Quantification of lowered cholesterol oxidation in guinea pigs with latent vitamin C deficiency

Abstract

Fifty‐two male guinea pigs fed on a scorbutigenic diet were divided into a control group (10 mg ascorbicacid per animal per day) and a group with latent vitamin C deficiency (2 weeks on the scorbutigenic diet only, followed by a maintaining dose of 0.5 mg ascorbic acid per animal per day). After 13 weeks, 26‐14C‐cholesterol was administered intraperitoneally to all the animals, in which the14C excretion in the expired CO2 and the urine and cholesterol specific activity in the blood serum and liver were then studied at intervals of 24 hr and 1, 3, 5, 7, 9 and 11 weeks. The ascorbic acid concentration in the liver and spleen of the control animals was five times higher than in vitain C‐deficient animals. The total cholesterol concentration in serum and liver was significantly higher in the vitamin C‐deficient guinea pigs. A two‐pool analysis of the disappearance curves of serum cholesterol specific activity showed that the size of the cholesterol pool A (blood and tissues with rapid cholesterol exchange) was greater in the vitamin C‐deficient animals. The rate of the transformation of cholesterol to bile acids was estimated as the ratio of14CO2 expired to liver cholesterol specific activity. Latent vitamin C deficiency caused significant slowing down of this process (controls: 11.8±0.6; vitamin C deficiency: 8.3±0.4 mg/24 r/500 g w/w). A significant correlation between the liver ascorbic acid concentration and the rate of cholesterol transformation to bile acids was found. The results demonstrate that ascorbic acid is necessary for a normal course of cholesterol catabolism. In latent vitamin C deficiency, the rate of cholesterol catabolism slows down and cholesterol consequently accumulates in the blood and liver of vitamin C‐deficient guinea pigs.

Vitamin C supplement use may protect against gallstones: an observational study on a randomly selected population

“…The role of vitamin C in bile acid biogenesis has mainly been analysed in guinea pigs [3-9]. Cholesterol is converted to bile acids in the liver, and the rate limiting process depends on vitamin C concentration in the hepatocytes [3,4].…”

Cholesterol metabolism in inherently scorbutic rats (ODS rats).

“…Although the accumulation of TC in serum of ODS-od/od rats fed with a commercial diet was not so much higher than the results of experiments using guinea pigs chronically fed with a vitamin C-deficient diet (15,16), ODS-od/od rats fed with a cholesterol supplied diet resulted in a significant increase of TC in serum and liver. Our result is the same as that of Horio et al using ODS rats fed with a diet supplied 0.5% cholesterol and 0 .25% cholic acid (17).…”

“…From the above results, exogenous loading of an inadequately large dose of lipid, we also can assume that ODS-od/od rats have a disorder in the excretion pathway of choles terol. Ginter (16) reported that vitamin C is a cofactor of a key enzyme, 7a hydroxylase, in this pathway to bile acid (18). There have been only a few reports proving this hypothesis because the method of measurement of this enzyme is not easy.…”

The Role of Ascorbic Acid in the Mosaic of Coronary Heart Disease: Lipid Metabolism and Antioxidant Functions.

“…The role of AA in lipid metabolism has been studied extensively in guinea pigs as, like humans, they are incapable of synthesizing AA. Long term hypovitaminosis C resulted in the accumulation of cholesterol in blood serum and/or a number of tissues, including the liver and the thoracic aorta [9], possibly due to a decreased rate of cholesterol catabolism [ 10,11 ] . In genetically modified rats unable to synthesize AA, AA deficiency resulted in elevated serum and liver concentrations of cholesterol regardless of whether rats were fed a normal or cholesterol-containing diet [12] .…”

“…AA may influence lipid metabolism in different ways. In guinea pigs, the catabolism of cholesterol to bile acids is hindered by low AA levels [11,[54][55][56][57]. A significant linear correlation has been observed between the rate of cholesterol conversion to bile acids and the AA concentration in the liver of guinea pigs [ii, 55].…”