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Luo WJ, Dong XW, Ye H, Zhao QS, Zhang QB, Guo WY, Liu HW, Xu F. Vitamin D 1,25-Dihydroxyvitamin D 3 reduces lipid accumulation in hepatocytes by inhibiting M1 macrophage polarization. World J Gastrointest Oncol 2024; 16:4685-4699. [PMID: 39678811 PMCID: PMC11577380 DOI: 10.4251/wjgo.v16.i12.4685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 09/09/2024] [Accepted: 10/08/2024] [Indexed: 11/12/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD), which is a significant liver condition associated with metabolic syndrome, is the leading cause of liver diseases globally and its prevalence is on the rise in most nations. The protective impact of vitamin D on NAFLD and its specific mechanism remains unclear. AIM To examine the role of vitamin D in NAFLD and how vitamin D affects the polarization of hepatic macrophages in NAFLD through the vitamin D receptor (VDR)-peroxisome proliferator activated receptor (PPAR)γ pathway. METHODS Wild-type C57BL/6 mice were provided with a high-fat diet to trigger NAFLD model and administered 1,25-dihydroxy-vitamin D [1,25(OH)2D3] supplementation. 1,25(OH)2D3 was given to RAW264.7 macrophages that had been treated with lipid, and a co-culture with AML12 hepatocytes was set up. Lipid accumulation, lipid metabolism enzymes, M1/M2 phenotype markers, proinflammatory cytokines and VDR-PPARγ pathway were determined. RESULTS Supplementation with 1,25(OH)2D3 relieved hepatic steatosis and decreased the proinflammatory M1 polarization of hepatic macrophages in NAFLD. Administration of 1,25(OH)2D3 suppressed the proinflammatory M1 polarization of macrophages induced by fatty acids, thereby directly relieving lipid accumulation and metabolism in hepatocytes. The VDR-PPARγ pathway had a notable impact on reversing lipid-induced proinflammatory M1 polarization of macrophages regulated by the administration of 1,25(OH)2D3. CONCLUSION Supplementation with 1,25(OH)2D3 improved hepatic steatosis and lipid metabolism in NAFLD, linked to its capacity to reverse the proinflammatory M1 polarization of hepatic macrophages, partially by regulating the VDR-PPARγ pathway. The involvement of 1,25(OH)2D3 in inhibiting fatty-acid-induced proinflammatory M1 polarization of macrophages played a direct role in relieving lipid accumulation and metabolism in hepatocytes.
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Affiliation(s)
- Wen-Jing Luo
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Xian-Wen Dong
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Hua Ye
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Qiao-Su Zhao
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Qiu-Bo Zhang
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Wen-Ying Guo
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Hui-Wei Liu
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
| | - Feng Xu
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
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Marginean CM, Pirscoveanu D, Cazacu SM, Popescu MS, Marginean IC, Iacob GA, Popescu M. Non-Alcoholic Fatty Liver Disease, Awareness of a Diagnostic Challenge—A Clinician’s Perspective. GASTROENTEROLOGY INSIGHTS 2024; 15:1028-1053. [DOI: 10.3390/gastroent15040071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease globally. NAFLD is a complex pathology, considered to be the hepatic expression of metabolic syndrome (MetS). It is supposed to become the main indication for liver transplantation in the coming years and is estimated to affect 57.5–74.0% of obese people, 22.5% of children and 52.8% of obese children, with 50% of individuals with type 2 diabetes being diagnosed with NAFLD. Recent research has proved that an increase in adipose tissue insulin resistance index is an important marker of liver injury in patients with NAFLD. Despite being the main underlying cause of incidental liver damage and a growing worldwide health problem, NAFLD is mostly under-appreciated. Currently, NAFLD is considered a multifactorial disease, with various factors contributing to its pathogenesis, associated with insulin resistance and diabetes mellitus, but also with cardiovascular, kidney and endocrine disorders (polycystic ovary syndrome, hypothyroidism, growth hormone deficiency). Hepatitis B and hepatitis C, sleep apnea, inflammatory bowel diseases, cystic fibrosis, viral infections, autoimmune liver diseases and malnutrition are some other conditions in which NAFLD can be found. The aim of this review is to emphasize that, from the clinician’s perspective, NAFLD is an actual and valuable key diagnosis factor for multiple conditions; thus, efforts need to be made in order to increase recognition of the disease and its consequences. Although there is no global consensus, physicians should consider screening people who are at risk of NAFLD. A large dissemination of current concepts on NAFLD and an extensive collaboration between physicians, such as gastroenterologists, internists, cardiologists, diabetologists, nutritionists and endocrinologists, is equally needed to ensure we have the knowledge and resources to address this public health challenge.
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Affiliation(s)
- Cristina Maria Marginean
- Internal Medicine Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Denisa Pirscoveanu
- Neurology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Sergiu Marian Cazacu
- Research Center of Gastroenterology and Hepatology, Gastroenterology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Marian Sorin Popescu
- Internal Medicine Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | | | - George Alexandru Iacob
- Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mihaela Popescu
- Endocrinology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Amorim R, Soares P, Chavarria D, Benfeito S, Cagide F, Teixeira J, Oliveira PJ, Borges F. Decreasing the burden of non-alcoholic fatty liver disease: From therapeutic targets to drug discovery opportunities. Eur J Med Chem 2024; 277:116723. [PMID: 39163775 DOI: 10.1016/j.ejmech.2024.116723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/24/2024] [Accepted: 07/25/2024] [Indexed: 08/22/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) presents a pervasive global pandemic, affecting approximately 25 % of the world's population. This grave health issue not only demands urgent attention but also stands as a significant economic concern on a global scale. The genesis of NAFLD can be primarily attributed to unhealthy dietary habits and a sedentary lifestyle, albeit certain genetic factors have also been recorded to contribute to its occurrence. NAFLD is characterized by fat accumulation in more than 5 % of hepatocytes according to histological analysis, or >5.6 % of lipid volume fraction in total liver weight in patients. The pathophysiology of NAFLD/non-alcoholic steatohepatitis (NASH) is multifactorial and the mechanisms underlying the progression to advanced forms remain unclear, thereby representing a challenge to disease therapy. Despite the substantial efforts from the scientific community and the large number of pre-clinical and clinical trials performed so far, only one drug was approved by the Food and Drug Administration (FDA) to treat NAFLD/NASH specifically. This review provides an overview of available information concerning emerging molecular targets and drug candidates tested in clinical studies for the treatment of NAFLD/NASH. Improving our understanding of NAFLD pathophysiology and pharmacotherapy is crucial not only to explore new molecular targets, but also to potentiate drug discovery programs to develop new therapeutic strategies. This knowledge endeavours scientific efforts to reduce the time for achieving a specific and effective drug for NAFLD or NASH management and improve patients' quality of life.
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Affiliation(s)
- Ricardo Amorim
- CNC-UC, Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB, Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal
| | - Pedro Soares
- CIQUP-IMS/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal
| | - Daniel Chavarria
- CIQUP-IMS/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal
| | - Sofia Benfeito
- CIQUP-IMS/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal
| | - Fernando Cagide
- CIQUP-IMS/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal
| | - José Teixeira
- CNC-UC, Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB, Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal
| | - Paulo J Oliveira
- CNC-UC, Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB, Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal.
| | - Fernanda Borges
- CIQUP-IMS/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal.
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Służały P, Paśko P, Galanty A. Natural Products as Hepatoprotective Agents-A Comprehensive Review of Clinical Trials. PLANTS (BASEL, SWITZERLAND) 2024; 13:1985. [PMID: 39065511 PMCID: PMC11280762 DOI: 10.3390/plants13141985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/18/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024]
Abstract
The hepatoprotective effects of natural products have been a significant focus in recent decades due to the growing demand for the help in the treatment of hepatic impairments. This review specifically delves into the findings of clinical trials involving 13 selected natural products, namely plants and their derived compounds (e.g., artichoke, berberine, and turmeric), algae (e.g., spirulina), probiotics, and other products like phospholipids and vitamin D. A literature search was performed in the Scopus database, PubMed, and Google Scholar, covering all articles found up to June 2024. Artichoke, berberine, chlorella, chicory, green tea, probiotics, phospholipids, schisandra, silymarin, spirulina, and vitamin D caused a decrease in liver enzymes, while for cinnamon and turmeric such an effect was either not observed or not convincing. The presented results indicate that some natural products might satisfactorily improve hepatic outcomes in NAFLD, NASH, and other liver disorders; however, further studies and metanalyses are needed to clearly demonstrate their effectiveness.
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Affiliation(s)
- Piotr Służały
- Department of Pharmacognosy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland;
| | - Paweł Paśko
- Department of Food Chemistry and Nutrition, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland;
| | - Agnieszka Galanty
- Department of Pharmacognosy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland;
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Wang H, Ma Q, Chen Y, Luo L, Ye J, Zhong B. Optimized strategy among diet, exercise, and pharmacological interventions for nonalcoholic fatty liver disease: A network meta-analysis of randomized controlled trials. Obes Rev 2024; 25:e13727. [PMID: 38509775 DOI: 10.1111/obr.13727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 01/23/2024] [Accepted: 01/30/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND Emerging treatment methods, including exercise, diet, and drugs, for nonalcoholic fatty liver disease have been proposed. However, the differences in their efficacy have not been determined. We aimed to compare the effects of these treatments excluding surgery via a systematic review and network meta-analysis of randomized controlled trials. DATA SOURCE The data sources included PubMed, Embase, Web of Science and Cochrane up to February 1st, 2023. The endpoints consisted of body mass index (BMI), serum markers of metabolism and liver injury markers, liver fat content, and stiffness. RESULTS A total of 174 studies with 10,183 patients were included in this meta-analysis. In terms of improving BMI, Pan-agonist of peroxisome proliferator-activated receptors (PPAR) is the best treatment with the highest SUCRA (surface under the cumulative ranking) of 84.8% (mean = -3.40, 95% CI -5.55, -1.24) by the comparative effectiveness ranking. GLP-1 (glucagon-like peptide-1) has the best effect in improving the liver fat content based on the MRI-PDFF, steatosis score (SUCRA 99.7%, mean = -2.19, 95% CI -2.90, -1.48) and ballooning score (SUCRA 61.2%, mean = -0.82, 95% CI -4.46, 2.83). CONCLUSIONS Pan-agonist of PPAR was the most efficacious regimen in lowering BMIs, whereas GLP-1R agonists achieved the highest efficacy of steatosis improvement in this network meta-analysis.
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Affiliation(s)
- Hao Wang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Qianqian Ma
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Infectious Diseases, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Youpeng Chen
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Ling Luo
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junzhao Ye
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bihui Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Ebrahimpour-Koujan S, Sohrabpour AA, Giovannucci E, Vatannejad A, Esmaillzadeh A. Effects of vitamin D supplementation on liver fibrogenic factors, vitamin D receptor and liver fibrogenic microRNAs in metabolic dysfunction-associated steatotic liver disease (MASLD) patients: an exploratory randomized clinical trial. Nutr J 2024; 23:24. [PMID: 38413933 PMCID: PMC10898146 DOI: 10.1186/s12937-024-00911-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 01/03/2024] [Indexed: 02/29/2024] Open
Abstract
BACKGROUND AND AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global metabolic problem which can lead to irreversible liver fibrosis. It has been shown that vitamin D and its receptors contribute to fibrogenic pathways in the liver. However, the effect of vitamin D supplementation on liver fibrosis related factors have not been examined. This double blinded placebo controlled clinical trial was designed to investigate the effects on vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients. METHODS Forty six MASLD patients after block matching for sex and BMI were randomly assigned to receive 4000 IU/d vitamin D or placebo for 12 weeks. Weight, height and waist circumference were measured. Serum fibrogenic microRNAs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, PTH, blood fasting glucose, serum fasting insulin, lipid profile, ALT and AST were determined at the baseline and at the end of the trial. Insulin resistance and insulin sensitivity were calculated using the HOMA-IR and QUICKI equation. RESULTS Supplementation with vitamin D for 12 weeks led to the significant increases in serum 25(OH) vitamin D, VDR and HDL-C compared to placebo (P < 0.001, P = 0.008 and P < 0.001). There were significant decreases in ALT, AST, FBS and LDL-C levels in the vitamin D group as compared to the placebo (P < 0.05). Laminin and hyaluronic acid concentrations were significantly decreased in the vitamin D group as compared to the placebo group, by -10.6 and - 28.7 ng/mL, respectively. Supplementation with vitamin D for 12 weeks resulted in a significant lower MiR-21 and MiR-122 gene expressions compared to the placebo group (P = 0.01 and P < 0.001, respectively). DISCUSSION As the first randomized controlled trial on the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients, we found a significant reduction in some liver fibrogenic factors, in liver transaminases and corresponding changes in some fibrosis-related MiRs and some metabolic factors. Further clinical trials with larger sample sizes and direct measures of liver fibrosis are needed to confirm these findings. TRIAL REGISTRATION NUMBER (available at: http://www.irct.ir , identifier: IRCT201405251485N13), Registration date: 14-03-2017.
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Affiliation(s)
- Soraiya Ebrahimpour-Koujan
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, PO Box 14155-6117, Tehran, Iran
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Ali Sohrabpour
- The Liver, Pancreatic, and Biliary Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Edward Giovannucci
- Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Akram Vatannejad
- Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Ahmad Esmaillzadeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, PO Box 14155-6117, Tehran, Iran.
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular -Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
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Emam RF, Soliman AF, Darweesh SK, AbdElmagid RA, Ibrahim OM, Mohamed DM. Steatosis regression assessed by cap after Vitamin 'D' supplementation in NAFLD patients with Vitamin 'D' deficiency. Eur J Gastroenterol Hepatol 2024; 36:101-106. [PMID: 37942743 DOI: 10.1097/meg.0000000000002653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and previous studies suggested a relationship between vitamin D deficiency and NAFLD. It is suggested that vitamin D supplementation may have significant beneficial effect on liver biochemistry and histology. OBJECTIVE This study aims to assess the degree of possible steatosis regression using controlled attenuation parameter (CAP) in NAFLD patients with vitamin D deficiency after vitamin D supplementation and evaluating its effect on lipid profile and transaminases. PATIENTS AND METHODS This study was conducted on 100 NAFLD patients with vitamin D deficiency. They received 10000 IU/week of vitamin D orally for 3 months. CAP was used to assess hepatic steatosis and fibrosis before/after intervention. Transaminases, lipid profile, and vitamin D levels were evaluated before/after treatment. RESULTS Serum AST, ALT, cholesterol, TG, LDL and HDL showed a significant reduction posttreatment in patients with both normal and elevated baseline levels ( P < 0.001). The posttreatment mean CAP showed a significant reduction (300.44 ± 37.56 vs. 265 ± 36.19 dB/ml) ( P < 0.001), and there was a significant improvement in the mean fibrosis values by LSM (5.32 ± 1.53 vs. 4.86 ± 1.28 KPa) ( P = 0.001). After supplementation, serum vitamin D level was raised significantly in the majority of patients ( P < 0.001); however, only 13% of them reached sufficient levels (>30 ng/ml), insufficient levels (20-29 ng/ml) was reached in 83% and 5% showed vitamin D deficiency (<20 ng/ml). CONCLUSION A significant improvement was detected in hepatic steatosis (by CAP); mean values of LSM, transaminases and lipid profile after three months of oral vitamin D supplementation.
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Affiliation(s)
- Rabab Fouad Emam
- Hepato-gastroenterology and Endemic Medicine Department, Faculty of Medicine, Cairo University
| | - Ahmed Fouad Soliman
- Hepato-gastroenterology and Endemic Medicine Department, Faculty of Medicine, Cairo University
| | - Samar Kamal Darweesh
- Hepato-gastroenterology and Endemic Medicine Department, Faculty of Medicine, Cairo University
| | | | - Ola Mohamed Ibrahim
- Clinical and Chemical pathology Department, Student's Hospital, Cairo University
| | - Dina Mahmoud Mohamed
- Hepato-gastroenterology and Endemic Medicine Department, Student's Hospital, Cairo University, Cairo, Egypt
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Stepan MD, Vintilescu ȘB, Streață I, Podeanu MA, Florescu DN. The Role of Vitamin D in Obese Children with Non-Alcoholic Fatty Liver Disease and Associated Metabolic Syndrome. Nutrients 2023; 15:2113. [PMID: 37432275 DOI: 10.3390/nu15092113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 04/20/2023] [Accepted: 04/26/2023] [Indexed: 07/12/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents a complex chronic condition, which in the absence of screening-monitoring markers and effective standardized treatment is one of the most important issues in pediatric pathology. In this study, we analyzed the role of vitamin D supplementation in obese children with/without NAFLD and the impact on the components of the associated metabolic syndrome (MS). The study included 22 children with simple obesity (SO) and 50 with NAFLD, aged between 6 and 14 years, who received regimen-based therapy or vitamin D supplementation in case of deficiency. Anthropometric and paraclinical data associated with MS were statistically compared before and after treatment. It was observed that there was a statistical association of NAFLD with MS components, which were present both in SO and in the 6-9 years group. Vitamin D deficiency was associated with the presence of obesity, NAFLD and MS components, and correction of the deficiency induced a tendency to normalize the associated parameters. In the case of a treatment strictly based on the regimen, we found decreases in vitamin D values and additional alteration of some parameters. Supplementation with vitamin D potentiates the effects of the specific regimen, and the effects seem to be dependent on the MS components.
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Affiliation(s)
- Mioara Desdemona Stepan
- Department of Infant Care-Pediatrics-Neonatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ștefănița Bianca Vintilescu
- Department of Infant Care-Pediatrics-Neonatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ioana Streață
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania
| | | | - Dan Nicolae Florescu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
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Mohamed AA, Halim AA, Mohamed S, Mahmoud SM, Bahgat Eldemiry EM, Mohamed RS, Shaheen MM, Naguib GG, Muharram NM, Khalil MG, Saed S, Ibrahim R, Salah Seif A, Kamal N, Nasraldin K, Abdelrahman AE, El Borolossy R. The effect of high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients. A randomized placebo controlled trial. Front Pharmacol 2023; 14:1149967. [PMID: 36998617 PMCID: PMC10043211 DOI: 10.3389/fphar.2023.1149967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 03/02/2023] [Indexed: 03/15/2023] Open
Abstract
Background and Aim: Non-alcoholic fatty liver (NAFLD) is one of the most common progressive metabolic disorders worldwide. There are increasing scientific interests nowadays for the association between vitamin D status and Non-alcoholic fatty liver. Earlier studies have revealed that vitamin D deficiency is highly prevalent in Non-alcoholic fatty liver patients that contributes to poor outcomes. Hence, the present study aimed to assess the efficacy and safety of oral cholecalciferol on Non-alcoholic fatty liver patients.Subjects and Methods: This study was conducted on 140 patients that were randomized either to group 1 that received the standard conventional therapy in addition to placebo or group 2 that received the standard conventional therapy in addition to cholecalciferol during the 4 months study period.Results: At the end of the study group 2 revealed significant decrease (p < 0.05) in the mean serum level of TG, LDL-C, TC, hsCRP as compared to their baseline results and group 1 results. Additionally, a significant improvement in the serum levels of ALT (p = 0.001) was seen in group 2 at the end of the study when compared to group 1. Whereas group 1 did not show any change in these parameters when compared to group 2 and their baseline results.Conclusion: Cholecalciferol was shown to have beneficial effects on serum ALT levels, hsCRP levels and lipid profile of NAFLD patients.Clinical Trial Registration:https://prsinfo.clinicaltrials.gov/prs-users-guide.html, identifier NCT05613192
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Affiliation(s)
- Amal Ahmed Mohamed
- Department of Biochemistry and Molecular Biology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Ahmed Abdel Halim
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Sahar Mohamed
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | | | | | - Rasha Sobh Mohamed
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Gina G. Naguib
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Nashwa M. Muharram
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Mona G. Khalil
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt
| | - Salma Saed
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Randa Ibrahim
- Clinical and Chemical Pathology Department, Nutrition Institute, Cairo, Egypt
| | - Ahmed Salah Seif
- Tropical Medicine Hepatology and Gastroenterology Department, Shebeen El-Kom Teaching Hospital, Menoufia, Egypt
| | - Noha Kamal
- Clinical Pathology Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research and Higher Education, Gulf Medical University (GMU), Cairo, Egypt
| | - Karima Nasraldin
- Faculty of Biotechnology, Modern Science and Arts University, Cairo, Egypt
| | - Ali Elsaid Abdelrahman
- Diagnostic and Intervention Radiology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Radwa El Borolossy
- Department of Clinical Pharmacy, Faculty of Pharmacy Ain Shams University, Cairo, Egypt
- *Correspondence: Radwa El Borolossy,
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Manoppo JIC, Pateda V, Prayogo C, Langi FLFG, Nurkolis F, Tsopmo A. Relationships of 25-hydroxyvitamin D levels and non-alcoholic fatty liver disease in obese children: A possible strategy to promote early screening of NAFLD. Front Nutr 2022; 9:1025396. [PMID: 36407527 PMCID: PMC9667029 DOI: 10.3389/fnut.2022.1025396] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 10/11/2022] [Indexed: 09/29/2023] Open
Affiliation(s)
- Jeanette Irene Christiene Manoppo
- Department of Pediatrics, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
- Department of Pediatrics, Prof. R. D. Kandou General Hospital, Manado, Indonesia
| | - Vivekenanda Pateda
- Department of Pediatrics, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
- Department of Pediatrics, Prof. R. D. Kandou General Hospital, Manado, Indonesia
| | - Cindy Prayogo
- Department of Pediatrics, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia
- Department of Pediatrics, Prof. R. D. Kandou General Hospital, Manado, Indonesia
| | | | - Fahrul Nurkolis
- Department of Biological Sciences, Faculty of Sciences and Technology, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga Yogyakarta), Yogyakarta, Indonesia
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Ravaioli F, Pivetti A, Di Marco L, Chrysanthi C, Frassanito G, Pambianco M, Sicuro C, Gualandi N, Guasconi T, Pecchini M, Colecchia A. Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease. Int J Mol Sci 2022; 23:9016. [PMID: 36012285 PMCID: PMC9409132 DOI: 10.3390/ijms23169016] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/09/2022] [Accepted: 08/11/2022] [Indexed: 12/12/2022] Open
Abstract
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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Affiliation(s)
- Federico Ravaioli
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
- Department of Medical and Surgical Sciences, University of Bologna, 40128 Bologna, Italy
| | - Alessandra Pivetti
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Lorenza Di Marco
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Christou Chrysanthi
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Gabriella Frassanito
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Martina Pambianco
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Chiara Sicuro
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Noemi Gualandi
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Tomas Guasconi
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Maddalena Pecchini
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
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12
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Rahimpour Z, Hoseini R, Behpour N. Alterations of liver enzymes and lipid profile in response to exhaustive eccentric exercise: vitamin D supplementation trial in overweight females with non-alcoholic fatty liver disease. BMC Gastroenterol 2022; 22:372. [PMID: 35927637 PMCID: PMC9354270 DOI: 10.1186/s12876-022-02457-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 07/31/2022] [Indexed: 11/10/2022] Open
Abstract
Background Eccentric exhaustive exercise (EEE) training has been known as a promising training modality to enhance performance and stimulate adaptation in healthy individuals or patients that might also cause abnormal liver enzymes and lipid profiles. Vitamin D (Vit D) supplementation is believed to improve the condition of Non-Alcoholic Fatty Liver Disease (NAFLD) patients. However, there is limited evidence on the effect of Vit D supplementation on the EEE-induced alterations. This study aimed to investigate the effect of short-term supplementation of Vit D on the liver enzymes and lipid profile alterations following EEE in overweight women with NAFLD. Methods In this clinical trial, 22 overweight women with NAFLD were randomly divided into experimental and control (n = 11 in each). The experimental group consumed 2000 IU of Vit D per day for six weeks; the control group consumed a lactose placebo daily with the same color, shape, and warmth percentage. Two treadmill EEE sessions were performed before and after the six-week Vit D supplementation. Blood was taken from the antecubital vein to measure the liver enzymes, lipid profile, and Vit D at four stages: Pre 1(before the first EEE session), Post 1(after the first EEE session), Pre 2 (before the second EEE session), and Post 2 (after the second EEE session). Results The results indicate that Vit D supplementation significantly reduced Bodyweight (BW; P = 0.047), Body Mass Index (BMI; P = 0.044), Body Fat Percentage (BFP; P = 0.001), and Waist Hip Ratio (WHR; P = 0.001) in the experimental group. Additionally, the results showed increased liver enzymes (ALT, AST, and GGT) and lipid profile (TC, TG, and LDL) following EEE. While the HDL levels decreased significantly after EEE. Compared with control, the results of the independent t-test showed significantly lower ALT (P = 0.001; P = 0.001), AST (P = 0.001; P = 0.001), and GGT (P = 0.001; P = 0.001); while significantly higher Vit D (P = 0.001, P = 0.001) in the experimental in both Pre 2 and Post 2; receptively. Also, significantly lower TC (P = 0.001; P = 0.001), TG (P = 0.048; P = 0.001), and LDL (P = 0.001; P = 0.001); while significantly higher HDL (P = 0.001, P = 0.001) were observed in the experimental group compared to the control in both Pre 2 and Post 2; receptively. Conclusions Vit D supplementation reduces the liver enzymes and improves lipid profile alterations following EEE in overweight women with NAFLD. Thus, Vit D supplementation can be considered a functional supplement to improve the EEE-induced alteration. Trial registration: The trial was in the Iranian Clinical Trial Registration Center under the (IRCT20201130049538N1) on 05/07/2021.
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Affiliation(s)
- Zahra Rahimpour
- Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran
| | - Rastegar Hoseini
- Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran.
| | - Nasser Behpour
- Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran
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13
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Sindhughosa DA, Wibawa IDN, Mariadi IK, Somayana G. Additional treatment of vitamin D for improvement of insulin resistance in non-alcoholic fatty liver disease patients: a systematic review and meta-analysis. Sci Rep 2022; 12:7716. [PMID: 35546181 PMCID: PMC9095833 DOI: 10.1038/s41598-022-11950-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 04/27/2022] [Indexed: 12/13/2022] Open
Abstract
Insulin resistance provides an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Several studies already evaluate vitamin D supplementation for NAFLD patients in relation to insulin resistance. The results obtained still carry conflicting results. This study aimed to evaluate the effect of additional treatment of vitamin D for the improvement of insulin resistance in NAFLD patients. Relevant literatures were obtained from PubMed, Google Scholar, COCHRANE, and Science Direct database. The obtained studies were analyzed using fixed effect model or random effect model. Seven eligible studies with a total of 735 participants were included. Vitamin D supplementation improves insulin resistance in NAFLD patients, marked by reduced Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), with pooled mean difference - 1.06 (p = 0.0006; 95% CI - 1.66 to - 0.45). Vitamin D supplementation increase the level of vitamin D serum with pooled mean difference of 17.45 (p = 0.0002; 95% CI 8.33 to 26.56). Vitamin D supplementation decrease ALT levels, with pooled mean difference of - 4.44 (p = 0.02; 95% CI - 8.24 to - 0.65). No effect was observed for AST levels. Vitamin D supplementation provides beneficial effects on the improvement of insulin resistance in NAFLD patients. This supplementation may reduce HOMA-IR in such patients. It may serve as a potential adjunctive treatment for NAFLD patients.
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Affiliation(s)
- Dwijo Anargha Sindhughosa
- Internal Medicine Residency Program, Udayana University/Sanglah General Hospital, Denpasar, Bali, Indonesia
| | - I Dewa Nyoman Wibawa
- Gastroenterohepatology Division, Department of Internal Medicine, Udayana University/Sanglah General Hospital, Denpasar, Bali, Indonesia.
| | - I Ketut Mariadi
- Gastroenterohepatology Division, Department of Internal Medicine, Udayana University/Sanglah General Hospital, Denpasar, Bali, Indonesia
| | - Gde Somayana
- Gastroenterohepatology Division, Department of Internal Medicine, Udayana University/Sanglah General Hospital, Denpasar, Bali, Indonesia
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14
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Rezaei S, Tabrizi R, Nowrouzi-Sohrabi P, Jalali M, Shabani-Borujeni M, Modaresi S, Gholamalizadeh M, Doaei S. The Effects of Vitamin D Supplementation on Anthropometric and Biochemical Indices in Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Front Pharmacol 2021; 12:732496. [PMID: 34803681 PMCID: PMC8595299 DOI: 10.3389/fphar.2021.732496] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 10/06/2021] [Indexed: 01/10/2023] Open
Abstract
Background: Vitamin D was reported to be associated with non-alcoholic fatty liver disease (NAFLD). This systematic review and meta-analysis aimed to investigate the effects of the vitamin D supplementation on anthropometric and biochemical indices in patient with NAFLD. Methods: PubMed, Web of science, Scopus, and Embase databases were explored to identify all randomized controlled trial (RCT) investigating the effects of vitamin D supplementation on anthropometric and biochemical indices in patients with NAFLD. A random-effects model was used to pool weighted mean difference (WMD) and corresponding 95% confidence intervals (CIs). The statistical heterogeneity among the studies was assessed using I2 statistic (high ≥ 50%, low < 50%) and Cochran's Q-test. Results: Sixteen RCTs were included in this meta-analysis. The results identified that high-density lipoprotein-cholesterol (HDL-C) level significantly increased following vitamin D supplementation (P = 0.008). Vitamin D reduced body weight (P = 0.007), body mass index (P = 0.002), waist circumstance (WC) (P = 0.02), serum alanine transaminase (ALT) (P = 0.01), fasting blood sugar (FBS) (P = 0.01), homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.004), and calcium (P = 0.01). No significant changes were found on body fat, triglyceride (TG), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, and adiponectin following vitamin D supplementation. Conclusion: Vitamin D had significant effects on anthropometric and biochemical indices including HDL-C, body weight, BMI, WC, serum ALT, serum FBS, HOMA-IR, and calcium. Vitamin D supplementation can be considered as an effective strategy in management of patients with NAFLD. Systematic Review Registration: [website], identifier [registration number].
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Affiliation(s)
- Shahla Rezaei
- Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Tabrizi
- Non-Communicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Peyman Nowrouzi-Sohrabi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Jalali
- Nutrition Research Center, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mojtaba Shabani-Borujeni
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shayan Modaresi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Gholamalizadeh
- Student Research Committee, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeid Doaei
- Research Center of Health and Enviroment, School of Health, Guilan University of Medical Sciences, Rasht, Iran
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15
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Bjelakovic M, Nikolova D, Bjelakovic G, Gluud C. Vitamin D supplementation for chronic liver diseases in adults. Cochrane Database Syst Rev 2021; 8:CD011564. [PMID: 34431511 PMCID: PMC8407054 DOI: 10.1002/14651858.cd011564.pub3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Vitamin D deficiency is often reported in people with chronic liver diseases. Improving vitamin D status could therefore be beneficial for people with chronic liver diseases. OBJECTIVES To assess the beneficial and harmful effects of vitamin D supplementation in adults with chronic liver diseases. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and enquired experts and pharmaceutical companies as to additional trials. All searches were up to November 2020. SELECTION CRITERIA Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of evidence. MAIN RESULTS We included 27 randomised clinical trials with 1979 adult participants. This review update added 12 trials with 945 participants. We assessed all trials as at high risk of bias. All trials had a parallel-group design. Eleven trials were conducted in high-income countries and 16 trials in middle-income countries. Ten trials included participants with chronic hepatitis C, five trials participants with liver cirrhosis, 11 trials participants with non-alcoholic fatty liver disease, and one trial liver transplant recipients. All of the included trials reported the baseline vitamin D status of participants. Participants in nine trials had baseline serum 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), whilst participants in the remaining 18 trials were vitamin D insufficient (less than 20 ng/mL). Twenty-four trials administered vitamin D orally, two trials intramuscularly, and one trial intramuscularly and orally. In all 27 trials, the mean duration of vitamin D supplementation was 6 months, and the mean follow-up of participants from randomisation was 7 months. Twenty trials (1592 participants; 44% women; mean age 48 years) tested vitamin D3 (cholecalciferol); three trials (156 participants; 28% women; mean age 54 years) tested vitamin D2; four trials (291 participants; 60% women; mean age 52 years) tested 1,25-dihydroxyvitamin D; and one trial (18 participants; 0% women; mean age 52 years) tested 25-hydroxyvitamin D. One trial did not report the form of vitamin D. Twelve trials used a placebo, whilst the other 15 trials used no intervention in the control group. Fourteen trials appeared to be free of vested interest. Eleven trials did not provide any information on clinical trial support or sponsorship. Two trials were funded by industry. We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on all-cause mortality (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.51 to 1.45; 27 trials; 1979 participants). The mean follow-up was 7 months (range 1 to 18 months). We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) (follow-up: 12 months); serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants); myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants); thyroiditis (RR 0.33, 95% CI 0.01 to 7.91; 1 trial; 68 participants); circular haemorrhoidal prolapse (RR 3.00, 95% CI 0.14 to 65.9; 1 trial; 20 participants); bronchopneumonia (RR 0.33, 95% CI 0.02 to 7.32; 1 trial 20 participants); and non-serious adverse events. The certainty of evidence for all outcomes is very low. We found no data on liver-related morbidity such as gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, ascites, or liver cancer. There were also no data on health-related quality of life. The evidence is also very uncertain regarding the effect of vitamin D versus placebo or no intervention on rapid, early, and sustained virological response in people with chronic hepatitis C. AUTHORS' CONCLUSIONS Given the high risk of bias and insufficient power of the included trials and the very low certainty of the available evidence, vitamin D supplementation versus placebo or no intervention may increase or reduce all-cause mortality, liver-related mortality, serious adverse events, or non-serious adverse events in adults with chronic liver diseases. There is a lack of data on liver-related morbidity and health-related quality of life. Further evidence on clinically important outcomes analysed in this review is needed.
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Affiliation(s)
- Milica Bjelakovic
- Clinic of Gastroenterology and Hepatology, Clinical Centre Nis, Nis, Serbia
| | - Dimitrinka Nikolova
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Goran Bjelakovic
- Clinic of Gastroenterology and Hepatology, Clinical Centre Nis, Nis, Serbia
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Internal Medicine, Medical Faculty, University of Nis, Nis, Serbia
| | - Christian Gluud
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Capital Region, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
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16
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Komolafe O, Buzzetti E, Linden A, Best LM, Madden AM, Roberts D, Chase TJ, Fritche D, Freeman SC, Cooper NJ, Sutton AJ, Milne EJ, Wright K, Pavlov CS, Davidson BR, Tsochatzis E, Gurusamy KS. Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 7:CD013157. [PMID: 34280304 PMCID: PMC8406904 DOI: 10.1002/14651858.cd013157.pub2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD. OBJECTIVES • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low-certainty evidence). The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates. Data were probably because of the very short follow-up period (2 months to 28 months). It takes follow-up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow-up. AUTHORS' CONCLUSIONS The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non-alcohol-related fatty liver disease. Accordingly, high-quality randomised comparative clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow-up of 8 years (to find meaningful differences in clinically important outcomes).
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Affiliation(s)
| | - Elena Buzzetti
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Lawrence Mj Best
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Angela M Madden
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Thomas Jg Chase
- Department of General Surgery, Homerton University Hospital NHS Foundation Trust, London, UK
| | | | - Suzanne C Freeman
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Nicola J Cooper
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Alex J Sutton
- Department of Health Sciences, University of Leicester, Leicester, UK
| | | | - Kathy Wright
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Chavdar S Pavlov
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Kurinchi Selvan Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
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17
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Guo XF, Wang C, Yang T, Li S, Li KL, Li D. Vitamin D and non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Food Funct 2021; 11:7389-7399. [PMID: 32966467 DOI: 10.1039/d0fo01095b] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The results of randomized controlled trials (RCTs) investigating supplemental vitamin D on aminotransferases and cardio-metabolic risk factors in subjects with non-alcoholic fatty liver disease (NAFLD) have been inconsistent. The present study aimed to quantitatively evaluate whether supplementation with vitamin D has beneficial effects in treatment of NAFLD. A systematical literature search was performed with Cochrane Library, PubMed, Scopus databases and Web of Science up to June 2020. The mean changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglyceride (TAG) were calculated as standard mean difference (SMD) using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were performed to identify the sources of heterogeneity. Ten trials with a total of 544 NAFLD subjects were included for data synthesis. The summary estimates indicated that supplemental vitamin D significantly reduced the levels of serum/plasma fasting glucose (-0.22; 95%CI: -0.39, -0.04), insulin (-0.68; 95%CI: -1.22, -0.14) and HOMA-IR (-1.32; 95%CI: -2.30, -0.34), and marginally reduced the ALT (-0.18; 95%CI: -0.39, 0.04) and TAG (-10.38; 95%CI: -21.09, 0.34) levels. However, the pooled effect did not support that supplemental vitamin D was beneficial for concentrations of AST, TC, HDL-C and LDL-C. The present study provides substantial evidence that supplemental vitamin D has favorable effects on glycemic control and insulin sensitivity in NAFLD patients. Vitamin D could be as an adjuvant pharmacotherapy of NAFLD.
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Affiliation(s)
- Xiao-Fei Guo
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
| | - Chong Wang
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
| | - Ting Yang
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
| | - Shan Li
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
| | - Ke-Lei Li
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
| | - Duo Li
- Institute of Nutrition & Health, Qingdao University, Qingdao, China. and Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China
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18
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Al-ghamdi HA, Al Fayez FF, Bima AI, Khawaji TM, Elsamanoudy AZ. Study of Cellular Senescence and Vitamin D Deficiency in Nonalcoholic Fatty Liver Disease and The Potential Protective Effect of Vitamin D Supplementation. J Clin Exp Hepatol 2021; 11:219-226. [PMID: 33746447 PMCID: PMC7952998 DOI: 10.1016/j.jceh.2020.07.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 07/11/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a pathological process characterized by excessive hepatic fatty deposition with possible involvement of vitamin D deficiency and cellular senescence. The aim of this study is to investigate the pathophysiologic role of vitamin D deficiency and cellular senescence in NAFLD development. Moreover, it aims to investigate the potential protective role of vitamin D supplementation. METHODS This is an experimental Case/Control study. Forty-five male albino rats were enrolled in this study. Animals were divided into four groups: negative and positive control groups (10 for each group), a model of NAFLD (11) and vitamin D-treated NAFLD groups (14). At the end of the experiment, all rats were subjected to the following investigation; biochemical estimation of serum 25 hydroxycholecalciferol, senescence marker protein-30 (SMP-30), lipid profile and calculation of homeostatic model of insulin resistance (HOMA-IR). RESULTS NAFLD group shows a significant increase in glucose, insulin levels, and HOMA- IR compared with both normal controls. This finding indicates the intimate association between insulin resistance and NAFLD pathogenesis. Moreover, it was found that NAFLD group shows a significant decrease in SMP-30 level compared with normal controls. While vitamin D-treated NAFLD group shows significant increased SMP-30 and decrease in HOMA-IR in comparison with nontreated NAFLD group. CONCLUSION Vitamin D deficiency and increased cellular senescence are key features of NAFLD. Vitamin D supplementation could play a protective role, which needs further investigation including clinical human study.
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Affiliation(s)
- Hasen A. Al-ghamdi
- Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Fayza F. Al Fayez
- Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abdulhadi I. Bima
- Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Taghreed M. Khawaji
- Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ayman Z. Elsamanoudy
- Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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19
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Dharmarajan TS. Vitamin D. GERIATRIC GASTROENTEROLOGY 2021:653-682. [DOI: 10.1007/978-3-030-30192-7_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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20
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Kaisar HH, Halima ASA. Association of vitamin D supplementation with serum leptin and metabolic parameters in Egyptian patients with non-alcoholic steatohepatitis: a prospective study. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-020-00049-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD, a common cause of liver disease, with increased chance of progression to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Circulating leptin is increased in patients with NASH. It is an independent positive predictor of the severity of hepatic steatosis. Vitamin D is a lipophilic molecule essential to maintain calcium and phosphate balance. Moreover, it has antifibrotic, antiproliferative, and anti-inflammatory effects on the liver. Vitamin D deficiency is a worldwide condition and very common in patients with NASH. Low serum vitamin D has been shown to predispose to intrahepatic lipid accumulation leading to NAFLD. The aim of this study was to investigate the association of vitamin D supplementation with serum leptin and metabolic parameters in Egyptian patients with non-alcoholic steatohepatitis
Results
Patients with NASH group had statistically significant higher values of diastolic blood pressure (94.3 ± 11.9 mmHg, p < 0.0001), glycated hemoglobin (8.0 ± 2.4%, p < 0.0001), fasting blood sugar (165.6 ± 62.0 mg/dL, p < 0.0001), fasting insulin level (24.2 ± 3.0 μU/ml, p < 0.0001), homeostatic model assessment of insulin resistance (HOMA-IR) (1.8 ± 0.7, p < 0.0001), alanine transferase (ALT) (78.2 ± 36.7 U/L, p < 0.0001), aspartate transferase (AST) (108.6 ± 85.6 U/L, p < 0.0001), NAFLD fibrosis score (− 0.78 ± 0.9, p < 0.0001), total cholesterol (233.0 ± 40.9 mg/dL, p = 0.0011), low-density lipoprotein (117.5 ± 41.6 mg/dL, p = 0.0084), and triglycerides (229.7 ± 62.1 mg/dL, p < 0.0001) than the control group. Moreover, they had lower serum vitamin D level (15.6 ± 6.6 ng/ml, p = 0.0004) and higher serum leptin level (35.9 ± 28.4 ng/ml, p < 0.0001) than the control group. Following vitamin D supplementation, there was a statistically significant reduction in HbA1c (6.8 ± 1.3%, p = 0.0055), fasting blood sugar (136.1 ± 32.7 mg/dL, p = 0.0094), fasting insulin level (22.9 ± 1.8 μU/ml, p = 0.0236), HOMA-IR (1.4 ± 0.4, p = 0.0026), ALT (55.3 ± 21.3 U/L, p = 0.0010), AST (73.1 ± 54.2 U/L, p = 0.0297), and triglycerides (203.6 ± 49.8 mg/dL, p = 0.0415) in patients with NASH. There was a statistically significant increase in serum vitamin D level (33.0 ± 7.6 ng/ml, p < 0.0001) and decrease in serum leptin level (23.5 ± 12.9 ng/ml, p = 0.0140) after treatment.
Conclusions
Vitamin D supplementation in patients with NASH in a dose of 4000 IU/day for 12 weeks improves severity of hepatic inflammation, decreases insulin resistance, improves glycemic control, corrects dyslipidemia, and protects against lipotoxicity by inhibition of serum leptin.
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21
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Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update. Nutrients 2020; 12:nu12113302. [PMID: 33126575 PMCID: PMC7693133 DOI: 10.3390/nu12113302] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 10/26/2020] [Accepted: 10/27/2020] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic liver disease worldwide; it ranges from simple steatosis to steatohepatitis (NASH) and, potentially, cirrhosis and hepatocarcinoma. NAFLD is also an independent risk factor for type 2 diabetes, cardiovascular diseases, and mortality. As it is largely associated with insulin resistance and related disorders, NAFLD has been recently re-named as Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD). At present, there are no approved pharmacological treatments for this condition. Vitamin D is a molecule with extensive anti-fibrotic, anti-inflammatory, and insulin-sensitizing properties, which have been proven also in hepatic cells and is involved in immune-metabolic pathways within the gut–adipose tissue–liver axis. Epidemiological data support a relationship hypovitaminosis D and the presence of NAFLD and steatohepatitis (NASH); however, results from vitamin D supplementation trials on liver outcomes are controversial. This narrative review provides an overview of the latest evidence on pathophysiological pathways connecting vitamin D to NAFLD, with emphasis on the effects of vitamin D treatment in MAFLD by a nonsystematic literature review of PubMed published clinical trials. This article conforms to the Scale for Assessment of Narrative Review Articles (SANRA) guidelines. Evidence so far available supports the hypothesis of potential benefits of vitamin D supplementation in selected populations of NAFLD patients, as those with shorter disease duration and mild to moderate liver damage.
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Kibler L, Heinze CR, Webster CRL. Serum vitamin D status in sick cats with and without cholestatic liver disease. J Feline Med Surg 2020; 22:944-952. [PMID: 31916866 PMCID: PMC10814402 DOI: 10.1177/1098612x19895081] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Vitamin D deficiency accompanies chronic cholestatic liver disease (CLD) in humans. The vitamin D status of cats with CLD is unknown. The objectives of this study were to describe serum vitamin D concentrations in cats with CLD and to determine if they correlated with indices of liver disease severity. METHODS Thirty-six cats with CLD, defined by increases in serum bilirubin and serum alanine aminotransferase, and 23 sick cats with non-hepatobiliary diseases were prospectively enrolled. Serum 25-hydroxyvitamin D (25[OH]D), parathyroid hormone (PTH) and ionized calcium were measured. Signalment, clinical signs, comorbidities, diet history, serum bilirubin, liver enzyme activity, albumin, phosphorus, white blood cell count, prothrombin time and final hepatic cytologic/histopathologic diagnosis, when available, were recorded. RESULTS Median serum 25(OH)D levels were similar in cats with CLD (89.5 nmol/l; range 21-112 nmol/l) and sick cats (89.0 nmol/l; range 49-115 nmol/l). Overall 12/36 (33%) cats with CLD and 4/23 (17%) sick cats had 25(OH)D levels below the lower limit of the reference interval (<65 nmol/l). Median PTH concentrations in cats with CLD were significantly higher (0.95 pmol/l; range 0-11.3 pmol/l) than in sick cats (0.70 pmol/l; range 0.5-6 pmol/l). In cats with CLD, 6/36 (17%) had high PTH levels in contrast to only 1/23 (4%) sick cats. In cats with CLD, 25(OH)D concentrations did not correlate with serum bilirubin, albumin or serum liver enzymes but were moderately negatively correlated with white blood cell count (r = - 0.402, P = 0.013). Cats with hepatic lipidosis had the highest prevalence of 25(OH)D concentrations that fell below the reference interval. CONCLUSIONS AND RELEVANCE Many cats with CLD have serum 25(OH)D concentrations below the lower limit of the reference interval. Further study is warranted to determine the clinical relevance and whether supplementation would provide benefits.
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Affiliation(s)
- Lesli Kibler
- Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA
| | - Cailin R Heinze
- Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA
| | - Cynthia RL Webster
- Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA
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Wei Y, Wang S, Meng Y, Yu Q, Wang Q, Xu H, Yuan H, Li X, Chen L. Effects of Vitamin D Supplementation in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Int J Endocrinol Metab 2020; 18:e97205. [PMID: 33257903 PMCID: PMC7695226 DOI: 10.5812/ijem.97205] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 05/31/2020] [Accepted: 06/02/2020] [Indexed: 02/06/2023] Open
Abstract
CONTEXT Vitamin D (VD) has been found to play a key role in nonalcoholic fatty liver disease (NAFLD). This meta-analysis explored the effects of VD supplementation in patients with NAFLD. METHODS The PubMed, EMBASE, and the Cochrane Library databases were searched to find randomized control trials (RCTs) that measured the changes between the VD supplement group and the control group until May 2019. Standard mean difference (SMD) with 95% confidence intervals (CI) was calculated when data units were different, otherwise weighted mean difference (WMD) and 95% CI was calculated. Heterogeneity was assessed using the I2 statistic. RESULTS Eight RCTs with 624 individuals were extracted. The main indicators, including serum alanine aminotransferase (WMD = -0.052; 95% CI: -3.740, 3.636; P = 0.978) and aspartate aminotransferase concentrations (WMD = -0.479; 95% CI: -2.791, 1.833; P = 0.685) were not significantly different between the intervention and placebo groups. In addition, no significant intergroup difference was observed in the following secondary indicators: fasting blood glucose (WMD = 0.466; 95% CI: -5.313, -10.879; P = 0.061), homeostasis model assessment (WMD = 0.380, 95% CI: -0.162, 0.923; P = 0.169), serum insulin concentration (WMD = 0.760; 95% CI: -0.532, 2.052; P = 0.249), high-density lipoprotein (WMD = -0.012; 95% CI: -0.188, 0.164; P = 0.891), and low-density lipoprotein (WMD = -0.115; 95% CI: -3.849, -3.620; P = 0.952). CONCLUSIONS The results indicate that VD supplementation does not improve liver enzymes, insulin resistance, glucose metabolism parameters, and lipid levels in patients with NAFLD.
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Affiliation(s)
- Yali Wei
- Institute of Nutrition and Food Hygiene, School of Public Health, Shandong University, Jinan, China
| | - Shuli Wang
- Department of Medical Imaging, Shandong Provincial Hospital Affiliated of Shandong University, Jinan, China
| | - Yan Meng
- Department of Nutrition, Shandong Provincial Hospital Affiliated of Shandong University, Jinan, China
| | - Qingtao Yu
- Department of Endocrinology, The People Hospital of Huaiyin Jinan, Jinan, China
| | - Qian Wang
- Department of Nutrition, Shandong Provincial Hospital Affiliated of Shandong University, Jinan, China
| | - Hongzhao Xu
- Institute of Nutrition and Food Hygiene, School of Public Health, Shandong University, Jinan, China
| | - Huacai Yuan
- Institute of Nutrition and Food Hygiene, School of Public Health, Shandong University, Jinan, China
| | - Xiaoxu Li
- Department of Nutrition, Shandong Provincial Hospital Affiliated of Shandong University, Jinan, China
| | - Liyong Chen
- Department of Nutrition, Shandong Provincial Hospital Affiliated of Shandong University, Jinan, China
- Corresponding Author: Department of Nutrition, Shandong Provincial Hospital Affiliated of Shandong University, Jinan, China.
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24
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Cimini FA, Barchetta I, Carotti S, Morini S, Cavallo MG. Overview of studies of the vitamin D/vitamin D receptor system in the development of non-alcoholic fatty liver disease. World J Gastrointest Pathophysiol 2019; 10:11-16. [PMID: 31559105 PMCID: PMC6751507 DOI: 10.4291/wjgp.v10.i2.11] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 08/09/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. NAFLD is known to be associated with obesity, type 2 diabetes, metabolic syndrome and increased cardiovascular events: for these reasons, it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment. The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled; consequently, at moment there are not effective treatments. In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation, inflammation and fibrosis, to the vitamin D/vitamin D receptor (VD/VDR) axis, showing a strong association between hypovitaminosis D and the diagnosis of NAFLD. However, the data currently available, including clinical trials with VD supplementation, still provides a contrasting picture. The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR. Based on recent data from literature, we focused in particular on the hypothesis that VDR itself, independently from its traditional ligand VD, may have a crucial function in promoting hepatic fat accumulation. This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.
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Affiliation(s)
- Flavia Agata Cimini
- Department of Experimental Medicine, Sapienza University of Rome, Rome I-00161, Italy
| | - Ilaria Barchetta
- Department of Experimental Medicine, Sapienza University of Rome, Rome I-00161, Italy
| | - Simone Carotti
- Department of Medicine and Surgery, Laboratory of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico of Rome, Rome I-00128, Italy
| | - Sergio Morini
- Department of Medicine and Surgery, Laboratory of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico of Rome, Rome I-00128, Italy
| | - Maria Gisella Cavallo
- Department of Experimental Medicine, Sapienza University of Rome, Rome I-00161, Italy
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Sangouni AA, Ghavamzadeh S, Jamalzehi A. A narrative review on effects of vitamin D on main risk factors and severity of Non-Alcoholic Fatty Liver Disease. Diabetes Metab Syndr 2019; 13:2260-2265. [PMID: 31235166 DOI: 10.1016/j.dsx.2019.05.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 05/21/2019] [Indexed: 02/06/2023]
Abstract
The global prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing rapidly. Many studies have been conducted on the treatment of NAFLD; nevertheless, there is still no approved drug treatment for this disease. Although the pathogenesis of NAFLD is not fully understood, but inflammation, insulin resistance, oxidative stress, obesity and dyslipidemia are among the main causes. Epidemiological studies have shown that hypovitaminosis D is associated with these factors causing NAFLD. In addition, rate of Vitamin D deficiency has been shown to be directly related to the severity of NAFLD. Accordingly, it is believed that vitamin D may help to treatment of NAFLD by improving the above-mentioned risk factors. The purpose of this review is to survey the recent advances in the field of Vitamin D efficacy on risk factors and the severity of NAFLD based on existing evidence, especially the clinical efficiency of vitamin D supplementation in patients with NAFLD.
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Affiliation(s)
- Abbas Ali Sangouni
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran; Department of Human Nutrition, Medicine Faculty, Urmia University of Medical Sciences, Urmia, Iran
| | - Saeid Ghavamzadeh
- Department of Human Nutrition, Medicine Faculty, Urmia University of Medical Sciences, Urmia, Iran; Food and Beverage Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran.
| | - Atena Jamalzehi
- Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
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Jahn D, Dorbath D, Schilling AK, Gildein L, Meier C, Vuille-Dit-Bille RN, Schmitt J, Kraus D, Fleet JC, Hermanns HM, Geier A. Intestinal vitamin D receptor modulates lipid metabolism, adipose tissue inflammation and liver steatosis in obese mice. Biochim Biophys Acta Mol Basis Dis 2019; 1865:1567-1578. [PMID: 30905785 DOI: 10.1016/j.bbadis.2019.03.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 03/06/2019] [Accepted: 03/19/2019] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Hypovitaminosis D is common in the obese population and patients suffering from obesity-associated disorders such as type 2 diabetes and fatty liver disease, resulting in suggestions for vitamin D supplementation as a potential therapeutic option. However, the pathomechanistic contribution of the vitamin D-vitamin D receptor (VDR) axis to metabolic disorders is largely unknown. METHODS We analyzed the pathophysiological role of global and intestinal VDR signaling in diet-induced obesity (DIO) using global Vdr-/- mice and mice re-expressing an intestine-specific human VDR transgene in the Vdr deficient background (Vdr-/- hTg). RESULTS Vdr-/- mice were protected from DIO, hepatosteatosis and metabolic inflammation in adipose tissue and liver. Furthermore, Vdr-/- mice displayed a decreased adipose tissue lipoprotein lipase (LPL) activity and a reduced capacity to harvest triglycerides from the circulation. Intriguingly, all these phenotypes were partially reversed in Vdr-/- hTg animals. This clearly suggested an intestine-based VDR activity on systemic lipid homeostasis. Scrutinizing this hypothesis, we identified the potent LPL inhibitor angiopoietin-like 4 (Angptl4) as a novel transcriptional target of VDR. CONCLUSION Our study suggests a VDR-mediated metabolic cross-talk between gut and adipose tissue, which significantly contributes to systemic lipid homeostasis. These results have important implications for use of the intestinal VDR as a therapeutic target for obesity and associated disorders.
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Affiliation(s)
- Daniel Jahn
- University Hospital Würzburg, Division of Hepatology, Würzburg, Germany
| | - Donata Dorbath
- University Hospital Würzburg, Division of Hepatology, Würzburg, Germany
| | | | - Lisa Gildein
- University Hospital Würzburg, Division of Hepatology, Würzburg, Germany
| | - Chantal Meier
- University of Zürich, Institute of Physiology, Zürich, Switzerland
| | | | - Johannes Schmitt
- University Hospital Würzburg, Division of Hepatology, Würzburg, Germany
| | - Daniel Kraus
- University Hospital Würzburg, Division of Nephrology, Würzburg, Germany
| | - James C Fleet
- Purdue University, Department of Nutrition Science, West Lafayette, IN, USA
| | - Heike M Hermanns
- University Hospital Würzburg, Division of Hepatology, Würzburg, Germany
| | - Andreas Geier
- University Hospital Würzburg, Division of Hepatology, Würzburg, Germany; University Hospital Zürich, Division of Gastroenterology and Hepatology, Zürich, Switzerland.
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Javed Z, Papageorgiou M, Deshmukh H, Kilpatrick ES, Mann V, Corless L, Abouda G, Rigby AS, Atkin SL, Sathyapalan T. A Randomized, Controlled Trial of Vitamin D Supplementation on Cardiovascular Risk Factors, Hormones, and Liver Markers in Women with Polycystic Ovary Syndrome. Nutrients 2019; 11:nu11010188. [PMID: 30658483 PMCID: PMC6356309 DOI: 10.3390/nu11010188] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 01/10/2019] [Accepted: 01/15/2019] [Indexed: 01/10/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) increases the risk of metabolic syndrome and non-alcoholic-fatty-liver disease (NAFLD). Vitamin D supplementation may exert positive effects on liver biochemistry in patients with NAFLD; however, its effects on PCOS are unknown. This randomized, double-blind, placebo-controlled study explored the effect of vitamin D supplementation on cardiovascular risk factors (high-sensitivity C-reactive protein (hs-CRP), weight, body mass index (BMI), lipid profile, glucose levels, insulin levels, the homeostatic model assessment-insulin resistance (HOMA-IR), hormones (free androgen index (FAI), testosterone, sex hormone binding globulin (SHBG), and liver markers (alanine aminotransferase (ALT), hyaluronic acid (HA), N-terminal pro-peptide of type III procollagen (PIIINP), tissue inhibitor of metallo-proteinases-1 (TIMP-1), and the enhanced liver fibrosis (ELF) score). Forty women with PCOS were recruited and randomized to vitamin D (3200 IU) or placebo daily for 3 months. All outcomes were measured at baseline and 3 months follow-up (FU). Greater increases in vitamin D levels were shown in the supplementation group (vitamin D, baseline: 25.6 ± 11.4 nmol/L, FU: 90.4 ± 19.5 nmol/L vs. placebo, baseline: 30.9 ± 11.1 nmol/L, FU: 47.6 ± 20.5 nmol/L, p < 0.001). Between groups comparisons (% baseline change) revealed significant differences in ALT (p = 0.042) and a weak effect indicating a greater reduction in the HOMA-IR in the vitamin D group (p = 0.051). No further between group differences were seen in other cardiovascular risk factor, liver markers, or hormones. This study supports beneficial effects of vitamin D supplementation on liver markers and modest improvements in insulin sensitivity in vitamin D deficient women with PCOS.
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Affiliation(s)
- Zeeshan Javed
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull HU3 2JZ, UK.
| | - Maria Papageorgiou
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull HU3 2JZ, UK.
- Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna 1090, Austria.
| | - Harshal Deshmukh
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull HU3 2JZ, UK.
| | - Eric S Kilpatrick
- Department of Pathology, Sidra Medical and Research Centre, Doha PO Box 26999, Qatar.
| | - Vincent Mann
- Gastroenterology Research Department, Hull Royal Infirmary, Hull HU3 2JZ, UK.
| | - Lynsey Corless
- Gastroenterology Research Department, Hull Royal Infirmary, Hull HU3 2JZ, UK.
| | - George Abouda
- Gastroenterology Research Department, Hull Royal Infirmary, Hull HU3 2JZ, UK.
| | - Alan S Rigby
- Hull York Medical School, University of Hull, Hull HU3 2JZ, UK.
| | - Stephen L Atkin
- Weill Cornell Medical College Qatar, Education City, Doha PO Box 24144, Qatar.
| | - Thozhukat Sathyapalan
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull HU3 2JZ, UK.
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