Possible Cytoprotective Effect of Alcohol

Ethanol is a poison.  But the difference between poison and
medicine sometimes is only a matter of dosage.



For decades, there have been studies that purport to show a small
benefit from regular consumption of small amounts of ethanol, with
obvious problems caused by excessive alcohol consumption.
 Physicians, however, are divided about what to do with this
information.  Do we recommend that people have one alcohol
beverage per day, or do we remain silent on the subject?



One reason to be reluctant to recommend moderate drinking, as opposed
to abstinence, is that it is very difficult to prove that such
recommendations would help anyone.  It is one thing to show an
association between moderate drinking and improved health; however,
that does not mean that teetotalers who start drinking moderately will
experience any benefit at all, much less have the population experience
more benefit than harm.



There is another reason to be hesitant about making such a
recommendation.  That is, we do not know how the intervention
would work, on a molecular level.  Although it is not strictly
necessary that we know the mechanism of action, it would help us feel
more comfortable that the recommendation makes sense.  



So now we have evidence that gives an inkling of what the mechanism
might be, with regard to protection against dementia and heart disease:

href="http://www3.interscience.wiley.com/journal/121529858/abstract">Alcohol
in Moderation, Cardioprotection, and Neuroprotection: Epidemiological
Considerations and Mechanistic Studies

Collins M, et al "Alcohol in moderation, cardioprotection, and
neuroprotection: epidemiological considerations and mechanistic
studies" Alcoholism: Clinical and Experimental Research
2008; DOI: 10.1111/j.1530-0277.2008.00828.x

In contrast to many years of important research and
clinical attention to the pathological effects of alcohol (ethanol)
abuse, the past several decades have seen the publication of a number
of peer-reviewed studies indicating the beneficial effects of
light-moderate, nonbinge consumption of varied alcoholic beverages, as
well as experimental demonstrations that moderate alcohol exposure can
initiate typically cytoprotective mechanisms. A considerable body of
epidemiology associates moderate alcohol consumption with significantly
reduced risks of coronary heart disease and, albeit currently a less
robust relationship, cerebrovascular (ischemic) stroke. Experimental
studies with experimental rodent models and cultures (cardiac myocytes,
endothelial cells) indicate that moderate alcohol exposure can promote
anti-inflammatory processes involving adenosine receptors, protein
kinase C (PKC), nitric oxide synthase, heat shock proteins, and others
which could underlie cardioprotection. Also, brain functional
comparisons between older moderate alcohol consumers and nondrinkers
have received more recent epidemiological study. In over half of nearly
45 reports since the early 1990s, significantly reduced risks of
cognitive loss or dementia in moderate, nonbinge consumers of alcohol
(wine, beer, liquor) have been observed, whereas increased risk has
been seen only in a few studies. Physiological explanations for the
apparent CNS benefits of moderate consumption have invoked alcohol's
cardiovascular and/or hematological effects, but there is also
experimental evidence that moderate alcohol levels can exert direct
"neuroprotective" actions—pertinent are several studies in
vivo and rat brain organotypic cultures, in which antecedent or
preconditioning exposure to moderate alcohol neuroprotects against
ischemia, endotoxin, β-amyloid, a toxic protein intimately
associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1
envelope protein. The alcohol-dependent neuroprotected state
appears linked to activation of signal transduction processes
potentially involving reactive oxygen species, several key protein
kinases, and increased heat shock proteins. Thus to a
certain extent, moderate alcohol exposure appears to trigger analogous
mild stress-associated, anti-inflammatory mechanisms in the heart,
vasculature, and brain that tend to promote cellular survival pathways.
[emphasis added]

Note that the paper does not present original research findings.
 Rather, the authors describe the results of a literature
review and roundtable discussion.  



It is important to recognize several caveats in the interpretation of
this paper.  For one, much of the research they reviewed was
done in animals other than humans.  Also, there are many
different kinds of alcohol beverages.  Some but not all
contain biologically active components, such as resveratrol, that
introduce confounding variables.  



Importantly, the authors note that not all studies found benefit.
 More than half of the epidemiological studies did suggest
benefit, but a few indicated potential harm.  



All the work regarding the molecular mechanisms is interesting.
 Perhaps some day will will learn enough to be able to produce
a pharmaceutical product that provides just as much benefit as a glass
of wine per day, at a cost that is merely six times greater than the
cost of the natural product.  And perhaps it will get rid of
the known risks, instead presenting us with the potential for new,
unknown risks.