Individual Differences in Blood Alcohol Concentrations after Moderate Drinking Are Mainly Regulated by Gastric Emptying Rate Together with Ethanol Distribution Volume

Abstract

Blood alcohol concentration (BAC) differs greatly among individuals, even when people of the same sex and age drink alcohol under the same drinking conditions. In this study, we investigated the main factors involved in the internal reg-ulation of individual differences in BAC, focusing on the alcohol dehydrogenase 1B (ADH1B) genotype, blood acetal-dehyde concentration (BAcH), amount of habitual alcohol consumption, pharmacokinetic parameters of BAC, distribution volume of ethanol (Vd), and gastric emptying rate (GER) under the same drinking conditions. Twenty healthy Japanese males aged between 40 and 59 years old and having the aldehyde dehydrogenase 2 (ALDH2) genotype of ALDH 2*1/*2 were recruited for this study. The subjects were given 0.32 g ethanol/kg body weight in the form of commercially available beer (5%, v/v). The results showed that BAC-max differed greatly among individuals with a more than two-fold variation. When the BAC-time curve was compared among ADH1B genotypes (ADH1B*1/*1, *1/*2, and *2/*2), there were no differences in BAC among the genotypes. Although BAcH, monthly alcohol consumption, elimination rate of blood ethanol (β value) and ethanol disappearance rate from the body (EDR) can affect BAC, all of them had no correlations with BAC-max. However, Vd (liter/kg), ΔPlasma glucose concentration (ΔPGC = PGC30 min ? PGC0 min) and the serum concentration of gastric inhibitory polypeptide (GIP) did correlate with BAC-max. Model 2 in multiple linear regression analysis showed the optimal model for Vd and GIP with positive correlations with BAC-max. As GIP and ΔPGC are both reflected by gastric emptying rate (GER), we concluded that the individual differences in BAC after moderate drinking are mainly regulated by GER together with Vd. These findings demonstrate that together with body water content, the gastrointestinal tract plays an important role in the regulation of individual differences in BAC, involving first pass metabolism of ethanol.

Share and Cite:

S. Oshima, T. Haseba, C. Masuda, E. Kakimi, M. Sami, T. Kanda and Y. Ohno, "Individual Differences in Blood Alcohol Concentrations after Moderate Drinking Are Mainly Regulated by Gastric Emptying Rate Together with Ethanol Distribution Volume," Food and Nutrition Sciences, Vol. 3 No. 6, 2012, pp. 732-737. doi: 10.4236/fns.2012.36099.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] R. Guo and J. Ren, “Alcohol and Acetaldehyde in Public Health: From Marvel to Menace,” International Journal of Environmental Research and Public Health, Vol. 7, No. 4, 2010, pp. 1285-1301. http://www.mdpi.com/1660-4601/7/4/1285/ doi:10.3390/ijerph7041285
[2] S. Harada, D. P. Agarwal and H. W. Goedde, “Aldehyde Dehydrogenase Deficiency as Cause of Facial Flushing Reaction to Alcohol in Japanese,” Lancet, Vol. 2, No. 8253, 1981, p. 982. doi:10.1016/S0140-6736(81)91172-7
[3] G. S. Peng, M. F. Wang, C. Y. Chen, S. U. Luu, H. C. Chou, T. K. Li and S. J. Yin, “Involvement of Acetaldehyde for Full Protection against Alcoholism by Homozygosity of the Variant Allele of Mitochondrial Aldehyde Dehydrogenase Gene in Asians,” Pharmacogenetics, Vol. 9, No. 4, 1999, pp. 463-476.
[4] Y. Mizoi, K. Yamamoto, Y. Ueno, T. Fukunaga and S. Harada, “Involvement of Genetic Polymorphism of Alcohol and Aldehyde Dehydrogenases in Individual Variation of Alcohol Metabolism,” Alcohol and Alcoholism, Vol. 29, No. 6, 1994, pp. 707-710. http://alcalc.oxfordjournals.org/content/29/6/707.long
[5] S. Oshima, T. Haseba, C. Masuda, Y. Abe, M. Sami, T. Kanda and Y. Ohno, “Alcohol Metabolism at Moderate Drinking in Healthy Men. Comparison between Differences of Alcohol Beverages, with and without Meal, and Genetic Polymorphism,” Japanese Journal of Alcohol Studies and Drug Dependence, Vol. 46, No. 3, 2011, pp. 357-367.
[6] H. R. Thomasson, J. D. Beard and T. K. Li, “ADH2 Gene Polymorphisms Are Determinants of Alcohol Pharmacokinetics,” Alcoholism: Clinical and Experimental Research, Vol. 19, No. 6, 1995, pp. 1494-1499. doi:10.1111/j.1530-0277.1995.tb01013.x
[7] C. S. Lieber, L. M. DeCarli, L. Feinman, Y. Hasumura, M. Korsten, S. Matsuzaki and R. Teschke, “Effect of Chronic Alcohol Consumption on Ethanol and Acetaldehyde Metabolism,” Advances in Experimental Medicine and Biology, Vol. 59, 1975, pp. 185-227.
[8] A. H. Tzamaloukas, J. E. Jackson, J. C. Gallegos, D. A. Long and M. M. McLane, “Distribution Volume of Ethanol as a Measure of Body Water,” Mineral and Electrolyte Metabolism, Vol. 11, No. 2, 1985, pp. 123-130.
[9] A. W. Marshall, D. Kingstone, M. Boss and M. Y. Morgan, “Ethanol Elimination in Males and Females: Relationship to Menstrual Cycle and Body Composition,” Hepatology, Vol. 3, No. 5, 1983, pp. 701-706. doi:10.1002/hep.1840030513
[10] R. T. Gentry, E. Baraona and C. S. Lieber, “Agonist: Gastric First Pass Metabolism of Alcohol,” Journal of Laboratory and Clinical Medicine, Vol. 123, No. 1, 1994, pp. 21-26.
[11] R. P. Roine, R. T. Gentry, R. T. Lim Jr, E. Helkkonen, M. Salaspuro and C. S. Lieber, “Comparison of Blood Alcohol Concentrations after Beer and Whiskey,” Alcoholism: Clinical and Experimental Research, Vol. 17, No. 3, 1993, pp. 709-711. doi:10.1111/j.1530-0277.1993.tb00824.x
[12] R. T. Lim Jr., R. T. Gentry, D. Ito, H. Yokoyama, E. Baraona and C. S. Lieber, “First-Pass Metabolism of Ethanol Is Predominantly Gastric,” Alcoholism: Clinical and Experimental Research, Vol. 17, No. 6, 1993, pp. 13371344. doi:10.1111/j.1530-0277.1993.tb05250.x
[13] S. Oshima, C. Masuda, E. Kakimi, M. Sami, T. Kanda, T. Haseba and Y. Ohno, “Gastric First Pass Metabolism Plays an Important Role in the Food-Induced Lowering of Blood Alcohol Concentration and AUC, Enhanced by the Delay of Gastric Empting,” Alcohol and Biomedical Research, Vol. 30, 2011, pp. 64-71.
[14] T. Okada and Y. Mizoi, “Studies on the Problem of Blood Acetaldehyde Determination in Man and Level after Alcohol Intake,” Japanese Journal of Alcohol Studies and Drug Dependence, Vol. 17, No. 2, 1982, pp. 141-159.
[15] D. Kozutsumi, M. Arita, A, Kawashima, M, Adachi and M. Takami, “An Improved Method for Acetaldehyde Determination in Blood by High-Performance Liquid Chromatography and Solid-Phase Extraction,” Journal of Chromatographic Science, Vol. 40, No. 10, 2002, pp. 477-482.
[16] J. M. Polak, S. R. Bloom, M. Kuzio, J. C. Brown and A. G. Pearse, “Cellular Localization of Gastric Inhibitory Polypeptide in the Duodenum and Jejunum,” Gut, Vol. 14, No. 4, 1973, pp. 284-288. doi:10.1136/gut.14.4.284
[17] I. G. Cleator and R. H. Gourlay, “Release of Immunoreactive Gastric Inhibitory Polypeptide (IR-GIP) by Oral Ingestion of Food Substances,” American Journal of Surgery, Vol. 130, No. 2, 1975, pp. 128-135. doi:10.1016/0002-9610(75)90360-8
[18] K. B. Lauritsen, H. J. Frederiksen, A. Uhrenholdt and J. J. Holst, “The Correlation between Gastric Emptying Time and the Response of GIP and Enteroglucagon to Oral Glucose in Duodenal Ulcer Patients,” Scandinavian Journal of Gastroenterology, Vol. 17, No. 4, 1982, pp. 513516. doi:10.3109/00365528209182241
[19] M. Horowitz, M. A. Edelbroek, J. M. Wishart and J. W. Straathof, “Relationship between Oral Glucose Tolerance and Gastric Emptying in Normal Healthy Subjects,” Diabetologia, Vol. 36, No. 9, 1993, pp. 857-862. doi:10.1007/BF00400362
[20] A. Karamanlis, R. Chaikomin, S. Doran, M. Bellon, F. D. Bartholomeusz, J. M. Wishart, K. L. Jones, M. Horowitz and C. K. Rayner, “Effects of Protein on Glycemic and Incretin Responses and Gastric Emptying after Oral Glucose in Healthy Subjects,” American Journal of Clinical Nutrition, Vol. 86, No. 5, 2007, pp. 1364-1368. http://www.ajcn.org/content/86/5/1364.long
[21] J. E. Stevens, O. H. Gilja, D. Gentilcore, T. Hausken, M. Horowitz and K. L. Jones, “Measurement of Gastric Emptying of a High-Nutrient Liquid by 3D Ultrasonography in Diabetic Gastroparesis,” Neurogastroenterology and Motility, Vol. 23, No. 3, 2011, pp. 220-225. doi:10.1111/j.1365-2982.2010.01630.x
[22] M. Y. Eng, S. E. Luczak and T. L. Wall, “ALDH2, ADH1B, and ADH1C Genotypes in Asians: A Literature Review,” Alcohol Research & Health, Vol. 30, No. 1, 2007, pp. 22-27.
[23] H. J. Edenberg, “Regulation of the Mammalian Alcohol Dehydrogenase Genes,” Progress in Nucleic Acid Research & Molecular Biology, Vol. 64, 2000, pp. 295-341. doi:10.1016/S0079-6603(00)64008-4
[24] A. G. Dawson, “Ethanol Oxidation in Systems Containing Soluble and Mitochondrial Fractions of Rat Liver. Regulation by Acetaldehyde,” Biochemical Pharmacology, Vol. 32, No. 14, 1983, pp. 2157-2165. doi:10.1016/0006-2952(83)90221-6
[25] Y. Ueno, J. Adachi, H. Imamichi, A. Nishimura and Y. Tatsuno, “Effect of the Cytochrome P-450IIE1 Genotype on Ethanol Elimination Rate in Alcoholics and Control Subjects,” Alcoholism: Clinical and Experimental Research, Vol. 20, No. 1, 1996, pp. 17A-21A. doi:10.1111/j.1530-0277.1996.tb01720.x
[26] S. Kechagias, K. A. J?nsson and A. W. Jones, “Impact of Gastric Emptying on the Pharmacokinetics of Ethanol as Influenced by Cisapride,” British Journal of Clinical Pharmacology, Vol. 48, No. 5, 1999, pp. 728-732. doi:10.1046/j.1365-2125.1999.00080.x
[27] A. Franke, I. A. Nakchbandi, A. Schneider, H. Harder and M. V. Singer, “The Effect of Ethanol and Alcoholic Beverages on Gastric Emptying of Solid Meals in Humans,” Alcohol and Alcoholism, Vol. 40, No. 3, 2005, pp. 187193. doi:10.1093/alcalc/agh138
[28] K. L. Wu, R. Chaikomin, S. Doran, K. L. Jones, M. Horowitz and C. K. Rayner, “Artificially Sweetened versus Regular Mixers Increase Gastric Emptying and Alcohol Absorption,” American Journal of Medicine, Vol. 119, No. 9, 2006, pp. 802-804. doi:10.1016/j.amjmed.2006.02.005
[29] J. Caballeria, M. Frezza, R. Hernández-Mu?oz, C. DiPadova, M. A. Korsten, E. Baraona and C. S. Lieber, “Gastric Origin of the First-Pass Metabolism of Ethanol in Humans: Effect of Gastrectomy,” Gastroenterology, Vol. 97, No. 5, 1989, pp. 1205-1209.
[30] D. M. Pestalozzi, R. Bühler, J. P. von Wartburg and M. Hess, “Immunohistochemical Localization of Alcohol Dehydrogenase in the Human Gastrointestinal Tract,” Gastroenterology, Vol. 85, No. 5, 1983, pp. 1011-1016.
[31] H. K. Seitz and G. P?schl, “The Role of Gastrointestinal Factors in Alcohol Metabolism,” Alcohol and Alcoholism, Vol. 32, No. 5, 1997, pp. 543-549. doi:10.1093/oxfordjournals.alcalc.a008294
[32] R. D. Johnson, M. Horowitz, A. F. Maddox, J. M. Wishart and D. J. Shearman, “Cigarette Smoking and Rate of Gastric Emptying: Effect on Alcohol Absorption,” British Medical Journal, Vol. 302, No. 20, 1991, pp. 20-23. doi:10.1136/bmj.302.6767.20
[33] C. M. Oneta, U. A. Simanowski, M. Martinez, A. Allali-Hassani, X. Parés, N. Homann, C. Conradt, R. Waldherr, W. Fiehn, C. Coutelle and H. K. Seitz, “First Pass Metabolism of Ethanol Is Strikingly Influenced by the Speed of Gastric Emptying,” Gut, Vol. 43, No. 5, 1998, pp. 612-619. doi:10.1136/gut.43.5.612
[34] K. B. Lauritsen and A. J. Moody, “The Response of Gastric Inhibitory Polypeptide (GIP) and Insulin to Glucose in Duodenal Ulcer Patients,” Diabetologia, Vol. 14, No. 3, 1978, pp. 149-153. doi:10.1007/BF00429773
[35] D. Gentilcore, R. Chaikomin, K. L. Jones, A. Russo, C. Feinle-Bisset, J. M. Wishart, C. K. Rayner and M. Horowitz, “Effects of Fat on Gastric Emptying of and the Glycemic, Insulin, and Incretin Responses to a Carbohydrate Meal in Type 2 Diabetes,” Journal of Clinical Endocrinology & Metabolism, Vol. 91, No. 6, 2006, pp. 20622067. doi:10.1210/jc.2005-2644

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.