Women may be more susceptible to alcohol-induced liver damage, say researchers who base their hypothesis on a study involving rats. Female rodents given alcohol and a special diet had more severe liver damage at the end of the research than their male counterparts did, report doctors at the University of Pittsburgh, whose findings were released at a medical conference in May.¹

"Our aim was to determine whether chronic alcohol ingestion in male and female rats resulted in … subsequent liver injury, using two diets differing in carbohydrate and fatty acid composition and degree of liver injury," wrote Patricia Eagon, PhD, in the university's Department of Molecular Genetics and Biochemistry, and her colleagues.

Pathology of ALD

The liver is the major organ responsible for metabolizing alcohol. Thus, it is more vulnerable to the effects of injury induced by alcohol consumption. Alcoholic liver disease (ALD) involves three main conditions: fatty liver (steatosis), alcoholic hepatitis, and cirrhosis. Heavy drinking for just a few days can lead to steatosis, the earliest stage of alcoholic liver disease and the most common liver disorder caused by alcohol. Drinking heavily for longer periods can lead to alcoholic hepatitis, an inflammation of the liver that includes obvious symptoms like nausea, lack of appetite, vomiting, fever, jaundice, and sometimes, confusion. Alcoholic hepatitis is a red flag that cirrhosis may soon follow. Cirrhosis is a major cause of death in the United States. It is characterized by scar tissue (fibrosis) that replaces healthy liver cells, leading to major liver dysfunction.

Treatment for alcoholic liver disease might include lifestyle changes such as abstinence from alcohol, reducing weight and stopping smoking; nutritional therapy; medications; and sometimes, liver transplantation.²

Diving Deeper Into the Origins

It has been known that women face greater risks of severe liver damage from consuming alcohol compared to men,^3,4 Eagon and her fellow researchers noted.

Previous studies have also shown that alcoholic liver damage is caused chiefly by the escape of poisons known as endotoxins released by bacteria that live in the intestinal tract.⁵ That underlying cause "wasn't totally new to us," Eagon said, in a telephone interview. However, the exact reasons why there were differences in the extent of liver disease between males and females weren't well known.

The researchers used two groups of rats for their study. The first group was given alcohol with either a high-carbohydrate or a high fat diet. The second group was fed no alcohol with either diet. The study lasted for two months. The high fat diet was based on fatty fish oils that included highly unsaturated fats, whereas the high-carb diet contained a mixture of vegetable oils that contained the same amount of fat, but included monounsaturated and polyunsaturated fats. One of this study's co-investigators, Amin Nanji, MD, in the department of Pathology at Harvard Medical School, had previously shown that the fish oil-based diet played a key part in accelerating liver injury in ALD.⁶

Dietary Influence on Female Liver Damage

At the end of the study, Eagon's team measured the extent of liver injury in all rats, including the amount of fatty liver and liver inflammation, in either males or females. They also measured levels of endotoxins. High levels of these substances in parts of the rat's bodies other than the intestine would be an indicator that they were involved in the liver injury found.

Much higher levels of endotoxins that had migrated from the intestine to abdominal lymph nodes and the bloodstream were found in the female rats given alcohol and the high fish oil diet as compared to the other groups, Eagon's team reported. Liver enzymes, which had also been measured, were significantly higher in all the animals, but more pronounced in the female rats given alcohol and high fish oil diets. Additionally, liver inflammation was found only in this group.

"So it's alcohol plus fish oil" that is the key to inducing this type of injury in women, Eagon explained. "There's something about the highly unsaturated fatty acids in the diet that cause the gut injury, and only in the females," she said. "And why that it, I wish we knew right now. That's the next experiment."

Further, all rats that had evidence of alcoholic liver disease after consuming the high vegetable oil-based diet had no levels of endotoxins in the abdominal lymph nodes or bloodstream. But liver injury was "enhanced" in female animals fed the high fish oil-based diet that included alcohol, Eagon and her colleagues stated.

Take-Home Message

It's not always possible to replicate study findings in rats to human beings. But Eagon warns that women who consume alcohol should be cautious, noting their higher degree of susceptibility to its toxic effects in the liver.

In the meantime, she hopes to continue investigating this phenomenon. "The intestinal function in the setting of alcoholism is not very well understood. There's almost no literature on it, as I found when I was trying to put this study together," she told Priority Healthcare. "So, the next step would be to investigate why these highly unsaturated fatty acids affect the gut this way."

Does this mean women should avoid alcohol and diets high in fish oils? Not necessarily, Eagon stressed. "I think people shouldn’t overdo it, just like anything else," she said. "They shouldn't overdo alcohol and they shouldn't overdo fish oil. Everything in moderation."

That advice doesn't apply to people who are already diagnosed with hepatitis. They should completely avoid alcohol, experts strongly caution.⁷

The findings were presented at the annual Digestive Disease Week 2005 conference in Chicago. 

1. Eagon PK, Elm MS, Yang R et al. Alcohol-induced changes in gut permeability and liver injury are influenced by sex and dietary fatty acids. Digestive Disease Week 2005. 2005 May 14-19. Chicago, IL.

2. National Institute on Alcohol Abuse and Alcoholism. National Institutes of Health. Alcoholic Liver Disease. Available at: http://www.niaaa.nih.gov/publications/aa64/aa64.htm. Accessed June 22, 2005.

3. Kovacs EJ, Messingham KA. Influence of alcohol and gender on immune response. Alcohol Res Health 2002;26(4):257-63.

4. Thomasson HR. Gender differences in alcohol metabolism. Physiological responses to ethanol. Recent Dev Alcohol 1995;12:163-79.

5. Wheeler MD. Endotoxin and Kupffer cell activation in alcoholic liver disease. Alcohol Res Health 2003;27(4):300-6.

6. Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Dannanberg AJ. Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration. J Pharmacol Exp Ther 2001 Nov;299(2):638-44.

7. The Merck Manual. Acute Viral Hepatitis. Available at: http://www.merck.com/mmhe/sec10/ch137/ch137b.html?qt=hepatitis%20alcohol%20consumption&alt=sh. Accessed June 29, 2005.