Российский физиологический журнал им. И.М. Сеченова, 2023, T. 109, № 12, стр. 1763-1779

Свободный холин крови как биомаркер физиологического статуса организма

Е. И. Савельева 1*, М. А. Ленинский 1, Н. В. Гончаров 12

1 НИИ гигиены, профпатологии и экологии человека
г.п. Кузьмоловский, Ленинградская обл., Россия

2 Институт эволюционной физиологии и биохимии им. И.М. Сеченова РАН
Санкт-Петербург, Россия

* E-mail: saveleva@gpeh.ru

Поступила в редакцию 12.09.2023
После доработки 11.10.2023
Принята к публикации 16.10.2023

Аннотация

Холин является важнейшим нутриентом. С недостаточным потреблением холина связывают митохондриальные дисфункции, оксидативный стресс и обусловленные этими процессами риски развития неалкогольной жировой болезни печени, сердечно-сосудистой патологии, мышечной дистрофии, патологии развития нервной трубки плода. При этом избыточное потребление холина связывают с накоплением в крови уремического токсина – триметиламиноксида, биопредшественником которого является не фосфатидилхолин, а свободный холин крови. Содержание холина и его метаболитов в плазме крови ассоциировано с разными типами сосудистых патологий, позволяет прогнозировать тяжесть течения сердечно-сосудистых и других ассоциированных с ними заболеваний. Противоречивые сведения о норме и отклонениях от нормы содержания свободного холина в плазме крови в числе прочих факторов обусловлены недостаточным вниманием к стабилизации содержания свободного холина в плазме крови на этапах, предшествующих инструментальному анализу. Использование ЭДТА в качестве антикоагулянта и соблюдение холодового режима (не выше 4°С) сразу же после отбора крови и до инструментального анализа позволяет избежать роста концентрации холина в плазме ex vivo.

Ключевые слова: свободный холин, плазма крови, стабилизация, биомаркер, риски, высокоэффективная жидкостная хроматография, тандемное масс-спектрометрическое детектирование

Список литературы

  1. Zeisel SH (2000) Choline: an essential nutrient for humans. Nutrition 16 (7–8): 669–671. https://doi.org/10.1016/s0899-9007(00)00349-x

  2. Goh YO, Cheam G, Wang Y (2021) Understanding Choline Bioavailability and Utilization: First Step Toward Personalizing Choline Nutrition. J Agric Food Chem 69: 10774–10789. https://doi.org/10.1021/acs.jafc.1c03077

  3. Shim E, Park E (2022) Choline intake and its dietary reference values in Korea and other countries: a review. Nutr Res Pract 16: 126–133. https://doi.org/10.4162/nrp.2022.16.S1.S126

  4. Rucker RB, Zempleni J, Suttie JW, McCormick DB (2007) Handbook of vitamins (4th ed). Taylor & Francis 459–477.

  5. Plotnikoff GA, Dobberstein L, Raatz S (2023) Nutritional Assessment of the Symptomatic Patient on a Plant-Based Diet: Seven Key Questions. Nutrients 15: 1387. https://doi.org/10.3390/nu15061387

  6. Osipova D, Kokoreva K, Lazebnik L, Golovanova E, Pavlov C, Dukhanin A, Orlova S, Starostin K (2022) Regression of Liver Steatosis Following Phosphatidylcholine Administration: A Review of Molecular and Metabolic Pathways Involved. Front Pharmacol 13: 797923. https://doi.org/10.3389/fphar.2022.797923

  7. Corbin KD, Zeisel SH (2012) Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression". Current Opinion Gastroenterol 28(2): 159–165. https://doi.org/10.1097/MOG.0b013e32834e7b4b

  8. Chen X, Xue H, Fang W, Chen K, Chen S, Yang W, Shen, T, Chen X, Zhang P, Ling W (2019) Adropin protects against liver injury in nonalcoholic steatohepatitis via the Nrf 2 mediated antioxidant capacity. Redox Biol 21: 101068.https://doi.org/10.1016/J.REDOX.2018.101068

  9. Dietary reference values for choline (2016) EFSA J 14(8). https://doi.org/10.2903/j.efsa.2016.44842016

  10. Richman EL, Kenfield SA, Stampfer MJ, Giovannucci EL, Zeisel SH, Willett WC, Chan JM (2012) Choline intake and risk of lethal prostate cancer: incidence and survival. Am J Clin Nutrit 96 (4): 855–863. https://doi.org/10.3945/ajcn.112.039784

  11. Han P, Bidulescu A, Barber JR, Zeisel SH, Joshu CE, Prizment AE, Vitolins MZ, Platz EA (2019) Dietary choline and betaine intakes and risk of total and lethal prostate cancer in the Atherosclerosis Risk in Communities (ARIC) Study. Cancer Causes Control 30(4): 343–354. https://doi.org/10.1007/s10552-019-01148-4

  12. Zeisel SH (2006) Choline: critical role during fetal development and dietary requirements in adults. Annu Rev Nutr 26: 229–250. https://doi.org/10.1146/annurev.nutr.26.061505.11

  13. Obeid R, Derbyshire E, Schön C (2022) Association between Maternal Choline, Fetal Brain Development, and Child Neurocognition: Systematic Review and Meta-Analysis of Human Studies. Advanc Nutrit 13(6): 2445–2457. https://doi.org/10.1093/advances/nmac082

  14. Buchman AL (2009) The addition of choline to parenteral nutrition. Gastroenterology 137: 119–128. https://doi.org/10.1053/j.gastro.2009.08.010

  15. Troisi J, Cinque C, Giugliano L, Symes S, Richards S, Adair D, Cavallo P, Sarno L, Scala G, Caiazza M, Guida M (2019) Metabolomic change due to combined treatment with myo-inositol, D-chiro-inositol and glucomannan in polycystic ovarian syndrome patients: a pilot study. J Ovar Res 12(1): 25. https://doi.org/10.1186/s13048-019-0500-x

  16. Deprince A, Haas JT, Staels B (2020) Dysregulated lipid metabolism links NAFLD to cardiovascular disease. Mol Metab 42: 101092. https://doi.org/10.1016/j.molmet.2020.101092

  17. Du X, Wu Z, Xu Y, Liu Y, Liu W, Wang T, Li C, Zhang C, Yi F, Gao L, Liang X, Ma C (2018) Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice. Cell Mol Immunol 16(11): 878–886. https://doi.org/10.1038/s41423-018-0032-0

  18. Chen Z, Tian R, She Z, Cai J, Li H (2020) Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radical Biol Med 152: 116−141. https://doi.org/10.1016/j.freeradbiomed.2020.02.025

  19. García-Ruiz C, Fernández-Checa JC (2018) Mitochondrial Oxidative Stress and Antioxidants Balance in Fatty Liver Disease. Hepatol Communicat 2(12): 1425–1439. https://doi.org/10.1002/hep4.1271

  20. Teodoro JS, Rolo AP, Duarte FV, Simões AM, Palmeira CM (2008) Differential alterations in mitochondrial function induced by a choline-deficient diet: Understanding fatty liver disease progression. Mitochondrion 8(5–6): 367–376. https://doi.org/10.1016/j.mito.2008.07.008

  21. Tanaka S, Miyanishi K, Kobune M, Kawano Y, Hoki T, Kubo T, Hayashi T, Sato T, Sato Y, Takimoto R, Kato J (2013) Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. J Gastroenterol 48(11): 1249–1258. https://doi.org/10.1007/s00535-012-0739-0

  22. Pei K, Gui T, Kan D, Feng H, Jin Y, Yang Y, Zhang Q, Du Z, Gai Z, Wu J, Li Y (2020) An Overview of Lipid Metabolism and Nonalcoholic Fatty Liver Disease. BioMed Res Int 1–12: 4020249. https://doi.org/10.1155/2020/4020249

  23. Ashraf NU, Altaf M (2018) Epigenetics: An emerging field in the pathogenesis of nonalcoholic fatty liver disease. Mutat Res Rev Mut Res 778: 1–12. https://doi.org/10.1016/j.mrrev.2018.07.002

  24. Yoo N, Jeon S, Nam Y, Park Y-J, Won SB, Kwon Y (2015) Dietary Supplementation of Genistein Alleviates Liver Inflammation and Fibrosis Mediated by a Methionine-Choline-Deficient Diet in db/db Mice. J Agricult Food Chem 63(17): 4305–4311. https://doi.org/10.1021/acs.jafc.5b00398

  25. Alves FM, Caldow MK, Trieu J, Naim T, Montgomery MK, Watt MJ, Lynch GS, Koopman R (2019) Choline administration attenuates aspects of the dystrophic pathology in mdx mice. Clin Nutrit Exp 24: 83–91. https://doi.org/10.1016/j.yclnex.2018.12.005

  26. Payne F, Lim K, Girousse A, Brown RJ, Kory N, Robbins A, Xue Y, Sleigh A, Cochran E, Adams C, Dev Borman A, Russel-Jones D, Gorden P, Semple RK, Saudek V, O’Rahilly S, Walther TC, Barroso I, Savage DB (2014) Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease. Proc Natl Acad Sci U S A 111(24): 8901–8906. https://doi.org/10.1073/pnas.1408523111

  27. Dave N, Judd J M, Decker A,Winslow W, Sarette P, Villarreal Espinosa O, Tallino S, Bartholomew SK, Bilal A, Sandler J, McDonough I,Winstone J K, Blackwood E A, Glembotski C, Karr T, Velazquez R (2023) Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimer’s disease hallmarks. Aging Cell 22: e13775. https://doi.org/10.1111/acel.13775

  28. Penry JT, Manore MM (2008) Choline: An Important Micronutrient for Maximal Endurance-Exercise Performance? Int J Sport Nutr Exerc Metab 18(2): 191–203. https://doi.org/10.1123/ijsnem.18.2.191

  29. Dibella M, Thomas MS, Alyousef H, Millar C, Blesso C, Malysheva O (2020) Choline intake as supplement or as a component of eggs increases plasma choline and reduces interleukin-6 without modifying plasma cholesterol in participants with metabolic syndrome. Nutrients12: 1e. https://doi.org/10.3390/nu12103120

  30. Rankovic A, Godfrey H, Grant CE, Shoveller AK, Bakovic M, Kirby G (2023) Serum metabolomic analysis of the dose-response effect of dietary choline in overweight male cats fed at maintenance energy requirements. PLoS One 18(1): e0280734. https://doi.org/10.1371/journal.pone.0280734

  31. Zhan X, Fletcher L, Huyben D, Cai H, Dingle S, Qi N, Huber L-A, Wang B, Li J (2023) Choline supplementation regulates gut microbiome diversity, gut epithelial activity, and the cytokine gene expression in gilts. Front Nutr 10: 1101519. https://doi.org/10.3389/fnut.2023.1101519

  32. Velazquez R, Ferreira E, Knowles S, Fux C, Rodin A, Winslow W, Oddo S (2019) Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell 18: e13037. https://doi.org/10.1111/acel.13037

  33. Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z (2016) Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 165: 111–124. https://doi.org/10.1016/j.cell.2016.02.011

  34. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472: 57–63. https://doi.org/10.1038/nature09922

  35. Zhu W, Romano KA, Li L, Buffa JA, Sangwan N, Prakash P (2021) Gut microbes impact stroke severity via the trimethylamine N-Oxide pathway. Cell Host Microbe 29: 1199–1208. https://doi.org/10.1016/j.chom.2021.05.002

  36. Yang S, Li X, Yang F, Zhao R, Pan X, Liang J (2019) Gut microbiota-dependent marker TMAO in promoting cardiovascular disease: inflammation mechanism, clinical prognostic, and potential as a therapeutic target. Front Pharmacol 10: 1360. https://doi.org/10.3389/fphar.2019.01360

  37. Romano KA, Vivas EI, Amador-Noguez D, Rey FE (2015) Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite Trimethylamine-N-Oxide. mBio 6: e02481-14. https://doi.org/10.1128/mBio.02481-14

  38. Yoo W, Zieba JK, Foegeding NJ, Torres TP, Shelton CD, Shealy NG (2021) High-Fat Diet–Induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide. Science 373: 813–818. https://doi.org/10.1126/science.aba3683

  39. Ren D, Liu Y, Zhao,Y, Yang X (2016) Hepatotoxicity and endothelial dysfunction induced by high choline diet and the protective effects of phloretin in mice. Food Chem Toxicol 94: 203–212. https://doi.org//10.1016/j.fct.2016.06.004

  40. Pan XF, Yang JJ, Shu XO, Moore SC, Palmer ND, Guasch-Ferré M, Herrington DM, Harada S, Eliassen H, Wang TJ, Gerszten RE, Albanes D, Tzoulaki I, Karaman I, Elliott P, Zhu H, Wagenknecht LE, Zheng W, Cai H, Cai Q, Matthews CE, Menni C, Meyer KA, Lipworth LP, Ose J, Fornage M, Ulrich CM, Yu D (2021) Associations of circulating choline and its related metabolites with cardiometabolic biomarkers: an international pooled analysis. Am J Clin Nutr 114(3): 893–906. https://doi.org/10.1093/ajcn/nqab152

  41. Mujica M, Lewis E, Jacobs R, Letourneau N, Bell R, Field C, Lamers Y (2020) Plasma Free Choline Concentration Did Not Reflect Dietary Choline Intake in Early and Late Pregnancy: Findings from the APrON Study. Curr Dev Nutr 4(Suppl 2): 1825.https://doi.org/10.1093/cdn/nzaa067_052

  42. Zeisel SH (2010) Choline. In: Coates PM, Betz JM, Blackman MR (eds). Encyclopedia of Dietary Supplements. 2nd ed. London and New York. Informa Healthcare 136–143.

  43. Finglas PM (2000) Dietary Reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin and choline. Trends Food Sci Technol 11(8): 296–297. https://doi.org/10.1016/s0924-2244(01)00010-3

  44. Wiedeman AM, Dyer RA, Green TJ, Xu Z, Barr SI, Innis SM, Kitts DD (2018) Variations in plasma choline and metabolite concentrations in healthy adults. Clin Biochem 60: 77–83. https://doi.org/10.1016/j.clinbiochem.2018.08.002

  45. Gossell-Williams M, Fletcher H, McFarlane-Anderson N, Jacob A, Patel J, Zeisel S (2005) Dietary intake of choline and plasma choline concentrations in pregnant women in Jamaica. West Indian Med J 54(6): 355–359. https://doi.org/10.1590/s0043-31442005000600002

  46. Holm PI, Ueland PM, Kvalheim G, Lien EA (2003) Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clin Chem 49: 286–294. https://doi.org/10.1373/49.2.286

  47. Mlodzik-Czyzewska MA, Malinowska AM, Szwengiel A, Chmurzynska A (2002) Associations of plasma betaine, plasma choline, choline intake, and MTHFR polymorphism (rs1801133) with anthropometric parameters of healthy adults are sex-dependent. J Hum Nutr Diet 35: 701– 712. https://doi.org/10.1111/jhn.13046

  48. Arias N, Arboleya S, Allison J, Kaliszewska A, Higarza SG, Gueimonde M, Arias JL (2020) The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases. Nutrients 12 (8): 2340. https://doi.org/10.3390/nu12082340

  49. Choline – dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline – NCBI bookshelf n.d.

  50. Siddiqui A, Shah Z, Jahan RN, Othman I, Kumari Y (2021) Mechanistic role of boswellic acids in Alzheimer’s disease: emphasis on anti-inflammatory properties. Biomed Pharmacother 144: 112250. https://doi.org/10.1016/J.BIOPHA.2021.112250

  51. Wu G, Zhang L, Li T, Zuniga A, Lopaschuk GD, Li L, Jacobs RL, Vance DE (2013) Choline supplementation promotes hepatic insulin resistance in phosphatidylethanolamine N-methyltransferase-deficient mice via increased glucagon action. J Biol Chem 288(2): 837–847. https://doi.org/10.1074/jbc.M112.415117

  52. Dibaba DT, Johnson KC, Kucharska-Newton AM, Meyer K, Zeisel SH, Bidulescu A (2020) The Association of Dietary Choline and Betaine with the Risk of Type 2 Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 43(11): 2840–2846. https://doi.org/10.2337/dc20-0733

  53. Danne O, Möckel M (2010) Choline in acute coronary syndrome: an emerging biomarker with implications for the integrated assessment of plaque vulnerability. Expert Rev Mol Diagnost 10(2): 159–171. https://doi.org/10.1586/erm.10.2

  54. Van Wijk N, Watkins C, Böhlke M, Maher T, Hageman R, Kamphuis P, Wurtman R (2012) Plasma choline concentration varies with different dietary levels of vitamins B6, B12 and folic acid in rats maintained on choline-adequate diets. Br J Nutrit 107(10): 1408–1412. https://doi.org/10.1017/S0007114511004570

  55. Nurk E, Refsum H, Bjelland I, Drevon CA, Tell GS, Ueland PM, Vollset SE, Engedal K, Nygaard HA, Smith DA (2013) Plasma free choline, betaine and cognitive performance: the Hordaland Health Study. Br J Nutrit 109(3): 511–519. https://doi.org/10.1017/S0007114512001249

  56. Øyen J, Gjesdal CG, Karlsson T, Svingen GF, Tell GS, Strand E, Drevon CA, Vinknes KJ, Meyer K, Ueland PM, Nygård O (2017) Dietary Choline Intake Is Directly Associated with Bone Mineral Density in the Hordaland Health Study. J Nutrition 147(4): 572–578. https://doi.org/10.3945/jn.116.243006

  57. Watson GA, Sanz-Garcia E, Zhang W-J, Liu ZA, Yang SC, Wang B, Liu S, Kubli S, Berman H, Pfister T, Genta S, Spreafico A, Hansen AR, Bedard PL, Lheureux S, Razak A, Cescon D, Butler MO, Xu W, Chen E (2022) Increase in serum choline levels predicts for improved progression-free survival (PFS) in patients with advanced cancers receiving pembrolizumab. J Immun Therapy Cancer 10(6): e004378 https://doi.org/10.1136/jitc-2021-004378

  58. Li S, Guo B, Song J, Deng X, Cong Y, Li P, Zhao K, Liu L, Xiao G, Xu F, Ye Y, Zhao Z, Yu M, Xu Y, Sang J, Zhang J (2012) Plasma choline-containing phospholipids: potential biomarkers for colorectal cancer progression. Metabolomics 9(1): 202–212. https://doi.org/10.1007/s11306-012-0439-z

  59. Mafra D, Cardozo L, Ribeiro-Alves M, Bergmane P, Shiels PG, Stenvinkel P (2022) Short Report: Choline plasma levels are related to Nrf2 transcriptional expression in chronic kidney disease? Clin Nutrition ESPEN 50: 318–321. https://doi.org/10.1016/j.clnesp.2022.06.008

  60. Schartum-Hansen H, Pedersen ER, Svingen GF, Ueland P M, Seifert R, Ebbing M, Strand E, Bleie Ø, Nygård O (2014) Plasma choline, smoking, and long-term prognosis in patients with stable angina pectoris. Eur J Prevent Cardiol 22(5): 606–614. https://doi.org/10.1177/2047487314524867

  61. Garbuzenko DV, Belov DV (2021) Non-alcoholic fatty liver disease as an independent factor of cardiometabolic risk of cardiovascular diseases. Exp Clin Gastroenterol 10: 22–34. https://doi.org/10.31146/1682-8658-ecg-194-10-22-34

  62. Ying J, Rahbar MH, Hallman DM, Hernandez LM, Spitz MR, Forman MR, Gorlova OY (2013) Associations between Dietary Intake of Choline and Betaine and Lung Cancer Risk. PLoS One 8(2): e54561. https://doi.org/10.1371/journal.pone.0054561

  63. Konstantinova SV, Tell GS, Vollset SE, Nygård O, Bleie Ø, Ueland PM (2008) Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women. J Nutr 138(5): 914–920. https://doi.org/10.1093/jn/138.5.914

  64. Park S, Choi SG, Yoo SM, Son JH, Jung YK (2014) Choline dehydrogenase interacts with SQSTM1/p62 to recruit LC3 and stimulate mitophagy. Autophagy 10(11): 1906–1920. https://doi.org/10.4161/auto.32177

  65. Wang, Z, Tang WHW, Buffa JA, Fu X, Britt EB, Koeth RA, Levison BS, Fan Y, Wu Y, Hazen SL (2014) Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J 35(14): 904–910. https://doi.org/10.1093/eurheartj/ehu002

  66. Zuo H, Svingen GFT, Tell GS, Ueland PM, Vollset SE, Pedersen ER, Ulvik A, Meyer K, Nordrehaug JE, Nilsen DWT, Bønaa KH, Nygård O (2018) Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association with Atrial Fibrillation Risk: Results From 3 Prospective Cohorts with Different Health Profiles. J Am Heart Assoc 7(8): e008190. https://doi.org/10.1161/jaha.117.008190

  67. Roe AJ, Zhang S, Bhadelia RA, Johnson EJ, Lichtenstein AH, Rogers GT, Rosenberg IH, Smith CE, Zeisel SH, Scott TM (2017) Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults. Am J Clin Nutr 105(6): 1283–1290. https://doi.org/10.3945/ajcn.116.137158

  68. Gessner A, di Giuseppe R, Koch M, Fromm MF, Lieb W, Maas R (2020) Trimethylamine-N-oxide (TMAO) determined by LC-MS/MS: distribution and correlates in the population-based PopGen cohort. Clin Chem Labor Med 58(5): 733–740. https://doi.org/10.1515/cclm-2019-1146

  69. Cho CE, Aardema NDJ, Bunnell ML, Larson DP, Aguilar SS, Bergeson JR, Malysheva OV, Caudill MA, Lefevre M (2020) Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men. Nutrients 12(8): 2220. https://doi.org/10.3390/nu12082220

  70. Rahimi P, Joseph Y (2019) Enzyme-based biosensors for choline analysis: A review. Trends Analyt Chem 110: 367–374. https://doi.org/10.1016/j.trac.2018.11.035

  71. Saucerman JR, Winstead CE, Jones TM (1984) Quantitative Gas Chromatographic Headspace Determination of Choline in Adult and Infant Formula Products. J Assoc Anal Chem 67(5): 982–985. https://doi.org/10.1093/jaoac/67.5.982

  72. Zhang L, LiuY, Chen G (2004) Simultaneous determination of allantoin, choline and l-arginine in Rhizoma Dioscoreae by capillary electrophoresis. J Chromat A 1043(2): 317–321. https://doi.org/10.1016/j.chroma.2004.06.003

  73. Lin L, Li R, Wang L, Qiu Y (2018) Determination of choline, putrescine and cadaverine in boletus by ion chromatography with suppressed conductivity detection. Chin J Chromat 36(11): 1189. https://doi.org/10.3724/sp.j.1123.2018.06027

  74. Shadlaghani A, Farzaneh M, Kinser D, Reid RC (2019) Direct Electrochemical Detection of Glutamate, Acetylcholine, Choline, and Adenosine Using Non-Enzymatic Electrodes. Sensors 19(3): 447. https://doi.org/10.3390/s19030447

  75. Garcia E, Shalaurova I, Matyus SP, Wolak-Dinsmore J, Oskardmay DN, Connelly MA (2022) Quantification of choline in serum and plasma using a clinical nuclear magnetic resonance analyzer. Clin Chim Acta 524: 106–112. https://doi.org/10.1016/j.cca.2021.11.031

  76. Ocque AJ, Stubbs JR, Nolin TD (2015) Development and validation of a simple UHPLC-MS/MS method for the simultaneous determination of trimethylamine N-oxide, choline, and betaine in human plasma and urine. J Pharm Biomed Anal 109: 128–135. https://doi.org/10.1016/j.jpba.2015.02.040

  77. Rox K, Rath S, Pieper DH, Vital M, Brönstrup M (2021) A simplified LC-MS/MS method for the quantification of the cardiovascular disease (CVD) biomarker trimethylamine-Noxide (TMAO) and its precursors. J Pharm Anal 11(4): 523–528. https://doi.org/10.1016/j.jpha.2021.03.007

  78. Garcia E, Shalaurova I, Matyus SP, Wolak-Dinsmore J, Oskardmay DN, Connelly MA (2022) Quantification of choline in serum and plasma using a clinical nuclear magnetic resonance analyzer. Clin Chim Acta 524: 106–112. https://doi.org/10.1016/j.cca.2021.11.031

  79. Awwad HM, Kirsch SH, Geise J, Obeid R (2014) Measurement of concentrations of whole blood levels of choline, betaine, and dimethylglycine and their relations to plasma levels. J Chromat B 957: 41–45. https://doi.org/10.1016/j.jchromb.2014.02.030

  80. Yue B, Pattison E, Roberts WL, Rockwood AL, Danne O, Lueders C, Möckel M (2008) Choline in Whole Blood and Plasma: Sample Preparation and Stability. Clin Chem 54(3): 590–593. https://doi.org/10.1373/clinchem.2007.094201

  81. Kaplan A (2021) Preparation, Storage, and Characteristics of Whole Blood, Blood Components, and Plasma Derivatives. Transfus Med 11: 59–89. https://doi.org/10.1002/9781119599586.ch5

  82. Ohkawa R, Kurano M, Sakai N, Kishimoto T, Nojiri T, Igarashi K, Hosogaya S, Ozaki Y, Dohi T, Miyauchi K, Daida H, Aoki J, Okubo S, Ikeda H, Tozuka M, Yatomi Y (2018) Measurement of plasma choline in acute coronary syndrome: importance of suitable sampling conditions for this assay. Scient Rep 8(1): 4725. https://doi.org/10.1038/s41598-018-23009-x

  83. Burdeynaya AL, Afanasyeva OI, Klesareva EA, Tmoyan NA, Razova OA, Afanasyeva MI, Ezhov MV, Pokrovsky SN (2021) Role of inflammation, autotaxin and lipoprotein (a) in degenerative aortic valve stenosis in patients with coronary artery disease. Cardiovasc Ther Prevent 20(2): 2598. https://doi.org/10.15829/1728-8800-2021-2598

  84. Klatt KC (2023) Choline and phosphatidylcholine. Encycloped Human Nutrit 162–174. https://doi.org/10.1016/b978-0-12-821848-8.00020-2

  85. Liu L, Jin X, Wu Y, Yang M, Xu T, Li X, Ren J, Yan LL (2020) A Novel Dried Blood Spot Detection Strategy for Characterizing Cardiovascular Diseases. Front Cardiovasc Med 7: 542519. https://doi.org/10.3389/fcvm.2020.542519

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