Benefit from direct LDL-C measurement and overcome the limitations of the Friedewald estimation

The Friedewald calculation is a common approach to determine low-densitiy lipoprotein (LDL-C) in clinical laboratory. It estimates LDL-C as: Total cholesterol (TC) minus high-density lipoprotein-cholesterol (HDL-C) minus triglycerides (TG)/5, but the method only approximates LDL-C and is subject to well-established limitations. Although calculated LDL-C levels in healthy patients correlate well with directly measured LDL-C, they do not match in patients with lipid disturbances, diabetes, coronary or other atherosclerotic disease [1]. Furthermore, the Friedewald equation shows limitations under certain conditions since the quotient (TG)/5) is used to estimate the very-low-density lipoprotein cholesterol (VLDL-C) concentration. It assumes that virtually all plasma triglycerides are carried on VLDL, and that the TG - cholesterol ratio of VLDL is constant at about 5:1 [2].

Limitations of the Friedewald formula

Since the equation is prone to inaccuracy at high VLDL, low LDL-C and/or high TG levels, studies recommend caution when using Friedewald`s equation in pathological conditions that result in lipid disturbances such as diabetes, the metabolic syndrome, kidney disease, and severe liver damage.

Due to the increase in the rate of diabetes, metabolic syndrome and other lipid disturbances on the one hand and the reduction of LDL-C treatment goals in high cardiovascular risk patients on the other hand, precise and accurate clinical tools become even more important. The direct assays for LDL-C represent remarkable technologic breakthroughs with great potential for improving lipoprotein analysis.


1. Senti M, Pedro-Botet J, Rubiés-Prat J, et al. Secondary prevention of coronary heart disease in patients with extracoronary atherosclerosis: a need for accuracy of low density lipoporotein determination. Angiology. 1996;47(3):241–246.
2. William T Friedewald, Robert I Levy, Donald S Fredrickson, Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, Without Use of the Preparative Ultracentrifuge, Clinical Chemistry, Volume 18, Issue 6, 1 June 1972, Pages 499–502.