* 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.
• Alcohol may protect against heart disease by raising levels of high-density lipoprotein, the "good" form of cholesterol.Originally Posted by New Scientist magazine, 14 October 2000
–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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Thread: The Toxicity of Ethanol
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11-09-2004, 03:52 AM #1
How Alcohol is Toxic to the Body
Last edited by Diab0lic; 11-09-2004 at 04:02 AM.
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11-09-2004, 03:54 AM #2
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 oeso****us 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, oeso****us, 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 oeso****us 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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11-09-2004, 03:55 AM #3
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 Anonymous® 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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11-09-2004, 12:45 PM #4
Bump for the evening crew
Heres a load of alcohol related statistics.Last edited by Diab0lic; 11-09-2004 at 12:48 PM.
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11-09-2004, 05:32 PM #5
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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11-10-2004, 01:52 AM #6
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.
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11-10-2004, 11:07 AM #7
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11-10-2004, 02:50 PM #8
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11-16-2004, 11:12 PM #9
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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11-23-2004, 02:35 AM #10
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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05-28-2007, 08:47 PM #11
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05-29-2007, 12:32 AM #12
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05-29-2007, 12:40 AM #13
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05-29-2007, 06:38 PM #14
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05-29-2007, 07:10 PM #15
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05-29-2007, 07:35 PM #16
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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05-29-2007, 07:47 PM #17
- Join Date: Aug 2006
- Location: Pennsylvania, United States
- Posts: 13,540
- Rep Power: 76164
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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12-22-2007, 12:02 PM #18
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01-18-2008, 12:58 PM #19
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03-28-2008, 07:47 AM #20
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