Association of Serum 25‑hydroxyvitamin D Levels and Liver Enzymes in a Nationally Representative Sample of Iranian Adolescents: The Childhood and Adolescence Surveillance and Prevention of Adult Noncommunicable Disease Study

Maryam Bahreynian, Mostafa Qorbani, Mohammad Esmaeil Motlagh, Ramin Heshmat, Majid Khademian, Roya Kelishadi

Abstract


Background: Hypovitaminosis D is highly prevalent and has several adverse health effects. This study aims to assess the relationship of serum concentrations of 25‑hydroxyvitamin D (25[OH] D) and liver enzymes in adolescents.

Methods: This population‑based cross‑sectional survey was conducted among a nationally representative multistage sample of 1095 adolescents (52% boys), aged 10–18 years, living in different provinces of Iran. Serum 25(OH)D concentration <30 ng/ mL was considered as hypovitaminosis D, and liver enzymes (alanine aminotransaminase [ALT]
and aspartate aminotransaminase [AST]) of >40 U/L was considered as high level. To determine the association between serum 25(OH)D categories and elevated levels of liver enzymes, multiple regression models and linear regression analysis were applied, after adjustment for potential confounders. Odds ratios (95% confdence interval) of serum 25(OH)D and elevated liver enzymes were assessed by logistic regression analysis.

Results: Higher rates of Vitamin D defciency were documented among individuals with increased levels of liver enzymes. Compared to boys, median of 25(OH)D was lower in girls with elevated levels of liver function tests (12.75 vs. 25.60 ng/mL for ALT and 13 vs. 14.10 ng/mL for AST), with marginally signifcant gender differences regarding AST.

Conclusions: We found a relatively high frequency of hypovitaminosis D among adolescents with abnormal liver function. Further prospective studies are needed to examine these associations from early life.

Keywords: Adolescent, liver function tests, Vitamin D


Full Text:

PDF

References


Holick MF. Vitamin D: Extraskeletal health. Rheum Dis Clin

North Am 2012;38:141‑60.

Bener A, Al‑Ali M, Hoffmann GF. High prevalence of Vitamin D

deficiency in young children in a highly sunny Humid country:

A global health problem. Minerva Pediatr 2009;61:15‑22.

Shin YH, Shin HJ, Lee YJ. Vitamin D status and childhood

health. Korean J Pediatr 2013;56:417‑23.

Bruyère O, Malaise O, Neuprez A, Collette J, Reginster JY.

Prevalence of Vitamin D inadequacy in European postmenopausal

women. Curr Med Res Opin 2007;23:1939‑44.

Rovner AJ, O’Brien KO. Hypovitaminosis D among healthy

children in the United States: A review of the current evidence.

Arch Pediatr Adolesc Med 2008;162:513‑9.

Flores M, Macias N, Lozada A, Sánchez LM, Díaz E,

Barquera S, et al. Serum 25‑hydroxyvitamin D levels among

mexican children ages 2 y to 12 y: A national survey. Nutrition

;29:802‑4.

Muhairi SJ, Mehairi AE, Khouri AA, Naqbi MM, Maskari FA,

Al Kaabi J, et al. Vitamin D deficiency among healthy

adolescents in Al Ain, United Arab Emirates. BMC Public

Health 2013;13:33.

Turer CB, Lin H, Flores G. Prevalence of Vitamin D

deficiency among overweight and obese US children. Pediatrics

;131:e152‑61.

Neyestani TR, Hajifaraji M, Omidvar N, Eshraghian MR,

Shariatzadeh N, Kalayi A, et al. High prevalence of Vitamin D

deficiency in school‑age children in Tehran, 2008: A red alert.

Public Health Nutr 2012;15:324‑30.

Ardestani PM, Salek M, Keshteli AH, Nejadnik H, Amini M,

Hosseini SM, et al. Vitamin D status of 6‑ to 7‑year‑old children

living in Isfahan, Iran. Endokrynol Pol 2010;61:377‑82.

Kaykhaei MA, Hashemi M, Narouie B, Shikhzadeh A, Rashidi H,

Moulaei N, et al. High prevalence of Vitamin D deficiency in

Zahedan, Southeast Iran. Ann Nutr Metab 2011;58:37‑41.

Boot AM, Krenning EP, de Muinck Keizer‑Schrama SM. The

relation between 25‑hydroxyvitamin D with peak bone mineral

density and body composition in healthy young adults. J Pediatr

Endocrinol Metab 2011;24:355‑60.

Jenab M, Bueno‑de‑Mesquita HB, Ferrari P, van Duijnhoven FJ,

Norat T, Pischon T, et al. Association between pre‑diagnostic

circulating Vitamin D concentration and risk of colorectal cancer

in European populations: A nested case‑control study. BMJ

;340:b5500.

Holick MF. Vitamin D: Importance in the prevention of cancers,

type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr

;79:362‑71.

Temmerman JC. Vitamin D and cardiovascular disease. J Am

Coll Nutr 2011;30:167‑70.

Harel Z, Flanagan P, Forcier M, Harel D. Low Vitamin D status

among obese adolescents: Prevalence and response to treatment.

J Adolesc Health 2011;48:448‑52.

Ganji V, Zhang X, Shaikh N, Tangpricha V. Serum

‑hydroxyvitamin D concentrations are associated with

prevalence of metabolic syndrome and various cardiometabolic

risk factors in US children and adolescents based on

assay‑adjusted serum 25‑hydroxyvitamin D data from NHANES

‑2006. Am J Clin Nutr 2011;94:225‑33.

Shin YH, Kim KE, Lee C, Shin HJ, Kang MS, Lee HR, et al.

High prevalence of Vitamin D insufficiency or deficiency in

young adolescents in Korea. Eur J Pediatr 2012;171:1475‑80.

Madden K, Feldman HA, Smith EM, Gordon CM, Keisling SM,

Sullivan RM, et al. Vitamin D deficiency in critically ill children.

Pediatrics 2012;130:421‑8.

Sharief S, Jariwala S, Kumar J, Muntner P, Melamed ML.

Vitamin D levels and food and environmental allergies in the

United States: Results from the National Health and Nutrition

Examination Survey 2005‑2006. J Allergy Clin Immunol

;127:1195‑202.

Brehm JM, Acosta‑Perez E, Klei L, Roeder K, Barmada M,

Boutaoui N, et al. Vitamin D insufficiency and severe asthma

exacerbations in Puerto Rican children. Am J Respir Crit Care

Med 2012;186:140‑6.

Camurdan OM, Döğer E, Bideci A, Celik N, Cinaz P. Vitamin D

status in children with hashimoto thyroiditis. J Pediatr Endocrinol

Metab 2012;25:467‑70.

Arteh J, Narra S, Nair S. Prevalence of Vitamin D deficiency in

chronic liver disease. Dig Dis Sci 2010;55:2624‑8.

Malham M, Jørgensen SP, Ott P, Agnholt J, Vilstrup H,

Borre M, et al. Vitamin D deficiency in cirrhosis relates to

liver dysfunction rather than aetiology. World J Gastroenterol

;17:922‑5.

Putz‑Bankuti C, Pilz S, Stojakovic T, Scharnagl H, Pieber TR,

Trauner M, et al. Association of 25‑hydroxyvitamin D levels

with liver dysfunction and mortality in chronic liver disease.

Liver Int 2012;32:845‑51.

Skaaby T, Husemoen LL, Borglykke A, Jørgensen T,

Thuesen BH, Pisinger C, et al. Vitamin D status, liver enzymes,

and incident liver disease and mortality: A general population

study. Endocrine 2014;47:213‑20.

Stokes CS, Krawczyk M, Reichel C, Lammert F, Grünhage F.

Vitamin D deficiency is associated with mortality in patients

with advanced liver cirrhosis. Eur J Clin Invest 2014;44:176‑83.

Mohammadi B, Najafi M, Farahmand F, Motamed F,

Ghajarzadeh M, Mohammadi J, et al. Prevalence of vitamin D

deficiency and rickets in children with cholestasis in Iran. Acta

Med Iran 2012;50:482‑5.

Kelishadi R, Heshmat R, Motlagh ME, Majdzadeh R,

Keramatian K, Qorbani M, et al. Methodology and early findings

of the third survey of CASPIAN study: A national school‑based

surveillance of students’ high risk behaviors. Int J Prev Med

;3:394‑401.

Kelishadi R, Ardalan G, Motlagh ME, Shariatinejad K,

Heshmat R, Poursafa P, et al. National report on the

association of serum Vitamin D with cardiometabolic risk

factors in the pediatric population of the Middle East and

North Africa (MENA): The CASPIAN‑III study. Nutrition

;30:33‑8.

Kelishadi R, Abtahi SH, Qorbani M, Heshmat R,

Esmaeil Motlagh M, Taslimi M, et al. First national report

on aminotransaminases’ percentiles in children of the Middle

East and North Africa (MENA): The CASPIAN‑III study.

Hepat Mon 2012;12:e7711.

Zúñiga S, Firrincieli D, Housset C, Chignard N. Vitamin D

and the Vitamin D receptor in liver pathophysiology. Clin Res

Hepatol Gastroenterol 2011;35:295‑302.

Pappa HM, Bern E, Kamin D, Grand RJ. Vitamin D status in

gastrointestinal and liver disease. Curr Opin Gastroenterol

;24:176‑83.

Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A,

Luderer HF, et al. Vitamin D and human health: Lessons from

Vitamin D receptor null mice. Endocr Rev 2008;29:726‑76.

Bikle DD. Vitamin D insufficiency/deficiency in gastrointestinal

disorders. J Bone Miner Res 2007;22 Suppl 2:V50‑4.

Hovsepian S, Amini M, Aminorroaya A, Amini P, Iraj B.

Prevalence of Vitamin D deficiency among adult population of

Isfahan city, Iran. J Health Popul Nutr 2011;29:149‑55.

Moussavi M, Heidarpour R, Aminorroaya A, Pournaghshband Z,

Amini M. Prevalence of Vitamin D deficiency in Isfahani high

school students in 2004. Horm Res 2005;64:144‑8.

Sahu M, Bhatia V, Aggarwal A, Rawat V, Saxena P, Pandey A,

et al. Vitamin D deficiency in rural girls and pregnant

women despite abundant sunshine in Northern India. Clin

Endocrinol (Oxf) 2009;70:680‑4.

Di Bonito P, Sanguigno E, Di Fraia T, Forziato C, Boccia G,

Saitta F, et al. Association of elevated serum alanine

aminotransferase with metabolic factors in obese children:

Sex‑related analysis. Metabolism 2009;58:368‑72.

Kelishadi R, Cook SR, Adibi A, Faghihimani Z, Ghatrehsamani S,

Beihaghi A, et al. Association of the components of the

metabolic syndrome with non‑alcoholic fatty liver disease among

normal‑weight, overweight and obese children and adolescents.

Diabetol Metab Syndr 2009;1:29.

Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE.

Influence of gender, race, and ethnicity on suspected fatty liver

in obese adolescents. Pediatrics 2005;115:e561‑5.

Jamali R, Pourshams A, Amini S, Deyhim MR, Rezvan H,

Malekzadeh R, et al. The upper normal limit of serum alanine

aminotransferase in Golestan Province, Northeast Iran. Arch Iran

Med 2008;11:602‑7.

Poustchi H, George J, Esmaili S, Esna‑Ashari F, Ardalan G,

Sepanlou SG, et al. Gender differences in healthy ranges for

serum alanine aminotransferase levels in adolescence. PLoS One

;6:e21178.

Kariv R, Leshno M, Beth‑Or A, Strul H, Blendis L, Kokia E,

et al. Re‑evaluation of serum alanine aminotransferase upper

normal limit and its modulating factors in a large‑scale

population study. Liver Int 2006;26:445‑50.

Mohamadnejad M, Pourshams A, Malekzadeh R,

Mohamadkhani A, Rajabiani A, Asgari AA, et al. Healthy ranges

of serum alanine aminotransferase levels in Iranian blood donors.

World J Gastroenterol 2003;9:2322‑4.

Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF.

Decreased bioavailability of Vitamin D in obesity. Am J Clin

Nutr 2000;72:690‑3.

Targher G, Bertolini L, Scala L, Cigolini M, Zenari L, Falezza G,

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;17:517‑24.

Rochling FA. Evaluation of abnormal liver tests. Clin

Cornerstone 2001;3:1‑2.

Kangin M, Turhanoglu M, Gulsun S, Cakabay B. Seroprevalence

of hepatitis B and C among children in endemic areas of Turkey.

Hepat Mon 2010;10:36‑41.