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Metabolism is the bodys process of converting ingested substances to other compounds. Metabolism results in some substances becoming more, and some less, toxic than those originally ingested. Metabolism involves a number of processes. A primary mode of detoxification in the body is referred to as oxidation. Via oxidation, ethanol (alcohol in a more generic form) is detoxified and thus removed from the bloodstream. This prevents the alcohol from accumulating and destroying various cells and organs in general. However, if an excessive amount of alcohol escapes metabolism, it is excreted unchanged and is detectable in the breath and in urine. Until all the alcohol consumed has been metabolized, it is distributed throughout the body, affecting the brain and other tissues.
Figure 1: The enzymes alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1), and catalase all contribute to oxidative metabolism of alcohol. ADH, present in the fluid of the cell (i.e., cytosol), converts alcohol (i.e., ethanol) to acetaldehyde. This reaction involves an intermediate carrier of electrons, nicotinamide adenine dinucleotide (NAD +), which is reduced by two electrons to form NADH. Catalase, located in cell bodies called peroxisomes, requires hydrogen peroxide (H2O2) to oxidize alcohol. CYP2E1, present predominantly in the cells microsomes, assumes an important role in metabolizing ethanol to acetaldehyde at elevated ethanol concentrations. Acetaldehyde is metabolized mainly by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria to form acetate and NADH. ROS, reactive oxygen species.
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After the consumption of one standard drink, the amount of alcohol in the drinkers blood (blood alcohol concentration, or BAC) peaks within 30 to 45 minutes. (A standard drink is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80-proof distilled spirits, all of which contain the same amount of alcohol.) The BAC curve, shown below, provides an estimate of the time needed to absorb and metabolize different amounts of alcohol (Widmark, 1932). Alcohol is typically metabolized more slowly than it is absorbed. As the metabolism of alcohol is slow and thus rate limiting, consumption needs to be controlled and monitored so as to prevent accumulation in the body and therefore subsequent intoxication.
2. Alcohol withdrawal
Evidence suggests that a hangover is a mild manifestation of the Alcohol Withdrawal (AW) syndrome in non-alcohol- dependent drinkers. The reasons are the following: Signs and symptoms of hangover and mild AW overlap. The Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale (an instrument widely used to assess the severity of a withdrawal episode in alcoholdependent patients) measures withdrawal-associated items. These include nausea and vomiting; tremor; sweating; anxiety; agitation; headache; disturbances in touch, hearing, and vision; orientation (e.g., awareness of the date and location). The hangover condition is actually a state of central nervous system excitation, despite the perceived sedation and malaise. Alcohol re-administration (hair of the dog that bit you) alleviates the unpleasantness of both AW syndrome and hangovers suggest that the two experiences share a common process.
Blood alcohol concentration (BAC) after the rapid consumption of different amounts of alcohol by eight adult fasting male subjects.* (Adapted from Wilkinson et al., Journal of Pharmacokinetics and Biopharmaceutics5(3):207-224, 1977.) N.B. 100 mg% is the legal level of intoxication in most States. 50 mg% is the level at which deterioration of driving skills begins. (JAMA 255:522-527, 1986.)
2. Gender
The overall absorption and metabolism of alcohol has been shown to be different between men and women. Women have higher BACs after consuming the same amount of alcohol as men. The difference in BACs between women and men has been attributed to the reduced volume of body fluid in women. This is akin to dropping the same amount of alcohol into a smaller pail of water.
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In most people, ALDH metabolizes acetaldehyde quickly, so this intermediate metabolite does not accumulate in high concentrations, although small amounts are present in the blood during alcohol intoxication. In some people and especially those of south east Asian descent, however, genetic variants of the ALDH enzyme permit acetaldehyde to accumulate. Those people routinely flush, sweat, and become ill after consuming small amounts of alcohol. Because of the similarity between the acetaldehyde reaction and a hangover, some investigators have suggested that acetaldehyde causes hangovers. Although free acetaldehyde is never present in the blood after blood alcohol levels reach zero, the toxic effects of acetaldehyde produced during alcohol metabolism may persist into the hangover period and accentuate all the other physiological effects alcohol has on the body.
All three have been shown to reduce some of the effects of intoxication, but it has been difficult to develop an effective amethystic agent because alcohol is so well absorbed and distributed throughout the body. The use of functional foods by the general public as health supplements to improve general health and prevent the incidence of chronic diseases such as cardiovascular disease, diabetes and cancer has become a major area of interest within both the nutrition and medical communities. Of these, probiotics have been best studied with regard to disease prevention and most actively promoted commercially to the western public. Fermented foods containing large quantities of these beneficial bacteria have been consumed for a prolonged period of time in Europe to promote good health. Peer reviewed literature suggest that the probiotics in these foods may aid in preventing major health problems, such as postoperative gram- negative sepsis and other nosocomial infections in hospitalized patients, and in preventing gastroenteritis in daycare centers and retirement homes (Rolf 2000 and Bengmark 1998). Although the utility of classic probiotics is well understood, modern technology has turned increasingly to the use of multiple microbial agents microbial consortia. Microbial consortia are ubiquitous in nature and are implicated in processes of great importance to humans, from environmental remediation and wastewater treatment to assistance in food digestion. Research efforts thus far have involved the ability to manipulate the behavior of various microbial populations, thereby enforcing focus on specific applications. Some of these applications include degradation of organic compounds in aqueous environments, animal husbandry and, more importantly, human health. Biologically, the utility of engineered microbial consortia with multiple interacting microbial populations shows much promise. This is firstly because consortia can perform complicated functions in appropriate time frames that individual populations cannot and secondly because consortia are often be more resistant to environmental fluctuations. These biological traits typically rely on two organizing features. First, members of the consortium communicate with one another by a variety of mechanisms. For instance, the trading of various metabolites or the exchange of dedicated molecular signals would allow for the detection of various individual in the consortia and thus allow for appropriate biochemical responses to the presence of others in the consortium {Keller, 2006 #29}. This communication pathway enables the second important feature namely the division of labor. A stylized mechanistic model is much like that in a bee-hive not only where dedicated tasks are carried out by specialized workers but each task relies on the output of other key areas. As such, the overall output of the consortium rests on a combination of tasks performed by constituent individuals or sub-populations.
4. Non-alcohol factors
a) Compounds other than alcohol in beverages, especially methanol. Investigators now believe these compounds, known as congeners, contribute to a beverages intoxicating effects and to a subsequent hangover. b) Use of other drugs, especially nicotine i. Most heavy drinkers smoke cigarettes and anecdotal evidence suggests that smoking while drinking increases the so-called hangover effect. c) Personality type d) Family history for alcoholism
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References
CARMICHAEL, F. J., ISRAEL, Y., CRAWFORD, M., MINHAS, K., SALDIVIA, V., SANDRIN, S., CAMPISI, P. & ORREGO, H. 1991. Central nervous system effects of acetate: contribution to the central effects of ethanol. J Pharmacol Exp Ther, 259, 403-8. KELLER, L. & SURETTE, M. G. 2006. Communication in bacteria: an ecological and evolutionary perspective. Nat Rev Microbiol, 4, 249-58. LIEBER, C. S. 1994. Hepatic and metabolic effects of ethanol: pathogenesis and prevention. Ann Med, 26, 325-30. LIEBER, C. S., GENTRY, R. T. & BARAONA, E. 1994. First pass metabolism of ethanol. Alcohol Alcohol Suppl, 2, 163-9. WIDMARK, E. M. P. 1932. Die theoretischen Grundlagen und die praktische Verwendbarkeit der gerichtlich-medizinischen Alkoholbestimmung, Berlin.
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