Plasma Choline Concentration Was Not Increased After a 6-Month Egg Intervention in 6-9-Month-Old Malawian Children: Results from a Randomized Controlled Trial

Megan G Bragg, Elizabeth L Prado, Charles D Arnold, Sarah J Zyba, Kenneth M Maleta, Bess L Caswell, Brian J Bennett, Lora L Iannotti, Chessa K Lutter, Christine P Stewart, Megan G Bragg, Elizabeth L Prado, Charles D Arnold, Sarah J Zyba, Kenneth M Maleta, Bess L Caswell, Brian J Bennett, Lora L Iannotti, Chessa K Lutter, Christine P Stewart

Abstract

Background: Eggs are a rich source of choline, an essential nutrient important for child growth and development. In a randomized trial of 1 egg/d in young children in Ecuador, an egg intervention led to significant improvements in growth, which were partially mediated by increased plasma choline concentration. A similar trial in Malawi (clinicaltrials.gov: NCT03385252) found little improvement in child growth or development.

Objectives: We aimed to evaluate the effect of 1 egg/d for 6 mo on plasma choline concentrations in Malawian children enrolled in a randomized trial.

Methods: Infants aged 6-9 mo in rural Malawi were randomly assigned to receive 1 egg/d (n = 331) or serve as a nonintervention control (n = 329) for 6 mo. Anthropometric, developmental, and dietary data were collected at baseline and 6-mo follow-up, along with a blood draw. Plasma choline, betaine, dimethylglycine, trimethylamine N-oxide (TMAO), and DHA were measured at both time points using ultrahigh performance liquid chromatography-tandem MS (n = 200 per group). Linear regression analysis was used to determine the difference in plasma choline and related metabolites between groups after 6 mo of intervention.

Results: Plasma choline, betaine, dimethylglycine, and DHA concentrations did not differ between groups at 6-mo follow-up. Plasma TMAO was significantly (26%; 95% CI: 7%, 48%) higher in the egg intervention group in a fully adjusted model.

Conclusions: Provision of 1 egg/d for 6 mo did not result in increases in plasma choline or related metabolites, except TMAO. This could partially explain the lack of effect on growth and development. Additional interventions are needed to improve choline status, growth, and development in this population.

Keywords: LMIC; choline; complementary foods; development; growth; trimethylamine N-oxide.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Participant flow diagram for this secondary analysis of the Mazira Project.

References

    1. Zeisel SH. The fetal origins of memory: the role of dietary choline in optimal brain development. J Pediatr. 2006;149(5):S131–6.
    1. Headey DD, Alderman HH. The relative caloric prices of healthy and unhealthy foods differ systematically across income levels and continents. J Nutr. 2019;149(11):2020–33.
    1. Wiedeman AM, Barr SI, Green TJ, Xu Z, Innis SM, Kitts DD. Dietary choline intake: current state of knowledge across the life cycle. Nutrients. 2018;10(10):1513.
    1. Iannotti LL, Lutter CK, Bunn DA, Stewart CP. Eggs: the uncracked potential for improving maternal and young child nutrition among the world' s poor. Nutr Rev. 2014;72(6):355–68.
    1. Iannotti LL, Lutter CK, Stewart CP, Gallegos Riofrío CA, Malo C, Reinhart G, Palacios A, Karp C, Chapnick M, Cox Ket al. . Eggs in early complementary feeding and child growth: a randomized controlled trial. Pediatrics. 2017;140(1):e20163459.
    1. Iannotti LL, Lutter CK, Waters WF, Riofrío CAG, Malo C, Reinhart G, Palacios A, Karp C, Chapnick M, Cox Ket al. . Eggs early in complementary feeding increase choline pathway biomarkers and DHA: a randomized controlled trial in Ecuador. Am J Clin Nutr. 2017;106:1382–9.
    1. Stewart CP, Caswell B, Iannotti L, Lutter C, Arnold CD, Chipatala R, Prado EL, Maleta K. The effect of eggs on early child growth in rural Malawi: the Mazira Project randomized controlled trial. Am J Clin Nutr. 2019;110(4):1026–33.
    1. Prado EL, Maleta KM, Caswell BL, George M, Oakes LM, DeBolt MC, Bragg MG, Arnold CD, Iannotti L, Lutter CKet al. . Early child development outcomes of a randomized trial providing one egg per day to children age 6 to 15 months in Malawi. J Nutr. 2020;150(7):1933–42.
    1. Caswell B, Arnold C, Lutter C, Iannotti L, Chipatala R, Werner E, Maleta K, Stewart C. Impacts of an egg intervention on nutrient intake adequacy among young Malawian children. Matern Child Nutr. 2021;17(3):e13196.
    1. Mun JG, Legette LL, Ikonte CJ, Mitmesser SH. Choline and DHA in maternal and infant nutrition: synergistic implications in brain and eye health. Nutrients. 2019;11(5):1125.
    1. Lutter CK, Caswell BL, Arnold CD, Iannotti LL, Maleta K, Chipatala R, Prado EL, Stewart CP. Impacts of an egg complementary feeding trial on energy intake and dietary diversity in Malawi. Matern Child Nutr. 2021;17(1):e13055.
    1. WHO Multicentre Growth Reference Study Group . WHO child growth standards based on length/height, weight and age. Acta Paediatr Suppl. 2006;450:76–85.
    1. Gladstone M, Lancaster GA, Umar E, Nyirenda M, Kayira E, van den Broek NR, Smyth RL. The Malawi Developmental Assessment Tool (MDAT): the creation, validation, and reliability of a tool to assess development in rural African settings. PLoS Med. 2010;7(5):e1000273.
    1. Coates J, Swindale A, Bilinsky P. Household Food Insecurity Access Scale (HFIAS) for measurement of food access: indicator guide. Washington (DC): Food and Nutrition Technical Assistance III Project; 2007.
    1. Wang Z, Levison BS, Hazen JE, Donahue L, Li X-M, Hazen SL. Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry. Anal Biochem. 2014;455:35–40.
    1. Erhardt JG, Estes JE, Pfeiffer CM, Biesalski HK, Craft NE. Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J Nutr. 2004;134(11):3127–32.
    1. Institute of Medicine . Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington DC: National Academies Press; 1998.
    1. Fischer LM, da Costa KA, Galanko J, Sha W, Stephenson B, Vick J, Zeisel SH. Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma. Am J Clin Nutr. 2010;92(2):336–46.
    1. Wiedeman AM, Whitfield KC, March KM, Chen NN, Kroeun H, Sokhoing L, Sophonneary P, Dyer RA, Xu Z, Kitts DDet al. . Concentrations of water-soluble forms of choline in human milk from lactating women in Canada and Cambodia. Nutrients. 2018;10(3):381.
    1. Abratte CM, Wang W, Li R, Axume J, Moriarty DJ, Caudill MA. Choline status is not a reliable indicator of moderate changes in dietary choline consumption in premenopausal women. J Nutr Biochem. 2009;20(1):62–9.
    1. Li Z, Vance DE. Phosphatidylcholine and choline homeostasis. J Lipid Res. 2008;49(6):1187–94.
    1. Ganz AB, Cohen VV, Swersky CC, Stover J, Vitiello GA, Lovesky J, Chuang JC, Shields K, Fomin VG, Lopez YSet al. . Genetic variation in choline-metabolizing enzymes alters choline metabolism in young women consuming choline intakes meeting current recommendations. Int J Mol Sci. 2017;18(2):252.
    1. Silver MJ, Corbin KD, Hellenthal G, da Costa K-A, Dominguez-Salas P, Moore SE, Owen J, Prentice AM, Hennig BJ, Zeisel SH. Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort. FASEB J. 2015;29(8):3426–35.
    1. Bragg MG, Caswell B, Maleta K, Stewart C. Choline intake in Malawian children aged 6-9 and 12-15 months in an egg intervention trial. Curr Dev Nutr. 2020;4(Suppl 2):816.
    1. Yakes Jimenez E, Mangani C, Ashorn P, Harris WS, Maleta K, Dewey KG. Breast milk from women living near Lake Malawi is high in docosahexaenoic acid and arachidonic acid. Prostaglandins Leukot Essent Fatty Acids. 2015;95:71–8.
    1. Martínez-del Campo A, Bodea S, Hamer HA, Marks JA, Haiser HJ, Turnbaugh PJ, Balskus EP. Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria. mBio. 2015;6(2):e00042–15.
    1. Romano KA, Vivas EI, Amador-Noguez D, Rey FE. Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. mBio. 2015;6(2):e02481.
    1. Yang S, Li X, Yang F, Zhao R, Pan X, Liang J, Tian L, Li X, Liu L, Xing Yet al. . Gut microbiota-dependent marker TMAO in promoting cardiovascular disease: inflammation mechanism, clinical prognostic, and potential as a therapeutic target. Front Pharmacol. 2019;10:1360.
    1. Haghikia A, Li XS, Liman TG, Bledau N, Schmidt D, Zimmermann F, Kränkel N, Widera C, Sonnenschein K, Haghikia Aet al. . Gut microbiota-dependent TMAO predicts risk of cardiovascular events in patients with stroke and is related to proinflammatory monocytes. Arterioscler Thromb Vasc Biol. 2018;38(9):2225–35.
    1. Andraos S, Jones B, Lange K, Clifford SA, Thorstensen EB, Kerr JA, Wake M, Safferty R, Burgner DP, O'Sullivan JM. Trimethylamine N-oxide (TMAO) is not associated with cardiometabolic phenotypes and inflammatory markers in children and adults. Curr Dev Nutr. 2021;5(1):nzaa179.
    1. Wilcox J, Skye SM, Graham B, Zabell A, Li XS, Li L, Shelkay S, Fu X, Neale S, O'Laughlin Cet al. . Dietary choline supplements, but not eggs, raise fasting TMAO levels in participants with normal renal function: a randomized clinical trial. Am J Med. 2021;134(9):1160–9.e3.
    1. DiMarco DM, Missimer A, Murillo AG, Lemos BS, Malysheva OV, Caudill MA, Blesso CN, Fernandez ML. Intake of up to 3 eggs/day increases HDL cholesterol and plasma choline while plasma trimethylamine-N-oxide is unchanged in a healthy population. Lipids. 2017;52(3):255–63.
    1. Zhu C, Sawrey-Kubicek L, Bardagjy AS, Houts H, Tang X, Sacchi R, Randolph JM, Steinberg FM, Zivkovic AM. Whole egg consumption increases plasma choline and betaine without affecting TMAO levels or gut microbiome in overweight postmenopausal women. Nutr Res. 2020;78:36–41.
    1. West AA, Shih Y, Wang W, Oda K, Jaceldo-Siegl K, Sabaté J, Haddad E, Rajaram S, Caudill MA, Burns-Whitmore B. Egg n-3 fatty acid composition modulates biomarkers of choline metabolism in free-living lacto-ovo-vegetarian women of reproductive age. J Acad Nutr Diet. 2014;114(10):1594–600.
    1. Miller CA, Corbin KD, Da Costa KA, Zhang S, Zhao X, Galanko JA, Blevins T, Bennett BJ, O'Connor A, Zeisel SH. Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study. Am J Clin Nutr. 2014;100(3):778–86.
    1. National Statistical Office (NSO) [Malawi], ICF . Malawi demographic and health survey 2015–16. Zomba, Malawi and Rockville (MD): NSO and ICF;2017.
    1. Münger LH, Garcia-Aloy M, Vázquez-Fresno R, Gille D, Rosana ARR, Passerini A, Soria-Florido MT, Pimentel G, Sajed T, Wishart DSet al. . Biomarker of food intake for assessing the consumption of dairy and egg products. Genes Nutr. 2018;13:26.
    1. Thompson FE, Kirkpatrick SI, Subar AF, Reedy J, Schap TE, Wilson MM, Krebs-Smith SM. The National Cancer Institute's dietary assessment primer: a resource for diet research. J Acad Nutr Diet. 2015;115(12):1986–95.
    1. Noerman S, Kärkkäinen O, Mattsson A, Paananen J, Lehtonen M, Nurmi T, Tuomainen TP, Voutilainen S, Hanhineva K, Virtanen JK. Metabolic profiling of high egg consumption and the associated lower risk of type 2 diabetes in middle-aged Finnish men. Mol Nutr Food Res. 2019;63(5):e1800605.
    1. Stewart CP, Iannotti LL, Lutter CK, Maleta KM. The Mazira Project: an evaluation of eggs during complementary feeding in rural Malawi [Internet]. clinicaltrialsgov identifier. NCT03385252. Available from: .
    1. Zeisel SH. Choline nutritional status: development of a biomarker panel [Internet]. clinicaltrialsgov identifier. NCT03726671. Available from: .

Source: PubMed

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