Pjh. Jones et al., DIETARY-CHOLESTEROL FEEDING SUPPRESSES HUMAN CHOLESTEROL-SYNTHESIS MEASURED BY DEUTERIUM INCORPORATION AND URINARY MEVALONIC ACID LEVELS, Arteriosclerosis, thrombosis, and vascular biology, 16(10), 1996, pp. 1222-1228
The objective of this study was to measure the response of cholesterol
biosynthesis in subjects to three different amounts of dietary choles
terol: 50 (low), 350 (medium), and 650 (high) mg cholesterol per 2800
kcal. Individuals with low (n=7), normal (n=12), and elevated (n=11) p
lasma cholesterol concentrations consumed in random order solid-food t
est diets (15%, 55%, and 30% of energy as protein, carbohydrate, and f
at, re spectively) at each dietary cholesterol level. The three diets
were consumed for 4 weeks each, and each dietary phase was separated b
y a 4-week washout period. During the final week of each diet, 0.7 g D
2O was given per kilogram of body water and deuterium incorporation in
to the erythrocyte cholesterol pool was measured for 24 hours. Urinary
mevalonate levels were also determined in samples obtained during two
consecutive 24-hour periods. Both techniques provided measurements of
whole-body cholesterol biosynthesis. In all subjects the cholesterol
synthesis rate as measured by deuterium incorporation was significantl
y lower (P<.05) after the transition from low- to medium- and low- to
high-cholesterol diets. Urinary mevalonate excretion decreased after t
he change from the medium- to high- (P<.05) and low- to high- (P<.01)
cholesterol diets. Although correspondence between the two methods was
poor, they bath indicated some suppression of cholesterol synthesis b
y dietary cholesterol. The response of cholesterogenesis to different
amounts of dietary cholesterol was related to the rate of synthesis un
der depressed conditions of the low-cholesterol diet. These findings i
ndicate modest downregulation of synthesis in response to dietary chol
esterol in humans, independent of plasma cholesterol levels.