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Difference between revisions of "Choline"

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* There appear to be no studies showing that those eating a plant-based diet are more prone to the health risks related to choline deficiency than those not on a plant-based diet. There is evidence, shown below, that getting choline from plant-based sources may be protective against risks that arise from animal-based choline.
 
* There appear to be no studies showing that those eating a plant-based diet are more prone to the health risks related to choline deficiency than those not on a plant-based diet. There is evidence, shown below, that getting choline from plant-based sources may be protective against risks that arise from animal-based choline.
* A study in the New England Journal of Medicine recommends a high-fiber or meatless diet to avoid excess choline, which can increase the likelihood of stroke, heart disease, and mortality.<ref>Tang, W.H. Wilson, Zeneng Wang, Bruce S. Levison, Robert A. Koeth, Earl B. Britt, Xiaoming Fu, Yuping Wu, and Stanley L. Hazen. “Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk.” New England Journal of Medicine 368, no. 17 (April 25, 2013): 1575–84. Accessed January 20, 2020. https://doi.org/10.1056/NEJMoa1109400.</ref>
+
* A study in the New England Journal of Medicine recommends a high-fiber or meatless diet to avoid excess choline, which can increase the likelihood of stroke, heart disease, and mortality.<ref name=":1">Tang, W.H. Wilson, Zeneng Wang, Bruce S. Levison, Robert A. Koeth, Earl B. Britt, Xiaoming Fu, Yuping Wu, and Stanley L. Hazen. “Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk.” New England Journal of Medicine 368, no. 17 (April 25, 2013): 1575–84. Accessed January 20, 2020. https://doi.org/10.1056/NEJMoa1109400.</ref>
 
* Another study also found that high choline intake is linked to heart disease, but noted that vegans and vegetarians are protected from its effects.<ref>Zhu, Weifei, Zeneng Wang, W. H. Wilson Tang, and Stanley L. Hazen. “Gut Microbe-Generated Trimethylamine N -Oxide From Dietary Choline Is Prothrombotic in Subjects.” Circulation 135, no. 17 (April 25, 2017): 1671–73. Accessed January 20, 2020. https://doi.org/10.1161/CIRCULATIONAHA.116.025338.</ref>
 
* Another study also found that high choline intake is linked to heart disease, but noted that vegans and vegetarians are protected from its effects.<ref>Zhu, Weifei, Zeneng Wang, W. H. Wilson Tang, and Stanley L. Hazen. “Gut Microbe-Generated Trimethylamine N -Oxide From Dietary Choline Is Prothrombotic in Subjects.” Circulation 135, no. 17 (April 25, 2017): 1671–73. Accessed January 20, 2020. https://doi.org/10.1161/CIRCULATIONAHA.116.025338.</ref>
* Other research has supported this by showing that since vegans have different gut flora to omnivores, they produce very little TMAO.<ref>Koeth, Robert A., Zeneng Wang, Bruce S. Levison, Jennifer A. Buffa, Elin Org, Brendan T. Sheehy, Earl B. Britt, et al. “Intestinal Microbiota Metabolism of l -Carnitine, a Nutrient in Red Meat, Promotes Atherosclerosis.” Nature Medicine 19, no. 5 (May 2013): 576–85. Accessed January 21, 2020. https://doi.org/10.1038/nm.3145.</ref>
+
* Other research shows that since vegans have different gut flora to omnivores, they produce very little TMAO,<ref>Koeth, Robert A., Zeneng Wang, Bruce S. Levison, Jennifer A. Buffa, Elin Org, Brendan T. Sheehy, Earl B. Britt, et al. “Intestinal Microbiota Metabolism of l -Carnitine, a Nutrient in Red Meat, Promotes Atherosclerosis.” Nature Medicine 19, no. 5 (May 2013): 576–85. Accessed January 21, 2020. https://doi.org/10.1038/nm.3145.</ref> a byproduct of choline which is linked to chronic kidney disease disease, .<ref>Moraes, Cristiane, Denis Fouque, Ana Claudia F. Amaral, and Denise Mafra. “Trimethylamine N-Oxide From Gut Microbiota in Chronic Kidney Disease Patients: Focus on Diet.” Journal of Renal Nutrition 25, no. 6 (November 2015): 459–65. Accessed January 20, 2020. https://doi.org/10.1053/j.jrn.2015.06.004.</ref><ref>Tang, W.H. Wilson, Zeneng Wang, David J. Kennedy, Yuping Wu, Jennifer A. Buffa, Brendan Agatisa-Boyle, Xinmin S. Li, Bruce S. Levison, and Stanley L. Hazen. “Gut Microbiota-Dependent Trimethylamine N -Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease.” Circulation Research 116, no. 3 (January 30, 2015): 448–55. Accessed January 20, 2020. https://doi.org/10.1161/CIRCRESAHA.116.305360.
 +
</ref> stroke, and heart disease.<ref name=":1" />
 
* Egg consumption has been linked to an increased risk of prostate cancer, and researchers suggest that choline may be the culprit.<ref>Richman, Erin L, Stacey A Kenfield, Meir J Stampfer, Edward L Giovannucci, Steven H Zeisel, Walter C Willett, and June M Chan. “Choline Intake and Risk of Lethal Prostate Cancer: Incidence and Survival.” The American Journal of Clinical Nutrition 96, no. 4 (October 1, 2012): 855–63. Accessed January 20, 2020. https://doi.org/10.3945/ajcn.112.039784.</ref><ref>Richman, E. L., S. A. Kenfield, M. J. Stampfer, E. L. Giovannucci, and J. M. Chan. “Egg, Red Meat, and Poultry Intake and Risk of Lethal Prostate Cancer in the Prostate-Specific Antigen-Era: Incidence and Survival.” Cancer Prevention Research 4, no. 12 (December 1, 2011): 2110–21. Accessed January 20, 2020. https://doi.org/10.1158/1940-6207.CAPR-11-0354.</ref><ref>Richman, Erin L, Meir J Stampfer, Alan Paciorek, Jeanette M Broering, Peter R Carroll, and June M Chan. “Intakes of Meat, Fish, Poultry, and Eggs and Risk of Prostate Cancer Progression.” The American Journal of Clinical Nutrition 91, no. 3 (March 1, 2010): 712–21. Accessed January 20, 2020. https://doi.org/10.3945/ajcn.2009.28474.</ref>
 
* Egg consumption has been linked to an increased risk of prostate cancer, and researchers suggest that choline may be the culprit.<ref>Richman, Erin L, Stacey A Kenfield, Meir J Stampfer, Edward L Giovannucci, Steven H Zeisel, Walter C Willett, and June M Chan. “Choline Intake and Risk of Lethal Prostate Cancer: Incidence and Survival.” The American Journal of Clinical Nutrition 96, no. 4 (October 1, 2012): 855–63. Accessed January 20, 2020. https://doi.org/10.3945/ajcn.112.039784.</ref><ref>Richman, E. L., S. A. Kenfield, M. J. Stampfer, E. L. Giovannucci, and J. M. Chan. “Egg, Red Meat, and Poultry Intake and Risk of Lethal Prostate Cancer in the Prostate-Specific Antigen-Era: Incidence and Survival.” Cancer Prevention Research 4, no. 12 (December 1, 2011): 2110–21. Accessed January 20, 2020. https://doi.org/10.1158/1940-6207.CAPR-11-0354.</ref><ref>Richman, Erin L, Meir J Stampfer, Alan Paciorek, Jeanette M Broering, Peter R Carroll, and June M Chan. “Intakes of Meat, Fish, Poultry, and Eggs and Risk of Prostate Cancer Progression.” The American Journal of Clinical Nutrition 91, no. 3 (March 1, 2010): 712–21. Accessed January 20, 2020. https://doi.org/10.3945/ajcn.2009.28474.</ref>
* TMAO has also been linked to chronic kidney disease.<ref>Moraes, Cristiane, Denis Fouque, Ana Claudia F. Amaral, and Denise Mafra. “Trimethylamine N-Oxide From Gut Microbiota in Chronic Kidney Disease Patients: Focus on Diet.” Journal of Renal Nutrition 25, no. 6 (November 2015): 459–65. Accessed January 20, 2020. https://doi.org/10.1053/j.jrn.2015.06.004.</ref><ref>Tang, W.H. Wilson, Zeneng Wang, David J. Kennedy, Yuping Wu, Jennifer A. Buffa, Brendan Agatisa-Boyle, Xinmin S. Li, Bruce S. Levison, and Stanley L. Hazen. “Gut Microbiota-Dependent Trimethylamine N -Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease.” Circulation Research 116, no. 3 (January 30, 2015): 448–55. Accessed January 20, 2020. https://doi.org/10.1161/CIRCRESAHA.116.305360.
 
</ref>
 
* In some people, excess choline consumption causes a strong fishy body odor, including the breath, urine, and sweat.<ref>Rehman, H. U. “Fish Odour Syndrome.” Postgraduate Medical Journal 75, no. 886 (August 1, 1999): 451–52. Accessed January 20, 2020. https://doi.org/10.1136/pgmj.75.886.451.</ref>
 
 
* One of the most common symptoms of choline deficiency is the development of non-alcoholic fatty liver disease (NAFLD).<ref>Corbin, Karen, and Steven Zeisel. “Choline Metabolism Provides Novel Insights into Nonalcoholic Fatty Liver Disease and Its Progression.” Current Opinion in Gastroenterology 28, no. 2 (March 2012): 159–65. Accessed January 21, 2020. https://doi.org/10.1097/MOG.0b013e32834e7b4b.</ref> However, plant-based and vegetarian diets have been shown to reduce the risk of NAFLD, making it unlikely that these diets are deficient in choline.<ref>Chiu, Tina H., Ming-Nan Lin, Wen-Harn Pan, Yen-Ching Chen, and Chin-Lon Lin. “Vegetarian Diet, Food Substitution, and Nonalcoholic Fatty Liver.” Ci Ji Yi Xue Za Zhi = Tzu-Chi Medical Journal 30, no. 2 (June 2018): 102–9. Accessed January 21, 2020. https://doi.org/10.4103/tcmj.tcmj_109_17.</ref><ref>Mazidi, Mohsen, and Andre Pascal Kengne. “Higher Adherence to Plant-Based Diets Are Associated with Lower Likelihood of Fatty Liver.” Clinical Nutrition 38, no. 4 (August 2019): 1672–77. Accessed January 21, 2020. https://doi.org/10.1016/j.clnu.2018.08.010.</ref>
 
* One of the most common symptoms of choline deficiency is the development of non-alcoholic fatty liver disease (NAFLD).<ref>Corbin, Karen, and Steven Zeisel. “Choline Metabolism Provides Novel Insights into Nonalcoholic Fatty Liver Disease and Its Progression.” Current Opinion in Gastroenterology 28, no. 2 (March 2012): 159–65. Accessed January 21, 2020. https://doi.org/10.1097/MOG.0b013e32834e7b4b.</ref> However, plant-based and vegetarian diets have been shown to reduce the risk of NAFLD, making it unlikely that these diets are deficient in choline.<ref>Chiu, Tina H., Ming-Nan Lin, Wen-Harn Pan, Yen-Ching Chen, and Chin-Lon Lin. “Vegetarian Diet, Food Substitution, and Nonalcoholic Fatty Liver.” Ci Ji Yi Xue Za Zhi = Tzu-Chi Medical Journal 30, no. 2 (June 2018): 102–9. Accessed January 21, 2020. https://doi.org/10.4103/tcmj.tcmj_109_17.</ref><ref>Mazidi, Mohsen, and Andre Pascal Kengne. “Higher Adherence to Plant-Based Diets Are Associated with Lower Likelihood of Fatty Liver.” Clinical Nutrition 38, no. 4 (August 2019): 1672–77. Accessed January 21, 2020. https://doi.org/10.1016/j.clnu.2018.08.010.</ref>
  

Revision as of 10:55, 24 January 2020

This draft has been assigned to User:Bethany.Chester and will be moved to the main namespace when completed.

Fact Sheet

Assertion

  • This fact sheet supports the assertion that choline from animal sources is not necessary and may be harmful to health.

Context

  • Choline is an essential nutrient, important for brain health and a number of other physiological functions.[1]
  • Although choline is readily available in plant foods.[2], the fact that choline is most highly concentrated in animal-derived foods such as eggs and meat[3] has led to claims that vegans are at risk of becoming deficient in choline.

Research

  • There appear to be no studies showing that those eating a plant-based diet are more prone to the health risks related to choline deficiency than those not on a plant-based diet. There is evidence, shown below, that getting choline from plant-based sources may be protective against risks that arise from animal-based choline.
  • A study in the New England Journal of Medicine recommends a high-fiber or meatless diet to avoid excess choline, which can increase the likelihood of stroke, heart disease, and mortality.[4]
  • Another study also found that high choline intake is linked to heart disease, but noted that vegans and vegetarians are protected from its effects.[5]
  • Other research shows that since vegans have different gut flora to omnivores, they produce very little TMAO,[6] a byproduct of choline which is linked to chronic kidney disease disease, .[7][8] stroke, and heart disease.[4]
  • Egg consumption has been linked to an increased risk of prostate cancer, and researchers suggest that choline may be the culprit.[9][10][11]
  • One of the most common symptoms of choline deficiency is the development of non-alcoholic fatty liver disease (NAFLD).[12] However, plant-based and vegetarian diets have been shown to reduce the risk of NAFLD, making it unlikely that these diets are deficient in choline.[13][14]

Conflicting Information

  • A 2019 article published in the journal BMJ (British Medical Journal) generated a flurry of media buzz, raising concerns about choline deficiency in those eating plant-based diets. In the media, the article was referred to as a study, but in reality it is an editorial and the author did not carry out any of her own research. Moreover, she has ties to the egg and meat industries and so the article cannot be considered unbiased.[15]
  • Two studies carried out in 2004 and 2009 appeared to show that low choline intake in pregnant women could increase the risk of babies being born with neural tube defects.[16][17] However, more recent research does not support this claim.[18][19][20] In contrast, up to 70 percent of neural tube defects are linked to inadequate folic acid intake,[21][22][23] and those eating plant-based or vegetarian diets typically have higher folate levels than omnivores.[24][25]

Other Sources

  • The National Institutes for Health (NIH) state that cruciferous vegetables and some beans are "rich in choline." They show that soybeans contain more choline than ground beef, chicken breast, or cod, while mushrooms and potatoes contain more than tuna and dairy products. Quinoa, wheat germ, and kidney beans are also good sources.[3]
  • The Physicians' Committee for Responsible Medicine recommends choosing plant-based sources of choline because animal sources (such as eggs) are often very high in saturated fat. It points out that high saturated fat consumption increases the risk of heart disease and dementia.[26]
  • Eggs, which are by far the greatest dietary source of choline, are extremely high in cholesterol and have been shown to significantly increase the risk of heart disease.[27] The USDA's Dietary Guidelines recommend eating "as little dietary cholesterol as possible."[28]
  • Tom Sanders, Professor Emeritus of Nutrition and Dietetics at King's College London, has stated that "There is no justification for suggesting that plant-based diets risk damaging brain development...My own research on vegans and those of others in Europe and USA find the growth and development of vegans and vegetarians is normal." He points out that the body can make some of its own choline and that the nutrient is "abundant" in several plant-based foods.[29]

General Information

  • Despite eating a diet high in animal products,[30] most people in the USA do not achieve the Adequate Intake (AI) for choline, yet the actual rates of choline deficiency are very low.[31]. This suggests the AI is not accurate.[3]
  • In the USA, recommendations for the Adequate Intake (AI) of choline are based on very limited data (one study done on adult men). The AI for women and other age groups has been extrapolated from this data and so may not be accurate. Additionally, the original study was limited as it only compared intakes of 500 mg/day and 50 mg/day, finding that the latter caused deficiency. Intermediary values were not considered, so the recommended AI may be higher than true requirements[32][33] — especially as the body produces some of its own choline.[34][35]
  • The European Food Safety Authority sets the AI for adults at a lower figure of 400 mg/day. This figure is based on the average intake of healthy populations, and is arguably more accurate than the study mentioned above. However, it still does not establish the minimum amount of choline required for good health.[36]

See Also

Plain Text

Meta

This fact sheet was originally authored by Bethany Chester with contributions by Greg Fuller. The contents may have been edited since that time by others.

Footnotes

  1. Zeisel, Steven H., and Kerry-Ann da Costa. “Choline: An Essential Nutrient for Public Health.” Nutrition Reviews 67, no. 11 (November 2009): 615–23. Accessed January 23, 2020. https://doi.org/10.1111/j.1753-4887.2009.00246.x.
  2. Patterson, Kristine Y. et al. “USDA Database for the Choline Content of Common Foods.” USDA, January 2008. Accessed January 21, 2020. https://data.nal.usda.gov/system/files/Choln02.pdf.
  3. 3.0 3.1 3.2 “Office of Dietary Supplements - Choline.” Accessed January 20, 2020. https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/.
  4. 4.0 4.1 Tang, W.H. Wilson, Zeneng Wang, Bruce S. Levison, Robert A. Koeth, Earl B. Britt, Xiaoming Fu, Yuping Wu, and Stanley L. Hazen. “Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk.” New England Journal of Medicine 368, no. 17 (April 25, 2013): 1575–84. Accessed January 20, 2020. https://doi.org/10.1056/NEJMoa1109400.
  5. Zhu, Weifei, Zeneng Wang, W. H. Wilson Tang, and Stanley L. Hazen. “Gut Microbe-Generated Trimethylamine N -Oxide From Dietary Choline Is Prothrombotic in Subjects.” Circulation 135, no. 17 (April 25, 2017): 1671–73. Accessed January 20, 2020. https://doi.org/10.1161/CIRCULATIONAHA.116.025338.
  6. Koeth, Robert A., Zeneng Wang, Bruce S. Levison, Jennifer A. Buffa, Elin Org, Brendan T. Sheehy, Earl B. Britt, et al. “Intestinal Microbiota Metabolism of l -Carnitine, a Nutrient in Red Meat, Promotes Atherosclerosis.” Nature Medicine 19, no. 5 (May 2013): 576–85. Accessed January 21, 2020. https://doi.org/10.1038/nm.3145.
  7. Moraes, Cristiane, Denis Fouque, Ana Claudia F. Amaral, and Denise Mafra. “Trimethylamine N-Oxide From Gut Microbiota in Chronic Kidney Disease Patients: Focus on Diet.” Journal of Renal Nutrition 25, no. 6 (November 2015): 459–65. Accessed January 20, 2020. https://doi.org/10.1053/j.jrn.2015.06.004.
  8. Tang, W.H. Wilson, Zeneng Wang, David J. Kennedy, Yuping Wu, Jennifer A. Buffa, Brendan Agatisa-Boyle, Xinmin S. Li, Bruce S. Levison, and Stanley L. Hazen. “Gut Microbiota-Dependent Trimethylamine N -Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease.” Circulation Research 116, no. 3 (January 30, 2015): 448–55. Accessed January 20, 2020. https://doi.org/10.1161/CIRCRESAHA.116.305360.
  9. Richman, Erin L, Stacey A Kenfield, Meir J Stampfer, Edward L Giovannucci, Steven H Zeisel, Walter C Willett, and June M Chan. “Choline Intake and Risk of Lethal Prostate Cancer: Incidence and Survival.” The American Journal of Clinical Nutrition 96, no. 4 (October 1, 2012): 855–63. Accessed January 20, 2020. https://doi.org/10.3945/ajcn.112.039784.
  10. Richman, E. L., S. A. Kenfield, M. J. Stampfer, E. L. Giovannucci, and J. M. Chan. “Egg, Red Meat, and Poultry Intake and Risk of Lethal Prostate Cancer in the Prostate-Specific Antigen-Era: Incidence and Survival.” Cancer Prevention Research 4, no. 12 (December 1, 2011): 2110–21. Accessed January 20, 2020. https://doi.org/10.1158/1940-6207.CAPR-11-0354.
  11. Richman, Erin L, Meir J Stampfer, Alan Paciorek, Jeanette M Broering, Peter R Carroll, and June M Chan. “Intakes of Meat, Fish, Poultry, and Eggs and Risk of Prostate Cancer Progression.” The American Journal of Clinical Nutrition 91, no. 3 (March 1, 2010): 712–21. Accessed January 20, 2020. https://doi.org/10.3945/ajcn.2009.28474.
  12. Corbin, Karen, and Steven Zeisel. “Choline Metabolism Provides Novel Insights into Nonalcoholic Fatty Liver Disease and Its Progression.” Current Opinion in Gastroenterology 28, no. 2 (March 2012): 159–65. Accessed January 21, 2020. https://doi.org/10.1097/MOG.0b013e32834e7b4b.
  13. Chiu, Tina H., Ming-Nan Lin, Wen-Harn Pan, Yen-Ching Chen, and Chin-Lon Lin. “Vegetarian Diet, Food Substitution, and Nonalcoholic Fatty Liver.” Ci Ji Yi Xue Za Zhi = Tzu-Chi Medical Journal 30, no. 2 (June 2018): 102–9. Accessed January 21, 2020. https://doi.org/10.4103/tcmj.tcmj_109_17.
  14. Mazidi, Mohsen, and Andre Pascal Kengne. “Higher Adherence to Plant-Based Diets Are Associated with Lower Likelihood of Fatty Liver.” Clinical Nutrition 38, no. 4 (August 2019): 1672–77. Accessed January 21, 2020. https://doi.org/10.1016/j.clnu.2018.08.010.
  15. Derbyshire, Emma. “Could We Be Overlooking a Potential Choline Crisis in the United Kingdom?” BMJ Nutrition, Prevention & Health 2, no. 2 (December 1, 2019): 86–89. Accessed January 20, 2020. https://doi.org/10.1136/bmjnph-2019-000037.
  16. Shaw, G. M., S. L. Carmichael, W. Yang, S. Selvin, and D. M. Schaffer. “Periconceptional Dietary Intake of Choline and Betaine and Neural Tube Defects in Offspring.” American Journal of Epidemiology 160, no. 2 (July 15, 2004): 102–9. Accessed January 21, 2020. https://doi.org/10.1093/aje/kwh187.
  17. Shaw, Gary M., Richard H. Finnell, Henk J. Blom, Suzan L. Carmichael, Stein Emil Vollset, Wei Yang, and Per M. Ueland. “Choline and Risk of Neural Tube Defects in a Folate-Fortified Population:” Epidemiology 20, no. 5 (September 2009): 714–19. Accessed January 21, 2020. https://doi.org/10.1097/EDE.0b013e3181ac9fe7.
  18. Mills, James L, 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.” The American Journal of Clinical Nutrition 100, no. 4 (October 1, 2014): 1069–74. Accessed January 21, 2020. https://doi.org/10.3945/ajcn.113.079319.
  19. Carmichael, Suzan L., Wei Yang, and Gary M. Shaw. “Periconceptional Nutrient Intakes and Risks of Neural Tube Defects in California.” Birth Defects Research Part A: Clinical and Molecular Teratology 88, no. 8 (2010): 670–78. Accessed January 21, 2020. https://doi.org/10.1002/bdra.20675.
  20. Chandler, Angela L., Charlotte A. Hobbs, Bridget S. Mosley, Robert J. Berry, Mark A. Canfield, Yan Ping Qi, Anna Maria Siega‐Riz, and Gary M. Shaw. “Neural Tube Defects and Maternal Intake of Micronutrients Related to One-Carbon Metabolism or Antioxidant Activity.” Birth Defects Research Part A: Clinical and Molecular Teratology 94, no. 11 (2012): 864–74. Accessed January 21, 2020. https://doi.org/10.1002/bdra.23068.
  21. “Neural Tube Defects (NTDs) | Duke Molecular Physiology Institute.” Accessed January 21, 2020. https://dmpi.duke.edu/neural-tube-defects-ntds.
  22. Berry, Robert J., Zhu Li, J. David Erickson, Song Li, Cynthia A. Moore, Hong Wang, Joseph Mulinare, et al. “Prevention of Neural-Tube Defects with Folic Acid in China.” New England Journal of Medicine 341, no. 20 (November 11, 1999): 1485–90. Accessed January 21, 2020. https://doi.org/10.1056/NEJM199911113412001.
  23. Green, Nancy S. “Folic Acid Supplementation and Prevention of Birth Defects.” The Journal of Nutrition 132, no. 8 (August 1, 2002): 2356S-2360S. Accessed January 21, 2020. https://doi.org/10.1093/jn/132.8.2356S.
  24. Majchrzak, D., I. Singer, M. Männer, P. Rust, D. Genser, K.-H. Wagner, and I. Elmadfa. “B-Vitamin Status and Concentrations of Homocysteine in Austrian Omnivores, Vegetarians and Vegans.” Annals of Nutrition and Metabolism 50, no. 6 (2006): 485–91. Accessed January 21, 2020. https://doi.org/10.1159/000095828.
  25. Koebnick, Corinna, Ulrike A. Heins, Ingrid Hoffmann, Pieter C. Dagnelie, and Claus Leitzmann. “Folate Status during Pregnancy in Women Is Improved by Long-Term High Vegetable Intake Compared with the Average Western Diet.” The Journal of Nutrition 131, no. 3 (April 1, 2001): 733–39. Accessed January 21, 2020. https://doi.org/10.1093/jn/131.3.733.
  26. Physicians Committee for Responsible Medicine. “Clearing Up Choline Confusion.” Accessed January 20, 2020. https://www.pcrm.org/news/blog/clearing-choline-confusion.
  27. Zhong, Victor W., Linda Van Horn, Marilyn C. Cornelis, John T. Wilkins, Hongyan Ning, Mercedes R. Carnethon, Philip Greenland, et al. “Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality.” JAMA 321, no. 11 (March 19, 2019): 1081. Accessed January 21, 2020. https://doi.org/10.1001/jama.2019.1572.
  28. “A Closer Look Inside Healthy Eating Patterns - 2015-2020 Dietary Guidelines | Health.Gov.” Accessed January 22, 2020. https://health.gov/dietaryguidelines/2015/guidelines/chapter-1/a-closer-look-inside-healthy-eating-patterns/.
  29. Gilliver, Liam. “Rachel Riley Defends Plant-Based Diet Amid Concerns Around Choline.” Vegan News, Plant Based Living, Food, Health & more. Accessed January 21, 2020. https://www.plantbasednews.org/news/rachel-riley-defends-plant-based-diet.
  30. Bloomfield, Hanna E., Robert Kane, Eva Koeller, Nancy Greer, Roderick MacDonald, and Timothy Wilt. Benefits and Harms of the Mediterranean Diet Compared to Other Diets. VA Evidence-Based Synthesis Program Reports. Washington (DC): Department of Veterans Affairs (US), 2015. http://www.ncbi.nlm.nih.gov/books/NBK379574/.
  31. Bloomfield, Hanna E., Robert Kane, Eva Koeller, Nancy Greer, Roderick MacDonald, and Timothy Wilt. Benefits and Harms of the Mediterranean Diet Compared to Other Diets. VA Evidence-Based Synthesis Program Reports. Washington (DC): Department of Veterans Affairs (US), 2015. http://www.ncbi.nlm.nih.gov/books/NBK379574/.
  32. Folate, Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on, Other B. Vitamins, and And Choline. Choline. National Academies Press (US), 1998. Accessed January 21, 2020. https://www.ncbi.nlm.nih.gov/books/NBK114308/.
  33. Zeisel, S. H., K. A. Da Costa, P. D. Franklin, E. A. Alexander, J. T. Lamont, N. F. Sheard, and A. Beiser. “Choline, an Essential Nutrient for Humans.” FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 5, no. 7 (April 1991): 2093–98.
  34. “Dietary Reference Intakes: The Essential Guide to Nutrient Requirements”. Accessed January 22, 2020. https://doi.org/10.17226/11537.
  35. Hollenbeck, Clarie B. “An Introduction to the Nutrition and Metabolism of Choline.” Central Nervous System Agents in Medicinal Chemistry 12, no. 2 (June 2012): 100–113. Accessed January 21, 2020. https://doi.org/10.2174/187152412800792689.
  36. “Dietary Reference Values for Choline.” EFSA Journal 14, no. 8 (2016): e04484. Accessed January 22, 2020. https://doi.org/10.2903/j.efsa.2016.4484.