Influence of Chronic Ascorbic Acid Deficiency and Excessive Ascorbic Acid Intake on Bile Acid Metabolism and Bile Composition in the Guinea Pig

Holloway, David E.; Rivers, Jerry M.

doi:10.1093/jn/111.3.412

Cited by 57 publications

(29 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…been determined, but a reduction in 7-␣-hydroxylase activity has been demonstrated in vitamin C-deficient guinea pigs (30)(31)(32). Although further investigation is clearly needed, our results re-emphasize the importance of proper vitamin C intake to maintain a plasma lipoprotein profile that is associated with reduced risk for coronary heart disease.…”

Section: Discussionmentioning

confidence: 47%

Aortic wall damage in mice unable to synthesize ascorbic acid

Maeda

Hagihara

Nakata

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

228

239

View full text Add to dashboard Cite

By inactivating the gene for L-gulono-␥-lactone oxidase, a key enzyme in ascorbic acid synthesis, we have generated mice that, like humans, depend on dietary vitamin C. Regular chow, containing about 110 mg͞kg of vitamin C, is unable to support the growth of the mutant mice, which require L-ascorbic acid supplemented in their drinking water (330 mg͞liter). Upon withdrawal of supplementation, plasma and tissue ascorbic acid levels decreased to 10 -15% of normal within 2 weeks, and after 5 weeks the mutants became anemic, began to lose weight, and die. Plasma total antioxidative capacities were approximately 37% normal in homozygotes after feeding the unsupplemented diet for 3-5 weeks. As plasma ascorbic acid decreased, small, but significant, increases in total cholesterol and decreases in high density lipoprotein cholesterol were observed. The most striking effects of the marginal dietary vitamin C were alterations in the wall of aorta, evidenced by the disruption of elastic laminae, smooth muscle cell proliferation, and focal endothelial desquamation of the luminal surface. Thus, marginal vitamin C deficiency affects the vascular integrity of mice unable to synthesize ascorbic acid, with potentially profound effects on the pathogenesis of vascular diseases. Breeding the vitamin C-dependent mice with mice carrying defined genetic mutations will provide numerous opportunities for systematic studies of the role of antioxidants in health and disease.

show abstract

Section: Discussionmentioning

confidence: 47%

Aortic wall damage in mice unable to synthesize ascorbic acid

Maeda

Hagihara

Nakata

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

228

239

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Discussionmentioning

confidence: 62%

Cholesterol metabolism in inherently scorbutic rats (ODS rats).

Kono

Hayakawa

Asai

et al. 1988

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

View full text Add to dashboard Cite

SummaryWe observed the cholesterol metabolism of a colony of Wistar rats with a hereditary defect in vitamin C synthesizing ability (the ODS (osteogenic disorder-Shionogi) rats) in six kinds of experiments . Female ODS rats aged 36 days had a low HDL (high-density lipoprotein) cholesterol level in serum as compared with age-matched control rats in spite of the absence of scorbutic symptoms. Female ODS rats aged 63 days which revealed severe scorbutic symptoms had a very low HDL cholesterol level (mean value; 17mg/dl). And male ODS rats, whose lives had been prolonged by supplementing with L-ascorbic acid, also had lower serum HDL-cholesterol and had increased total cholesterol in serum and liver when the acid supplement dose was relatively insufficient. On the other hand, we examined HDLz and HDL3-cholesterol levels in serum to determine the mechanism of low HDL-cholesterol. As a result, we observed a low HDLz-cholesterol level in ODS rats but normal HDL3 cholesterol level. But the authors observed no decrease of LCAT (lecithin: cholesterol acyltransferase) activity in serum of ODS rats . These results could be due to disturbance of lipid metabolism in a vitamin C-deficient condition, that is to say, there might be abnormalities of the cholesterol excretion pathway of bile acid from liver, and maturity of the HDL cholesterol particle due to other factors except that of LCAT activity .

show abstract

“…It was originally believed that vitamin C's cholesterol lowering effects was due to its role as a cofactor for the enzyme 7-alphahydroxylase, the rate limiting enzyme in the transformation of cholesterol to bile acids. 66 However this hypothesis has been disconfirmed in subsequent research which showed that plasma vitamin C concentrations had no effect on the rates of bile acid production in the liver. 53,67 Therefore vitamin C might play out its role in the mechanisms responsible for the removal of cholesterol from the blood.…”

Section: Discussionmentioning

confidence: 99%