Mice were fed diets containing 0, 10, or 35 mmol of choline per kg of diet for 3 weeks. At the end of the diet period, a methionine load was administered. Two hours after the methionine load, choline-deficient mice had plasma homocysteine concentrations twice those of choline-fed mice. In a second study, eight men were fed a choline-adequate diet (550 mg per 70 kg of body weight per day) for 10 days, and then a choline-deficient diet (approximately 50 mg/day) until they developed fatty liver, or for a maximum of 42 days. Among the four men judged to be choline-depleted on the basis of having developed fatty liver, the mean plasma homocysteine concentration 4 hours after a methionine load (100 mg/kg of body weight) was 35% higher than among the men judged not to be choline-depleted (p < 0.05). These results suggest that choline deficiency accentuated the rise in plasma homocysteine concentrations following a methionine load, in both humans and mice.

Comment: Hyperhomocysteinemia is a risk factor for cardiovascular disease, stroke, habitual abortion, thrombophlebitis, and osteoporosis. Elevated homocysteine concentrations can be caused by decreased methylation of homocysteine to methionine, as occurs in folic acid deficiency. A parallel pathway exists for methylation of homocysteine, in which betaine, a metabolite of choline, is the methyl donor. Choline and betaine appear to be more effective than folic acid for suppressing increases in homocysteine levels induced by a meal or a methionine load, whereas betaine (and presumably choline) is somewhat less effective than folic acid in decreasing fasting plasma homocysteine levels. Choline/betaine and folic acid modulate homocysteine metabolism by different mechanisms, each of which appears to play an important role in regulating homocysteine levels. Good food sources of choline include eggs, beef, wheat germ, and soybeans. Foods high in betaine include wheat germ, wheat bran, whole wheat, spinach, and beets.

da Costa KA, et al. Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load. Am J Clin Nutr 2005;81:440-444.