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Emam RF, Soliman AF, Darweesh SK, AbdElmagid RA, Ibrahim OM, Mohamed DM. Steatosis regression assessed by cap after Vitamin 'D' supplementation in NAFLD patients with Vitamin 'D' deficiency. Eur J Gastroenterol Hepatol 2024; 36:101-106. [PMID: 37942743 DOI: 10.1097/meg.0000000000002653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and previous studies suggested a relationship between vitamin D deficiency and NAFLD. It is suggested that vitamin D supplementation may have significant beneficial effect on liver biochemistry and histology. OBJECTIVE This study aims to assess the degree of possible steatosis regression using controlled attenuation parameter (CAP) in NAFLD patients with vitamin D deficiency after vitamin D supplementation and evaluating its effect on lipid profile and transaminases. PATIENTS AND METHODS This study was conducted on 100 NAFLD patients with vitamin D deficiency. They received 10000 IU/week of vitamin D orally for 3 months. CAP was used to assess hepatic steatosis and fibrosis before/after intervention. Transaminases, lipid profile, and vitamin D levels were evaluated before/after treatment. RESULTS Serum AST, ALT, cholesterol, TG, LDL and HDL showed a significant reduction posttreatment in patients with both normal and elevated baseline levels ( P < 0.001). The posttreatment mean CAP showed a significant reduction (300.44 ± 37.56 vs. 265 ± 36.19 dB/ml) ( P < 0.001), and there was a significant improvement in the mean fibrosis values by LSM (5.32 ± 1.53 vs. 4.86 ± 1.28 KPa) ( P = 0.001). After supplementation, serum vitamin D level was raised significantly in the majority of patients ( P < 0.001); however, only 13% of them reached sufficient levels (>30 ng/ml), insufficient levels (20-29 ng/ml) was reached in 83% and 5% showed vitamin D deficiency (<20 ng/ml). CONCLUSION A significant improvement was detected in hepatic steatosis (by CAP); mean values of LSM, transaminases and lipid profile after three months of oral vitamin D supplementation.
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Affiliation(s)
- Rabab Fouad Emam
- Hepato-gastroenterology and Endemic Medicine Department, Faculty of Medicine, Cairo University
| | - Ahmed Fouad Soliman
- Hepato-gastroenterology and Endemic Medicine Department, Faculty of Medicine, Cairo University
| | - Samar Kamal Darweesh
- Hepato-gastroenterology and Endemic Medicine Department, Faculty of Medicine, Cairo University
| | | | - Ola Mohamed Ibrahim
- Clinical and Chemical pathology Department, Student's Hospital, Cairo University
| | - Dina Mahmoud Mohamed
- Hepato-gastroenterology and Endemic Medicine Department, Student's Hospital, Cairo University, Cairo, Egypt
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2
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Trotta MC, Herman H, Balta C, Rosu M, Ciceu A, Mladin B, Gesualdo C, Lepre CC, Russo M, Petrillo F, Pieretti G, Simonelli F, Rossi S, D’Amico M, Hermenean A. Oral Administration of Vitamin D3 Prevents Corneal Damage in a Knock-Out Mouse Model of Sjögren's Syndrome. Biomedicines 2023; 11:biomedicines11020616. [PMID: 36831152 PMCID: PMC9953695 DOI: 10.3390/biomedicines11020616] [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: 01/24/2023] [Revised: 02/14/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
BACKGROUND Vitamin D deficiency has been associated with dry eye development during Sjögren's syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. METHODS 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C-) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). RESULTS The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C-), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. CONCLUSIONS Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye.
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Affiliation(s)
- Maria Consiglia Trotta
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy
| | - Hildegard Herman
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Revolutiei Av., 310414 Arad, Romania
| | - Cornel Balta
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Revolutiei Av., 310414 Arad, Romania
| | - Marcel Rosu
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Revolutiei Av., 310414 Arad, Romania
| | - Alina Ciceu
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Revolutiei Av., 310414 Arad, Romania
| | - Bianca Mladin
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Revolutiei Av., 310414 Arad, Romania
| | - Carlo Gesualdo
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Via Luigi de Crecchio 6, 80138 Naples, Italy
| | - Caterina Claudia Lepre
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy
| | - Marina Russo
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy
| | - Francesco Petrillo
- PhD Course in Translational Medicine, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Gorizio Pieretti
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Via Luigi de Crecchio 6, 80138 Naples, Italy
| | - Francesca Simonelli
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Via Luigi de Crecchio 6, 80138 Naples, Italy
| | - Settimio Rossi
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Via Luigi de Crecchio 6, 80138 Naples, Italy
- Correspondence:
| | - Michele D’Amico
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy
| | - Anca Hermenean
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Revolutiei Av., 310414 Arad, Romania
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Qi KJ, Zhao ZT, Zhang W, Yang F. The impacts of vitamin D supplementation in adults with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials. Front Pharmacol 2022; 13:1033026. [PMID: 36278155 PMCID: PMC9581173 DOI: 10.3389/fphar.2022.1033026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 09/09/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Studies have shown the association of vitamin D status with the development of metabolic syndrome (MetS), which has attracted an extensive research interest with inconsistent results. Therefore, we hypothesized that vitamin D supplementation (VDS) will benefit adults with MetS. Aims: To test our hypothesis, we performed a meta-analysis to evaluate the effect of VDS on MetS in adults using relevant biomarkers such as anthropometric parameters, blood pressure, blood lipid profile, glycemia, oxidative stress and vitamin D toxicity (VDT). Methods: Randomized controlled trials published in PubMed, Web of Science, embase and the Cochrane Library between 2012 and 2022 on the effect of VDS on MetS in adults were searched. The language was limited to English. A meta-analysis performed using RevMan 5.4 and Stata 14.0 software, sensitivity analysis, and evaluation of the risk of bias and general quality of the resulting evidence were conducted. Results: Eventually, 13 articles were included in this meta-analysis. Overall, VDS significantly increased the endline serum 25-hydroxyvitamin D levels as compared to the control [MD:17.41, 95% CI (14.09, 20.73), p < 0.00001]. VDS did not affect waist circumference, body mass index, body fat percentage and VDT biomarkers, but decreased waist-to-hip ratio and blood pressure (p < 0.01). VDS significantly decreased fasting plasma glucose (FPG) [MD: 3.78; 95% CI (−6.52, −1.03), p = 0.007], but did not affect the levels of blood high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG). Pooled estimate of nine papers indicated a significant reduction of fasting insulin (FI) (p = 0.006), and homeostasis model assessment of insulin resistance (p = 0.0001). The quantitative insulin check index levels were moderately increased (p = 0.007) without any impact on the glycosylated hemoglobin type A1C (HbA1c). For the oxidative stress parameters, VDS significantly lowered the levels of malondialdehyde and hypersensitive C-reactive protein (p < 0.05). Conclusion: Results of this meta-analysis demonstrate that VDS only reduces insulin resistance and hypertension but not the blood lipid profile and HbA1c. It appears that the evidence for the benefit of VDS in adults with MetS is inconclusive. Further clinical studies are still needed.
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Chen XY, Wang C, Huang YZ, Zhang LL. Nonalcoholic fatty liver disease shows significant sex dimorphism. World J Clin Cases 2022; 10:1457-1472. [PMID: 35211584 PMCID: PMC8855265 DOI: 10.12998/wjcc.v10.i5.1457] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 12/02/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), which has been renamed metabolic dysfunction-associated fatty liver disease, is a growing global medical problem. The incidence of NAFLD and its associated end-stage liver disease is increasing each year, and many research advancements have been achieved to date. This review focuses on the current knowledge of the sex differences in NAFLD and does not elaborate on areas without differences. Studies have revealed significant sex differences in the prevalence, influencing factors, pathophysiology, complications and therapies of NAFLD. Men have a higher incidence than women. Compared with women, men exhibit increased visceral fat deposition, are more susceptible to leptin resistance, lack estrogen receptors, and tend to synthesize fatty acids into fat storage. Male patients will experience more severe hepatic fibrosis and a higher incidence of liver cancer. However, once NAFLD occurs, women show a faster progression of liver fibrosis, higher levels of liver cell damage and inflammation and are less likely to undergo liver transplantation than men. In general, men have more risk factors and more severe pathophysiological reactions than women, whereas the development of NAFLD is faster in women, and the treatments for women are more limited than those for men. Thus, whether sex differences should be considered in the individualized prevention and treatment of NAFLD in the future is worth considering.
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Affiliation(s)
- Xing-Yu Chen
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Cong Wang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Yi-Zhou Huang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Li-Li Zhang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
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Szymczak-Pajor I, Miazek K, Selmi A, Balcerczyk A, Śliwińska A. The Action of Vitamin D in Adipose Tissue: Is There the Link between Vitamin D Deficiency and Adipose Tissue-Related Metabolic Disorders? Int J Mol Sci 2022; 23:956. [PMID: 35055140 PMCID: PMC8779075 DOI: 10.3390/ijms23020956] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 01/09/2022] [Accepted: 01/10/2022] [Indexed: 12/11/2022] Open
Abstract
Adipose tissue plays an important role in systemic metabolism via the secretion of adipocytokines and storing and releasing energy. In obesity, adipose tissue becomes dysfunctional and characterized by hypertrophied adipocytes, increased inflammation, hypoxia, and decreased angiogenesis. Although adipose tissue is one of the major stores of vitamin D, its deficiency is detective in obese subjects. In the presented review, we show how vitamin D regulates numerous processes in adipose tissue and how their dysregulation leads to metabolic disorders. The molecular response to vitamin D in adipose tissue affects not only energy metabolism and adipokine and anti-inflammatory cytokine production via the regulation of gene expression but also genes participating in antioxidant defense, adipocytes differentiation, and apoptosis. Thus, its deficiency disturbs adipocytokines secretion, metabolism, lipid storage, adipogenesis, thermogenesis, the regulation of inflammation, and oxidative stress balance. Restoring the proper functionality of adipose tissue in overweight or obese subjects is of particular importance in order to reduce the risk of developing obesity-related complications, such as cardiovascular diseases and diabetes. Taking into account the results of experimental studies, it seemed that vitamin D may be a remedy for adipose tissue dysfunction, but the results of the clinical trials are not consistent, as some of them show improvement and others no effect of this vitamin on metabolic and insulin resistance parameters. Therefore, further studies are required to evaluate the beneficial effects of vitamin D, especially in overweight and obese subjects, due to the presence of a volumetric dilution of this vitamin among them.
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Affiliation(s)
- Izabela Szymczak-Pajor
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, Poland;
| | - Krystian Miazek
- Institute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, 15 Wroblewskiego, 93-590 Lodz, Poland;
| | - Anna Selmi
- Department of Molecular Biophysics, University of Lodz, 141/143 Pomorska, 90-236 Lodz, Poland; (A.S.); (A.B.)
| | - Aneta Balcerczyk
- Department of Molecular Biophysics, University of Lodz, 141/143 Pomorska, 90-236 Lodz, Poland; (A.S.); (A.B.)
| | - Agnieszka Śliwińska
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, Poland;
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MEMİÇ-İNAN C, SÖKÜLMEZ-KAYA P, AKAR S. Frequency of vitamin d deficiency in patients with lumbar spinal stenosis and its relationship with obesity, depression, and pain intensity: a cross-sectional study. REV NUTR 2022. [DOI: 10.1590/1678-9865202235e220020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
ABSTRACT Objective This study was conducted to determine the frequency of vitamin D deficiency in patients with lumbar spinal stenosis and to define the relationship between vitamin D levels and obesity, depression, and pain intensity. Methods This study was conducted with 69 patients (Male = 32, Female = 37) diagnosed with lumbar spinal stenosis. The participants’ 25(OH)D levels were measured by radioimmunoassay. In addition, bone metabolic status, including bone mineral density and bone turnover markers, was also evaluated. The Beck Depression Inventory was used to determine the depression statuses of the patients, while the McGill Melzack Pain Questionnaire was administered to measure pain intensity. The results were evaluated at a significance level of p<0.05. Results Vitamin D deficiency (<20 ng/mL) was found in 76.8% of the patients. Binary logistic regression analysis showed a significantly higher frequency of vitamin D deficiency in patients who: 1) had higher body mass indexes (OR 3.197, 95% CI 1.549-6.599); 2) fared higher in Beck’s depression score (OR 1.817, 95% CI 1.027–3.217); and 3) were female rather than male (OR 1.700, 95% CI 0.931-3.224) (p<0.05). Conclusion In this study, vitamin D deficiency was prevalent in lumbar spinal stenosis patients. In addition, obese, depressed, and female individuals have higher risks of vitamin D deficiency.
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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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9
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Karras SN, Koufakis T, Dimakopoulos G, Adamidou L, Karalazou P, Thisiadou K, Bais A, Tzotzas T, Manthou E, Makedou K, Kotsa K. Vitamin D equilibrium affects sex-specific changes in lipid concentrations during Christian Orthodox fasting. J Steroid Biochem Mol Biol 2021; 211:105903. [PMID: 33933575 DOI: 10.1016/j.jsbmb.2021.105903] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/07/2021] [Accepted: 04/26/2021] [Indexed: 01/06/2023]
Abstract
We aimed to evaluate sex differences in changes of lipid profiles in a cohort of metabolically healthy adults following Orthodox fasting (OF), as well as to assess a potential role of vitamin D status in mediating these variations. 45 individuals (24 premenopausal females, 53.3 %) with mean age 48.3 ± 9.1 years and mean Body Mass Index 28.7 ± 5.8 kg/m2 were prospectively followed for 12 weeks. Anthropometry, dietary and biochemical data regarding serum lipids, and vitamin D status were collected at baseline, 7 weeks after the implementation of OF, and 5 weeks after fasters returned to their standard dietary habits (12 weeks from baseline). According to 25-hydroxy-vitamin D [25(OH)D] measurements, participants were divided into two groups: those with concentrations above and below the median of values. Females with 25(OH)D concentrations below the median manifested a non-significant reduction by approximately 15 % in total and low-density lipoprotein cholesterol during the fasting period, followed by a significant increase 5 weeks after OF cessation (170.7 vs. 197.5 and 99.6 vs. 121.0 mg/dl respectively, p < 0.001). In contrast, males with 25(OH)D levels below the median demonstrated an inverse, non-significant trend of increase in lipid concentrations during the whole study period. Our findings suggest strikingly different inter-gender lipid responses to a dietary model of low-fat, mediated by vitamin D status. Further studies are necessary to reveal the underlying mechanisms and assess the importance of these differences with respect to cardiovascular health and the benefit of vitamin D supplementation strategies.
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Affiliation(s)
- Spyridon N Karras
- Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Theocharis Koufakis
- Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Georgios Dimakopoulos
- Medical Statistics, Epirus Science and Technology Park Campus of the University of Ioannina, Ioannina, Greece
| | - Lilian Adamidou
- Department of Dietetics and Nutrition, AHEPA University Hospital, Thessaloniki, Greece
| | - Paraskevi Karalazou
- Laboratory of Biochemistry, AHEPA General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Katerina Thisiadou
- Laboratory of Biochemistry, AHEPA General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Alkiviadis Bais
- Aristotle University of Thessaloniki, Laboratory of Atmospheric Physics, Thessaloniki, Greece
| | | | - Eleni Manthou
- Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Kali Makedou
- Laboratory of Biochemistry, AHEPA General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Kalliopi Kotsa
- Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece.
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10
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Mu Y, Li J, Kang JH, Eto H, Zai K, Kishimura A, Hyodo F, Mori T, Katayama Y. A Lipid-Based Nanocarrier Containing Active Vitamin D 3 Ameliorates NASH in Mice via Direct and Intestine-Mediated Effects on Liver Inflammation. Biol Pharm Bull 2021; 43:1413-1420. [PMID: 32879216 DOI: 10.1248/bpb.b20-00432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The gut-liver axis may be involved in non-alcoholic steatohepatitis (NASH) progression. Pathogen-associated molecular patterns leak through the intestinal barrier to the liver via the portal vein to contribute to NASH development. Active vitamin D3 (1,25(OH)2D3) is a potential therapeutic agent to enhance the intestinal barrier. Active vitamin D3 also suppresses inflammation and fibrosis in the liver. However, the adverse effects of active vitamin D3 such as hypercalcemia limit its clinical use. We created a nano-structured lipid carrier (NLC) containing active vitamin D3 to deliver active vitamin D3 to the intestine and liver to elicit NASH treatment. We found a suppressive effect of the NLC on the lipopolysaccharide-induced increase in permeability of an epithelial layer in vitro. Using mice in which NASH was induced by a methionine and choline-deficient diet, we discovered that oral application of the NLC ameliorated the permeability increase in the intestinal barrier and attenuated steatosis, inflammation and fibrosis in liver at a safe dose of active vitamin D3 at which the free form of active vitamin D3 did not show a therapeutic effect. These data suggest that the NLC is a novel therapeutic agent for NASH.
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Affiliation(s)
- Yunmei Mu
- Graduate School of Systems Life Sciences, Kyushu University
| | - Jinting Li
- Graduate School of Systems Life Sciences, Kyushu University
| | - Jeong-Hun Kang
- Division of Biopharmaceutics and Pharmacokinetics, National Cerebral and Cardiovascular Center Research Institute
| | - Hinako Eto
- Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University
| | - Khadijah Zai
- Department of Pharmaceutical Science and Technology, Universitas Gadjah Mada
| | - Akihiro Kishimura
- Graduate School of Systems Life Sciences, Kyushu University.,Department of Applied Chemistry, Faculty of Engineering, Kyushu University.,Center for Future Chemistry, Kyushu University.,International Research Center for Molecular System, Kyushu University
| | - Fuminori Hyodo
- Department of Radiology, Frontier Science for Imaging, Gifu University School of Medicine
| | - Takeshi Mori
- Graduate School of Systems Life Sciences, Kyushu University.,Department of Applied Chemistry, Faculty of Engineering, Kyushu University.,Center for Future Chemistry, Kyushu University
| | - Yoshiki Katayama
- Graduate School of Systems Life Sciences, Kyushu University.,Department of Applied Chemistry, Faculty of Engineering, Kyushu University.,Center for Future Chemistry, Kyushu University.,International Research Center for Molecular System, Kyushu University
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11
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Valle M, Mitchell PL, Pilon G, St-Pierre P, Varin T, Richard D, Vohl MC, Jacques H, Delvin E, Levy E, Gagnon C, Bazinet L, Marette A. Cholecalciferol Supplementation Does Not Prevent the Development of Metabolic Syndrome or Enhance the Beneficial Effects of Omega-3 Fatty Acids in Obese Mice. J Nutr 2021; 151:1175-1189. [PMID: 33851198 PMCID: PMC8112766 DOI: 10.1093/jn/nxab002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 10/30/2020] [Accepted: 01/04/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood. OBJECTIVES We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice. METHODS We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA. RESULTS D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa. CONCLUSIONS Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese mice.
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Affiliation(s)
- Marion Valle
- Québec Heart and Lung Institute Research Centre, Faculty of Medicine, Laval University, Québec City, QC, Canada,Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada
| | - Patricia L Mitchell
- Québec Heart and Lung Institute Research Centre, Faculty of Medicine, Laval University, Québec City, QC, Canada,Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada
| | - Geneviève Pilon
- Québec Heart and Lung Institute Research Centre, Faculty of Medicine, Laval University, Québec City, QC, Canada,Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada
| | - Philippe St-Pierre
- Québec Heart and Lung Institute Research Centre, Faculty of Medicine, Laval University, Québec City, QC, Canada,Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada
| | - Thibault Varin
- Québec Heart and Lung Institute Research Centre, Faculty of Medicine, Laval University, Québec City, QC, Canada,Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada
| | - Denis Richard
- Québec Heart and Lung Institute Research Centre, Faculty of Medicine, Laval University, Québec City, QC, Canada,Department of Medicine, Laval University, Québec City, QC, Canada
| | - Marie-Claude Vohl
- Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada,School of Nutrition, Laval University, Québec, QC, Canada
| | - Hélène Jacques
- Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada,School of Nutrition, Laval University, Québec, QC, Canada
| | - Edgar Delvin
- Department of Nutrition and Biochemistry, Sainte Justine Hospital Research Centre, University of Montreal, Montreal, QC, Canada
| | - Emile Levy
- Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada,Department of Nutrition and Biochemistry, Sainte Justine Hospital Research Centre, University of Montreal, Montreal, QC, Canada
| | - Claudia Gagnon
- Québec Heart and Lung Institute Research Centre, Faculty of Medicine, Laval University, Québec City, QC, Canada,Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada,Department of Medicine, Laval University, Québec City, QC, Canada,Endocrinology and Nephrology Unit, Centre hospitalier universitaire de Québec Research Centre, Québec City, QC, Canada
| | - Laurent Bazinet
- Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada,Department of Food Sciences, Laboratory of Food Processing and ElectroMembrane Processes, Laval University, Québec City, QC, Canada
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12
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Parizadeh SM, Rezayi M, Jafarzadeh-Esfehani R, Avan A, Ghazizadeh H, Emadzadeh M, Sahebi R, Ferns GA, Ghayour-Mobarhan M. Association of vitamin D status with liver and kidney disease: A systematic review of clinical trials, and cross-sectional and cohort studies. INT J VITAM NUTR RES 2021; 91:175-187. [DOI: 10.1024/0300-9831/a000540] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Abstract. Background: Vitamin D deficiency (VDD) is a major public health problem. There are few comprehensive systematic reviews about the relationship between Vitamin D status and liver and renal disease in Iran. Methods: We systemically searched the following databases: Web of Science; PubMed; Cochrane Library; Scopus; Science Direct; Google Scholar and two Iranian databases (Scientific Information Database (SID) and IranMedex) up until November 2017 to identify all randomized control trials (RCTs), case control, cross-sectional and cohort studies investigating the association between vitamin D and any form of liver or kidney disease. Results: Vitamin D insufficiency, or deficiency (VDD), is highly prevalent in Iran, reports varying between 44.4% in Isfahan to 98% in Gorgan. There is also a high prevalence of VDD among patients with liver or kidney disease, and the administration of vitamin D supplements may have beneficial effects on lipid profile, blood glucose, liver function and fatty liver disease, and bone health. Low serum vitamin D levels are related with abnormalities in these laboratory and clinical parameters. Conclusion: VDD is prevalent in patients with chronic liver or renal disease in Iran. There appear to be several beneficial effects of vitamin D supplementation in vitamin D deficient patients with liver or kidney disease.
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Affiliation(s)
- Seyed Mostafa Parizadeh
- Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Rezayi
- Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Jafarzadeh-Esfehani
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamideh Ghazizadeh
- Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Category 2 Institutes and Centers under the Auspices of UNESCO, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Emadzadeh
- Clinical Research Unit, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Sahebi
- Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Gordon A. Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, UK
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Category 2 Institutes and Centers under the Auspices of UNESCO, Mashhad University of Medical Sciences, Mashhad, Iran
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13
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Evans M, Sulley AM, Crowley DC, Langston J, Guthrie N. Pain Bloc-R Alleviates Unresolved, Non-Pathological Aches and Discomfort in Healthy Adults—A Randomized, Double-Blind, Placebo-Controlled, Crossover Study. Nutrients 2020; 12:nu12061831. [PMID: 32575480 PMCID: PMC7353407 DOI: 10.3390/nu12061831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 06/10/2020] [Accepted: 06/11/2020] [Indexed: 11/25/2022] Open
Abstract
The lack of effective treatment for chronic discomfort without negative side effects highlights the need for alternative treatments. Pain Bloc-R is a natural health product composed of vitamins B6, B12, D, white willow bark extract, Angelica root extract, acetyl L-carnitine HCl, caffeine, L-theanine, Benfotiamine, and L-tetrahydropalmatine. The objective of this study was to compare the effects of Pain Bloc-R, acetaminophen, and placebo on unresolved aches and discomfort as assessed by the brief pain inventory (BPI) and modified Cornell musculoskeletal discomfort questionnaires. This randomized, double-blind, placebo-controlled, crossover study consisted of three 7-day periods with Pain Bloc-R, acetaminophen, or placebo, each separated by a 7-day washout. Twenty-seven healthy adults (ages 22–63 years) were randomized to receive the three interventions in different sequences. The BPI “pain at its worst” scores were significantly lower when participants took Pain Bloc-R than when they took acetaminophen (21.8% vs. 9.8% decrease, p = 0.026) after seven days of supplementation. Pain Bloc-R achieved a significant improvement in the “pain at its least” score, significantly decreased the interference of discomfort in walking, and significantly decreased musculoskeletal discomfort total scores (34%, p = 0.040) after seven days. In a post hoc subgroup analysis based on age and gender, male participants ≤45 years taking Pain Bloc-R reported significant reductions in pain severity and pain interference vs. acetaminophen. Pain Bloc-R performed as well as acetaminophen in managing unresolved non-pathological pain in otherwise healthy individuals.
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Affiliation(s)
- Malkanthi Evans
- KGK Science Inc., London, ON N6A 5R8, Canada; (A.M.S.); (D.C.C.); (N.G.)
- Correspondence:
| | - Abdul M. Sulley
- KGK Science Inc., London, ON N6A 5R8, Canada; (A.M.S.); (D.C.C.); (N.G.)
| | - David C. Crowley
- KGK Science Inc., London, ON N6A 5R8, Canada; (A.M.S.); (D.C.C.); (N.G.)
| | | | - Najla Guthrie
- KGK Science Inc., London, ON N6A 5R8, Canada; (A.M.S.); (D.C.C.); (N.G.)
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14
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Yuan L, Kardashian A, Sarkar M. NAFLD in women: Unique pathways, biomarkers and therapeutic opportunities. ACTA ACUST UNITED AC 2020; 18:425-432. [PMID: 32523869 DOI: 10.1007/s11901-019-00495-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Purpose of review In this review article we evaluate sex differences in the natural history of NAFLD and highlight distinct risk profiles of women with NAFLD, as well as unique treatment considerations and research gaps. Summary of findings Reproductive factors, such as menopausal status should be considered when evaluating NAFLD risk in women, as well as additional reproductive risk factors such as age at menarche, presence of polycystic ovary syndrome, and gestational diabetes. Women do appear to have lower risk for hepatocellular carcinoma from NASH, as well as lower mortality from NASH cirrhosis than men, although among women, NASH is now the leading indication for liver transplant. Data on sex differences in biomarker development and clinical trials are lacking, and researchers should be encouraged to evaluate biomarker performance by sex, and specifically report clinical trial endpoints in women.
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Affiliation(s)
- Liyun Yuan
- University of Southern California, Division of GI/Hepatology
| | - Ani Kardashian
- University of California, San Francisco, Division of GI/Hepatology
| | - Monika Sarkar
- University of California, San Francisco, Division of GI/Hepatology
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15
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A randomised controlled trial comparing the efficacy of micellised and fat-soluble vitamin D3 supplementation in healthy adults. Br J Nutr 2019; 121:859-865. [PMID: 30898175 DOI: 10.1017/s0007114518003215] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Nanoemulsion formulation of vitamin D3 have been shown to have better bioavailability than the coarse emulsion preparation in vitro and in vivo animal studies. In the absence of randomised trial in humans, comparing the efficacy of nanotechnology-based miscellised vitamin D3 over conventional vitamin D3, we undertook this study. A total of 180 healthy adults were randomised to receive either micellised (DePura, group A) or conventional vitamin D3 (Calcirol, group B) at a monthly dose of 60 000 IU (1500μg) for 6 months. The outcome parameters were serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), Ca, phosphate, alkaline phosphatase and urinary Ca:creatinine ratio. A total of eighty-nine subjects in group A and seventy-seven in group B completed the trial. Subjects in both the groups had a significant increase in their serum 25(OH)D levels following supplementation (group A: 21·5 (sd 10·9) to 76·7 (sd 18·8) nmol/l (P<0·001); group B: 22·8 (sd 10·4) to 57·8 (sd 16·0) nmol/l (P<0·001)). Participants in micellised group had an additional increase of 20·2 (95 % CI 14·0, 26·4) nmol/l in serum 25(OH)D levels (P<0·001). The difference between the groups was 17·5 (95 % CI 11·8, 23·1) nmol/l, which remained statistically significant (P<0·001) even after adjustment for age and sex. Significant decline in mean serum PTH was observed in both the groups. No hypercalcaemia or hypercalciuria was noted. Although supplementation with both the preparations resulted in a significant rise in serum 25(OH)D levels, micellised vitamin D3 appeared to be more efficacious in achieving higher levels of serum 25(OH)D.
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16
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Alloubani A, Akhu-Zaheya L, Samara R, Abdulhafiz I, Saleh A, Altowijri A. Relationship between Vitamin D Deficiency, Diabetes, and Obesity. Diabetes Metab Syndr 2019; 13:1457-1461. [PMID: 31336506 DOI: 10.1016/j.dsx.2019.02.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 02/12/2019] [Indexed: 01/08/2023]
Abstract
AIM This study aimed to assess the prevalence of VDD in Saudi Arabia, revealing the lifestyle and nutritional habits; and assesses the association between VDD, Diabetes Mellitus, and obesity. METHODS A descriptive, cross-sectional, and correlational design was used in this study. A convenience sampling method of 350 participants participated in the study. RESULTS The results revealed that the probability of having vitamin D Deficiency was higher among females (OR = 2.06, p > .05); younger age-whereby with each one year decrease in age there was about 0.03 probability of having Vitamin D Deficiency (B = -0.03; p > .05); individuals with higher incomes (OR = 1.44, p > .05); smokers (OR = 0.08, p > .05); and a lack of exposure to the sun (OR = 8.50; p > .05). In addition, exercise is also a predictor of Vitamin D deficiency (OR = 3.8; p > .05). Moreover, less Vitamin D intake (OR 9.7; p > .05), less intake of Calcium (OR = 12.2, p > .05); In addition increase one unit in the BMI, cholesterol, LDL, HDL, and FBS increased the log odd of having liability of Vitamin D deficiency by 3.2; 1.9, 1.8, 1.0, and 2.4 (p > .05). CONCLUSION Vitamin D Deficiency was prevalent in both males and females across different age groups in the citizens of Saudi. Because of the connection between Vitamin D Deficiency and main chronic disease, it is necessary to emphasize the need to recognize Vitamin D Deficiency screening for risk factors. It may be reasonable for the nutritionists, nurses, and physicians, to encourage the community on approaches to enhance dietary Vitamin D or suggest supplementation.
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Affiliation(s)
- Aladeen Alloubani
- Nursing Research & EBP Unit, King Hussein Cancer Center, Queen Rania Al Abdullah Street (next to Jordan University), P.O.Box 1269, Amman, 11941, Jordan; Harvard Medical School, USA.
| | - Laila Akhu-Zaheya
- Jordan University of Science and Technology, Ar Ramtha 3030, Ramtha, Jordan.
| | - Rama Samara
- Jordan University of Science and Technology, Ar Ramtha 3030, Ramtha, Jordan.
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17
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Fazelian S, Amani R, Paknahad Z, Kheiri S, Khajehali L. Effect of Vitamin D Supplement on Mood Status and Inflammation in Vitamin D Deficient Type 2 Diabetic Women with Anxiety: A Randomized Clinical Trial. Int J Prev Med 2019; 10:17. [PMID: 30820304 PMCID: PMC6390422 DOI: 10.4103/ijpvm.ijpvm_174_18] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Accepted: 07/21/2018] [Indexed: 12/21/2022] Open
Abstract
Background: Vitamin D plays an important role in nervous health and depression. Vitamin D deficiency and anxiety affect diabetic status. The purpose of this study was to determine the effect of vitamin D supplementation on anxiety, depression, and inflammation in diabetic women with anxiety. Methods: In this randomized controlled trial, totally 51 women with type 2 diabetes (T2DM) and vitamin D deficiency were randomly allocated to receive one oral pearl of 50,000 IU vitamin D3 (26 women) or a placebo (25 women) fortnightly for 16 weeks. Anthropometric indices, sun exposure, dietary intake, depression, anxiety, and stress scores and biochemical biomarkers including high sensitivity C-reactive protein (hs-CRP) and interleukin-10 (IL-10) were measured at the baseline and after 16-week supplementation. Results: Mean ± SD age of participant was 47.43 ± 9.57 years old. Baseline values were not different between the groups. Anxiety score changes were significantly lower in vitamin D group than the controls (P = 0.001). Within group comparison indicated that depression in supplement group with lower vitamin D levels was significantly reduced. Serum hs-CRP reduced (P = 0.01), while IL-10 concentrations increased (P = 0.04) in the intervention group. Conclusions: Vitamin D supplementation can improve mood status and anti-inflammatory biomarkers in female diabetics with anxiety and vitamin D deficiency.
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Affiliation(s)
- Siavash Fazelian
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Amani
- Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zamzam Paknahad
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Soleiman Kheiri
- Department of Epidemiology and Biostatistics, School of Health, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Leila Khajehali
- Internal Center, Imam Ali Hospital of Farokhshahr, Social Security Organization, Shahrekord, Iran
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18
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Hariri M, Zohdi S. Effect of Vitamin D on Non-Alcoholic Fatty Liver Disease: A Systematic Review of Randomized Controlled Clinical Trials. Int J Prev Med 2019; 10:14. [PMID: 30774848 PMCID: PMC6360993 DOI: 10.4103/ijpvm.ijpvm_499_17] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Accepted: 01/24/2018] [Indexed: 01/10/2023] Open
Abstract
New evidence suggests that low serum Vitamin D may cause nonalcoholic fatty liver disease (NAFLD). Hypovitaminosis D is associated with the severity and incidence of NAFLD. The objective of this study was to conduct a systematic review on randomized controlled trials (RCTs) assessing the effect of Vitamin D on serum metabolic profile among NAFLD patients. Databases including PubMed, Institute for Scientific Information Web of Science, Scopus, and Google Scholar were searched up to November 2016. RCTs which studied Vitamin D effect on metabolic profiles and liver function, and conducted among adults were included. Six articles were eligible to be considered in this systematic review. According to the result, Vitamin D supplementation might improve lipid profile and inflammatory mediators when compared with placebo. No article indicated significant effect of Vitamin D on liver enzymes except one article which revealed that Vitamin D together with calcium carbonate can reduce liver enzymes. Vitamin D supplementation may not improve anthropometric measures and glycemic index variables among patients with NAFLD. Vitamin D supplement might improve NAFLD symptoms, especially inflammatory mediators. More RCTs in different parts of world with different forms and doses of Vitamin D are necessary.
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Affiliation(s)
- Mitra Hariri
- Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Sara Zohdi
- Student Research Committee, Neyshabur University of Medical Sciences, Neyshabur, Iran
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19
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A comparison of serum fructosamine, 25-hydroxyvitamin D, calcium, and phosphorus levels in the first, second, and third trimester in obese and non-obese pregnant women with and without gestational diabetes mellitus. Int J Diabetes Dev Ctries 2019. [DOI: 10.1007/s13410-018-0631-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
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20
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Fazelian S, Paknahad Z, Khajehali L, Kheiri S, Amani R. The effects of supplementation with vitamin D on inflammatory biomarkers, omentin, and vaspin in women with type 2 diabetes: A randomized double‐blind placebo‐controlled clinical trial. J Food Biochem 2018. [DOI: 10.1111/jfbc.12631] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Siavash Fazelian
- Food Security Research Center, Department of Clinical Nutrition, School of Nutrition and Food Science Isfahan University of Medical Sciences Isfahan Iran
| | - Zamzam Paknahad
- Food Security Research Center, Department of Clinical Nutrition, School of Nutrition and Food Science Isfahan University of Medical Sciences Isfahan Iran
| | - Leila Khajehali
- Imam Ali Hospitals of Farokhshahr Social Security Organization Shahrekord Iran
| | - Soleiman Kheiri
- Departments of Epidemiology and Biostatistics, School of Health Shahrekord University of Medical Sciences Shahrekord Iran
| | - Reza Amani
- Food Security Research Center, Department of Clinical Nutrition, School of Nutrition and Food Science Isfahan University of Medical Sciences Isfahan Iran
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21
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Ghaly S, Kaakoush NO, Lloyd F, Gordon L, Forest C, Lawrance IC, Hart PH. Ultraviolet Irradiation of Skin Alters the Faecal Microbiome Independently of Vitamin D in Mice. Nutrients 2018; 10:nu10081069. [PMID: 30103486 PMCID: PMC6116187 DOI: 10.3390/nu10081069] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 08/02/2018] [Accepted: 08/06/2018] [Indexed: 01/01/2023] Open
Abstract
Reduced sunlight exposure has been associated with an increased incidence of Crohn’s disease and ulcerative colitis. The effect of ultraviolet radiation (UVR) on the faecal microbiome and susceptibility to colitis has not been explored. C57Bl/6 female mice were fed three different vitamin D-containing diets for 24 days before half of the mice in each group were UV-irradiated (1 kJ/m2) for each of four days, followed by twice-weekly irradiation of shaved dorsal skin for 35 days. Faecal DNA was extracted and high-throughput sequencing of the 16S RNA gene performed. UV irradiation of skin was associated with a significant change in the beta-diversity of faeces compared to nonirradiated mice, independently of vitamin D. Specifically, members of phylum Firmicutes, including Coprococcus, were enriched, whereas members of phylum Bacteroidetes, such as Bacteroidales, were depleted. Expression of colonic CYP27B1 increased by four-fold and IL1β decreased by five-fold, suggesting a UVR-induced anti-inflammatory effect. UV-irradiated mice, however, were not protected against colitis induced by dextran sodium sulfate (DSS), although distinct faecal microbiome differences were documented post-DSS between UV-irradiated and nonirradiated mice. Thus, skin exposure to UVR alters the faecal microbiome, and further investigations to explore the implications of this in health and disease are warranted.
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Affiliation(s)
- Simon Ghaly
- Telethon Kids Institute, The University of Western Australia, Perth, WA 6008, Australia.
- School of Medicine and Pharmacology, The University of Western Australia, Perth, WA 6009, Australia.
- Department of Gastroenterology and Hepatology, St. Vincent's Hospital, Sydney, NSW 2010, Australia.
| | - Nadeem O Kaakoush
- School of Medical Sciences, UNSW Sydney, Kensington, NSW 2033, Australia.
| | - Frances Lloyd
- School of Medicine and Pharmacology, The University of Western Australia, Perth, WA 6009, Australia.
| | - Lavinia Gordon
- Australian Genome Research Facility, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia.
| | - Cynthia Forest
- Department of Anatomical Pathology, PathWest, Fiona Stanley Hospital, Murdoch, WA 6150, Australia.
| | - Ian C Lawrance
- School of Medicine and Pharmacology, The University of Western Australia, Perth, WA 6009, Australia.
- Centre for Inflammatory Bowel Disease, St. John of God Hospital, Subiaco, WA 6008, Australia.
| | - Prue H Hart
- Telethon Kids Institute, The University of Western Australia, Perth, WA 6008, Australia.
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Sharifi N, Amani R. Vitamin D supplementation and non-alcoholic fatty liver disease: A critical and systematic review of clinical trials. Crit Rev Food Sci Nutr 2017; 59:693-703. [PMID: 29035092 DOI: 10.1080/10408398.2017.1389693] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Previous observational studies have found a relationship between vitamin D deficiency and non-alcoholic fatty liver disease (NAFLD). However, this type of study could not show the causal relationship between these two conditions. Therefore, we systematically and critically reviewed the available clinical trials to elucidate such relationship. We searched databases such as Medline, Scopus and Cochrane to identify the clinical trials that assessed the effects of vitamin D supplementation in adults with NAFLD. The outcome variables of interest were indicators of hepatic steatosis, liver enzymes, insulin resistance, inflammation and oxidative stress. A total of 6 studies were included in the qualitative analysis. Only in two studies the grade of hepatic steatosis decreased significantly after vitamin D supplementation. The changes in insulin resistance parameters were reported significant only in one. Of the 3 included studies that measured biomarkers of inflammation and oxidative stress, one revealed a significant decrease in these biomarkers after vitamin D supplementation. Findings from current review study provided new insight into the factors that could affect the therapeutic role of vitamin D in NAFLD. Factors such as gender differences, baseline serum status of vitamin D, co-supplementation with calcium and gene polymorphism should be considered when designing future clinical trials.
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Affiliation(s)
- Nasrin Sharifi
- a Research Center for Biochemistry and Nutrition in Metabolic Diseases , Kashan University of Medical Sciences , Kashan , Iran
| | - Reza Amani
- b Food Security Research Center, Department of Clinical Nutrition , School of Nutrition and Food Science, Isfahan University of Medical Sciences , Isfahan , Iran
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Dasarathy J, Varghese R, Feldman A, Khiyami A, McCullough AJ, Dasarathy S. Patients with Nonalcoholic Fatty Liver Disease Have a Low Response Rate to Vitamin D Supplementation. J Nutr 2017; 147:1938-1946. [PMID: 28814531 PMCID: PMC5610550 DOI: 10.3945/jn.117.254292] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 06/06/2017] [Accepted: 07/17/2017] [Indexed: 01/10/2023] Open
Abstract
Background: Hypovitaminosis D is associated with an increased severity of nonalcoholic fatty liver disease (NAFLD), but reports on the response to cholecalciferol (vitamin D3) supplementation are conflicting.Objective: The objective of this study was to determine if standard vitamin D3 supplementation is effective in NAFLD with hypovitaminosis D.Methods: Sixty-five well-characterized adults [age (mean ± SD): 51.6 ± 12.3 y] with biopsy-proven NAFLD were screened. Forty-two patients (the ratio of men to women was 13:29) had hypovitaminosis D (plasma 25-hydroxyvitamin D [25(OH)D] <30 ng/mL). An observational study was performed in NAFLD patients with hypovitaminosis D treated with 2000 IU cholecalciferol (vitamin D3) daily for 6 mo per clinical practice. Plasma 25(OH)D, hepatic and metabolic panels, and metabolic syndrome components were assessed before and after cholecalciferol supplementation. Body composition was measured by using bioelectrical impedance analysis. The primary outcome measure was plasma 25(OH)D ≥30 ng/mL at the end of the study. Secondary outcomes included change in serum transaminases, fasting plasma glucose, and insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Chi-square, Student's t tests, correlation coefficient, and multivariate analysis were performed.Results: Twenty-six (61.9%) patients had nonalcoholic steatohepatitis (NASH), and 16 (38.1%) had hepatic steatosis. After 6 mo of cholecalciferol supplementation, plasma 25(OH)D ≥30 ng/mL was observed in 16 subjects (38.1%; responders) whereas the remaining 26 patients (61.9%) were nonresponders with plasma 25(OH)D <30 ng/mL. Significantly fewer (P < 0.01) patients with NASH were responders (4 of 26, 15.4%) than those with hepatic steatosis (12 of 16, 75%). Baseline fasting serum alanine aminotransferase, plasma glucose, and HOMA-IR were similar in the responders and nonresponders, but the NASH score on the liver biopsy was lower (16.5%) in the responders (P < 0.001). Nonresponders had a higher fat mass (10.5%) and lower fat-free mass (10.4%) than responders did. End-of-treatment alanine aminotransferase and HOMA-IR improved only in responders. The baseline HOMA-IR and histological NASH score were independent predictors of nonresponse to cholecalciferol supplementation.Conclusions: Daily supplementation with 2000 IU cholecalciferol for 6 mo did not correct hypovitaminosis D in the majority of patients with NASH. Further studies are needed to determine if higher doses are effective. This trial was registered at clinicaltrials.gov as 13-00153.
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Affiliation(s)
| | | | | | - Amer Khiyami
- Pathology, Metro Health Medical Center, Cleveland, OH; and
| | - Arthur J McCullough
- Department of Gastroenterology and Hepatology, Pathobiology, Cleveland Clinic, Cleveland, OH
| | - Srinivasan Dasarathy
- Department of Gastroenterology and Hepatology, Pathobiology, Cleveland Clinic, Cleveland, OH
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24
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Pang Q, Zhou L, Jin H, Man ZR, Liu HC. Letter: non-alcoholic fatty liver disease and polycystic ovary syndrome-evidence for low vitamin D status contributing to the link. Aliment Pharmacol Ther 2017; 46:566-567. [PMID: 28776742 DOI: 10.1111/apt.14159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Q Pang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - L Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - H Jin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Z R Man
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - H C Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
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25
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Wintermeyer E, Ihle C, Ehnert S, Stöckle U, Ochs G, de Zwart P, Flesch I, Bahrs C, Nussler AK. Crucial Role of Vitamin D in the Musculoskeletal System. Nutrients 2016; 8:nu8060319. [PMID: 27258303 PMCID: PMC4924160 DOI: 10.3390/nu8060319] [Citation(s) in RCA: 128] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/10/2016] [Accepted: 05/11/2016] [Indexed: 12/17/2022] Open
Abstract
Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D’s central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported.
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Affiliation(s)
- Elke Wintermeyer
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Christoph Ihle
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Sabrina Ehnert
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Ulrich Stöckle
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Gunnar Ochs
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Peter de Zwart
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Ingo Flesch
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Christian Bahrs
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
| | - Andreas K Nussler
- Eberhard Karls Universität Tübingen, BG Trauma Center, Siegfried Weller Institut, Schnarrenbergstr. 95, Tübingen D-72076, Germany.
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