To investigate the association between early-life sugar restriction and frailty in adulthood, and to evaluate whether frailty mediates the relationship between early-life sugar restriction and chronic diseases.

A population based quasi-experimental cohort study.

This study was conducted using data from the UK Biobank. A total of 63,793 participants were included and classified according to early-life exposure to sugar restriction (never exposed, in utero only, in utero plus the first year postnatal, and in utero plus the first two postnatal years).

Frailty was assessed in adulthood using Fried’s 5-item phenotype criteria (unintentional weight loss, exhaustion, weakness, slow walking speed, and low physical activity), with frailty defined as ≥ 3 components. Multivariable linear and logistic regression models were used to evaluate associations between early-life sugar restriction and frailty. Mediation analyses were conducted to assess the role of frailty in the associations between early-life sugar restriction and multiple chronic diseases.

Early-life sugar restriction was associated with lower frailty levels and reduced odds of frailty in adulthood, with stronger associations observed for longer exposure durations (P for trend <0.01). In mediation analyses, frailty partially mediated the associations between early-life sugar restriction and selected chronic diseases, including osteoporosis and heart failure, while minimal mediation effects were observed for metabolic diseases.

Early-life sugar restriction is associated with a lower risk of frailty in adulthood. These findings highlight the potential long-term benefits of early-life nutritional environments on healthy aging and suggest that strategies targeting early-life diet and frailty prevention may help reduce the burden of age-related diseases in clinical and public health settings.