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

BackgroundNon-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.MethodsThis 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.ResultsSixty-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.ConclusionsOral 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.Trial registrationThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0638-y) contains supplementary material, which is available to authorized users.

Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta‐Analysis

“…A total of 31 trials, involving 2751 participants, were eligible for inclusion in the review . Of these, 29 trials (2641 participants) had data suitable for inclusion in the trial‐level meta‐analyses; IPD were obtained from 24 trials (2051 participants).…”

Relationship between adipose tissue dysfunction, vitamin D deficiency and the pathogenesis of non-alcoholic fatty liver disease

“…In our study, the participants underwent a 24-wk course of high-dose oral vitamin D supplementation and no effect was shown on either the hepatic fat content or on markers of hepatic injury, i.e ., serum transaminases, CK-18 and PIIINP[158]. …”

Procollagen‐III peptide identifies adipose tissue‐associated inflammation in type 2 diabetes with or without nonalcoholic liver disease

“…For this study, we analysed data from 62 consecutive T2DM subjects referring to our diabetes outpatient clinics at Sapienza University of Rome, Italy, and participating to the Eudract 2011‐003010‐17 trial (http://www.clinicaltrialsregister.eu). In brief, this is a monocentric, randomized, double‐blind, placebo‐controlled trial investigating the efficacy and safety of 24‐week oral high‐dose vitamin D supplementation in T2DM patients with NAFLD evaluated by magnetic resonance imaging (MRI). All study participants underwent clinical work‐up and fasting blood sampling for metabolic and inflammatory profiling.…”

“…Data were calculated from AT area at L1‐L2, L2‐L3, L3‐L4, and L4‐L5 levels; free‐form regions of interest and manual threshold were used to select fat tissue within VAT and SAT slides. More details on MRI acquisition have been provided elsewhere …”