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

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.