Serum lathosterol levels in human subjects reflect changes in whole body cholesterol synthesis induced by lovastatin but not dietary cholesterol.

We measured serum lathosterol levels and whole body cholesterol synthesis by sterol balance in 12 human subjects on a metabolic ward in four randomly allocated, 6-7 week periods: 1) lovastatin (40 mg b.i.d.) + low cholesterol diet (mean 246 mg/day); 2) lovastatin + high cholesterol diet (mean 1071 mg/day); 3) low cholesterol diet alone; and 4) high cholesterol diet alone. Whole body cholesterol synthesis was significantly reduced both by lovastatin (P = 0.0004) and by high dietary cholesterol (P = 0.0005). Serum total lathosterol (micrograms/dl) was reduced by lovastatin (P < 0.0001), but was not significantly altered (and actually tended to increase) during consumption of the high cholesterol diet, presumably because eggs contained appreciable lathosterol as demonstrated by direct analysis. Results were similar for total versus free lathosterol and for lathosterol expressed as micrograms/dl serum versus micrograms/100 mg cholesterol. We conclude that serum lathosterol does not reflect changes in cholesterol synthesis induced by dietary cholesterol. Studies using serum lathosterol as an indicator of cholesterol synthesis must be carefully controlled for dietary cholesterol.