Peripheral Blood DNA Methylation Changes after Omega-3 Fatty Acid Treatment Indicate Anti-inflammatory Effects and Individual Variability

Background Omega-3 or n-3 polyunsaturated fatty acids (PUFAs) are widely studied for health benefits based on potential anti-inflammatory effects. However, the factors involved in mediating the anti-inflammatory responses to n-3 PUFAs are not fully understood; furthermore, many effects from n-3 PUFA treatment are not well characterized in humans. Of interest is the role of DNA methylation (DNAm) in mediating the effects of n-3 PUFAs on inflammation. Objective We aimed to characterize the effects of n-3 PUFA treatment on DNAm in inflammation-related signaling pathways in PBMCs of women at high risk of breast cancer Methods PBMCs of women at high risk of breast cancer were obtained at 0 and 6 months of n-3 PUFA treatment in a previously reported dose finding trial (n=10 matched pairs in the 5 g/day EPA+DHA dose arm).[53] DNA methylation of PBMCs were assayed using reduced representation bisulfite sequencing to obtain genome-wide methylation profiles on a single nucleotide level. Analyses were performed to investigate the effects of n-3 PUFA treatment on DNAm both genome-wide and within a set of candidate genes. Results A large number of differentially methylated CpGs (DMCs) in gene promoters (24,842 DMCs in 5507 genes) showed significant enrichment for hypermethylation in both the candidate gene and genome-wide analyses. Using these DNAm changes, pathway analysis identified significantly hypermethylated signaling networks after n-3 PUFA treatment, such as the Toll-like Receptor pathway. Based on analyses of data per individual, DNAm changes from n-3 PUFA treatment appear highly variable between study participants. Conclusions Dietary n-3 PUFA supplementation for six months is associated with DNAm changes in PBMCs with potential for anti-inflammatory effects. PBMC DNAm profiles may offer a novel means of assessing individual response to n-3 PUFAs. This observation warrants further investigation in future n-3 PUFA intervention studies.