Impact of Methyl-Donor Micronutrient Supplementation on DNA Methylation Patterns: A Systematic Review and Meta-Analysis of in vitro, Animal, and Human Studies.
Jhulia Caroline N L da Mota, Amanda A Ribeiro, Lucas M Carvalho, Gabriel P Esteves, Sofia M Sieczkowska, Karla F Goessler, Bruno Gualano, Carolina F Nicoletti
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引用次数: 0
Abstract
Background: DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation levels, and altered ingestion of folate, choline, betaine, B vitamins and methionine may impact genes both globally and at the level of promoter regions. Despite this, the role of methyl-donor micronutrient supplementation on DNA methylation profiles is currently unclear.
Objectives: The aims of this systematic review and meta-analysis were to identify and synthesize the evidence about methyl-donor nutrient supplementation on DNA methylation.
Methods: A systematic literature search was performed in Medline, Embase, Scopus, and Web of Science databases with a combination of terms related to DNA methylation assessment, supplementation, and methyl-donor nutrients. Studies (in vitro, animal models, or human clinical trials) were included if DNA methylation levels after any kind of methyl-donor micronutrient supplementation or treatment was investigated. Studies were assessed for bias using Revised Cochrane risk-of-bias tool for randomized trials, risk-of-bias in Non-randomized Studies of Interventions or Systematic Review Centre for Laboratory Animal Experimentation tools. Data were extracted from studies measuring DNA methylation levels in any sample or tissue, following any kind of methyl-donor micronutrient supplementation or treatment. Separate random-effects meta-analyses were performed for animal model studies and human clinical trials that examined the effects of folic acid supplementation on DNA methylation.
Results: Fifty-seven studies were included in this systematic review: 18 human clinical trials, 35 in animal model, and 4 in vitro studies. Concerning overall risk of bias, most of the studies were classified as "high risk" or "some concerns." Meta-analysis with meta-regression from studies in animal models showed that folic acid dose significantly affected DNA methylation and that high and very high doses showed increases in DNA methylation when compared to low doses. However, meta-analysis of human clinical trials showed that folic acid supplementation did not promote significant changes in DNA methylation when compared to placebo.
Conclusion: Folic acid supplementation may change global DNA methylation levels in animals supplemented with high, as compared to low, doses. Heterogeneity in studies and supplementation protocols make it difficult to establish clinical recommendations. However, these effects, even if small, might be of clinical importance in the management of patients with diseases related to DNA hypomethylation.
背景:DNA甲基化模式与多种代谢紊乱直接相关。甲基供体微量营养素的状况与DNA甲基化水平有关,叶酸、胆碱、甜菜碱、B族维生素和甲硫氨酸的摄入改变可能会在全球和启动子区域水平上影响基因。尽管如此,甲基供体微量营养素补充对DNA甲基化特征的作用目前尚不清楚。目的:本系统综述和荟萃分析的目的是识别和综合甲基供体营养素补充对DNA甲基化的影响。方法:在MEDLINE、EMBASE、SCOPUS和Web of Sciences数据库中进行系统的文献检索,结合与DNA甲基化评估、补充和甲基供体营养素相关的术语。如果研究了任何类型的甲基供体微量营养素补充或治疗后的DNA甲基化水平,则包括研究(体外、动物模型或人类临床试验)。使用随机试验的改良Cochrane偏倚风险工具、非随机干预研究中的偏倚风险或实验室动物实验系统审查中心工具评估研究的偏倚。数据是从测量任何样本或组织中DNA甲基化水平的研究中提取的,在任何类型的甲基供体微量营养素补充或治疗后。分别对动物模型研究和人体临床试验进行了随机效应荟萃分析,研究了补充叶酸对DNA甲基化的影响。结果:57项研究被纳入系统综述:18项人体临床试验,35项动物模型研究和4项体外研究。关于偏倚的总体风险,大多数研究被归类为“高风险”或“一些担忧”。动物模型研究的荟萃分析和荟萃回归显示,叶酸剂量显著影响DNA甲基化,与低剂量相比,高剂量和极高剂量显示DNA甲基化增加。然而,来自人类临床试验的荟萃分析表明,与安慰剂相比,补充叶酸不会促进DNA甲基化的显著变化。结论:与低剂量相比,高剂量补充叶酸可能会改变动物的整体DNA甲基化水平。研究和补充方案的异质性使得制定临床建议变得困难。然而,这些影响,即使很小,也可能对DNA低甲基化相关疾病患者的管理具有临床重要性。
期刊介绍:
Lifestyle Genomics aims to provide a forum for highlighting new advances in the broad area of lifestyle-gene interactions and their influence on health and disease. The journal welcomes novel contributions that investigate how genetics may influence a person’s response to lifestyle factors, such as diet and nutrition, natural health products, physical activity, and sleep, amongst others. Additionally, contributions examining how lifestyle factors influence the expression/abundance of genes, proteins and metabolites in cell and animal models as well as in humans are also of interest. The journal will publish high-quality original research papers, brief research communications, reviews outlining timely advances in the field, and brief research methods pertaining to lifestyle genomics. It will also include a unique section under the heading “Market Place” presenting articles of companies active in the area of lifestyle genomics. Research articles will undergo rigorous scientific as well as statistical/bioinformatic review to ensure excellence.