Abstract Atherosclerosis, the primary pathological basis of most cardiovascular diseases, remains a leading global cause of mortality, highlighting the need for effective interventions. Krill oil (KO) and fish oil (FO) are key sources of cardiovascular-protective ω-3 fatty acids but possess distinct profiles: KO provides superior bioavailability via phospholipids, whereas FO offers higher absolute concentrations of eicosapentaenoic and docosahexaenoic acids. We hypothesized that combining KO and FO might leverage their complementary properties. This study therefore evaluated their individual and combined effects against atherosclerosis in apolipoprotein E knockout (apoE ⁻ / ⁻ ) mice fed a high-fat diet. Mice were treated with KO, FO, a medium-dose (M-KO-FO) or high-dose (H-KO-FO) combination, atorvastatin, or assigned to the model group for 14 weeks. The M-KO-FO regimen produced the most robust outcomes, significantly reducing the aortic atherosclerotic plaque area by 39.22% compared to the model group ( p < 0.01), with efficacy comparable to atorvastatin. Mechanistically, M-KO-FO concurrently ameliorated disordered lipid metabolism by significantly lowering serum levels of LDL-C and the quantitative indicators of arteriosclerosis severity (non-HDL-C, AI, and AIP) ( p < 0.05 or p < 0.01), and markedly reduced hepatic steatosis ( p < 0.01). In parallel, it suppressed vascular inflammation, as evidenced by the significant downregulation of key aortic pro-inflammatory mediators (IL-6, MCP-1, VCAM-1, ICAM-1; p < 0.01). These results demonstrate that the medium-dose KO-FO combination may be an effective intervention, conferring significant atheroprotection through concurrent modulation of lipid metabolism and inflammation. In contrast, monotherapy with either KO or FO at the tested dose conferred more restricted benefits.
Yao et al. (Sat,) studied this question.