Startseite Medizin Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers
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Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers

  • Apolline Imbard EMAIL logo , Yvo M. Smulders , Rob Barto , Desiree E.C. Smith , Robert M. Kok , Cornelis Jakobs und Henk J. Blom
Veröffentlicht/Copyright: 12. September 2012

Abstract

Background: Choline is essential for mammalian cell function. It plays a critical role in cell membrane integrity, neurotransmission, cell signaling and lipid metabolism. Moreover, choline is involved in methylation in two ways: a) its synthesis requires methyl groups donated by S-adenosyl-methionine (AdoMet); and b) choline oxidation product betaine methylates homocysteine (Hcy) to methionine (Met) and produces dimethylglycine. This later donates one carbon units to tetrahydrofolate (THF).

Methods: To evaluate the correlations of choline and betaine with folate, AdoMet, S-anenosyl-homocysteine (AdoHcy), total homocysteine (tHcy), and DNA methylation, choline, betaine and dimethylglycine were measured by LC-MS/MS in plasma of 109 healthy volunteers, in whom folate, AdoMet, AdoHcy, tHcy, and DNA methylation have previously been reported.

Results: Using a bivariate model, choline and betaine showed strong positive correlations with folate (r=0.346 and r=0.226), AdoHcy (r=0.468 and r=0.296), and correlated negatively with AdoMet/AdoHcy ratio (r=–0.246 and r=–0.379). Only choline was positively correlated with AdoMet (r=0.453). Using a multivariate linear regression model, choline correlated strongly with folate (β=17.416), AdoMet (β=61.272), and AdoHcy (β=9.215). Betaine correlated positively with folate (β=0.133) and negatively with tHcy (β=–0.194) ratio. Choline is an integral part of folate and methylation pathways.

Conclusions: Our data highlight the importance of integrating choline in studies concerning addressing pathological conditions related to folate, homocysteine and methylation metabolism.


Corresponding author: Apolline Imbard, Biochemistry-Hormonology Laboratory, Robert Debré Hospital, 48 Boulevard Serurier, 75019 Paris, France Phone: +33 01 40034722, Fax: +33 01 40034790

The authors would like to thank the volunteers from the hospital personnel for their participation in this study.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Zeisel SH. Choline: an essential nutrient for humans. Nutrition 2000;16:669–71.10.1016/S0899-9007(00)00349-XSuche in Google Scholar

2. Savendahl L, Mar MH, Underwood LE, Zeisel SH. Prolonged fasting in humans results in diminished plasma choline concentrations but does not cause liver dysfunction. Am J Clin Nutr 1997;66:622–5.10.1093/ajcn/66.3.622Suche in Google Scholar PubMed

3. Compher CW, Kinosian BP, Stoner NE, Lentine DC, Buzby GP. Choline and vitamin B12 deficiencies are interrelated in folate-replete long-term total parenteral nutrition patients. JPEN J Parenter Enteral Nutr 2002;26:57–62.10.1177/014860710202600157Suche in Google Scholar PubMed

4. Innis SM, Hasman D. Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis. J Nutr 2006;136:2226–31.10.1093/jn/136.8.2226Suche in Google Scholar PubMed

5. da Costa KA, Badea M, Fischer LM, Zeisel SH. Elevated serum creatine phosphokinase in choline-deficient humans: mechanistic studies in C2C12 mouse myoblasts. Am J Clin Nutr 2004;80:163–70.10.1093/ajcn/80.1.163Suche in Google Scholar PubMed

6. Medicine Io. Dietary reference intakes for folate, thiamin, riboflavin, niacin, vitamin B12, panthothenic acid, biotin, and choline. 1998;1:390–422.Suche in Google Scholar

7. Fischer LM, daCosta KA, Kwock L, Stewart PW, Lu TS, Stabler SP, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr 2007;85:1275–85.10.1093/ajcn/85.5.1275Suche in Google Scholar PubMed PubMed Central

8. Velzing-Aarts FV, Holm PI, Fokkema MR, van der Dijs FP, Ueland PM, Muskiet FA. Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy. Am J Clin Nutr 2005;81:1383–9.10.1093/ajcn/81.6.1383Suche in Google Scholar PubMed

9. Zeisel SH. Importance of methyl donors during reproduction. Am J Clin Nutr 2009;89:673S–7S.10.3945/ajcn.2008.26811DSuche in Google Scholar PubMed PubMed Central

10. Shaw GM, Finnell RH, Blom HJ, Carmichael SL, Vollset SE, Yang W, et al. Choline and risk of neural tube defects in a folate-fortified population. Epidemiology 2009;20:714–9.10.1097/EDE.0b013e3181ac9fe7Suche in Google Scholar PubMed

11. Rogers AE. Methyl donors in the diet and responses to chemical carcinogens. Am J Clin Nutr 1995;61:659S–65S.10.1093/ajcn/61.3.659SSuche in Google Scholar PubMed

12. Park CS, Cho K, Bae DR, Joo NE, Kim HH, Mabasa L, et al. Methyl-donor nutrients inhibit breast cancer cell growth. In Vitro Cell Dev Biol Anim 2008;44:268–72.10.1007/s11626-008-9096-ySuche in Google Scholar PubMed

13. Niculescu MD, Yamamuro Y, Zeisel SH. Choline availability modulates human neuroblastoma cell proliferation and alters the methylation of the promoter region of the cyclin-dependent kinase inhibitor 3 gene. J Neurochem 2004;89:1252–9.10.1111/j.1471-4159.2004.02414.xSuche in Google Scholar PubMed PubMed Central

14. Xu X, Gammon MD, Zeisel SH, Bradshaw PT, Wetmur JG, Teitelbaum SL, et al. High intakes of choline and betaine reduce breast cancer mortality in a population-based study. FASEB J 2009;23:4022–8.10.1096/fj.09-136507Suche in Google Scholar PubMed PubMed Central

15. da Costa KA, Niculescu MD, Craciunescu CN, Fischer LM, Zeisel SH. Choline deficiency increases lymphocyte apoptosis and DNA damage in humans. Am J Clin Nutr 2006;84:88–94.10.1093/ajcn/84.1.88Suche in Google Scholar PubMed PubMed Central

16. Ueland PM. Choline and betaine in health and disease. J Inherit Metab Dis 2011;34:3–15.10.1007/s10545-010-9088-4Suche in Google Scholar PubMed

17. Li Z, Vance DE. Phosphatidylcholine and choline homeostasis. J Lipid Res 2008;49:1187–94.10.1194/jlr.R700019-JLR200Suche in Google Scholar PubMed

18. Kim YI, Miller JW, da Costa KA, Nadeau M, Smith D, Selhub J, et al. Severe folate deficiency causes secondary depletion of choline and phosphocholine in rat liver. J Nutr 1994;124:2197–203.10.1093/jn/124.11.2197Suche in Google Scholar PubMed

19. Horne DW, Cook RJ, Wagner C. Effect of dietary methyl group deficiency on folate metabolism in rats. J Nutr 1989;119:618–21.10.1093/jn/119.4.618Suche in Google Scholar PubMed

20. Zeisel SH, Zola T, daCosta KA, Pomfret EA. Effect of choline deficiency on S-adenosylmethionine and methionine concentrations in rat liver. Biochem J 1989;1;259:725–9.10.1042/bj2590725Suche in Google Scholar PubMed PubMed Central

21. Holm PI, Ueland PM, Kvalheim G, Lien EA. Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clin Chem 2003;49:286–94.10.1373/49.2.286Suche in Google Scholar PubMed

22. Melse-Boonstra A, Holm PI, Ueland PM, Olthof M, Clarke R, Verhoef P. Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations. Am J Clin Nutr 2005;81:1378–82.10.1093/ajcn/81.6.1378Suche in Google Scholar

23. Holm PI, Bleie O, Ueland PM, Lien EA, Refsum H, Nordrehaug JE, et al. Betaine as a determinant of postmethionine load total plasma homocysteine before and after B-vitamin supplementation. Arterioscler Thromb Vasc Biol 2004;24:301–7.10.1161/01.ATV.0000114569.54976.31Suche in Google Scholar

24. Smulders YM, Smith DE, Kok RM, Teerlink T, Gellekink H, Vaes WH, et al. Red blood cell folate vitamer distribution in healthy subjects is determined by the methylenetetrahydrofolate reductase C677T polymorphism and by the total folate status. J Nutr Biochem 2007;18:693–9.10.1016/j.jnutbio.2006.11.010Suche in Google Scholar

25. Struys EA, Jansen EE, de Meer K, Jakobs C. Determination of S-adenosylmethionine and S-adenosylhomocysteine in plasma and cerebrospinal fluid by stable-isotope dilution tandem mass spectrometry. Clin Chem 2000;46:1650–6.10.1093/clinchem/46.10.1650Suche in Google Scholar

26. Kok RM, Smith DE, Barto R, Spijkerman AM, Teerlink T, Gellekink HJ, et al. Global DNA methylation measured by liquid chromatography-tandem mass spectrometry: analytical technique, reference values and determinants in healthy subjects. Clin Chem Lab Med 2007;45:903–11.10.1515/CCLM.2007.137Suche in Google Scholar

27. Green S. How many subjects does it take to do a regression analysis? Multivar Behav Res 1991;26:499–510.10.1207/s15327906mbr2603_7Suche in Google Scholar

28. 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;20:62–9.10.1016/j.jnutbio.2007.12.002Suche in Google Scholar

29. Allen RH, Stabler SP, Lindenbaum J. Serum betaine, N,N-dimethylglycine and N-methylglycine levels in patients with cobalamin and folate deficiency and related inborn errors of metabolism. Metabolism 1993;42:1448–60.10.1016/0026-0495(93)90198-WSuche in Google Scholar

30. Konstantinova SV, Tell GS, Vollset SE, Nygard O, Bleie O, Ueland PM. Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women. J Nutr 2008;138:914–20.10.1093/jn/138.5.914Suche in Google Scholar PubMed

31. Lever M, Slow S. The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clin Biochem 2010;43:732–44.10.1016/j.clinbiochem.2010.03.009Suche in Google Scholar PubMed

32. Lever M, Sizeland PC, Frampton CM, Chambers ST. Short and long-term variation of plasma glycine betaine concentrations in humans. Clin Biochem 2004;37:184–90.10.1016/j.clinbiochem.2003.11.004Suche in Google Scholar PubMed

33. McGregor DO, Dellow WJ, Lever M, George PM, Robson RA, Chambers ST. Dimethylglycine accumulates in uremia and predicts elevated plasma homocysteine concentrations. Kidney Int 2001;59:2267–72.10.1046/j.1523-1755.2001.00743.xSuche in Google Scholar PubMed

34. Chiuve SE, Giovannucci EL, Hankinson SE, Zeisel SH, Dougherty LW, Willett WC, et al. The association between betaine and choline intakes and the plasma concentrations of homocysteine in women. Am J Clin Nutr 2007;86:1073–81.10.1093/ajcn/86.4.1073Suche in Google Scholar PubMed PubMed Central

35. Cho E, Zeisel SH, Jacques P, Selhub J, Dougherty L, Colditz GA, et al. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr 2006;83:905–11.10.1093/ajcn/83.4.905Suche in Google Scholar PubMed PubMed Central

36. Molloy AM, Mills JL, Cox C, Daly SF, Conley M, Brody LC, et al. Choline and homocysteine interrelations in umbilical cord and maternal plasma at delivery. Am J Clin Nutr 2005;82:836–42.10.1093/ajcn/82.4.836Suche in Google Scholar PubMed

37. Abratte CM, Wang W, Li R, Moriarty DJ, Caudill MA. Folate intake and the MTHFR C677T genotype influence choline status in young Mexican American women. J Nutr Biochem 2008;19:158–65.10.1016/j.jnutbio.2007.02.004Suche in Google Scholar PubMed PubMed Central

38. Jacob RA, Jenden DJ, Allman-Farinelli MA, Swendseid ME. Folate nutriture alters choline status of women and men fed low choline diets. J Nutr 1999;129:712–7.10.1093/jn/129.3.712Suche in Google Scholar PubMed

39. Craciunescu CN, Johnson AR, Zeisel SH. Dietary choline reverses some, but not all, effects of folate deficiency on neurogenesis and apoptosis in fetal mouse brain. J Nutr 2010;140:1162–6.10.3945/jn.110.122044Suche in Google Scholar PubMed PubMed Central

40. Finkelstein JD. Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine. Clin Chem Lab Med 2007;45:1694–9.10.1515/CCLM.2007.341Suche in Google Scholar PubMed

41. Cook RJ, Horne DW, Wagner C. Effect of dietary methyl group deficiency on one-carbon metabolism in rats. J Nutr 1989;119:612–7.10.1093/jn/119.4.612Suche in Google Scholar PubMed

42. Caudill MA, Dellschaft N, Solis C, Hinkis S, Ivanov AA, Nash-Barboza S, et al. Choline intake, plasma riboflavin, and the phosphatidylethanolamine N-methyltransferase G5465A genotype predict plasma homocysteine in folate-deplete Mexican-American men with the methylenetetrahydrofolate reductase 677TT genotype. J Nutr 2009;139:727–33.10.3945/jn.108.100222Suche in Google Scholar PubMed PubMed Central

43. Veenema K, Solis C, Li R, Wang W, Maletz CV, Abratte CM, et al. Adequate intake levels of choline are sufficient for preventing elevations in serum markers of liver dysfunction in Mexican American men but are not optimal for minimizing plasma total homocysteine increases after a methionine load. Am J Clin Nutr 2008;88:685–92.10.1093/ajcn/88.3.685Suche in Google Scholar PubMed PubMed Central

44. Setoue M, Ohuchi S, Morita T, Sugiyama K. Choline deprivation induces hyperhomocysteinemia in rats fed low methionine diets. J Nutr Sci Vitaminol (Tokyo) 2008;54:483–90.10.3177/jnsv.54.483Suche in Google Scholar PubMed

45. Noga AA, Stead LM, Zhao Y, Brosnan ME, Brosnan JT, Vance DE. Plasma homocysteine is regulated by phospholipid methylation. J Biol Chem 2003;278:5952–5.10.1074/jbc.M212194200Suche in Google Scholar PubMed

46. Jacobs RL, Stead LM, Devlin C, Tabas I, Brosnan ME, Brosnan JT, et al. Physiological regulation of phospholipid methylation alters plasma homocysteine in mice. J Biol Chem 2005;280:28299–305.10.1074/jbc.M501971200Suche in Google Scholar PubMed

47. Craig SA. Betaine in human nutrition. Am J Clin Nutr [Review] 2004;80:539–49.10.1093/ajcn/80.3.539Suche in Google Scholar PubMed

48. Holm PI, Ueland PM, Vollset SE, Midttun O, Blom HJ, Keijzer MB, et al. Betaine and folate status as cooperative determinants of plasma homocysteine in humans. Arterioscler Thromb Vasc Biol 2005;25:379–85.10.1161/01.ATV.0000151283.33976.e6Suche in Google Scholar PubMed

49. Lever M, George PM, Dellow WJ, Scott RS, Chambers ST. Homocysteine, glycine betaine, and N,N-dimethylglycine in patients attending a lipid clinic. Metabolism 2005;54:1–14.10.1016/j.metabol.2004.07.007Suche in Google Scholar PubMed

50. Kerins DM, Koury MJ, Capdevila A, Rana S, Wagner C. Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine. Am J Clin Nutr 2001;74:723–9.10.1093/ajcn/74.6.723Suche in Google Scholar PubMed

Received: 2012-5-13
Accepted: 2012-8-18
Published Online: 2012-09-12
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

Artikel in diesem Heft

  1. Masthead
  2. Masthead
  3. Editorial
  4. Special issue on advances and controversies in B vitamins and choline
  5. Reviews
  6. B-Vitamin dependent methionine metabolism and alcoholic liver disease
  7. Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis
  8. Proteomics of vitamin B12 processing
  9. Unexpected high plasma cobalamin/Proposal for a diagnostic strategy
  10. Clinical recognition and aspects of the cerebral folate deficiency syndromes
  11. Choline-containing phospholipids: relevance to brain functional pathways
  12. The ‘golden age’ of DNA methylation in neurodegenerative diseases
  13. Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease
  14. The diagnostic utility of folate receptor autoantibodies in blood
  15. Red cell or serum folate: what to do in clinical practice?
  16. Formate: an essential metabolite, a biomarker, or more?
  17. The role of homocysteine in bone remodeling
  18. Mini Reviews
  19. Neuroprotective actions of perinatal choline nutrition
  20. Normal prions as a new target of cobalamin (vitamin B12) in rat central nervous system
  21. Molecular mechanisms underlying the potentially adverse effects of folate
  22. Betaine homocysteine methyltransferase (BHMT)-dependent remethylation pathway in human healthy and tumoral liver
  23. Hydrogen sulfide as an oxygen sensor
  24. Opinion Paper
  25. B vitamin therapy for homocysteine: renal function and vitamin B12 determine cardiovascular outcomes
  26. Research Articles
  27. One year B and D vitamins supplementation improves metabolic bone markers
  28. Effect of 1 year B and D vitamin supplementation on LINE-1 repetitive element methylation in older subjects
  29. Aqueous humor glycation marker and plasma homocysteine in macular degeneration
  30. Homocysteine plasma levels in patients treated with antiepileptic drugs depend on folate and vitamin B12 serum levels, but not on genetic variants of homocysteine metabolism
  31. Trends in clinical laboratory homocysteine testing from 1997 to 2010: the impact of evidence on clinical practice at a single institution
  32. Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320)
  33. Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers
  34. Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain
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