Cognitive and behavioural effects of high-fat, high-sugar diet reversal: a systematic review and meta-analysis of animal studies

Abstract

In addition to their effects on physical and metabolic health, high-fat, high-sugar (HFHS) diets are associated with neurocognitive impairment and behavioural effects. It is not clear whether these impairments persist or recover when the HFHS diet is replaced with a healthy diet, i.e. diet reversal. We performed a systematic review and meta-analysis of the effects of diet reversal on cognition and behaviour in rodent studies. Our review included 27 studies which fed rodents HFHS diets for a minimum of two weeks, replaced this diet with healthy chow for at least 24 h, and then assessed cognition, anxiety, depression, motivation or locomotor activity. Meta-analyses revealed that diet reversal significantly improved memory performance relative to rodents maintained on HFHS diets (g = 0.46, 95% CI [0.16, 0.76], p=.004) but did not restore memory to the level of chow-fed controls (g = −0.28 [−0.49,–0.06], p=.013). Meta-regressions revealed test- and diet-dependent effects of diet reversal, with significant memory improvements in studies using the novel object location test, or high-fat diets, but not high-sugar or combined HFHS diets. Diet reversal had no significant effects on tests of anxiety-like or depression-like behaviour, motivation, or locomotor activity. Heterogeneity estimates were moderate to high across domains, and risk of bias was generally low. Results demonstrate that diet-induced cognitive impairments are amenable to healthy diet intervention in controlled animal models, underscoring the need for public health nutrition strategies designed to reduce intake of foods high in sugar and fat.