Effect of 1- and 2-Month High-Dose Alpha-Linolenic Acid Treatment on 13 C-Labeled Alpha-Linolenic Acid Incorporation and Conversion in Healthy Subjects

Abstract

Scope: The study aims at identifying 1) the most sensitive compartment among plasma phospholipids, erythrocytes, and LDL for studying alpha-linolenic acid (ALA) conversion, and 2) whether ALA incorporation and conversion is saturable after administration of ¹³ C-labeled ALA-rich linseed oil (LO). The effect of a daily intake of 7 g nonlabeled LO (>43% w/w ALA) for 1 month after bolus administration of 7 g ¹³ C-labeled LO on day 1, and for 2 months after bolus administration of 7 g ¹³ C-labeled LO on day 1 and day 29 on ¹³ C-ALA incorporation and conversion into its higher homologs is investigated in healthy volunteers.

Methods and results: Incorporation and conversion of LO-derived ¹³ C-labeled ALA is quantified by applying compartmental modeling. After bolus administration, a fractional conversion of approximately 30% from ¹³ C-ALA to ¹³ C-DHA is calculated as reflected by the LDL compartment. Treatment with LO for 8 weeks induces a mean reduction of ¹³ C-ALA conversion to ¹³ C-DHA by 48% as reflected by the LDL compartment, and a mean reduction of the ¹³ C-ALA incorporation into LDL by 46%.

Conclusion: A 2-month dietary intake of a high dose of LO is sufficient to reach saturation of ALA incorporation into LDL particles, which are responsible for ALA distribution in the body.

Keywords: ALA conversion; LDL; compartment model; linseed oil; omega-3 fatty acids.

Figure 1

Study design. Blood was collected 0, 2, 4, 10, 24, 48, 72, and 96 h as well as 1, 2, 3, and 4 weeks after administration of the labeled LO.

Figure 2

Tracer Model of ALA metabolism during the intervention phases I and II. The syringe depicts ¹³C‐ALA administration. The q1 compartment represents the dietary intake of ¹³C‐ALA, while the q2 compartment represents the ¹³C‐labeled n‐3 fatty acids in the blood. The other circles denoted q3, q4, q5, and q6 represent the ¹³C‐labeled ALA, EPA, DPA, and DHA in LDL, respectively. Two delay compartments, d8 and d11, consider the delayed transfer of the ¹³C‐n‐3 fatty acids. The delay d11 accounts for the further hepatic and extrahepatic exchange of the ¹³C‐n‐3 fatty acids. The closed circles s1–s4 represent the blood samples drawn to analyze the ¹³C‐labeled n‐3 fatty acids in LDL.

Figure 3

Graphical analysis of the model‐predicted fit through the experimental‐averaged data (closed triangles) during phases I and II. The amount of ALA tracer A), EPA tracer B), DPA tracer C), and DHA tracer D) was obtained applying the nonlinear least‐squares fitting.

Figure 4

Time‐dependent courses of proportion of n‐3 fatty acids in plasma phospholipids A) and tracer/total n‐3 fatty acid in erythrocytes B) and tracer/trace in LDL C) after oral administration of 7 g ¹³C‐labeled LO at the beginning of intervention phases I and II. Blood was drawn in each intervention phase 0, 2, 4, 10, 24, 48, 72, 96, 168, 336, 504, and 672 h after administration of the labeled LO. The corresponding n‐3 fatty acids were analyzed in the respective compartment.