(OR03-05-25) Impact of Dietary α-Linolenic Acid and Genetic Variation on Circulating Polyunsaturated Fatty Acids in Individuals With Elevated Glycemic Status

Objectives: This study aimed to investigate the effects of α-linolenic acid (ALA) supplementation and genetic variation on circulating polyunsaturated fatty acids (PUFAs) in individuals with elevated glycemic status.

Methods: A randomized, double-blind, placebo-controlled, crossover trial was conducted among 94 participants (HbA1c: 5.7–8.0% or fasting blood glucose: 6.1–8.4 mmol/L). Participants were randomly assigned to receive either 4.5 g/day of flaxseed oil (FO; providing 2.5 g ALA) or corn oil (CO; < 0.1 g ALA) for two 12-week intervention periods, separated by a 12-week washout phase. Circulating fatty acid composition was analyzed using gas chromatography-mass spectrometry. Single nucleotide polymorphisms (SNPs) within the FADS and ELOVL gene clusters were genotyped using a gene microarray. Data were analyzed using an intention-to-treat approach, with mixed-effect linear models to assess time and intervention effects.

Results: The mean age of participants was 51.2 ± 5.6 years, with a mean body mass index (BMI) of 25.5 ± 3.4 kg/m² and 80.9% male. Compared to the CO group, FO supplementation significantly increased the proportion of total n-3 PUFAs in plasma by 0.31% (least squares mean: 0.31, 95% CI: 0.15, 0.47), including 0.21% (95% CI: 0.13, 0.30) for ALA, 0.07% (95% CI: 0.01, 0.13) for eicosapentaenoic acid (EPA), and 0.05% (95% CI: 0.03, 0.07) for docosapentaenoic acid (DPA) (P < 0.05 for all). Similar changes were observed in erythrocytes. Additionally, smaller increases in the proportion of plasma DPA were observed among carriers of rs174555-C (FADS1; β = -0.067, P = 0.014), rs174602-C (FADS2; β = -0.066, P = 0.014), rs1000778-A (FADS3; β = -0.061, P = 0.019), and rs174455-G (FADS3; β = -0.056, P = 0.024). Participants with low unweighted polygenic risk score (PRS) for plasma DPA had higher increment in the proportion of plasma DPA (0.111%, 95% CI: 0.034, 0.187) compared with those who had high unweighted PRS (-0.058%, 95% CI: -0.134, 0.018, P = 0.002).

Conclusions: Twelve weeks of ALA supplementation (2.5 g/day) improved circulating n-3 PUFA profiles in individuals with elevated glycemic status. Genetic variations in the FADS gene cluster modulated these effects, highlighting the role of genetic factors in dietary response.

Funding Sources: This study is supported by the National Natural Science Fund for Excellent Young Scientists of the National Natural Science Foundation of China (82222061).