Low-Fat Diet Alleviates Perimenopausal Symptoms by Reducing Methylation Levels of PDE4C and NPAS2 Genes: A Randomized Controlled Trial

Background: Perimenopausal syndrome (PMS) significantly impacts the quality of life in women during the perimenopausal phase. Despite being the primary treatment, hormone replacement therapy has notable limitations. Consequently, dietary interventions, particularly low-fat diets, have garnered international attention as an alternative. Methods: The prospective Randomized Controlled Trial (RCT), approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University, enrolled 62 perimenopausal women. Participants were divided into two groups: a low-fat diet group and a menopausal hormone therapy (MHT) group, with interventions lasting eight weeks. Both groups underwent assessments for perimenopausal symptoms, lipid profile, and oxidative stress markers, including superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS), before and after the interventions. Additionally, DNA methylation levels of the PDE4C and NPAS2 genes were measured in 10 women from the low-fat diet group before and after the intervention. Results: Both the low-fat diet and hormone supplementation improved specific perimenopausal symptoms, reduced specific lipid levels, and had a positive effect on oxidative stress markers. The low-fat diet proved more effective than hormone replacement in improving the serum lipid profile and also resulted in reductions in methylation at specific sites of the PDE4C and NPAS2 genes. Conclusions: A low-fat diet may alleviate perimenopausal symptoms, lower lipid levels, and alter gene methylation sites. Clinical Trial Registration: The study has been registered on https://www.chictr.org.cn/ (registration number: ChiCTR2400084007).