Researchers from the Université de Sherbrooke in Canada conducted a 12-week randomized controlled trial in 72 healthy adults, reporting that participants receiving krill oil showed around 1.5-fold greater increases in plasma EPA and DHA than those taking fish oil, despite both groups receiving about 1.1 gram a day of omega-3 fatty acids.
“Omega-3 fatty acids (ω-3 FAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are recognized for their health benefits,” the research team wrote in The American Journal of Clinical Nutrition.
“However, their circulating levels after supplementation may be modulated by several factors, including sex, carriage of the apolipoprotein E4 allele (APOE4) and the chemical form of the supplement. Krill-oil delivers ω-3 FAs primarily as phospholipids (PL), whereas fish oil provides them as triglycerides (TG).”
The study, funded by the Canadian Institutes of Health Research, used fish oil capsules obtained from Neptune Wellness Solutions and SuperbaBoost krill oil capsules from Aker BioMarine.
Beyond dose, toward next-gen phospholipid
The findings contribute to an ongoing discussion around how the chemical form of omega-3s—not just the amount delivered—may shape bioavailability, retention and potentially downstream health effects.
While fish oil remains the dominant format in the category, phospholipid-bound omega-3s have increasingly been positioned as a more efficient or functionally distinct delivery system. The study points to krill oil’s phospholipid structure and particularly its phosphatidylcholine content as responsible for the stronger plasma response observed.
“The higher plasma EPA and DHA concentrations found with krill oil in this study are probably not related to higher absorption of EPA and DHA from krill oil supplements,” the researchers wrote. “The greater plasma ω-3 enrichment observed with krill oil may reflect differences in the digestive and post-absorptive handling of phospholipid-bound versus triglyceride-bound fatty acids.”
Previous studies suggest that krill’s phospholipid structure promotes incorporation into circulating membrane lipids, potentially leading to higher and more sustained blood levels of omega-3 fatty acids. In contrast, fish oil omega-3s are more commonly incorporated into neutral storage fats such as triglycerides.
Sex effects, no genotype differences
The Université de Sherbrooke researchers also explored whether sex and APOE4 carrier status influenced response to supplementation. Each test group included 10 APOE4 carriers and 26 non-carriers, with a comparable sex distribution (26 females and 10 males in the fish oil group; 27 females and 9 males in the krill oil group) and a median age of 59 years.
Findings indicated a significant time-by-sex interaction for EPA regardless of supplement type, with females showing greater increases than males over the course of the trial. DHA responses, however, did not significantly differ by sex.
“This aligns with previous findings from our group where females had higher EPA levels in the plasma PL following ω-3 FAs supplementation, whereas plasma DHA increases were not influenced by sex,” the researchers wrote. “These findings highlight that sex-specific physiology and supplement formulation both play critical roles in modulating ω-3 FAs concentrations in plasma.”
Meanwhile, although APOE4 carriers and non-carriers both showed increases in omega-3 levels, the differences between genotype groups were not statistically significant, suggesting the krill oil advantage observed in the study was maintained regardless of APOE4 status, at least within this cohort.
Carriers of the APOE4 gene—the strongest genetic risk factor for Alzheimer’s disease—have impaired brain transport of omega-3s because the gene alters how the body processes and utilizes them.
“Krill oil increased plasma ω-3 FAs more than fish oil, regardless of APOE4 genotype,” Individuals with higher ω-3 FA requirements may achieve adequate enrichment with lower doses of krill oil compared to fish oil supplementation.”
While promising, the researchers cautioned against overinterpreting the findings from a predominantly healthy female sample population, noting that they cannot automatically be extended to older adults, people with chronic disease or cognitively impaired populations.
They also highlighted that higher plasma EPA and DHA levels do not necessarily translate into superior clinical outcomes and that plasma enrichment alone does not confirm improved tissue uptake or functional benefit.
Source: The American Journal of Clinical Nutrition, doi: 10.1016/j.ajcnut.2026.101346. “Krill oil increase plasma omega-3 fatty acids more than fish oil in healthy adults: a double blind randomized controlled trial”. Authors: Insaf Loukil et al.
