Stable Isotope Ratios as Biomarkers of Diet for Health Research

Abstract

Diet is a leading modifiable risk factor for chronic disease, but it remains difficult to measure accurately due to the error and bias inherent in self-reported methods of diet assessment. Consequently, there is a pressing need for more objective biomarkers of diet for use in health research. The stable isotope ratios of light elements are a promising set of candidate biomarkers because they vary naturally and reproducibly among foods, and those variations are captured in molecules and tissues with high fidelity. Recent studies have identified valid isotopic measures of short- and long-term sugar intake, meat intake, and fish intake in specific populations. These studies provide a strong foundation for validating stable isotopic biomarkers in the general US population. Approaches to improve specificity for specific foods are needed; for example, by modeling intake using multiple stable isotope ratios or by isolating and measuring specific molecules linked to foods of interest.

Keywords: carbon-13; isotope ratio mass spectrometry; nitrogen-15; nutritional epidemiology; sulfur-34.

Figure 1

Naturally occurring stable isotopes of light elements common in biological molecules.

Figure 2

Delta demystified

Figure 3

Measurement of carbon isotope ratios by continuous flow-isotope ratio mass spectrometry (CF-IRMS). A) Elemental analysis – isotope ratio mass spectrometry (EA-IRMS), in which solid samples are combusted and separated into gases by an elemental analyzer before being introduced into the IRMS. B) Gas chromatography – Combustion – isotope ratio mass spectrometry (GC-C-IRMS), in which samples are injected into a gas chromatograph for separation prior to combustion and introduction into the isotope ratio mass spectrometer. Figure used with permission from Reference , copyright Royal Society of Chemistry.

Figure 4

The distribution of δ¹³C values (‰) in C3 and C4 plants, based on approximately 1000 analyses from five different laboratories. Figure adapted with permission from Reference , copyright Oxford University Press.

Figure 5

The stepwise increase in δ¹⁵N values in with trophic level, or position in a food web. Figure adapted with permission from Reference , copyright Pearson-Benjamin Cummings.

Figure 6

Carbon turnover captured in plasma, whole blood, and claw of house sparrows. Figure used with permission from Reference , copyright John Wiley and Sons.

Figure 7

The shift in δ¹³C values (‰) of bone collagen from skeletons recovered from Archaic, Early Woodland, and Late Woodland sites in North America. The dramatic increase in δ¹³C values following 1000 AD reflect the advent of corn agriculture and significant corn consumption. Figure used with permission from Reference , original data from References and . Copyright John Wiley and Sons.

Figure 8

Associations between fingernail δ¹³C, δ¹⁵N, and δ³⁴S values (‰) sampled from Inuit residents of Uummannaq District, Greenland (n = 82) and residents of Denmark (n = 32). Abbreviations: AIR, reference standard for nitrogen, V-CDT, Vienna Cañon Diablo Troilite (reference standard for sulfur), V-PDB, Vienna Pee-Dee Belemnite (reference standard for carbon). Figure used with permission from Reference , copyright Elsevier Publishing.

Figure 9

The association between the ω-3 fatty acid eicosapentaenoic acid [as % red blood cell (RBC) fatty acids] and (a) RBC δ¹⁵N values and (b) hair δ¹⁵N values in Yup’ik adults (n = 497 and 44, respectively) living in Southwest Alaska. Both % EPA and δ¹⁵N values increase with intake of marine foods (fish and marine mammals). Figure adapted with permission from References and , copyright American Society for Nutrition.

Figure 10

(a) Modeled total sugar intake, based on red blood cell (RBC) δ¹³C and δ¹⁵N versus actual total sugar intake in 68Yup’ik adults living in Southwest Alaska. (b) δ¹³C_alanine vs. sugar-sweetened beverage (SSB) intake in 68Yup’ik adults living in Southwest Alaska. Reproduced with permission from References and , copyright American Society for Nutrition.