Background/Aim: This study hypothesized an association between healthy dietary patterns, hypermethylation of the tumor necrosis factor-α (TNF-α) promoter and decreased risk of metabolic changes. Methods: Forty normal-weight young women were involved in this cross-sectional study. DNA was isolated from white blood cells, and CpG site methylation in TNF-α was analyzed by Sequenom EpiTyper. The quality of the diet was assessed by Healthy Eating Index (HEI-2005). Results: Contradicting our hypothesis, HEI-2005 score was negatively associated with CpG5 (r = -0.460, p = 0.003) and TNF-α total methylation (r = -0.355, p = 0.026). A higher intake of fruits was related to lower insulin, HOMA-IR, and TNF-α methylation. No other dietary pattern was related to TNF-α methylation. TNF-α total methylation correlated positively with systolic blood pressure (r = 0.323; p = 0.042) and CpG5 methylation with body mass index (r = 0.333, p = 0.036). Furthermore, fiber intake was negatively associated with the CpG5 (r = -0.324, p = 0.041) and TNF-α total methylation (r = -0.434, p = 0.005), whereas vitamin C intake was negatively associated with TNF-α total methylation (r = -0.411, p = 0.009). Intakes of apples and citrus fruits were negatively associated with TNF-α total methylation. Conclusion: A healthy dietary pattern and higher fruit intake (particularly apples and citrus fruits) were related to better glucose tolerance in healthy subjects, which could be mediated by lower TNF-α methylation.

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