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Original Communication

Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population

Published Online:https://doi.org/10.1024/0300-9831/a000667

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.

References

  • 1 Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005–23. First citation in articleCrossref MedlineGoogle Scholar

  • 2 Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10(11):686–90. First citation in articleCrossref MedlineGoogle Scholar

  • 3 Adams LA, Lymp JF, Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: A population-based cohort study. Gastroenterology. 2005;129(1):113–21. First citation in articleCrossref MedlineGoogle Scholar

  • 4 Vernon G, Baranova A, Younossi ZM. Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274–85. First citation in articleCrossref MedlineGoogle Scholar

  • 5 Kwok RM, Torres DM, Harrison SA. Vitamin D and nonalcoholic fatty liver disease (NAFLD): Is it more than just an association? Hepatology. 2013;58(3):1166–74. First citation in articleCrossref MedlineGoogle Scholar

  • 6 Lu L, Yu Z, Pan A, Hu FB, Franco OH, Li H, et al. Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly chinese individuals. Diabetes Care. 2009;32(7):1278–83. First citation in articleCrossref MedlineGoogle Scholar

  • 7 Kitson MT, Roberts SK. D-livering the message: The importance of vitamin D status in chronic liver disease. J Hepatol. 2012;57(4):897–909. First citation in articleCrossref MedlineGoogle Scholar

  • 8 Mitri J, Muraru MD, Pittas AG. Vitamin D and type 2 diabetes: A systematic review. Eur J Clin Nutr. 2011;65(9):1005–15. First citation in articleCrossref MedlineGoogle Scholar

  • 9 George PS, Pearson ER, Witham MD. Effect of vitamin D supplementation on glycaemic control and insulin resistance: A systematic review and meta-analysis. Diabet Med. 2012;29(8):e142–50. First citation in articleCrossref MedlineGoogle Scholar

  • 10 Cai J, Zhang Z, Liu J, Xiao X, Wang C, Deng M, et al. Correlation between serum 25-OH vitamin D expression and non-alcoholic fatty liver disease. Exp Ther Med. 2020;19(3):1681–6. First citation in articleMedlineGoogle Scholar

  • 11 Lee I, Park E, Cho J. Association of nonalcoholic fatty liver disease with serum vitamin D levels in combination of physical fitness in Korean older adults. J Steroid Biochem Mol Biol. 2020;198:105569. First citation in articleCrossref MedlineGoogle Scholar

  • 12 Chakraborty A, Choudhury A, Saha A. Development of non-alcoholic fatty liver disease (NAFLD) in young obese tribal subjects of Tripura: Link between low 25 (OH) vitamin-D levels and immune modulators. J Assoc Physicians India. 2019;67(8):52–6. First citation in articleMedlineGoogle Scholar

  • 13 Chen LW, Chien CH, Kuo SF, Yu CY, Lin CL, Chien RN. Low vitamin D level was associated with metabolic syndrome and high leptin level in subjects with nonalcoholic fatty liver disease: A community-based study. BMC Gastroenterol. 2019;19(1):126. First citation in articleCrossref MedlineGoogle Scholar

  • 14 Izadi A, Aliasghari F, Gargari BP, Ebrahimi S. Strong association between serum vitamin D and vaspin levels, AIP, VAI and liver enzymes in NAFLD patients. Int J Vitam Nutr Res. 2020;90(1–2):59–66. First citation in articleLinkGoogle Scholar

  • 15 Liu S, Liu Y, Wan B, Zhang H, Wu S, Zhu Z, et al. Association between vitamin D status and non-alcoholic fatty liver disease: A population-based study. J Nutr Sci Vitaminol (Tokyo). 2019;65:303–8. First citation in articleCrossref MedlineGoogle Scholar

  • 16 Cipponeri E, Vitturi N, Mariano V, Boscari F, Galasso S, Crepaldi C, et al. Vitamin D status and non-alcoholic fatty liver disease in patients with type 1 diabetes. J Endocrinol Invest. 2019;42(9):1099–107. First citation in articleCrossref MedlineGoogle Scholar

  • 17 Leitão J, Carvalhana S, Silva AP, Velasco F, Medeiros I, Alves AC, et al. No evidence for lower levels of serum vitamin D in the presence of hepatic steatosis: A study on the Portuguese general population. Int J Med Sci. 2018;15(14):1778–86. First citation in articleCrossref MedlineGoogle Scholar

  • 18 Alberti KG, Zimmet P, Shaw J. Metabolic syndrome: A new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006;23(5):469–80. First citation in articleCrossref MedlineGoogle Scholar

  • 19 Cleeman JI. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–97. First citation in articleCrossref MedlineGoogle Scholar

  • 20 Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009;2(5–6):231–7. First citation in articleCrossref MedlineGoogle Scholar

  • 21 Nishida C, Ko GT, Kumanyika S. Body fat distribution and non communicable diseases in populations: Overview of the 2008 WHO Expert Consultation on Waist Circumference and Waist-Hip Ratio. Eur J Clin Nutr. 2010;64(1):2–5. First citation in articleCrossref MedlineGoogle Scholar

  • 22 World Health Organization. Physical status: The use and interpretation of anthropometry. Report of a WHO Expert Committee. Technical Report Series No. 854. Geneva: WHO; 1995:1–452. First citation in articleGoogle Scholar

  • 23 Roth H, Schmidt-Gayk H, Weber H, Niederau C. Accuracy and clinical implications of seven 25-hydroxyvitamin D methods compared with liquid chromatography–tandem mass spectrometry as a reference. Ann Clin Biochem. 2008;45(Pt 2):153–9. First citation in articleCrossref MedlineGoogle Scholar

  • 24 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostatic model assessment: Insulin resistance and beta-cell function from fasting glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9. First citation in articleCrossref MedlineGoogle Scholar

  • 25 Wehr E, Gruber HJ, Giuliani A, Möller R, Pieber TR, Obermayer-Pietsch B. The lipid accumulation product is associated with impaired glucose tolerance in PCOS women. J Clin Endocrinol Metab. 2011;96(6):986–90. First citation in articleCrossrefGoogle Scholar

  • 26 Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–54. First citation in articleCrossref MedlineGoogle Scholar

  • 27 Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: Natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43(8):617–49. First citation in articleCrossref MedlineGoogle Scholar

  • 28 Kleiner D, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21. First citation in articleCrossref MedlineGoogle Scholar

  • 29 Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81. First citation in articleCrossref MedlineGoogle Scholar

  • 30 Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin d deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. First citation in articleCrossref MedlineGoogle Scholar

  • 31 Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16(7):713–6. First citation in articleCrossref MedlineGoogle Scholar

  • 32 Pérez-Hernández N, Aptilon-Duque G, Nostroza-Hernández MC, Vargas-Alarcón G, Rodríguez-Pérez JM, Blachman-Braun R. Vitamin D and its effects on cardiovascular diseases: A comprehensive review. Korean J Intern Med. 2016;31(6):1018–29. First citation in articleCrossref MedlineGoogle Scholar

  • 33 Manson JE, Brannon PM, Rosen CJ, Taylor CL. Vitamin D deficiency – is there really a pandemic? N Engl J Med. 2016;375(19):1817–20. First citation in articleCrossref MedlineGoogle Scholar

  • 34 Padovani RM, Amaya-Farfán J, Colugnati FAB, Colugnati B, Domene SMA. Dietary reference intakes: Aplicabilidade das tabelas em estudos nutricionais. Rev Nutr. 2006;19(6):741–60. First citation in articleCrossrefGoogle Scholar

  • 35 Orwoll E, Nielson CM, Marshall LM, Lambert L, Holton KF, Hoffman AR, et al. Vitamin D deficiency in older men. J Clin Endocrinol Metab. 2009;94:1214–22. First citation in articleCrossref MedlineGoogle Scholar

  • 36 Silva BCC, Camrgoosil BM, Fujii JB, Dias EP, Soares MMS. Prevalência de deficiência e insuficiência de vitamina D e sua correlação com PTH, marcadores de remodelação óssea e densidade mineral óssea, em pacientes ambulatoriais. Arq Bras Endrocrinol Metab. 2008;52(3):482–8. First citation in articleCrossref MedlineGoogle Scholar

  • 37 Eloi M, Horvath DV, Szejnfeld VL, Ortega JC, Rocha DA, Szejnfeld J, et al. Vitamin D deficiency and seasonal variation over the years in São Paulo, Brazil. Osteoporos Int. 2016;27(12):3449–56. First citation in articleCrossref MedlineGoogle Scholar

  • 38 Peracchi OA, Terreri MT, Munekata RV, Len CA, Sarni RO, Lazaretti-Castro M, et al. Low serum concentrations of 25-hydroxyvitamin D in children and adolescents with systemic lupus erythematosus. Braz J Med Biol Res. 2014;47(8):721–6. First citation in articleCrossref MedlineGoogle Scholar

  • 39 Arantes HP, Kulak CA, Fernandes CE, Zerbini C, Bandeira F, Barbosa IC, et al. Correlation between 25-hydroxyvitamin D levels and latitude in Brazilian postmenopausal women: From the Arzoxifene Generations Trial. Osteoporos Int. 2013;24(10):2707–12. First citation in articleCrossref MedlineGoogle Scholar

  • 40 Maeda SS, Borba VZC, Camargo MBR, Silva DW, Borges JLC, Bandeira F, et al. Recomendações da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) para o diagnóstico e tratamento da hipovitaminose D. Arq Bras Endocrinol Metab. 2014;58(5):411–33. First citation in articleCrossref MedlineGoogle Scholar

  • 41 Kücükazman M, Ata N, Dal K, Yeniova AO, Kefeli A, Basyigit S, et al. The association of vitamin D deficiency with nonalcoholic fatty liver disease. Clinics. 2014;69:542–6. First citation in articleCrossref MedlineGoogle Scholar

  • 42 Dasarathy J, Periyalwar P, Allampati S, Bhinder V, Hawkins C, Brandt P, et al. Hypovitaminosis D is associated with increased whole body fat mass and greater severity of nonalcoholic fatty liver disease. Liver Int. 2014;34(6):118–27. First citation in articleCrossref MedlineGoogle Scholar

  • 43 Hao Y, Ma XJ, Luo YQ, Ni J, Dou JX, Hu YQ, et al. Serum vitamin D is associated with non-alcoholic fatty liver disease in Chinese males with normal weight and liver enzymes. Acta Pharmacol Sin. 2014;35(9):1150–6. First citation in articleCrossref MedlineGoogle Scholar

  • 44 Geier A, Eichinger M, Stirnimann G, Semela D, Tay F, Seifert B, et al. Treatment of non-alcoholic steatohepatitis patients with vitamin D: A double-blinded, randomized, placebo-controlled pilot study. Scand J Gastroenterol. 2018;53(9):1114–20. First citation in articleCrossref MedlineGoogle Scholar

  • 45 Choi DH, Jung CH, Mok JO, Kim CH, Kang SK, Kim BY. Nonalcoholic fatty liver disease and abdominal fat accumulation according to vitamin D status in patients with type 2 diabetes. J Obes Metab Syndr. 2018;27(1):53–60. First citation in articleCrossref MedlineGoogle Scholar

  • 46 Ngo DT, Sverdlov AL, McNeil JJ, Horowitz JD. Does vitamin D modulate asymmetric dimethylarginine and c-reactive protein concentrations? Am J Med. 2010;123(4):335–41. First citation in articleCrossref MedlineGoogle Scholar

  • 47 Zhai H, Wang NJ, Han B, Li Q, Chen Y, Zhu CF, et al. Low vitamin D levels and non-alcoholic fatty liver disease, evidence for their independent association in men in East China: A cross-sectional study (Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China)). Br J Nutr. 2016;115(8):1352–9. First citation in articleCrossref MedlineGoogle Scholar

  • 48 Sezer OB, Bulus D, Hizli S, Liu J, Xiu L, Qin J, et al. Low 25-hydroxyvitamin D level is not an independent risk factor for hepatosteatosis in obese children. J Pediatr Endocrinol Metab. 2016;29(7):783–8. First citation in articleCrossref MedlineGoogle Scholar

  • 49 Anty R, Hastier A, Canivet CM, Patouraux S, Schneck AS, Ferrari-Panaia P, et al. Severe vitamin D deficiency is not associated with liver damage in morbidly obese patients. Obes Surg. 2016;26(9):2138–43. First citation in articleCrossref MedlineGoogle Scholar

  • 50 Saberi B, Dadabhai AS, Mullin GE. Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data. World J Hepatol. 2018;10(1):142–54. First citation in articleCrossref MedlineGoogle Scholar

  • 51 Jaruvongvanich V, Ahuja W, Sanguankeo A, Wijarnpreecha K, Upala S. Vitamin D and histologic severity of nonalcoholic fatty liver disease: A systematic review and meta-analysis. Dig Liver Dis. 2017;49(6):618–22. First citation in articleCrossref MedlineGoogle Scholar

  • 52 Musso G, Gambino R, Cassader M. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Prog Lipid Res. 2009;48(1):1–26. First citation in articleCrossref MedlineGoogle Scholar

  • 53 Ahmadieh H, Azar ST, Lakkis N, Arabi A. Hypovitaminosis D in patients with type 2 diabetes mellitus: A relation to disease control and complications. ISRN Endocrinology. 2013;2013:641098. First citation in articleCrossref MedlineGoogle Scholar

  • 54 Al-Daghri M, Al-Attas OS, Alokail MS, Alkharfy KM, Al-Othman A, Draz HM, et al. Hypovitaminosis D associations with adverse metabolic parameters are accentuated in patients with Type 2 diabetes mellitus: A body mass index-independent role of adiponectin? J Endocrinol Invest. 2013;36(1):1–6. First citation in articleMedlineGoogle Scholar

  • 55 Eliades M, Spyrou E. Vitamin D: A new player in non-alcoholic fatty liver disease? World J Gastroenterol. 2015;21(6):1718–27. First citation in articleCrossref MedlineGoogle Scholar

  • 56 Seida JC, Mitri J, Colmers IN, Majumdar SR, Davidson MB, Edwards AL, et al. Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: A systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(10):3551–60. First citation in articleCrossref MedlineGoogle Scholar

  • 57 Mathieu C, Gysemans C, Giulietti A, Deeg D, Seidell J, Lips P. Vitamin D and diabetes. Diabetologia. 2005;48(7):1247–57. First citation in articleCrossref MedlineGoogle Scholar

  • 58 Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980;209(4458):823–5. First citation in articleCrossref MedlineGoogle Scholar

  • 59 Ortlepp JR, Metrikat J, Albrecht M, Von Korff A, Hanrath P, Hoffmann R. The vitamin D receptor gene variant and physical activity predicts fasting glucose levels in healthy young men. Diabet Med. 2003;20(6):451–4. First citation in articleCrossref MedlineGoogle Scholar

  • 60 Chung GE, Kim D, Kwak MS, Yang JI, Yim JY, Lim SH, et al. The serum vitamin D level is inversely correlated with nonalcoholic fatty liver disease. Clin Mol Hepatol. 2016;22(1):146–51. First citation in articleCrossref MedlineGoogle Scholar

  • 61 Souza WN, Norde MM, Oki E, Rogero MM, Marchioni DM, Fisberg RM, et al. Association between 25-hydroxyvitamin D and inflammatory biomarker levels in a cross-sectional population-based study, São Paulo, Brazil. Nutr Res. 2016;36(1):1–8. First citation in articleCrossref MedlineGoogle Scholar