Alcohol in moderation, cardioprotection, and neuroprotection: epidemiological considerations and mechanistic studies.
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, beta-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.
Collins
Michael A
MA
Department of Cell Biology, Neurobiology & Anatomy, Loyola University Chicago Stritch School of Medicine, 2160 S. 1st Avenue, Maywood, IL 60153, USA. mcollin@lumc.edu
Neafsey
Edward J
EJ
Mukamal
Kenneth J
KJ
Gray
Mary O
MO
Parks
Dale A
DA
Das
Dipak K
DK
Korthuis
Ronald J
RJ
D000428:Alcohol Drinking / Q000453:epidemiology* / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002316:Cardiotonic Agents; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003704:Dementia / Q000453:epidemiology / Q000517:prevention & control; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D018696:Neuroprotective Agents; D009569:Nitric Oxide / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
D000975:Antioxidants; D002316:Cardiotonic Agents; D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D013267:Stilbenes; D009569:Nitric Oxide; D000431:Ethanol; D011493:Protein Kinase C; D000077185:Resveratrol