Introduction

The herbal industry is a multi-billion dollar industry. Milk thistle extract consistently ranks as one of the most widely used herbal remedies. Milk thistle is probably best known for its alleged role in liver health, but is also promoted for diabetes, hyperlipidemia and even cancer. Fact or fiction?

What Is Milk Thistle?

Milk thistle is a natural herb, also known as Silybum marinanum, Mary thistle and holy thistle. It is a member of the aster family and grows well in southern Europe, Australia and both north and south America.

The legend behind the name is interesting. The thistle has red-purple colored flowers. It also has green leaves with white fluid coursing through the veins of the leaves.

Legend has it that Mary, Joseph and baby Jesus were fleeing for safety and Mary stopped to nurse Jesus en route. Some of the breast milk fell on a rock and milk thistle sprung up from the rock as a sign that it could be safely used by nursing mothers. Hence the name.

That being said, milk thistle is not commonly used as a human lactagoue (something used to increase milk supply) but it is used today in animal husbandry to promote milk production.

It has been used as a medicinal herb since the time of ancient Greece.

While, milk thistle is often interchangeably called Silymarin, technically ‘silymarin’ is the name given to the bioactive flavolignans (silybin, silibinin, silydianin, silychristin) found in milk thistle.

Despite the facts that milk thistle has been used for over 2000 years in traditional medicine and that milk thistle is often called silymarin, ‘silymarin’ was only first identified in 1968. (This is already confusing if you ask me).

Milk thistle gets its name from the milky white sap in the leaves but the fruits actually contain the medicinal compounds. The fruits are often mistakenly called seeds. (More confusion).  Milk thistle fruits contain up to 6% silymarin.

Most milk thistle products are standardized preparations of the fruits which contain 70-80% silymarin.

Milk thistle is available as capsules, powder, creams and tinctures via health food stores, pharmacies, direct mail companies and online stores. In Europe it is also available as a water soluble intravenous formulation.

Amazon offers over 1000 milk thistle products (If you sell it, they will come). You can buy 55lbs of milk thistle for a whopping $2250.

Can You Get Milk Thistle From Food?

Various parts of milk thistle have been used as a food source in Europe. Leaves are used in salads, stalks are eaten like asparagus, the fruits are used as a coffee substitute while the  flowers are eaten like artichokes. However as mentioned above, the fruits contain the active ingredient and consumption of milk thistle fruits is not a widespread practice.

Is There Any Research?

There are 841 publications on milk thistle which includes 600 clinical trials. Let’s compare this to ribavirin which has been the mainstay of treatment for hepatitis C which has 15, 532 papers and 1969 trials. Milk thistle is the poor cousin here.

Does Milk Thistle Help The Liver?

There is significant interest in milk thistle and the liver.

The history behind this is very interesting and helps us to understand the current interest in milk thistle for all things liver related.

The death cap mushroom (Amanita phylloides) causes potentially fatal liver hemorrhage. As per history, the musician Schubert picked wild mushrooms and brought them to a restaurant to be cooked. The chef correctly identified the mushrooms as death cap mushrooms and refused to cook them. Schubert decided to cook the mushroom himself and his entire family (except his son who was out of the house) died from death cap mushroom poisoning. If only he had served the death cap mushrooms with a garnish of milk thistle fruits as we will see.

In the 1960s, researchers wondered if milk thistle could potentially help with death cap mushroom poisoning. Milk thistle is now approved in some European countries for this indication but it does not have FDA approval.

There are interesting case reports of US physicians getting special FDA exemptions to import parenteral milk thistle for patients with death cap poisoning (1,2)

Due to a small number of case reports of the success of milk thistle in death cap mushroom poisoning, some investigators (and many patients) have explored the possibility that milk thistle could work for other forms of hepatitis.

Many of these studies focus on viral hepatitis and specifically hepatitis B and C.

When we (physicians) assess a patient with viral hepatitis we look at their liver enzymes called transaminases. People with active hepatitis tend to have raised liver enzymes such as AST and ALT. However if the liver disease progresses to cirrhosis we can see liver tests within the normal range as there it too little normal liver left to release AST or ALT.

We also measure the amount of circulating virus in the blood which is known as the viral load. A high viral load carries a worse prognosis than a low viral load. Finally we look for fibrosis of the liver which is an architectural change in the substance of the liver using a liver biopsy or fibroscan.

I practice in a viral hepatology clinic every week and not a week goes by without some patient mentioning milk thistle to me.

Canadian investigators published a meta-analysis of milk thistle in the Journal of Viral Hepatitis in 2005 (3). They conducted what they described as an ‘exhaustive search’ and identified 148 papers. They found that milk thistle had no effect on the viral load (amount of circulating hepatitis B or C in the blood) or on the liver histology.

They thought that it might be ‘likely’ that milk thistle reduced liver transaminases in these patients. While it would be good to see a reduction in the liver enzymes, it does not mean much prognostically without a concomitant reduction viral load. Next.

In 2009 a Cochrane review looked at the role of milk thistle in alcoholic and/or hepatitis B or C (4) . This was a collaborative project between investigators in Denmark and UCSF.

Just to explain the referencing, this review was done in 2005 and again in 2007 and was then updated in 2009. The data presented here represents the data from the 2009 review although the reference used (as per Cochrane citation recommendations) is the 2007 paper. (I hate anomalies as you can see).

They identified 13 trials with 915 patients that were of interest. The quality of the research was low and only 46% were considered adequately double-blinded. Milk thistle had no effect on mortality, complications of liver disease or liver histology.

Liver related mortality was reduced when all trials were pooled. However this effect was not seen in a sub-analysis which was confined to high-quality trials.

It would be reasonable to ask why milk thistle seems to work for death cap poisoning and not other forms of hepatitis. This all comes down to pathophysiology. Death cap mushrooms damage the hepatocellular wall while viral hepatitis acts intracellularly.

It is incredibly easy to sit here and summarize negative data. It is painfully hard to communicate negative data to patients who (for whatever reason) have put their hopes into a herbal remedy such as milk thistle.

Just to put this into context, some people clear hepatitis B and C infections. Others do not. The on-going viral replication damages the liver and the effects of damage compound over time.

We have no eradication therapy for hepatitis B. People with a high hepatitis B viral load need life-long treatment to suppress the virus. If the medication is stopped for any reason the virus can rebound to a higher level and this is potentially very dangerous.

We now have effective 12 week treatment courses for hepatitis C and for all genotypes of hepatitis C. This compares to five years ago when we had to treat hepatitis C with a year of treatment that included a very poorly tolerated injectable medication called interferon.

Not everyone can get access to the uber-expensive 12 week treatment course. No wonder people are looking for safe and effective alternatives. It is like a double blow if (for whatever reason patients cannot access the new directly acting agents for hepatitis C) and then they are told by the same gatekeepers of treatment that milk thistle will not work.

Bottom Line

Even though I truly wish it were different, there is no evidence that milk thistle works for the liver.

Does It Protect Against Cancer?

There are a number of small clinical studies which address this issue.

The first study of 37 participants post radical prostactectomy randomized patients to either silymarin 750mg plus selenium 240mcg or placebo for six months (5). The study found that there were statistically significant differences in the levels of tumor markers (associated with prostate cancer progression) in the treatment arm of the study. However there was no clinical correlation so we do not know if this translated into an clinical benefit or not.

A second study relating to prostate cancer enrolled 6 patients with localized prostate cancer scheduled for a prostatectomy and 6 matched controls (6). Patients in the treatment arm received silybin-phytosome for 14-31 days (mean was 20 days) prior to surgery.

The study found that oral silybin-phytosome achieves high blood concentrations transiently, but low levels of silibinin are seen in prostate tissue. The authors questioned whether the low levels seen in the prostate were due to too low a dose or a short half life. Either way, the low level noted in the tissue samples call into question the utility of silibinin in this patient population.

A similar type of study looked at twelve breast cancer patients who received silybin-phosphatidylcholine, 2.8 g daily for 4 weeks prior to surgery (7).

Unlike the prostate cancer patients, sibylline selectively accumulates in breast tumor tissue. This led the authors to suggest that ‘the findings provide the basis for a future phase II biomarker trial in breast cancer prevention’.

Finally a study in liver cancer failed to find the maximum tolerated dose or clinical impact of milk thistle extract (8). Only three patients with advanced hepatocellular carcinoma were enrolled and they died soon after enrollment into the study.

Bottom Line

There is no proof that milk thistle has anti-cancer effects in humans.

Does It Help Lower High Cholesterol?

A study of a proprietary blend of Berberis aristata/Silybum marianum was tested in 175 euglycemic, dyslipidemic subjects, intolerant to statins at high dosages (9).

During the run-in period, statins were stopped for 1 month, then they were re-introduced at the half of the previously taken dose. Subsequently, patients were randomized to placebo or the proprietary blend at dinner and tea for 6 months.

The total cholesterol, LDL-C and triglyceride levels did not change with reduction of statin dosage taken with the proprietary blend, while they increased in the placebo group.

What does this mean? Actually this study is really deceptive. In this study, the berberine was being used as the lipid lowering agent to compensate for the reduced dose of statin. However berberine has very low bioavailability. Milk thistle was used to modify the activity of p-glycoprotein and increase the bioavailability. Simply put, milk thistle was acting as an excipient or pharmaco-enhancer and not an active drug.

And for the ‘piece de resistance’ as my near neighbors in France would say, the lead author on the paper is the patient holder for the proprietary blend. Give me a break here. I have unapologetically discounted any other studies on berberine, milk thistle and cholesterol from this review.

An Italian study shows that a combination of combination of red yeast rice, Silybum marianum and octasonol was effective in improving lipid profiles(10). We cannot extract the effects of milk thistle from the other agents used in this study.

Bottom line

There is no proof that milk thistle has anything to do with cholesterol.

Does it Prevent or Control Diabetes?

A study by Iranian pharmacologists looked at the effect of silymarin in 51 patients with type 2 diabetes (11) . The study participants were randomized to silymarin 200mg three times daily plus standard of care or placebo plus standard of care.

There was a statistically significant decrease in the HbA1C (which is a marker of long term glucose control), fasting blood sugar, cholesterol and LDL. This is promising but this is a small study.

It is interesting to note the positive effect on the blood lipid levels (which we did not find in the other studies on cholesterol). However it must be said that this study shows a positive effect of silymarin in a short term small study of diabetic patients. This does not mean that we can extrapolate the findings in lipids to the non-diabetic population.

Another study from Iran found positive effects of milk thistle in 40 diabetic patients in terms of antioxidant status (SOD, GPX and TAC) and inflammatory markers (hs-CRP) (12)  .

Bottom Line

One study shows a positive effect of silymarin on glycemic control in diabetics. However this study was small and short-term and as such could not be taken as the final word of the subject and more studies are needed.

Does It Help Prevent Gallstones?

Milk thistle has been used in traditional medicine in the treatment of gallstones and is believed to increase bile flow. There are no clinical trials looking at milk thistle and gallstones or cholecystitis. Studies in rats showed that milk thistle can help artificially induced cholestasis (13)

Bottom Line

The relationship (if any) between gallstones and milk thistle has not been studied in the human species.

Does It Have Anti-aging Effects?

The potential anti-aging efficacy of silymarin was tested in the Caenorhabditis elegans model system (14). I honestly had no idea what a Caenorhabditis elegan was but have since discovered that it is a nematode or worm.

The study showed that C. elegans treated with 25μM and 50μM silymarin concentrations enjoyed an increased mean lifespan of 10.1% and 24.8% respectively compared to untreated controls. The worms were then paralysed by being exposed to temperatures of 23 degrees C and silymarin slowed down the speed of onset of paralysis.

The results were generously interpreted as evidence that silymarin is a potential hormetin for preventing aging and age-related diseases. Another new word for me today. A hormetin is a substance that can cause a favourable response to low doses of a toxin.

Bottom Line

There is no human data that silymarin has an anti-aging effect.

Is Milk Thistle (and or Supplementation) Safe?

The 2009 Cochrane review of milk thistle (mentioned above) in hepatitis noted no major side effects (4). In general side effects of milk thistle are mild and limited to gastrointestinal upset.

Milk thistle may cause allergic reactions especially in people who are allergic to related plants such as ragweed, daisy and marigold.

There are theoretical concerns that milk thistle may lower levels of blood glucose and care is advised in patients taking glucose lowering drugs to avoid unintentional hypoglycemia. Ironically, despite the alleged origin of the name of milk thistle, some resources caution against the use of milk thistle in pregnant and breastfeeding women.

Milk thistle may have some pro-estrogenic activity and is generally contraindicated in women with fibroids, endometriosis, breast and uterine cancer. It is recommended that milk thistle be avoided in people taking any of the following medications:

  • anti-pyschotics
  • birth control pills or hormone replacement therapy
  • allergy medication
  • lipid lowering statin medication
  • anti-anxiety drugs and
  • antiplatelet/oral anticoagulants.

Conclusion

If we discount the worm, rat and ‘oh so conflicted patent holding authors’, we are not left with much. With the high level interest in milk thistle, there is no doubt that the current studies and reviews will not be the last word on this subject. In fact, the National Institutes for health are conducting a study of high dose intravenous milk thistle as some die-hard milk thistle fans believe that the negative studies that we have seen are simply due to use of the wrong dose and the wrong mode of administration.

Is this wishful thinking or visionary? Only time will tell. Meantime I have learned two great news words, vermifuge and hormetin.

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