U shaped curve of alcohol consumption

Cancer, Diabetes, Osteoporosis etc.
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Kasper
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U shaped curve of alcohol consumption

Post by Kasper »

From: http://www.bmj.com/content/325/7357/191

Non-drinkers and heavy drinkers have higher all cause mortality rates than light drinkers—the U shaped curve. The precise shape and location of the U are likely to depend on age and sex, but this has not been quantified.

Models for ischaemic heart disease from Corrao and others (used in main analysis) and derived from English and others
Image

This U shape is not true for all diseases:
Image

Risk of all cause mortality (relative to non-drinkers) by level of alcohol consumption in womenand men
Image

Dr. Monte tries to give an explanation for this U shaped curve:

"Hypothesis:
Formaldehyde produced from dietary and environmental methanol metabolized in
situ at the non-hepatic sites of class I alcohol dehydrogenase (ADH I) may play a
role in many diseases of civilization (DOC). Ethanol may in turn act as a
competitive inhibitor of methanol’s conversion to formaldehyde by ADH I, as
reflected in the U-shaped curve of alcohol consumption.
....
A compelling explanation of the dose region of adverse effects of the Ushaped
curve with high ethanol consumption, which shows increased risk of these
same diseases, could be the mechanism by which humans habituate to high
consumption of ethanol. The induction of the P450 hepatic microsomal ethanoloxidizing
system[#175] results in a considerably higher clearance rate of ethanol
from the bloodstream for an extended period of time, thus accounting for more
consumption leading to statistically less time of protection. Small amounts of
supplemental alcohol not sufficient to induce P450 might be expected to prolong
the residence time and avoid gaps in the protection afforded by ethanol in
preventing methanol placed formaldehyde. It appears that the average person,
whether or not an imbiber, may typically have endogenous ethanol in the
blood[#174] produced by gut fermentation.[#363] This ethanol must pass through the
liver via the hepatic portal vein coincidently with dietary methanol absorbed from
the gut contents. The liver has the highest concentration of ADH I in the body.
Even traces of ethanol in the blood, however, would seem to indicate the absence
of available sites remaining for the oxidation of the much less competitive
methanol, allowing most dietary methanol to pass freely into the general
circulation.
What follows is a biochemical game of musical chairs as methanol travels
round and round the circulation waiting for the ethanol levels to reach zero and the
music to stop. The closest ADH I free to service the methanol will convert it to
formaldehyde. If this happens in the liver, where there are ample supplies of
aldehyde dehydrogenase, metabolism to carbon dioxide will proceed safely. In
mammary epithelium, however, where human class I alcohol dehydrogenase is
highly expressed[#358] but active aldehyde dehydrogenase[#216] is scarce, methanol
placed formaldehyde could become a problem. Formaldehyde is a class I
carcinogen[#11] and mutagen[#449] with methanol providing its only easy avenue into
this tissue. In the vasculature of the brain[#218] and other ADH I positive organs, the
consequences may be similarly troublesome. The obvious way to prevent
formaldehyde from damaging this sensitive tissue is to keep the music playing, a
solution dependent on our ability to answer the following questions: Just how
much ethanol is essential in this seemingly inscrutable U-shaped curve? What
measures should we take to combat this chemical Trojan horse, thereby reducing
the methanol contamination in the diet of civilization and making it more like the
diet of our ancient ancestors? Both research areas present intriguing inquiries, but
as a food scientist, I would stress the relative ease and greater benefits of
investigating the latter.

One hypothesis for the difference between the sexes is that men have a higher activity of the enzyme ADH, as I mentioned earlier, which metabolizes methanol and converts it to formaldehyde. More formaldehyde circulating in your blood would naturally have more opportunity to cause greater damage.
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Oscar
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Re: U shaped curve of alcohol consumption

Post by Oscar »

It seems to me that the blood-thinning effect of alcohol plays a role in delaying fatal ischaemic heart disease incidents, before the amount consumed gets more problematic. That non-drinkers would have a higher risk only works with comparatively unhealthy diets.
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