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Alcohol Metabolism

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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.

The Metabolic Process

When alcohol is consumed, it first passes from the stomach and small intestines into the blood. This process is referred to as absorption. The alcohol is then metabolized via metabolites (biological chemicals that break down other chemicals). In the liver, an enzyme called alcohol dehydrogenase (ADH) mediates and catalyzes the conversion of alcohol to acetaldehyde. Acetaldehyde is rapidly converted to acetate by other enzymes and is eventually metabolized via the citric acid cycle to carbon dioxide and water. Alcohol also is metabolized in the liver by the enzyme cytochrome P450IIE1 (CYP2E1), which is typically increased after chronic drinking (Lieber, 1994, Lieber et al., 1994). Most of the alcohol consumed is metabolized in the liver, but the small quantity that remains un-metabolized permits alcohol concentration to be measured in breath and urine. It is important to note that the liver can metabolize a certain amount of alcohol in a defined time frame regardless of the amount that has been consumed. This rate of alcohol metabolism depends, in part, on the amount of metabolizing enzymes in the liver, which varies among individuals and appears to have genetic determinants. For example, metabolic differences for alcohol have been shown between Asians (and some Native Americans with Asian genetics) and Caucasians. On average, approximately 50% of Asians have lower levels of aldehyde dehydrogenase. In these cases, the ingested alcohol is metabolized rapidly early in the chain of biotransformation, but the process then stalls at the aldehyde dehydrogenase phase allowing for an accumulation of alcoholic by-products. These by-products such as acetate typically cause adverse reactions of increased heart rate, facial flushing and in more severe cases motor impairment (Carmichael et al., 1991).

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.

The Effects of Acute Alcohol Metabolism/ Abuse

The physiological manifestations of the toxic effects of excessive alcohol consumption or the hangover as is most commonly referred to as can be broken down into a series of steps. Overall, alcohol disrupts the bodys circadian rhythms, inducing a jet lag that accounts for some of the deleterious effects of a hangover.

1. Direct effects of alcohol

Dehydration Electrolyte imbalance Gastrointestinal disturbances Low blood sugar Sleep and biological rhythm disturbances Headache

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.)

Factors Influencing Alcohol Absorption and Metabolism

1. Food
The presence of food, the type of food and when the alcohol is consumed all impact how quickly the stomach empties its contents into the intestine and therefore the rate at which alcohol is absorbed.

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.

3. Alcohol metabolism (i.e., acetaldehyde toxicity)

Alcohol undergoes a two-step process in its metabolism (figure 1). Enzymatic activity results in the (alcohol dehydrogenase - ADH) metabolism of alcohol to an intermediate product, acetaldehyde; then a second enzyme (aldehyde dehydrogenase - ALDH) metabolizes acetaldehyde to acetate. Acetaldehyde is a chemically reactive substance that binds to proteins and other biologically important compounds. At higher concentrations, it causes toxic effects, such as a rapid pulse, sweating, skin flushing, nausea, and vomiting which are signs of the intoxication/ hangover process.

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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

Alcohol Management Techniques

Historically, there have been no documented alcohol management techniques that speed up the metabolism of alcohol, but considerable research has been devoted to examining drugs that counteract some of the effects of alcohol or limit overall alcohol absorption. These so-called sobering-up agents are referred to as amethystic agents, named after the amethyst stone because of its absorption quality. One possible drug is RO15-4513. This experimental drug works by displacing alcohol from the GABA receptor, the neurotransmitter receptor that mediates some of alcohols CNS effects. RO15-4513 isnt widely available because it only counteracts some of the effects of alcohol and is known to cause seizure. Naloxone is another possible treatment. It is typically used in a clinical setting to reverse respiratory depression and coma associated overdoses. Other possible amethystic agents include ibuprofen, lithium carbonate (a drug usually used to treat mania in bipolar disorder), and thyrotropin-releasing hormone.

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The Triclyst Solution

Triclyst technology is sourced from a complex bioengineered microbial consortium that shows superior bio-catalytic activity in vivo. Several benefits have been shown when introducing these consortia into the Gastro-Intestinal (GI) tract. Triclyst technology promises to be a new generation technique in alcohol management. The microbial consortium delivered to the gastric and enteric tracts produces enzymes and small molecule metabolites that speed up the digestion of alcohol thereby limiting damage. The Triclyst blend of biocatalysts also improves digestion of solid foods in the GI tract which also has a beneficial effect on alcohol absorption.

About Triclyst Technology

Triclyst technology is a highly refined bio-engineering process that creates a composite biocatalyst consisting of beneficial probiotics, enzymes and small molecule metabolites. This powerful blend of biocatalysts speeds up metabolic processes in our bodies and offers a unique 100% natural approach to activating and invigorating human metabolism. Research has shown that Triclyst technology has multiple human health benefits: Speeds up metabolic activity Increases nutrient absorption during digestion Improves stamina and strength through increased energy production Provides potent anti-oxidant and antiinflammatory properties Neutralizes and eliminates toxins Assists in alcohol metabolism Naturally reduces body odors and bad breath

Supporting Scientific Research

1. Double Blind Placebo Study
A 111-patient double blind placebo controlled study was performed in Bangkok, Thailand, over a period of three months to test the safety, efficacy and potential pharmacology of Triclysts microbial consortium on human health. Importantly, there was no evidence suggesting long or short-term toxicity of these species on human health. Several beneficial effects were noted, including a reduction in the inflammatory/infective processes that occur in the body. This was highlighted by a reduction in levels of ESR, CRP and white blood cells noted between the treatment and placebo groups. Clinically, the patients recruited into the treatment group also reported a reduction in the amount of gastro-intestinal manifestations noted over the course of the three months. Other health benefits were noted incidentally in the study. A beneficial effect on high-density lipoproteins (HDL) was noted in patients in the treatment sample group. In addition modest antioxidant effects were also noted in this study.

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.

2. Precursor Alcohol Efficacy Study

A preliminary alcohol efficacy study has been conducted suggesting the following benefits while using dietary supplements containing the Triclyst blend of biocatalysts: 1. Assists in preventing hangover (Reduces alcohol levels by up to 69% within 40 minutes of a drinking episode); 2. Helps protect the liver from damage; 3. Reduces bad breath; 4. Aids gastro-intestinal health; 5. Improves digestion. Confirmatory double-blind placebo controlled clinical studies are being conducted to validate these findings.

Juventa Technologies | 150 N. Michigan Ave, Suite 2800 Chicago, IL 60601 USA |