches have been proposed, such as [113]:

  • Berberine combinations, which increases the bioavailability of silybin and the two act together in synergy [16]
  • Other flavonoids (such as quercetin) may increase its absorption [1]
  • Fats, proteins, amino acids, and cholesterol may increase its absorption [1]
  • Vitamin E may help dissolve silybin and increases bioavailability [1]
  • Soluble water extracts
  • Silymarin complexes with phospholipids like phosphatidylcholine (Siliphos)
  • Liposomal silymarin
  • Nano-silymarin or nano-silybin [1]
  • Purified extracts from the fruit [114]
  • Mixing it into small particles (micelles) with bile salts [1]
  • Soft gels [115]
  • Advanced formulations (microemulsions or solid dispersion systems)
  • Modifying silybin by binding it to sugars to make it water-soluble (still in the research phase) [116+]

Potential Synergies

Milk Thistle Side Effects & Precautions

Side Effects

The main adverse effects reported are [2, 124].

  • Nausea, stomach pain, and discomfort (most common)
  • Mild diarrhea
  • Headaches
  • Joint pain
  • Skin allergies, itching, and eczema
  • Fatigue and insomnia
  • Nasal congestion, runny nose, sneezing
  • Impotence (rare)
  • Anaphylaxis (serious life-threatening allergic reaction) (very rare)

Drug Interactions

Not much is known about milk thistle’s food and drug interactions [2].

Herb-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.

Milk thistle may excessively lower blood sugar in people on antidiabetic drugs.

Some cellular studies found that milk thistle may affect CYP enzymes in the liver that metabolize drugs; human studies suggest this effect is minor, but interactions are possible [125].

Some animal studies suggest it may interact with anti-seizure medications. Exercise caution and consult your doctor if you are taking anti-seizure drugs or have epilepsy [97, 98].

Pregnancy and Children

Children, pregnant and breastfeeding women should avoid milk thistle due to a lack of proper safety data.

Milk Thistle for Dogs and Cats

Milk thistle is sometimes used in cats and dogs. But bioavailability is an issue, as in humans. If you’re looking to use milk thistle for your pets, rather go with a formulation of milk thistle combined with phosphatidylcholine, which has been researched in dogs [126].

Follow the dosage recommended by your vet, which should be adapted to your cat or dog based on their size/weight.

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About the Author

Ana Aleksic

MSc (Pharmacy)
Ana received her MS in Pharmacy from the University of Belgrade.
Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.

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