Alcohol

ALCOHOL

There is perhaps no other recreational drug that has had such a profound effect on human societies as alcohol. It is imbibed, in some form or another, by almost all societies. In this newsletter I will provide a biopsychosocial commentary on its usage, effects, metabolism, complications, and on breathalyzers. When the word alcohol is used here, it refers specifically to ethanol, because ethanol is usually the fermentation product in alcoholic beverages. But first some preliminaries.

The history of alcohol and the disingenuous claims of its medical and social benefits

Alcohol, usually in the form of ethanol (C2H5OH), is produced as a fermentation product by bacteria and fungi. A wide range of carbon-based compounds from most parts of plants are used as the primary energy source. These include grapes and other berries, fruits (apples, pears, etc.), roots and tubers (e.g., potatoes), grains and grasses, stems, and leaves. Some of the earliest evidence for human production of alcohol can be found in clay pots dating to 7000-6600 BCE and discovered in the Yellow River Valley. Rice, honey, and fruits were fermented, and the alcohol products were likely used in social, religious, or medical practices. Alcohol fermentation was introduced independently by many other cultures, but it seems that these occurred later. Besides the obvious medical uses (e.g., as an antiseptic), alcohol has previously been touted as having medical and social benefits. Recent meta-analyses of the putative medical benefits have been highly critical of previous reports that claimed alcohol, especially when associated with red wines, can protect against cardiovascular and other diseases when imbibed in limited quantities, of the order of one standard glass every other day. While this is an appealing claim, the benefits appear to be entirely overstated, something that astute medical practitioners were always wary about. The most recent reviews lead to the conclusion that no amount of alcohol consumption, in any beverage, is beneficial, although minimal consumption may not have any adverse long-term sequelae. This is another reminder that clinical research must always be subjected to the most stringent review. Discerning researchers always have a healthy dose of skepticism, and the motivations of funders should be considered. One can also ask: are there any social benefits to alcohol consumption? As advertising agencies are keen to illustrate, alcohol is, in some circumstances, a social lubricant. Whether this represents a benefit is really a question for sociologists and those in the mental health professions. And, of course, the conviviality that may accompany alcohol consumption must always be weighed up against the much more obvious social costs. The association between alcohol abuse and societal problems in South Africa like domestic and other violence, social disintegration, mental health problems, road traffic accidents, and so much more makes for horrendous reading. It would be wholly disingenuous to tout the benefits of alcohol consumption in social settings without contrasting them with the far greater costs to society and the economy.

The acute effects of alcohol consumption and measuring blood alcohol concentration in expired air

The absorption of alcohol begins immediately after ingestion, first through the mucus membranes in the mouth, then the gastric mucosa and small intestine. Ethanol is a small molecule and easily traverses cell membranes or enters the synaptic junctions in the central nervous system (CNS). The CNS is, of course, where most of the acute effects of alcohol ingestion occur. Alcohol is a nervous system depressant. It binds strongly to GABA (gamma-aminobutyric acid) receptors, thereby activating inhibitory cascades, which in turn lead to sedation, cognitive dysfunction, decreased coordination, muscle relaxation, and many other neurological and psychosocial effects. The short-term pleasurable effects of alcohol consumption are due to increases in neurotransmitters like dopamine and serotonin, as well as endorphins. These effects are, of course, temporary, but explain the anxiolytic effects, sense of well-being, and interactions that appeal to social drinkers. The pleasure effects are not experienced uniformly. Side-effects like nausea and headache may be more prominent and others with relative or functional enzyme deficiencies (like the alcohol dehydrogenase and acetaldehyde dehydrogenase relative deficiencies common in Asians) experience both pleasurable and unpleasant toxic effects more acutely. The conventional teaching is that the body metabolizes ethanol at 0.016g% per hour. So, for example, it will take 10 hours for a person with a blood alcohol reading of 0.16 to reach zero. This is, however, hugely variable based on genetic polymorphisms, medications, co-ingestion of other drugs, alcohol consumption history, weight, fat composition, smoking, liver function, co-consumption of food, hydration status, etc. This means that estimating blood alcohol levels based on consumption is, at best, guesswork. From a legal perspective, exhibiting signs and symptoms of alcohol consumption typically override the BAC (blood alcohol concentration) measurement even if it is below the 'legal' limit. Alcohol is a volatile organic compound so once it reaches the lungs via the circulatory system, it readily diffuses into the alveoli and is expired during respiration. Breathalyzers work by detecting the ethanol concentration in expired air. As the individual expires, the device continuously monitors the sample breath using an infrared cell (other more complex methods are available in portable breathalyzers, but the infrared cell method is most common). The concentration of ethanol increases as expiration continues. Once the ethanol level stabilizes, a reading is obtained from an infrared cell. Ethanol absorbs infrared wavelengths—the greater the concentration of ethanol in expired air the more the infrared beam is absorbed.

Ethanol metabolism

The first step in ethanol metabolism results in acetaldehyde production and three possible enzymes perform this biochemical step (Figure 1). Most of the ethanol is oxidized via alcohol dehydrogenase. Cytochrome P450 2E1 (CYP2E1) is also capable of ethanol oxidation, but it is usually only induced when ethanol concentrations are very high. Catalase metabolizes only a small fraction of alcohol. Acetaldehyde is a highly toxic compound and is further oxidized to acetate by aldehyde dehydrogenase. Acetate can be catalyzed to acetyl-CoA by acetyl-CoA synthetase, and the acetyl-CoA formed feeds into the citric acid cycle or may be used in lipid biosynthesis. Ethanol consumption is, therefore, a rich energy source and in addition to the chronic complications discussed below, is a common cause of weight gain. Small amounts of alcohol may also interact with fatty acids to form compounds called fatty acid ethyl esters (FAEEs). These are toxic, especially to hepatic and pancreatic cells.

Complications of alcohol abuse

The chronic complications of alcohol are due to ethanol itself, acetaldehyde, and other biochemical by-products. In addition to the effects on neurotransmission and the increase in endorphin release, which may have long-term sequelae like the depletion of serotonin and dopamine stores, alcohol is itself toxic. Ethanol is an organic solvent and anyone who has carried out practical laboratory work will attest to the ease with which ethanol damages cell membranes. Acetaldehyde is highly toxic. It forms adducts with proteins and nucleic acids. Some of these acetaldehyde-protein and acetaldehyde-DNA adducts are irreversible, which means that cellular functions are globally compromised, and DNA damage is common. Acetaldehyde toxicity spares no cell type, and it is unsurprising therefore that chronic alcohol abuse affects all physiological systems. One of the toxic by-products of alcohol metabolism is the reactive oxygen species. These also cause oxidation of biomolecules and may induce apoptosis. Finally, alcohol withdrawal is an extremely dangerous long-term complication. In chronic alcohol abuse, the abrupt cessation of alcohol use can trigger delirium tremens, which is the most severe form of withdrawal. Left untreated, the mortality rate is approximately 35%. A symptom triggered regimen of benzodiazepines is still the mainstay treatment. Barbiturates, anticonvulsants, adrenergic drugs, and GABA agonists are also used.

Closing remark

Alcohol is an extremely hazardous toxin. It is clear that were any other medication, toxin, or recreational drug associated with the hazardous effects such as those related to alcohol, they would be made illegal without hesitation. Of course, attempts were made to outlaw alcohol production (the prohibition years in the USA) and its usage has previously been regulated (e.g., during the COVID pandemic). These were, however, spectacular failures, which underlines the profound psychosocial effects of alcohol consumption.