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.

The transition of a society from traditional to market-based diets (termed the nutrition transition) has been associated with profound changes in culture and health. We are developing biomarkers to track the nutrition transition in the Yup'ik Eskimo population of Southwest Alaska based on naturally occurring variations in the relative abundances of carbon and nitrogen stable isotopes (δ(15)N and δ(13)C values). Here, we provide three pieces of evidence toward the validation of these biomarkers. First, we analyzed the δ(15)N and δ(13)C values of a comprehensive sample of Yup'ik foods. We found that δ(15)N values were elevated in fish and marine mammals and that δ(13)C values were elevated in market foods containing corn or sugar cane carbon. Second, we evaluated the associations between RBC δ(15)N and δ(13)C values and self-reported measures of traditional and market food intake (n = 230). RBC δ(15)N values were correlated with intake of fish and marine mammals (r = 0.52; P < 0.0001). RBC δ(13)C values were correlated with intake of market foods made from corn and sugar cane (r = 0.46; P < 0.0001) and total market food intake (r = 0.46; P < 0.0001). Finally, we assessed whether stable isotope ratios captured population-level patterns of traditional and market intake (n = 1003). Isotopic biomarkers of traditional and market intake were associated with age, community location, sex, and cultural identity. Self-report methods showed variations by age and cultural identity only. Thus, stable isotopes show potential as biomarkers for monitoring dietary change in indigenous circumpolar populations.

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