The dose response relationships between alcohol and chronic

The dose–response relationships between alcohol and chronic disease typically vary by sex, with women experiencing higher risks at comparatively lower levels of intake (Shield et al., 2013) due to different grams to moles calculator and metabolism of alcohol (Mumenthaler et al., 1999). New studies will also allow for determining a threshold for alcohol consumption associated with the risk of pancreatitis.
Methods
Results
Discussion There were differential dose–response relationships between men and women with respect to alcohol consumption, as well as type of pancreatitis. The dose–response relationship between the level of alcohol consumption and CP was linear, and monotonically increasing with no identifiable threshold. On the contrary, the relation between average alcohol consumption and AP was non-linear (J-shaped) among women, and monotonically increasing among men. High alcohol consumption was consistently associated with an increased risk for pancreatitis at the alcohol consumption level above 40g/day (higher than previously reported) (Irving et al., 2009). There are two plausible explanations for a J-shaped relationship between alcohol consumption and AP as it appeared in women. First, the beneficial effect may be explained by contamination of the reference group that included ex-drinkers who quit drinking due to health problems and were at increased risk of developing pancreatitis. Two studies reported on the risk of pancreatitis in former drinkers (Lin et al., 2001; Morton et al., 2004). In comparison to lifetime abstainers, former drinkers showed an elevated risk for any pancreatitis (RR=2.20, 95%CI: 1.45–3.34), and there was no beneficial association (RR=1.01, 95%CI: 0.82–1.24) of moderate alcohol consumption (<40g/day). There were not enough data to stratify this relationship by pancreatitis diagnosis or sex. The second explanation is related to the distribution of etiological factors for different types of pancreatitis in men and women, and accordingly, the pathogenesis and natural history of the disease. Specifically, alcohol consumption is the predominant cause of CP in Western countries, with the proportion of cases of alcoholic pancreatitis reaching 80% and sometimes even 95% (Braganza et al., 2011; Pezzilli, 2009). The pathophysiology of CP is based on damage to acinar cells of the pancreas (mediated by sustained elevation of the cytosolic Ca levels) (Gerasimenko et al., 2014), which start releasing synthesized pancreatic enzymes into interstitium (pancreastasis), thus triggering inflammation (Braganza et al., 2011). While a number of agents and factors can trigger pancreastasis, it was indicated that alcohol metabolism plays a significant role in it as it is associated with the production of reactive oxygen species (ROS) via acetaldehyde pathway (Gonzalez, 2005) and fatty acid ethyl esters (FAEE) via non-oxidative route (Pandol and Raraty, 2007; Witt et al., 2007) which in turn cause injury to acinar cells and activate stellate cells (Braganza et al., 2011). Since the quantities of alcohol metabolites and their impact directly correlate with the amounts of alcohol consumed, the relationship between alcohol consumption level and the risk of CP is monotonic. The interaction between alcohol and other etiological factors in AP is quite similar to CP from pathobiological standpoint — a cascade of intra- and extracellular reactions leads to FAEE-induced increase of the Ca release that in turn leads to necrosis of pancreatic acinar cells (Gerasimenko et al., 2014). At the same time a more complex interplay between variety of etiological factors is observed — alcohol is the second leading cause of AP after gallstones and biliary problems leading to them (Lankisch et al., 2015). It was shown that low alcohol consumption is reducing the risk of symptomatic choledocholithiasis, and thus lowering the risk of biliary AP (Leitzmann et al., 1999).