The Friedewald equation is used to calculate VLDL-c (very low density lipoprotein cholesterol) and LDL-c (low density lipoprotein cholesterol) levels in a lipoprotein estimation test. In this method, total cholesterol, triglycerides and HDL-c (high density lipoprotein cholesterol) are directly estimated using reagents. The formula published by Friedewald WT et al in 19721 was validated by Warnick GR and colleagues in 1990.2
VLDL-c = Triglycerides/5
LDL-c = Total cholesterol – (HDL-c + VLDL-c)
Limitation of Friedewald equation
This method of indirect LDL-c estimation becomes unreliable when the triglyceride (TG) levels are high. In that case direct LDL-c measurements have to be resorted to. Friedewald equation was introduced to reduce the time and cost needed for ultracentrifugation in case of direct LDL-c measurement in 1972. Now a days, many laboratories are switching to direct LDL-c measurements in all situations to avoid errors and give better reliability to LDL-c values.
Friedewald equation is not very accurate for estimation of VLDL-c. Friedewald and colleagues had pointed this out in their original publication in 1972 itself. But at that time VLDL-c levels were low compared to LDL-c and the inaccuracy was tolerable.
LDL-c values are also not very accurate at the low levels which are currently targeted in those with coronary artery disease. At low levels, Friedewald equation underestimates LDL-c values. This is more important now as hypertriglyceridemia is increasingly common because of obesity, insulin resistance, and diabetes mellitus (metabolic syndrome). 3
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502.
Warnick GR, Knopp RH, Fitzpatrick V, Branson L. Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints. Clin Chem. 1990 Jan;36(1):15-9.
Martin SS, Blaha MJ, Elshazly MB, Brinton EA, Toth PP, McEvoy JW, Joshi PH, Kulkarni KR, Mize PD, Kwiterovich PO, Defilippis AP, Blumenthal RS, Jones SR. Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications. J Am Coll Cardiol. 2013 Aug 20;62(8):732-9.