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Red blood cell ¹⁵N: a novel biomarker of dietary eicosapentaenoic acid and docosahexaenoic acid intake

¹ From the Center for Alaska Native Health Research, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK (DMO, MAJ, MJW, AB, and BL), and the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (ARK).

² The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Research Resources, the National Institutes of Health, or the National Science Foundation.

³ Supported by a Centers of Biomedical Research Excellence grant from the NIH NCRR (P20 RR16430) and undergraduate research awards to MJW and MAJ from Alaska EPSCOR (NSF 0346770), Alaska INBRE (NIH NCRR RR016466), and the UAF Center for Research Services.

⁴ Address reprint requests and correspondence to DM O'Brien, Institute of Arctic Biology, PO Box 757000, University of Alaska Fairbanks, Fairbanks, AK 99775-7000. E-mail: ffdo{at}uaf.edu

Background: The long-chain omega-3 (n–3) fatty acids derived from fish, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a reduced risk of cardiovascular disease and other chronic diseases. Study of the associations between EPA and DHA intake and disease requires a valid biomarker of dietary intake; however, the direct measurement of tissue fatty acid concentrations is expensive and time consuming.

Objective: Because the nitrogen stable isotope ratio (¹⁵N/¹⁴N, expressed as ¹⁵N) is elevated in fish, we investigated whether ¹⁵N is a valid alternative biomarker of EPA and DHA intake.

Design: We examined the relation between red blood cell (RBC) ¹⁵N and RBC EPA and DHA in a community-based sample of 496 Yup'ik Eskimos with widely varying intake of n–3 fatty acids. We also assessed the correlation between ¹⁵N and dietary EPA and DHA intake based on 24-h dietary recalls and 3-d food records completed by a subset of 221 participants.

Results: RBC ¹⁵N was strongly correlated with RBC EPA and DHA (r = 0.83 and 0.75, respectively). These correlations differed only modestly by sex and age class. RBC ¹⁵N also correlated with dietary EPA and DHA intake (r = 0.47 and 0.46, respectively) and did not differ by sex and age.

Conclusions: The results strongly support the validity of RBC ¹⁵N as a biomarker of EPA and DHA intake. Because the analysis of RBC ¹⁵N is rapid and inexpensive, this method could facilitate wide-scale assessment of EPA and DHA intake in clinical and epidemiologic studies.