Development, Prevention, and Treatment of Alcohol-Induced Organ Injury: The Role of Nutrition

Abstract

Alcohol and nutrition have the potential to interact at multiple levels. For example, heavy alcohol consumption can interfere with normal nutrition, resulting in overall malnutrition or in deficiencies of important micronutrients, such as zinc, by reducing their absorption or increasing their loss. Interactions between alcohol consumption and nutrition also can affect epigenetic regulation of gene expression by influencing multiple regulatory mechanisms, including methylation and acetylation of histone proteins and DNA. These effects may contribute to alcohol-related organ or tissue injury. The impact of alcohol-nutrition interactions has been assessed for several organs and tissues, including the intestine, where heavy alcohol use can increase intestinal permeability, and the liver, where the degree of malnutrition can be associated with the severity of liver injury and liver disease. Alcohol-nutrition interactions also play a role in alcohol-related lung injury, brain injury, and immune dysfunction. Therefore, treatment involving nutrient supplementation (e.g., with zinc or S-adenosylmethionine) may help prevent or attenuate some types of alcohol-induced organ damage.

Figure 1

Drinking levels and their consequences. In the United States, drinking levels are expressed in terms of standard drinks consumed—that is, the number of alcoholic beverages drunk, each containing about 0.6 fluid ounce or 14 grams of pure alcohol. The Dietary Guidelines for Americans 2015–2020 defines moderate drinking as consuming up to 2 drinks/day for men and up to 1 drink/day for women. The Substance Abuse and Mental Health Services Administration defines binge drinking as consuming 5 or more (for men) or 4 or more (for women) alcoholic drinks on the same occasion on at least 1 day in the past 30 days (National Institute on Alcohol Abuse and Alcoholism 2016). High-intensity drinking refers to drinking at levels far beyond the binge threshold, resulting in high peak blood alcohol concentrations. Some studies define high-intensity drinking as two or more times the gender-specific binge drinking thresholds (Patrick et al. 2016); others use a higher threshold (Johnston et al. 2016). Some individuals drink considerably more than this. For example, one study found that patients admitted to a National Institutes of Health treatment facility with a diagnosis of alcohol use disorder consumed the equivalent of 13 drinks per day (Vatsalaya et al. 2016). In these drinkers, the metabolic effects of alcohol and altered nutrient intake may set the stage for alcohol–nutrient interactions and organ injury.

Figure 2

Chronic alcohol user who had been consuming large amounts of beer before admission. Note classical skin lesions of zinc deficiency around the eyes, nose, and mouth.

Figure 3

Zinc therapy positively affects multiple mechanisms of alcohol-induced organ injury. Thus, zinc enhances the gut barrier and tight junctions, thereby reducing gut permeability and the risk of transfer of bacterial endotoxin into the blood (i.e., endotoxemia). In addition, zinc decreases proinflammatory cytokine production and oxidative stress and ensures proper functioning of important zinc-dependent regulatory proteins (e.g., zinc-finger proteins). Through these and other mechanisms, zinc supplementation can improve liver injury and may attenuate lung and brain dysfunction.

Figure 4

Alcohol (EtOH) consumption combined with dietary intake of unsaturated fatty acids (USFs) (e.g., linoleic acid [LA]) can have numerous deleterious effects on the intestine, blood, and liver. In the intestine, this combination changes the bacterial composition (microbiome) and interferes with various aspects of the body’s defense systems, thereby increasing intestinal permeability. This leads to endotoxemia and liver injury. NOTE: TLR = toll-like receptor.

Figure 5

Effects of saturated fat (SF) and unsaturated fat (USF) diets on endotoxemia, intestinal tight junctions, gut microbiome, and liver injury in response to chronic alcohol (EtOH) feeding. (A) Plasma endotoxin levels assessed by plasma lipopolysaccharide (LPS) measurement. Alcohol feeding significantly increases LPS levels in the plasma when combined with a USF diet. (B) Levels of the mRNA for the tight-junction protein zonula occuldens-1 (ZO-1) in the intestine. Animals receiving a USF diet showed greater disruption of tight junctions (i.e., lower ZO-1 levels) than animals receiving a SF diet; this effect was exacerbated with alcohol feeding. (C) Comparative analysis of the relative abundance of different phyla of gut bacteria in mice fed ethanol and different types of dietary lipids. The phyla abundance is indicated by the color bars. (D) Liver injury was evaluated by plasma alanine aminotransferase (ALT) activity. In animals receiving a USF diet, but not in those receiving a SF diet, alcohol feeding caused significant liver injury. NOTE: Horizontal bars indicate statistically significant differences.