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

BMC Medicine

Jun 2016

DOI: 10.1186/s12916-016-0638-y

Citations:165

Influential Citations:4

Interventional (Human) Studies

Enhanced Details

Methods

Monocentric randomized, double-blind, placebo-controlled trial at Sapienza University, Rome; 65 adults with type 2 diabetes and ultrasound- and MRI-confirmed NAFLD; age 25–70 years; mean age 58.7 ± 9.9; 70% male; mean diabetes duration 6.5 ± 5.5 years.

Intervention

Cholecalciferol 2000 IU/day, taken orally (8 drops daily), for 24 weeks.

Results

25(OH)D increased significantly in the active group (to about 89.8 nmol/L at 12 weeks; 96% reached ≥50 nmol/L and 71% ≥75 nmol/L by 24 weeks) but hepatic fat fraction and other hepatic injury biomarkers (CK18-M30, P3NP), liver enzymes, FLI, metabolic and cardiovascular parameters did not differ from placebo after 24 weeks. An ABI difference emerged (β = -0.10; P = 0.03) but was not significant after adjustment for multiple comparisons. Conclusion: 24 weeks of high-dose cholecalciferol does not improve hepatic steatosis or metabolic/cardiovascular outcomes in T2D patients with NAFLD; longer or alternative interventions may be needed.

Limitations

Small, single-center trial; short duration (24 weeks); no liver biopsy; not all participants were vitamin D deficient at baseline; dropout/loss to follow-up.

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. show less