The Carbon Stable Isotope Ratio (CIR) as an Objective Biomarker of Added Sugar Intake: A Scoping Review of Current Evidence in Human Nutrition

Objective biomarkers of dietary intake are needed to advance nutrition research. The carbon stable isotope ratio (C /C ; CIR) holds promise as an objective biomarker of added sugar (AS) and sugar-sweetened beverage (SSB) intake. This systematic scoping review presents the current evidence on CIRs from human studies. Search results (through April 12, 2024) yielded 6,297 studies and 24 final articles. Studies were observational (n=12), controlled feeding (n=10), or dietary interventions (n=2). CIRs were sampled from blood (n=23), hair (n=5), breath (n= 2), and/or adipose tissue (n=1). Most (n=17) conducted whole tissue (i.e., bulk) analysis, eight used compound specific isotope analysis (CSIA), and/or two studies used methods appropriate for analyzing breath. Studies were conducted in three concentrated geographic regions of the U.S. (n=7 Virginia; n=5 Arizona; n=4 Alaska), with only two studies conducted in other countries. Studies that used CSIA to examine the CIR from the non-essential amino acid alanine (CIR-Ala; n=4) and CIR analyzed from breath (n=2) provided the most robust evidence for CIR as an objective biomarker of AS and SSBs (R range 0.36-0.91). Studies using bulk analysis of hair or blood showed positive, but modest and more variable associations with AS and SSBs (R range 0.05-0.48). Few studies showed no association, particularly in non-U.S. populations and those with low AS and SSB intakes. Two studies provided evidence for CIR to detect changes in SSB intake in response to dietary interventions. Overall, the most compelling evidence supports CIR-Ala as an objective indicator of AS intake and breath CIR as an indicator of short term AS intake. Considering how to adjust for underlying dietary patterns remains an important area of future work and emerging methods using breath and CSIA warrant additional investigation. More evidence is needed to refine the utility and specificity of CIRs to measure AS and SSB intake.