Abstract
Urinary excretion of mevalonic acid was investigated as an indicator of cholesterol synthesis. In normolipemic volunteers, excretion of mevalonic acid averaged 3.51 +/- 0.59 (SD) micrograms/kg x day1; (n = 24) and was not different from patients with hypercholesterolemia (3.30 +/- 0.92 micrograms/kg x day1; n = 24). In patients with cerebrotendineous xanthomatosis, the excretion was significantly higher (8.55 +/- 1.92 micrograms/kg x day1; n = 6, P < 0.001) but comparable to volunteers treated with cholestyramine (6.69 +/- 2.6 micrograms/kg x day1; n = 5). A significant correlation was found between 24-h excretion of mevalonic acid and cholesterol synthesis (r = 0.835; n = 35; P < 0.001). The coefficient of variation of excretion of mevalonic acid during 3 consecutive days was small (9.8%; n = 7). However, urinary output of mevalonic acid was significantly higher during the night (164 +/- 14 micrograms/12-h) than during the day (129 +/- 9 micrograms/12-h; n = 11; P < 0.05). In patients treated with simvastatin (40 mg/day) for 6 weeks, the ratio of mevalonic acid to creatinine in a morning urine sample decreased significantly compared to pretreatment values (110 +/- 25 micrograms/g vs. 66 +/- 25 micrograms/g; P < 0.001). Furthermore, the ratio of mevalonic acid to creatinine in a morning urine sample correlated with the ratio from the 24-h collection period (r = 0.714; n = 34; P < 0.001). The results indicate that the analysis of urinary mevalonic acid, either in 24-h collection or in a single morning sample, is an attractive method for evaluation of long and very short term changes of the rates of cholesterol synthesis.
Highlights
Urinary excretion of mevalonic acid was investigated as an indicator of cholesterol synthesis
These results demonstrate that there were no differences in the rates excretion of Lindathal et al Urinary mevalonic acid as indicator of cholesterol synthesis 2195
Measuring cholesterol synthesis provides us with important information on cholesterol homeostasis under various physiological conditions, disease states, and
Summary
Urinary excretion of mevalonic acid was investigated as an indicator of cholesterol synthesis. In the metabolic steady state, the serum concentrations of mevalonic acid reflect the activity of hepatic HMGCoA reductase, including its peak concentrations at night and low concentrations during the day that may vary 2- to 5-fold over 24 h [2] Despite this diurnal variation in serum concentrations of mevalonic acid, a significant correlation between mevalonic acid in fasting serum and total cholesterol synthesis measured by the fecal balance method has been observed under metabolic ward conditions [3]. Popjak et al [4] and Parker et al [2] noted a large variation on different days in the serum concentrations of individual subjects For this reason, it may be difficultto estimate cholesterol synthesis rates in outpatients by measuring serum concentrations of mevalonic acid.
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