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Old 05-08-2005, 10:10 AM   #1
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Default Alcohol: The Health Dangers & Other Info


The purpose of this thread is to explain the major toxic effects alcohol has on the body and some of the possible consequences of that toxicity. It is taken from my lecture notes from a stage 3 "intro to toxicology" paper I sat. Most of it is my own words and is all taken from my notes to try and explain specific ideas and terms.

This is only really a brief overview and is designed to cover the major points of toxicity only. I will provide some links to more in depth sources at the end.

If you see someone on the forum asking about alcohol and its effect on health and training then send them here. Anyway here goes. I have tried to keep it understandable for most people, but there really is no other way to describe this properly. Hope it helps

This said, alcohol can be enjoyed in moderation or on occasion by almost everyone, its moderation which is the key


The Toxic Effects Of Ethanol

Ethanol Toxicity includes:

Type A: Dose-dependent (pharmacological)
Type B: Idiosyncratic toxicity due to genetic polymorphisms
Type C: Chronic damage that is different from acute
Type D: DNA damage (promotion)
Type E: Embryotoxicity
Type F: Pharmacodynamic and pharmacokinetic interactions

Type A: Pharmacology

• Ethanol has been shown to affect both receptor-activated ion channels and voltage-gated ion channels. These are different cell receptor types in the brain.
• The acute intoxicating and incoordinating effects of ethanol are probably related to
–inhibition of subtypes of NMDA-glutamate receptor ion channels (excitatory cells)
–and potentiation of certain subtypes of GABAa receptor ion channels. (inhibitory cells)
• Effects on these channels, as well as glycine, nicotinic cholinergic, serotonergic, and other ion channels are likely to contribute to the euphoric, sedative, and other acute actions of ethanol. These mechanism contribute to the psychological dependence seen with ethanol.

Testosterone

• Alcohol is directly toxic to the testes, causing reduced testosterone levels in men.
• In a study of normal healthy men who received alcohol for 4 weeks, testosterone levels declined after only 5 days and continued to fall throughout the study period .
• Prolonged testosterone deficiency may contribute to a "femininization" of male sexual characteristics, for example breast enlargement.
• In addition, animal studies have shown that acute alcohol administration affects the release of hormones from the hypothalamus and pituitary.

Myeloid Suppression

• Ethanol can cause a dose-dependent suppression of bone marrow proliferation in vitro at physiological concentrations. This supresses blood cell production and immune function.
• Clinically, reduced bone marrow granulocyte production has been reported in acutely intoxicated patients in the absence of infection etc.
• Acetaldehyde may be responsible. Acetaldehyde is what the body metabolises ethanol to initialy.

Type B: Ethanol Metabolism

•Ethanol is metabolized by the enzymes alcohol dehydrogenase and cytochrome CYP2E1 to acetaldehyde, which in turn is metabolized by the enzyme aldehyde dehydrogenase to acetic acid.

Genetic Polymorphisms in Ethanol Metabolism

• Genetic polymorphisms have been identified for the enzymes ADH, ALDH and CYP2E1. This means that some people express these enzymes more than others, some people have deficient enzymes and some have none at all.
• Alcohol dehydrogenase: several forms in humans, of which ADH2 is the most important.
• There is a preponderance of ADH2 in heavy drinkers. This is induced by the drinking
• Polymorphisms in ADH3 do not appear to have major effect on the rate of ethanol metabolism but may be involved in some of the toxic effects of alcohol.



• Alcohol may protect against heart disease by raising levels of high-density lipoprotein, the "good" form of cholesterol.
–Among people who drank moderately, the highest levels of HDL were seen in those with two copies of ADH3*2. This can mean that infrequent and sensible alcohol consumption can have the effect of lowering cholesterol at levels lower than will produce most of this chronic damage. So the benefit outweighs the risk and it seems to actually be healthy to have 1/2 a glass of red wine per day.

CYP2E1

• CYP2E1 can also generate a free radical from ethanol. Radicals attack molecules like protein and DNA.

• Several mutations exist, which leads to expression of a catalytically less active form.
• There are significant inter-ethnic differences in the frequency of CYP2E1 polymorphisms, but its role in alcohol toxicity is still controversial.
–A polymorphism exists in which a mutant allele results in ~10X increase in protein expression, with a 4X increase in risk of developing alcoholic liver disease.
• CYP2E1 is stabilised by the presence of alcohol, so degradation is decreased and enzyme activity increased.


Aldehyde Dehydrogenase

• Several forms in humans: ALDH2 is the most important.
• Mutations in ALDH2 can result in a decreased tolerance: Mutant forms ALDH2 *1/*2 and ALDH2 *2/*2 can lead to facial flushing after a single glass of beer.
• There is wide inter-ethnic variability in the expression of ADH2 and ALDH2 enzymes. Some races are very alcohol intolerant.
• Japanese have a high incidence of ADH2 *2/*2 and ALDH2 *2*2, which results in a lack of tolerance
–Alcoholism and alcoholic liver disease in Japan is associated with ADH2 *1/*1 and ALDH2 *1/*1.


Asthma

• Many Japanese patients with asthma experience episodes or exacerbation of asthma after alcohol consumption.
• This phenomenon is not seen in Caucasians and is specific to Asians.
• This has been thought to be attributable to a difference in alcohol metabolism, in particular the metabolism of acetaldehyde, between Asians and Caucasians.

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Old 05-08-2005, 10:11 AM   #2
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Type C: Alcohol-Induced Liver Injury

• The prevalence of liver cirrhosis in the population correlates well with per capita consumption of ethanol, regardless of the type of beverage consumed.
• The risk of developing cirrhosis increases with the total amount of ethanol consumed over a lifetime.
• Patients with alcoholic liver disease die by 2 main causes:
• Haemodynamic Problems
• Liver Failure

Haemodynamic Problems

• An increase in interhepatic pressure due to inflammation and fibrosis caused by cirrhosis results in an increased pressure in the artery supplying the liver
• Blood flow diverts through collateral pathways which normally return the portal blood to the systemic circulation, thereby bypassing the liver.
• There is a lack of clearance of toxins from the body, particularly endotoxins from the gut flora.
• Collaterals have a tendency to rupture as they have thin walls, so that the patient can rupture one from coughing and bleed to death into his oesophagus or abdominal cavity.

Liver Failure

• The liver is unable to detoxify a number of noxious substances, some of which can affect brain function leading to hepatic encephalopathy. This is swelling of the brain from toxic insult
• There is a progressive loss of cognitive function this leads to alcoholic dementia and eventually to coma and death. This is a common cause of dementia.
• There is a decrease in the levels of, e.g. serum albumin and prothrombin, which are synthesized in the liver, resulting in decreased transport of bilirubin, and hence jaundice, and increased clotting time

Liver Failure and TNFa

• TNFa levels increase, resulting in increased levels of IL-1 and IL-6. This is an inflammatory response which leads to muscle atrophy; hypermetabolism; fever; anorexia; choleostasis (a form of liver disease).

• Inhibition of TNFa function by administration of anti-TNFa antibodies can block ethanol-induced hepatotoxicity, as well as CCl4- paracetamol- and endotoxin-induced liver damage


Type D: Alcohol and Genotoxicity

• Alcohol is a major risk factor for aerodigestive cancers, i.e. mouth, oesophagus, larynx and liver.
• There is no convincing evidence that ethanol can initiate DNA damage, but it may act as a promoter of DNA damage, possibly through free radical formation.
• The effects of alcohol in cancers of the larynx mouth and oesophagus may be due to modulation of other carcinogens such as nitrosamines found in tobacco smoke. This means that alcohol can make tobacco smoke more carcingenic than it already is.

Alcohol and Cancer

• Liver cancer or hepatocellular carcinoma (HCC) is one of the most common cancers in the world.
• The majority of people who develop HCC have cirrhosis, thus cirrhosis can also be considered a pre-cancerous state.
• Alcohol may also aid cancer development with known human carcinogenic influences such as hepatitis B & C.
• The possible small cancer risk faced by moderate drinkers may be more than offset by a decrease in the risk of cardiovascular death.

Type E: Foetal Alcohol Syndrome

• Children are characterised by small birth weight, microcephaly (small heads), cleft palate, reduction in the width of the palpebral tissues and maxillary hypoplasia.
• There are also cardiac anomalies in some children. All children have some form of developmental delay.

• As many as 30% of children from alcoholic mothers may have FAS.
• Mothers taking > 2 oz of alcohol a day are at risk.

• In a large prospective study, 1 or 2 drinks/day were associated with a substantially increased risk of producing a growth-retarded infant.
• Moderate drinking is associated with an increased risk of spontaneous abortion in 1st or 2nd trimester.
• The human syndrome may not be due to ethanol: poor protein intake; pyridoxine or other vitamin B deficiency; alcohol contaminants (e.g. Pb) may be important.
• Acetaldehyde can cause the same syndrome in experimental animals.
• There may be a genetic deficiency in mitochondrial aldehyde dehydrogenase

Type F: Ethanol and other drugs

Pharmacodynamic interactions:

–i) Addition or synergy: These include hypnotics, opioids, physchotropic drugs such as cannabis, sedative H antagonists and anticonvulsants. Alcohol will increase the effects of other sedatives, making, accident, or overdose more likely.
–ii) Antagonism: E.g. Poor control of diabetes due to the hypoglycaemic effect of alcohol. Alcohol effects most hormones including insulin.

Pharmacokinetic interactions

–i) Inhibition: Acute, high doses of ethanol will inhibit any other drug metabolized by CYP2E1, and increase the blood concentration and possible toxicity of that drug.
–ii) Induction: Chronic administration induces the overexpression of the enzyme CYP2E1. This may decrease the blood concentrations of other other drugs metabolised by this enzyme and decrease their effectiveness.
–Iii) Diuresis: Ethanol is a diuretic. This may have the effect of dehydrating the body and also enhancing the elimination of other drugs or compounds in the blood.

Ethanol and Paracetamol

• paracetamol (acetominophen) undergoes bioactivation catalyzed by CYP2E1. Chronic alcoholics may be more susceptible to liver damage due to “normal” therapeutic doses of paracetamol
–this is based on anecdotal evidence.
• metabolism of ethanol to acetaldehyde can deplete liver antioxidant stores and make the liver more susceptible to toxic insult by other drugs/ chemicals.
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Old 05-08-2005, 10:14 AM   #3
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Images CAUTION: MEDICAL IMAGES!

End Stage Liver Cirrhosis

Another Example of Liver Cirrhosis

Advanced cirrhosis with jaundice and ascites

Chart Showing Main features of Fetal Alcohol Syndrome

Baby with FAS

Gynecomastia from impaired liver unable to metabolise estrogens

One of the possible adverse effects of ethanol toxicity


Links

The National Institute On Alcohol Abuse And Alcoholism

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is a part of the National Institutes of Health (NIH), a component of the U.S. Department of Health and Human Services


Alcoholics Anonymous

Alcoholics Anonymousฎ is a fellowship of men and women who share their experience, strength and hope with each other that they may solve their common problem and help others to recover from alcoholism.


Alcohol Screening

provides online self-assessment tools and health-based information to help
individuals identify risky drinking patterns or current alcohol problems


Alcohol & Alcoholism

Alcohol and Alcoholism publishes papers on biomedical, psychological and sociological aspects of alcoholism and alcohol research


National Organisation On Foetal Alcohol Syndrome

Protecting children and families by fighting the leading known cause of mental retardation and birth defects.


New Scientist - Alcohol: The Inside Story

Everything you ever wanted to know about alcohol but were too drunk to ask.


Alcohol & Teen Drinking

Alcohol abuse and alcohol dependence are not only adult problems - they also affect a significant number of adolescents and young adults between the ages of 12 and 20


Center of Alcohol Studies

The Center of Alcohol Studies (CAS) is a multidisciplinary institute dedicated to acquisition and dissemination of knowledge on psychoactive substance use and related phenomena with primary emphasis on alcohol use and consequences


Medline - Search jounal Articles Online

Search engine for the National Library of Medicine journal database. Look up medical articles


Heres a load of alcohol related statistics.

Here is an article on alcohol by Par Deus

Here is the second part to that article by Par Deus




This thread doesnt even begin to touch the huge effect alcohol has on a social level. The huge cost to healthcare, social and family dysfunction, the domestic violence, the assaults, murders, rapes, car crashes, accidents, arguements, ...........Thats another story altogether. There is plenty of information on these factors also.


I hope this has helped some people understand that alcohol is bad for you in large amounts or for extended periods. Infrequent drinking in moderation is OK, and even provides some health benefits. Drinking will affect your bodybuilding efforts depnding on how much you drink. Now you see how many ways alcohol is damaging, the question " will alcohol affect my gains?" can be answered.

When they say drink in moderation, they mean it

Post questions/comments here and I will do my best to help.
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Old 05-08-2005, 10:18 AM   #4
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Here's some links to the abstracts of scientific studies on the effects of ethanol in humans.

Alcohol ingestion decreases both diurnal and nocturnal secretion of leptin in healthy individuals.

Testosterone increases in men after a low dose of alcohol.

Alcoholic liver disease

Using an animal model to assess the long-term behavioral and biological consequences of adolescent abuse and exposure to alcohol.

Effects of acute alcohol intoxication on pituitary-gonadal axis hormones, pituitary-adrenal axis hormones, beta-endorphin and prolactin in human adolescents of both sexes.

Negative consequences of intercollegiate athlete drinking: the role of drinking motives

Effects of alcohol on food and energy intake in human subjects: evidence for passive and active over-consumption of energy.

Alcohol misuse among college athletes: self-medication for psychiatric symptoms?

Alcohol and energy drink--can combined consumption of both beverages modify automobile driving fitness?

Alcohol and its effects on sprint and middle distance running.

Alcohol-attributable deaths and years of potential life lost--United States, 2001

Alcohol-induced neurodegeneration: when, where and why?

Alcohol and cancer.



Here are some links to some databases concerning alcohol, nutrition and health

Alcohol Research & Health is a publication providing coverage and analysis of health care issues. Here is the database of their articles

Here is a large database regarding the effects of alcohol on the stomach

Here is a database of nutrition information for over 100 brands of Beer.

Here is a database of nutrition information for 20 different types of wine

Here is a database of nutrition information for 20 types of common liquor
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Old 05-09-2005, 01:38 AM   #5
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Nice. good thing I'll never drink! too many risks involved... Well maybe when I'm older, I'll do it on special occassions.

Great post!
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Old 05-21-2005, 05:52 AM   #6
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AWESOME awesome post
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Old 05-21-2005, 05:32 PM   #7
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when i was younger i drank like a fool, now when i drink which isnt very often its very moderated with the few exceptions of once or twice a year. but when im cycling i try to stay as far away as possible. and if i do have a drink while on its 1 or 2 with lots of water in between follwed by tamoxifen before bed.
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Old 07-02-2006, 04:50 PM   #8
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Around 2 years ago, I drank like a manic. I loved alcho. But, I've cut down from it.
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Old 07-03-2006, 08:26 AM   #9
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I used to drink like a idiot and hit the nightclubs and just get smashed, I can't beleive all the $ I wasted along the way also..lol jezzz to be young and dumb!.. It also did'nt help that my Opa died from alcohol abuse, it kind of runs in the family 'alcoholism', I now only drink on special occassion like Xmas and Newyears where I will have a nice meal with friends/family and maybe 2-3 glasses of wine and thats about it! heavy alcohol use is a dead end road! trust me!
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Old 07-03-2006, 03:35 PM   #10
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Good post, very thorough. I used to get smashed every weekend, but now I probably only drink once a month and never more than 1 drink/hour which is the rate at which your liver can clear the alcohol from your system. I also drink a bottle of water for each drink. I also only drink light beer... never mixed drinks.

Actually, when bulking, it is not a bad idea to have 1-2 beers or a glass of wine every couple of days. I wouldn't recommend it when cutting because of the empty calories, but the test boost from a low dose can be used to a bb'ers advantage.
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Old 07-04-2006, 06:56 AM   #11
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I read this after I have already finished two beers... great...
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Old 07-12-2006, 02:16 PM   #12
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Awesome post(s)!
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Old 07-12-2006, 02:18 PM   #13
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