European Journal of Nutrition

, Volume 53, Issue 8, pp 1727–1735 | Cite as

The impact of cereal grain consumption on the development and severity of non-alcoholic fatty liver disease

  • Michael Georgoulis
  • Meropi D. KontogianniEmail author
  • Nafsika Tileli
  • Aikaterini Margariti
  • Elisabeth Fragopoulou
  • Dina Tiniakos
  • Rodessa Zafiropoulou
  • George Papatheodoridis
Original Contribution



There is evidence that dietary habits contribute to the presence and severity of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to explore any associations between consumption of grains and the development and severity of NAFLD.


Seventy-three consecutive NAFLD patients were enrolled. Additionally, 58 controls matched for age, sex and body mass index with 58 patients were also included. Consumption of grains was estimated through a semi-quantitative food frequency questionnaire. Medical history, anthropometric indices, body composition analysis, physical activity data, biochemical and inflammatory markers were available for all the participants. Liver stiffness measurement by transient elastography was performed in 58 and liver biopsy in 34 patients.


In patients, consumption of whole grains was associated with lower abdominal fat level (β = −0.24, p = 0.02) and lower levels of insulin resistance index (β = −0.28, p = 0.009), while it also correlated inversely with interleukin-6 levels (ρ = −0.23, p = 0.05). Consumption of whole grains was associated with lower likelihood of having histological steatohepatitis (OR 0.97, 95 % CI 0.94–1.000), after adjusting for sex and energy intake, but the association became weaker after further adjusting for abdominal fat or interleukin-6 levels. In the case–control analysis, consumption of refined grains was associated with higher odds of having NAFLD (OR 1.021, 95 % CI 1.001–1.042), after adjusting for age, sex, energy intake, abdominal fat level, HOMA-IR, LDL, adiponectin and TNF-α.


Although refined grain consumption increased the likelihood of having NAFLD, whole-grain consumption favorably affected clinical characteristics of patients with NAFLD and tended to be associated with less severe disease.


Non-alcoholic fatty liver Cereals Inflammation Insulin resistance Case–control 



We would like to thank Prof. Mary Yannakoulia for her valuable comments during the writing of the manuscript. This research was supported financially by a research grant from the Hellenic Foundation of Gastroenterology & Nutrition.

Conflict of interest

All authors declare no conflicts of interest.


  1. 1.
    Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ (2012) The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 142:1592–1609. doi: 10.1053/j.gastro.2012.04.001 CrossRefGoogle Scholar
  2. 2.
    Levene AP, Goldin RD (2012) The epidemiology, pathogenesis and histopathology of fatty liver disease. Histopathology 61:141–152. doi: 10.1111/j.1365-2559.2011.04145.x CrossRefGoogle Scholar
  3. 3.
    Tsochatzis E, Papatheodoridis GV, Archimandritis AJ (2006) The evolving role of leptin and adiponectin in chronic liver diseases. Am J Gastroenterol 101:2629–2640. doi: 10.1111/j.1572-0241.2006.00848.x CrossRefGoogle Scholar
  4. 4.
    Tsochatzis EA, Manolakopoulos S, Papatheodoridis GV, Archimandritis AJ (2009) Insulin resistance and metabolic syndrome in chronic liver diseases: old entities with new implications. Scand J Gastroenterol 44:6–14. doi: 10.1080/00365520802273058 CrossRefGoogle Scholar
  5. 5.
    Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34:274–285. doi: 10.1111/j.1365-2036.2011.04724.x CrossRefGoogle Scholar
  6. 6.
    Sullivan S (2010) Implications of diet on nonalcoholic fatty liver disease. Curr Opin Gastroenterol 26:160–164. doi: 10.1097/MOG.0b013e3283358a58 CrossRefGoogle Scholar
  7. 7.
    Mouzaki M, Allard JP (2012) The role of nutrients in the development, progression, and treatment of nonalcoholic fatty liver disease. J Clin Gastroenterol 46:457–467. doi: 10.1097/MCG.0b013e31824cf51e CrossRefGoogle Scholar
  8. 8.
    Williams PG (2012) Evaluation of the evidence between consumption of refined grains and health outcomes. Nutr Rev 70:80–99. doi: 10.1111/j.1753-4887.2011.00452.x CrossRefGoogle Scholar
  9. 9.
    Lefevre M, Jonnalagadda S (2012) Effect of whole grains on markers of subclinical inflammation. Nutr Rev 70:387–396. doi: 10.1111/j.1753-4887.2012.00487.x CrossRefGoogle Scholar
  10. 10.
    Ye EQ, Chacko SA, Chou EL, Kugizaki M, Liu S (2012) Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain. J Nutr 142:1304–1313. doi: 10.3945/jn.111.155325 CrossRefGoogle Scholar
  11. 11.
    Ross AB, Godin JP, Minehira K, Kirwan JP (2013) Increasing whole grain intake as part of prevention and treatment of nonalcoholic Fatty liver disease. Int J Endocrinol 2013:585876. doi: 10.1155/2013/585876 CrossRefGoogle Scholar
  12. 12.
    World Medical Association declaration of Helsinki (1997) Recommendations guiding physicians in biomedical research involving human subjects. JAMA, J Am Med Assoc 277:925–926CrossRefGoogle Scholar
  13. 13.
    Goulet J, Nadeau G, Lapointe A, Lamarche B, Lemieux S (2004) Validity and reproducibility of an interviewer-administered food frequency questionnaire for healthy French-Canadian men and women. Nutr J 3:13. doi: 10.1186/1475-2891-3-13 CrossRefGoogle Scholar
  14. 14.
    Trichopoulou A, Lagiou P (1999) Dietary guidelines for adults in Greece. Arch Hell Med 16:516–524Google Scholar
  15. 15.
    Nanos GD, Gerasopoulos DG (2001) Fruits, Vegetable, Legumes and Grains. In: Zampelas A, Stavrinos V, Wolinsky I, Matalas AL (eds) The mediterranean diet: constituents and health promotion. CRC Press LLC, Boca RatonGoogle Scholar
  16. 16.
    Manios Y, Moschonis G, Koutsikas K, Papoutsou S, Petraki I, Bellou E, Naoumi A, Kostea S, Tanagra S (2009) Changes in body composition following a dietary and lifestyle intervention trial: the postmenopausal health study. Maturitas 62:58–65. doi: 10.1016/j.maturitas.2008.11.005 CrossRefGoogle Scholar
  17. 17.
    Browning LM, Mugridge O, Chatfield MD, Dixon AK, Aitken SW, Joubert I, Prentice AM, Jebb SA (2010) Validity of a new abdominal bioelectrical impedance device to measure abdominal and visceral fat: comparison with MRI. Obesity (Silver Spring) 18:2385–2391. doi: 10.1038/oby.2010.71 CrossRefGoogle Scholar
  18. 18.
    Friedewald WT, Levy RIFD (1972) Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502Google Scholar
  19. 19.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefGoogle Scholar
  20. 20.
    Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94:2467–2474. doi: 10.1111/j.1572-0241.1999.01377.x CrossRefGoogle Scholar
  21. 21.
    Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321. doi: 10.1002/hep.20701 CrossRefGoogle Scholar
  22. 22.
    Shi L, Liu ZW, Li Y, Gong C, Zhang H, Song LJ, Huang CY, Li M (2012) The prevalence of nonalcoholic fatty liver disease and its association with lifestyle/dietary habits among university faculty and staff in Chengdu. Biomed Environ Sci 25:383–391. doi: 10.3967/0895-3988.2012.04.002 Google Scholar
  23. 23.
    Toshimitsu K, Matsuura B, Ohkubo I, Niiya T, Furukawa S, Hiasa Y, Kawamura M, Ebihara K, Onji M (2007) Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition 23:46–52. doi: 10.1016/j.nut.2006.09.004 CrossRefGoogle Scholar
  24. 24.
    Liu S (2002) Intake of refined carbohydrates and whole grain foods in relation to risk of type 2 diabetes mellitus and coronary heart disease. J Am Coll Nutr 21:298–306CrossRefGoogle Scholar
  25. 25.
    Giugliano D, Ceriello A, Esposito K (2006) The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol 48:677–685. doi: 10.1016/j.jacc.2006.03.052 CrossRefGoogle Scholar
  26. 26.
    Krawczyk M, Bonfrate L, Portincasa P (2010) Nonalcoholic fatty liver disease. Best Pract Res Clin Gastroenterol 24:695–708. doi: 10.1016/j.bpg.2010.08.005 CrossRefGoogle Scholar
  27. 27.
    Wirström T, Hilding A, Gu HF, Östenson C-G, Björklund A (2013) Consumption of whole grain reduces risk of deteriorating glucose tolerance, including progression to prediabetes. Am J Clin Nutr 97:179–187. doi: 10.3945/ajcn.112.045583 CrossRefGoogle Scholar
  28. 28.
    Murtaugh MA, Jacobs DR Jr, Jacob B, Steffen LM, Marquart L (2003) Epidemiological support for the protection of whole grains against diabetes. Proc Nutr Soc 62:143–149CrossRefGoogle Scholar
  29. 29.
    Sahyoun NR, Jacques PF, Zhang XL, Juan W, McKeown NM (2006) Whole-grain intake is inversely associated with the metabolic syndrome and mortality in older adults. Am J Clin Nutr 83:124–131Google Scholar
  30. 30.
    McKeown NM, Troy LM, Jacques PF, Hoffmann U, O’Donnell CJ, Fox CS (2010) Whole- and refined-grain intakes are differentially associated with abdominal visceral and subcutaneous adiposity in healthy adults: the Framingham Heart Study. Am J Clin Nutr 92:1165–1171. doi: 10.3945/ajcn.2009.29106 CrossRefGoogle Scholar
  31. 31.
    Liu S, Willett WC, Manson JE, Hu FB, Rosner B, Colditz G (2003) Relation between changes in intakes of dietary fiber and grain products and changes in weight and development of obesity among middle-aged women. Am J Clin Nutr 78:920–927Google Scholar
  32. 32.
    McKeown NM, Yoshida M, Shea MK, Jacques PF, Lichtenstein AH, Rogers G, Booth SL, Saltzman E (2009) Whole-grain intake and cereal fiber are associated with lower abdominal adiposity in older adults. J Nutr 139:1950–1955. doi: 10.3945/jn.108.103762 CrossRefGoogle Scholar
  33. 33.
    Fardet A (2010) New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutr Res Rev 23:65–134. doi: 10.1017/S0954422410000041 CrossRefGoogle Scholar
  34. 34.
    Salas-Salvado J, Martinez-Gonzalez MA, Bullo M, Ros E (2011) The role of diet in the prevention of type 2 diabetes. Nutr Metab Cardiovasc Dis 21(Suppl 2):B32–B48. doi: 10.1016/j.numecd.2011.03.009 CrossRefGoogle Scholar
  35. 35.
    Tilg H, Moschen AR (2008) Insulin resistance, inflammation, and non-alcoholic fatty liver disease. Trends Endocrinol Metab 19:371–379. doi: 10.1016/j.tem.2008.08.005 CrossRefGoogle Scholar
  36. 36.
    Lutsey PL, Jacobs DR Jr, Kori S, Mayer-Davis E, Shea S, Steffen LM, Szklo M, Tracy R (2007) Whole grain intake and its cross-sectional association with obesity, insulin resistance, inflammation, diabetes and subclinical CVD: the MESA Study. Br J Nutr 98:397–405. doi: 10.1017/S0007114507700715 CrossRefGoogle Scholar
  37. 37.
    Nettleton JA, Steffen LM, Mayer-Davis EJ, Jenny NS, Jiang R, Herrington DM, Jacobs DR Jr (2006) Dietary patterns are associated with biochemical markers of inflammation and endothelial activation in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 83:1369–1379Google Scholar
  38. 38.
    Yannakoulia M, Yiannakouris N, Melistas L, Kontogianni MD, Malagaris I, Mantzoros CS (2008) A dietary pattern characterized by high consumption of whole-grain cereals and low-fat dairy products and low consumption of refined cereals is positively associated with plasma adiponectin levels in healthy women. Metabolism 57:824–830. doi: 10.1016/j.metabol.2008.01.027 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Michael Georgoulis
    • 1
  • Meropi D. Kontogianni
    • 1
    Email author
  • Nafsika Tileli
    • 1
  • Aikaterini Margariti
    • 2
  • Elisabeth Fragopoulou
    • 1
  • Dina Tiniakos
    • 3
  • Rodessa Zafiropoulou
    • 2
  • George Papatheodoridis
    • 2
    • 4
  1. 1.Department of Nutrition and DieteticsHarokopio UniversityAthensGreece
  2. 2.2nd Department of Internal Medicine, Hippokration Hospital of AthensUniversity of Athens Medical SchoolAthensGreece
  3. 3.Laboratory of Histology & Embryology, Medical SchoolNational & Kapodistrian University of AthensAthensGreece
  4. 4.Department of Gastroenterology, Laiko Hospital of AthensUniversity of Athens Medical SchoolAthensGreece

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