Possible Interaction: Ethanol and Folate

“ Alcohol may act through altered status of folate and vitamin B12, two vitamins required for DNA methylation and nucleotide synthesis, and thus cell integrity.”

“Using avian and mouse vertebrate models, we demonstrated that FA supplementation prevents CHD induced by alcohol , lithium, or elevation of the metabolite homocysteine, a marker for FA deficiency.”

“ Chronic alcohol use negatively impacts folate homeostasis, but its effect on mitochondrial folate uptake is not clear.”

“It is known that ethanol inhibits folate , choline, and vitamin A/retinoic acid metabolism at multiple steps.”

“Thus supplementation of folate , choline and vitamin A to mothers may mitigate the effects of the alcohol and reduce the severity or prevalence of FAS.”

“New animal studies demonstrate that folate prevents cardiovascular defects induced by the drug lithium, homocysteine, or alcohol , but protection occurs at a higher concentration than currently used in vitamin supplements.”

“ Chronic alcohol feeding of rats (4 wk; 36% of calories … ethanol) led to a significant decrease in folate uptake by freshly isolated primary pancreatic acinar cells compared with cells from pair-fed controls; this … was associated with a parallel decrease in the level of expression of RFC and PCFT.”

“A 1-h treatment of HPT cells with ethanol (> or = 65 mmol/L) reduced the apically directed transport of folate by 20-25% without affecting the basolateral transport.”

“ Ethanol directly reduces the reabsorption of folate in the renal proximal tubule (PT) by acting on either of 2 folate transport proteins, the reduced folate carrier (RFC) and the folate receptor (FR).”

“The increase in folate transporters partly counteracts the inhibitory effects of ethanol on folate transport activity, which explains the lower magnitude of ethanol's effect on transport with subchronic exposure compared with that with acute exposure.”

“These studies demonstrate that ethanol decreases the reabsorptive transport of folate by renal PT cells, which would increase urinary folate excretion.”

“Therefore, the supply of metabolically related nutrients such as folate may play a role in the hepatotoxic effects of ethanol.”

“Although a mechanistic link between alcohol and impaired folate metabolism in the genesis of cancer is still not definitively established, such a link should be pursued in future studies because of the intimate metabolic relation between alcohol and folate metabolism.”

“In addition, some evidence indicates that alcohol may redirect the utilization of folate toward serine synthesis and thereby may interfere with a critical function of methylenetetrahydrofolate, thymidine synthesis.”

“With regard to one-carbon metabolism, alcohol can negatively affect folate levels, and the folate perturbation affects DNA methylation and DNA synthesis, which is important in carcinogenesis.”