AmJ Clin Nutr., 2026, Apr 7:101311. doi: 10.1016/j.ajcnut.2026.101311

Determining the half-life and turnover rate of EPA, n-3 docosapentaenoic acid, and DHA in humans using the natural abundance of carbon-13: a secondary analysis of a randomized clinical trial

Symington, A Wu, D Chen, CT et al.

Background: Tools to measure omega-3 (n-3) polyunsaturated fatty acid (PUFA) half-lives and turnover deserve attention, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play vital roles in the body. Plants and marine life vary in fixed carbon-13 signatures (δ13C), allowing in vivo tracing.  Objectives: To determine the half-lives and turnover of n-3 PUFAs using δ13C in this secondary analysis.  Methods: During a 28-d randomized crossover study (6-wk wash-in phase/washout phase), 12 participants (aged 19-34 y) were supplemented with 4.2 g/d α-linolenic acid (ALA) (flax oil) or 4.3 g/d DHA, 1.0 g/d EPA, and 0.2 g/d docosapentaenoic acid (n-3 DPA) (fish oil). Blood was collected on days 0, 1, 3, 7, 14, and 28. Plasma n-3 PUFA δ13C signatures were analyzed by gas chromatography-isotope ratio mass spectrometry (GC-IRMS) to calculate half-lives and turnover.  Results: δ13C signatures of flax oil ALA, fish oil EPA, n-3 DPA, and DHA were -33.2 ± 1.4, -26.3 ± 2.2, -26.2 ± 1.5, and -25.4 ± 1.3 mUr, respectively. Baseline signatures were not statistically different. Over time, δ13C of EPA, n-3 DPA, and DHA converged toward the isotopic signature of the fish oil supplement (P < 0.05). Using δ13C signatures, half-lives of EPA, n-3 DPA, and DHA (3.4 ± 2.7, 6.4 ± 5.3, and 6.3 ± 8.9 d, mean ± SD, respectively) and turnover rates (61.9 ± 53.1, 6.0 ± 2.9, and 78.0 ± 44.5 nmol/mL/d, respectively) were calculated.  Conclusions:This is the first study to investigate n-3 PUFA half-lives and turnover in humans using GC-IRMS and the natural variance of 13C in commercial fish oils. These results were similar to preclinical model values and other clinically used methods but added the first estimate for n-3 DPA half-life and turnover rate. Compound-specific isotope analysis is a valuable tool in human studies for determining n-3 PUFA half-lives and turnover rate, as well as factors affecting them, including diet, exercise, sex, genetics, and disease.

 

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