BackgroundWe investigated the interference of vitamin C (VitC), glycerol fructose, lipoprotein X (LpX) and lipemia on the analysis of serum lipids. MethodsSerum were collected from 44 patients with VitC infusion, serum lipid concentrations before and after VitC auto-oxidation were compared. Serum of 31 patients with glycerol fructose infusion were collected, triglycerides (TG) measured by glycerol blanking and non-blanking reagents were compared. Forty-four serum samples suspected to contain LpX were collected, LDL-C measured by reagents from five manufacturers were compared. Lipemia samples were collected, LDL-C measured using five different reagents were compared. The interference rate was considered unacceptable if it was greater than 1/2 total allowable error (TEa). ResultsIn patients with VitC infusion, the interference rates of TG and total cholesterol (TC) were −59% (−123%, −28%) and −15% (−21%, −11%), respectively. In patients with glycerol fructose infusion, the interference rate of TG was 13% (4%, 113%). LpX interference led to increased LDL-C results for most reagents. Lipemia caused great interference with LDL-C analysis. ConclusionVitC, glycerol fructose, LpX and lipemia significantly interfered with lipid assays. The reagent formulation should be improved to get reliable results.