Sarah H. Nash, Alan R. Kristal, Andrea Bersamin, Scarlett E. Hopkins, Bert B. Boyer, Diane M. O'Brien

The carbon isotope ratio (δ¹³C) is elevated in corn- and cane sugar-based foods and has recently shown associations with sweetener intake in multiple U.S. populations. However, a high carbon isotope ratio is not specific to corn- and sugar cane-based sweeteners, as other foods, including meats and fish, also have elevated δ¹³C. This study examines whether the inclusion of a second marker, the nitrogen isotope ratio (δ¹⁵N), can control for confounding dietary effects on δ¹³C and improve the validity of isotopic markers of sweetener intake. The study participants are from the Yup'ik population of southwest Alaska and consume large and variable amounts of fish and marine mammals known to have elevated carbon and nitrogen isotope ratios. Sixty-eight participants completed 4 weekly 24-h recalls followed by a blood draw. RBC δ¹³C and δ¹⁵N were used to predict sweetener intake, including total sugars, added sugars, and sugar-sweetened beverages. A model including both δ¹³C and δ¹⁵N explained more than 3 times as much of the variation in sweetener intake than did a model using only δ¹³C. Because carbon and nitrogen isotope ratios are simultaneously determined in a single, high-throughput analysis, this dual isotope marker provides a simple method to improve the validity of stable isotope markers of sweetener intake with no additional cost. We anticipate that this multi-isotope approach will have utility in any population where a stable isotope biomarker is elevated in several food groups and there are appropriate "covariate" isotopes to control for intake of foods not of research interest.