Azodi OS, Orsini N, Andrén-Sandberg Å, Wolk A. Effect of type of alcoholic beverage in causing acute pancreatitis. Brit J Surgery 2011;DOI: 10.1002/bjs.7632.
Background: The effect of different alcoholic beverages and drinking behaviour on the risk of acute pancreatitis has rarely been studied. The aim of this study was to investigate the effect of different types of alcoholic beverage in causing acute pancreatitis.
Methods: A follow-up study was conducted, using the Swedish Mammography Cohort and Cohort of Swedish Men, to study the association between consumption of spirits, wine and beer and the risk of acute pancreatitis. No patient with a history of chronic pancreatitis was included and those who developed pancreatic cancer during follow-up were excluded. Multivariable Cox proportional hazards models were used to estimate rate ratios.
Results: In total, 84,601 individuals, aged 46-84 years, were followed for a median of 10 years, of whom 513 developed acute pancreatitis. There was a dose–response association between the amount of spirits consumed on a single occasion and the risk of acute pancreatitis. After multivariable adjustments, there was a 52 per cent (risk ratio 1·52, 95 per cent confidence interval 1·12 to 2·06) increased risk of acute pancreatitis for every increment of five standard drinks of spirits consumed on a single occasion. The association weakened slightly when those with gallstone-related pancreatitis were excluded. There was no association between consumption of wine or beer, frequency of alcoholic beverage consumption including spirits, or average total monthly consumption of alcohol (ethanol) and the risk of acute pancreatitis.
Conclusion: The risk of acute pancreatitis was associated with the amount of spirits consumed on a single occasion but not with wine or beer consumption.
Background Alcohol consumption has often been found to be a risk factor for acute pancreatitis1 and, as the authors point out, a number of biologic mechanisms for such an association have been suggested.2-5 Overall the risk is rather low, as only 1-3% of heavy drinkers develop acute pancreatitis after 10-20 years of follow up.6,7 This study evaluated beverage-specific risk among subjects enrolled in a prospectively collected database that included information on the amount of alcohol consumed on a single occasion, frequency of drinking, total alcohol intake, and a number of potential confounders.
Specific comments on the paper: This study is based on a very large population-based cohort of men and women in Sweden, 513 of whom developed acute pancreatitis. Data collected included details on education and, for most subjects, data on body weight, smoking, diet, history of diabetes, and history of gall-bladder disease. Very complex and appropriate statistical analytic methods were used.
The investigators found no relation between the number of drinks at one time for wine or beer, but an increase in risk of acute pancreatitis with larger amounts of spirits consumed per drinking occasion. Overall, the average total amount of alcohol consumed, or the frequency of such consumption, did not relate to the risk of acute pancreatitis.
Spirits drinkers averaged greater amounts of alcohol and had less education than consumers of wine and beer, raising a question about potential confounding. For example, in the top tertile of each beverage, the average number of drinks per occasion was 5.0 for spirits, but only 2.7 for wine and 3.0 for beer; these data led several Forum reviewers to believe that the primary difference according to type of beverage may actually be the amount consumed per occasion.
One reviewer stated: “It is easier to consume five standard drinks of sprits more quickly than five standard drinks of beer or wine, if only because of volume effects. Ergo, the maximum blood alcohol levels for the five standard drink spirit drinkers may well have been higher than for beer and wine.” The reviewer added: “The authors search for esoteric explanations for higher risk from spirits may simply have been missing the fact that acute pancreatitis may be more likely with higher peak blood alcohol levels.”
On the other hand, in the analyses in this paper the higher risk for spirits drinkers was unchanged when adjustment was made for the total intake of alcohol, frequency of alcohol consumption, and other potential confounders. For example, the crude rate ratio for an increment of 5 standard drinks of spirits was 1.54, and in two multivariable adjustment models it was 1.52 and 1.59 (all statistically significant). This suggests that the higher risk for spirits drinkers could be real, and not due to residual confounding.
Potential biologic mechanisms for observed differences by type of beverage: The authors state that potential causes for this difference between the consumption of spirits and of other alcoholic beverages may be because spirits does not have the antioxidants present in the other types of beverage. The authors of the paper also state that in experimental studies, other constituents in spirits such as long-chain alcohols have been shown to be more potent than ethanol in inducing oxidative stress.
However, a Forum reviewer commented: “The suggested mechanism where the increased risk is generated by oxidative stress not being balanced by the antioxidants present in wine or beer seems to be too speculative. One must consider the effect of the concentration of alcohol in the drinks and its toxic effect as a lipid solvent (a physical effect different from a biochemical effect), as well as its metabolism through Cyt P450-producing oxidants. In general terms, this kind of ‘physical injury’ activates a biological response that, when exaggerated, may cause tissue damage. The ‘antioxidants’ present in wine and beer could help prevent this response to injury.” A further reason that spirits consumption may increase risk relates to diet, as it has been shown that spirits drinkers have lower intake of fruits and vegetables than do wine or beer drinkers. A “healthier” diet could provide further antioxidant activity and lower the risk of pancreatitis.
1. Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet 2008;371:143–152.
2. Palmieri VO, Grattagliano I, Palasciano G. Ethanol induces secretion of oxidized proteins by pancreatic acinar cells. Cell Biol Toxicol 2007;23:459–464.
3. Siech M, Zhou Z, Zhou S, Bair B, Alt A, Hamm S, et al. Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL). Am J Physiol Gastrointest Liver Physiol 2009;297:G1163–G1171.
4. Sutton R, Criddle D, Raraty MG, Tepikin A, Neoptolemos JP, Petersen OH. Signal transduction, calcium and acute pancreatitis. Pancreatology 2003;3:497–505.
5. Kubisch CH, Gukovsky I, Lugea A, Pandol SJ, Kuick R, Misek DE, et al. Long-term ethanol consumption alters pancreatic gene expression in rats: a possible connection to pancreatic injury. Pancreas 2006;33:68–76.
6. Kristiansen L, Gronbaek M, Becker U, Tolstrup JS. Risk of pancreatitis according to alcohol drinking habits: a population-based cohort study. Am J Epidemiol 2008;168:932–937.
7. Lankisch PG, Lowenfels AB, Maisonneuve P. What is the risk of alcoholic pancreatitis in heavy drinkers? Pancreas 2002;25:411–412.
A very well-done analysis from scientists in Sweden has related the type of alcoholic beverage, and the amount consumed per occasion, to the risk of acute pancreatitis. The study suggests that a greater number of drinks per occasion (“binge drinking”) of spirits increases the risk of acute pancreatitis, but no such relation was seen for the consumption of beer or wine. Forum reviewers suggested that a faster rate of drinking, with a greater rise in BAC, for spirits drinkers may be an important factor in the observed higher risk of pancreatitis; the increased risk may not necessarily be due to lower levels of antioxidants or to the presence of other toxic substances in spirits.
In any case, the average total alcohol consumption did not affect the risk of pancreatitis; instead, it was the number of drinks consumed per occasion (of spirits, in this study) that was associated with an increase in risk. Residual confounding by the pattern of drinking, diet, or by other lifestyle factors could still be operating, and it will require replication of these results in other studies to support the conclusions of the authors.
* * *
Contributions to this critique by the International Scientific Forum on Alcohol Research were made by the following members:
Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy.
Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia.
Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway.
Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark.
Ross McCormick PhD, MSC, MBChB, Associate Dean, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA.
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA.