Journal of Dietary Supplements ISSN: 1939-0211 (Print) 1939-022X (Online) Journal homepage: https://www.tandfonline.com/loi/ijds20 Choline: The Neurocognitive Essential Nutrient of Interest to Obstetricians and Gynecologists Taylor C. Wallace, Jan Krzysztof Blusztajn, Marie A. Caudill, Kevin C. Klatt & Steven H. Zeisel To cite this article: Taylor C. Wallace, Jan Krzysztof Blusztajn, Marie A. Caudill, Kevin C. Klatt & Steven H. Zeisel (2019): Choline: The Neurocognitive Essential Nutrient of Interest to Obstetricians and Gynecologists, Journal of Dietary Supplements, DOI: 10.1080/19390211.2019.1639875 To link to this article: https://doi.org/10.1080/19390211.2019.1639875 Published online: 06 Aug 2019. Submit your article to this journal View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ijds20 JOURNAL OF DIETARY SUPPLEMENTS https://doi.org/10.1080/19390211.2019.1639875 Choline: The Neurocognitive Essential Nutrient of Interest to Obstetricians and Gynecologists Taylor C. Wallace, PhD, CFS, FACNa,b, Jan Krzysztof Blusztajn, PhDc, Marie A., PhD, RD Caudilld, Kevin C. Klatt, PhDe, and Steven H., MD, PhD Zeiself aDepartment of Nutrition and Food Studies, George Mason University, Fairfax, VA, USA; bThink Healthy Group, Inc, Washington, DC, USA; cDepartment of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA; dDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA; eUSDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA; fResearch Institute, University of North Carolina, Kannapolis, NC, USA ABSTRACT KEYWORDS Choline is an essential nutrient for proper liver, muscle, and brain brain; choline; cognition; functions as well as for lipid metabolism and cellular membrane dietary guidelines; placenta; composition and repair. Humans can produce small amounts of cho- shortfall nutrient line via the hepatic phosphatidylethanolamine N-methyltransferase pathway; however, most individuals must consume this vitamin through the diet to prevent deficiency. An individual’s dietary requirement for choline is dependent on common genetic variants in genes required for choline, folate, and one-carbon metabolism. Both the American Academy of Pediatrics and American Medical Association have recently reinforced the importance of maternal cho- line intake during pregnancy and lactation and recognize that failure to provide choline and other key essential nutrients during the first 1,000 days postconception may result in lifelong deficits in brain function despite subsequent nutrient repletion. Given that dietary intake for the majority of the US population, including subpopula- tions such as pregnant women, women of childbearing age, and vegetarians, falls well below the current adequate intake, there is a need to develop better policies and improve consumer education around the importance of this essential nutrient for human health. This comprehensive expert review summarizes the current scientific evidence on choline and health in relation to interests of obstetri- cians and gynecologists. KEY MESSAGES There is compelling evidence that demonstrates obtaining the cur- rent adequate intake (AI) for choline is problematic for the majority of the US population; excessive intakes above the tolerable upper intake level (UL) are absent. The dietary requirement for choline is dependent on common gen- etic variants in genes required for choline, folate, and one-carbon metabolism. Continuing education is needed for health professionals on the importance of choline-rich foods in the diet. Choline must be integrated into the prenatal supplement regimen. Research suggests not achieving the AI is likely detrimental to cogni- tive function in the developing fetus and infant. Adverse neuro- logical consequences due to suboptimal maternal intakes are likely to be identified in future clinical research. CONTACT Taylor C. Wallace [email protected] Department of Nutrition and Food Studies, George Mason University, MS: 1F7, 4400 University Drive, Fairfax, VA 22030. ß 2019 Taylor & Francis Group, LLC 2 T. C. WALLACE ET AL. Introduction Choline (2-hydroxyethyl-trimethyl-ammonium) is a trimethylated, positively charged, quaternary, saturated amine that is an essential micronutrient with critical structural and regulatory roles in the body (Institute of Medicine 1998). It is a source of methyl groups needed to make the primary methyl donor S-adenosylmethionine (SAM), a part of the neurotransmitter acetylcholine, and a major component of the phospholipids that compromise cell membranes (sphingomyelin and phosphatidylcholine), thus contribu- ting to their fluidity and structural integrity (Institute of Medicine 1998). The choline derivative, phosphatidylcholine, is a main constituent of very low-density lipoproteins (VLDLs) and is required for hepatic VLDL secretion and thus the removal of fat from the liver (Institute of Medicine 1998; Yao and Vance 1988). Choline is a precursor for betaine, an important osmolyte in the kidney glomerulus that facilitates water resorption from the kidney tubule (Kempson and Montrose 2004). Humans can endogenously pro- duce small amounts of choline via the hepatic phosphatidylethanolamine N-methyl- transferase (PEMT) pathway; however, most people must consume this nutrient exogenously to prevent deficiency (Institute of Medicine 1998). In premenopausal women, the gene for the enzyme catalyzing biosynthesis of endogenous choline is induced by estrogen (Resseguie et al. 2007), and some premenopausal nonpregnant women may have lower than average requirements for dietary choline (Fischer et al. 2007). Genetic polymorphisms can increase the choline requirement (Ganz, Cohen et al. 2017; Ganz, Klatt et al. 2017); almost half of premenopausal women have a gene poly- morphism that makes biosynthesis of choline unresponsive to estrogen (Fischer et al. 2007). Thus, these women have a similar choline requirement as men (Zeisel and Caudill 2010). Choline and esters of choline are ubiquitous in food; however, animal products typic- ally contain higher amounts of choline compared to plant foods. The most common forms of choline in foods are fat-soluble phosphatidylcholine and sphingomyelin, as well as water-soluble phosphocholine, glycerophosphocholine, and free choline (USDA 2008). The bioavailability of free choline appears to be high: studies of cytidine-50- diphosphocholine (CDP-choline) show virtually complete absorption of free choline after hydrolysis in the small intestine (Secades and Lorenzo 2006). Pancreatic and mucosal enzymes liberate free choline from about half of the fat-soluble forms and from some water-soluble forms (Hollenbeck 2012). Bioavailability of phosphatidylcho- line varies depending on the food source, from about 100% in soybeans to 24% in can- ola meal (Emmert and Baker 1997). Foods naturally containing choline include chicken liver (3 oz: 247 mg); salmon (3 oz: 187 mg); eggs (1 large egg with yolk: 147 mg); shiitake mushrooms (1/2 cup: 58 mg); chicken, broilers or fryers (3 oz: 56 mg); beef, grass-fed strip steak (3 oz: 55 mg); wheat germ (1 oz toasted: 51 mg); milk (8 oz: 38 mg); brussels sprouts (1/2 cup: 32 mg); and almonds (1 oz: 15 mg). Select plant foods such as cruciferous vegetables and certain beans are good sources of choline, contributing approximately 10% of the daily recom- mended intake (Zeisel and da Costa 2009). Foods, particularly plant foods, also contain betaine, which cannot be converted to choline but can be used as a methyl donor, thereby sparing some of the choline requirement. In animal models, a minimum 50% of the dietary requirement of choline is still needed, but the remaining 50% can be spared JOURNAL OF DIETARY SUPPLEMENTS 3 Table 1. Mean intakes of choline from foods and beverages in the United States, 2011–2014. Age (y) Mean intake (mg/d)a AI (mg/d)b Above AI (%)a UL (mg/d)b Above UL (%) Males 1–3 221 ± 7.6 200 61 ± 4.9 1000 0.0 ± 0.0 4–8 242 ± 4.2 250 42 ± 2.5 1000 0.0 ± 0.0 9–13 290 ± 5.2 375 14 ± 1.8 2000 0.0 ± 0.0 14–18 346 ± 11.1 550 5 ± 2.1 3000 0.0 ± 0.0 19–30 412 ± 7.5 550 17 ± 2.2 3500 0.0 ± 0.0 31–50 421 ± 9.1 550 14 ± 2.5 3500 0.0 ± 0.0 51–70 391 ± 7.8 550 10 ± 1.6 3500 0.0 ± 0.0 71 351 ± 8.2 550 4 ± 1.1 3500 0.0 ± 0.0 Females 1–3 205 ± 4.8 200 40 ± 4.1 1000 0.0 ± 0.0 4–8 211 ± 4.7 250 20 ± 3.3 1000 0.0 ± 0.0 9–13 231 ± 7.2 375 <3 2000 0.0 ± 0.0 14–18 223 ± 7.9 400 <3 3000 0.0 ± 0.0 19–30 271 ± 6.6 425 <3 3500 0.0 ± 0.0 31–50 280 ± 5.5 425 5 ± 1.5 3500 0.0 ± 0.0 51–70 275 ± 5.4 425 4 ± 1.0 3500 0.0 ± 0.0 71 253 ± 6.0 425 <3 3500 0.0 ± 0.0 AI, adequate intake; NHANES, National Health and Nutrition Examination Survey; UL, tolerable upper intake level. aData source: What We Eat in America, NHANES 2011–2014, individuals aged 1 year, excluding breast-fed children and pregnant or lactating females. Provided courtesy of Moshfegh (2018). bCurrent gender and life-stage AI as defined by the Institute of Medicine (1998). by intake of betaine (Craig 2004; Dilger et al. 2007). Choline is available commercially as an ingredient in many fortified foods and dietary supplements as choline bitartrate or choline chloride. The US Food and Drug Administration (2017) has mandated forti- fication of non-milk-based infant formula to the level present in human breast milk since 1985. The National Academy of Medicine (NAM; formerly the Institute of Medicine [IOM]) Food and Nutrition Board (FNB) has recognized choline as an essential nutrient since 1998 and established dietary reference intakes (DRIs) for individuals in the United States and Canada (Institute of Medicine 1998)(Table 1). The adequate intake (AI) is 425 and 550 mg/day for women and men, respectively, based on prevention of liver damage.