Cited by 1,328Alcohol Consumption and Health EffectsSubstance Abuse Treatment and OutcomesPharmacogenetics and Drug Metabolism

High Blood Alcohol Levels in Women: The Role of Decreased Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism

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Frezza, Mario, di Padova, Carlo, Pozzato, Gabriele, Terpin, Maddalena, Baraona, Enrique, Lieber, Charles S.·1990·New England Journal of Medicine

Abstract

After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease. Recently, we documented significant "first-pass metabolism" of ethanol due to its oxidation by gastric tissue. We report a study of the possible contribution of this metabolism to the sex-related difference in blood alcohol concentrations in 20 men and 23 women. Six in each group were alcoholics. The first-pass metabolism was determined on the basis of the difference in areas under the curves of blood alcohol concentrations after intravenous and oral administration of ethanol (0.3 g per kilogram of body weight). Alcohol dehydrogenase activity was also measured in endoscopic gastric biopsies. In nonalcoholic subjects, the first-pass metabolism and gastric alcohol dehydrogenase activity of the women were 23 and 59 percent, respectively, of those in the men, and there was a significant correlation (rs = 0.659) between first-pass metabolism and gastric mucosal alcohol dehydrogenase activity. In the alcoholic men, the first-pass metabolism and gastric alcohol dehydrogenase activity were about half those in the nonalcoholic men; in the alcoholic women, the gastric mucosal alcohol dehydrogenase activity was even lower than in the alcoholic men, and first-pass metabolism was virtually abolished. We conclude that the increased bioavailability of ethanol resulting from decreased gastric oxidation of ethanol may contribute to the enhanced vulnerability of women to acute and chronic complications of alcoholism.

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  1. [2]2. Lamboeuf Y, la Droitte P, de Saint-Blanquat G. The gastro-intestinal metabolism of ethanol in the rat: effect of chronic alcoholic intoxication. Arch Int Pharmacodyn Ther 1983; 261:157-69.
  2. [14]14. Jones BM, Jones MK. Male and female intoxication levels for three alcohol doses or do women really get higher than men? Alcohol Tech Rep 1976; 5:11-4.
  3. [21]21. Leatherbarrow RJ. Enzfitter: a non-linear regression data analysis program for the IBM PC. Amsterdam: Elsevier, 1987.
  4. [20]20. Dixon M, Webb EC. Enzymes. 3rd ed. New York: Academic Press, 1979.
  5. [24]24. Snedecor GW, Cochran WG. Statistical methods. 7th ed. Ames, Iowa: Iowa State University Press, 1980.

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Authors
Frezza, M., di Padova, C., Pozzato, G., Terpin, M., Baraona, E., & Lieber, C. S.
Affiliations
  • University of Trieste (IT)
  • Mount Sinai Hospital (US)
Venue
New England Journal of Medicine
Published
1990-01-11
Volume
322
Issue
2
Pages
95-99
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W2955761657
Cited by
1,328
References
27
Citations by year
2026: 34 · 2025: 42 · 2024: 27 · 2023: 26 · 2022: 42 · 2021: 40 · 2020: 36 · 2019: 50 · 2018: 27 · 2017: 30 · 2016: 34 · 2015: 34 · 2014: 35 · 2013: 30 · 2012: 36
FWCI
66.53
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5p50aa003508-18)
  • National Institute on Alcohol Abuse and Alcoholism (AA-03508)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
sex differences, blood alcohol concentration, alcohol metabolism, first-pass metabolism, gastric alcohol dehydrogenase, alcoholism, alcoholic liver disease
MeSH terms
Adult, Alcohol Oxidoreductases, Ethanol, Alcoholism, Biological Availability, Female, Gastric Mucosa, Humans, Male, Metabolic Clearance Rate, Middle Aged, Oxidation-Reduction, Sex Factors

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