Gender differences in medium-chain dicarboxylic aciduria in alcoholic men and women.
OBJECTIVE
Women appear to be more vulnerable to developing alcoholic liver disease than men. In rats, we previously found that the response of certain pathways of fatty acid metabolism to alcohol feeding was less efficient in females than in males, resulting in striking accumulation of fatty acids in the liver of the female rats. We sought to determine whether similar differences occurred in humans.


METHODS
Urinary excretion of medium chain (C6-C10) dicarboxylic acids (final products of fatty acid omega-oxidation) was determined in 40 recently drinking alcoholic subjects (24 men and 16 women) and 21 nonalcoholic subjects (12 men and nine women). Sebacic (C10), suberic (C8), and adipic (C6) acids were measured in urine by gas chromatography/mass spectrometry, and their excretion was expressed per mg of creatinine.


RESULTS
In nonalcoholic subjects, there was no gender difference in dicarboxylic aciduria. By contrast, alcoholic men (but not alcoholic women) developed dicarboxylic hyperaciduria. Alcoholic men had a marked increase in adipic acid excretion and in the adipic/sebacic (C6/C10) ratio (an index of peroxisomal beta-oxidation), whereas the values in alcoholic women did not differ from those in nonalcoholic women.


CONCLUSIONS
The lack of response in alcoholic women could contribute to an aggravation of liver injury by promoting deleterious accumulation of fatty acids.
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000652:urine*; D000437:Alcoholism / Q000201:enzymology / Q000652:urine*; D003998:Dicarboxylic Acids / Q000737:chemistry / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000652:urine; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D013997:Time Factors