SCIENCE OF ALCOHOL METABOLISM

Alcohol Metabolism

How does the human body break down alcohol?

ADH + ALDH Enzymes

Alcohol metabolism is carried out by alcohol dehydrogenase enzymes (ADH) and aldehyde dehydrogenase enzymes (ALDH) in the body1.  These enzymes require specific cofactors and coenzymes to perform their job.

Cofactors & Coenzymes

Zinc and nicotinamide adenine dinucleotide (NAD) are the essential cofactors and coenzymes required by ADH and ALDH enzymes to break alcohol down. During alcohol consumption, these co-factors and co-enzymes are used up2.

Acetaldehyde Build Up

Depletion of these cofactors & coenzymes when drinking causes the build-up of acetaldehyde, a toxic by-product of alcohol metabolism.  Hangover symptoms are primarily caused by the build up of acetaldehyde 3.


ADH + ALDH Enzymes

The alcohol metabolism process is conducted by a family of Alcohol dehydrogenase enzymes (ADH) and Aldehyde dehydrogenase enzymes (ALDH) in the body1.  Alcohol is converted to Acetaldehyde by the ADH enzyme. Then Acetaldehyde is converted to Acetate by the ALDH enzyme.

These enzymes require cofactors and coenzymes to perform their reactions.  In the human ADH and ALDH enzymes, Zinc is used to holds the alcohol in it place and Nicotinamide adenine dinucleotide (NAD) which is constructed from Nicotinamide, is used to break it down. When enzymes run out of cofactors they stop working. Acetaldehyde is a toxic molecule and when it builds up it causes hangover symptoms.

Recoverthol replaces the cofactors that are used up. Providing additional fuel for the enzymes to function. This allows the enzymes to remove acetaldehyde effectively.


Cofactors & Coenzymes

So what are these cofactors and coenzymes? Cofactors and coenzymes are essential for enzymes function, without them the enzymes are inactive. Cofactors, mostly metal ions such as Zinc, and coenzymes, are inorganic and organic molecules that assist enzymes during the catalysis of reactions.

The ADH and ALDH activity is solely dependent on the level of available cofactors and co-enzymes.  Regardless of the enzymes level (genetic factors), the efficient activity of this enzyme is promoted when there are enough cofactors and coenzymes available to perform the reaction. 

The levels of these cofactors and coenzymes also deplete during alcohol consumption2. Lack of these cofactors & coenzymes leads to the inefficient metabolism of alcohol, and the build up acetaldehyde.  Inefficient metabolism of alcohol is due to low activity of ADH and ALDH enzyme3.  Hence, Recoverthol promotes efficient enzyme activity in the metabolism of alcohol by ADH and ALDH enzymes.

You may be surprised to know that your body contains these cofactors and coenzymes naturally- but only enough to process about 1-2 standard drinks (depending on you weight, gender and other factors). Recoverthol simply helps to replenish the cofactors and coenzymes (i.e. the ingredients of Recoverthol) that your body uses up when you drink, supporting the ongoing metabolism of alcohol.

That is why Recoverthol works best if you add it to your first drink to fortify you drink with extra dose of these cofactors and coenzymes. Recoverthol’s unique formulation together with its targeted delivery method, allows necessary fuel to reach the ADH and ALDH enzymes at the same time as alcohol. This is why you add it to your first drink.


Acetaldehyde Build Up

Inefficient metabolism of alcohol leads to the build up of acetaldehyde, a toxic molecule that is damaging to the body’s organs, and causes the symptoms commonly know as hangover.  Factors effecting the severity and onset of acetaldehyde build up depend on genetic factors, gender, age, weight, fatty liver syndrome (hepatic steatosis) and the amount of alcohol consumed. 

The concentration of the oxidized form of nicotinamide adenine dinucleotide (NAD+) reaches its rate-limiting state shortly after ingestion and remains constant.  Ethanol elimination is approximately zeroth order, supporting the suggestion that the reaction is limited by the amount of enzyme, co-enzyme, or both4(D.M. Umulis et al).

Research has shown that people can carry different variations of the ADH and ALDH enzyme.  Some variants work more efficiently in metabolising alcohol than others.  This means that some people can have toxic acetaldehyde build up more rapidly in the body as they have either a fast variant of the ADH enzyme or a slow ALDH variant. 

The variant of ADH and ALDH enzyme that a person carries can also influence how much alcohol they consume.  Acetaldehyde build up in the body may also increase an individual’s risk of developing an addiction to alcohol.  For example, a particular variant of the ADH enzyme called ADH1B*2 is common in people of Chinese, Japanese and Korean descent. 

This enzyme may protect individuals against alcoholism as ADH1B*2 metabolises alcohol very efficiently which leads to increased levels of acetaldehyde and causes unpleasant sensations such as nausea, facial flushing and a rapid heartbeat even when only moderate amounts of alcohol are consumed. 

Studies have also linked acetaldehyde to some of the behavioural and physiological effects that have previously been linked to alcohol itself.  Other factors affecting the severity and onset of acetaldehyde build up also depend on gender, age, weight, fatty liver syndrome (hepatic steatosis) and the amount of alcohol consumed.

The body conducts the alcohol metabolism process at a rate of 0.016% per hour. It doesn’t matter if you are 6’4” or 4’6,” or if you drink red wine or moonshine.  Once your blood alcohol concentration (BAC) reaches a certain level, no matter how it got to that level, your body needs time to break the alcohol down and remove it from your system.

adh aldh nad

Herbal Ingredients in Hangover Products

The inefficient metabolism of alcohol leads to the build up of acetaldehyde. Acetaldehyde is primarily responsible for hangover symptoms. It makes sense, therefore, to reduce the build up of acetaldehyde when drinking, not to simply try to mask the symptoms caused by acetaldehyde with herbal ingredients.

Most pre-drinking and post-drinking hangover products contain a blend of amino acids, vitamins, minerals and herbal ingredients. The mechanism of action of the herbal ingredients in commercially available hangover products is mostly unknown, however, some studies have shown that the herbal ingredients used in hangover products may:

  • Counteract the inflammatory response produced by alcohol consumption
  • Enhance the ADH and ALDH activities in the liver
  • Reduce the reported severity of nausea and vomiting

It is important to understand that the concentration of the nutrients and vitamins in commercially available hangover products are usually sub-therapeutic, and there is no sound scientific evidence to support the efficacy of these small concentrations and/or the combinations of ingredients used. In other words, studies have been conducted on much higher doses of these ingredients than are present in commercially available products, which only contain micrograms or milligrams of these herbs.

Adding herbal ingredients that only mask the side effects of acetaldehyde may not be such a good thing, as acetaldehyde has already done damage. Research has also shown that most of these herbal ingredients may contain dangerous insecticides, due to production methods on farms and lack of raw ingredient related substance testing at the point of manufacturing.

https://www.scientificamerican.com/article/herbal-supplement-dangers/

https://www.forbes.com/sites/emilywillingham/2013/11/07/study-herbal-supplements-full-of-contaminants-substitutes-and-fillers/#694eca23960f

https://toxnet.nlm.nih.gov/cpdb/pdfs/FDATestimonyHerbalMedicine.pdf

https://www.cbsnews.com/news/report-many-supplements-contain-lead-arsenic/

These magical herbal ingredients may also give a false belief that users can drink as much as they want, and not get a hangover.

Liver Support Ideology ?

The majority of commercial hangover supplements follow a liver support ideology. Our preliminary studies suggest that body systems other than the liver may have an important role to play in alcohol metabolism, especially in relation to the rapid onset of acetaldehyde build up in Asian flush syndrome. This leads to the investigation of alternative culprits such as the stomach and gut bacteria that also contain ADH, and contribute to alcohol metabolism. Although the use of liver tonic formulations may be beneficial to promote recovery from acetaldehyde build-up after alcohol consumption, Recoverthol works by preventing the acetaldehyde build up in the first place.

The science behind Recoverthol is very simple. It only contains the fuel that ADH and ALDH enzymes need naturally to do their job. You need to replenish these cofactors as you use them up during alcohol consumption. Recoverthol gives you an extra does of these cofactors when you need them the most. That’s why you add it to your drink. This also allows these cofactors and coenzymes to reach the ADH and ALDH enzymes at the same time as alcohol does. Just like when you exercise you need to replenish the fluid you lose, you need to replenish these cofactors when you metabolise alcohol. Otherwise you will run out of fuel for the enzymes, resulting in acetaldehyde build up.

Recoverthol contains only a unique combination of the cofactors and co-enzymes in its formulation that replenish the amount used up during the metabolism of alcohol. It only contains what ADH and ALDH enzymes need to do their job.

The formulation of Recoverthol together with how it is used (targeted delivery method), simply aims to reduces the build up of acetaldehyde and reduce symptoms of hangover.

What Causes a Hangover?

There is no way to avoid or prevent a hangover, other than to avoid alcohol altogether.  There are seven major biochemical reactions to alcohol metabolism.

Alcohol, and too much of it, triggers a cascade of reactions in your body that contribute to the symptoms known as a hangover.  These include:

  • Increased Urination: Alcohol is a diuretic. For every 200 ml of alcohol consumed, you will produce 320ml of urine.Alcohol inhibits the secretion of vasopressin. When this enzyme is suppressed, water is sent right to your bladder (along with electrolytes) to be excreted, causing you to urinate more often.
  • Dehydration: Increased urination can lead you to become quickly dehydrated and as your body draws water from your brain to function that may leave you feeling fatigued or dizzy.
  • Acetaldehyde build-up: When alcohol reaches your liver an enzyme called alcohol dehydrogenase breaks it down into acetaldehyde. Acetaldehyde is far more toxic than alcohol (by up to 30-fold).  So during the alcohol metabolism process your body again attempts to break it down with the enzyme acetaldehyde dehydrogenase and glutathione, a powerful antioxidant that is crucial for liver detoxification (glutathione contains high levels of cysteine, which is why taking this in supplement form may help avoid hangover symptoms).  Together, this powerful alcohol metabolism detox duo can break down the acetaldehyde into harmless acetate (which is similar to vinegar). However, when you drink too much alcohol your stores of glutathione become depleted which allows acetaldehyde to build up in your body, causing the toxic hangover effect.  It should be noted that women have less acetaldehyde dehydrogenase and glutathione than men which is why women may have a more severe reaction to drinking the same amount of alcohol as a man of similar weight.
  • Congeners: Congeners are ingredients produced as byproducts of fermentation and distillation. They include acetone, acetaldehyde, tannins and some flavorants in different alcoholic beverages.  Congeners are thought to make the effects of a hangover worse and it slows the alcohol metabolism process.   They are found in higher amounts in darker liquors (such as brandy, whiskey,and red wine) than clear liquors like vodka or gin.
  • Glutamine rebound: Alcohol inhibits glutamine, a natural stimulant in your body. This is partly why alcohol has a depressive effect that may make you fall asleep easily… at first.  After you’ve stopped drinking your body will work overtime increasing glutamine levels, which is why you’ll ultimately wake up more often and have a more restless night’s sleep after you drink.  This glutamine rebound may contribute to the fatigue, tremors, anxiety, restlessness and even increased blood pressure that are often felt during a hangover.
  • Disruptions to your stomach lining, blood vessels, and blood sugar: Alcohol is irritating to your stomach lining and leads to an increased production of stomach acid.  This can cause nausea, vomiting and stomach pain. Alcohol can also lead to dips in your blood sugar level, which can lead to shakiness, mood swings, fatigue and seizures.  Also, alcohol may cause your blood vessels to expand which may trigger headaches.
    Inflammatory response: Finally, alcohol also provokes an inflammatory response in your body during the alcohol metabolism process in which your immune system may trigger agents that provoke hangover symptoms including memory problems, decreased appetite and trouble concentrating.

References:

  1. Swift, M.D., Ph.D.; and Dena Davidson, Ph.D. Alcohol Hangover. Mechanisms and Mediators. Alcohol Health & Research World. Vol. 22, No. 1, 1998
  2. McElfresh KC, McDonald JF. The effect of alcohol stress on nicotinamide adenine dinucleotide (NAD+) levels in Drosophila. Biochem Genet. 1983 Apr;21(3-4):365-74
  3. Michael Hardman, Rachel A. Page, Mark S. Wiseman andKathryn E. Crow. REGULATION OF RATES OF ETHANOL METABOLISM AND LIVER [NAD+]/[NADH] RATIO. Department of Chemistry and Biochemistry Massey University Palmerston North New Zealand
  4. David M. Umulis1,  Nihat M. Gu¨rmen,  Prashant Singh, H. Scott Fogler A physiologically based model for ethanol and acetaldehyde metabolism in human beings. Alcohol 35 (2005) 3–12
  5. Pittler, M.X. & White A.R. (2003). Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial. CMAJ, 169 (12)
  6. Kim, H. & Kim, Y.J. (2017). A standardized extract of the fruit of Hovenia dulcis alleviated alcohol-induced hangover in healthy subjects with heterozygous ALDH2: A randomized, controlled, crossover trial. J Ethnopharmacol, 14;209:167-174. doi: 10.1016/j.jep.2017.07.028. Epub 2017 Jul 24
  7. Tamayo, C. & Diamond, S. (2007). Review of Clinical Trials Evaluating Safety and Efficacy of Milk Thistle (Silybum marianum [L.] Gaertn.). Integr Cancer Ther, 6(2):146-57.
  8. Osuna-Martínez, U., Reyes-Esparza J. & Rodríguez-Fragoso, L. (2014). Cactus (Opuntia ficus-indica): A Review on its Antioxidants Properties and Potential Pharmacological Use in Chronic Diseases. Nat Prod Chem Res, 2:6 DOI: 10.4172/2329-6836.1000153
  9. Lee, M.H. & Kwak J.K. (2014). Red ginseng relieves the effects of alcohol consumption and hangover symptoms in healthy men: a randomized crossover study. Food Funct, 5(3):528-34
  10. McGregor, N.R. (2007). Pueraria lobata (Kudzu root) hangover remedies and acetaldehyde-associated neoplasm risk. Alcohol, 41 469-478
  11. Lee H.S, Isse T., Kawamoto T, Baik H.W., Park J.Y. & Yang M. (2013). Effect of Korean pear (Pyruspyrifolia cv. Shingo) juice on hangover severity following alcohol consumption. Food Chem Toxicol, 58:101-6
  12. Lete, I. & Allue, J. (2016). The Effectiveness of Ginger in the Prevention of Nausea and Vomiting during Pregnancy and Chemotherapy. Integr Med Insights, 11: 11–17.

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