Effect of chronic alcohol consumption on total plasma homocysteine level in rats

Alcohol Clin Exp Res. 2000 Mar;24(3):259-64.

Abstract

Background: Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B12, or vitamin B6. Population-based studies indicate that folate is the strongest vitamin determinant of hyperhomocysteinemia and, in most settings, folate supplementation effectively lowers elevated homocysteine levels. However, it is not clear whether folate deficiency is the cause of alcohol-related hyperhomocysteinemia.

Methods: In the present study, 10 male Sprague Dawley rats were fed ethanol-containing Lieber-DeCarli diets with 13 mg of folic acid per kilogram of diet. This represents a folate intake more than 20 times the basal requirement. Ethanol represented 36% of total energy, which yielded a concentration of 6.2% (vol/vol). The same number of rats were pair-fed with isocaloric control diets that contained an identical level of folate in which ethanol was entirely replaced by maltodextrin.

Results: At the end of 4 weeks, alcohol-fed rats did not show any significant reduction in plasma or hepatic folate concentrations, plasma pyridoxal-5'-phosphate concentration, or plasma vitamin B12 concentration. On the other hand, alcohol-fed rats were significantly hyperhomocysteinemic (17.24 +/- 4.63 micromol/liter,p < 0.01) compared to the nonalcohol group (10.73 +/- 2.76 micromol/liter). Alcohol-fed rats also had a significantly lower hepatic S-adenosylmethionine and higher hepatic S-adenosylhomocysteine levels.

Conclusions: Chronic alcohol consumption produces hyperhomocysteinemia by a mechanism that is related to interference with one-carbon metabolism, and not through vitamin depletion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / blood*
  • Animals
  • Folic Acid / blood
  • Folic Acid / pharmacology
  • Hematinics / blood
  • Hematinics / pharmacology
  • Homocysteine / blood*
  • Hyperhomocysteinemia / blood*
  • Hyperhomocysteinemia / chemically induced
  • Male
  • Pyridoxine / blood
  • Rats
  • Rats, Sprague-Dawley
  • Vitamin B 12 / blood

Substances

  • Hematinics
  • Homocysteine
  • Folic Acid
  • Pyridoxine
  • Vitamin B 12