Quantifying conversion of alpha-linolenic acid (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA): a systematic review of animal and human studies utilizing carbon-13 ALA

The capacity for humans to synthesize long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), from α-linolenic acid (ALA) remains debated, owing in part to inconsistent estimates of conversion efficiency. Given the growing application of compound-specific isotope analysis (CSIA) in fatty acid metabolism research, we aimed to summarize the evidence on ALA to EPA/DHA conversion from studies using 13 C-labelled ALA. Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to May 27, 2026. Animal and human studies that administered 13 C-ALA and quantified conversion to 13 C-EPA or 13 C-DHA were included. Thirty studies were reviewed (13 in animals and 17 in humans). Studies were evaluated using the OHAT risk of bias tool for both human and animal studies. Conversion was commonly estimated by percent tracer dose ( n = 13), and percent distribution among total labelled fatty acids ( n = 3) or labelled n-3 PUFAs ( n = 4). Fewer studies reported fractional conversion ( n = 2) or synthesis/turnover rates ( n = 2). Percent distribution yielded the highest estimates of conversion to 13 C-DHA, which ranged from 30 to 85% in fetal and pup liver, 3.5–12.1% in human infant plasma, and 0–9.2% in adult plasma. Percent tracer estimates were < 1% in the developing brain, ≤ 1.6% in liver, and ≤ 0.2% in plasma/serum in animal studies, and < 0.5% in adult human plasma. In mice, conversion of dietary ALA to whole-body DHA was estimated to be 9.5%, suggesting substantial underestimation when conversion is estimated from plasma alone. Potential modifiers of n-3 PUFA conversion includes dietary fatty acid composition, sex, age, and genetics, whereas heterogeneity in conversion estimates may arise from differences in background diet, sampling timeframe and method used to quantify conversion. Continued application of 13 C-ALA studies in vegetarians and vegans, and across healthy and disease states may provide further insight into factors associated with altered n-3 PUFA metabolism.