Matthew Messer

Matthew Messer


Choline was declared an essential micronutrient as late as 1998, so its health impact is still being researched to this very day. (1) Even in this relatively short timespan, it has become clear that a deficiency can lead to numerous problems, which concern millions of people. This is less than surprising, considering that more than 90% of people do not consume enough choline. (2,3) In part, this is because the best sources of choline are foods that contain a lot of dietary cholesterol so people have begun to reduce their consumption. Luckily, restrictions on eating eggs have been lifted by now, which is good news, as eggs are the best source of choline.  

What health issues can a choline deficiency cause? 

Liver problems and muscle weakness 

Choline is a vital nutrient for the health of the liver: the main cause of non-alcohol-related fatty liver disease and liver damage may be choline deficiency. (4) In a study aiming at determining the sufficient intake of choline, participants were given a choline-deficient diet for forty-two days. Nearly eighty percent developed a fatty liver by the end of the study and sustained muscle damage. (5) The negative effects could be reversed with an increase in choline intake.  

Pregnancy complications 

Besides vitamin B9, choline plays an important role in preventing irregularities in the closure of the neural tube. In a survey among women with the highest choline intake, neural tube closure issues were much rarer at birth. (6) During pregnancy, choline intake is especially important: in a randomized controlled trial, a daily choline intake of 930 mg – nearly double the recommended dose – positively influenced the children’s ability to withstand stress as compared to a daily choline intake of 480 mg. (7) choline deficiency can increase levels of homocysteine, which is also considered a risk factor when it comes to pregnancy complications. (8) 

Cognitive functions, memory deterioration 

Choline is an important neurotransmitter, the predecessor of acetylcholine, which is connected with the worsening of cognitive abilities when deficient. It is further important in building the membranes of all cells, including nerve cells. In a 2011 study, it was observed that those who supplemented choline had better cognitive abilities than those who consumed little choline. (9) 

Countless studies on animals have proven its role in preventing certain illnesses of the nervous system and in preserving cognitive function, as a review in 2017 reported. (10) So, a sufficient intake of choline is already during pregnancy, and subsequently for a lifetime, to develop one's nervous system and to maintain cognitive functions into old age. 

Cardiovascular diseases 

One of the most important links between choline and cardiovascular diseases is the level of the aforementioned homocysteine, which can increase due to choline deficiency. How great the role of homocysteine in the development of cardiovascular disease is not fully known yet, but monitoring studies suggested that a higher level leads to greater risk. (12) Additionally, higher intake of choline and betaine coincided with lower levels in several indicators of inflammation, than with insufficient intake of choline. (19) 

It’s worth a mention that our gut flora is capable of turning choline into a molecule called TMAO, which, according to certain studies, can be connected with the risk of cardiovascular disease. (20) To be safe, it might be a good idea to disperse choline-rich meals throughout the day, and to cover part of our intake with betaine. In the course of one study, two eggs in one meal did not yet increase the TMAO level, and betaine produces only minimal TMAO. (21,22) Additionally, betaine influenced the level of blood lipids more positively than choline. (23) 

Risk of cancer  

A meta-analysis published in 2016 stated that those who consumed large amounts of choline and betaine had a lower risk of cancer. Their combined consumption proved most effective, reducing the development of cancers by 40%. Every additional 100 mg of choline + betaine lead to an 11% risk reduction in the monitoring studies. (24)

  1. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US); 1998. PMID: 23193625. 

  2. Wallace TC, Fulgoni VL. Usual Choline Intakes Are Associated with Egg and Protein Food Consumption in the United States. Nutrients. 2017 Aug 5;9(8):839. doi: 10.3390/nu9080839. PMID: 28783055; PMCID: PMC5579632. 

  3. Derbyshire E. Could we be overlooking a potential choline crisis in the United Kingdom? BMJ Nutrition, Prevention & Health 2019;bmjnph-2019-000037. doi: 10.1136/bmjnph-2019-000037 

  4. Corbin KD, Zeisel SH. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr Opin Gastroenterol. 2012 Mar;28(2):159-65. doi: 10.1097/MOG.0b013e32834e7b4b. PMID: 22134222; PMCID: PMC3601486. 

  5. Fischer LM, daCosta KA, Kwock L, Stewart PW, Lu TS, Stabler SP, Allen RH, Zeisel SH. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr. 2007 May;85(5):1275-85. doi: 10.1093/ajcn/85.5.1275. PMID: 17490963; PMCID: PMC2435503. 

  6. 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. doi: 10.1093/aje/kwh187. PMID: 15234930. 

  7. Jiang X, Yan J, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen F, Caudill MA. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J. 2012 Aug;26(8):3563-74. doi: 10.1096/fj.12-207894. Epub 2012 May 1. PMID: 22549509. 

  8. Vollset SE, Refsum H, Irgens LM, Emblem BM, Tverdal A, Gjessing HK, Monsen AL, Ueland PM. Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study. Am J Clin Nutr. 2000 Apr;71(4):962-8. doi: 10.1093/ajcn/71.4.962. PMID: 10731504. 

  9. Poly C, Massaro JM, Seshadri S, Wolf PA, Cho E, Krall E, Jacques PF, Au R. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr. 2011 Dec;94(6):1584-91. doi: 10.3945/ajcn.110.008938. Epub 2011 Nov 9. PMID: 22071706; PMCID: PMC3252552. 

  10. Blusztajn JK, Slack BE, Mellott TJ. Neuroprotective Actions of Dietary Choline. Nutrients. 2017;9(8):815. Published 2017 Jul 28. doi:10.3390/nu9080815 

  11. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002 Feb 14;346(7):476-83. doi: 10.1056/NEJMoa011613. PMID: 11844848. 

  12. Peng HY, Man CF, Xu J, Fan Y. Elevated homocysteine levels and risk of cardiovascular and all-cause mortality: a meta-analysis of prospective studies. J Zhejiang Univ Sci B. 2015;16(1):78-86. doi:10.1631/jzus.B1400183 

  13. Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017 Aug 17;8(8):CD006612. doi: 10.1002/14651858.CD006612.pub5. PMID: 28816346; PMCID: PMC6483699. 

  14. larke R, Halsey J, Lewington S, Lonn E, Armitage J, Manson JE, Bønaa KH, Spence JD, Nygård O, Jamison R, Gaziano JM, Guarino P, Bennett D, Mir F, Peto R, Collins R; B-Vitamin Treatment Trialists' Collaboration. Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals. Arch Intern Med. 2010 Oct 11;170(18):1622-31. doi: 10.1001/archinternmed.2010.348. PMID: 20937919. 

  15. Pan Y, Guo LL, Cai LL, Zhu XJ, Shu JL, Liu XL, Jin HM. Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials. Br J Nutr. 2012 Aug;108(3):400-7. doi: 10.1017/S0007114511007033. Epub 2012 Jan 16. PMID: 22244447. 

  16. da Costa KA, Gaffney CE, Fischer LM, Zeisel SH. Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load. Am J Clin Nutr. 2005 Feb;81(2):440-4. doi: 10.1093/ajcn.81.2.440. PMID: 15699233; PMCID: PMC2424020. 

  17. Olthof MR, Brink EJ, Katan MB, Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr. 2005 Jul;82(1):111-7. doi: 10.1093/ajcn.82.1.111. PMID: 16002808. 

  18. Alfthan G, Tapani K, Nissinen K, Saarela J, Aro A. The effect of low doses of betaine on plasma homocysteine in healthy volunteers. Br J Nutr. 2004 Oct;92(4):665-9. doi: 10.1079/bjn20041253. PMID: 15522136. 

  19. Detopoulou P, Panagiotakos DB, Antonopoulou S, Pitsavos C, Stefanadis C. Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study. Am J Clin Nutr. 2008 Feb;87(2):424-30. doi: 10.1093/ajcn/87.2.424. PMID: 18258634. 

  20. Kanitsoraphan C, Rattanawong P, Charoensri S, Senthong V. Trimethylamine N-Oxide and Risk of Cardiovascular Disease and Mortality. Curr Nutr Rep. 2018 Dec;7(4):207-213. doi: 10.1007/s13668-018-0252-z. PMID: 30362023. 

  21. Miller CA, Corbin KD, da Costa KA, et al. Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study. Am J Clin Nutr. 2014;100(3):778-786. doi:10.3945/ajcn.114.087692 

  22. Wang Z, Tang WH, Buffa JA, et al. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J. 2014;35(14):904-910. doi:10.1093/eurheartj/ehu002 

  23. Annie J Roe, Shucha Zhang, Rafeeque A Bhadelia, Elizabeth J Johnson, Alice H Lichtenstein, Gail T Rogers, Irwin H Rosenberg, Caren E Smith, Steven H Zeisel, Tammy M Scott, Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults, The American Journal of Clinical Nutrition, Volume 105, Issue 6, June 2017, Pages 1283–1290, 

  24. Sun, S., Li, X., Ren, A. et al. Choline and betaine consumption lowers cancer risk: a meta-analysis of epidemiologic studies. Sci Rep 6, 35547 (2016). 

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