The association between dietary intakes of choline and its metabolite betaine (as determined by a food-frequency questionnaires) and the risk of neural-tube defects (NTDs) was assessed in a case-control study in California that included 424 cases and 440 control infants without birth defects. After adjustment for intake of dietary and supplemental folic acid, dietary methionine, and other potential confounding variables, the odds ratios for NTD in the 3 increasing quartiles of choline intake relative to the lowest quartile were 0.63 (95% CI, 0.42-0.99), 0.65 (0.39-1.07), and 0.51 (0.25-1.07), respectively. The risk of NTDs also decreased with increasing intake of betaine. NTD risk was lowest for women whose diets were rich in choline, betaine, and methionine. For women whose intake was above the 75th percentile compared with below the 25th percentile for all 3 nutrients, the odds ratio was 0.17 (95% CI, 0.04-0.76).
Comment: These results suggest that choline and betaine play a role in the development of the neural tube, and that inadequate intake of these nutrients may increase the risk of NTDs. The recommended Adequate Intake for choline is 425 mg/day for adult females and 550 mg/day for lactating females (because human milk contains large amounts of choline). Pregnant women are being advised to consume 425 mg/day, but that amount may be suboptimal, considering the increased nutritional needs associated with pregnancy. In contrast, more than half of the women in the present study consumed less than 372 mg of choline per day, suggesting that marginal choline status is prevalent among pregnant American women.
Foods rich in choline include eggs, wheat germ, whole grains, liver, and fish. Foods high in betaine include whole grains, spinach, and beets. Of note, white bread contains substantially less choline and betaine than do whole grains. At some future time, the processed-food industry will probably consider fortifying white flour with choline and betaine, as they did a few years ago with folic acid, and with pyridoxine before that, and with thiamine, riboflavin, niacin, and iron before that. Then, all we'd need to do would be to add back the magnesium, potassium, calcium, manganese, zinc, copper, selenium, molybdenum, chromium, pantothenic acid, vitamin E, essential fatty acids, fiber, and all of the as-yet undiscovered nutrients, and we will have created a perfect food.
Shaw GM, et al. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol 2004;160:102-109.
