Skip to main content

Advertisement

SpringerLink
Log in

Biphasic effect of alcohol intake on the development of fatty liver disease

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Fatty liver is an important clinical feature not only in alcoholic and non-alcoholic fatty liver diseases, but in other chronic liver diseases as well. Our aim was to elucidate the effect and relationship between habitual alcohol intake and obesity in the development of fatty liver disease.

Methods

We enrolled 8,029 subjects undergoing abdominal ultrasonography with general medical examinations, and analyzed the factors associated with fatty liver based on daily alcohol intake, body mass index (BMI), and waist circumference.

Results

For fatty liver, BMI, waist circumference, total cholesterol, triglycerides, and fasting plasma glucose were significant and independent risk factors. Heavy alcohol intake (50 g/day) was a significant risk factor for fatty liver in women (odds ratio [OR], 3.35). Analysis based on the presence or absence of obesity revealed that moderate alcohol intake was a significant negative risk factor for fatty liver in both male and female obese (BMI ≥25 kg/m2) subjects (OR, 0.74 for non-obese and 0.39 for obese patients, respectively). Heavy alcohol intake was also a significant negative risk factor in obese males (0.62). In contrast, heavy alcohol intake was a risk factor in non-obese males (OR, 1.29) and in all females (OR, 2.22 for non-obese and 6.6 for obese patients, respectively).

Conclusions

The influence of alcohol intake on fatty liver differed depending on the level of alcohol consumption, gender, and the presence of obesity, and showed biphasic effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ALD:

Alcoholic liver disease

ALT:

Alanine aminotransferase

NAFLD:

Non-alcoholic fatty liver disease

BMI:

Body mass index

WC:

Waist circumference

AST:

Aspartate aminotransferase

GGT:

Gamma-glutamyl transferase

TC:

Total cholesterol

HDL:

High-density lipoprotein

TG:

Triglycerides

FPG:

Fasting plasma glucose

LDL:

Low-density lipoprotein

NASH:

Nonalcoholic steatohepatitis

OR:

Odds ratio

CI:

Confidence interval

References

  1. Bedogni G, Miglioli L, Masutti F, et al. Incidence and natural course of fatty liver in the general population: the Dionysos study. Hepatology. 2007;46:1387–91.

    Article  PubMed  Google Scholar 

  2. Pendino GM, Mariano A, Surace P, et al. Prevalence and etiology of altered liver tests: a population—based survey in a Mediterranean town. Hepatology. 2005;41:1151–9.

    Article  PubMed  Google Scholar 

  3. Ruhl CE, Everhart JE. Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population. Clin Gastroenterol Hepatol. 2005;3:1260–8.

    Article  CAS  PubMed  Google Scholar 

  4. Bizzaro N, Tremolada F, Casarin C, et al. Serum alanine aminotransferase levels among volunteer blood donors: effect of sex, alcohol intake and obesity. Ital J Gastroenterol. 1992;24:237–41.

    CAS  PubMed  Google Scholar 

  5. Kondili LA, Taliani G, Cerga G, et al. Correlation of alcohol consumption with liver histological features in non–cirrhotic patients. Eur J Gastroenterol Hepatol. 2005;17:155–9.

    Article  CAS  PubMed  Google Scholar 

  6. Maher JJ. Alcoholic steatosis and steatohepatitis. Semin Gastrointest Dis. 2002;13:31–9.

    PubMed  Google Scholar 

  7. Zhou YJ, Li YY, Nie YQ, et al. Prevalence of fatty liver disease and its risk factors in the population of South China. World J Gastroenterol. 2007;13:6419–24.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Bellentani S, Saccoccio G, Masutti F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med. 2000;132:112–7.

    Article  CAS  PubMed  Google Scholar 

  9. Michitaka K, Nishiguchi S, Aoyagi Y, et al. Etiology of liver cirrhosis in Japan: a nationwide survey. J Gastroenterol. 2010;45:86–94.

    Article  PubMed  Google Scholar 

  10. Suzuki A, Angulo P, St Sauver J, et al. Light to moderate alcohol consumption is associated with lower frequency of hypertransaminasemia. Am J Gastroenterol. 2007;102:1912–9.

    Article  PubMed  Google Scholar 

  11. Dunn W, Xu R, Schwimmer JB. Modest wine drinking and decreased prevalence of suspected non-alcoholic fatty liver disease. Hepatology. 2008;47:1947–54.

    Article  PubMed  Google Scholar 

  12. Gunji T, Matsuhashi N, Sato H, et al. Light and moderate alcohol consumption significantly reduces the prevalence of fatty liver in the Japanese male population. Am J Gastroenterol. 2009;104:2189–95.

    Article  PubMed  Google Scholar 

  13. Hiramine Y, Imamura Y, Uto H, et al. Alcohol drinking patterns and the risk of fatty liver in Japanese men. J Gastroenterol. 2011;46:519–28.

    Article  CAS  PubMed  Google Scholar 

  14. Miyake T, Kumagi T, Hirooka M, et al. Body mass index is the most useful predictive factor for the onset of nonalcoholic fatty liver disease: a community—based retrospective longitudinal cohort study. J Gastroenterol. 2013;48:413–22.

    Article  PubMed  Google Scholar 

  15. Sogabe M, Okahisa T, Hibino S, Yamanoi A. Usefulness of differentiating metabolic syndrome into visceral fat type and subcutaneous fat type using ultrasonography in Japanese males. J Gastroenterol. 2012;47:293–9.

    Article  CAS  PubMed  Google Scholar 

  16. Nishioji K, Sumida Y, Kamaguchi M, et al. Prevalence of and risk factors for non-alcoholic fatty liver disease in a non-obese Japanese population, 2011–2012. J Gastroenterol. 2015;50:95–108.

    Article  CAS  PubMed  Google Scholar 

  17. Eguchi Y, Hyogo H, Ono M, et al. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J Gastroenterol. 2012;47:586–95.

    Article  CAS  PubMed  Google Scholar 

  18. Tanaka K, Hyogo H, Ono M, et al. Upper limit of normal serum alanine aminotransferase levels in Japanese subjects. Hepatol Res. 2014;44:1196–207.

    Article  CAS  PubMed  Google Scholar 

  19. The World Medical Association, Inc. Declaration of Helsinki; Ethical principle for medical research involving human subject. Seoul: WMA General Assembly; 2008.

  20. Examination Committee of Criteria for ‘Obesity Disease’ in Japan; Japan Society for the Study of Obesity. New criteria for ‘obesity disease’ in Japan. Circ J. 2002;66:987–92.

    Article  Google Scholar 

  21. Guy J, Peters MG. Liver disease in women: the influence of gender on epidemiology, natural history, and patient outcomes. Gastroenterol Hepatol (NY). 2013;9:633–9.

    Google Scholar 

  22. Becker U, Deis A, Sorensen TI, et al. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology. 1996;23:1025–9.

    Article  CAS  PubMed  Google Scholar 

  23. Lieber CS. Gender differences in alcohol metabolism and susceptibility. In: Wilsnack RW, Wilsnack SC, editors. Gender and alcohol: individual and social perspectives. Piscataway: Rutgers Center of Alcohol Studies; 1997. p. 77–89.

    Google Scholar 

  24. Nolen-Hoeksema S. Gender differences in risk factors and consequences for alcohol use and problems. Clin Psychol Rev. 2004;24:981–1010.

    Article  PubMed  Google Scholar 

  25. Frezza M, di PC, Pozzato G, Terpin M, Baraona E, Lieber CS. High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first–pass metabolism. N Engl J Med. 1990;322:95–9.

    Article  CAS  PubMed  Google Scholar 

  26. Ikejima K, Enomoto N, Iimuro Y, et al. Estrogen increases sensitivity of hepatic Kupffer cells to endotoxin. Am J Physiol. 1998;274(4 pt 1):G669–76.

    CAS  PubMed  Google Scholar 

  27. Dixon JB, Bhathal PS, O’ Brien PE. Non-alcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001;121:91–100.

    Article  CAS  PubMed  Google Scholar 

  28. Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high–calorie diet. Nature. 2006;444:337–42.

    Article  CAS  PubMed  Google Scholar 

  29. Tomie Furuya D, Binsack R, Onishi ME, et al. Low ethanol consumption induces enhancement of insulin sensitivity in liver of normal rats. Life Sci. 2005;77:1813–24.

    Article  PubMed  Google Scholar 

  30. Schulze MB, Hoffmann K, Manson JE, et al. Dietary pattern, inflammation, and incidence of type 2 diabetes in women. Am J Clin Nutr. 2005;82:675–84.

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Davies MJ, Baer DJ, Judd JT, et al. Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial. JAMA. 2002;287:2559–62.

    Article  CAS  PubMed  Google Scholar 

  32. Feng L, Gao L, Guan Q, et al. Long–term moderate ethanol consumption restore insulin sensitivity in high–fat–fed rats by increasing SLCA4 (GLUT4) in the adipose tissue by AMP–activated kinase activation. J Endocrinol. 2008;199:95–104.

    Article  CAS  PubMed  Google Scholar 

  33. Sierksma A, Patel H, Ouchi N, et al. Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor–alpha, and insulin sensitivity. Diabetes Care. 2004;27:184–9.

    Article  CAS  PubMed  Google Scholar 

  34. Yang CM, Carlson GP. Effects of ethanol on glutathione conjugation in rat liver and lung. Biochem Pharmacol. 1991;41:923–9.

    Article  CAS  PubMed  Google Scholar 

  35. Guarino MP, Afonso RA, Raimundo N, et al. Hepatic glutathione and nitric oxide are critical for hepatic insulin sensitizing substance action. Am J Physiol Gastrointest Liver Physiol. 2003;284:G588–94.

    Article  CAS  PubMed  Google Scholar 

  36. Feng L, Han B, Wang R, et al. The frequency of daily ethanol consumption influences the effect of ethanol on insulin sensitivity in rats fed a high–fat diet. Br J Nutr. 2012;107:850–7.

    Article  CAS  PubMed  Google Scholar 

  37. Lopez-Garcia E, Guallar-Castillon P, Leon-Muñoz L, et al. Prevalence and determinants of metabolically healthy obesity in Spain. Atherosclerosis. 2013;231:152–7.

    Article  CAS  PubMed  Google Scholar 

  38. Xu YY, Bhavani K, Wands JR, et al. Ethanol inhibits insulin receptor substrate–1 tyrosine phosphorylation and insulin–stimulated neuronal thread protein gene expression. Biochem J. 1995;310:125–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Bhavani K, de la Monte SM, Brown NV, et al. Effect of ethanol on p36 protein kinase substrate and insulin receptor substrate 1 expression and tyrosyl phosphorylation in human hepatocellular carcinoma cells. Alcohol Clin Exp Res. 1995;19:441–6.

    Article  CAS  PubMed  Google Scholar 

  40. Onishi Y, Honda M, Ogihara T, et al. Ethanol feeding induces insulin resistance with enhanced PI 3–kinase activation. Biochem Biophys Res Commun. 2003;303:788–94.

    Article  CAS  PubMed  Google Scholar 

  41. Lindtner C, Scherer T, Zielinski E, et al. Binge drinking induces whole–body insulin resistance by impairing hypothalamic insulin action. Sci Transl Med. 2013;5:170ra14.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Yki-Järvinen H, Nikkilä EA. Ethanol decreases glucose utilization in healthy man. J Clin Endocrinol Metab. 1985;61:941–5.

    Article  PubMed  Google Scholar 

  43. Yki-Järvinen H, Koivisto VA, Ylikahri R, et al. Acute effects of ethanol and acetate on glucose kinetics in normal subjects. Am J Physiol. 1988;254:E175–80.

    PubMed  Google Scholar 

  44. O’Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Am J Gastroenterol. 2010;105:14–32.

    Article  PubMed  Google Scholar 

  45. Mendenhall CL. Anabolic steroid therapy as an adjunct to diet in alcoholic hepatic steatosis. Am J Dig Dis. 1968;13:783–91.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Professor Kyuichi Tanikawa (International Institute for Liver Research) for his excellent advice; the entire medical staff at Eguchi Hospital, Kochi Medical School, and Kawamura Clinic for assistance; and members of the Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD) for their excellent advice. The authors have no conflicts of interest to declare. This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan (2014 non-numbered). All authors approved the final version of the article and the guarantor of the article is Hideyuki Hyogo. Author contributions are described as follows: (a) substantial contributions to the conception and design; or the acquisition, analysis, or interpretation of the data: MO, HT, TE, CT, YK, and NO; (b) drafting of the article or critical revision for important intellectual content: HT, HH, MO, YE. and KF; (c) final approval of the version to be published: all authors; (d) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved: HT, HH, MO, and YE.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Saga Medical School, Saga, Japan

    Hirokazu Takahashi, Chika Tsuji, Yoichiro Kitajima, Kazuma Fujimoto & Keizo Anzai

  2. Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan

    Masafumi Ono & Toshiji Saibara

  3. Division of Hepatology, Saga Medical School, Saga, Japan

    Yuichiro Eguchi

  4. Department of Gastroenterology and Metabolism, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Hideyuki Hyogo & Kazuaki Chayama

  5. Clinical Gastroenterology, Eguchi Hospital, Saga, Japan

    Chika Tsuji, Yoichiro Kitajima, Naofumi Ono & Takahisa Eguchi

Authors
  1. Hirokazu Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masafumi Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideyuki Hyogo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chika Tsuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoichiro Kitajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naofumi Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takahisa Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazuma Fujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kazuaki Chayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Toshiji Saibara
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Keizo Anzai
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yuichiro Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideyuki Hyogo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takahashi, H., Ono, M., Hyogo, H. et al. Biphasic effect of alcohol intake on the development of fatty liver disease. J Gastroenterol 50, 1114–1123 (2015). https://doi.org/10.1007/s00535-015-1058-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-015-1058-z

Keywords

Search

Navigation