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Ji Z, Wolfson J. Reinforced Borrowing Framework: Leveraging Auxiliary Data for Individualized Inference. Stat Med 2024; 43:5837-5848. [PMID: 39556882 PMCID: PMC11639645 DOI: 10.1002/sim.10267] [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: 05/16/2023] [Revised: 10/11/2024] [Accepted: 10/16/2024] [Indexed: 11/20/2024]
Abstract
Increasingly during the past decade, researchers have sought to leverage auxiliary data for enhancing individualized inference. Many existing methods, such as multisource exchangeability models (MEM), have been developed to borrow information from multiple supplemental sources to support parameter inference in a primary source. MEM and its alternatives decide how much information to borrow based on the exchangeability of the primary and supplemental sources, where exchangeability is defined as equality of the target parameter. Other information that may also help determine the exchangeability of sources is ignored. In this article, we propose a generalized reinforced borrowing framework (RBF) leveraging auxiliary data for enhancing individualized inference using a distance-embedded prior which uses data not only about the target parameter but also uses different types of auxiliary information sources to "reinforce" inference on the target parameter. RBF improves inference with minimal additional computational burden. We demonstrate the application of RBF to a study investigating the impact of the COVID-19 pandemic on individual activity and transportation behaviors, where RBF achieves 20%-40% lower MSE compared with existing methods.
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Affiliation(s)
- Ziyu Ji
- Division of Biostatistics & Health Data Science, School of Public HealthUniversity of MinnesotaMinneapolisMinnesotaUSA
| | - Julian Wolfson
- Division of Biostatistics & Health Data Science, School of Public HealthUniversity of MinnesotaMinneapolisMinnesotaUSA
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Wu Q, Luo Y, Lu H, Xie T, Hu Z, Chu Z, Luo F. The Potential Role of Vitamin E and the Mechanism in the Prevention and Treatment of Inflammatory Bowel Disease. Foods 2024; 13:898. [PMID: 38540888 PMCID: PMC10970063 DOI: 10.3390/foods13060898] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/01/2024] [Accepted: 03/12/2024] [Indexed: 01/06/2025] Open
Abstract
Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease, and it is a multifactorial disease of the intestinal mucosa. Oxidative stress damage and inflammation are major risk factors for IBD. Vitamin E has powerful antioxidant and anti-inflammatory effects. Our previous work and other investigations have shown that vitamin E has a positive effect on the prevention and treatment of IBD. In this paper, the source and structure of vitamin E and the potential mechanism of vitamin E's role in IBD were summarized, and we also analyzed the status of vitamin E deficiency in patients with IBD and the effect of vitamin E supplementation on IBD. The potential mechanisms by which vitamin E plays a role in the prevention and treatment of IBD include improvement of oxidative damage, enhancement of immunity, maintenance of intestinal barrier integrity, and suppression of inflammatory cytokines, modulating the gut microbiota and other relevant factors. The review will improve our understanding of the complex mechanism by which vitamin E inhibits IBD, and it also provides references for doctors in clinical practice and researchers in this field.
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Affiliation(s)
- Qi Wu
- Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha 410004, China; (Q.W.); (H.L.); (T.X.); (Z.H.); (Z.C.)
| | - Yi Luo
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, China;
| | - Han Lu
- Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha 410004, China; (Q.W.); (H.L.); (T.X.); (Z.H.); (Z.C.)
| | - Tiantian Xie
- Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha 410004, China; (Q.W.); (H.L.); (T.X.); (Z.H.); (Z.C.)
| | - Zuomin Hu
- Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha 410004, China; (Q.W.); (H.L.); (T.X.); (Z.H.); (Z.C.)
| | - Zhongxing Chu
- Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha 410004, China; (Q.W.); (H.L.); (T.X.); (Z.H.); (Z.C.)
| | - Feijun Luo
- Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha 410004, China; (Q.W.); (H.L.); (T.X.); (Z.H.); (Z.C.)
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Wang Y, Li G, Lv J, Zhou Y, Ma H. Vitamin E reduces inflammation and improves cognitive disorder and vascular endothelial functions in patients with leukoaraiosis. Int J Neurosci 2023; 133:1346-1354. [PMID: 35645223 DOI: 10.1080/00207454.2022.2079505] [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: 11/30/2021] [Accepted: 05/11/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Leukoaraiosis (LA) is a disease manifested by demyelination and gliosis in white matter, mainly caused by cerebrovascular diseases. LA is closely related to the expression level of inflammatory factors, oxidative stress, and vascular endothelial dysfunction in patients. Vitamin E may play antioxidant and anti-inflammatory roles in various diseases. We aimed to explore the effects of vitamin E on the patients with LA. METHODS A total of 160 patients with LA were recruited in this research. Matrix metalloproteinase-9 (MMP-9), MMP-2, C-reactive protein (CRP), complement 3 (C3), C4, nitric oxide (NO), and endothelin (ET) levels were evaluated by ELISA. The Mini-Mental State Examination (MMSE) was used for cognitive impairment assessment. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were analyzed by commercial kits. RESULTS The levels of CRP, C3, and C4 significantly decreased in the serum of LA patients after the administration of vitamin E. The levels of MMP-2 and MPP-9 showed a significant decrease in the administered group. Vitamin E significantly inhibited the expression of MDA, while significantly upregulated the expression of SOD. Significant increase in NO production and significant downregulation of ET expression occurred in vitamin E groups. MMSE score was significantly increased by vitamin E. CONCLUSION In conclusion, vitamin E showed effects on the alleviation of inflammatory response, oxidative stress, endothelial damage, and cognitive dysfunction. Thus, vitamin E could be a potential drug for the clinical treatment of LA patients.
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Affiliation(s)
- Yan Wang
- Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Guoce Li
- Department of MRI, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Jianping Lv
- Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Yingwen Zhou
- Department of MRI, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Hongxia Ma
- Department of Nursing, Cangzhou Central Hospital, Cangzhou, Hebei, China
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Wang MY, Prabahar K, Găman MA, Zhang JL. Vitamin E supplementation in the treatment on nonalcoholic fatty liver disease (NAFLD): Evidence from an umbrella review of meta-analysis on randomized controlled trials. J Dig Dis 2023; 24:380-389. [PMID: 37503812 DOI: 10.1111/1751-2980.13210] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 06/11/2023] [Accepted: 07/25/2023] [Indexed: 07/29/2023]
Abstract
OBJECTIVE We conducted this umbrella review of meta-analysis on randomized controlled trials to clarify the effects of vitamin E administration on alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), degrees of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS PubMed, MEDLINE, SCOPUS, EMBASE, and Web of Science were searched to identify pertinent articles published up to June 2023. To calculate the overall effect size (ES) and confidence intervals (CI), random-effects model was used. RESULTS Six meta-analyses were included in the umbrella review. By pooling ES based on the random-effects model, we found that vitamin E supplementation significantly decreased ALT (ES -6.47, 95% CI -11.73 to -1.22, P = 0.01), AST (ES -5.35, 95% CI -9.78 to -0.93, P = 0.01), degrees of fibrosis (ES -0.24, 95% CI -0.36 to -0.12, P < 0.001) and steatosis (ES -0.67, 95% CI -0.88 to -0.45, P < 0.001) in NAFLD patients, but had no effect on GGT. In the subgroup analyses, we detected that fibrosis scores notably decreased when vitamin E dosage was >600 IU/day (ES -0.25, 95% CI -0.41 to -0.10, P = 0.002) and when the treatment duration was ≥12 months (ES -0.24, 95% CI -0.37 to -0.12, P < 0.001). CONCLUSION Vitamin E administration improves ALT, AST, fibrosis, and steatosis in NAFLD subjects. Fibrosis scores were significantly reduced when vitamin E dosage exceeded 600 IU/day or with a treatment duration of at least 12 months.
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Affiliation(s)
- Ming Yue Wang
- School of Pharmacy, Nantong University, Nantong, Jiangsu Province, China
- Department of Pharmacy, Yancheng Third People's Hospital, Yancheng, Jiangsu Province, China
| | - Kousalya Prabahar
- Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Mihnea-Alexandru Găman
- Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Jin Lin Zhang
- School of Pharmacy, Nantong University, Nantong, Jiangsu Province, China
- Department of Pharmacy, Tumor Hospital Affiliated to Nantong University, Nantong, Jiangsu Province, China
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5
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de Oliveira VA, Oliveira IKF, Pereira IC, Mendes LKF, Carneiro da Silva FC, Torres-Leal FL, de Castro E Sousa JM, Paiva ADA. Consumption and supplementation of vitamin E in breast cancer risk, treatment, and outcomes: A systematic review with meta-analysis. Clin Nutr ESPEN 2023; 54:215-226. [PMID: 36963866 DOI: 10.1016/j.clnesp.2023.01.032] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/17/2023] [Accepted: 01/27/2023] [Indexed: 02/03/2023]
Abstract
BACKGROUND Robust evidence have shown diet or dietary components in playing a direct role on cancer chemoprevention such as breast cancer (BC), and also prevention against cancer therapy side effects. In this context, vitamin E isoforms have been associated with tumor suppression pathways, mainly related to proliferation, invasion, metastasis, tumor metabolism and chemoresistance. OBJECTIVE Therefore, we performed a systematic review with meta-analysis to assess the effects of vitamin E consumption and/or supplementation on breast cancer risk, treatment, and outcomes. METHODS The studies were selected in the electronic databases PubMed, Science Direct, Scopus and Web of Science. RESULTS A total of 22 articles were selected, which nine manuscripts we perform the meta-analysis. The summary effect estimate did not indicate any significant association between consumption versus non-consumption of total vitamin E and breast cancer risk. After assessing the effects of vitamin E supplementation on breast cancer risk, only two had data for comparison and vitamin E supplementation presented no impact on breast cancer risk. However, the summary effect estimate from the included studies indicated that vitamin E consumption was inversely associated with breast cancer recurrence in the control group. There are no significant results regarding dietary or supplemental vitamin E intake and BC risk reduction. CONCLUSION Finally, regarding recurrence, survival, and mortality, the results indicated that vitamin E consumption was inversely associated with breast cancer recurrence, although no association was found for breast cancer mortality.
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Affiliation(s)
- Victor Alves de Oliveira
- Departament of Nutrition, Campus Senador Helvídio Nunes de Barros - CSHNB, Federal University of Piauí - UFPI, Picos, PI, Brazil; Post-graduate Program of Food and Nutrition, Federal University of Piauí - UFPI, PI, Brazil.
| | | | - Irislene Costa Pereira
- Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN) Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piaui, Teresina, Brazil
| | - Layza Karyne Farias Mendes
- Departament of Nutrition, Campus Senador Helvídio Nunes de Barros - CSHNB, Federal University of Piauí - UFPI, Picos, PI, Brazil
| | | | - Francisco Leonardo Torres-Leal
- Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN) Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piaui, Teresina, Brazil
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Brigelius-Flohé R. Vitamin E research: Past, now and future. Free Radic Biol Med 2021; 177:381-390. [PMID: 34756995 DOI: 10.1016/j.freeradbiomed.2021.10.029] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 10/07/2021] [Accepted: 10/09/2021] [Indexed: 12/13/2022]
Abstract
The early history of vitamin E from its discovery by Herbert M. Evans and Katharine J. S. Bishop in 1922 up to its chemical synthesis by Paul Karrer and coworkers in 1938 and the development of the concept that vitamin E acts as an antioxidant in vivo are recalled. Some more recent results shedding doubt on this hypothesis are reviewed. They comprise influence of vitamin E on enzyme activities, signaling cascades, gene expression and bio-membrane structure. The overall conclusion is that our knowledge of the vitamin's mechanism of action still remains fragmentary. The metabolism of tocopherols and tocotrienols is presented and discussed in respect to bioactivity of the metabolites, interference with drug metabolism and the future design of clinical trials. Some strategies are recommended how to reach the final goal: the identification of the primary vitamin E target(s) and the analysis of the downstream events up to the physiological phenomena.
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Affiliation(s)
- Regina Brigelius-Flohé
- German Institute of Human Nutrition Potsdam Rehbrücke, Arthur-Scheunert-Alle 114-116, 14558, Nuthetal, Germany.
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Traber MG, Head B. Vitamin E: How much is enough, too much and why! Free Radic Biol Med 2021; 177:212-225. [PMID: 34699937 DOI: 10.1016/j.freeradbiomed.2021.10.028] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 09/08/2021] [Accepted: 10/11/2021] [Indexed: 12/12/2022]
Abstract
α-Tocopherol (α-T) is a required dietary nutrient for humans and thus is a vitamin. This narrative review focuses on vitamin E structures, functions, biological determinants and its deficiency symptoms in humans. The mechanisms for the preferential α-T tissue enrichment in the human body include the α-T transfer protein (TTPA) and the preferential metabolism of non-α-T forms. Potential new α-T biomarkers, pharmacokinetic data, and whether there are better approaches to evaluate and set the α-T dietary requirement are discussed. Finally, the possible role of α-T supplements in delay of chronic diseases and the evaluation of vitamin E safety are considered.
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Affiliation(s)
- Maret G Traber
- Linus Pauling Institute, USA; School of Biological and Population Health Sciences, College of Public Health and Human Sciences, USA.
| | - Brian Head
- Linus Pauling Institute, USA; Molecular and Cell Biology Program, Oregon State University, Corvallis, OR, USA
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8
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Depaoli S, Lai K, Yang Y. Bayesian Model Averaging as an Alternative to Model Selection for Multilevel Models. MULTIVARIATE BEHAVIORAL RESEARCH 2021; 56:920-940. [PMID: 32619364 DOI: 10.1080/00273171.2020.1778439] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
We investigated the Bayesian model averaging (BMA) technique as an alternative method to the traditional model selection approaches for multilevel models (MLMs). BMA synthesizes the information derived from all possible models and comes up with a weighted estimate. A simulation study compared BMA with additional modeling techniques, including the single "best" model approach, Bayesian MLM using informative, diffuse, and inaccurate priors, and restricted maximum likelihood. A two-level random intercept and random slope model was examined with these modeling techniques. Generated data used two types of true models: a full MLM and a reduced MLM. Findings of the simulation study suggested that BMA was a trustworthy alternative to traditional model comparison and selection approaches through the Bayesian and the frequentist frameworks. We also include an empirical example highlighting the extension of MLMs into the BMA framework, as well as model interpretation.
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Affiliation(s)
- Sarah Depaoli
- Psychological Sciences, University of California, Merced
| | - Keke Lai
- Psychological Sciences, University of California, Merced
| | - Yuzhu Yang
- Psychological Sciences, University of California, Merced
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9
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Abdel-Maboud M, Menshawy A, Menshawy E, Emara A, Alshandidy M, Eid M. The efficacy of vitamin E in reducing non-alcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression. Therap Adv Gastroenterol 2020; 13:1756284820974917. [PMID: 33335561 PMCID: PMC7724271 DOI: 10.1177/1756284820974917] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 10/29/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population. Clinical trials have questioned the role of vitamin E in the treatment of NAFLD with or without other interventions, with still no firm conclusion reached. This study aims to examine the efficiency of vitamin E alone or combined in the management of NAFLD. METHODS We performed a systematic literature search on PubMed, Scopus, Embase, Ovid, EBSCO host, Science Direct, Web of Science, and Cochrane CENTRAL for randomized controlled trials (RCTs) of the role of vitamin E alone or combined in NAFLD patients. Extracted manuscripts reported data on biochemical, histological, anthropometric, and metabolic outcomes. Baseline characteristics, settings, dosage, and frequency were also collected. RESEARCH A total of 1317 patients from 15 RCTs were included in our systematic review and meta-analysis. Vitamin E was superior at improving alanine aminotransferase (ALT), aspartate aminotransferase (AST), NAFLD activity score (NAS), and fibrosis in short- and long-term follow up in the adult population, and long-term follow up in the pediatric population. Improvements in metabolic outcomes were best noticed in pediatric patients. Results from multiple regression models showed a significant association between ALT-AST levels and vitamin E dose. AST levels had a significant effect on NAS, and patients with a baseline AST > 50 IU/l showed more promising results. Changes in weight and body mass index (BMI) were strongly associated with changes in NAS. CONCLUSION Current evidence affirms that vitamin E - whether alone or combined - improves biochemical and histological outcomes in adults and pediatric patients.
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Affiliation(s)
| | - Amr Menshawy
- Faculty of Medicine, Al-Azhar University, Cairo,
Egypt
| | | | - Amany Emara
- Faculty of Medicine, Al-Azhar University, Cairo,
Egypt
| | | | - Muhammad Eid
- Faculty of Medicine, Al-Azhar University, Cairo,
Egypt
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10
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Asbaghi O, Sadeghian M, Nazarian B, Sarreshtedari M, Mozaffari-Khosravi H, Maleki V, Alizadeh M, Shokri A, Sadeghi O. The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials. Sci Rep 2020; 10:17234. [PMID: 33057114 PMCID: PMC7560744 DOI: 10.1038/s41598-020-73741-6] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 09/17/2020] [Indexed: 12/15/2022] Open
Abstract
The previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (− 0.52, 95% CI − 0.80, − 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose–response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (Pnon-linearity = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.
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Affiliation(s)
- Omid Asbaghi
- Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Mehdi Sadeghian
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
| | - Behzad Nazarian
- Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | | | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Vahid Maleki
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Clinical Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Alizadeh
- Department of Clinical Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. .,Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Azad Shokri
- Social Determinants of Health Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Gerash University of Medical Sciences, Gerash, Iran
| | - Omid Sadeghi
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran. .,Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, P.O. Box 14155-6117, Tehran, Iran.
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11
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Tang JT, Mao YM. Pharmacotherapy of nonalcoholic steatohepatitis: Reflections on the existing evidence. J Dig Dis 2017; 18:607-617. [PMID: 29106066 DOI: 10.1111/1751-2980.12557] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2017] [Revised: 09/05/2017] [Accepted: 10/29/2017] [Indexed: 12/11/2022]
Abstract
Pharmacotherapy for nonalcoholic fatty liver disease (NAFLD) has not yet been approved by the US Food and Drug Administration. Over the past decade, a large number of clinical studies have explored the safety and efficacy of different drugs in treating nonalcoholic steatohepatitis (NASH), including diet pills, antioxidants, insulin sensitizers, lipid-lowering agents, anti-inflammatory cytokines, cytoprotective agents and intestinal probiotics. Based on the evidence from randomized controlled trials a number of academic groups have developed guidelines for the diagnosis and management of NAFLD and NASH. In this article, we discussed the current situation of NASH pharmacotherapy.
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Affiliation(s)
- Jie Ting Tang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
| | - Yi Min Mao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
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12
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Klebanoff MJ, Corey KE, Chhatwal J, Kaplan LM, Chung RT, Hur C. Bariatric surgery for nonalcoholic steatohepatitis: A clinical and cost-effectiveness analysis. Hepatology 2017; 65:1156-1164. [PMID: 27880977 DOI: 10.1002/hep.28958] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 10/11/2016] [Accepted: 11/18/2016] [Indexed: 12/14/2022]
Abstract
UNLABELLED Nonalcoholic steatohepatitis (NASH) affects 2%-3% of the US population and is expected to become the leading indication for liver transplantation in the next decade. Bariatric surgery may be an effective but expensive treatment for NASH. Using a state-transition model, our analysis assessed the effectiveness and cost-effectiveness of surgery to manage NASH. We simulated the benefits and harms of laparoscopic Roux-en-Y gastric bypass surgery in patients defined by weight class (overweight, mild obesity, moderate obesity, and severe obesity) and fibrosis stage (F0-F3). Comparators included intensive lifestyle intervention (ILI) and no treatment. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios were calculated. Our results showed that surgery and ILI in obese patients (with F0-F3) increased QALYs by 0.678-2.152 and 0.452-0.618, respectively, compared with no treatment. Incremental cost-effectiveness ratios for surgery in all F0-F3 patients with mild, moderate, or severe obesity were $48,836/QALY, $24,949/QALY, and $19,222/QALY, respectively. In overweight patients (with F0-F3), surgery increased QALYs by 0.050-0.824 and ILI increased QALYs by 0.031-0.164. In overweight patients, it was cost-effective to reserve treatment only for F3 patients; the incremental cost-effectiveness ratios for providing surgery or ILI only to F3 patients were $30,484/QALY and $25,367/QALY, respectively. CONCLUSIONS Surgery was both effective and cost-effective for obese patients with NASH, regardless of fibrosis stage; in overweight patients, surgery increased QALYs for all patients regardless of fibrosis stage, but was cost-effective only for patients with F3 fibrosis; our results highlight the promise of bariatric surgery for treating NASH and underscore the need for clinical trials in this area. (Hepatology 2017;65:1156-1164).
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Affiliation(s)
- Matthew J Klebanoff
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA.,Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA.,Yale University School of Medicine, New Haven, CT
| | - Kathleen E Corey
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - Jagpreet Chhatwal
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA.,Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - Lee M Kaplan
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - Raymond T Chung
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - Chin Hur
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA.,Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA.,Harvard Medical School, Boston, MA
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Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J, Cruciani G, Lorkowski S, Özer NK. Vitamin E: Emerging aspects and new directions. Free Radic Biol Med 2017; 102:16-36. [PMID: 27816611 DOI: 10.1016/j.freeradbiomed.2016.09.017] [Citation(s) in RCA: 267] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 09/11/2016] [Accepted: 09/22/2016] [Indexed: 12/30/2022]
Abstract
The discovery of vitamin E will have its 100th anniversary in 2022, but we still have more questions than answers regarding the biological functions and the essentiality of vitamin E for human health. Discovered as a factor essential for rat fertility and soon after characterized for its properties of fat-soluble antioxidant, vitamin E was identified to have signaling and gene regulation effects in the 1980s. In the same years the cytochrome P-450 dependent metabolism of vitamin E was characterized and a first series of studies on short-chain carboxyethyl metabolites in the 1990s paved the way to the hypothesis of a biological role for this metabolism alternative to vitamin E catabolism. In the last decade other physiological metabolites of vitamin E have been identified, such as α-tocopheryl phosphate and the long-chain metabolites formed by the ω-hydroxylase activity of cytochrome P-450. Recent findings are consistent with gene regulation and homeostatic roles of these metabolites in different experimental models, such as inflammatory, neuronal and hepatic cells, and in vivo in animal models of acute inflammation. Molecular mechanisms underlying these responses are under investigation in several laboratories and side-glances to research on other fat soluble vitamins may help to move faster in this direction. Other emerging aspects presented in this review paper include novel insights on the mechanisms of reduction of the cardiovascular risk, immunomodulation and antiallergic effects, neuroprotection properties in models of glutamate excitotoxicity and spino-cerebellar damage, hepatoprotection and prevention of liver toxicity by different causes and even therapeutic applications in non-alcoholic steatohepatitis. We here discuss these topics with the aim of stimulating the interest of the scientific community and further research activities that may help to celebrate this anniversary of vitamin E with an in-depth knowledge of its action as vitamin.
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Affiliation(s)
- Francesco Galli
- Department of Pharmaceutical Sciences, University of Perugia, Laboratory of Clinical Biochemistry and Nutrition, Via del Giochetto, 06126 Perugia, Italy.
| | - Angelo Azzi
- USDA-HNRCA at Tufts University, 711 Washington St., Boston, MA 02111, United States.
| | - Marc Birringer
- Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, Leipziger Straße 123, 36037 Fulda, Germany.
| | - Joan M Cook-Mills
- Allergy/Immunology Division, Northwestern University, 240 E Huron, Chicago, IL 60611, United States.
| | | | - Jan Frank
- Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 28, 70599 Stuttgart, Germany.
| | - Gabriele Cruciani
- Department of Chemistry, Biology and Biotechnology, University of Perugia, Italy.
| | - Stefan Lorkowski
- Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 25, 07743 Jena, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany.
| | - Nesrin Kartal Özer
- Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research Center (GEMHAM), Marmara University, 34854 Maltepe, Istanbul, Turkey.
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Patel V, McGurk M. Use of pentoxifylline and tocopherol in radiation-induced fibrosis and fibroatrophy. Br J Oral Maxillofac Surg 2016; 55:235-241. [PMID: 28027781 DOI: 10.1016/j.bjoms.2016.11.323] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 11/27/2016] [Indexed: 12/14/2022]
Abstract
Radiation-induced fibrosis in the head and neck is a well-established pathophysiological process after radiotherapy. Recently pentoxifylline and tocopherol have been proposed as treatments to combat the late complications of radiation-induced fibrosis and a way of dealing with osteoradionecrosis. They both have a long history in the management of radiation-induced fibrosis at other anatomical sites. In this paper we review their use in sites other than the head and neck to illustrate the potential benefit that they offer to our patients.
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Affiliation(s)
- V Patel
- Oral Surgery Dept, Floor 23, Guys Dental Hospital, London Bridge, London, SE1 9RT.
| | - M McGurk
- Department of Oral and Maxillofacial Surgery, Atrium 3, 3rd Floor, Bermondsey Wing, Guy's Hospital, London, SE1 9RT.
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15
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Vitamin E and the risk of pneumonia: using the I 2 statistic to quantify heterogeneity within a controlled trial. Br J Nutr 2016; 116:1530-1536. [PMID: 27780487 DOI: 10.1017/s0007114516003408] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Analyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50-69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I 2 statistic. The I 2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I 2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89 % (95 % CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I 2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92 % (95 % CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69 % among participants who had the least exposure to smoking and exercised during leisure time (7·6 % of the ATBC participants), and vitamin E increased pneumonia risk by 68 % among those who had the highest exposure to smoking and did not exercise (22 % of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.
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Sawangjit R, Chongmelaxme B, Phisalprapa P, Saokaew S, Thakkinstian A, Kowdley KV, Chaiyakunapruk N. Comparative efficacy of interventions on nonalcoholic fatty liver disease (NAFLD): A PRISMA-compliant systematic review and network meta-analysis. Medicine (Baltimore) 2016; 95:e4529. [PMID: 27512874 PMCID: PMC4985329 DOI: 10.1097/md.0000000000004529] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The prevalence of nonalcoholic fatty liver disease (NAFLD) has significantly increased over the last decades. Despite existence of several interventions, there remains unclear which interventions work the best. METHODS A systematic review and network meta-analysis of randomized trials comparing efficacy of all treatment options in NAFLD were performed to determine comparative efficacy and safety of interventions in the management of NAFLD. Several electronic databases were searched up to Nov 15, 2015. Outcomes include liver histological outcomes (i.e., fibrosis), all-cause mortality, cirrhosis, and safety. A network meta-analysis was applied to estimate pooled risk ratios (RR). Quality of evidence was assessed using GRADE criteria. RESULTS A total of 44 studies (n = 3802) were eligible. When compared with placebo, obeticholic acid (OCA) was the only intervention that significantly improved fibrosis with RR (95% CI) of 1.91 (1.15, 3.16), while pentoxyfylline (PTX) demonstrated improved fibrosis without statistical significance with RR (95% CI) of 2.27 (0.81, 6.36). Only thiazolidinedione (TZD) and vitamin E use resulted in significant increase in resolution of NASH, while OCA, TZD, and vitamin E significantly improved other outcomes including NAS, steatosis, ballooning, and inflammation outcomes. Quality of evidence varied from very low (i.e., metformin, PTX on mean change of ballooning grade) to high (OCA, TZD, vitamin E on improving histological outcomes). Limitations of this study were lack of relevant long-term outcomes (e.g., cirrhosis, death, safety), possible small study effect, and few head-to-head studies. CONCLUSIONS Our study suggests potential efficacy of OCA, TZD, and vitamin E in improving histologic endpoints in NAFLD. These findings are however based on a small number of studies. Additional studies are awaited to strengthen this network meta-analysis.
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Affiliation(s)
- Ratree Sawangjit
- Clinical Pharmacy Research Unit (CPRU), Department of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Mahasarakham, Thailand
- School of Pharmacy, Monash University Malaysia, Selangor, Malaysia
| | - Bunchai Chongmelaxme
- Center of Pharmaceutical Outcomes Research, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok
| | - Pochamana Phisalprapa
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok
| | - Surasak Saokaew
- School of Pharmacy, Monash University Malaysia, Selangor, Malaysia
- Center of Pharmaceutical Outcomes Research, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok
- Center of Health Outcome Research and Therapeutic Safety, School of Pharmaceutical Sciences,University of Phayao, Phayao
| | - Ammarin Thakkinstian
- Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Kris V. Kowdley
- Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle
| | - Nathorn Chaiyakunapruk
- School of Pharmacy, Monash University Malaysia, Selangor, Malaysia
- Center of Pharmaceutical Outcomes Research, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok
- School of Pharmacy, University of Wisconsin, Madison, WI
- School of Population Health, University of Queensland, Brisbane, QLD, Australia
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Rinella ME, Lominadze Z, Loomba R, Charlton M, Neuschwander-Tetri BA, Caldwell SH, Kowdley K, Harrison SA. Practice patterns in NAFLD and NASH: real life differs from published guidelines. Therap Adv Gastroenterol 2016; 9:4-12. [PMID: 26770262 PMCID: PMC4699276 DOI: 10.1177/1756283x15611581] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Management guidelines from the American Association for the Study of Liver Diseases/American College of Gastroenterology/American Gastroenterology Association published in 2012 for nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) recommend weight loss, vitamin E and pioglitazone as effective therapies for the treatment of biopsy-confirmed NASH. However, little is known about how physicians in the US diagnose NASH or whether published guidelines are being followed. METHODS We assessed current diagnostic and treatment patterns of the management of NAFLD and NASH among academic gastroenterologists and hepatologists in the US using a standardized survey developed to collect information regarding respondents' practice environments, diagnostic techniques, and medication usage in patients with NAFLD/NASH. RESULTS We invited 482 gastroenterologists and hepatologists, predominantly from academic centers, of whom 163 completed the survey. Only 24% of providers routinely perform liver biopsy, predominantly among patients with elevated serum aminotransferases. Vitamin E is prescribed regularly by 70% while only 14% routinely prescribe pioglitazone. Despite recommendations to the contrary, ~25% prescribe pioglitazone or vitamin E without biopsy confirmation of NASH. Metformin is used as frequently as pioglitazone despite its proven lack of efficacy in NASH. Overall, 40-73% adhere to published guidelines, depending on the specific question. There was no significant difference seen in adherence to guidelines between gastroenterologists and hepatologists. CONCLUSION This survey suggests that clinical practice patterns among gastroenterologists and hepatologists for the management of NASH frequently diverge from published practice guidelines. Although liver biopsy remains the gold standard to diagnose NASH, less than 25% of respondents routinely require it to make the diagnosis of NASH. We conclude that NASH is underdiagnosed in gastroenterology and hepatology practices, highlighting the need to refine noninvasive diagnostic tools.
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Affiliation(s)
| | - Zurabi Lominadze
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Rohit Loomba
- Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla CA, USA
| | | | | | - Stephen H. Caldwell
- Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Kris Kowdley
- Division of Gastroenterology and Hepatology, Swedish Hospital Medical Center, Seattle Washington, USA
| | - Stephen A. Harrison
- Division of Gastroenterology and Hepatology, Brooke Army Medical Center, San Antonio, Texas, USA
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18
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Rondanelli M, Faliva MA, Peroni G, Moncaglieri F, Infantino V, Naso M, Perna S. Focus on Pivotal Role of Dietary Intake (Diet and Supplement) and Blood Levels of Tocopherols and Tocotrienols in Obtaining Successful Aging. Int J Mol Sci 2015; 16:23227-49. [PMID: 26404241 PMCID: PMC4632695 DOI: 10.3390/ijms161023227] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 09/11/2015] [Accepted: 09/21/2015] [Indexed: 12/14/2022] Open
Abstract
Numerous specific age-related morbidities have been correlated with low intake and serum levels of tocopherols and tocotrienols. We performed a review in order to evaluate the extant evidence regarding: (1) the association between intake and serum levels of tocopherols and tocotrienols and age-related pathologies (osteoporosis, sarcopenia and cognitive impairment); and (2) the optimum diet therapy or supplementation with tocopherols and tocotrienols for the treatment of these abnormalities. This review included 51 eligible studies. The recent literature underlines that, given the detrimental effect of low intake and serum levels of tocopherols and tocotrienols on bone, muscle mass, and cognitive function, a change in the lifestyle must be the cornerstone in the prevention of these specific age-related pathologies related to vitamin E-deficient status. The optimum diet therapy in the elderly for avoiding vitamin E deficiency and its negative correlates, such as high inflammation and oxidation, must aim at achieving specific nutritional goals. These goals must be reached through: accession of the elderly subjects to specific personalized dietary programs aimed at achieving and/or maintaining body weight (avoid malnutrition); increase their intake of food rich in vitamin E, such as derivatives of oily seeds (in particular wheat germ oil), olive oil, hazelnuts, walnuts, almonds, and cereals rich in vitamin E (such as specific rice cultivar rich in tocotrienols) or take vitamin E supplements. In this case, vitamin E can be correctly used in a personalized way either for the outcome from the pathology or to achieve healthy aging and longevity without any adverse effects.
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Affiliation(s)
- Mariangela Rondanelli
- Department of Public Health, Experimental and Forensic Medicine, School of Medicine, Endocrinology and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di Pavia, Pavia 27100, Italy.
| | - Milena Anna Faliva
- Department of Public Health, Experimental and Forensic Medicine, School of Medicine, Endocrinology and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di Pavia, Pavia 27100, Italy.
| | - Gabriella Peroni
- Department of Public Health, Experimental and Forensic Medicine, School of Medicine, Endocrinology and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di Pavia, Pavia 27100, Italy.
| | - Francesca Moncaglieri
- Department of Public Health, Experimental and Forensic Medicine, School of Medicine, Endocrinology and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di Pavia, Pavia 27100, Italy.
| | - Vittoria Infantino
- Department of Public Health, Experimental and Forensic Medicine, School of Medicine, Endocrinology and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di Pavia, Pavia 27100, Italy.
| | - Maurizio Naso
- Faculty of Medicine and Surgery, Department of Clinical Sciences, University of Milano, Milan 20100, Italy.
| | - Simone Perna
- Department of Public Health, Experimental and Forensic Medicine, School of Medicine, Endocrinology and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di Pavia, Pavia 27100, Italy.
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19
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Abstract
Lifestyle modifications and optimization of the management of cardiometabolic comorbidities are currently the mainstay of treatment for patients with nonalcoholic fatty liver disease. Pharmacotherapy to halt or reverse hepatic histological injury and prevent the development of end-stage liver disease is specifically offered to patients with nonalcoholic steatohepatitis (NASH) and those with advanced fibrosis. In this review, the authors discuss the state of the art of various pharmacological agents for NASH. The efficacy of vitamin E and pioglitazone is reasonably well established in a selected group of patients with NASH. Current data do not offer convincing evidence for efficacy of pentoxifylline, long-chain polyunsaturated fatty acids, angiotensin receptor blockers, metformin, or ursodeoxycholic acid. They also discuss the state of several emerging agents for treating NASH including the farsenoid X receptor ligand, obeticholic acid.
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Affiliation(s)
- Samer Gawrieh
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
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20
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Polimeni L, Del Ben M, Baratta F, Perri L, Albanese F, Pastori D, Violi F, Angelico F. Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis. World J Hepatol 2015; 7:1325-1336. [PMID: 26052378 PMCID: PMC4450196 DOI: 10.4254/wjh.v7.i10.1325] [Citation(s) in RCA: 148] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Revised: 12/01/2014] [Accepted: 03/18/2015] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and more severe liver complications such as cirrhosis, hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity, insulin resistance, hypertension, and dyslipidaemia, and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and, to a lesser extent, to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus, oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed, with conflicting results. In particular, vitamin E supplementation has been suggested for the treatment of non-diabetic, non-cirrhotic adults with active NASH, although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol, silybin, L-carnitine and pentoxiphylline. No trial so far, has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New, large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.
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21
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Zerbinati C, Galli F, Regolanti R, Poli G, Iuliano L. Gas chromatography-mass spectrometry microanalysis of alpha- and gamma-tocopherol in plasma and whole blood. Clin Chim Acta 2015; 446:156-62. [PMID: 25916693 DOI: 10.1016/j.cca.2015.04.026] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 04/11/2015] [Accepted: 04/11/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Assessing vitamin E status in humans is critical for nutritional evaluation and verification of clinical and biological compliance of supplemented subjects. An accurate analytical method for measuring the two main vitamin E isoforms, i.e. α- and γ-tocopherol (α- and γ-TOH) in small volumes of plasma can facilitate the application of this analysis to clinical trials and in situations where a limited amount of sample is available. METHODS We have developed a micro method, which uses only 5 μL plasma, based on isotope dilution, trimethylsilation and GC-MS. The method was validated according to the guidelines of the International Conference on Harmonization of analytical procedures. The method was also applied to 5 μL of whole blood for the potential use in conditions were the availability of specimens is limited. RESULTS Accurate quantitation of α-TOH and γ-TOH was achieved at levels ≥ 0.417 μM and ≥ 0.007 μM, respectively. Within-day coefficient of variation was 1.31% and 4.70% for α-TOH and γ-TOH, respectively. Between-day coefficient of variation was 1.32% and 2.88% for α-TOH and γ-TOH, respectively. Recovery, assessed at three concentration levels, ranged 98-103% and 100-102% for α-TOH and γ-TOH, respectively. The method allowed the detection of α-TOH and γ-TOH in 5 μL whole blood and in membranes of red blood cells washed from 5 μL of blood as well. The analytical performance was assessed in plasma from a cohort of Italian healthy subjects (n = 205). The mean plasma concentrations were 28.01 ± 6.31 and 0.68 ± 0.48 μM (mean ± SD) for α-TOH and γ-TOH, respectively. Alpha-TOH correlated with total cholesterol (r = 0.617, p < 0.0001) and triglycerides (r = 0.420, p < 0.0001) while γ-TOH correlated modestly with total cholesterol (r = 0.213, p < 0.0001) but not with triglycerides. γ-TOH, but not α-TOH, was significantly lower in smokers than in non-smokers (0.72 ± 0.50 vs. 0.56 ± 0.37, μM, mean ± SD, p = 0.017). Given the high sensitivity, the method allowed to be applied to 5 μM whole blood without specific modification. CONCLUSIONS This micro-method represents an analytical advancement in α- and γ-TOH assay that is available to accurately verify the nutritional status and compliance after supplementation in large-scale settings, and to measure the two vitamers in conditions where sample availability is limited.
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Affiliation(s)
- C Zerbinati
- Department of Medico-Surgical Sciences and Biotechnologies, Laboratory of Vascular Biology and Mass Spectrometry, Sapienza University of Rome, Latina, Italy
| | - F Galli
- Department of Internal Medicine, Laboratory of Clinical Biochemistry and Nutrition, University of Perugia, Perugia, Italy
| | - R Regolanti
- Department of Medico-Surgical Sciences and Biotechnologies, Laboratory of Vascular Biology and Mass Spectrometry, Sapienza University of Rome, Latina, Italy
| | - G Poli
- Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
| | - L Iuliano
- Department of Medico-Surgical Sciences and Biotechnologies, Laboratory of Vascular Biology and Mass Spectrometry, Sapienza University of Rome, Latina, Italy.
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22
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Jiang S, Pan Z, Li H, Li F, Song Y, Qiu Y. Meta-analysis: low-dose intake of vitamin E combined with other vitamins or minerals may decrease all-cause mortality. J Nutr Sci Vitaminol (Tokyo) 2015; 60:194-205. [PMID: 25078376 DOI: 10.3177/jnsv.60.194] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
It has been suggested that vitamin E alone or combined with other vitamins or minerals can prevent oxidative stress and slow oxidative injury-related diseases, such as cardiovascular disease and cancer. A comprehensive search of PubMed/MEDLINE, EMBASE and the Cochrane Library was performed. Relative risk was used as an effect measure to compare the intervention and control groups. A total of 33 trials were included in the meta-analysis. Neither vitamin E intake alone (RR=1.01; 95% CI, 0.97 to 1.04; p=0.77) nor vitamin E intake combined with other agents (RR=0.97; 95% CI, 0.89 to 1.06; p=0.55) was correlated with all-cause mortality. Subgroup analyses revealed that low-dose vitamin E supplementation combined with other agents is associated with a statistically significant reduction in all-cause mortality (RR=0.92; 95% CI, 0.86 to 0.98; p=0.01), and vitamin E intake combined with other agents is associated with a statistically significant reduction in mortality rates among individuals without probable or confirmed diseases (RR=0.92; 95% CI, 0.86 to 0.99; p=0.02). Neither vitamin E intake alone nor combined with other agents is associated with a reduction in all-cause mortality. But a low dose (<400 IU/d) of vitamin E combined with other agents is correlated with a reduction in all-cause mortality, and vitamin E intake combined with other agents is correlated with a reduction in the mortality rate among individuals without probable or confirmed diseases.
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Affiliation(s)
- Shan Jiang
- Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
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23
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Loffredo L, Perri L, Di Castelnuovo A, Iacoviello L, De Gaetano G, Violi F. Supplementation with vitamin E alone is associated with reduced myocardial infarction: a meta-analysis. Nutr Metab Cardiovasc Dis 2015; 25:354-363. [PMID: 25779938 DOI: 10.1016/j.numecd.2015.01.008] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 01/22/2015] [Accepted: 01/23/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Previous meta-analyses of interventional trials with vitamin E provided negative results but it remains unclear if this vitamin has some influence on cardiovascular events when supplemented alone. The aim of this study was to compare the effect of vitamin E alone or in combination with other antioxidants on myocardial infarction. METHODS AND RESULTS Pubmed, ISI Web of Science, SCOPUS and Cochrane database were searched without language restrictions. We investigated randomized clinical trials studying the effect of vitamin E supplementation on myocardial infarction. Sixteen randomized controlled trials of vitamin E treatment were analyzed in this meta-analysis. The dose range for vitamin E was 33-800IU. Follow-up ranged from 0.5 to 9.4 years. Compared to controls, vitamin E given alone significantly decreased myocardial infarction (3.0% vs 3.4%) (random effects R.R.: 0.82; 95% C.I., 0.70-0.96; p = 0.01). This effect was driven by reduction of fatal myocardial infarction (random effects R.R.: 0.84; 95% C.I., 0.73-0.96; p = 0.01). CONCLUSIONS When supplemented alone, vitamin E reduces myocardial infarction in interventional trials while it appears ineffective when associated with other antioxidants.
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Affiliation(s)
- L Loffredo
- I Clinica Medica, Sapienza University of Rome, Italy.
| | - L Perri
- I Clinica Medica, Sapienza University of Rome, Italy
| | - A Di Castelnuovo
- Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, IS, Italy
| | - L Iacoviello
- Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, IS, Italy
| | - G De Gaetano
- Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, IS, Italy
| | - F Violi
- I Clinica Medica, Sapienza University of Rome, Italy
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24
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Sato K, Gosho M, Yamamoto T, Kobayashi Y, Ishii N, Ohashi T, Nakade Y, Ito K, Fukuzawa Y, Yoneda M. Vitamin E has a beneficial effect on nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Nutrition 2014; 31:923-30. [PMID: 26059365 DOI: 10.1016/j.nut.2014.11.018] [Citation(s) in RCA: 137] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Revised: 11/14/2014] [Accepted: 11/21/2014] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Vitamin E is often used in the treatment of nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH); however, the magnitude of treatment response associated with vitamin E in improving liver function and histology in NAFLD/NASH has not, to our knowledge, been quantified systematically. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs) using vitamin E in the treatment of NAFLD/NASH. METHODS PubMed, Medline, and Cochrane Library Full Text Database, and Japan Medical-Literature Database (Igaku Chuo Zasshi) were searched until March 2014, and five RCTs were identified for meta-analysis. RESULTS According to a random effect model analysis of the five studies, vitamin E significantly reduced aspartate transaminase (AST) by -19.43 U/L, alanine aminotransferase (ALT) by -28.91 U/L, alkaline phosphatase (ALP) by -10.39 U/L, steatosis by -0.54 U/L, inflammation by -0.20 U/L, and hepatocellular ballooning by -0.34 U/L compared with the control group. Vitamin E treatment with NASH adult patients showed obvious reductions in not only AST of -13.91 U/L, ALT by -22.44 U/L, steatosis of -0.67 U/L, inflammation of -0.20 U/L, but also fibrosis of -0.30 U/L compared to the control treatment. CONCLUSIONS Vitamin E significantly improved liver function and histologic changes in patients with NAFLD/NASH.
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Affiliation(s)
- Ken Sato
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan.
| | - Masahiko Gosho
- Advanced Medical Research Center, Aichi Medical University, Nagakute, Japan
| | - Takaya Yamamoto
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Yuji Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Norimitsu Ishii
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Tomohiko Ohashi
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Yukiomi Nakade
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Kiyoaki Ito
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Yoshitaka Fukuzawa
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Masashi Yoneda
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
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Nonalcoholic Fatty liver disease: pathogenesis and therapeutics from a mitochondria-centric perspective. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2014; 2014:637027. [PMID: 25371775 PMCID: PMC4211163 DOI: 10.1155/2014/637027] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 07/31/2014] [Accepted: 07/31/2014] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of disorders characterized by the accumulation of triglycerides within the liver. The global prevalence of NAFLD has been increasing as the obesity epidemic shows no sign of relenting. Mitochondria play a central role in hepatic lipid metabolism and also are affected by upstream signaling pathways involved in hepatic metabolism. This review will focus on the role of mitochondria in the pathophysiology of NAFLD and touch on some of the therapeutic approaches targeting mitochondria as well as metabolically important signaling pathways. Mitochondria are able to adapt to lipid accumulation in hepatocytes by increasing rates of beta-oxidation; however increased substrate delivery to the mitochondrial electron transport chain (ETC) leads to increased reactive oxygen species (ROS) production and eventually ETC dysfunction. Decreased ETC function combined with increased rates of fatty acid beta-oxidation leads to the accumulation of incomplete products of beta-oxidation, which combined with increased levels of ROS contribute to insulin resistance. Several related signaling pathways, nuclear receptors, and transcription factors also regulate hepatic lipid metabolism, many of which are redox sensitive and regulated by ROS.
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Firneisz G. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age? World J Gastroenterol 2014; 20:9072-9089. [PMID: 25083080 PMCID: PMC4112878 DOI: 10.3748/wjg.v20.i27.9072] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Revised: 01/10/2014] [Accepted: 05/14/2014] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.
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Peverill W, Powell LW, Skoien R. Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation. Int J Mol Sci 2014; 15:8591-638. [PMID: 24830559 PMCID: PMC4057750 DOI: 10.3390/ijms15058591] [Citation(s) in RCA: 282] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2014] [Revised: 03/20/2014] [Accepted: 04/17/2014] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis and inflammation and, in some patients, progressive fibrosis leading to cirrhosis. An understanding of the pathogenesis of NASH is still evolving but current evidence suggests multiple metabolic factors critically disrupt homeostasis and induce an inflammatory cascade and ensuing fibrosis. The mechanisms underlying these changes and the complex inter-cellular interactions that mediate fibrogenesis are yet to be fully elucidated. Lipotoxicity, in the setting of excess free fatty acids, obesity, and insulin resistance, appears to be the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence contribute to activation of the inflammasome via a variety of intra- and inter-cellular signalling mechanisms leading to fibrosis. Current evidence suggests that periportal components, including the ductular reaction and expansion of the hepatic progenitor cell compartment, may be involved and that the Th17 response may mediate disease progression. This review aims to provide an overview of the pathogenesis of NASH and summarises the evidence pertaining to key mechanisms implicated in the transition from steatosis and inflammation to fibrosis. Currently there are limited treatments for NASH although an increasing understanding of its pathogenesis will likely improve the development and use of interventions in the future.
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Affiliation(s)
- William Peverill
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.
| | - Lawrie W Powell
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.
| | - Richard Skoien
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.
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Sahini N, Borlak J. Recent insights into the molecular pathophysiology of lipid droplet formation in hepatocytes. Prog Lipid Res 2014; 54:86-112. [PMID: 24607340 DOI: 10.1016/j.plipres.2014.02.002] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Revised: 02/17/2014] [Accepted: 02/21/2014] [Indexed: 12/11/2022]
Abstract
Triacyglycerols are a major energy reserve of the body and are normally stored in adipose tissue as lipid droplets (LDs). The liver, however, stores energy as glycogen and digested triglycerides in the form of fatty acids. In stressed condition such as obesity, imbalanced nutrition and drug induced liver injury hepatocytes accumulate excess lipids in the form of LDs whose prolonged storage leads to disease conditions most notably non-alcoholic fatty liver disease (NAFLD). Fatty liver disease has become a major health burden with more than 90% of obese, nearly 70% of overweight and about 25% of normal weight patients being affected. Notably, research in recent years has shown LD as highly dynamic organelles for maintaining lipid homeostasis through fat storage, protein sorting and other molecular events studied in adipocytes and other cells of living organisms. This review focuses on the molecular events of LD formation in hepatocytes and the importance of cross talk between different cell types and their signalling in NAFLD as to provide a perspective on molecular mechanisms as well as possibilities for different therapeutic intervention strategies.
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Affiliation(s)
- Nishika Sahini
- Centre for Pharmacology and Toxicology, Hannover Medical School, 30625 Hannover, Germany
| | - Jürgen Borlak
- Centre for Pharmacology and Toxicology, Hannover Medical School, 30625 Hannover, Germany.
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KASL clinical practice guidelines: management of nonalcoholic fatty liver disease. Clin Mol Hepatol 2013; 19:325-48. [PMID: 24459637 PMCID: PMC3894432 DOI: 10.3350/cmh.2013.19.4.325] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Accepted: 11/07/2013] [Indexed: 02/06/2023] Open
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Angulo-Molina A, Reyes-Leyva J, López-Malo A, Hernández J. The Role of Alpha Tocopheryl Succinate (α-TOS) as a Potential Anticancer Agent. Nutr Cancer 2013; 66:167-76. [DOI: 10.1080/01635581.2014.863367] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Jun DW. [The role of diet in non-alcoholic fatty liver disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2013; 61:243-51. [PMID: 23756665 DOI: 10.4166/kjg.2013.61.5.243] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Prevalence of non-alcoholic fatty liver disease (NAFLD) is about 20-25% in Korean adults population. Obesity is strongly associated with NAFLD and the prevention of obesity is a major public issue. Unfortunately, pharmacological treatment of obesity and NAFLD remains uncertain. Only weight loss by dietary changes been shown to lead to histological improvement in fatty liver. So the nutrition therapy is a cornerstone of treatment for NAFLD. Epidemiologic studies show that saturated fat, trans-fatty acid, carbohydrate, and simple sugar have strong correlation with intrahepatic fat accumulation. But, true associations with specific nutrients still remain unclear. Recently, fructose consumption has been rising in many countries and several epidemiologic studies show that fructose consumption has strong correlation with metabolic diseases. The consumption of excessively added sugar in the pathogenesis of steatohepatitis has received attention. Most clinicians agree with lifestyle modification are effective in histologic improvement. Total energy intake restriction is the most important action to reduce intrahepatic fat accumulation. Macronutrient composition may also have correlation with the development of NAFLD. To reduce the incidence of NAFLD, public statements on optimal dietary education program have been issused. Various specific dietary programs are suggested. Among them low fat diet and low carbohydrate diet are suggested in patients with NAFLD. However, there is no ideal diet to obtain the histological improvement in NAFLD. Further randomised controlled studies about specific diet are needed to determine the long-term benefit and histological improvement by ideal diet. Tailoring diet therapy to a patient's lifestyle is more important than universal specific dietary program.
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Affiliation(s)
- Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
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Traber MG. Mechanisms for the prevention of vitamin E excess. J Lipid Res 2013; 54:2295-306. [PMID: 23505319 PMCID: PMC3735929 DOI: 10.1194/jlr.r032946] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Revised: 03/04/2013] [Indexed: 02/07/2023] Open
Abstract
The liver is at the nexus of the regulation of lipoprotein uptake, synthesis, and secretion, and it is the site of xenobiotic detoxification by cytochrome P450 oxidation systems (phase I), conjugation systems (phase II), and transporters (phase III). These two major liver systems control vitamin E status. The mechanisms for the preference for α-tocopherol relative to the eight naturally occurring vitamin E forms largely depend upon the liver and include both a preferential secretion of α-tocopherol from the liver into the plasma for its transport in circulating lipoproteins for subsequent uptake by tissues, as well as the preferential hepatic metabolism of non-α-tocopherol forms. These mechanisms are the focus of this review.
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Affiliation(s)
- Maret G Traber
- Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
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Goldenstein H, Levy NS, Lipener YT, Levy AP. Patient selection and vitamin E treatment in diabetes mellitus. Expert Rev Cardiovasc Ther 2013; 11:319-26. [PMID: 23469912 DOI: 10.1586/erc.12.187] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
In diabetes, there is an increase in oxidative stress due to elevated glucose levels in the plasma. High glucose promotes glycosylation, of both plasma and cellular proteins, which particularly affects the endothelial-cell lining of the blood vessel wall and interferes with its normal function. Thus, diabetes mellitus patients suffer from a higher incidence of cardiovascular complications such as atherosclerosis as compared with the nondiabetic population. Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and prevents heme-iron mediated oxidation. There are three different types of Hp, which differ in their antioxidant ability. Several clinical studies have shown that the Hp 2-2 genotype is associated with higher incidence of cardiovascular diseases among diabetics. Vitamin E, a low-cost, easy-to-use antioxidant, was found to decrease the risk of developing cardiovascular diseases in Hp 2-2 diabetic patients. This review summarizes several studies that show the importance of vitamin E supplementation in a specific subgroup of patients, diabetic individuals carrying the Hp 2-2 genotype.
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Affiliation(s)
- Hagit Goldenstein
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 1 Efron Street, Bat Galim PO 9649, Haifa, 31096, Israel.
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Kryscio RJ, Abner EL, Schmitt FA, Goodman PJ, Mendiondo M, Caban-Holt A, Dennis BC, Mathews M, Klein EA, Crowley JJ. A randomized controlled Alzheimer's disease prevention trial's evolution into an exposure trial: the PREADViSE Trial. J Nutr Health Aging 2013; 17:72-5. [PMID: 23299383 DOI: 10.1007/s12603-012-0083-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVES To summarize the ongoing prevention of Alzheimer's disease (AD) by vitamin E and selenium (PREADViSE) trial as an ancillary study to SELECT (a large prostate cancer prevention trial) and to present the blinded results of the first year as an exposure study. DESIGN PREADViSE was designed as a double blind randomized controlled trial (RCT). SETTING SELECT terminated after median of 5.5 years of exposure to supplements due to a futility analysis. Both trials then converted into an exposure study. PARTICIPANTS In the randomized component PREADViSE enrolled 7,547 men age 62 or older (60 if African American). Once the trial terminated 4,246 of these men volunteered for the exposure study. Demographics were similar for both groups with exposure volunteers having baseline mean age 67.3 ± 5.2 years, 15.3 ± 2.4 years of education, 9.8% African Americans, and 22.0% reporting a family history of dementia. INTERVENTION In the RCT men were randomly assigned to either daily doses of 400 IU of vitamin E or placebo and 200 µg of selenium or placebo using a 2x2 factorial structure. MEASUREMENTS In the RCT, participants completed the memory impairment screen (MIS), and if they failed, underwent a longer screening (based on an expanded Consortium to Establish a Registry in AD [CERAD] battery). CERAD failure resulted in visits to their clinician for medical examination with records of these examinations forwarded to the PREADViSE center for further review. In the exposure study, men are contacted by telephone and complete the telephone version of the memory impairment screen (MIS-T) screen. If they fail the MIS-T, a modified telephone interview of cognitive status (TICS-M) exam is given. A failed TICS-M exam also leads to a visit to their clinician for an in-depth examination and forwarding of records for a centralized consensus diagnosis by expert clinicians. A subgroup of the men who pass the MIS-T also take the TICS-M exam for validation purposes. RESULTS While this ancillary trial was open to all 427 SELECT clinical sites, only 130 (30.0%) of the sites chose to participate in PREADViSE. Staff turnover at the sites presented challenges when training persons unfamiliar with cognitive testing procedures to conduct the memory screens. In the RCT few participants (1.6%) failed the MIS screen and among those who passed this screen a significant practice effect was encountered. In the exposure study 3,581 men were reached by phone in year 1, 15.7% could not be reached after 5 calls, and of those contacted 6.0% refused the screen even after consenting to the procedures at their clinical site. Most notable is that the failure rate for the MIS-T increased fourfold to 7.2%. Of the 257 men who took the TICS-M, 84.0% failed and were asked to contact their physicians for a more detailed memory assessment, and approximately half of these had some form of dementia or cognitive impairment. Several of these dementia cases are not AD. CONCLUSION Partnering with SELECT led to an AD prevention trial conducted at a very reasonable cost by taking advantage of the experience and efficient clinical trial management found in a cancer cooperative group (Southwest Oncology Group or SWOG). Once unblinded, the RCT and exposure study data have the potential to yield new information on long term exposure to antioxidant supplements under controlled conditions.
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Affiliation(s)
- R J Kryscio
- University of Kentucky Sanders-Brown Center on Aging, Department of Biostatistics, Lexington, KY, USA
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Mullin GE. The Use of Complementary and Alternative Medicine for Liver Disease. Nutr Clin Pract 2013; 28:138-139. [DOI: 10.1177/0884533612471766] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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Masuoka HC, Chalasani N. Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals. Ann N Y Acad Sci 2013; 1281:106-22. [PMID: 23363012 PMCID: PMC3646408 DOI: 10.1111/nyas.12016] [Citation(s) in RCA: 194] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world and its incidence is increasing rapidly. NAFLD is a spectrum ranging from simple steatosis, which is relatively benign hepatically, to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis. Obesity, insulin resistance, type 2 diabetes mellitus, and dyslipidemia are the most important risk factors for NAFLD. Due to heavy enrichment with metabolic risk factors, individuals with NAFLD are at significantly higher risk for cardiovascular disease. Individuals with NAFLD have higher incidence of type 2 diabetes. The diagnosis of NAFLD requires imaging evidence of hepatic steatosis in the absence of competing etiologies including significant alcohol consumption. Liver biopsy remains the gold standard for diagnosing NASH and for determining prognosis. Weight loss remains a cornerstone of treatment. Weight loss of ∼5% is believed to improve steatosis, whereas ∼10% weight loss is necessary to improve steatohepatitis. A number of pharmacologic therapies have been investigated to treat NASH, and agents such as vitamin E and thiazolidinediones have shown promise in select patient subgroups.
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Affiliation(s)
- Howard C Masuoka
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Kryscio RJ, Abner EL, Schmitt FA, Goodman PJ, Mendiondo M, Caban-Holt A, Dennis BC, Mathews M, Klein EA, Crowley JJ. A randomized controlled Alzheimer’s disease prevention trial’s evolution into an exposure trial: The preadvise trial. J Nutr Health Aging 2013. [DOI: 10.1007/s12603-013-0004-0] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Ibrahim JG, Chen MH, Chu H. Bayesian methods in clinical trials: a Bayesian analysis of ECOG trials E1684 and E1690. BMC Med Res Methodol 2012. [PMID: 23194570 PMCID: PMC3571975 DOI: 10.1186/1471-2288-12-183] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background E1684 was the pivotal adjuvant melanoma trial for establishment of high-dose interferon (IFN) as effective therapy of high-risk melanoma patients. E1690 was an intriguing effort to corroborate E1684, and the differences between the outcomes of these trials have embroiled the field in controversy over the past several years. The analyses of E1684 and E1690 were carried out separately when the results were published, and there were no further analyses trying to perform a single analysis of the combined trials. Method In this paper, we consider such a joint analysis by carrying out a Bayesian analysis of these two trials, thus providing us with a consistent and coherent methodology for combining the results from these two trials. Results The Bayesian analysis using power priors provided a more coherent flexible and potentially more accurate analysis than a separate analysis of these data or a frequentist analysis of these data. The methodology provides a consistent framework for carrying out a single unified analysis by combining data from two or more studies. Conclusions Such Bayesian analyses can be crucial in situations where the results from two theoretically identical trials yield somewhat conflicting or inconsistent results.
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Affiliation(s)
- Joseph G Ibrahim
- Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA.
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Abstract
PURPOSE OF REVIEW Oxidative stress plays a central role in the transition from simple steatosis to nonalcoholic steatohepatitis (NASH). An effective therapeutic strategy is to target reduction in oxidative stress in NASH patients. The aim of this review is to discuss the role of oxidative stress in NASH and biological activities of vitamin E and present available evidence on the therapeutic efficacy of vitamin E in NASH. RECENT FINDINGS In Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial, vitamin E therapy demonstrated a significant improvement in steatosis, inflammation, ballooning, and resolution of steatohepatitis in adult patients with aggressive NASH, who do not have diabetes or cirrhosis. Although vitamin E showed a significant resolution of NASH in children, a sustained reduction of alanine aminotransferase was not attained in The Treatment of nonalcoholic fatty liver disease (NAFLD) in Children (TONIC) trial. SUMMARY The prevalence of NAFLD is likely to increase over time due to the epidemics of obesity and diabetes. Presently, there is no definitive treatment for NAFLD. Based on available evidence, vitamin E (RRR-α-tocopherol) is only recommended in NASH adults without diabetes or cirrhosis and with aggressive histology. Validation is needed in children before its use can be recommended. Longer follow-up of randomized controlled trials are needed to assess long-term vitamin E safety.
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Affiliation(s)
- Tommy Pacana
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0341, USA.
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Conn VS, Ruppar TM, Phillips LJ, Chase JAD. Using meta-analyses for comparative effectiveness research. Nurs Outlook 2012; 60:182-90. [PMID: 22789450 DOI: 10.1016/j.outlook.2012.04.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2011] [Revised: 04/16/2012] [Accepted: 04/22/2012] [Indexed: 10/28/2022]
Abstract
Comparative effectiveness research seeks to identify the most effective interventions for particular patient populations. Meta-analysis is an especially valuable form of comparative effectiveness research because it emphasizes the magnitude of intervention effects rather than relying on tests of statistical significance among primary studies. Overall effects can be calculated for diverse clinical and patient-centered variables to determine the outcome patterns. Moderator analyses compare intervention characteristics among primary studies by determining whether effect sizes vary among studies with different intervention characteristics. Intervention effectiveness can be linked to patient characteristics to provide evidence for patient-centered care. Moderator analyses often answer questions never posed by primary studies because neither multiple intervention characteristics nor populations are compared in single primary studies. Thus, meta-analyses provide unique contributions to knowledge. Although meta-analysis is a powerful comparative effectiveness strategy, methodological challenges and limitations in primary research must be acknowledged to interpret findings.
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Affiliation(s)
- Vicki S Conn
- Meta-Analysis Research Center, School of Nursing, University of Missouri, Columbia, MO 65211, USA.
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Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol 2012; 107:811-26. [PMID: 22641309 DOI: 10.1038/ajg.2012.128] [Citation(s) in RCA: 301] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Naga Chalasani
- Indiana University School of Medicine, Indianapolis, 46202, USA.
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Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55:2005-23. [PMID: 22488764 DOI: 10.1002/hep.25762] [Citation(s) in RCA: 2580] [Impact Index Per Article: 198.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Naga Chalasani
- Indiana University School of Medicine, Indianapolis, IN, USA.
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Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012; 142:1592-609. [PMID: 22656328 DOI: 10.1053/j.gastro.2012.04.001] [Citation(s) in RCA: 1332] [Impact Index Per Article: 102.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2012] [Indexed: 02/06/2023]
Affiliation(s)
- Naga Chalasani
- Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med 2011; 51:1000-13. [PMID: 21664268 PMCID: PMC3156342 DOI: 10.1016/j.freeradbiomed.2011.05.017] [Citation(s) in RCA: 559] [Impact Index Per Article: 39.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2011] [Revised: 05/13/2011] [Accepted: 05/17/2011] [Indexed: 02/07/2023]
Abstract
The mechanistic properties of two dietary antioxidants that are required by humans, vitamins C and E, are discussed relative to their biological effects. Vitamin C (ascorbic acid) is an essential cofactor for α-ketoglutarate-dependent dioxygenases. Examples are prolyl hydroxylases, which play a role in the biosynthesis of collagen and in down-regulation of hypoxia-inducible factor (HIF)-1, a transcription factor that regulates many genes responsible for tumor growth, energy metabolism, and neutrophil function and apoptosis. Vitamin C-dependent inhibition of the HIF pathway may provide alternative or additional approaches for controlling tumor progression, infections, and inflammation. Vitamin E (α-tocopherol) functions as an essential lipid-soluble antioxidant, scavenging hydroperoxyl radicals in a lipid milieu. Human symptoms of vitamin E deficiency suggest that its antioxidant properties play a major role in protecting erythrocyte membranes and nervous tissues. As an antioxidant, vitamin C provides protection against oxidative stress-induced cellular damage by scavenging of reactive oxygen species, by vitamin E-dependent neutralization of lipid hydroperoxyl radicals, and by protecting proteins from alkylation by electrophilic lipid peroxidation products. These bioactivities bear relevance to inflammatory disorders. Vitamin C also plays a role in the function of endothelial nitric oxide synthase (eNOS) by recycling the eNOS cofactor, tetrahydrobiopterin, which is relevant to arterial elasticity and blood pressure regulation. Evidence from plants supports a role for vitamin C in the formation of covalent adducts with electrophilic secondary metabolites. Mechanism-based effects of vitamin C and E supplementation on biomarkers and on clinical outcomes from randomized, placebo-controlled trials are emphasized in this review.
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Affiliation(s)
- Maret G Traber
- Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
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Complete Restoration of Refractory Mandibular Osteoradionecrosis by Prolonged Treatment with a Pentoxifylline-Tocopherol-Clodronate Combination (PENTOCLO): A Phase II Trial. Int J Radiat Oncol Biol Phys 2011; 80:832-9. [DOI: 10.1016/j.ijrobp.2010.03.029] [Citation(s) in RCA: 197] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2009] [Revised: 02/08/2010] [Accepted: 03/10/2010] [Indexed: 11/22/2022]
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Agler AH, Kurth T, Gaziano JM, Buring JE, Cassano PA. Randomised vitamin E supplementation and risk of chronic lung disease in the Women's Health Study. Thorax 2011; 66:320-5. [PMID: 21257986 DOI: 10.1136/thx.2010.155028] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The oxidant/antioxidant balance in lung tissue is hypothesised to contribute to the risk of chronic obstructive pulmonary disease (COPD). Observational studies consistently report higher antioxidant status associated with lower COPD risk, but few randomised studies have been reported. METHODS A post hoc analysis of 38,597 women without chronic lung disease at baseline was conducted in the Women's Health Study (WHS) to test the effect of vitamin E on the risk of incident chronic lung disease. The WHS is a randomised double-blind placebo-controlled factorial trial of vitamin E (600 IU every other day) and aspirin (100 mg every other day) in female health professionals aged≥45 years. Using Cox proportional hazards models, the effect of randomised vitamin E assignment on self-reported physician-diagnosed chronic lung disease was evaluated. RESULTS During 10 years of follow-up (376,710 person-years), 760 first occurrences of chronic lung disease were reported in the vitamin E arm compared with 846 in the placebo arm (HR 0.90; 95% CI 0.81 to 0.99; p=0.029). This 10% reduction in the risk of incident chronic lung disease was not modified by cigarette smoking, age, randomised aspirin assignment, multivitamin use or dietary vitamin E intake (minimum p for interaction=0.19). Current cigarette smoking was a strong predictor of chronic lung disease risk (HR 4.17; 95% CI 3.70 to 4.70; vs. never smokers). CONCLUSIONS In this large randomised trial, assignment to 600 IU vitamin E led to a 10% reduction in the risk of chronic lung disease in women.
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Navia JL, Byers T, Djordjevic D, Hentges E, King J, Klurfeld D, Llewellyn C, Milner J, Skrypec D, Weed D. Integrating the totality of food and nutrition evidence for public health decision making and communication. Crit Rev Food Sci Nutr 2011; 50 Suppl 1:1-8. [PMID: 21132578 PMCID: PMC3024840 DOI: 10.1080/10408398.2010.526825] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The interpretation and integration of epidemiological studies detecting weak associations (RR < 2) with data from other study designs (e.g., animal models and human intervention trials) is both challenging and vital for making science-based dietary recommendations in the nutrition and food safety communities. The 2008 ILSI North America “Decision-Making for Recommendations and Communication Based on Totality of Food-Related Research” workshop provided an overview of epidemiological methods, and case-study examples of how weak associations have been incorporated into decision making for nutritional recommendations. Based on the workshop presentations and dialogue among the participants, three clear strategies were provided for the use of weak associations in informing nutritional recommendations for optimal health. First, enable more effective integration of data from all sources through the use of genetic and nutritional biomarkers; second, minimize the risk of bias and confounding through the adoption of rigorous quality-control standards, greater emphasis on the replication of study results, and better integration of results from independent studies, perhaps using adaptive study designs and Bayesian meta-analysis methods; and third, emphasize more effective and truthful communication to the public about the evolving understanding of the often complex relationship between nutrition, lifestyle, and optimal health.
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Affiliation(s)
- Juan L Navia
- McNeil Nutritionals LLC, Ft. Washington, Pennsylvania
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