Sugar rationing in the first 1000 days of life and risk of frailty: evidence from a natural experiment

OBJECTIVES: 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. DESIGN: A population based quasi-experimental cohort study. SETTING AND PARTICIPANTS: 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). MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: 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.