Co-Authors:
Cecil, H.C.
Bitman, J.
Svoboda, J.A.
Thompson, M.J.
Abstract:
Six branched and straight chain secondary or tertiary amines with chain lengths of 12 to 18 carbons and two azasteroids, 25-aza-5 alpha-cholestane and 25-azacoprostane, were fed to mature White Leghorn hens, and their effectiveness was compared with 20,25-diazacholesterol dihydrochloride (SC-12937), an azasteroid known to lower egg cholesterol. Feed consumption, body weight, egg production, egg and plasma cholesterol and desmosterol, and plasma total lipid were measured. The 6 amines were fed at 200 ppm, and only the C12 branched chain amine N,N,3,711-pentamethyldodecanamine reduced plasma and egg cholesterol with a concomitant increase in desmosterol. After 4 weeks, plasma desmosterol was 0, 13, 60, and 75% of total sterol for control, 200 ppm C12 branched chain amine, 5 ppm diazacholesterol, and 5 ppm azacholestane, respectively. Egg production was severely reduced to 6 and 0% by feeding 5 ppm azacholestane for 2 and 4 weeks, respectively, and to 69 and 36% by feeding 5 ppm diazacholesterol. After 4 weeks egg cholesterol was 79 and 36% of the total sterol for the 200 ppm C12 branched chain amine and 5 ppm diazacholesterol, respectively. Concomitant increases in desmosterol accompanied all reductions in cholesterol. The depletion and repletion rates of egg cholesterol were measured in a subsequent experiment. After 2-1/2 weeks of feeding the test substances, egg cholesterol was reduced with concomitant increases in desmosterol. Egg cholesterol was 100, 71, and 50% of the total egg sterol for control, 200 ppm, and 400 ppm C12 branched chain amine, respectively: 58, 13, and 3% for .1, .5, and 1.0 ppm azacholestane; 28, 29, and 18% for 1, 2.5, and 5 ppm azacholesterol; and 23% for 1 ppm azacoprostane. The experimental diets were then withdrawn, and egg cholesterol repletion was studied biweekly. Egg cholesterol was repleted to 100% of the total sterol after withdrawal times of 2 weeks for C12 branched chain amine, 8 weeks for azacoprpostane, 14 to 16 weeks for diazacholesterol, 10 to 16 weeks for the lower levels of azacholestane, and longer than 16 weeks for 1 ppm azacholestane. The increase in desmosterol accompaning the demonstrated reduction in egg cholesterol, particularly with azasteroids, causes one to question the usefulness of this approach to lower cholesterol.