The Benefits of Milk Thistle (Silymarin) in Prevention and

Treatment of Alcoholic Liver Disease Spring 2011

Perry Eliassen, Allison Krippene, Stephanie Thompson
Department of Food Science & Human Nutrition, Colorado State University, Fort Collins, CO

ABSTRACT
Liver disorders are recent and frequent medical problems
occurring in people for a variety of reasons including
environmental factors, diet and excessive alcohol
consumption. There is an increased desire for natural
remedies rather than pharmaceuticals for the treatment of
liver diseases such as cirrhosis, hepatitis, and other alcoholic-
related diseases. The following presentation looks at the
benefits of milk thistle and its active role in the treatment and
prevention of alcoholic liver disease. Milk thistle (silybum
marianum) contains several natural sources of antioxidants
that are hepatoprotective. These protective properties are
effective in regulating cell membrane permeability,
leukotriene inhibition and free radical (ROS) scavenging in the
liver. When taken properly silymarin can be effective in
treating and preventing alcoholic liver disease.
OBJECTIVE
To explain the antioxidant effects of milk thistle
(silymarin) and its benefits in the prevention and treatment
of alcoholic liver disease.
BACKGROUND
Alcoholic Liver Disease:
While the liver is one of the largest organs in the human
body, it is responsible for the metabolism of various
substances, including harmful toxins such as alcohol. Alcoholic
liver disease can result from heavy drinking over time and
includes three conditions: fatty liver, alcoholic hepatitis, and
cirrhosis (1). The earliest stage of alcoholic liver disease
involves a fatty liver, or steatosis, which refers to the
accumulation of excessive amounts of fat inside liver cells. In
some patients, this may be accompanied by liver inflammation
(hepatitis), resulting in a more severe condition called
steatohepatitis. Fatty liver and steatohepatitis may be
reversible with abstinence from alcohol; however, if drinking
continues this may lead to end-stage alcoholic liver disease, or
cirrhosis, in which scar tissue replaces healthy liver tissue
(fibrosis), thus impairing the liver’s ability to repair cell
damage (1). Symptoms of alcoholic liver disease include
jaundice (caused by elevated bilirubin), fever, abdominal pain,
nausea, vomiting, edema (caused by low serum albumin), and
possible esophageal varices.
Milk Thistle:
Milk thistle (silybum marianum) is a thorny pink flowering
plant that belongs to the Asteraceae plant family and is native
to southern Europe, southern Russia, northern Africa, and the
A N A LY S I S
Silymarin has metabolic and cell-regulating effects, namely carrier mediated regulation of
cell membrane permeability, inhibition of the 5-lipogenase pathways, scavenging of reactive
oxygen species (free-radical scavenging), and action on DNA expression.
1. Regulation of cell membrane permeability:
- Silybin increases the stability of hepatocytes against xenobiotic (ie. alcohol-induced) injury.
- The phallodin-transporting system is the membranous site of the action of silymarin. This
may be part of the hepatic system that clears portal blood of bile acids, lipophillic hormones or
xenobiotics. A similar transport mechanism inhibited by silybin has been described for A.
phalloides (xenotoxin). Therefore silymarin is able to reduce the cellular absorption of
xenobiotics thereby exerting cellular protection (3).
- Alcohol and xenobiotics share the same oxidative microsomal pathway. This pathway is
mainly located in the endoplasmic reticulum of hepatocytes.
2. Leukotriene Inhibition:
- Concentrations of silybin on Kupffer celles at 15 umol/L can cause inhibition of Leukotriene
B4 (LTB4) at the 5-lipoxygenase pathway. LTB4, which is a potent chemo-attractant, is able to
induce the formation of reactive oxygen species (ROS), which are highly reactive free-radicals Adapted from Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver
(3). diseases. DRUGS. November 2001; 61(14): 2035-2063.
- Ethyl alcohol increases the production of LTB4, which leads to ROS formation (4).
- Inhibition of the 5-lipogenase pathway is achieved at silybin concentrations that are able to
be reached in vivo. This selective inhibition can partly account for hepatoprotective properties
of silybin.
3. Reactive Oxygen Species (ROS) scavenging:
- The flavonoid structure of silybin makes it easy to form an intracellular hydrogen bond, and
thus be a free-radical (ROS) scavenger of active and stable oxygen radicals (Diagram 2).
Adapted from Haiying F, Mingzhang L, Muroya Y et al. Free radical scavenging reactions and
- Alcohol produces ROS through the 5-lipooxygenase pathway and is thus able to be partially antioxidant activities of silybin: Mechanistic aspects and pulse radiolytic studies. free radical res.
scavenged by the antioxidant properties of silybin. This reduces ROS in the liver (Diagram 1).
September 2009; 43(9): 887-897.

Middle East (8). The seeds of this plant contain a flavonoid
called silymarin, which is a mixture of flavonolignans
(polyphenols that are part flavonoid and part lignan) of which
include silybin (2). Silybin, also known as silibinin, is the main
component of silymarin and functions as an antihepatotoxic
agent due its antioxidant properties. Because of these
antioxidant properties, silybin, and therefore silymarin, may
be helpful in treating liver disease and preventing the liver
from toxins such as alcohol.
Adapted from http://themadpriest.com/blog/?p=51
Adapted from http://cueflash.com/decks/pathology_chapter_18_images
- Alcohol radicals are most effectively scavenged by silybin due to the structure of the
hydrogen bonding abilities of silybin (5).
- Silymarin has shown to be an effective antioxidant in assays including, total antioxidant
activity, reducing power, oxygen and hydrogen peroxide scavenging when compared to
standard antioxidant compounds of BHA and BHT (6).
A P P L I C AT I O N
Milk thistle, also known as silymarin is composed of four different components:
flavonolignans, silydinanin, silychristine and silybin. An extraction of silymarin for milk thistle
contains 70% silymarin and 30% active silymarin compounds. These active compounds of milk
thistle are protective of the liver due to their increased lipid peroxidation (7). Like most
supplements, there is no FDA approval to account for all present items (3). Between 20-50% of
silymarin is absorbed after oral ingestion, 10% enters the bile and between 2-8% is then
excreted through the urine. (8). Silymarin is safe to consume and there are very few small
adverse effects in human trials. Due to low solubility it is almost impossible for takers to
consume toxic levels of silymarin (3). In a study of 3500 patients that contained 2637 with liver
disease the frequency of adverse effects was 1% with the most common complaints of bloating,
nausea and diarrhea. A safe dose is an oral dose between 240-900 mg/day taken in two to three
doses. There are different medications containing silymarin that have greater absorption in the
body than supplement silymarin or milk thistle. In Europe Madus Legalon is a water soluble
derivative of silibin (a compound of silymarin) containing 70 or 140 mg silymarin and is given in
one to two doses a day for a total of 420 mg a day. Another medication is Silipide. Since
silymarin and its compound silibin is not very bioavailable to the body, phosphatidycholine is
used to increase absorption and bioavailibilty to the body. Silipide is one part silibin and two
parts phosphatidycholin and standardized in Silibin equivalents. This oral dose is ten times more
bioavailable to the body than regular silymarin or silibin (8).
CONCLUSION
Liver disease is one of the most common problems in human health. Common
liver dysfunctions include alcoholic liver disease and its components of cirrhosis,
and hepatitis (9). As people are looking for other options besides pharmaceuticals,
milk thistle is arising as a supplement shown to help fight liver disorders due to its
protective effects on the liver (10). Through supplementation milk thistle can help
in regulating cell membrane permeability, leukotriene inhibition and free radical
scavenging. With these qualities and with its high safety factors, milk thistle can
be effective in treating and preventing alcoholic liver disease.
REFERENCES
1. Gramenzi A, Caputo F, Bilelli M et al. Review article: alcoholic liver disease- pathophysiological aspects and risk
factors. aliment pharm therap. 2006; 24: 1151-1161.
2. Kṝen V, Walterova D. Silybin and silymarin- new effects and applications. biomed pap. 2005; 149(1): 29-41.
3. Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. DRUGS. November 2001;
61(14): 2035-2063.
(DIAGRAM 1)
4. Beck I T, Boyd A J, Dinda P K. Evidence for the involvement of 5-lipoxgenase products in ethanol-induced
intestinal plasma protein loss. am j physiol-gastr l. 1988; 254(4): G483-488.
5. Haiying F, Mingzhang L, Muroya Y et al. Free radical scavenging reactions and antioxidant activities of silybin:
Mechanistic aspects and pulse radiolytic studies. free radical res. September 2009; 43(9): 887-897.
6. Koksal E, Gulcin I, Beyza S, Sarikaya O, Bursal E. In vitro antioxidant activity of silymarin. j enzym inhib med ch.
April 2009; 24(2): 395-405.
7. Pares A, Planas M, Caballeria J, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of
a controlled, double-blind, randomized and multicenter trial. j hepatol. 1998; 28: 615-621
8. Abenavoli L, Capasso C, Milic N, Capasso F. Milk thistle in liver disease: past, present and future. phytother res.
June 2010; 24 : 1424-1432.
9. Shaker E, Hahmound H, Mnaa S. Silymarin, the antioxidant component and Silybin marianum extracts prevent
liver damage. food chem toxicol. December 2009; 48: 803-806.
10. Boerth J, Strong K. The clinical utility of milk thistle (Silybum marianum) in cirrhosis of the liver. j herb
pharmacother . June 2002; 2(2):7-11.