Periconceptional Dietary Intake of Choline and Betaine and Neural Tube Defects in Offspring

Abstract

Periconceptional intake of folic acid prevents some neural tube defects (NTDs). Other nutrients may also contribute to NTD etiologies; a likely candidate is choline. Similar to folic acid, choline is involved in one-carbon metabolism for methylation of homocysteine to methionine. The authors investigated whether maternal periconceptional dietary intakes of choline and its metabolite betaine influence NTD risk. Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. In-person interviews were conducted with mothers of 424 NTD cases and with mothers of 440 nonmalformed controls. A standard 100-item food frequency questionnaire was used to assess nutrient intake. Dietary intakes of choline were associated with reduced NTD risks. Controlling for intake of supplemental folic acid, dietary folate, dietary methionine, and other covariates did not substantially influence risk estimates for choline. NTD risk estimates were lowest for women whose diets were rich in choline, betaine, and methionine. That is, for women whose intake was above the 75th percentile compared with below the 25th percentile for all three nutrients, the odds ratio was 0.17 (95% confidence interval: 0.04, 0.76). Study findings for dietary components other than folic acid offer additional clues about the complex etiologies of NTDs.

Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women

“…Furthermore, the validity for the major food sources of B vitamins was also good, so we have no reason to assume that it would be different for B vitamins (Ocke et al, 1997a). Furthermore, our estimates of daily betaine, choline and folate intakes were well in line with other studies in western population (Melse-Boonstra et al, 2002;Shaw et al, 2004;Brink et al, 2005;Fischer et al, 2005;Larsson et al, 2005;Slow et al, 2005;Cho et al, 2006). Therefore we feel confident that the estimated intakes of betaine, choline and folate in our study are reliable.…”

“…Intake of betaine from foods is estimated to be 200-400 mg/day (Shaw et al, 2004;Fischer et al, 2005). Main food sources of betaine are wheat bran, wheat germ, spinach, pretzels, shrimps and wheat bread (Zeisel et al, 2003).…”

“…Choline is present in the human diet primarily as lecithin, which is the trivial name for phosphatidylcholine. Intake of choline moieties from foods is estimated at 400-600 mg/day (Shaw et al, 2004;Fischer et al, 2005). Main food sources of choline are beef liver, chicken liver, eggs, wheat germ, bacon, dried soybeans and pork (Zeisel et al, 2003).…”

Phosphatidylethanolamine N‐methyltransferase (PEMT) gene polymorphisms and risk of spina bifida

“…The observation of a reduction in risk associated with a compound genotype, which was not influenced by maternal choline intake, is difficult to interpret. As we recently demonstrated, the mothers' dietary intake of choline was associated with reduced offspring risks for all NTDs, as well as for spina bifida and anencephaly, separately [Shaw et al, 2004]. It has been consistently reported that pregnant women with elevated Hcy levels have an increased risk of having an NTD affected child [Mills et al, 1995].…”

“…Included for the study were 360 infants with spina bifida (cases) and 595 non-malformed infants (controls). A subset of samples was derived from a dataset that included detailed maternal interview information on important covariates such as maternal periconceptional vitamin use and choline intake [Shaw et al, 2004]. All samples were obtained with approval from the State of California Health and Welfare Agency Committee for the Protection of Human Subjects.…”