LDL cholesterol (Friedewald equation)

What is this for?

Most lipid panels do not measure LDL directly; they calculate it. The Friedewald equation subtracts HDL and an estimate of VLDL — taken as triglycerides divided by five — from the total cholesterol. That VLDL estimate is the equation's weak point, and it fails when triglycerides are high.

How to use it

1. Enter total cholesterol, HDL, and triglycerides from the same lipid panel. Unit dropdowns convert from mmol/L automatically.
2. If triglycerides exceed 400 mg/dL, the calculation is blocked and non-HDL cholesterol is offered instead.
3. Note the non-HDL value regardless — it is a valid target at any triglyceride concentration and is increasingly used as a co-primary goal.

Worked example

A lipid panel shows total cholesterol 200 mg/dL, HDL 50 mg/dL, triglycerides 150 mg/dL. Calculate the LDL.

Answer: VLDL = 150 ÷ 5 = 30. LDL = 200 − 50 − 30 = 120 mg/dL. Non-HDL cholesterol is 200 − 50 = 150 mg/dL.

Clinical pearls & pitfalls

• The 400 mg/dL triglyceride limit is a hard boundary, not a caution. Above it the equation systematically underestimates LDL and can lead to undertreatment of a high-risk patient.
• Non-HDL cholesterol requires no fasting and no triglyceride assumption, which is why it has become a preferred secondary target — particularly in diabetes and metabolic syndrome.
• Friedewald was derived on fasting samples. Non-fasting triglycerides run higher, which inflates the VLDL estimate and depresses the calculated LDL. Current guidance accepts non-fasting panels for screening but not for calculated LDL in hypertriglyceridaemia.
• The Martin–Hopkins equation replaces the fixed divisor of 5 with an adjustable factor and is more accurate at low LDL and higher triglycerides. Many laboratories have adopted it.
• A calculated LDL below about 70 mg/dL is less accurate by Friedewald, which matters increasingly as treatment targets fall.

Assumptions & limitations

• Invalid above a triglyceride of 400 mg/dL — PharmCalc blocks rather than returning a misleading number.
• Requires a fasting sample for reliable results; non-fasting triglycerides distort the VLDL estimate.
• Not valid in type III hyperlipoproteinaemia (dysbetalipoproteinaemia) or in the presence of chylomicrons, where the VLDL composition assumption fails entirely.
• Less accurate at low LDL concentrations, which is where much modern therapy operates.
• An estimate, not a measurement. Where the value will change management at a threshold, request a direct LDL.

References

• 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(6):499-502.
• Grundy SM, et al. 2018 AHA/ACC/Multisociety guideline on the management of blood cholesterol. Circulation. 2019;139(25):e1082-e1143.
• Martin SS, et al. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels. JAMA. 2013;310(19):2061-2068.
• Sampson M, et al. A new equation for calculation of low-density lipoprotein cholesterol in patients with normolipidemia and/or hypertriglyceridemia. JAMA Cardiol. 2020;5(5):540-548.

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