Dietary antioxidant lack, impaired hepatic glutathione reserve, and cholesterol gallstones

Clin Chim Acta. 2004 Nov;349(1-2):157-65. doi: 10.1016/j.cccn.2004.06.022.

Abstract

Background: Theoretical considerations and experimental studies suggest a causal connection between micronutrient antioxidant insufficiency and the development of human gallstones.

Methods: Fasting plasma/serum samples from 24 patients with cholesterol gallstones-on unchanged lifestyles-were analysed for the four main micronutrient antioxidants, glutathione and factors that impact or report upon glutathione homeostasis. The results were assessed by comparison with laboratory referent ranges.

Results: The vitamin E:cholesterol ratio was lower in patients than controls (P=0.021) as also concentrations of beta-carotene (P=0.001) and vitamin C (P=0.001) but not selenium (P=0.280). A fall in plasma glutathione (P=0.001) was also accompanied by lower values of pyridoxyl-5-phosphate (the coenzyme that participates in vitamin B6-dependent enzyme reactions) which is involved in glutathione biosynthesis (P<0.001), and of folate (P=0.012) but not vitamin B12 (P=0.377) that participate in its regeneration via the methionine-homocysteine pathway. Despite these defects, values for plasma homocysteine were not significantly different from controls (P=0.092)-an anomaly rationalised by poor levels of precursor methionine (P=0.003) and cysteine (P=0.046).

Conclusions: Micronutrient antioxidant-including sulphur amino acid-lack, with disturbed glutathione homeostasis, are features of cholesterol gallstone disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antioxidants*
  • Cell Membrane / metabolism
  • Cholesterol / metabolism*
  • Databases, Factual
  • Diet*
  • Female
  • Gallstones / epidemiology
  • Gallstones / metabolism*
  • Glutathione / metabolism*
  • Hepatocytes / metabolism
  • Humans
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Reference Standards
  • Sex Factors
  • United Kingdom
  • Vitamins / metabolism

Substances

  • Antioxidants
  • Vitamins
  • Cholesterol
  • Glutathione