Criteria for Acceptable Dietary Intake Biomarkers.

Dietary intake biomarkers that can be written as actual intake, plus 'error' that is independent of actual intake and confounding factors can substitute for actual intake in disease association analyses. Also, such biomarkers can be used to develop calibration equations using self-reported diet and participant measures, and biomarker-calibrated intakes can be calculated in larger cohorts for use in disease association analyses. Criteria for biomarkers, and for biomarker-calibrated intakes, arise by working back from properties needed for valid disease association analyses. Accordingly, arguments for a potential biomarker are strengthened if error components are small relative to actual intakes, and important sources of reduced sensitivity or specificity are not apparent. Feeding study biomarker development can then involve regression of actual intake on putative biomarkers, with regression R2 values playing a role in biomarker evaluation. In comparison, 'predictive' biomarker status, as argued in this issue by Freedman and colleagues for 24-hour urinary sucrose plus fructose as biomarker for total sugars, involves regression of potential biomarker on actual intake and other variables, with parameter stability across populations and limited within-person variability as criteria. The choice of criteria for biomarkers and for biomarker-calibrated intakes, is discussed here, in the context of total sugars intake. See related article by Freedman et al., p. 1227.