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Muller de Moura Sarmento S, Gomes Schmitt E, Smolski dos Santos L, Erminda Schreiner G, Tamborena Malheiros R, Klock C, Casanova Petry C, Gonçalves IL, Manfredini V. Vitamin D supplementation: Biochemical and inflammatory effects in non-pathological Wistar rats. Toxicol Rep 2025; 14:101901. [PMID: 39897401 PMCID: PMC11786669 DOI: 10.1016/j.toxrep.2025.101901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/13/2024] [Accepted: 01/07/2025] [Indexed: 02/04/2025] Open
Abstract
Vitamin D3 (VD3) is shown to be a biochemical and physiological modulator of the body. Debates about route of administration, prescribed dosage and serum levels have arisen, and thus the interaction of VD3 with the body in overdose. Using an experimental model of Wistar rats of both sexes, rats were subdivided into 5 groups, which represents a control group, and 4 groups with VD3 treatments (2.500, 7.000, 14.000 and 21.000 IU/kg/week) for one month. Thereafter biochemical, hormonal, inflammatory and histological analyses were performed. Regarding the biochemical findings, there was an increase in the levels of the AST in comparison of the control group with the treatments with higher doses (14.000 IU and 21.000 IU). Furthermore, changes in the inflammatory cytokine profile were identified at doses of 14,000 IU and 21,000 IU, with an increase in inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) and a decrease in the anti-inflammatory IL-10. Histological evaluation of the liver tissue also revealed changes at the highest doses. Finally, in the evaluation of a murine physiological model, it showed that the supplementation of VD3 in overdoses there was an inflammatory exacerbation in the body, suggesting that the VD3 supplementation should be administered with caution, and takes into account physiological factors of the individual.
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Affiliation(s)
| | - Elizandra Gomes Schmitt
- Pós-Graduate Program in Biochemistry, Federal University of Pampa, BR 472, Km 585, Uruguaiana, RS, Brazil
| | - Laura Smolski dos Santos
- Pós-Graduate Program in Biochemistry, Federal University of Pampa, BR 472, Km 585, Uruguaiana, RS, Brazil
| | - Gênifer Erminda Schreiner
- Pós-Graduate Program in Biochemistry, Federal University of Pampa, BR 472, Km 585, Uruguaiana, RS, Brazil
| | - Rafael Tamborena Malheiros
- Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, Universidade Federal do Pampa, Campus Uruguaiana, Rio Grande do Sul, Brazil
| | - Clóvis Klock
- Grupo Infolaudo e Medicina Diagnóstica, Erechim, Rio Grande do Sul, Brazil
| | | | - Itamar Luís Gonçalves
- Universidade Regional Integrada Alto-Uruguai e das Missões, Sete de Setembro Avenue, 1621, Erechim, Rio Grande do Sul, Brazil
| | - Vanusa Manfredini
- Pós-Graduate Program in Biochemistry, Federal University of Pampa, BR 472, Km 585, Uruguaiana, RS, Brazil
- Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, Universidade Federal do Pampa, Campus Uruguaiana, Rio Grande do Sul, Brazil
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Chung SI, Liang L, Han H, Park KH, Lee JH, Park JW. Vitamin D Attenuates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obesity Murine Model. Yonsei Med J 2025; 66:75-86. [PMID: 39894040 PMCID: PMC11790407 DOI: 10.3349/ymj.2024.0038] [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: 03/22/2024] [Revised: 07/15/2024] [Accepted: 08/09/2024] [Indexed: 02/04/2025] Open
Abstract
PURPOSE Obesity and metabolic syndrome are acknowledged as key factors contributing to the development of non-alcoholic fatty liver disease (NAFLD). Vitamin D (VitD) is a multifaceted secosteroid hormone known for its anti-fibrotic and anti-inflammatory properties, with its deficiency often linked to obesity. Our study aimed to investigate whether VitD supplementation could mitigate the liver pathology associated with NAFLD. MATERIALS AND METHODS The NAFLD model was developed by subjecting male C57BL/6 mice to a high-fat diet (HFD) for 14 weeks. These mice were supplemented with VitD through intraperitoneal injection at a dosage of 7 µg/kg, administered three times per week for 7 weeks. RESULTS HFD resulted in VitD deficiency, insulin resistance, and increased liver weight. It elevated serum levels of liver aminotransferases and triglyceride, ultimately leading to steatohepatitis with fibrosis. This model exhibited increased levels of transforming growth factor (TGF)-β1, pro-inflammatory cytokines, HNF4α transcription factors, reactive oxygen species (ROS), renin-angiotensin system activity, and epithelial-mesenchymal transitions (EMT) within the liver. Supplementation with VitD resulted in the recovery of liver weight, improvement in histologic features associated with steatohepatitis, and reduction in alanine aminotransferases and triglyceride levels induced by the HFD. Additionally, it mitigated the HFD-induced over-expressions of TGF-β1 and fibrosis-related genes, along with pro-inflammatory cytokines and ROS. Notably, no adverse effect was found due to VitD supplementation in this model. CONCLUSION VitD ameliorates steatohepatitis within obesity-induced NAFLD through its multifaceted pathways. VitD supplementation emerges as a potentially safe, cost-effective, and direct treatment approach for NAFLD patients dealing with obesity or metabolic dysfunction.
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Affiliation(s)
- Sook In Chung
- Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea
| | - Lin Liang
- Graduate School of Medicine, Yonsei University, Seoul, Korea
| | - Heejae Han
- Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Hee Park
- Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea
| | - Jae-Hyun Lee
- Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea
| | - Jung-Won Park
- Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
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Liang Y, Jiang X, Zhao X, Tang T, Fan X, Wang R, Yang M, Qi K, Zhang Y, Li P. Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway. iScience 2024; 27:111262. [PMID: 39713736 PMCID: PMC11661986 DOI: 10.1016/j.isci.2024.111262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/26/2024] [Accepted: 10/23/2024] [Indexed: 12/24/2024] Open
Abstract
Increasing evidence points toward vitamin D (VD) having lipometabolism and immune-related properties to protect against related metabolic diseases through influencing DNA methylation with inconsistent results. Simultaneously, its relatively precise molecular metabolism on the progression of metabolic-associated fatty liver disease (MAFLD) remains uncertain. Here, we report an unprecedented role and possible mechanism for VD supplementation on the alleviation of high-fat diet (HFD)-induced MAFLD. Over time, our results demonstrated that metabolic disorders in the HFD-induced MAFLD were aggravated with a certain time-response dependence and accompanied by reduced VD metabolites. All these could be alleviated under sufficient VD supplementation in vivo and vitro. It was partially by inhibiting the expressions of DNMT1 to reverse the epigenetic patterns on the VD metabolism genes and TGFβR1, which ultimately triggered the TGFβ1/Smad3 pathway to result in the development of MAFLD. Furthermore, the protective effects of VD were weakened by the treatment with gene silencing of DNMT1.
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Affiliation(s)
- Yueqing Liang
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Xueyi Jiang
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Xinfeng Zhao
- Department of Chemistry and Materials Science, Hebei University, Baoding City, Hebei Province 071002, China
| | - Tiantian Tang
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Xiuqin Fan
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Rui Wang
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Mengyi Yang
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Kemin Qi
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Yi Zhang
- Department of Chemistry and Materials Science, Hebei University, Baoding City, Hebei Province 071002, China
| | - Ping Li
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, 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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Lee HA, Lee HA, Kim HY. Evolution of characteristics of MASLD with and without diabetes: a meta-analysis of placebo arms. Sci Rep 2024; 14:28951. [PMID: 39578601 PMCID: PMC11584620 DOI: 10.1038/s41598-024-79428-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 11/08/2024] [Indexed: 11/24/2024] Open
Abstract
BACKGROUND We explored the changes in metabolic dysfunction-associated steatotic liver disease (MASLD) severity over time by analyzing data from the placebo arms of randomized controlled trials (RCTs), focusing on the presence of diabetes. METHODS RCTs on MASLD that included a placebo arm were identified using a systematic search of the literature. Primary outcomes were changes in hepatic steatosis and fibrosis. RESULTS The meta-analysis included 8 RCTs involving 386 patients without diabetes and 24 RCTs involving 637 patients with diabetes. The pooled estimate of mean change in steatosis grade was - 0.1 in patients without diabetes, and - 0.37 in patients with diabetes (P = 0.066). The mean change in fibrosis stage was 0.05 in patients without diabetes, and - 0.03 in patients with diabetes (P = 0.359). The mean change in nonalcoholic fatty liver disease activity score was - 0.55 in patients without diabetes, and - 1.50 in patients with diabetes (P = 0.100). The mean change in ALT and AST were significantly larger in patients without diabetes compared to those with diabetes (P < 0.05). CONCLUSION Placebo treatment had a greater effect in improving liver steatosis in patients with diabetes compared to those without. These findings highlight the importance of tailored treatment strategies in MASLD, particularly considering diabetes status.
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Affiliation(s)
- Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University College of Medicine, Seoul, Korea
| | - Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, Korea.
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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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Oliveira INND, Macedo-Silva A, Coutinho-Cruz L, Sanchez-Almeida J, Tavares MPS, Majerowicz D. Effects of vitamin D supplementation on metabolic syndrome parameters in patients with obesity or diabetes in Brazil, Europe, and the United States: A systematic review and meta-analysis. J Steroid Biochem Mol Biol 2024; 243:106582. [PMID: 38992391 DOI: 10.1016/j.jsbmb.2024.106582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 07/05/2024] [Accepted: 07/09/2024] [Indexed: 07/13/2024]
Abstract
Plasma 25-dihydroxyvitamin D levels appear reduced in patients with obesity or type 2 diabetes, as reported in several observational studies. However, the association between these reduced hormone levels and metabolic parameters is unclear. In any case, vitamin D supplementation in patients with Metabolic Syndrome is standard. Still, the impacts of this supplementation on conditions such as glycemia, blood pressure, and lipidemia are debatable. Based on this question, we carried out a systematic review and meta-analysis of randomized clinical trials in Brazil, Europe, and the United States that analyzed the effects of vitamin D supplementation on Metabolic Syndrome parameters in patients with obesity or type 2 diabetes. Our search yielded 519 articles and included 12 randomized controlled trials in the meta-analysis. Vitamin D supplementation had no effect on any of the outcomes analyzed (fasting blood glucose and insulinemia, glycated hemoglobin, HOMA index, systolic and diastolic blood pressure, weight, waist circumference, total cholesterol, LDL and HDL, and triglycerides). However, subgroup analyses indicated that using vitamin D up to 2000 IU daily reduced participants' fasting blood glucose and glycated hemoglobin. Furthermore, the intervention reduced diastolic blood pressure only in participants with vitamin D deficiency. At least two studies showed a high risk of bias using the Rob2 protocol. According to the GRADE protocol, the evidence quality varied from moderate to very low. These results indicate that vitamin D supplementation does not improve patients' metabolic parameters and that the association between plasma 25-dihydroxyvitamin D levels and Metabolic Syndrome may not be causal but caused by other confounding characteristics. However, in any case, the quality of evidence is still low, and more randomized clinical trials are essential to clarify these relationships.
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Affiliation(s)
| | - Alessa Macedo-Silva
- Programa de Pós-Graduação em Biociências, Universidade do Estado do Rio de Janeiro, Brazil
| | | | | | | | - David Majerowicz
- Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Brazil; Programa de Pós-Graduação em Biociências, Universidade do Estado do Rio de Janeiro, Brazil.
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Afraie M, Bahrami P, Kohnepoushi P, Khateri S, Majidi L, Saed L, Zamani K, Baharm HM, Moradi Y, Moradpour F. The Effect of Vitamin D Supplementation on Glycemic Control and Cardiovascular Risk Factors in Type 2 Diabetes: An Updated Systematic Review and Meta-Analysis of Clinical Trials. J Diabetes Res 2024; 2024:9960656. [PMID: 39290798 PMCID: PMC11407890 DOI: 10.1155/2024/9960656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 05/07/2024] [Accepted: 06/04/2024] [Indexed: 09/19/2024] Open
Abstract
Background and Aims: The purpose of this meta-analysis was to investigate the effect of vitamin D supplementation on hemoglobin A1C (HbA1C), fasting blood sugar (FBS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), systolic blood pressure (SBP), and the total vitamin D level in patients with Type 2 diabetes (T2DM). Methods: A systematic search was conducted in databases such as PubMed (Medline), Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov using relevant keywords from January 1990 to January 2024. After screening and extracting data, a qualitative evaluation of articles was performed using the Cochrane risk-of-bias tool for randomized trials (RoB 2). Results: The findings revealed that vitamin D supplementation significantly decreased the mean HbA1C (SMD: -0.15; 95% CI: -0.29, -0.20; I square: 79.76%; p value < 0.001) and mean FBS (SMD: -0.28; 95% CI: -0.40, -0.15; I square: 70.13%; p value < 0.001), lowered SBP (SMD: -0.06; 95% CI: -0.16, -0.05; I square: 39.63%; p value = 0.23), and reduced LDL (SMD: -0.11; 95% CI: -0.28, -0.05; I square: 73.66%; p value < 0.001). Furthermore, vitamin D supplementation increased the average HDL (SMD: 0.13; 95% CI: 0.04, 0.29; I square: 79.33%; p value < 0.001) and vitamin D levels (SMD: 1.78; 95% CI: 1.53, 2.04; I square: 91.92%; p value < 0.001) in patients with T2DM. Subgroup analyses showed that weight gain, BMI, and duration of the disease could reduce the effect of vitamin D supplementation on diabetes control in affected patients. Conclusion: The results also indicated that taking vitamin D supplements in the amount of 50,000 IU had a significant effect on reducing the indicators related to diabetes control. Based on the combined evidence, the findings of this meta-analysis suggest that vitamin D supplementation can significantly improve glycemic control and reduce the risk of complications associated with T2DM, especially cardiovascular diseases (CVDs).
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Affiliation(s)
- Maryam Afraie
- Student Research CommitteeKurdistan University of Medical Sciences, Sanandaj, Kurdistan, Iran
| | - Pourya Bahrami
- Student Research CommitteeKurdistan University of Medical Sciences, Sanandaj, Kurdistan, Iran
| | - Parisa Kohnepoushi
- Student Research CommitteeKurdistan University of Medical Sciences, Sanandaj, Kurdistan, Iran
| | - Sorour Khateri
- Department of Physical Medicine and RehabilitationHamedan University of Medical Sciences, Hamedan, Iran
| | - Lobat Majidi
- Department of Physical Medicine and RehabilitationHamedan University of Medical Sciences, Hamedan, Iran
| | - Lotfollah Saed
- Department of Internal MedicineSchool of MedicineKurdistan University of Medical Sciences, Sanandaj, Iran
| | - Kamran Zamani
- Student Research CommitteeKurdistan University of Medical Sciences, Sanandaj, Kurdistan, Iran
| | - Hedyeh Mohammadi Baharm
- Student Research CommitteeKurdistan University of Medical Sciences, Sanandaj, Kurdistan, Iran
| | - Yousef Moradi
- Social Determinants of Health Research CenterResearch Institute for Health DevelopmentUniversity of Medical Sciences, Sanandaj, Kurdistan, Iran
| | - Farhad Moradpour
- Social Determinants of Health Research CenterResearch Institute for Health DevelopmentUniversity of Medical Sciences, Sanandaj, Kurdistan, Iran
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Derogar Kasmaei SR, Parastouei K, Hosseini Ahangar B, Saberifiroozi M, Taghdir M. Effects of vitamin D supplementation on the glycaemic indices, lipid profile and liver function tests in patients with cirrhosis: a double-blind randomised controlled trial. BMJ Nutr Prev Health 2024; 7:e000938. [PMID: 39882304 PMCID: PMC11773653 DOI: 10.1136/bmjnph-2024-000938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 08/09/2024] [Indexed: 01/31/2025] Open
Abstract
Background Liver cirrhosis is considered a progressive disease that can eventually result in death. Vitamin D deficiency is prevalent in patients with cirrhosis. Few studies have been conducted on the effect of vitamin D supplementation in patients with cirrhosis. Objectives The aim of this study was to identify the effect of vitamin D supplementation on lipid profile, glycaemic indices and liver function tests in patients with cirrhosis. Methods Sixty patients with cirrhosis were involved in this double-blind, randomised controlled clinical trial. During the intervention, patients received one 50 000 IU pearl of vitamin D supplement or placebo per week for 12 weeks. Before and after supplementation, we assessed serum 25-hydroxy-vitamin-D3 (25(OH) D3), glycaemic indices (insulin, haemoglobin A1c, fasting blood glucose (FBG) and homeostatic model assessment for insulin resistance (HOMA-IR)), lipid profile and liver function tests. Results Baseline variables were not significantly different between groups. The present study indicated that over the 12 weeks, vitamin D supplementation significantly increased serum 25(OH) D3 (p<0.001), and also significantly decreased FBG (p=0.006), and HOMA-IR (p=0.001). Conclusions Vitamin D supplementation significantly improves FBG and HOMA-IR as well as serum 25(OH) D3 in patients with cirrhosis. Trial registration number The protocol of the study was registered at the Iranian Registry of Clinical Trials (IRCT) (IRCT20140502017522N2).
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Affiliation(s)
| | - Karim Parastouei
- Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Behnam Hosseini Ahangar
- Baqiyatallah Research Center for Gastroenterology and Liver Disease (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mehdi Saberifiroozi
- Liver and Pancreatobiliary Disease Research Center (LPDRC), Digestive Disease Research Institute, Tehran University of Medical Science, Tehran, Iran
| | - Maryam Taghdir
- Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
- Department of Nutrition and Food Hygiene - Faculty of Health, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Seidita A, Cusimano A, Giuliano A, Meli M, Carroccio A, Soresi M, Giannitrapani L. Oxidative Stress as a Target for Non-Pharmacological Intervention in MAFLD: Could There Be a Role for EVOO? Antioxidants (Basel) 2024; 13:731. [PMID: 38929170 PMCID: PMC11201095 DOI: 10.3390/antiox13060731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 06/11/2024] [Accepted: 06/13/2024] [Indexed: 06/28/2024] Open
Abstract
Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD.
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Affiliation(s)
- Aurelio Seidita
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90146 Palermo, Italy; (A.S.); (A.G.); (M.M.); (A.C.)
- Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy;
| | - Alessandra Cusimano
- Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy;
| | - Alessandra Giuliano
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90146 Palermo, Italy; (A.S.); (A.G.); (M.M.); (A.C.)
| | - Maria Meli
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90146 Palermo, Italy; (A.S.); (A.G.); (M.M.); (A.C.)
| | - Antonio Carroccio
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90146 Palermo, Italy; (A.S.); (A.G.); (M.M.); (A.C.)
| | - Maurizio Soresi
- Unit of Internal Medicine, University Hospital “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy;
| | - Lydia Giannitrapani
- Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy;
- Unit of Internal Medicine, University Hospital “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy;
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11
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Lu Q, Liang Q, Xi Y. The effects of vitamin D supplementation on serum lipid profiles in people with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Front Nutr 2024; 11:1419747. [PMID: 38903615 PMCID: PMC11188582 DOI: 10.3389/fnut.2024.1419747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 05/27/2024] [Indexed: 06/22/2024] Open
Abstract
Introduction People with type 2 diabetes (T2D) are highly susceptible to the development of cardiovascular diseases. Previous studies have suggested that the application of vitamin D may offer potential benefits in improving lipid profiles, but these effects remain controversial. Methods This systematic review and meta-analysis focused on the effects of vitamin D supplementation on serum lipid profiles in people with T2D. Randomized controlled trials (RCTs) assessing the effects of vitamin D supplementation on lipid profiles and published before September 19th, 2023, were identified in PubMed, Embase, and Cochrane Library. This review protocol was registered in the PROSPERO (CRD42023461136). The random-effects model was employed to estimate unstandardized mean differences (MD) and 95% confidence intervals (CIs). The quality of studies was assessed by the Cochrane Risk of Bias tool 2. Results Overall, 20 RCTs involving 1711 participants were included. Results indicated that vitamin D supplementation significantly improves serum high-density lipoprotein (HDL) (MD: 1.63 mg/dL, 95% CI: 0.19 to 3.08, P = 0.03), and triglyceride (TG) levels (MD: -8.56 mg/dL, 95% CI: -15.23 to -1.89, P = 0.01). However, vitamin D supplementation failed to improve low-density lipoprotein (LDL) levels and total cholesterol (TC) levels. Subgroup analyses and meta-regressions suggested that higher doses of vitamin D supplementation and shorter duration of intervention were more likely to have favorable effects on lipid profiles. Moreover, participants with lower baseline BMI and higher serum 25-hydroxy vitamin D levels exhibited greater improvements in lipid profiles following vitamin D supplementation. Conclusions This meta-analysis highlighted the effects of vitamin D supplementation on improving serum HDL and TG levels while not exhibiting significant improvements in LDL and TC levels. Further long-term and high-quality studies are still needed to draw more precise conclusions. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=461136.
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Affiliation(s)
- Qingyang Lu
- School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Qingyue Liang
- Discipline of Nutrition and Dietetics, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Yue Xi
- Centre for International Collaboration, Office of Hong Kong, Macao and Taiwan Affairs, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
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12
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Aggeletopoulou I, Tsounis EP, Triantos C. Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Novel Mechanistic Insights. Int J Mol Sci 2024; 25:4901. [PMID: 38732118 PMCID: PMC11084591 DOI: 10.3390/ijms25094901] [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: 03/15/2024] [Revised: 04/23/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition characterized by abnormal fat accumulation in the liver, often associated with metabolic disorders. Emerging evidence suggests a potential link between vitamin D deficiency and the development and progression of MASLD. The current review provides a concise overview of recent studies uncovering novel mechanistic insights into the interplay between vitamin D and MASLD. Several epidemiological studies have highlighted a significant association between low vitamin D levels and an increased risk of MASLD. Vitamin D, traditionally known for its role in bone health, has now been recognized as a key player in various physiological processes, including immune regulation and inflammation. Experimental studies using animal models have demonstrated that vitamin D deficiency exacerbates liver steatosis and inflammation, suggesting a potential protective role against MASLD. Mechanistically, vitamin D appears to modulate MASLD through multiple pathways. Firstly, the vitamin D receptor (VDR) is abundantly expressed in liver cells, indicating a direct regulatory role in hepatic function. Activation of the VDR has been shown to suppress hepatic lipid accumulation and inflammation, providing a mechanistic basis for the observed protective effects. Additionally, vitamin D influences insulin sensitivity, a critical factor in MASLD pathogenesis. Improved insulin sensitivity may mitigate the excessive accumulation of fat in the liver, thus attenuating MASLD progression. In parallel, vitamin D exhibits anti-inflammatory properties by inhibiting pro-inflammatory cytokines implicated in MASLD pathophysiology. Experimental evidence suggests that the immunomodulatory effects of vitamin D extend to the liver, reducing inflammation and oxidative stress, key drivers of MASLD, and the likelihood of hepatocyte injury and fibrosis. Understanding the complex interplay between vitamin D and MASLD provides a basis for exploring targeted therapeutic strategies and preventive interventions. As vitamin D deficiency is a modifiable risk factor, addressing this nutritional concern may prove beneficial in mitigating the burden of MASLD and associated metabolic disorders.
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Affiliation(s)
| | | | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
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Ramalingam L, Mabry B, Menikdiwela KR, Moussa H, Moustaid-Moussa N. Enhanced Metabolic Effects of Fish Oil When Combined with Vitamin D in Diet-Induced Obese Male Mice. Biomolecules 2024; 14:474. [PMID: 38672490 PMCID: PMC11048485 DOI: 10.3390/biom14040474] [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: 03/01/2024] [Revised: 03/30/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Vitamin D (vit D) and fish oil (FO) both offer unique health benefits, however, their combined effects have not been evaluated in obesity and nonalcoholic fatty liver disease (NAFLD). Hence, we hypothesized that vit D and FO supplementation would have additive effects in reducing obesity-associated inflammation and NAFLD. Male C57BL6 mice were split into four groups and fed a high fat (HF) diet supplemented with a low (HF; +200 IU vit D) or high dose of vitamin D (HF + D; +1000 IU vit D); combination of vit D and FO (HF-FO; +1000 IU vit D); or only FO (HF-FO; +200 IU vit D) for 12 weeks. We measured body weight, food intake, glucose tolerance, and harvested epididymal fat pad and liver for gene expression analyses. Adiposity was reduced in groups supplemented with both FO and vit D. Glucose clearance was higher in FO-supplemented groups compared to mice fed HF. In adipose tissue, markers of fatty acid synthesis and oxidation were comparable in groups that received vit D and FO individually in comparison to HF. However, the vit D and FO group had significantly lower fatty acid synthesis and higher oxidation compared to the other groups. Vit D and FO also significantly improved fatty acid oxidation, despite similar fatty acid synthesis among the four groups in liver. Even though we did not find additive effects of vit D and FO, our data provide evidence that FO reduces markers of obesity in the presence of adequate levels of vit D.
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Affiliation(s)
- Latha Ramalingam
- Nutrigenomics, Inflammation and Obesity Research Laboratory, Department of Nutritional Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA (K.R.M.)
- Obesity Research Institute, Office of Research & Innovation, Texas Tech University (TTU), Lubbock, TX 79409, USA
| | - Brennan Mabry
- Nutrigenomics, Inflammation and Obesity Research Laboratory, Department of Nutritional Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA (K.R.M.)
| | - Kalhara R. Menikdiwela
- Nutrigenomics, Inflammation and Obesity Research Laboratory, Department of Nutritional Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA (K.R.M.)
- Obesity Research Institute, Office of Research & Innovation, Texas Tech University (TTU), Lubbock, TX 79409, USA
| | - Hanna Moussa
- Obesity Research Institute, Office of Research & Innovation, Texas Tech University (TTU), Lubbock, TX 79409, USA
- Department of Physics & Astronomy, College of Arts & Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA
| | - Naima Moustaid-Moussa
- Nutrigenomics, Inflammation and Obesity Research Laboratory, Department of Nutritional Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA (K.R.M.)
- Obesity Research Institute, Office of Research & Innovation, Texas Tech University (TTU), Lubbock, TX 79409, USA
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Wang Y, Yi H, Sun W, Yu H, Tao W, Yu X, Jia D, Liu Y, Pandol SJ, Li L. Comparative Efficacy of Drug Interventions on NAFLD Over 24 Weeks: A Traditional and Network Meta-Analysis of Randomized Controlled Trials. Drugs 2024; 84:425-439. [PMID: 38478331 DOI: 10.1007/s40265-024-02015-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/26/2024] [Indexed: 05/19/2024]
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD), currently referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), affects approximately 38% of the world's population, yet no pharmacological therapies have been approved for treatment. We conducted a traditional and network meta-analysis to comprehensively assess the effectiveness of drug regimens on NAFLD, and continued to use the old terminology for consistency. METHODS Randomized, placebo-controlled trials (RCTs) investigating drug therapy in an adult population diagnosed with NAFLD with or without diabetes mellitus were included. We assessed the quality of RCTs via the Risk of Bias 2 (ROB 2) tool. When I2 < 50%, we chose a random-effects model, otherwise a fixed-effects model was selected. A random effects model was applied in the network meta-analysis. The odds ratio (OR), weighted mean difference (WMD) or standard mean difference (SMD) with 95% confidence interval (CI) were used for outcome evaluation. The primary endpoint was the resolution of nonalcoholic steatohepatitis (NASH) without the worsening of liver fibrosis. Other endpoints included histological findings and metabolic changes. The PROSPERO Registration ID was CRD42023404309. RESULTS Thiazolidinediones (TZDs), vitamin E plus pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists and fibroblast growth factor-21 (FGF-21) analogue had a higher surface under the cumulative ranking curve (SUCRA = 76.6, 73.0, 72.0 and 71.6) regarding NASH resolution. Improvement of liver fibrosis stage (≥ 1) was observed with obeticholic acid 25 mg/day (OR 2.01, 95% CI 1.35-2.98), lanifibranor 1200 mg/day (OR 2.39, 95% CI 1.19-4.82) and silymarin (OR 4.54, 95% CI 1.18-17.43) in traditional meta-analysis. CONCLUSIONS The results of the comprehensive analysis suggested hypoglycemic drug therapy as an effective intervention for NAFLD, with or without diabetes mellitus. A prioritized selection of TZDs, vitamin E plus pioglitazone, GLP-1 receptor agonists and FGF-21 analogue may be considered for NASH resolution. Obeticholic acid, lanifibranor and silymarin could be considered for the improvement of liver fibrosis. Each medication was relatively safe compared with placebo.
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Affiliation(s)
- Yifan Wang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - He Yi
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Weixia Sun
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Hekai Yu
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Wenxuan Tao
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Xiaojin Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Dianrong Jia
- Department of Endocrinology, Taizhou Jiangyan Hospital of Traditional Chinese Medicine, Taizhou, 225500, China
| | - Yingzhao Liu
- Department of Endocrinology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212000, China
| | - Stephen J Pandol
- Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
- Basic and Translational Pancreatic Research, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, 210009, China.
- Department of Clinical Science and Research, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
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15
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Ye H, Li Y, Liu S, Zhang X, Liang H, Wang Y, Wang R, Liu H, Wen Y, Jing C, Wang L. Association between serum 25-hydroxyvitamin D and vitamin D dietary supplementation and risk of all-cause and cardiovascular mortality among adults with hypertension. Nutr J 2024; 23:33. [PMID: 38459491 PMCID: PMC10924411 DOI: 10.1186/s12937-024-00914-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 01/09/2024] [Indexed: 03/10/2024] Open
Abstract
BACKGROUND The relationship between vitamin D status and mortality among adults with hypertension remains unclear. METHODS This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). RESULTS The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22-2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15-3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54-1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61-0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52-0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58-0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45-0.88) and without CVD (HR = 0.61, 95%CI = 0.40-0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. CONCLUSIONS This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.
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Affiliation(s)
- Haowen Ye
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yexin Li
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No.601 Huangpu Ave West, Guangzhou, Guangdong, 510632, China
- Guangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong, 510632, China
| | - Shaomin Liu
- Department of Oncology Medilcal Center, The First People's Hospital of Zhaoqing, Zhaoqing, China
| | - Xiaofang Zhang
- Department Clinical Experimental Center, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Huanzhu Liang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No.601 Huangpu Ave West, Guangzhou, Guangdong, 510632, China
- Guangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong, 510632, China
| | - Ying Wang
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ruxin Wang
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Han Liu
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yun Wen
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Chunxia Jing
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No.601 Huangpu Ave West, Guangzhou, Guangdong, 510632, China.
- Guangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong, 510632, China.
| | - Lihong Wang
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Jinan 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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Chen D, Zhang Y, Zhou Y, Liu Y. Association between circulating biomarkers and non-alcoholic fatty liver disease: An integrative Mendelian randomization study of European ancestry. Nutr Metab Cardiovasc Dis 2024; 34:404-417. [PMID: 37973425 DOI: 10.1016/j.numecd.2023.09.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/18/2023] [Accepted: 09/19/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND AND AIM Circulating biomarkers provide potential diagnostic or prognostic information on disease presentation, progression or both. Early detection of circulating risk biomarkers is critical for non-alcoholic fatty liver disease (NAFLD) prevention. We aimed to systematically assess the potential causal relationship of genetically predicted 60 circulatory biomarkers with NAFLD using a two-sample Mendelian randomization (MR) design. METHODS AND RESULTS We extracted instrumental variables for 60 circulating biomarkers, and obtained genome-wide association data for NAFLD from 3 sources [(including Anstee, FinnGen and UK Biobank (N ranges: 19264-377988)] among individuals of European ancestry. Our primary method was inverse-variance weighted (IVW) MR, with a series of additional and sensitivity analyses to test the hypothesis of MR. MR results showed that genetically predicted higher density lipoprotein-cholesterol (odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.77-0.96) and vitamin D (OR = 0.39, 95% CI: 0.19-0.78) levels decreased the risk of NAFLD, whereas genetically predicted higher alanine (OR = 1.68, 95% CI: 1.21-2.33), histidine (OR = 1.21, 95% CI: 1.00-1.46), lactate (OR = 2.64, 95% CI: 1.09-6.39), triglycerides (OR = 1.16, 95% CI: 1.05-1.13), ferritin (OR = 1.17, 95% CI: 1.01-1.37), serum iron (OR = 1.23, 95% CI: 1.07-1.41) and transferrin saturation (OR = 1.16, 95% CI: 1.05-1.29), component 4 (OR = 1.10, 95% CI: 1.01-1.20), interleukin-1 receptor antagonist (OR = 1.12, 95% CI: 1.04-1.21) and interleukin-6 (OR = 1.62, 95% CI: 1.14-2.30) levels increased the risk of NAFLD. CONCLUSIONS The findings might aid in elucidating the underlying processes of these causal relationships and provide strong evidence for focusing on high-risk populations and the therapeutic management of specific biomarkers.
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Affiliation(s)
- Dongze Chen
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing 100142, China.
| | - Yali Zhang
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100083, China.
| | - Yi Zhou
- Shenzhen Health Development Research and Data Management Center, Shenzhen, China.
| | - Yuyang Liu
- Shenzhen Health Development Research and Data Management Center, Shenzhen, China.
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Ferenc K, Jarmakiewicz-Czaja S, Filip R. What Does Sarcopenia Have to Do with Nonalcoholic Fatty Liver Disease? Life (Basel) 2023; 14:37. [PMID: 38255652 PMCID: PMC10820621 DOI: 10.3390/life14010037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/11/2023] [Accepted: 12/16/2023] [Indexed: 01/24/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. As the second stage of developing steatosis, nonalcoholic hepatitis (NASH) carries the risk of fibrosis, cirrhosis, and hepatocellular carcinoma. Sarcopenia is defined as a condition characterized by a decrease in muscle mass and functional decline. Both NAFLD and sarcopenia are global problems. The pathophysiological mechanisms that link the two entities of the disease are insulin resistance, inflammation, nutritional deficiencies, impairment of myostatin and adiponectin, or physical inactivity. Furthermore, disorders of the gut-liver axis appear to induce the process of developing NAFLD and sarcopenia. The correlations between NAFLD and sarcopenia appear to be bidirectional, so the main objective of the review was to determine the cause-and-effect relationship between the two diseases.
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Affiliation(s)
- Katarzyna Ferenc
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland;
| | | | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland;
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
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Ji Y, Wei CB, Gu W, Hou LL. Relevance of vitamin D on NAFLD and liver fibrosis detected by vibration controlled transient elastography in US adults: a cross-sectional analysis of NHANES 2017-2018. Ann Med 2023; 55:2209335. [PMID: 37155562 PMCID: PMC10167885 DOI: 10.1080/07853890.2023.2209335] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 04/26/2023] [Indexed: 05/10/2023] Open
Abstract
BACKGROUND The connection between vitamin D to non-alcoholic fatty liver disease (NAFLD) is still unclear. Herein, the relationship of vitamin D with NAFLD and liver fibrosis (LF) detected by vibration controlled transient elastography was investigated in US adults. METHODS The National Health and Nutrition Examination Survey of 2017-2018 was employed for our analysis. Participants were categorized as having either vitamin D deficiency (<50 nmol/L) or vitamin D sufficiency (≥50 nmol/L). A controlled attenuation parameter score of ≥ 263 dB/m was employed to define NAFLD. Significant LF was identified by the liver stiffness measurement value of ≥ 7.9 kPa. Multivariate logistic regression was adopted to explore the relationships. RESULTS Among the 3407 participants, the prevalence of NAFLD and LF was 49.63% and 15.93% respectively. Compared to participants without NAFLD, no significant difference in serum vitamin D was observed in NALFD participants (74.26 vs. 72.24 nmol/L; p = 0.21). Using multivariate logistic regression analysis, no obvious connection of vitamin D status to NAFLD (sufficiency vs. deficiency, OR 0.89, 95%CI 0.70-1.13) was discovered. However, among NAFLD participants, the sufficiency of vitamin D represents a lower LF risk (OR 0.56, 95%CI 0.38-0.83). When evaluated in quartiles, in comparison to the lowest quartile, high vitamin D represents low LF risk in a dose-dependent manner (Q2 vs. Q1, OR 0.65, 95%CI 0.37-1.14; Q3 vs. Q1, OR 0.64, 95%CI 0.41-1.00; Q4 vs. Q1, OR 0.49, 95%CI 0.30-0.79). CONCLUSIONS No relationship was found between vitamin D and CAP-defined NAFLD. However, a positive connection of the high serum vitamin D to the reduced LF risk was found among NAFLD subjects.Key messages:Our study found no relationship between vitamin D and CAP-defined NAFLD in US adults.High serum vitamin D was inversely associated with liver fibrosis in a dose-dependent manner among NAFLD participants.
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Affiliation(s)
- Yuan Ji
- Health Management Center, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Chang-Bao Wei
- Department of Joint Surgery and Sports Medicine, Wuxi 9th People’s Hospital Affiliated to Suzhou Medical College of Soochow University, Wuxi, China
| | - Wei Gu
- Health Management Center, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Lin-Lin Hou
- Health Management Center, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
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20
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Garousi N, Tamizifar B, Pourmasoumi M, Feizi A, Askari G, Clark CCT, Entezari MH. Effects of lacto-ovo-vegetarian diet vs. standard-weight-loss diet on obese and overweight adults with non-alcoholic fatty liver disease: a randomised clinical trial. Arch Physiol Biochem 2023; 129:975-983. [PMID: 33689525 DOI: 10.1080/13813455.2021.1890128] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 01/13/2021] [Accepted: 02/07/2021] [Indexed: 12/18/2022]
Abstract
The aim of the study was to compare the effects of a lacto-ovo-vegetarian diet (LOV-D) vs. a standard weight-loss diet (SWL-D) on obese/overweight adults with NAFLD. Present randomised clinical trial recruited 75 overweight/obese adults with NAFLD, who were randomly assigned into LOV-D and SWL-D groups for 3 months. The LOV-D was designed based on eliminating meat, poultry, and fish; while including dairy products and eggs. The SWL-D was planned according to the standard food pyramid, which was free in all sources of food. Adherence to LOV-D significantly outperformed SWL-D in reducing levels of alanine aminotransferase (ALT), body weight, waist circumference, BMI, fasting blood sugar, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triacylglycerol (TG), cholesterol, low-density lipoprotein cholesterol (LDL-C), and systolic blood pressure (SBP). Furthermore, ultrasonography revealed a higher alleviation in NAFLD grade among LOV-D, compared with SWL-D. This study suggests that adherence to LOV-D for 3 months has beneficial effects on NAFLD improvement, anthropometric measures, glycaemic-related markers, and lipid profiles.
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Affiliation(s)
- Nazila Garousi
- Department of Clinical Nutrition, Food Security and Nutrition Research Center, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Babak Tamizifar
- Gastroenterlogy and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Makan Pourmasoumi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Awat Feizi
- Department of Epidemiology and Biostatistics, School of Public Health, Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gholamreza Askari
- Department of Community Nutrition, Food Security and Nutrition Research Center, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Cain C T Clark
- Centre for Intelligent Healthcare, Coventry University, Coventry, UK
| | - Mohammad Hasan Entezari
- Department of Clinical Nutrition, Food Security and Nutrition Research Center, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Deng M, Wen Y, Yan J, Fan Y, Wang Z, Zhang R, Ren L, Ba Y, Wang H, Lu Q, Fan H. Comparative effectiveness of multiple different treatment regimens for nonalcoholic fatty liver disease with type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis of randomised controlled trials. BMC Med 2023; 21:447. [PMID: 37974258 PMCID: PMC10655371 DOI: 10.1186/s12916-023-03129-6] [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: 02/20/2023] [Accepted: 10/25/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM. METHODS This systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes' certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373. RESULTS Four thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA1c) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA1c, with standard-treatment (STA-TRE) as reference (MD - 0.17, 95%CI - 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD - 11.72, 95%CI - 17.82 to - 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence. CONCLUSIONS The high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.
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Affiliation(s)
- Manjun Deng
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
- Qinghai Research Key Laboratory for Echinococcosis, Xining, 810000, Qinghai, China
| | - Yonghao Wen
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
| | - JingXin Yan
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
- Department of Interventional Therapy, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
| | - Yichen Fan
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
| | - Zhixin Wang
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
- Qinghai Research Key Laboratory for Echinococcosis, Xining, 810000, Qinghai, China
| | - Ruixia Zhang
- Department of Endocrinology, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
| | - Li Ren
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
- Qinghai Research Key Laboratory for Echinococcosis, Xining, 810000, Qinghai, China
| | - Yinggui Ba
- Department of Nephrology, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
| | - Haijiu Wang
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China
- Qinghai Research Key Laboratory for Echinococcosis, Xining, 810000, Qinghai, China
| | - Qian Lu
- Department of Hepatopancreatobiliary Surgery, Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China.
| | - Haining Fan
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, Qinghai, China.
- Qinghai Research Key Laboratory for Echinococcosis, Xining, 810000, Qinghai, China.
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22
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MacGirlley R, Phoswa WN, Mokgalaboni K. Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia. Nutrients 2023; 15:4575. [PMID: 37960227 PMCID: PMC10650901 DOI: 10.3390/nu15214575] [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: 10/11/2023] [Revised: 10/25/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Evidence from preclinical studies has found a correlation between the development of type 2 diabetes (T2D) and vitamin D deficiency. However, evidence from randomized controlled trials (RCTs) revealed inconclusive results on vitamin D supplementation. We explored the effect of vitamin D on inflammation and dyslipidemia in T2D. METHODS We comprehensively searched for RCTs evaluating the effect of vitamin D in T2D on PubMed. Data were analyzed using Review Manager 5.3 and reports, such as standardized mean difference (SMD) and 95% confidence intervals (CI) at a 5% significant level using a random effect model. RESULTS This study revealed a significant reduction in tumor necrosis factor-alpha (TNF-α) SMD = (-0.51, 95%CI (-0.93, -0.09); p = 0.02), high sensitivity C-reactive protein (hs-CRP) SMD = (-1.06, 95%CI (-1.67, -0.45); p < 0.05) in vitamin D compared to placebo. Additionally, interleukin-6 (IL-6) exhibited a marginal effect SMD = (-0.52, 95%CI (-1.05, 0.01), p = 0.05). Furthermore, a significant reduction in the level of triglycerides SMD = (-0.65, 95%CI (-1.11, -0.18), p < 0.05) was observed, concomitant to a significantly increased high-density lipoprotein (HDL) level SMD = (0.53, 95%CI (0.08, 0.98), p = 0.02). However, no statistically significant changes were observed in total cholesterols SMD = (-0.16, 95%CI (-0.57, 0.24), p = 0.43) and low-density lipoprotein (LDL) SMD = (-0.06, 95%CI (-0.37, 0.24), p = 0.67). CONCLUSIONS These findings suggest that vitamin D supplementation may be beneficial in ameliorating inflammation and dyslipidemia in T2D patients.
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Affiliation(s)
| | | | - Kabelo Mokgalaboni
- Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Florida Campus, Private Bag X6, Roodepoort 1710, South Africa; (R.M.); (W.N.P.)
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Korkmaz HA, Arya VB, Barisik V, Atila D, Coskunol F, Alci S, Cekdemir YE, Torlak D, Özkan B. The Association between Vitamin D Deficiency and Hepatosteatosis in Children and Adolescents with Obesity. Horm Res Paediatr 2023; 97:326-333. [PMID: 37793366 DOI: 10.1159/000533908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 08/25/2023] [Indexed: 10/06/2023] Open
Abstract
INTRODUCTION Increasingly, research groups have been studying the association of serum vitamin D and metabolic health indicators, especially in patients with obesity. We compared the serum 25-hydroxyvitamin D (25(OH)D) concentrations in children and adolescents who had obesity and hepatosteatosis with children and adolescents who had obesity without hepatosteatosis and investigated the relationship between serum 25(OH)D concentrations and severity of hepatosteatosis. We also aimed to assess the effect of vitamin D treatment after 6 months on hepatosteatosis and liver biochemistry. METHODS One hundred thirty-three patients with obesity (body mass index [BMI] >+2 standard deviations [SDs] for their age and gender) and vitamin D deficiency (serum 25(OH)D <12 ng/mL) were recruited. Anthropometric measurements, biochemical parameters (serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25(OH)D, glucose and insulin concentrations), and ultrasonographic findings of hepatosteatosis were recorded before and 6 months after Vitamin D treatment. χ2, Student's t tests, and multivariate analysis were performed. RESULTS Grade 1, 2, and 3 hepatosteatosis at baseline was present in 51 (38.4%), 43 (32.3%), and 10 (7.5%) subjects, respectively. Mean (± SD) serum 25(OH)D concentrations were significantly lower in those with hepatosteatosis (8.4 ± 2.4 ng/mL) compared with those without hepatosteatosis (9.9 ± 2.4 ng/mL, p < 0.005). Multivariable logistic regression analysis showed serum 25(OH)D concentration was the independent predictor for hepatosteatosis (p < 0.005), whereas age, sex, weight SD, BMI SD, and homeostasis model of assessment (HOMA)-insulin resistance (IR) were not (p > 0.05). There was no significant difference in BMI SD, HOMA-IR, and liver enzymes between subjects with and without hepatosteatosis (p > 0.05). Despite improvement in serum 25(OH)D concentrations at 6 months post-treatment (34.7 ± 10.6 ng/mL vs. 8.7 ± 2.4 ng/mL; p < 0.0001), there was no significant difference in the proportion of patients with different severity of hepatosteatosis as compared to before treatment (p = 0.88). CONCLUSION Serum 25(OH)D concentrations were lower in children and adolescents with obesity and hepatic steatosis as compared to those without hepatic steatosis, with an inverse association between the severity of hepatosteatosis and serum 25(OH)D concentrations. Vitamin D treatment in children and adolescents with obesity and hypovitaminosis D did not improve severity of hepatic steatosis on ultrasonography at 6 months.
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Affiliation(s)
- Hüseyin Anıl Korkmaz
- Division of Pediatric Endocrinology, Department of Pediatrics, Manisa City Hospital, Manisa, Turkey
- Division of Pediatric Endocrinology, Department of Pediatrics, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, Izmir, Turkey
| | - Ved Bhushan Arya
- Division of Pediatric Endocrinology, Variety Club Childre's Hospital, King's College Hospital NHS Foundation Trust, London, UK
- Faculty of Medicine and Life Science, King's College London, London, UK
| | - Vatan Barisik
- Department of Internal Medicine, Metropol Medical Center, Izmir, Turkey
| | | | - Fulya Coskunol
- Department of Pediatrics, Manisa City Hospital, Manisa, Turkey
| | - Serra Alci
- Department of Pediatrics, Umraniye Training and Research Hospital, Istanbul, Turkey
| | | | - Derun Torlak
- Department of Pediatrics, Acibadem University Hospital, Istanbul, Turkey
| | - Behzat Özkan
- Division of Pediatric Endocrinology, Department of Pediatrics, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, Izmir, Turkey
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Liu J, Song Y, Wang Y, Hong H. Vitamin D/vitamin D receptor pathway in non-alcoholic fatty liver disease. Expert Opin Ther Targets 2023; 27:1145-1157. [PMID: 37861098 DOI: 10.1080/14728222.2023.2274099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 10/18/2023] [Indexed: 10/21/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, but underlying mechanisms are not fully understood. In recent years, a growing body of evidence has emphasized the therapeutic role of vitamin D in NAFLD, but the specific mechanism remains to be investigated. AREAS COVERED This review summarized the roles of vitamin D/VDR (vitamin D receptor) pathway in different types of liver cells (such as hepatocytes, hepatic stellate cells, liver macrophages, T lymphocytes, and other hepatic immune cells) in case of NAFLD. Meanwhile, the effects of pathways in the gut-liver axis, adipose tissue-liver axis, and skeletal muscle-liver axis on the development of NAFLD were further reviewed. Relevant literature was searched on PubMed for the writing of this review. EXPERT OPINION The precise regulation of regional vitamin D/VDR signaling pathway based on cell-specific or tissue-specific function will help clarify the potential mechanism of vitamin D in NAFLD, which may provide new therapeutic targets to improve the safety and efficacy of vitamin D based drugs.
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Affiliation(s)
- Jingqi Liu
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Xiamen Institute of Geriatric Rehabilitation, Department of Geriatrics, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
| | - Yang Song
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
| | - Ye Wang
- Xiamen Institute of Geriatric Rehabilitation, Department of Geriatrics, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
| | - Huashan Hong
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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Kosmalski M, Frankowski R, Deska K, Różycka-Kosmalska M, Pietras T. Exploring the Impact of Nutrition on Non-Alcoholic Fatty Liver Disease Management: Unveiling the Roles of Various Foods, Food Components, and Compounds. Nutrients 2023; 15:2838. [PMID: 37447164 DOI: 10.3390/nu15132838] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/18/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
There is a need to introduce standardized treatment options for non-alcoholic fatty liver disease (NAFLD) due to its global prevalence and the complications of this disease. Many studies have revealed that food-derived substances may be beneficial in dealing with this disease. Therefore, this review aims to evaluate the recently published studies on the food-derived treatment options for NAFLD. A comprehensive search of the PubMed database using keywords such as "NAFLD", "nutrition", "food", "derived", "therapy", and "guidelines" yielded 219 relevant papers for our analysis, published from 2004 to 2023. The results show the significant benefits of food-derived treatment in NAFLD therapy, including improvements in liver histology, hepatic fat amounts, anthropometric measures, lipid profile, and other metabolic measures. The availability of the substances discussed makes them a significant adjuvant in the treatment of this disease. The usefulness of Viusid as additional therapy to diet and physical activity should be emphasized due to improvements in liver histology; however, many other substances lead to a decrease in liver fat amounts including, e.g., berberine or omega-3 fatty acids. In addition, the synbiotic Protexin seems to be useful in terms of NAFLD treatment, especially because it is effective in both obese and lean subjects. Based on the latest research results, we suggest revising the therapeutic recommendations for patients suffering from NAFLD.
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Affiliation(s)
- Marcin Kosmalski
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | - Rafał Frankowski
- Students' Research Club, Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | - Kacper Deska
- Students' Research Club, Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | | | - Tadeusz Pietras
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
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Khan MS, Kim HS, Kim R, Yoon SH, Kim SG. Dysregulated Liver Metabolism and Polycystic Ovarian Syndrome. Int J Mol Sci 2023; 24:ijms24087454. [PMID: 37108615 PMCID: PMC10138914 DOI: 10.3390/ijms24087454] [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: 03/09/2023] [Revised: 04/10/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
A significant fraction of couples around the world suffer from polycystic ovarian syndrome (PCOS), a disease defined by the characteristics of enhanced androgen synthesis in ovarian theca cells, hyperandrogenemia, and ovarian dysfunction in women. Most of the clinically observable symptoms and altered blood biomarker levels in the patients indicate metabolic dysregulation and adaptive changes as the key underlying mechanisms. Since the liver is the metabolic hub of the body and is involved in steroid-hormonal detoxification, pathological changes in the liver may contribute to female endocrine disruption, potentially through the liver-to-ovary axis. Of particular interest are hyperglycemic challenges and the consequent changes in liver-secretory protein(s) and insulin sensitivity affecting the maturation of ovarian follicles, potentially leading to female infertility. The purpose of this review is to provide insight into emerging metabolic mechanisms underlying PCOS as the primary culprit, which promote its incidence and aggravation. Additionally, this review aims to summarize medications and new potential therapeutic approaches for the disease.
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Affiliation(s)
- Muhammad Sohaib Khan
- College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang-si 10326, Republic of Korea
| | - Hee-Sun Kim
- Department of Obstetrics and Gynecology, Dongguk University Ilsan Medical Center, Goyang-si 10326, Republic of Korea
| | - Ranhee Kim
- Department of Obstetrics and Gynecology, Dongguk University Ilsan Medical Center, Goyang-si 10326, Republic of Korea
| | - Sang Ho Yoon
- Department of Obstetrics and Gynecology, Dongguk University Ilsan Medical Center, Goyang-si 10326, Republic of Korea
- Department of Obstetrics and Gynecology, Dongguk University Medical College, Goyang-si 10326, Republic of Korea
| | - Sang Geon Kim
- College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang-si 10326, Republic of Korea
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27
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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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Rizzo M, Colletti A, Penson PE, Katsiki N, Mikhailidis DP, Toth PP, Gouni-Berthold I, Mancini J, Marais D, Moriarty P, Ruscica M, Sahebkar A, Vinereanu D, Cicero AFG, Banach M, Al-Khnifsawi M, Alnouri F, Amar F, Atanasov AG, Bajraktari G, Banach M, Gouni-Berthold I, Bhaskar S, Bielecka-Dąbrowa A, Bjelakovic B, Bruckert E, Bytyçi I, Cafferata A, Ceska R, Cicero AF, Chlebus K, Collet X, Daccord M, Descamps O, Djuric D, Durst R, Ezhov MV, Fras Z, Gaita D, Gouni-Berthold I, Hernandez AV, Jones SR, Jozwiak J, Kakauridze N, Kallel A, Katsiki N, Khera A, Kostner K, Kubilius R, Latkovskis G, John Mancini G, David Marais A, Martin SS, Martinez JA, Mazidi M, Mikhailidis DP, Mirrakhimov E, Miserez AR, Mitchenko O, Mitkovskaya NP, Moriarty PM, Mohammad Nabavi S, Nair D, Panagiotakos DB, Paragh G, Pella D, Penson PE, Petrulioniene Z, Pirro M, Postadzhiyan A, Puri R, Reda A, Reiner Ž, Radenkovic D, Rakowski M, Riadh J, Richter D, Rizzo M, Ruscica M, Sahebkar A, Serban MC, Shehab AM, Shek AB, Sirtori CR, Stefanutti C, Tomasik T, Toth PP, Viigimaa M, Valdivielso P, Vinereanu D, Vohnout B, von Haehling S, Vrablik M, Wong ND, Yeh HI, Zhisheng J, Zirlik A. Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP). Pharmacol Res 2023; 189:106679. [PMID: 36764041 DOI: 10.1016/j.phrs.2023.106679] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 02/11/2023]
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.
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Affiliation(s)
- Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Via del Vespro 141, 90127 Palermo, Italy.
| | - Alessandro Colletti
- Department of Science and Drug Technology, University of Turin, Turin, Italy
| | - Peter E Penson
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece; School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, Medical School, University College London (UCL), London, UK
| | - Peter P Toth
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, IL, USA
| | - Ioanna Gouni-Berthold
- Department of Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany
| | - John Mancini
- Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - David Marais
- Chemical Pathology Division of the Department of Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa
| | - Patrick Moriarty
- Division of Clinical Pharmacology, Division of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Dragos Vinereanu
- Cardiology Department, University and Emergency Hospital, Bucharest, Romania, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
| | - Arrigo Francesco Giuseppe Cicero
- Hypertension and Cardiovascular disease risk research center, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy; IRCCS Policlinico S. Orsola-Malpighi, Bologna, Italy
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.
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Wang LL, Zhang PH, Yan HH. Functional foods and dietary supplements in the management of non-alcoholic fatty liver disease: A systematic review and meta-analysis. Front Nutr 2023; 10:1014010. [PMID: 36866059 PMCID: PMC9971819 DOI: 10.3389/fnut.2023.1014010] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 01/30/2023] [Indexed: 02/16/2023] Open
Abstract
Objective In this systematic review and meta-analysis, we aimed to clarify the overall effects of functional foods and dietary supplements in non-alcoholic fatty liver disease (NAFLD) patients. Methods Randomized controlled trials (RCTs) published in PubMed, ISI Web of Science, Cochrane library, and Embase from January 1, 2000 to January 31, 2022 were systematically searched to assess the effects of functional foods and dietary supplements in patients with NAFLD. The primary outcomes were liver-related measures, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic fibrosis and steatosis, while the secondary outcomes included body mass index (BMI), waist circumference (WC), triacylglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). These indexes were all continuous variables, so the mean difference (MD) was used for calculating the effect size. Random-effects or fixed-effects models were used to estimate the mean difference (MD). The risk of bias in all studies was assessed with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. Results Twenty-nine articles investigating functional foods and dietary supplements [antioxidants (phytonutrients and coenzyme Q10) = 18, probiotics/symbiotic/prebiotic = 6, fatty acids = 3, vitamin D = 1, and whole grain = 1] met the eligibility criteria. Our results showed that antioxidants could significantly reduce WC (MD: -1.28 cm; 95% CI: -1.58, -0.99, P < 0.05), ALT (MD: -7.65 IU/L; 95% CI: -11.14, -4.16, P < 0.001), AST (MD: -4.26 IU/L; 95% CI: -5.76, -2.76, P < 0.001), and LDL-C (MD: -0.24 mg/dL; 95% CI: -0.46, -0.02, P < 0.05) increased in patients with NAFLD but had no effect on BMI, TG, and TC. Probiotic/symbiotic/prebiotic supplementation could decrease BMI (MD: -0.57 kg/m2; 95% CI: -0.72, -0.42, P < 0.05), ALT (MD: -3.96 IU/L; 95% CI: -5.24, -2.69, P < 0.001), and AST (MD: -2.76; 95% CI: -3.97, -1.56, P < 0.0001) levels but did not have beneficial effects on serum lipid levels compared to the control group. Moreover, the efficacy of fatty acids for treating NAFLD was full of discrepancies. Additionally, vitamin D had no significant effect on BMI, liver transaminase, and serum lipids, while whole grain could reduce ALT and AST but did not affect serum lipid levels. Conclusion The current study suggests that antioxidant and probiotic/symbiotic/prebiotic supplements may be a promising regimen for NAFLD patients. However, the usage of fatty acids, vitamin D, and whole grain in clinical treatment is uncertain. Further exploration of the efficacy ranks of functional foods and dietary supplements is needed to provide a reliable basis for clinical application. Systematic review registration https://www.crd.york.ac.uk/prospero, identifier: CRD42022351763.
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Affiliation(s)
- Lei-lei Wang
- Department of Clinical Nutrition, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Pian-hong Zhang
- Department of Clinical Nutrition, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Hui-hui Yan
- Department of Gastroenterology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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Yuan S, Larsson SC. Inverse Association Between Serum 25-Hydroxyvitamin D and Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2023; 21:398-405.e4. [PMID: 35101633 DOI: 10.1016/j.cgh.2022.01.021] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/12/2022] [Accepted: 01/17/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND & AIMS Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
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Affiliation(s)
- Shuai Yuan
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Susanna C Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
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Farahmand MA, Daneshzad E, Fung TT, Zahidi F, Muhammadi M, Bellissimo N, Azadbakht L. What is the impact of vitamin D supplementation on glycemic control in people with type-2 diabetes: a systematic review and meta-analysis of randomized controlled trails. BMC Endocr Disord 2023; 23:15. [PMID: 36647067 PMCID: PMC9841647 DOI: 10.1186/s12902-022-01209-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 11/10/2022] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND There is conflicting evidence on the effect of vitamin D on glycemic control. Therefore, in the current meta-analyses, we aimed to assess the effect of vitamin D supplementation on the glycemic control of type 2 diabetes (T2D) patients. METHODS We conducted a comprehensive search in electronic databases including; PubMed/Medline, Web of Science, Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and NIH's Clinical Trials Registry, from the inception of each database up to January first, 2021. RESULTS A total of 46 randomized controlled trials (RCTs) consisting of 2164 intervention subjects and 2149 placebo controls were included in this meta-analysis. Pooled analyses for HbA1c showed a significant change between the intervention and placebo group, the weighted mean difference (WMD)(95% confidence interval(CI)) was -0.20%(-0.29, -0.11) with P < 0.001. Analyses for assessing changes in FPG found a significant reduction in the intervention group after vitamin D supplementation, the WMD (95%CI) was -5.02 mg/dl (-6.75,-3.28) with P < 0.001. The result of pooled analyses for HOMA-IR revealed a significant change between the intervention and control group, the WMD (95%CI) was -0.42(-0.76, -0.07) with P = 0.019. The subgroup analyses showed the most efficacy in a higher dose and short intervention period and in subjects with deficient vitamin D status. CONCLUSION Vitamin D supplementation might be beneficial for the reduction of FPG, HbA1c, and HOMA-IR in type 2 diabetes patients with deficient vitamin D status. This effect was especially prominent when vitamin D was given in large doses and for a short period of time albeit with substantial heterogeneity between studies and a probability of publication bias.
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Affiliation(s)
- Mohammad Ashraf Farahmand
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), PO BOX: 1416643931, Tehran, Iran
- Public Health Faculty, Kabul University of Medical Science (KUMS), Kabul, Afghanistan
| | - Elnaz Daneshzad
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Teresa T Fung
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, USA
- Department of Nutrition, Simmons University, Boston, MA, USA
| | - Fawzia Zahidi
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), PO BOX: 1416643931, Tehran, Iran
| | - Maryam Muhammadi
- Critical Nursing Care Department, Kabul University of Medical Science (KUMS), Kabul, Afghanistan
| | - Nick Bellissimo
- School of Nutrition, Toronto Metropolitan University, Toronto, ON, Canada
| | - Leila Azadbakht
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), PO BOX: 1416643931, Tehran, Iran.
- Diabetes Research Centre, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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Zhang JJ, Yu HC, Li Y, Zhang YB, Geng TT, Lu Q, Liao YF, Guo KQ, Du L, Ruan HL, Yang K, Liu G, Pan A. Association between serum 25-hydroxy vitamin D concentrations and mortality among individuals with metabolic dysfunction-associated fatty liver disease: a prospective cohort study. Am J Clin Nutr 2022; 116:1409-1417. [PMID: 36107812 DOI: 10.1093/ajcn/nqac260] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/26/2022] [Accepted: 09/13/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The association between serum 25-hydroxy vitamin D (25(OH)D) concentrations and mortality remains unclear among patients with metabolic dysfunction-associated fatty liver disease (MAFLD) or non-alcoholic fatty liver disease (NAFLD). OBJECTIVES To evaluate the association between serum 25(OH)D concentrations and mortality among individuals with MAFLD/NAFLD. METHODS The study included 4651 individuals with fatty liver disease (FLD) (3964 had MAFLD and 3968 had NAFLD) from the Third National Health and Nutrition Examination Survey. Fatty liver disease was identified by ultrasonographic detection of hepatic steatosis. Mortality was ascertained by linkage to the National Death Index up to 31 December 2019. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment of potential confounders. RESULTS Of 4651 individuals with FLD, 3427 individuals (69.7%) had both MAFLD and NAFLD. During median follow-ups of 25.8 and 26.1 years, we identified 1809 and 1665 deaths among 3964 participants with MAFLD and 3968 participants with NAFLD, respectively. Compared with participants with serum 25(OH)D concentrations ≤30.0 nmol/L, the multivariable-adjusted HR and 95% CI of all-cause mortality were 0.62 (0.43, 0.89) for participants with MAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.001), and 0.63 (0.42, 0.95) for participants with NAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.002). A nonlinearly inverse association was observed between serum 25(OH)D concentrations and all-cause mortality among participants with MAFLD (Poverall <0.001; Pnonlinear = 0.003) or NAFLD (Poverall <0.001; Pnonlinear = 0.009), with a threshold effect at around 50.0 nmol/L. The inverse association was stronger among participants with MAFLD aged <60 years (P-interaction = 0.001). CONCLUSIONS This study suggested a nonlinearly inverse association between serum 25(OH)D concentrations and all-cause mortality among patients with MAFLD/NAFLD, with a threshold effect at around 50.0 nmol/L of serum 25(OH)D.
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Affiliation(s)
- Ji-Juan Zhang
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Han-Cheng Yu
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yue Li
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yan-Bo Zhang
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Ting-Ting Geng
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Qi Lu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yun-Fei Liao
- Department of Endocrinology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Kun-Quan Guo
- Department of Endocrinology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China
| | - Liang Du
- Department of Endocrinology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China
| | - Hua-Ling Ruan
- Department of Endocrinology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China
| | - Kun Yang
- Department of Endocrinology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China
| | - Gang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - An Pan
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
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Pop TL, Sîrbe C, Benţa G, Mititelu A, Grama A. The Role of Vitamin D and Vitamin D Binding Protein in Chronic Liver Diseases. Int J Mol Sci 2022; 23:ijms231810705. [PMID: 36142636 PMCID: PMC9503777 DOI: 10.3390/ijms231810705] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/09/2022] [Accepted: 09/12/2022] [Indexed: 11/24/2022] Open
Abstract
Vitamin D (calciferol) is a fat-soluble vitamin that has a significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of vitamin D are cholecalciferol (vitamin D3, or VD3) and ergocalciferol (vitamin D2, or VD2). Besides its major role in maintaining an adequate level of calcium and phosphate concentrations, vitamin D is involved in cell growth and differentiation and immune function. Recently, the association between vitamin D deficiency and the progression of fibrosis in chronic liver disease (CLD) was confirmed, given the hepatic activation process and high prevalence of vitamin D deficiency in these diseases. There are reports of vitamin D deficiency in CLD regardless of the etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty liver disease, primary biliary cirrhosis, or autoimmune hepatitis). Vitamin D binding protein (VDBP) is synthesized by the liver and has the role of binding and transporting vitamin D and its metabolites to the target organs. VDBP also plays an important role in inflammatory response secondary to tissue damage, being involved in the degradation of actin. As intense research during the last decades revealed the possible role of vitamin D in liver diseases, a deeper understanding of the vitamin D, vitamin D receptors (VDRs), and VDBP involvement in liver inflammation and fibrogenesis could represent the basis for the development of new strategies for diagnosis, prognosis, and treatment of liver diseases. This narrative review presents an overview of the evidence of the role of vitamin D and VDBP in CLD, both at the experimental and clinical levels.
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Affiliation(s)
- Tudor Lucian Pop
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Claudia Sîrbe
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- Correspondence:
| | - Gabriel Benţa
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Alexandra Mititelu
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Alina Grama
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
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Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – April 2022 – AWMF-Registernummer: 021–025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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36
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Diaconu CT, Guja C. Nonalcoholic Fatty Liver Disease and Its Complex Relation with Type 2 Diabetes Mellitus—From Prevalence to Diagnostic Approach and Treatment Strategies. J Clin Med 2022; 11:jcm11175144. [PMID: 36079070 PMCID: PMC9456683 DOI: 10.3390/jcm11175144] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 08/28/2022] [Accepted: 08/30/2022] [Indexed: 11/30/2022] Open
Abstract
Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Mellitus (T2DM) are increasing rapidly worldwide, reaching epidemic proportions. Their association, based on common metabolic risk factors (obesity, insulin resistance (IR), unhealthy lifestyle), brings an additional risk of both hepatic and cardiovascular (CV) adverse clinical outcomes. The terminology of “NAFLD” is stigmatizing to some but not all patients, and a more practical one should be announced soon. Medical strategies can address both diseases simultaneously, as they have crossing pathophysiological mechanisms, mainly IR. Strategies vary from lifestyle intervention and pharmacological options, as more molecules designated for T2DM treatment may be helpful in NAFLD, to surgical procedures. This review focuses on the coexistence of NAFLD and T2DM, pointing out the utility of the appropriate terminology, its prevalence, and mortality rates among the diabetic population. Briefly, we have discussed the main pathophysiological mechanisms and the risk stratification algorithm for the development of NAFLD and nonalcoholic steatohepatitis (NASH) as well as the tools for evaluation of fibrosis. Finally, we have focused on the current therapeutic options for the treatment of NAFLD associated with T2DM.
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Affiliation(s)
- Cosmina-Theodora Diaconu
- Department of Diabetes, Nutrition and Metabolic Diseases, “Prof. Dr. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 030167 Bucharest, Romania
- Doctoral School of “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu 37, 020021 Bucharest, Romania
- Correspondence:
| | - Cristian Guja
- Department of Diabetes, Nutrition and Metabolic Diseases, “Prof. Dr. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 030167 Bucharest, Romania
- Department of Diabetes, Nutrition and Metabolic Diseases, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
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Aggeletopoulou I, Thomopoulos K, Mouzaki A, Triantos C. Vitamin D–VDR Novel Anti-Inflammatory Molecules—New Insights into Their Effects on Liver Diseases. Int J Mol Sci 2022; 23:ijms23158465. [PMID: 35955597 PMCID: PMC9369388 DOI: 10.3390/ijms23158465] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/26/2022] [Accepted: 07/28/2022] [Indexed: 02/05/2023] Open
Abstract
There is consistent evidence that vitamin D deficiency is strongly associated with liver dysfunction, disease severity, and poor prognosis in patients with liver disease. Vitamin D and its receptor (VDR) contribute to the regulation of innate and adaptive immune responses. The presence of genetic variants of vitamin D- and VDR-associated genes has been associated with liver disease progression. In our recent work, we summarized the progress in understanding the molecular mechanisms involved in vitamin D–VDR signaling and discussed the functional significance of VDR signaling in specific cell populations in liver disease. The current review focuses on the complex interaction between immune and liver cells in the maintenance of liver homeostasis and the development of liver injury, the interplay of vitamin D and VDR in the development and outcome of liver disease, the role of vitamin D- and VDR-associated genetic variants in modulating the occurrence and severity of liver disease, and the therapeutic value of vitamin D supplementation in various liver diseases. The association of the vitamin D–VDR complex with liver dysfunction shows great potential for clinical application and supports its use as a prognostic index and diagnostic tool.
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Affiliation(s)
- Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, GR-26504 Patras, Greece; (I.A.); (C.T.)
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, GR-26504 Patras, Greece;
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, GR-26504 Patras, Greece; (I.A.); (C.T.)
- Correspondence:
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, GR-26504 Patras, Greece;
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, GR-26504 Patras, Greece; (I.A.); (C.T.)
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Kim Y, Chang Y, Ryu S, Cho IY, Kwon MJ, Sohn W, Kim MK, Wild SH, Byrne CD. Resolution of, and Risk of Incident Non-alcoholic Fatty Liver Disease With Changes in Serum 25-hydroxy Vitamin D Status. J Clin Endocrinol Metab 2022; 107:e3437-e3447. [PMID: 35460237 DOI: 10.1210/clinem/dgac255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Indexed: 02/06/2023]
Abstract
CONTEXT A protective or causative role of vitamin D status on the risk of nonalcoholic fatty liver disease (NAFLD) remains inconclusive. OBJECTIVE To evaluate the association between changes in serum 25-hydroxyvitamin D [25(OH)D] status during follow-up and the risk of incident NAFLD and resolution of preexisting NAFLD. DESIGN A retrospective cohort study. SETTING Kangbuk Samsung Health Study based on routine health screening examinations. PARTICIPANTS Korean adults (mean age, 36.8 years; range, 18-96 years) who underwent comprehensive health examinations including assessment of serum 25(OH)D levels. MAIN OUTCOME MEASURES The main outcomes were (1) incidence and (2) resolution of NAFLD assessed by liver ultrasound. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% CIs for outcomes according to serum 25(OH)D levels. RESULTS Among 139 599 participants without NAFLD at baseline, 27 531 developed NAFLD during follow-up. Serum 25(OH)D levels were significantly and inversely associated with NAFLD development. Among 48 702 participants with NAFLD at baseline, 13 449 showed NAFLD resolution. Multivariable-adjusted HR (95% CI) for NAFLD resolution comparing 25(OH)D 10 to <20, 20 to <30, and ≥30 ng/mL to <10 ng/mL were 1.09 (1.03-1.15), 1.13 (1.06-1.21), and 1.21 (1.09-1.35), respectively. Additionally, an increase in 25(OH)D levels between baseline and the subsequent visit (median, 1.8 years) was associated with decreased NAFLD incidence, while persistently adequate 25(OH)D levels over time was associated with decreased incidence and increased resolution of NAFLD. CONCLUSIONS Maintaining adequate serum 25(OH)D concentrations may be beneficial for both prevention as well as resolution of NAFLD.
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Affiliation(s)
- Yejin Kim
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - In Young Cho
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Min-Jung Kwon
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won Sohn
- Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea
| | - Mi Kyung Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sarah H Wild
- Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- National Institute for Health and Care Research Southampton Biomedical Research Center, University Hospital Southampton, Southampton, UK
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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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Gázquez A, Sánchez-Campillo M, Barranco A, Rueda R, Chan JP, Kuchan MJ, Larqué E. Calcifediol During Pregnancy Improves Maternal and Fetal Availability of Vitamin D Compared to Vitamin D3 in Rats and Modifies Fetal Metabolism. Front Nutr 2022; 9:871632. [PMID: 35495908 PMCID: PMC9040672 DOI: 10.3389/fnut.2022.871632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 03/14/2022] [Indexed: 11/26/2022] Open
Abstract
The fetus depends on the transplacental transfer of vitamin D. Calcifediol (25-OH-D3) is the vitamin D metabolite that crosses the placenta. Previously, oral 25-OH-D3 improved serum 25-OH-D3 compared to vitamin D3 in non-pregnant subjects, although no studies are available in pregnant women. We evaluated the availability of oral 25-OH-D3 compared to vitamin D3 during pregnancy, as well as, their levels in the fetus and effect on metabolism-related proteins. Twenty female rats per group were fed with 25 μg/kg of diet of vitamin D3 (1,000 UI vitamin D/kg diet) or with 25 μg/kg diet of 25-OH-D3. We analyzed 25-OH-D3 levels in maternal and fetal plasma; protein levels of vitamin D receptor (VDR), fatty acid translocase (FAT), and scavenger-receptor class B type-1 (SR-B1) in both maternal liver and placenta; and protein levels of VDR and Glutamate decarboxylase (GAD67) in fetal brain. 25-OH-D3 doubled the concentration of 25-OH-D3 in both maternal and fetal plasma compared to vitamin D3. In addition, maternal liver VDR, FAT, and SR-BI increased significantly in the 25-OH-D3 group, but no changes were found in the placenta. Interestingly, 25-OH-D3 decreased GAD67 expression in the fetal brain and it also tended to decrease VDR (P = 0.086). In conclusion, 25-OH-D3 provided better vitamin D availability for both mother and fetus when administered during pregnancy compared to vitamin D3. No adverse effects on pregnancy outcomes were observed. The effects of 25-OH-D3 on the expression of VDR and GAD67 in fetal brain require further investigation.
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Affiliation(s)
- Antonio Gázquez
- Department of Animal Physiology, School of Biology, University of Murcia, Murcia, Spain
| | | | - Alejandro Barranco
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain
| | - Ricardo Rueda
- Research and Development Department, Abbott Nutrition SL, Granada, Spain
| | - Jia P. Chan
- Research and Development Department, Abbott Nutrition SL, Singapore, Singapore
| | - Matthew J. Kuchan
- Research and Development Department, Abbott Nutrition SL, Columbus, OH, United States
| | - Elvira Larqué
- Department of Animal Physiology, School of Biology, University of Murcia, Murcia, Spain
- *Correspondence: Elvira Larqué,
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Von-Hafe M, Borges-Canha M, Vale C, Leite AR, Sérgio Neves J, Carvalho D, Leite-Moreira A. Nonalcoholic Fatty Liver Disease and Endocrine Axes-A Scoping Review. Metabolites 2022; 12:298. [PMID: 35448486 PMCID: PMC9026925 DOI: 10.3390/metabo12040298] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/20/2022] [Accepted: 03/27/2022] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD often occurs associated with endocrinopathies. Evidence suggests that endocrine dysfunction may play an important role in NAFLD development, progression, and severity. Our work aimed to explore and summarize the crosstalk between the liver and different endocrine organs, their hormones, and dysfunctions. For instance, our results show that hyperprolactinemia, hypercortisolemia, and polycystic ovary syndrome seem to worsen NAFLD's pathway. Hypothyroidism and low growth hormone levels also may contribute to NAFLD's progression, and a bidirectional association between hypercortisolism and hypogonadism and the NAFLD pathway looks likely, given the current evidence. Therefore, we concluded that it appears likely that there is a link between several endocrine disorders and NAFLD other than the typically known type 2 diabetes mellitus and metabolic syndrome (MS). Nevertheless, there is controversial and insufficient evidence in this area of knowledge.
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Affiliation(s)
- Madalena Von-Hafe
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
| | - Marta Borges-Canha
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
- Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
| | - Catarina Vale
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
| | - Ana Rita Leite
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
| | - João Sérgio Neves
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
- Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
| | - Davide Carvalho
- Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
- Investigação e Inovação em Saúde (i3s), Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal
| | - Adelino Leite-Moreira
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; (M.V.-H.); (C.V.); (A.R.L.); (J.S.N.); (A.L.-M.)
- Serviço de Cirurgia Cardiotorácica do Centro Hospitalar Universitário de São João, 4200-319 Porto, Portugal
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Zhang B. EFFECT OF EXERCISE ON INSULIN RESISTANCE IN OBESE TYPE 2 DIABETES PATIENTS. REV BRAS MED ESPORTE 2022. [DOI: 10.1590/1517-8692202228012021_0434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
ABSTRACT Introduction: Type 2 diabetes mellitus (T2DM), also known as non-insulin-dependent diabetes mellitus (NIDDM), accounts for more than 90% of the total number of diabetes mellitus cases and often occurs in middle-aged and elderly people. Objective: To investigate the effect of exercise intervention on insulin resistance in obese type 2 diabetes patients. Methods: Eighty-six obese diabetic patients were screened as experimental subjects in physical examinations and randomly divided into observation and control groups. Visceral fat volume, fasting blood glucose, and fasting insulin of all subjects were measured before and after completion of the 6-month experimental implementation. The insulin resistance was calculated for both groups and the values for each indicator were compared statistically between groups. Results: Control of body weight, body mass index, blood glucose, blood lipids and insulin resistance index were better in the observation group than in the control group, and the difference was statistically significant (P < 0.05). Conclusions: Basal intervention with quantitative exercise can significantly improve insulin resistance in obese type 2 diabetes patients and the effect is better than treatment with diet and conventional exercise. Level of evidence II; Therapeutic studies - investigation of treatment results.
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Guo XF, Wang C, Yang T, Ma WJ, Zhai J, Zhao T, Xu TC, Li J, Liu H, Sinclair AJ, Li D. The effects of fish oil plus vitamin D3 intervention on non-alcoholic fatty liver disease: a randomized controlled trial. Eur J Nutr 2022; 61:1931-1942. [DOI: 10.1007/s00394-021-02772-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 12/03/2021] [Indexed: 01/10/2023]
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Xing Y, Cheng T, Zhou F, Ma H. The Association Between Vitamin D and Type 2 Diabetes Mellitus Complicated with Non-Alcoholic Fatty Liver Disease: An Observational Cross-Sectional Study. Diabetes Metab Syndr Obes 2022; 15:269-280. [PMID: 35140487 PMCID: PMC8819170 DOI: 10.2147/dmso.s348870] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/14/2022] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVE To investigate the association between vitamin D deficiency and NAFLD risk in patients with type 2 diabetes mellitus (T2DM). METHODS Overall, 434 patients with T2DM admitted to Hebei General Hospital from January 2019 to December 2019 were selected as the study subjects. According to abdominal ultrasound findings, patients were divided into the NAFLD group and the non-NAFLD group. Participants were divided into two study groups according to the 25-hydroxyvitamin D [25(OH)D] level. 25(OH)D deficiency was defined if 25(OH)D vitamin levels were <20 ng/mL. Chi-square test and one-way analysis of variance were used to compare groups. The relationship between 25(OH)D and NAFLD risk was analyzed using correlation and regression analyses. Furthermore, subgroup analyses were performed to verify the robustness of the results. RESULTS The 25(OH)D level in patients with T2DM complicated by NAFLD was significantly lower than in patients with T2DM only. Vitamin D deficiency was highly prevalent among T2DM patients with NAFLD. This study suggested that vitamin D deficiency was an independent factor for developing NAFLD in patients with T2DM. T2DM patients with vitamin D deficiency had 2.045 times higher risk of developing NAFLD than those without vitamin D deficiency. Vitamin D deficiency was associated with high NAFLD preference in T2DM patients with BMI >23kg/m2, but not those with BMI ≤23kg/m2. The significant correlation between vitamin D deficiency and NAFLD was found in participants with BMI >23kg/m2, age ≤65 years, without hypertension, TG <1.7mmol/l, HDL ≥1 mmol/l in men, ≥1.3 mmol/l in women, HBA1C ≤7%, or females. CONCLUSION This study suggests that T2DM people with BMI >23kg/m2 were more susceptible to NAFLD by vitamin D deficiency and that it is necessary to maintain optimal serum vitamin D levels in this population.
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Affiliation(s)
- Yuling Xing
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China
- Graduate School of Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China
| | - Tiantian Cheng
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China
- Department of Internal Medicine, School of Clinical Medicine, North China University of Science and Technology, Tangshan, 063210, Hebei, People’s Republic of China
| | - Fei Zhou
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China
- Graduate School of Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China
| | - Huijuan Ma
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China
- Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital Shijiazhuang, Hebei, 050051, People’s Republic of China
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China
- Correspondence: Huijuan Ma, Email
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Abstract
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease, worldwide. The molecular pathogenesis of NAFLD is complex, involving numerous signalling molecules including microRNAs (miRNAs). Dysregulation of miRNA expression is associated with hepatic inflammation, fibrosis and hepatocellular carcinoma. Although miRNAs are also critical to the cellular response to vitamin D, mediating regulation of the vitamin D receptor (VDR) and vitamin D’s anticancer effects, a role for vitamin D regulated miRNAs in NAFLD pathogenesis has been relatively unexplored. Therefore, this review aimed to critically assess the evidence for a potential subset of miRNAs that are both dysregulated in NAFLD and modulated by vitamin D. Comprehensive review of 89 human studies identified 25 miRNAs found dysregulated in more than one NAFLD study. In contrast, only 17 studies, including a protocol for a trial in NAFLD, had examined miRNAs in relation to vitamin D status, response to supplementation, or vitamin D in the context of the liver. This paper summarises these data and reviews the biological roles of six miRNAs (miR-21, miR-30, miR-34, miR-122, miR-146, miR-200) found dysregulated in multiple independent NAFLD studies. While modulation of miRNAs by vitamin D has been understudied, integrating the data suggests seven vitamin D modulated miRNAs (miR-27, miR-125, miR-155, miR-192, miR-223, miR-375, miR-378) potentially relevant to NAFLD pathogenesis. Our summary tables provide a significant resource to underpin future hypothesis-driven research, and we conclude that the measurement of serum and hepatic miRNAs in response to vitamin D supplementation in larger trials is warranted.
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Licata A, Zerbo M, Como S, Cammilleri M, Soresi M, Montalto G, Giannitrapani L. The Role of Vitamin Deficiency in Liver Disease: To Supplement or Not Supplement? Nutrients 2021; 13:nu13114014. [PMID: 34836267 PMCID: PMC8620546 DOI: 10.3390/nu13114014] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/28/2021] [Accepted: 11/02/2021] [Indexed: 12/12/2022] Open
Abstract
Over the past few years, growing interest has been shown for the impact of dietary requirements and nutritional factors on chronic diseases. As a result, nutritional programs have been reinforced by public health policies. The precise role of micronutrients in chronic liver disease is currently receiving particular attention since abnormalities in vitamin levels are often detected. At present, treatment programs are focused on correcting vitamin deficiencies, which are frequently correlated to higher rates of comorbidities with poor outcomes. The literature reviewed here indicates that liver diseases are often related to vitamin disorders, due to both liver impairment and abnormal intake. More specific knowledge about the role of vitamins in liver disease is currently emerging from various results and recent evidence. The most significant benefits in this area may be observed when improved vitamin intake is combined with a pharmacological treatment that may also affect the progression of the liver disease, especially in the case of liver tumors. However, further studies are needed.
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Affiliation(s)
- Anna Licata
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
- Correspondence: ; Tel.: +39-091-655-2280; Fax: +39-091-655-2156
| | - Maddalena Zerbo
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Silvia Como
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Marcella Cammilleri
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Maurizio Soresi
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Giuseppe Montalto
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Lydia Giannitrapani
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
- Institute for Biochemical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy
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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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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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Park E, Park EY. Inverse Association between Serum 25-hydroxyvitamin D Levels and Risk of Suspected Non-Alcoholic Fatty Liver Disease in Obese Population. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:8682. [PMID: 34444431 PMCID: PMC8394297 DOI: 10.3390/ijerph18168682] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/12/2021] [Accepted: 08/15/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Worldwide, vitamin D deficiency is a public health issue and the prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) are rapidly increasing. There are a limited number of studies assessing the association between serum levels of 25-hydroxyvitamin D (25(OH)D) and NAFLD risk in obese population. OBJECTIVE We evaluated the associations between serum 25(OH)D levels and risk of suspected NAFLD after stratification by obesity using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2014. METHODS This study included 25,755 subjects without significant alcohol consumption for the serum alanine aminotransferase (ALT) and hepatic steatosis index (HSI) analyses (8922 subjects for the serum gamma-glutamyl transferase (GGT) and fatty liver index (FLI) analyses), based on a cross-sectional study design. Serum 25(OH)D levels were measured using a Gamma counter with radioimmunoassay. A survey logistic regression model was applied to estimate ORs and 95% CIs. Restricted cubic smoothing splines were applied to evaluate nonlinear associations. RESULTS The risk of suspected NAFLD was reduced per unit of natural log-transformed serum 25(OH)D concentration in obese individuals (OR [95% (CI)]; for ALT, 0.80 [0.67, 0.96]; for GGT, 0.70 [0.49, 0.99; for FLI, 0.68 [0.47, 1.01]; for HSI, 0.70 [0.56, 0.87]). The ORs [95% CI] of suspected NAFLD changed across the quartiles: for serum ALT, from 1.02 [0.85, 1.23] to 0.72 [0.59, 0.87]; for serum GGT, from 0.79 [0.56, 1.13] to 0.64 [0.44, 0.92]; for FLI, from 0.98 [0.67, 1.44] to 0.70 [0.48, 1.02]; and for HSI, from 0.91 [0.73, 1.14] to 0.65 [0.52, 0.81] with dose-response relationships (all p for trend < 0.01). CONCLUSIONS This study suggests that vitamin D sufficiency for public health should be emphasized in order to prevent adverse health effects in obese populations.
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Affiliation(s)
- Eunjung Park
- Department of Public Health Sciences, Graduate Scholl of Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea;
| | - Eun Young Park
- Division of Cancer Prevention, National Cancer Control Institute, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Korea
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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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