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.

The carbon-13 isotopic signatures of flax oil ALA and fish oil EPA, n-3 DPA, and DHA were distinct from one another, enabling in vivo tracing.

• δ13C signatures were -33.2 ± 1.4 mUr for flax oil ALA, -26.3 ± 2.2 mUr for fish oil EPA, -26.2 ± 1.5 mUr for fish oil n-3 DPA, and -25.4 ± 1.3 mUr for fish oil DHA.
• Baseline plasma δ13C signatures of EPA, n-3 DPA, and DHA were not statistically different from one another.
• The difference in δ13C between plant-derived (flax) and marine-derived (fish) oils provided the isotopic contrast necessary for tracing.
• Participants were aged 19–34 years (n=12) in a 28-day randomized crossover design with 6-week wash-in and washout phases.

Plasma δ13C signatures of EPA, n-3 DPA, and DHA converged toward the isotopic signature of the fish oil supplement over the 28-day supplementation period.

• Convergence toward fish oil δ13C signatures was statistically significant over time (P < 0.05) for EPA, n-3 DPA, and DHA.
• Blood was collected on days 0, 1, 3, 7, 14, and 28 to track the temporal change in isotopic signatures.
• The study used gas chromatography-isotope ratio mass spectrometry (GC-IRMS) to measure compound-specific δ13C values.
• Supplementation doses were 4.3 g/d DHA, 1.0 g/d EPA, and 0.2 g/d n-3 DPA from fish oil.

The calculated plasma half-life of EPA was 3.4 ± 2.7 days, shorter than the half-lives of n-3 DPA and DHA.

• EPA half-life was 3.4 ± 2.7 days (mean ± SD).
• n-3 DPA half-life was 6.4 ± 5.3 days.
• DHA half-life was 6.3 ± 8.9 days.
• These values were described as similar to preclinical model values and values obtained by other clinically used methods.
• Half-lives were derived from the rate of change in δ13C signatures over the 28-day supplementation period.

Turnover rates of EPA, n-3 DPA, and DHA in plasma were calculated as 61.9 ± 53.1, 6.0 ± 2.9, and 78.0 ± 44.5 nmol/mL/d, respectively.

• EPA turnover rate was 61.9 ± 53.1 nmol/mL/d.
• n-3 DPA turnover rate was 6.0 ± 2.9 nmol/mL/d, the lowest of the three fatty acids measured.
• DHA turnover rate was 78.0 ± 44.5 nmol/mL/d, the highest of the three.
• Turnover rates were calculated alongside half-life estimates using the δ13C kinetic modeling approach.

This study provides the first estimate of n-3 DPA half-life and turnover rate in humans.

• Prior to this study, no human data existed for n-3 DPA half-life or turnover rate.
• The authors describe this as 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.
• n-3 DPA half-life was 6.4 ± 5.3 days and turnover was 6.0 ± 2.9 nmol/mL/d.
• The study used a secondary analysis framework of a previously conducted 28-day randomized crossover trial.

Compound-specific isotope analysis (CSIA) using naturally occurring carbon-13 variance in commercial oils is identified as a valid tool for measuring n-3 PUFA kinetics in humans.

• The method relies on fixed δ13C differences between plant-derived (C3 photosynthesis pathway) and marine-derived lipid sources.
• GC-IRMS was used to analyze compound-specific δ13C signatures in plasma fatty acids.
• Results were consistent with preclinical model values and other clinically used kinetic methods.
• The authors note that this approach can be extended to study factors affecting n-3 PUFA kinetics including diet, exercise, sex, genetics, and disease.
• No exogenous isotopic tracer was required, as the natural isotopic difference between supplement sources served as the tracer.