Effect of vitamin D and B12 levels on hepatosteatosis in overweight and obese children

Main Article Content

Civan H. Ayyıldız
Çakır E. Papatya
F. Palabıyık
M. Cömert


Background. The childhood non-alcoholic hepatosteatosis leads to significant morbidity and mortality in adulthood. In recent years, vitamin D and B12 deficiency has been controversially associated with non-alcoholic fatty liver disease. Therefore, we aimed to evaluate the relationship of vitamin levels and insulin resistance (IR) with non-alcoholic hepatosteatosis in obese and overweight children. Material and methods. A total of 167 overweight and obese children aged 5–18 years were enrolled in this prospective study. The anthropometric measurements including body weight, height, body mass index (BMI) (weight/height2, kg/m2) were recorded. Children and adolescents with ≥ 95th percentile of BMI for their age and gender were diagnosed with obesity, and BMI between the 85th and 94th percentiles was classified as overweight. Children and adolescents classified into two groups according to the presence of hepatosteatosis: normal liver and hepatosteatosis group. Additionally, hepatosteatosis grading was performed by ultrasonographic evaluation. Participants’ demographic characteristics, physical examination, imaging and laboratory findings including serum levels of vitamin B12, 25(OH)D analysis and insulin resistance index were documented and compared between groups. Results. One hundred and sixty-seven patients included in this study were: 103 (61.7 %) males, 64 (38.3 %) females, and the mean age of total participants was 11.48 ± 2.99 years. According to BMI-Z score, 26.3 % of individuals were defined as overweight and 73.7 % were obese. Hepatosteatosis was determined in 70.7 % (n = 118) of our cases and it was significantly higher in male patients (79.6 %) than in females (p = 0.001). Mean IR was statistically higher in non-alcoholic fatty liver disease group (11.15 ± 13.39) than in normal liver group (6.95 ± 6.20) (p = 0.029). Moreover, there were statistically significant differences found in IR levels according to severity of hepatosteatosis (p = 0.013). In addition, vitamin D and B12 deficiencies were not significantly associated with hepatosteatosis or severity of hepatosteatosis (p > 0.05). Also, no statistically significant differences were found in mean levels of vitamin D, vitamin B12 and IR between obese and overweight children. Conclusions. Our findings support the published data that vitamin D and B12 deficiencies do not contribute to the pathology of hepatosteatosis. In addition, insulin resistance has been demonstrated to be a risk factor for non-alcoholic fatty liver and hepatosteatosis severity.

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How to Cite
Ayyıldız, C. H., Çakır E. Papatya, F. Palabıyık, and M. Cömert. “Effect of Vitamin D and B12 Levels on Hepatosteatosis in Overweight and Obese Children”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 16, no. 3, Apr. 2020, pp. 209-14, doi:10.22141/2224-0721.16.3.2020.205268.
Original Researches


Centers for Disease Control and Prevention. Childhood obesity causes & consequences. 2016. Available from: https://www.cdc.gov/obesity/childhood/causes.html.

Bugianesi E, Bizzarri C, Rosso C, et al. Low Birthweight Increases the Likelihood of Severe Steatosis in Pediatric Non-Alcoholic Fatty Liver Disease. Am J Gastroenterol. 2017;112(8):1277‐1286. doi:10.1038/ajg.2017.140.

Dowla SA, Goss AM, Ashraf AP. Nonalcoholic Fatty Liver Disease in Children with Obesity. In: Debasis Bagchi, editor. Global Perspectives on Childhood Obesity. USA: Elsevier Science Publishing Co Inc; 2019. 255-268 pp.

Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-2273. doi:10.1001/jama.2015.5370.

Mahammad SA, Nawaz SS, Marx KP, Siddiqu IA. Relationship between serum vitamin B12, hyperhomocysteinemia in nonalcoholic fatty liver disease. International Journal of Bioassays. 2013;2(11):1508-1510. doi:10.21746/ijbio.2013.11.0018.

Baz-Hecht M, Goldfine AB. The impact of vitamin D deficiency on diabetes and cardiovascular risk. Curr Opin Endocrinol Diabetes Obes. 2010;17(2):113-119. doi:10.1097/MED.0b013e3283372859.

McGill AT, Stewart JM, Lithander FE, Strik CM, Poppitt SD. Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J. 2008;7:4. doi:10.1186/1475-2891-7-4.

Saberi B, Dadabhai AS, Nanavati J, Wang L, Shinohara RT, 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):142‐154. doi:10.4254/wjh.v10.i1.142.

Wang X, Li W, Zhang Y, Yang Y, Qin G. Association between vitamin D and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: results from a meta-analysis. Int J Clin Exp Med. 2015;8(10):17221-17234.

Koplay M, Gulcan E, Ozkan F. Association between serum vitamin B12 levels and the degree of steatosis in patients with nonalcoholic fatty liver disease. J Investig Med. 2011;59(7):1137‐1140. doi:10.2310/JIM.0b013e31822a29f5.

Nobili V, Giorgio V, Liccardo D, et al. Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease. Eur J Endocrinol. 2014;170(4):547‐553. doi:10.1530/EJE-13-0609.

Sezer OB, Buluş D, Hızlı Ş, Andıran N, Yılmaz D, Ramadan SU. Low 25-hydroxyvitamin D level is not an independent risk factor for hepatosteatosis in obese children. J Pediatr Endocrinol Metab. 2016;29(7):783‐788. doi:10.1515/jpem-2015-0426.

Neyzi O, Bundak R, Gökçay G, et al. Reference Values for Weight, Height, Head Circumference, and Body Mass Index in Turkish Children. J Clin Res Pediatr Endocrinol. 2015;7(4):280‐293. doi:10.4274/jcrpe.2183.

Shannon A, Alkhouri N, Carter-Kent C, et al. Ultrasonographic quantitative estimation of hepatic steatosis in children With NAFLD. J Pediatr Gastroenterol Nutr. 2011;53(2):190‐195. doi:10.1097/MPG.0b013e31821b4b61.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412‐419. doi:10.1007/BF00280883.

Welsh JA, Karpen S, Vos MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988-1994 to 2007-2010. J Pediatr. 2013;162(3):496‐500.e1. doi:10.1016/j.jpeds.2012.08.043.

Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004;158(6):531‐537. doi:10.1001/archpedi.158.6.531.

Targher G, Bertolini L, Scala L, et al. Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2007;17(7):517‐524. doi:10.1016/j.numecd.2006.04.002.

Wang X, Li W, Zhang Y, Yang Y, Qin G. Association between vitamin D and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: results from a meta-analysis. Int J Clin Exp Med. 2015;8(10):17221‐17234.

Dursun F, Gerenli N, Dur SMS, Kirmizibekmez H. The relationship between vitamin D level and hepatosteatosis in obese children. North Clin Istanb. 2018;6(1):28‐32. doi:10.14744/nci.2018.26097.

Katz K, Brar PC, Parekh N, Liu YH, Weitzman M. Suspected nonalcoholic Fatty liver disease is not associated with vitamin d status in adolescents after adjustment for obesity. J Obes. 2010;2010:496829. doi:10.1155/2010/496829.

Bolukbas FF, İgnak S, Demirel OU, et al. Relationship between serum Vitamin B12 levels and hepatic fibrosis detected by transient elastography (Fibroscan) in non-alcoholic fatty liver disease. Anatolian Clinic the Journal of Medical Sciences. 2017;22(3):141-148. doi:10.21673/anadoluklin.297152

Polyzos SA, Kountouras J, Patsiaoura K, et al. Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease. Int J Food Sci Nutr. 2012;63(6):659‐666. doi:10.3109/09637486.2011.649249.

Hirsch S, Poniachick J, Avendaño M, et al. Serum folate and homocysteine levels in obese females with non-alcoholic fatty liver. Nutrition. 2005;21(2):137‐141. doi:10.1016/j.nut.2004.03.022.

Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients. 2013;5(5):1544‐1560. doi:10.3390/nu5051544.

Fu JF, Shi HB, Liu LR, et al. Non-alcoholic fatty liver disease: An early mediator predicting metabolic syndrome in obese children?. World J Gastroenterol. 2011;17(6):735‐742. doi:10.3748/wjg.v17.i6.735.

Tominaga K, Fujimoto E, Suzuki K, Hayashi M, Ichikawa M, Inaba Y. Prevalence of non-alcoholic fatty liver disease in children and relationship to metabolic syndrome, insulin resistance, and waist circumference. Environ Health Prev Med. 2009;14(2):142‐149. doi:10.1007/s12199-008-0074-5.

Fraser A, Longnecker MP, Lawlor DA. Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999-2004. Gastroenterology. 2007;133(6):1814‐1820. doi:10.1053/j.gastro.2007.08.077.