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Milk Thistle & Silymarin Dosage + Side Effects & Interactions

Written by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Puya Yazdi
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) is claimed to boost detox and increase antioxidant defense. People traditionally use milk thistle for digestive, liver and gallbladder issues. Read on to learn about its potential side effects, dosage, 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.

Milk thistle is traditionally used for improving symptoms of liver disease, gallbladder issues, and indigestion. Clinical data to back up these uses is lacking, though.

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%)!

Silymarin is a specific milk thistle extract mixture. Its main active compound is silybin.

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].

Scientists hypothesize that milk thistle might scavenge free radicals and reduce inflammatory cytokines, but this hasn’t been confirmed in humans.

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.

Milk thistle 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.

Forms of Supplementation & Dosage

Dosage & Safety

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 [11].
  • 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 [12].

Look for milk thistle supplements that contain 50-70 % silymarin. Silybin content should also be on the label — the higher, the better.

Supplement Formulations

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 [13]:

  • Berberine combinations, which increases the bioavailability of silybin and the two act together in synergy [14]
  • 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 [15]
  • Mixing it into small particles (micelles) with bile salts [1]
  • Soft gels [16]
  • Advanced formulations (microemulsions or solid dispersion systems)
  • Modifying silybin by binding it to sugars to make it water-soluble (still in the research phase) [17+]
Milk thistle’s main active ingredient, silybin, has poor bioavailability. Theoretically, taking it with berberine, other flavonoids, or fats might help.

Potential Synergies

Milk Thistle Side Effects & Precautions

Side Effects

The main adverse effects reported are [2, 28].

  • 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 [29].

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 [30, 31].

Milk thistle may interact with prescription medications, including anti-diabetic drugs and anti-seizure medications. Consult your doctor before supplementing.

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 [32].

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

Takeaway

Milk thistle has a history of folk use for indigestion and liver disease. However, there’s not enough clinical research to determine its effectiveness.

Nonetheless, some people continue to supplement with milk thistle solely based on its long traditional use. It can also be used in cats and dogs.

Milk thistle is likely safe if used properly. Pregnant and breastfeeding women and young children should avoid it. Drug interactions are also possible.

When choosing a supplement, make sure its silymarin and silybin contents are specified–the higher, the better. Silymarin is a mix of flavonoids in milk thistle, silybin being the most active one.

Learn More

About the Author

Ana Aleksic

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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