Stearidonic acid (SDA), a highly unsaturated (n-3) PUFA, is effectively metabolized to EPA with a bioequivalence of ˜5:1 as determined by the omega-3 index, a biomarker for risk of cardiovascular disease. The AHA has recommended that individuals increase their consumption of highly unsaturated (n-3) PUFA, particularly EPA and DHA, but there are concerns about achieving the recommendations through fish consumption. SDA is considered a biological surrogate for EPA. SDA-enriched soybean oil whose SDA content is ˜30% could be a novel mechanism to seamlessly incorporate highly unsaturated (n-3) PUFA into the food supply; however, the effects of SDA are poorly understood, particularly at the transcriptional level. This paper reviews the human literature of the effects of dietary SDA on circulating lipids as directly compared with EPA at bioequivalent doses. These results were then compared to the effects of SDA on expression patterns of hepatic lipolytic and lipogenic genes in swine fed diets containing SDA at levels similar with those doses used in human trials. Supplementing SDA at doses of 3.7-4.2 g/d, of which the bioequivalence to EPA is ≤1 g/d, had little impact on modifying circulating TG and total, LDL, and HDL cholesterol, recapitulating the results with EPA at doses of 1.0-1.5 g/d. These results were generally supported by the gene expression patterns in swine. Although many lipolytic and lipogenic genes remained unchanged, several lipogenic genes were downregulated and a number of other biomarkers considered atheroprotective, such as C-reactive protein and paraoxonase, were favorably modified. J. Nutr. 142: 630S-634S, 2012.