Carbon Isotope Ratios as Biomarkers for Added Sugar Intake: Fundamental Limitations that Constrain Valid Application

Carbon isotope ratio (CIR; δ¹³C) analysis has been proposed as a biomarker for added sugar intake from C4 sources, but its specificity is limited. CIR biomarkers measure total C4 dietary carbon, conflating added sugars with other C4 foods like corn-fed meats and whole corn products. This lack of specificity varies across populations and food systems. Moreover, metabolic redistribution of dietary carbon means that δ¹³C signals in tissues reflect complex mixtures of sources and processes, not sugar intake alone. Attempts to adjust for confounders rely on self-reported dietary data, undermining the objectivity that CIR biomarkers aim to provide. Even under ideal conditions, CIR validity is insufficient for most nutritional research, especially when assessing causal relationships or meaningful effects. The shift in public health focus from "added sugars" to "free sugars," including C3-derived sources like fruit juice and honey, further limits CIR utility. Although CIR has proven useful for distinguishing dietary protein sources (e.g., marine compared with terrestrial), its application to added sugars faces persistent challenges. Resources may be better directed toward improving dietary assessment tools or developing more specific metabolomic markers, acknowledging that all current methods have limitations.