The Safety of Milk Thistle

A few months ago, founder Mike McAdams of Drinkwel reached out to me. This product is meant to be a vitamin for drinkers rather than just a hangover cure.

I told them that I was unsure about one of the ingredients in the mixture, milk thistle, as I'd heard reports that rather than being good for the liver it may actually cause harm.  

This caused a conversation that I thought I'd share. McAdams replied:

It's also funny you mention milk thistle because that was really our only ingredient that had an interaction paper on it. I've taken it on and off for a couple years but make sure my dosages are not too high. 

In case you're interested, here is what our doctor who helped formulate had to say (unfiltered): 

Milk thistle is probably the most well known liver protectant on the market. As far as alcohol intake, new studies have shown that milk thistle has both liver toxicity protection from ethanol [18] and protects against liver fibrosis in non-human primates [19]. 

Safety

There is the possibility of an adverse reaction with milk thistle (possible Pk interactions regarding the decrease of CYP, UGT, and P-Gp activity) [20]. These decreases seem limited so should not be a concern. Therefore, I believe this drug to be a safe and positive addition to the formulation.

and:

The biggest concern would be Milk thistle with only one interaction paper. I think for the most part its use in this formulation would be fine. It has been used for this type of treatment for numerous years without a major side effect case report being brought to light.

18.       Song, Z., et al., Silymarin protects against acute ethanol-induced hepatotoxicity in mice. Alcohol Clin Exp Res, 2006. 30(3): p. 407-13.

19.       Lieber, C.S., et al., Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. J Clin Gastroenterol, 2003. 37(4): p. 336-9.

20.       Wu, J.W., L.C. Lin, and T.H. Tsai, Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol, 2009. 121(2): p. 185-93.

I followed up with McAdams and he send some more information. Then I followed up with the National Institutes of Health. This is all below the jump. 

This information can also be found on the DrinkWel website.

Milk Thistle

Milk Thistle is typically used by some to treat liver cirrhosis, chronic hepatitis (liver inflammation), and gallbladder disorders. The National Cancer Institute and the National Institute of Nursing Research are also studying Milk Thistle for cancer prevention.[1] The United States National Library of Medicine has catalogued more than 300 scientific studies of Milk Thistle and its active compounds in their medicine database.

Milk Thistle’s liver supporting effect has been attributed to the antioxidant and free-radical scavenging properties of its flavonoid constituents – silymarin and silybin. Specifically, silymarin is a bioflavonoid complex that is actually a mixture of 3 flavanolignans, and is considered by some to be among the most potent liver protective substances available.[2][3][4][5]

Silymarin's ability to support the liver destruction and enhancing liver function relates largely to its ability to inhibit factors responsible for liver damage (such as free radicals) coupled with an ability to stimulate liver protein synthesis.[2][3][4][5]

Based on current research on the antioxidant properties of Milk Thistle, it may effectively minimize some of the adverse effects of alcoholic liver cirrhosis.[6][7] Milk Thistle is reported to be an anti-inflammatory and cell stabilizer that helps protect the liver against toxins, drugs and the effects of alcohol.[8] For example, silymarin increases the body’s supply of glutathione, an all purpose antioxidant and detoxifier produced in the liver. It even helps to regenerate injured liver cells.[9]

Might the Europeans be on to something? In some European countries, Milk Thistle extract is used as a prescription medicine to treat alcoholic cirrhosis, chronic hepatitis and alcohol-induced liver damage. For example, a German advisory panel established by the German Health Authorities (equivalent to the FDA in the U.S.) describes Milk Thistle extracts standardized to at least 70% silymarin as supportive against toxic liver damage and chronic inflammatory liver disease. [10] In fact, silymarin drugs and Milk Thistle standardized extracts can only be purchased in Germany at pharmacies with a doctor's prescription for liver problems.

Ingredient Research
1.    http://nccam.nih.gov/health/milkthistle/ataglance.htm
2.    Hikino, H. Kiso, Y., Wagner, H. and Fiegig, M., "Antihepatotoxic actions of flavonolignans from Silybum marianum
    fruits", Planta Medica, 1984, 50, pp 248-50
3.    Vogel, G., Trost, W., Braatz, R., et al., "Studies on pharmacodynamics, site and mechanism of action of silymarin
    the antihpatotoxic principle from Silybum marianum (L.) Gaert"., Arzneim-Forsch, 1975, 25, pp 179-85
4.    Wagner, H., Antihepatotoxic flavonoids", in Cody, V., Middleton, E. and Harbourne, J.D. (eds), Plant flavinoids in
    Biology and Medicine: Biochemical, Pharmacological and Structure-Activity relationships, Alan R. Liss, New York, NY
    1986, pp545-5
5.    Wagner, H., "Plant constituents with antihepatotoxic activity", in Beal, J.L. and Reinhard, E. (eds) Natural Products
    as Medicinal Agents, Hippokrates-Verlang, Stuttgart, 1981
6.    Saller, R., R. Meier, & R. Brignoli. 2001. The use of silymarin in the treatment of liver diseases. Drugs 61(41):
    2035-63.
7.    Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis
    of the liver. J Hepatol 1989;9(1):105-113.
8.    McCaleb, Rob "Milk Thistle - An Herbal Detoxifier", Better Nutrition for Today's Living, March 1993.
9.    Sonnenbichler J, Zetl I. Stimulating influence of a flavonolignan derivative on proliferation, RNA synthesis and
    protein synthesis in liver cells. In Assessment and Management of Hepatobiliary Disease, ed. L Okolicsanyi, G
    Csomos, G Crepaldi. Berlin: Springer-Verlag, 1987, 265-72.
10.    Blumenthal M, ed. The Complete German Commission E Monographs. Austin: 1998:169-170.

Additional Resources
1.    http://nccam.nih.gov/health/milkthistle/ataglance.htm
2.    http://en.wikipedia.org/wiki/Milk_thistle 

I followed the National Institute of Health link. This is what it says at the moment:

What the Science Says

    * There have been some studies of milk thistle on liver disease in humans, but these have been small. Some promising data have been reported, but study results at this time are mixed.
    * Although some studies conducted outside the United States support claims of oral milk thistle to improve liver function, there have been flaws in study design and reporting. To date, there is no conclusive evidence to prove its claimed uses.
    * Recent NCCAM-funded research includes a phase II study to better understand the use of milk thistle for chronic hepatitis C. Additional research, cofunded by NCCAM and the National Institute of Diabetes and Digestive and Kidney Diseases, includes studies of milk thistle for chronic hepatitis C and nonalcoholic steatohepatitis (liver disease that occurs in people who drink little or no alcohol).
    * The National Cancer Institute and the National Institute of Nursing Research are also studying milk thistle, for cancer prevention and to treat complications in HIV patients.

Side Effects and Cautions

    * In clinical trials, milk thistle generally has few side effects. Occasionally, people report a laxative effect, upset stomach, diarrhea, and bloating.
    * Milk thistle can produce allergic reactions, which tend to be more common among people who are allergic to plants in the same family (for example, ragweed, chrysanthemum, marigold, and daisy).
    * Tell your health care providers about any complementary and alternative practices you use. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care.

My Conclusions on Milk Thistle:

I'm no doctor, but I'm always a skeptic when it comes to untested natural remedies. Milk thistle doesn't appear to be bad for you (not that I understand what the reaction paper says), and the NIH information sounds more promising than pessimistic.

With regard to the DrinkWel product, at least we know that safety of its ingredients was considered.