The Health Implications of Alcohol Consumption

Alcohol is a large part of Australian culture and, for the most part, many of us don't give our habitual intake any thought. But given the health risks associated with its consumption, it is worth considering how often and how much we drink, and what we can do to reduce its impact on our health.

How Much Is Too Much?

A person's response and tolerance to alcohol depends on many factors including their weight, state of health, and other individual aspects. And, whilst there is no 'recommended amount’ a person should drink, the National Health and Medical Research Council (NHMRC) guidelines state: 

• The lifetime risk of harm from drinking alcohol increases with the amount consumed - for healthy men and women, drinking no more than two standard drinks on any day reduces the lifetime risk of harm from alcohol-related disease or injury.
• On a single occasion of drinking, the risk of alcohol-related injury increases with the amount consumed - for healthy men and women, drinking no more than four standard drinks on a single occasion reduces the risk of alcohol-related injury arising from that occasion.

*Lifetime risky drinkers are defined as people who consume more than 2 standard drinks per day (on average over a 12 month period). Single occasion risky drinkers are defined as people consuming 5 or more standard drinks on a single drinking occasion.

Metabolism Of Alcohol

Every time we ingest or imbibe anything, our body has to process and metabolise it. When it comes to compounds like alcohol, there is even more effort involved.

Upon ingestion, alcohol is absorbed from the stomach and small intestine by diffusion. Most absorption (80%) occurs from the small intestine due to its large surface area and rich blood supply. The rate of absorption varies with the emptying time of the stomach, with the rate slowing if it is consumed with food. Generally, the higher the alcohol concentration of the beverage, the faster the rate of absorption. However, above a certain concentration, the rate of absorption may decrease due to the delayed passage of alcohol from the stomach into the small intestine. Body tissues absorb alcohol at different rates. For example, muscle tissue absorbs alcohol more rapidly than fat tissue. This absorption into muscle tissue would mean that less alcohol is circulating in the bloodstream. 

Once absorbed into the bloodstream, alcohol is eliminated from the body by excretion and metabolism. Most alcohol is metabolised, or burned, in a manner similar to food, yielding carbon dioxide and water. Alcohol leaves the body in three ways: The kidney eliminates five percent of alcohol in the urine. The lungs exhale five percent of alcohol, which can be detected by breathalyser devices. The liver deals with the rest.

The two principal enzymes involved in ethanol oxidative metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). ADH is responsible for the metabolism of ethanol to acetaldehyde. ALDH catalyses the conversion of acetaldehyde to acetate. Much of the acetate produced by oxidation of acetaldehyde leaves the liver and circulates to peripheral tissues where it is activated to a key metabolite, acetyl CoA. The different isozymes account for the diversity of alcohol metabolism among individuals.[1]

CYP450 enzymes can also oxidise ethanol. CYP2E1 has the highest activity for oxidising alcohol to acetaldehyde, and this particular pathway results in the production of large amounts of reactive oxygen species (ROS). Independent of microsomal oxidation, alcohol can also be oxidised by catalase, another cellular enzyme.

Glutathionation is the primary phase 2 detoxification pathway via which conjugates are excreted.The glucoronidation pathway may also be utilised as ethanol can also be conjugated with glucuronic acid to form ethylglucuronide, which is readily excreted. However, cofactor availability and poor affinity for alcohol does limit this pathway.[1]

Elimination occurs at a constant rate for a given individual and understanding the rate of metabolism is critical to understanding the effects of alcohol. In general, the liver can process one ounce of liquor (approximately 30mL or one standard drink) in one hour. If more than this is consumed the system becomes saturated, and the additional alcohol will accumulate in the blood and body tissues until it can be metabolised.

Factors Influencing Metabolism

Food - food in the stomach can have a big influence on the absorption of alcohol. The food will dilute the alcohol and slow the emptying of the stomach into the small intestine, where alcohol is rapidly absorbed. Peak blood alcohol concentration (BAC) could be as much as three times higher in someone with an empty stomach than in someone who has eaten a meal before drinking. Eating regular meals and having snacks while drinking will keep you from getting too drunk too quickly.

Nationality - some people of Asian descent have more difficulty metabolising alcohol. An isozyme of ADH (beta 2 beta 2) is found more frequently in Asians than in caucasians, and an ALDH isozyme (ALDH2), although present in Asians, it is often in an inactive form. The presence of an inactive form of ALDH2 is thought to be responsible for an increase in acetaldehyde levels in the body. Acetaldehyde is considered responsible for the facial flushing reaction, nausea, headache, dizziness and rapid heartbeat often observed among Asians who have consumed alcohol. It is estimated that up to 50% of Asians are susceptible to these reactions to alcohol.[2] 

Gender - women should be aware that, over a lifetime, the risk of alcohol-related disease increases more quickly for women; and on a single occasion, women may reach higher blood alcohol levels than men who have consumed an equivalent amount of alcohol. This is due to smaller body mass and metabolic rate, and the fact that women produce less dehydrogenase than men. Furthermore, premenstrual hormonal changes cause intoxication to set in faster during the days right before a woman gets her period. Birth control pills or other medication with oestrogen will also slow down the rate at which alcohol is eliminated from the body.

Genetics - 13 different CYP2E1 polymorphisms have been identified that may be important risk factors for carcinogenicity of certain toxins including alcohol.

The Impact Of Alcohol

In addition to the immediate effect of alcohol ingestion (altered speech, hazy thinking, slowed reaction time, dulled hearing, impaired vision, weakened muscles, and foggy memory), regular consumption of alcohol can start to wreak havoc on overall health - inside and out. And drinking too much – on a single occasion or over time – can take a serious toll. 

Not only does alcohol deplete vital nutrients, it can cause some real problems to organs and tissues:

The Gastrointestinal (GI) System
Whilst in the stomach, alcohol acts as an irritant and increases digestive secretions (HCl acid), and in large amounts slow digestion. Chronic irritation may lead to damage to the lining of the stomach. Alcohol in combination with medications that cause GI irritation (i.e. aspirin) can cause gastritis, ulcers and severe bleeding.

The Liver
Even moderate social drinkers can experience liver damage such as a fatty liver, and hepatitis or cirrhosis can develop from heavy consumption. Fatty liver, where hepatocytes are swollen with fat globules and water, is the earliest stage of alcoholic liver disease followed by hepatitis. Alcohol can also inflame the pancreas, which affects digestion (and increases the risk of developing diabetes and pancreatic cancer).

The Brain
It only takes 30 seconds for the first amounts of alcohol to reach the brain after ingestion. Once there, alcohol acts primarily on nerve cells deep in the brain. As a central nervous system (CNS) depressant some neurotransmitters are inhibited, and judgement and coordination become impaired. Because of the way alcohol affects the brain it can alter your mood and behaviour, and in turn increase your risk for anxiety, depression and dementia. Heavy drinking can inhibit the firing of the nerve cells that control breathing resulting in respiratory depression, which can be fatal.

The Heart
Whilst there is some research that indicates alcohol has benefits to the heart, moderate to heavy drinking can create health risks such as a rise in blood pressure and high triglycerides. Of course excessive drinking can damage your heart resulting in problems like irregular heart beat, high blood pressure and stroke - and lead to cardiomyopathy, arrhythmia and death.

Drinking too much also puts pressure on the kidneys, and weakens the immune system (increasing susceptibility to getting sick). It also increases the risk of developing several types of cancer including mouth, throat and breast cancer.

You can read more about the detrimental effects of alcohol here.

Naturopathic Support

Alcohol consumption not only depletes a number of nutrients but also causes oxidative damage and depletes mitochondrial DNA in the liver, brain heart and skeletal muscles.[3] The empty calories (and sometimes what is eaten under the influence) can lead to weight gain. Alcohol also has a both a direct, and indirect impact on hormones which can lead to fluid retention, an irregular menstrual cycle, and break outs. Quality of sleep is also affected which has an impact on energy and concentration.

Where alcohol is consumed regularly, it is worth considering the following:

Practical Recommendations

• Don’t drink on an empty stomach 
• Aim for roughly 1 drink per hour
• Alternate each drink with water to maintain hydration and space out your alcoholic drinks
• Consider electrolyte replacements (especially magnesium)
• Be mindful of weekly intake
• Increase intake of antioxidant-rich fruit and vegetables, especially deeply pigmented produce and crucifiers vegetables

Nutritional Support

• Alcohol depletes many different nutrients, especially B vitamins - a good quality multivitamin every day is a great place to start, and on days that alcohol is consumed - take two. The vitamin cofactor NAD+ (derived from B3) is required for ADH and ALDH function.[4]
• Alcohol metabolism also taxes zinc levels as ADH is a zinc-containing enzyme. Zinc administration may improve the metabolism of alcohol.[5,6]
• The irritant effect of alcohol on the gastrointestinal system, and its sugar content, may also have an impact on the microbiome. As such, gastrointestinal support and regular probiotic consumption is recommended.[7,8]

Hepatic Support

• The herb milk thistle has protective and regenerative effects on the liver.[9,10,11] It is worth considering supplementation to buffer alcohol-induced liver damage. The herb is not only a powerful antioxidant but can reduce the production of inflammatory cytokines as well.[12]
• Given the glutathionation pathway is dependant on glutathione, supplementation and/or the use of cysteine and glutamine, is prudent. Nutrients that support glutathione production like selenium and alpha-lipoic acid are also a good idea.

Neurological Support

• Coenzyme Q10 (CoQ10) is an antioxidant with numerous benefits that include protecting the brain from the full impact of alcohol-induced damage. It appears that the addition of quercetin provides further benefits.[13] In a study on astrocytes, the mechanisms of CoQ10’s protective action appeared to be via suppression of oxidative stress, prevention of mitochondrial dysfunction as well as the blockade of the mitochondria-mediated cell death pathway, and enhancement of mitochondrial biogenesis.[14]
• Interestingly, acetyl-l-carnitine has also been shown to provide a protective effect against alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission.[15] In one particular study it was identified that alcohol intake reduces brain mitochondrial B-oxidation which, in turn, severely reduces the levels of complex I and V. A reduction in complex I is associated with a decrease in carnitine palmitoyltransferase 1 (cPT1) and cPT2 levels. This causes an increase in cytochrome C leakage, and a decrease in depolarisation of mitochondrial membrane potential and ATP (energy) production.[16]

References

1. Bernstein D. A practical approach to the spectrum of alcoholic liver disease, An issue of clinics in liver disease, Volume 16-4. 1st Edition. Saunders 2012. 
    
2. Suddendorf R. Research on alcohol metabolism among Asians and its implications for understanding causes of alcoholism. Public Health Rep 1989;104(6):615–620. [Full Text] 
    
3. Mansouri A, Demeilliers C, Amsellem S. et al. Acute ethanol administration oxidatively damages and depletes mitochondrial DNA in mouse liver, brain, heart, and skeletal muscles. J Pharmacol Exp Ther 2001;298(2):737-743. [Full Text] 
    
4. Sauve A. NAD+ and vitamin B3: from metabolism to therapies. J Pharmacol Exp Ther 2008;324(3):883-893. [Full Text] 
    
5. Caballeria J, Gimenez A, Andrew H.et al. Zinc administration improves gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol in alcohol-fed rats. Alcohol Clin Exp Res 1997;21(9):1619-1622. [Abstract] 
    
6. Das I, Burch RE, Hahn HK. Effects of zinc deficiency on ethanol metabolism and alcohol and aldehyde dehydrogenase activities. J Lab Clin Med 1984;104(4):610-617. [Abstract] 
    
7. Leclerc S, Matamoros S, Cani P. et al. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proc Natl Acad Sci USA 2014;111(42):E4485-E4493. [Full Text] 
    
8. Purohit V, Bode J, Bode C. et al. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol 2008;42(5):349-361. [Full Text] 
    
9. Choi YH, Chin YW, Kim YG. Herb-drug interactions: focus on metabolic enzymes and transporters. Arch Pharm Res 2011;34(11):1843-1863. [Abstract] 
    
10. National Toxicology Program. Toxicology and carcinogenesis studies of milk thistle extract (CAS No. 84604-20-6) in F344/N rats and B6C3F1 mice (Feed Studies). Natl Toxicol Program Tech Rep Ser. 2011;565:1-177. [Abstract] 
     
11. Shi S, Klotz U. Drug interactions with herbal medicines. Clin Pharmacokinet 2012 May;51(2):77-104. [Abstract] 
     
12. Liu S, Chen Z, Cao D. et al. A study on the protective effect of Silybum marianum extract on hepatic ischemia-reperfusion injury. Afr J Tradit Complement Altern Med 2013;10(5):310-312. [Full Text] 
     
13. Sashindran R, Balasundaram M, Jegathambigai R. et al. Evaluation of neuroprotective effect of quercetin and coenzyme Q10 in ethanol induced neurotoxicity in mice. Int J App Biol Pharma Technol 2015;6(1):67-71. [Abstract] 
     
14. Jing L, He M, Yue C. et al. Coenzyme Q10 protects astrocytes from ROS-induced damage through inhibition of mitochondria-mediated cell death pathway. Int J Biol Sci 2015;11(1):59-66. [Full Text] 
     
15. Rump T, Muneer P, Szlachetka A. et al. Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain. Free Radic Biol Med 2010;49(10):1494-1504. [Full Text] 
     
16. Hooray J, Rump T, Xiong H. Reduction of brain mitochondrial β-oxidation impairs complex I and V in chronic alcohol intake: the underlying mechanism for neurodegeneration. PLoS One 2013;8(8): e70833. [Full Text] 

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