A Person's Nutrition Affects Liver Function

by National Institute of Health

(Page 4 of 7)

Malnutrition, regardless of its causes, can lead to liver damage and impaired liver function. For example, children in underdeveloped countries whose diets do not contain enough protein can develop a disease called kwashiorkor. One symptom of this disorder is the accumulation of fat in the liver, a condition known as fatty liver. Studies performed during and after World War II indicated that severe malnutrition also could lead to liver injury in adults. However, in these cases other factors, including exposure to certain toxins or parasites that are prevalent in war-ravaged or underdeveloped countries, may have exacerbated the relationship between liver injury and poor nutrition.

Because malnutrition also is common in alcoholics, clinicians initially thought that malnutrition, rather than alcohol itself, was responsible for alcohol-induced liver injury. Over the past 40 years, however, a more balanced view has evolved. Studies in humans, primates, and rodents have established that alcohol can cause liver damage even in well-nourished people. Moreover, controlled studies using hospitalized participants have demonstrated that even subjects receiving an enriched diet could develop fatty liver if the carbohydrates in the diet were replaced with alcohol. Finally, epidemiological analyses have found a close correlation between per capita alcohol consumption and the likelihood of cirrhosis, indicating that alcohol itself contributes to liver disease.

It is becoming clear that nutritional effects and the toxic effects of alcohol often are intertwined at the biochemical level. For example, alcohol induces the MEOS to break down alcohol, but this breakdown also leads to the previously mentioned waste of energy observed in alcoholics who replace carbohydrates in their diet with alcohol. Similarly, alcohol promotes the breakdown of nutrients such as vitamin A, of which alcoholics may already consume too little with their diet.

Relationships Between Nutritional Factors and Alcohol Metabolism

As indicated in the previous sections, complex interactions exist between alcohol and its metabolism and other nutritional and metabolic factors. In the liver, alcohol is broken down primarily through two pathways: the enzyme alcohol dehydrogenase and the MEOS. Both of these pathways have several nutritional and metabolic consequences in heavy drinkers.

Pathways of Alcohol Metabolism

Alcohol is broken down in the liver primarily through two pathways: the alcohol dehydrogenase pathway and the microsomal ethanol-oxidizing system (MEOS). In people who consume alcohol at moderate levels and/or only occasionally, most of the alcohol is broken down by ADH, an enzyme found in the fluid that fills the cell (the cytosol). ADH converts alcohol (chemically known as ethanol) to acetaldehyde, a toxic and highly reactive molecule. During this reaction, hydrogen is removed from the alcohol and transferred to a molecule called nicotinamide adenine dinucleotide (NAD), converting it to reduced NAD (NADH). As described in the main article, NADH participates in numerous other metabolic reactions, passing on the hydrogen to other compounds, and excess cellular NADH levels have harmful effects on those cells. Subsequently, the acetaldehyde is converted to acetate by a second enzyme, aldehyde dehydrogenase.

The MEOS plays a role in alcohol metabolism, particularly after higher alcohol consumption. As the name implies, the reactions that make up the MEOS occur in microsomes, small sphere-shaped vesicles that are split off from a membrane-enclosed cell structure called the endoplasmic reticulum, which serves to transport molecules through and out of the cells. The main component of the MEOS is the enzyme cytochrome P450, which, like ADH, converts alcohol to acetaldehyde. This reaction also relies on oxygen and a molecule called reduced nicotinamide adenine dinucleotide phosphate (NADPH) and results in the formation of NADP and water. As byproducts of these reactions, highly reactive, oxygen-containing molecules called oxygen radicals or reactive oxygen species (ROS) are generated. These ROS can contribute to liver damage through a variety of mechanisms.

Although the rate at which ADH breaks down alcohol generally stays the same, the activity of the MEOS can be increased (induced) by alcohol consumption. Because the MEOS metabolizes not only alcohol but also other compounds (certain medications), enhanced MEOS activity resulting from high alcohol consumption also can alter the metabolism of those medications. This may contribute to harmful interactions between alcohol and those medications or otherwise influence the activity of those medications.

Of the several variants of cytochrome P450, a form called CYP2E1 is most prominent in alcohol metabolism. The activity of this molecule can increase up to fourfold following alcohol consumption. Other types of cytochrome P450, such as CYP1A2 and CYP3A4, also are involved in the breakdown of alcohol.

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