MTHFR and metabolic disease: Polymorphisms in genes like MTHFR, FUT2, and COMT significantly alter nutrient metabolism and utilization, predisposing individuals to specific health conditions such as cardiovascular disease, cognitive dysfunction, and metabolic disorders.8, 9, 10 In perimenopausal women, these effects are further intensified by the natural decline in estrogen, which itself impacts nutrient balance and energy metabolism.8