Limited sugar exposure in early life may prevent CVD events in adulthood

Restricting sugar exposure in utero and during infancy appears protective against the risks of several cardiovascular outcomes and delays disease onset later in life, suggests a study.

“Exposure to sugar rationing during the first 1,000 days of life was associated with lower cardiovascular risks in adulthood and slightly more favourable cardiac indices, suggesting long term cardiovascular benefits of early life sugar restriction,” the researchers said.

A total of 63,433 UK Biobank participants born between October 1951 and March 1956 without prevalent cardiovascular disease (CVD), multiple births, adoption, or birth outside the UK were included in this natural experiment study.

The research team quasi-experimentally assigned exposure based on birth date relative to the end of sugar rationing in 1953. They also used external validation cohorts from the Health and Retirement Study and the English Longitudinal Study of Ageing.

Cox and parametric hazard models adjusted for demographic, socioeconomic, lifestyle, parental health, and genetic factors and geographical controls were used to estimate hazard ratios (HRs). The researchers also measured multiple cardiac parameters in a subset undergoing cardiac magnetic resonance imaging.

Longer exposure to sugar rationing resulted in progressively reduced cardiovascular risks in adulthood. [BMJ 2025;391:e083890]

Individuals exposed to rationing in utero had lower risks of CVD (HR, 0.80, 95 percent confidence interval [CI], 0.73–0.90), myocardial infarction (HR, 0.75, 95 percent CI, 0.63–0.90), heart failure (HR, 0.74, 95 percent CI, 0.59–0.95), atrial fibrillation (HR, 0.76, 95 percent CI, 0.66–0.92), stroke (HR, 0.69, 95 percent CI, 0.53–0.89), and CVD mortality (HR, 0.73, 95 percent CI, 0.54–0.98) than those with no exposure.

Both incident diabetes and hypertension mediated 31.1 percent of the sugar rationing-CVD association, while birth weight contributed only 2.2 percent. Furthermore, sugar rationing led to a modest increase in left ventricular stroke volume index (0.73 mL/m², 95 percent CI, 0.05–1.41) and ejection fraction (0.84 percent, 95 percent CI, 0.40–1.28).

"Our results underscore the cardiac benefit of early life policies focused on sugar rationing during the first 1,000 days after conception,” the researchers said.

Mechanisms

The exact mechanisms behind the protective effects of early-life sugar rationing remain unclear, but several potential explanations have been suggested.

For instance, reduced maternal hyperglycaemia during pregnancy tends to reduce foetal insulin secretion, preventing adverse adaptations such as cardiomyocyte hypertrophy, vascular stiffness, and altered cardiac remodelling. [J Clin Endocrinol Metab 2020;105:e2581-2590]

Reduced sugar intake among pregnant women may also modulate oxidative stress and inflammation, which are major factors in foetal vascular development.

"Elevated glucose concentrations increase reactive oxygen species and activate pro-inflammatory pathways, such as NF-κB (nuclear factor κ light chain enhancer of activated B cells), in the placenta, impairing endothelial function and vascular reactivity,” the researchers said. [Springerplus 2016;5:532]

Furthermore, constrained sugar exposure during critical windows results in decreased concentrations of reactive oxygen species and in preserved bioavailability of nitric oxide, they added.

“Our findings provide implications for future randomized controlled trials targeting more refined interventions and mechanistic studies in each developmental phase,” the researchers said. “Further studies should investigate individual level dietary exposures and consider the interplay between genetic, environmental, and lifestyle factors to develop more personalized prevention strategies.”