Choline, B-vitamins and Neural Tube Defects
While the nutrient choline is not considered a vitamin in the strictest sense, as it can be synthesized by the body in limited amounts, it has nonetheless garnered research interest as it participates in the same group of biochemical reactions as B-vitamins such as folate and vitamin B12. In particular, as Zeisel explains, it may be especially important for expecting mothers and their infants. Choline is required for normal fetal development and the proper functioning of the liver and placenta. Additionally, there appears to be a strong biological need for choline in the developing fetus and infant, as large quantities are transferred via the placenta during pregnancy, and breast milk has a high choline concentration. Some researchers, such as Shaw and colleagues, have found low intakes of choline around the peri-conceptual period are linked with neural tube defects. The recent publication from Mills and co-workers looks at the relationship between choline status, genetic polymorphisms and neural tube defects (NTD).
The researchers looked at data from two separate groups of Irish women in case-control studies: in one group were 71 women carrying a child affected by an NTD and 214 pregnant women serving as controls, and in the other were 98 women who had previously carried a pregnancy affected by NTD and 386 control women. Concentrations of choline and related metabolites betaine and homocysteine were compared between the cases and controls. In addition, the effects that common genetic variants that affect choline and B-vitamin levels have on risk of NTD were examined.
The researchers did not find any statistically significant difference in choline levels between women who had had an NTD diagnosis, and those with no history of NTD and carrying an unaffected fetus. There also did not appear to be an effect whereby women with low folate levels and low choline levels were at greater risk of an NTD-affected pregnancy. Levels of homocysteine, which increase in response to B-vitamin deficiency, were however increased in women affected by NTD pregnancy.
When looking at genetic polymorphisms, one variant of the phosphatidylethanolamine N-methyltransferase (PEMT) gene was found at higher levels in women with a (history of) pregnancy affected by NTD. The enzyme that is produced by this gene is responsible for synthesis of choline in the body, and it is possible that small variations may affect choline status.
Although this study did not show an effect of choline levels on risk of NTDs, as yet there is no functional marker of choline deficiency. The population studied was well-nourished. Lower levels do not indicate that body systems that rely on choline are malfunctioning as long as intakes meet a certain minimum level to sustain health. The study confirms that elevated homocysteine levels, and certain genes that control these levels, are related to risk of NTD, as discussed previously by van der Put and colleagues.
Given that pregnant and lactating women have a higher requirement for choline, it seems prudent for this risk group to ensure an adequate supply. Aside from NTDs, choline may be important in other areas of infant health, as summarized by Jiang, West and Caudill. The USDA choline database provides a very comprehensive list of the choline content in many foods. Women planning a family, pregnant and lactating women should make sure that their choline intakes meet minimum recommendations.
James L Mills, Ruzong Fan, Lawrence C Brody, Aiyi Liu, Per M Ueland, Yifan Wang, Peadar N Kirke, Barry Shane, and Anne M Molloy. Maternal choline concentrations during pregnancy and choline-related genetic variants as risk factors for neural tube defects. Am J Clin Nutr 2014 ajcn.079319; First published online August 13, 2014. doi:10.3945/ajcn.113.079319
Jiang X, West AA, Caudill MA. Maternal choline supplementation: a nutritional approach for improving offspring health? Trends Endocrinol Metab. 2014 May;25(5):263-73. doi: 10.1016/j.tem.2014.02.001. Epub 2014 Mar 26. http://www.ncbi.nlm.nih.gov/pubmed/24680198
Pangilinan F, Molloy AM, Mills JL, Troendle JF, Parle-McDermott A, Signore C, O'Leary VB, Chines P, Seay JM, Geiler-Samerotte K, Mitchell A, VanderMeer JE, Krebs KM, Sanchez A, Cornman-Homonoff J, Stone N, Conley M, Kirke PN, Shane B, Scott JM, Brody LC. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects. BMC Med Genet. 2012 Aug 2;13:62. http://www.ncbi.nlm.nih.gov/pubmed/22856873
Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol. 2004 Jul 15;160(2):102-9. http://www.ncbi.nlm.nih.gov/pubmed/15234930/
van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ. Folate, homocysteine and neural tube defects: an overview. Exp Biol Med (Maywood). 2001 Apr;226(4):243-70. http://www.ncbi.nlm.nih.gov/pubmed/11368417
Zeisel SH. Nutrition in pregnancy: the argument for including a source of choline. Int J Womens Health. 2013 Apr 22;5:193-9. doi: 10.2147/IJWH.S36610.