Effects of dietary interventions on DNA methylation in adult humans: systematic review and meta-analysis
What this study found
Folic acid supplementation increases global DNA methylation in colorectal mucosa in a dose-dependent manner, a tissue-specific effect not observed in blood. Evidence for effects of other dietary factors on DNA methylation in humans remains limited due to heterogeneous methods and genomic loci. This finding may have relevance for colorectal cancer prevention, given hypomethylation is a common feature of colonic carcinogenesis; standardization of outcome measurements is needed to enable better cross-study comparisons.
- Study & population
- Adults (≥16 years) from mixed health statuses; study designs included randomized controlled trials (65%, n=39) and cross-over RCTs (12%, n=7); participants ranged from healthy individuals to patients with obesity, colorectal adenomas, ulcerative colitis and other risk factors; methylation measured in blood, colorectal mucosa and other tissues.
- Intervention
- Folic acid supplementation; typically 0.4 mg/day (400 µg/day) taken orally; sometimes combined with vitamin B12 (0.5 mg/day); duration varied across studies (examples include longer-term trials up to 3 years).
- Key limitation
- Heterogeneity in methylation assessment methods and loci; tissue- and method-specific responses; reliance on surrogate tissues in many studies; incomplete reporting of randomization, allocation concealment and blinding; potential publication bias; limited generalizability beyond colorectal mucosa; variability in…
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Open PDFOriginal abstract
Abstract DNA methylation is a key component of the epigenetic machinery that is responsible for regulating gene expression and, therefore, cell function. Patterns of DNA methylation change during development and ageing, differ between cell types, are altered in multiple diseases and can be modulated by dietary factors. However, evidence about the effects of dietary factors on DNA methylation patterns in humans is fragmentary. This study was initiated to collate evidence for causal links between dietary factors and changes in DNA methylation patterns. We carried out a systematic review of dietary intervention studies in adult humans using Medline, EMBASE and Scopus. Out of 22 149 screened titles, sixty intervention studies were included, of which 65% were randomised (n 39). Most studies (53%) reported data from blood analyses, whereas 27% studied DNA methylation in colorectal mucosal biopsies. Folic acid was the most common intervention agent (33%). There was great heterogeneity in the methods used for assessing DNA methylation and in the genomic loci investigated. Meta-analysis of the effect of folic acid on global DNA methylation revealed strong evidence that supplementation caused hypermethylation in colorectal mucosa (P=0·009). Meta-regression analysis showed that the dose of supplementary folic acid was the only identified factor (P<0·001) showing a positive relationship. In summary, there is limited evidence from intervention studies of effects of dietary factors, other than folic acid, on DNA methylation patterns in humans. In addition, the application of multiple different assays and investigations of different genomic loci makes it difficult to compare, or to combine, data across studies.