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  1. #1
    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    Post How Alcohol is Toxic to the Body

    * 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. The reference would be Tingle, M. Pharmcol305 - Introduction To Toxicology Lecture Notes, Department of Pharmacology and Clinical Pharmacology, The University of Auckland, 2003. Most of it is my own words and is 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


    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.

    Originally Posted by New Scientist magazine, 14 October 2000
    Some drinkers have more to celebrate than others

    • In a study of 396 people after a mild heart attack and 770 healthy controls to see which form of ADH3 they had, the researchers also looked at their alcohol intake.
    • Men with 2 copies of ADH3*2 who drank daily were the most protected from heart attack:
    –They had an ~ 86% reduction in risk, vs men with 2 copies of ADH3*1 who had less than one drink a week.
    • An independent study of 325 women confirmed the finding.
    • 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.
    Last edited by Diab0lic; 11-09-2004 at 04:02 AM.
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  2. #2
    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    Post

    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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  3. #3
    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    Images CAUTION: MEDICAL IMAGES!

    End Stage Liver Cirrhosis

    Standard 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 scientific studies on anything. Tutorial available online.


    Bodybuilding.com Forum Search: Alcohol

    Click to search for threads with "alcohol" in the title. Threads sorted from most recent.




    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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  4. #4
    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    Talking

    Last edited by Diab0lic; 11-09-2004 at 12:48 PM.
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    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    Heres A Link to Alcohol Related Articles on Bodybuilding.com


    * The url in the links section above to a forum search of alcohol related topics doesnt seem to be working anymore? Try HERE instead.
    Last edited by Diab0lic; 11-09-2004 at 05:37 PM.
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    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    Waiting for judgment day CanadianClub's Avatar
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    Smile

    nice
    "Opportunities multiply as they are seized" - Sun Tzu
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    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    SKINOVERSTEEL badboyslayer's Avatar
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    Thumbs up

    Brilliant thread!

    I'll be sure to use it as a great reference point for all of the alcohol and BB questions posted here
    "The individual has always had to struggle to keep from being overwhelmed by the tribe. He will be lonely often and sometimes frightened. But no price is too high to pay for the privilege of owning yourself" - Nietzsche
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    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    Exclamation

    Bump from the grave!

    read it drunk bastards!
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    Full of Pain Secret_Hope's Avatar
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    To the op: REPPED!! Awesome knowledge. Some of the links don't work though.
    Everybody's parents are crazy but it's scary when you can prove it.
    REPS:
    NEGS:
    You can trust me with the shipping...
    Good Traderz Thread post #1231, 1463, 2392, 2949
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    applesauce the destroyer sanpedro's Avatar
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    good times

    ethanol sucks
    .(>^_^).> <3

    |||----.(^_^).----|||
    cutting
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    swimming
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  14. #14
    ♞♞♞♞♞♞♞ Diab0lic's Avatar
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    Originally Posted by Secret_Hope View Post
    To the op: REPPED!! Awesome knowledge. Some of the links don't work though.
    Yeah, I originally posted this 3 years ago....
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  15. #15
    wow strong MCAT tweaked17's Avatar
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    tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000) tweaked17 has a reputation beyond repute. Second best rank possible! (+100000)
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    VERY well put together, even if it was three years ago!
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    Disclaimer: The above can at best be considered an opinion or an offering of advice, and should be treated as such.
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  16. #16
    Registered User skinny buckeye's Avatar
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    great job! that took some major effort...


    course you forgot one very important link...

    http://www.theonion.com/content/node/29565
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  17. #17
    SEAman First Class skinnyboipgh's Avatar
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    Smile Bookmarked!!

    A definitive treatment of the subject, which confirms my long-held belief there's nothing more counter-productive 2 BB objectives than alcohol.

    Should be required reading on here, esp. 4 the guys who ask if getting ****-faced once a week will hurt their progress!
    Best Regards,

    Ed

    To the optimist, the glass is half full . . .
    To the pessimist, the glass is half empty . . .
    To the engineer, the glass is twice as big as it needs to be.

    Journal: http://forum.bodybuilding.com/showthread.php?p=336405441#post336405441
    Helpful or encouraging posters in my journal get repped.
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  18. #18
    ~Mad Man of the Sea~ MacGyverDel's Avatar
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    Thumbs up

    Wow! Awesome thread DiabOlic.

    Definately book marked.

    Perfect time for a bump also.
    *More than just Muscle*

    ~~~ Just Do It! ~~~

    *** Tenton Made FTW ***
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  19. #19
    just skip it |ceman's Avatar
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    Thumbs up

    Good stuff Diab0lic!


    And....bump


    And...sticky this!
    Xtreme Formulations

    http://lifehacker.com/5811255/why-you-cant-win-an-argument-on-the-internet

    I worked out with a dumbbell yesterday. I feel *vigorous*. - http://forum.bodybuilding.com/showthread.php?t=153326891
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  20. #20
    ~Mad Man of the Sea~ MacGyverDel's Avatar
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    Cool Bump!

    Originally Posted by Diab0lic View Post
    Heres A Link to Alcohol Related Articles on Bodybuilding.com


    * The url in the links section above to a forum search of alcohol related topics doesnt seem to be working anymore? Try HERE instead.
    It's working fine now.
    *More than just Muscle*

    ~~~ Just Do It! ~~~

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