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Am J Clin Nutr. 2022 Jan 14; doi: 10.1093/ajcn/nqac004. Epub 2022 Jan 14.

An evaluation of the serum carbon isotope ratio as a candidate predictive biomarker for dietary animal protein ratio (animal protein/total protein) in a 15-d controlled feeding study of US adults.

The American journal of clinical nutrition

Diane M O'Brien, Virag Sagi-Kiss, Susana A Palma Duran, Chris Cunningham, Brian Barrett, Carol S Johnston, Douglas Midthune, Victor Kipnis, Laurence S Freedman, Natasha Tasevska


  1. Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK.
  2. College of Health Solutions, Arizona State University, Phoenix, AZ.
  3. Information Management Services, Inc., Rockville, MD.
  4. Division of Cancer Prevention, National Cancer Institute, Bethesda, MD.
  5. Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel.

PMID: 35030258 DOI: 10.1093/ajcn/nqac004


BACKGROUND: The serum natural abundance carbon isotope ratio (CIR) was recently identified as a candidate biomarker of animal protein intake in postmenopausal women. Such a biomarker would help clarify the relationship between dietary protein source (plant vs. animal) and chronic disease risk.

OBJECTIVES: To evaluate the performance of the serum CIR as a biomarker for dietary protein source in a controlled feeding study of men and women of diverse age and BMI.

DESIGN: We conducted a 15-d feeding study of 100 adults (age 18-70, 55% women) in Phoenix, AZ. Participants were provided individualized diets that approximated habitual food intakes. Serum was collected at the end of the feeding period for biomarker measurements.

RESULTS: Animal protein intake was 67 (55, 88) g/d (median, 25th, 75th), which was 64% of total protein. The serum CIR was positively correlated with animal protein and inversely correlated with plant protein intake, leading to a strong correlation (r2 = 0.76) with the dietary animal protein ratio (APR; animal/total protein). Regressing serum CIR on the APR, serum nitrogen isotope ratio (NIR), gender, age and body weight generated an R2 of 0.78. Following the measurement error model for predictive biomarkers, the resulting regression equation was then inverted to develop a calibrated biomarker equation for APR. Added sugar ratio (added/total sugars intake) and corn intakes also influenced the serum CIR but to a much lesser degree than the APR; variations in these intakes had only small effects on biomarker-estimated APR.

CONCLUSIONS: Based on our findings in this United States cohort of mixed sex and age, we propose the serum CIR alongside NIR as a predictive dietary biomarker of APR. We anticipate using this biomarker to generate calibrated estimates based on self-reported intake and ultimately to obtain more precise disease risk estimates according to dietary protein source.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Keywords: US adults; animal protein intake; biomarker calibration; biomarker of dietary intake; carbon isotope ratio; nitrogen isotope ratio; plant protein intake; predictive biomarker; stable isotope ratio

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