Additional treatment of vitamin D for improvement of insulin resistance in non-alcoholic fatty liver disease patients: a systematic review and meta-analysis

Sindhughosa, Dwijo Anargha; Wibawa, I Dewa Nyoman; Mariadi, I Ketut; Somayana, Gde

doi:10.1038/s41598-022-11950-x

Cited by 23 publications

(15 citation statements)

References 27 publications

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“…Consistent with a previous meta-analysis, which reported that VD supplementation decreases serum ALT ( 42 ), the present study demonstrated that 25(OH)D 3 was negatively correlated with circulating ALT in patients. To minimize the effect of BMI, we considered BMI as a covariate for multiple logistic regression analysis, aiming to reduce its confounding effect.…”

Section: Discussionsupporting

confidence: 92%

“…However, a previous cross-sectional study that randomly recruited 789 adult individuals from Portugal has reported that there is no correlation between serum VD and hepatic steatosis ( 41 ). A previous meta-analysis involving eight randomized controlled trials (RCTs) verified that VD supplementation has a protective effect on insulin resistance (IR) and decreases serum alanine aminotransferase (ALT) in NAFLD patients ( 42 ). A prospective cohort study in Korea reported that maintaining an adequate 25(OH)D 3 level (≥30 ng/mL) is associated with decreased incidence of NAFLD ( 43 ).…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Lian

Zhang

et al. 2023

Front. Endocrinol.

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IntroductionThe study aimed to explore the association of serum 25(OH)D3 and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and to determine whether the effect of vitamin D (VD) is mediated by activation of the peroxisome proliferator-activated receptor α (PPARα) pathway.MethodsThe study contained a case-control study, in vivo and in vitro experiments. A case-control study was conducted to compare serum parameters between NAFLD patients and controls and to evaluate the association of 25(OH)D3 and NAFLD. In vivo study, male Wistar rats were randomly divided into control and model groups, fed a standard chow diet and a high-fat diet (HFD), respectively, for 7 weeks to generate an NAFLD model. Then, the rats were treated with VD and a PPARα antagonist (MK886) for 7 weeks. Tissue and serum were collected and assessed by biochemical assays, morphological analysis, histological analysis, and western blot analysis. In vitro, HepG2 cells were incubated with oleic acid (OA) to induce steatosis, which was evaluated by staining. HepG2 cells were pretreated with MK886 followed by calcitriol treatment, and differences in lipid metabolism-related proteins were detected by western blot.ResultsNAFLD patients were characterized by impaired liver function, dyslipidemia, and insulin resistance. Serum 25(OH)D3 was negatively associated with alanine aminotransferase (ALT) in NAFLD. VD deficiency was a risk factor for patients with no advanced fibrosis. Adequate VD status (25(OH)D3 >20 ng/mL) had a protective effect in patients after adjustment for confounding variables. NAFLD rats showed hyperlipidemia with severe hepatic steatosis, systematic inflammation, and lower serum 25(OH)D3. VD treatment ameliorated hepatic steatosis both in NAFLD rats and OA-induced HepG2 cells. Further, MK886 inhibited the anti-steatosis effect of VD.ConclusionThe study revealed that an adequate VD level may act as a protective factor in NAFLD and that VD may alleviate hepatic steatosis via the PPARα signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Lian

Zhang

et al. 2023

Front. Endocrinol.

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“…Dasarathy et al found that a low vitamin D level can independently predict the severity of NAFLD [ 31 ]. Some clinical trials also demonstrated that vitamin D supplementation has therapeutic effects on patients with NAFLD, including a reduction in liver enzymes, weight, and BMI and an improvement in lipid profile, glycemic control, insulin resistance, and hepatic steatosis and fibrosis [ 32 , 33 , 34 , 35 ]. However, a few studies reported insignificant relationships between vitamin D status and histological severity of NAFLD [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Higher Serum 25-Hydroxyvitamin D Is Associated with Lower All-Cause and Cardiovascular Mortality among US Adults with Nonalcoholic Fatty Liver Disease

et al. 2022

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Aims: We aimed to assess the association between serum 25-hydroxyvitamin D (25(OH)D) levels with all-cause and cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). Methods: We performed a retrospective cohort study based on the US National Health and Nutrition Examination Survey 2001–2016 on adults aged ≥ 20 years. NAFLD was determined as a US Fatty Liver Index score ≥30 in the absence of other liver conditions. Weighted Cox proportional hazards regression models were applied to explore the relationship between serum 25(OH)D levels and mortality. Results: 898 all-cause deaths and 305 cardiovascular deaths were recorded over a median follow-up of 8.7 years. Compared with those in the severe deficiency group (below 25.0 nmol/L), the fully adjusted HRs and 95% CIs of NAFLD patients with sufficient serum 25(OH)D concentrations (≥75.0 nmol/L) were 0.36 (0.22, 0.60) for all-cause mortality and 0.14 (0.07, 0.29) for cardiovascular mortality. Each one-unit increase in the natural log-transformed serum 25(OH)D concentration was related to a 41% lower risk for all-cause deaths (HR = 0.59, 95% CI: 0.46, 0.77) and a 65% lower risk for cardiovascular deaths (HR = 0.35, 95% CI: 0.22, 0.58). Conclusions: Among NAFLD patients, increased serum 25(OH)D levels were independently associated with reduced risk for all-cause and cardiovascular deaths.

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“…Given such evidence, randomized controlled trials (RCTs) have found that additional vitamin D treatment may improve insulin resistance, marked by a decrease in Homeostasis Model Assessment Insulin Resistance (HOMA-IR) in patients with NAFLD [ 80 , 81 , 82 ]. These studies were included in a recent meta-analysis that analysed insulin resistance and serum ALT levels [ 83 ]. In a double-blinded, randomised, placebo-controlled trial, vitamin D3 treatment (50,000 IU for 12 weeks) improved HOMA-IR, serum ALT, AST, PCR, and adiponectin but without effect on body weight or serum lipids [ 84 ].…”

Section: Vitamin D In the Chronic Liver Diseasesmentioning

confidence: 99%

Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease

Ravaioli

Pivetti

Marco

et al. 2022

IJMS

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Vitamin D is a crucial nutrient with many pleiotropic effects on health and various chronic diseases. The purpose of this review is to provide a detailed report on the pathophysiological mechanisms underlying vitamin D deficiency in patients with chronic liver disease, addressing the different liver etiologies and the condition of advanced chronic liver disease (cirrhosis) with related complications. To date, patients with liver disease, regardless of underlying etiology, have been shown to have reduced levels of vitamin D. There is also evidence of the predictive role of vitamin D values in complications and progression of advanced disease. However, specific indications of vitamin D supplementation are not conclusive concerning what is already recommended in the general population. Future studies should make an effort to unify and validate the role of vitamin D supplementation in chronic liver disease.

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Additional treatment of vitamin D for improvement of insulin resistance in non-alcoholic fatty liver disease patients: a systematic review and meta-analysis

Cited by 23 publications

References 27 publications

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Higher Serum 25-Hydroxyvitamin D Is Associated with Lower All-Cause and Cardiovascular Mortality among US Adults with Nonalcoholic Fatty Liver Disease

Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease

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