Vitamin D supplementation for the treatment of non-alcoholic fatty liver disease: A randomized double blind placebo controlled trial

Dabbaghmanesh, Mohammad Hossein; Danafar, Farideh; Eshraghian, Ahad; Omrani, Gholamhossein Ranjbar

doi:10.1016/j.dsx.2018.03.006

Cited by 34 publications

(17 citation statements)

References 27 publications

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“…Whereas in animals, a large number of drugs (and classes) demonstrated significant efficacy across several outcome measures. This did not appear to be consistent with the results from human trials, for example we observed that vitamin D was associated with a significant reduction in NAS, however several trials have not found any benefit from its use in humans ( Barchetta et al, 2016 ; Dabbaghmanesh et al, 2018 ). In addition, the magnitude of effect observed in rodents was not consistent with human data.…”

Section: Discussioncontrasting

confidence: 82%

Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

Hunter

Hahn

Duret

et al. 2020

eLife

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The classical drug development pipeline necessitates studies using animal models of human disease to gauge future efficacy in humans, however there is a low conversion rate from success in animals to humans. Non-alcoholic fatty liver disease (NAFLD) is a complex chronic disease without any established therapies and a major field of animal research. We performed a meta-analysis with meta-regression of 603 interventional rodent studies (10,364 animals) in NAFLD to assess which variables influenced treatment response. Weight loss and alleviation of insulin resistance were consistently associated with improvement in NAFLD. Multiple drug classes that do not affect weight in humans caused weight loss in animals. Other study design variables, such as age of animals and dietary composition, influenced the magnitude of treatment effect. Publication bias may have increased effect estimates by 37-79%. These findings help to explain the challenge of reproducibility and translation within the field of metabolism.

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Section: Discussioncontrasting

confidence: 82%

Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

Hunter

Hahn

Duret

et al. 2020

eLife

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“…Vitamin D has recently gained more attention as researchers have noticed the high correlation of vitamin D deficiency and NAFLD [53,54,55,56,57,58]. Although vitamin D deficiency is common with NAFLD and NASH, data for the effectiveness of vitamin D supplementation has been unclear [53,56,58]. Nobili and Reif suggested that vitamin D may induce anti-fibrotic effects by suppressing hepatic stellate cell proliferation [54].…”

Section: Role Of Other Vitamins Minerals and Emerging Strategiesmentioning

confidence: 99%

“…Sharifi et al noted that vitamin D therapy reduced inflammatory markers in NAFLD such as C-reactive protein and malondialdehyde [59]. Despite this, multiple studies have failed to find a beneficial response to vitamin D supplementation in liver function or histology in patients with NAFLD [53,56,58]. Furthermore, vitamin D therapy is clinically limited due to its effect on calcium homeostasis and potential for hypercalcemia, a risk factor for NAFLD [53,60].…”

Section: Role Of Other Vitamins Minerals and Emerging Strategiesmentioning

confidence: 99%

The Role of Vitamin E in the Treatment of NAFLD

Perumpail

John

et al. 2018

Diseases

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There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

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“…This evidence is supported by data on the immune modulatory and insulin‐sensitizing properties of this hormone 42 . However, clinical trials failed to demonstrate positive effects of VD supplementation on hepatic fat content/fibro‐inflammation in NAFLD 43‐45 . Accordingly, although differential liver VDR expression was shown in advanced liver diseases, such as chronic C hepatitis, 18 NASH, 18 NAFLD 12,20 and hepatocarcinoma, 46 no correlation was found between hepatic VDR expression and circulating VD concentration.…”

Section: Discussionmentioning

confidence: 92%

Relationship between hepatic and systemic angiopoietin‐like 3, hepatic Vitamin D receptor expression and NAFLD in obesity

Barchetta

Cimini

Chiappetta

et al. 2020

Liver International

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Background & Aims Non‐alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and an independent risk factor for cardiovascular mortality. Angiopoietin‐like proteins (ANGPTLs) are targets for vitamin D receptor (VDR)‐mediated gene transcription and this axis may promote NAFLD. ANGPTL3 is a hepatokine which inhibits lipoprotein lipase and its experimentally induced inactivation reduces hepatosteatosis. Little is known on ANGPTL3 in human NAFLD and no data exist on its relationship with hepatic VDR/VD‐related genes. The aim of this research was to investigate hepatic ANGPTLs and VDR/VD‐related gene expression in human obesity in relation to NAFLD. Methods We conducted a cross‐sectional investigation on forty obese subjects with/without NAFLD. We evaluated hepatic ANGPTL3, ANGPTL4, ANGPTL8, LPL, VDR, CYP27A1 and CYP2R1 mRNA expression in liver biopsies by RT‐PCR; VDR expression was further investigated by immunohistochemistry; circulating ANGPTL3 was measured by Milliplex assay. Results Compared to non‐NAFLD, NAFLD individuals had significantly higher hepatic VDR, ANGPTL3 and LPL expression. ANGPTL3 correlated with steatosis grade, LPL, VDR, CYP27A1 and CYP2R1 expression. Plasma ANGPTL3 concentrations were positively associated with clinical/histological markers of NAFLD/NASH and with hepatic ANGPTL3 expression. Greater hepatic VDR expression was the main determinant of hepatic ANGPTL3 after adjusting for multiple confounders. Conclusions Hepatic ANGPTL3 expression correlates with greater VDR expression, presence and severity of NAFLD and translates in increased circulating ANGPTL3, likely as a result of its modulation by up‐regulated hepatic VDR in NAFLD. This study provides novel insights to potential mechanisms underlying ANGPTLs–mediated ectopic fat accumulation and NAFLD development in obesity.

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Vitamin D supplementation for the treatment of non-alcoholic fatty liver disease: A randomized double blind placebo controlled trial

Cited by 34 publications

References 27 publications

Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

The Role of Vitamin E in the Treatment of NAFLD

Relationship between hepatic and systemic angiopoietin‐like 3, hepatic Vitamin D receptor expression and NAFLD in obesity

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