* 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.
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.
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 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.
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.
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.
Thread: The Toxicity of Ethanol