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Clinical Chemistry and Laboratory Medicine (CCLM)

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Volume 43, Issue 10


Betaine: a key modulator of one-carbon metabolism and homocysteine status

Per Magne Ueland
  • LOCUS for Homocysteine and Related Vitamins, Institute of Medicine, University of Bergen, Bergen, Norway
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Pål I. Holm
  • LOCUS for Homocysteine and Related Vitamins, Institute of Medicine, University of Bergen, Bergen, Norway
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Steinar Hustad
  • LOCUS for Homocysteine and Related Vitamins, Institute of Medicine, University of Bergen, Bergen, Norway
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2011-09-21 | DOI: https://doi.org/10.1515/CCLM.2005.187


Betaine serves as a methyl donor in a reaction converting homocysteine to methionine, catalysed by the enzyme betaine-homocysteine methyltransferase. It has been used for years to lower the concentration of plasma total homocysteine (tHcy) in patients with homocystinuria, and has recently been shown to reduce fasting and in particular post-methionine load (PML) tHcy in healthy subjects.

Betaine exists in plasma at concentrations of about 30μmol/L; it varies 10-fold (from 9 to 90μmol/L) between individuals, but the intra-individual variability is small. Major determinants are choline, dimethylglycine and folate in plasma, folic acid intake and gender.

Recent studies have demonstrated that plasma betaine is a stronger determinant of PML tHcy than are vitamin B6 and folate. The betaine-PML tHcy relationship is attenuated after supplementation with B-vitamins, and is most pronounced in subjects with low folate. Betaine shows a weaker association with fasting tHcy (than with PML tHcy), and also this association is most pronounced in subjects with low folate. In pregnancy, plasma betaine declines until gestational week 20, and thereafter remains constant. From gestational week 20 onwards, fasting tHcy shows a strong inverse association with plasma betaine, and betaine becomes a stronger predictor than folate of fasting tHcy.

To conclude, betaine status is a component of an individual's biochemical make-up with ramifications to one-carbon metabolism. Betaine status should be investigated in pathologies related to altered metabolism of homocysteine and folate, including cardiovascular disease, cancer and neural tube defects.

Keywords: betaine; choline; dimethylglycine; folate; homocysteine


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About the article

Corresponding author: Dr. Per Magne Ueland, LOCUS for Homocysteine and Related Vitamins, Armauer Hansens hus, University of Bergen, 5021 Bergen, Norway Phone: +47-5597-3147, Fax: +47-5597-4605,

Published Online: 2011-09-21

Published in Print: 2005-10-01

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 43, Issue 10, Pages 1069–1075, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2005.187.

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