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.
Department of Dietetics, Manchester Royal Infirmary, Manchester, UK.
Helen V
HV
Worthington
Linda P
LP
Hunt
Rory F
RF
McCloy
Jop B
JB
Ubbink
Joan M
JM
Braganza
D000328:Adult; D000367:Age Factors; D000368:Aged; D000975:Antioxidants; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D016208:Databases, Factual; D004032:Diet; D005260:Female; D042882:Gallstones / Q000453:epidemiology / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D012737:Sex Factors; D006113:United Kingdom; D014815:Vitamins / Q000378:metabolism
D000975:Antioxidants; D014815:Vitamins; D002784:Cholesterol; D005978:Glutathione