title: No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic disorder worldwide, reaching prevalence up to 90 % in obese patients with type 2 diabetes (T2D), and representing an independent risk factor for cardiovascular mortality. Furthermore, the coexistence of T2D and NAFLD leads to higher incidence of diabetes' complications and additive detrimental liver outcomes. The existence of a close association between NAFLD and hypovitaminosis D, along with the anti-inflammatory and insulin-sensitizing properties of vitamin D, have been largely described, but vitamin D effects on hepatic fat content have never been tested in a randomized controlled trial. We assessed the efficacy and safety of 24-week oral high-dose vitamin D supplementation in T2D patients with NAFLD.
  
  
  METHODS
  This randomized, double-blind, placebo-controlled trial was carried out at the Diabetes Centre of Sapienza University, Rome, Italy, to assess oral treatment with cholecalciferol (2000 IU/day) or placebo in T2D patients with NAFLD. The primary endpoint was reduction of hepatic fat fraction (HFF) measured by magnetic resonance; as hepatic outcomes, we also investigated changes in serum transaminases, CK18-M30, N-terminal Procollagen III Propeptide (P3NP) levels, and Fatty Liver Index (FLI). Secondary endpoints were improvement in metabolic (fasting glycaemia, HbA1c, lipids, HOMA-IR, HOMA-β, ADIPO-IR, body fat distribution) and cardiovascular (ankle-brachial index, intima-media thickness, flow-mediated dilatation) parameters from baseline to end of treatment.
  
  
  RESULTS
  Sixty-five patients were randomized, 26 (cholecalciferol) and 29 (placebo) subjects completed the study. 25(OH) vitamin D significantly increased in the active treated group (48.15 ± 23.7 to 89.80 ± 23.6 nmol/L, P < 0.001); however, no group differences were found in HFF, transaminases, CK18-M30, P3NP levels or FLI after 24 weeks. Vitamin D neither changed the metabolic profile nor the cardiovascular parameters.
  
  
  CONCLUSIONS
  Oral high-dose vitamin D supplementation over 24 weeks did not improve hepatic steatosis or metabolic/cardiovascular parameters in T2D patients with NAFLD. Studies with a longer intervention period are warranted for exploring the effect of long time exposure to vitamin D.
  
  
  BACKGROUND
  This trial was approved on July 2011 by the Ethics Committee of Policlinico Umberto I, Sapienza University of Rome, Italy, and registered at www.clinicaltrialsregister.eu number 2011-003010-17.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Barchetta
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Ben
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelico
authors.affiliation: Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Di Martino
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fraioli
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Torre
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Saulle
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Perri
authors.affiliation: Microscopic and Ultrastructural Anatomy (CIR), University Campus Bio-Medico, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Morini
authors.affiliation: Endocrinology and Diabetes, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiberti
authors.affiliation: Endocrinology and Diabetes, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bertoccini
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Flavia Agata
authors.initials: FA
authors.lastname: Cimini
authors.affiliation: Endocrinology and Diabetes, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Panimolle
authors.affiliation: Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Catalano
authors.affiliation: Endocrinology and Diabetes, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.|Department of Medical Sciences, Endocrinology and Diabetes, University of Cagliari, Cagliari, Italy.
authors.forename: Marco Giorgio
authors.initials: MG
authors.lastname: Baroni
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy. gisella.cavallo@uniroma1.it.
authors.forename: Maria Gisella
authors.initials: MG
authors.lastname: Cavallo
mesh_terms: D000284:Administration, Oral; D002762:Cholecalciferol / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D012307:Risk Factors
chemical_list: D002762:Cholecalciferol
keywords: Fatty liver; NAFLD; Type 2 diabetes; Vitamin D supplementation