Alcohol appears to be hormetic:
The review of Pohorecky (1977) provides strong psychological, behavioral and biochemical evidence for alcohol (ethanol) affecting the experimental behavior of animals and humans in a biphasic dose–dependent manner, with low-doses being excitory and high-doses depressant. For non-human mammalian biological end points (including, amongst others, the liver, kidney, heart, spleen, endocrine, embryonic development and birth weight), Calabrese and Baldwin’s (2003c) assessment of the toxicological and pharmacological literature demonstrated ethanol-induced biphasic dose responses over a wide range. In most cases, the low-dose hormetic responses were judged to be statistically significant and reliable. They observed striking similarities across studies in both hormetic dose-ranges and hormetic dose–response magnitudes, with the maximum hormetic response approaching two-fold but was usually 25–40% greater than the control value. Furthermore, the maximum hormetic response was generally within a factor of 2–4 of the estimated NOAEL. They argued against a common explanatory mechanism, and for a diverse plethora of underlying mechanisms. They also stated that regardless of actual response mechanisms, the similarity of dose–response characteristics likely reflected an important overall regulatory strategy built into the framework of a homeostatic control system. Calabrese and Baldwin (2003c) further noted that these collective findings closely resembled the biphasic hormetic responses to a wide range of toxic chemical agents that they had previously reported (Calabrese and Baldwin, 1997).
While there are a considerable number of published investigations suggesting that chronic alcoholics have an increased susceptibility to infectious diseases (in particular pneumonia), Hallengren and Forsgren (1978) have presented evidence that at low to moderate blood alcohol concentrations there is an increased adherence, phagocytosis and chemotaxis of human polypmorphonuclear leucocytes. The magnitude of the detected response is consistent with that seen for hormetic responses, with the hormetic concentration range being about four-fold. It would appear that these results have important ramifications for biomedical researchers and clinicians.
Human health benefits of regular light-to-moderate alcohol consumption vis-à-vis abstinence include decreased risks of dementia, diabetes, osteoporosis, and cardiovascular disease and death (Standridge et al., 2004). Both case–control and cohort epidemiological studies have consistently shown that light-to-moderate drinkers are at lower risk of cardiovascular disease and death than nondrinkers, although heavier alcohol consumption can negatively affect the neurologic, gastrointestinal, hematologic, immune, psychiatric and musculoskeletal organ systems. The hormetic biphasic effects of alcohol consumption on total human mortality is a well studied and documented phenomenon with the basic J-shape of the dose–response curve confirmed in the vast majority of studies and being remarkably stable and independent of assessment measure (Gaziano and Buring, 1998; Rehm, 2000). For example, Gronbaek (2004) cited 19 separate epidemiological studies conducted over the last three decades that describe the impact of alcohol on total mortality as J-shaped, with a beneficial effect of regular light-to-moderate intake (10–40 g per day, or one to three alcoholic beverages), and a detrimental effect of both lower and higher intake. These studies have been reported by a large number of different research teams, with the effects observed in populations of different genders, races and nationalities. The total mortality risk reduction at light-to-moderate levels is likely due to lower risk of fatal cardiovascular disease without dramatic increases in other causes of death. Rehm (2000) notes that the J-shape results mainly from the beneficial effect of moderate alcohol consumption on ischemic cardiovascular conditions coupled with the detrimental effects of drinking on other health conditions. While the risk curves of detrimental effects may vary between linear, exponential or threshold effects, they always seem to be monotonic: the more consumption, the higher the disease-specific mortality risk. Rehm further notes that this means that the J-shaped curve should not be expected and cannot be found in populations with no or few coronary heart disease (CHD) deaths, for example, in some developing countries or in younger age groups.
Epidemiological studies indicate that all types of alcoholic beverages are associated with increased cancer risk at higher drinking levels, suggesting that ethanol itself causes the detrimental effect rather than any particular type of beverage. A great deal of recent research has focused on the possible benefits of specific alcoholic beverages. Some have postulated that wine’s polyphenolic antioxidants including resveratrol and proanthocyanidin reduce risk of cardiovascular disease. Resveratrol has been shown to exert its effects on cells by inducing a stress response mediated by the sirtuin protein family (Tissenbaum and Guarente, 2001; Howitz et al., 2003). At this point in time the totality of evidence suggests that the major beneficial component of alcoholic beverages on cardiovascular mortality is in fact ethanol per se rather than some other component (Rimm et al., 1996). Gronbaek (2004) states that it is likely that any apparent additional beneficial effect of wine on health in addition to the effect of ethanol itself is a consequence of confounding.
Several plausible mechanisms for the cardioprotective effect of light-to-moderate alcohol intake have been suggested (Korthuis, 2004; Standridge et al., 2004). One is its role in increasing plasma HDL cholesterol concentrations and in reducing low-density lipoprotein (LDL) cholesterol concentrations. Such changes have been suggested to account for approximately half of alcohol’s protective effect against CHD. (Commonly referred to as the good cholesterol, HDL binds with cholesterol and brings it back to the liver for elimination or reprocessing, thereby lowering total cholesterol levels in body tissues and its build-up on arterial walls, and in a sense reversing the atherosclerotic process.) Free radical scavenging and inhibition of LDL oxidation by free radicals have also been proposed as mechanisms; as well as reduction/inhibition of platelet adhesion and aggregation, clotting factor concentrations, vascular smooth muscle cell proliferation and migration, and inflammation involving monocytes and T lymphocytes. Of particular interest in light of previous reference to hsps heat shock proteins are animal studies showing that oxidative stress from low dose alcohol consumption induces several heat shock and antioxidant proteins, which may serve as cardioprotective proteins in hearts subsequently exposed to ischemia/reperfusion (I/R) injury (Sato et al., 2004). Also of interest is the surprising finding that alcoholics had significantly less DNA damage than controls and demonstrated higher capacity for DNA repair, possibly because excessive ethanol rather than damaging DNA (it is not genotoxic) induces antioxidant and repair enzymes (Pool-Zobel et al., 2004).
(Hat tip to Mangan.)