Early-life sugar rationing, brain aging, and long-term neurodegenerative and psychiatric health outcomes: a population-based natural experiment study.

Early-life nutrition is linked to adult brain health, yet evidence from quasi-experimental studies remains scarce. Leveraging the UK's historical sugar rationing as a natural experiment, we examined whether early-life sugar restriction reduces the risk of neurodegenerative and psychiatric disorders in later life. Among 60,394 UK Biobank participants (born 1951-1956), three groups were defined: in-utero-only, in utero plus 2 years, and non-rationed controls. Compared with non-rationed individuals, those exposed to sugar restriction during the first 1000 days after conception, showed significantly lower risks of all-cause dementia (by 27%), Alzheimer's disease (46%), depression (11%), and anxiety (20%). Dose-response analyses revealed stronger protective associations against depression and anxiety when postnatal sugar restriction extended beyond 6 months of age. Sex-stratified analyses showed consistent protective effects in women for Alzheimer's disease, depression, and anxiety. Neuroimaging revealed decelerated brain aging, reflected by a 0.39-year reduction in the brain age gap, alongside structural changes in reduced gray-white matter contrast and larger subcortical volumes, including the hippocampus and thalamus. Minimal associations were observed for in‑utero‑only exposure. These quasi-experimental findings suggest that early-life sugar restriction is associated with attenuated neurobiological aging and lower risks of dementia and psychiatric disorders, highlighting sugar intake as a potential modifiable factor of lifelong brain health.