Abstract
Caloric restriction (CR) robustly increases longevity/reduces morbidity in mammals, eg., breast cancer risk is generally decreased >90% in CR rodents. CR is usually dominant to other risk factors and are directly analogous to human data linking obesity with poor health outcomes, including cancer. We tested if biomarkers of diet in rats predicts future disease in humans.MethodsMetabolomics measurements in sera/plasma were conducted w/HPLC/Coularray detectors (N~600 rats, ~1700 humans). Classification/predictive power were tested, optimized, and validated using a series of megavariate data analysis approaches in sequential blinded cohorts.ResultsModels distinguish diet groups with >95% accuracy. Diets varying in extent/duration of CR were used to develop models for intermediate caloric intakes. Markers were adapted for human study, analytically validated at instrumentation (N=30; 100% blinded split accuracy) and sample collection levels (N=34; most stable under worst case conditions), then biologically validated (N~70 in triplicate, metabolites/profiles had intraclass correlation coefficients ~0.65–0.85). Marker profile scores reflects energy intake/risk of future breast cancer in 210 case/control pairs nested within the Nurses’ Health Study.ConclusionMetabolomics profiles offer a potential biochemical approach to validate nutritive status and contribute to risk analysis. NIH
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