The importance of genetic factors in alcoholism has been amply identified. Goodwin and coworkers studied adopted Danish men whose biologic parents were alcoholic and control subjects whose biologic parents were not alcoholic. All of the subjects had been adopted before the age of 5 weeks and had no knowledge of their biologic parentage. Twenty percent of the offspring of biologic alcoholic parents, but only 5 percent of the control subjects, had become alcoholics by the age of 25 to 29 years. A Swedish adoption study (Bohman) and one in the United States (Cadoret et al) corroborate these findings. Family studies disclose a threeto fourfold increased risk for alcoholism in sons and daughters of alcoholics, and twin studies show a twofold higher concordance rate for alcoholism in monozygotic than in dizygotic pairs. Details of these studies can be found in the comprehensive reviews of the genetics of alcoholism by Grove and Cadoret and by Schuckit and Winokur. The search goes on for a biologic trait, or marker, that would identify those who are genetically vulnerable to the development of alcoholism, but none has proved to be sufficiently practical or sensitive to identify all such persons (Reich).
Pharmacology and Physiology of Alcohol
Ethyl alcohol, or ethanol, is the active ingredient in beer, wine, whiskey, gin, vodka, and other alcoholic beverages. The stronger spirits contain enanthic ethers, which provide flavor but have no important pharmacologic properties. In some preparations, impurities such as amyl alcohol (fusel oil) and acetaldehyde act like alcohol but are more toxic.
Alcohol is metabolized chiefly by oxidation, less than 10 percent being excreted chemically unchanged in the urine, perspiration, and breath. The energy liberated by the oxidation of alcohol (7 kcal/g) can be utilized as completely as that derived from the metabolism of other carbohydrates. However, calories from alcohol are empty of nutrients such as proteins and vitamins and cannot be used in the repair of damaged tissue. All ingested alcohol, except that metabolized by alcohol dehydrogenase (ADH) in the stomach wall, is carried by the portal system to the liver. Here several enzyme systems independently oxidize alcohol to acetaldehyde. The most important of these, accounting for 80 to 90 percent of ethanol oxidation in vivo, are ADH and its isoenzymes. This reaction leads to the formation of acetaldehyde and the reduction of nicotinic acid dehydrogenase (NAD) to nicotinamide adenine dinucleotide (NADH). A second pathway of lesser importance involves catalase, which is located in the peroxisomes and mitochondria; a third uses the “microsomal ethanol oxidizing system” (MEOS), located mainly in the microsomes of the endoplasmic reticulum.
The details of the process by which acetaldehyde is metabolized are still not settled. Most likely it is converted by aldehyde dehydrogenase to acetate. Acetaldehyde has a number of unique biochemical effects that are not produced by alcohol alone. Persons who flush easily after ingestion of alcohol (Chinese, Japanese, and other Asians) differ from “nonflushers” with respect to the metabolism of acetaldehyde rather than to the metabolism of alcohol. The flushing reaction has been traced to a deficiency of aldehyde dehydrogenase activity (Harada et al). The low rate of alcoholism among Asians is said to be related to the flushing reaction (which is, in effect, a modified alcohol–disulfiram reaction; see further on), but this can hardly be the case, as North American Indians, a group with a high incidence of alcoholism, show the same reaction.