Comparative Effects of Intermittent and Continuous Energy Restriction on Metabolic and Cognitive Functions in Menopausal Rodent Models

Abstract

Calorie restriction is an important strategy to reduce the metabolic risks associated with aging. Various calorie restriction regimens have proved to be beneficial in menopause, but their comparative effects still remain a matter of debate. Therefore, this study aimed to compare the effects of continuous and intermittent energy restriction regimens on metabolic and cognitive functions in a VCD-induced menopausal rodent model. Thirty-six female Wistar rats were randomized into six groups (n = 6), comprising three non-menopausal and three menopausal groups. Within each category, animals were sub grouped into control (no restriction), continuous energy restriction (CER), or intermittent energy restriction (IER) regimens for 12 weeks. Menopause was induced using 4-vinylcyclohexene diepoxide and confirmed by plasma estradiol levels, estrous cycle monitoring, and ovarian histology. Body weight was recorded every week, while plasma glucose, insulin, and lipid levels were measured both before and after the intervention. Cognitive performance was evaluated pre- and post-intervention using the Novel Object Recognition task. Paired t-tests and two-way ANOVA were used to compare the outcome parameters within and between groups. The non-menopausal IER group exhibited a marked reduction in body weight compared with the ad libitum group, improved fasting glucose levels, and enhanced insulin sensitivity. The IER group had higher HDL and, lower LDL levels than other groups. Despite these metabolic improvements, neither intervention conferred measurable gains in cognitive performance. These findings suggest that IER confers superior metabolic benefits over CER in the menopausal state and may represent a promising, practical dietary strategy for mitigating menopause-associated metabolic risks.