Summary: A comprehensive systematic review and meta-analysis finds that cognitive harm from unhealthy diets is not always fully reversible. The study pooled results from 27 controlled preclinical experiments to evaluate whether memory deficits caused by high‑fat and high‑sugar diets recover after animals are returned to healthier eating.
Switching to a healthier diet does improve memory compared with continuing an unhealthy diet, but the recovery is often incomplete. The analysis highlights added sugar as a major obstacle to neurological recovery: memory impairments produced by high‑sugar or combined high‑fat/high‑sugar diets showed little to no evidence of full restoration.
Key Facts
- Incomplete brain recovery: Even after several weeks on a balanced diet, animals previously fed unhealthy diets did not regain memory performance equal to animals that never experienced poor nutrition.
- Added sugar limits recovery: The capacity for memory to recover depended on what the animals had eaten. Recovery was observed after exclusive high‑fat feeding, but prolonged exposure to added sugar—or to diets high in both fat and sugar—produced persistent cognitive deficits.
- Hippocampal focus: The long‑lasting impairments were specific to hippocampus‑dependent memory tasks. The hippocampus is central to learning, memory consolidation, and appetite regulation.
- Memory‑specific effect: Behavior outside memory circuits—such as anxiety‑like behavior, overall activity, or basic food‑motivation—showed no consistent improvement after diet reversal, suggesting the primary long‑term effect is on memory systems.
Source: University of Technology Sydney
Overview
As public concern grows about how modern diets affect long‑term health, researchers at the University of Technology Sydney (UTS) investigated whether the brain’s cognitive functions can recover after unhealthy eating is replaced by healthier nutrition. Their findings were published in Nutritional Neuroscience and are based on controlled animal experiments designed to isolate the effects of diet itself.
The team systematically reviewed rodent studies that first fed animals high‑fat and/or high‑sugar (HFHS) diets for at least two weeks, then switched them to healthier chow for a minimum of 24 hours, and finally assessed memory, anxiety‑ or depression‑like behaviours, motivation for food, or locomotor activity.
“Improving diet quality does benefit memory,” said Dr Simone Rehn, the study’s lead author. “However, those benefits were not complete. Even after weeks on a healthy diet, memory performance did not match that of animals never exposed to unhealthy diets.”
To detect consistent patterns beyond individual experiments, the researchers combined data across 27 preclinical studies in a meta‑analysis. Overall, animals switched to a healthy diet outperformed their counterparts that remained on HFHS diets. But the degree of recovery depended on the original diet: studies that used predominantly high‑fat diets showed clearer memory improvement after reversal, while studies using high‑sugar or combined HFHS diets demonstrated little recovery.
The lack of consistent recovery in anxiety, locomotor activity, or food motivation tests suggests the persistent effects are concentrated on memory circuits rather than reflecting a broad change in general behavior.
“The results point to added sugar as a likely key factor limiting recovery,” Dr Rehn added. “Sugar appears to induce lasting changes in hippocampal function that are harder to reverse.”
Dr Mike Kendig, senior author, emphasized the value of controlled animal models: “Human lifestyle changes typically involve many simultaneous factors—exercise, sleep, stress and routine changes—making it difficult to isolate diet’s direct effect on the brain. Rodent studies allow researchers to examine diet as the primary variable.”
He added: “While improving diet quality is beneficial and should be encouraged, these findings suggest prevention—avoiding prolonged exposure to diets high in added sugars and saturated fats—may be important for protecting long‑term brain health.”
Key Questions Answered:
A: Based on this meta‑analysis of animal studies, improvements in diet quality do lead to measurable memory gains compared with continuing unhealthy eating. However, full restoration to the cognitive level of animals that never experienced unhealthy diets was not observed. In other words, diet improvement helps but may not completely erase prior diet‑related memory damage.
A: The analysis suggests that added sugar produces persistent changes to hippocampal circuits that are more resistant to reversal than changes from high‑fat exposure alone. Studies that reversed high‑fat diets showed clearer cognitive rebound, whereas those involving added sugar showed little improvement, indicating sugar may cause longer‑lasting neural alterations.
A: In humans, dietary changes usually come with shifts in activity, stress, sleep and other lifestyle factors, which complicates efforts to isolate diet’s direct effects. Animal models provide controlled conditions that allow researchers to attribute observed brain and behavioral changes specifically to diet composition.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The full journal paper was reviewed for accuracy.
- Additional context was provided by editorial staff.
About this research
Author: Jacqueline Middleton
Source: University of Technology Sydney
Contact: Jacqueline Middleton – University of Technology Sydney
Image: Image credited to Neuroscience News
Original Research: Open access. “Cognitive and behavioural effects of high‑fat, high‑sugar diet reversal: a systematic review and meta‑analysis of animal studies” by Simone Rehn, Isabella Eikelis, Joanne M. Gladding, Laura A. Bradfield, and Michael D. Kendig. DOI: 10.1080/1028415X.2026.2664635
Abstract
Cognitive and behavioural effects of high‑fat, high‑sugar diet reversal: a systematic review and meta‑analysis of animal studies
High‑fat, high‑sugar (HFHS) diets are linked not only to metabolic and physical disorders but also to neurocognitive impairments and behavioural changes. It remains uncertain whether those impairments persist or remit once HFHS diets are replaced with healthier nutrition.
This systematic review and meta‑analysis evaluated the effects of diet reversal on cognition and behaviour in rodent studies. Included studies fed rodents HFHS diets for at least two weeks, followed by a switch to healthy chow for a minimum of 24 hours, and subsequent assessment of cognition, anxiety, depression, motivation, or locomotor activity. Twenty‑seven studies met these criteria.
Pooled results indicate that diet reversal significantly improved memory compared with animals that remained on HFHS diets (g = 0.46, 95% CI [0.16, 0.76], p = .004), but memory did not fully recover to the level of chow‑fed control animals (g = −0.28 [−0.49, −0.06], p = .013).
Meta‑regressions showed test‑ and diet‑dependent effects: significant memory gains occurred in studies using the novel object location test and in studies reversing high‑fat diets, but not in studies involving high‑sugar or combined HFHS diets. Diet reversal produced no reliable effects on anxiety‑ or depression‑like behaviour, motivational tests, or locomotor activity. Heterogeneity across studies was moderate to high, while assessed risk of bias was generally low.
These findings demonstrate that diet‑induced cognitive deficits can be partly mitigated by returning to healthier diets in controlled animal models, and they emphasize the importance of public health efforts to reduce intake of foods high in added sugars and unhealthy fats to protect long‑term brain health.