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

Abstract

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 30 micromol/L; it varies 10-fold (from 9 to 90 micromol/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.

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives

“…As Hcy generation is linked to the methylation of exogenous and endogenous substrates (Figure 1), the development of Hcy-related CVD may involve the metabolism of exogenous/endogenous methyl-accepting (consuming) substrates. Indeed, the present study found that nicotinamide load significantly increased the levels of plasma Hcy and decreased the levels of plasma betaine, a major labile methyl donor, 12 in normotensives. This finding, together with the observations that hypertensives had higher fasting plasma Hcy and nicotinamide levels, suggests that frequent high nicotinamide intake may be a risk factor for hyperhomocysteinemia.…”

“…The plasma Hcy levels were increased in both normotensives and hypertensives 5 h after nicotinamide loading (Po0.05 and P¼0.14, respectively; Figure 3a). The baseline levels of plasma betaine, a major labile methyl donor, 12 were slightly lower in hypertensives than in normotensives, but there was no statistically significant difference.…”

Nonsynonymous Polymorphisms in Genes in the One-Carbon Metabolism Pathway and Associations with Colorectal Cancer

“…However, it is possible that the observed associations reflect the influence of these genes on DNA methylation. Both BHMT and MTRR are involved in maintaining cellular levels of methionine; BHMT catalyzes the re-methylation of homocysteine to methionine, predominantly in the liver and kidney (49), whereas MTRR activates MTR, which also catalyzes the re-methylation of homocysteine to methionine in various tissues. (50,51) and spina bifida (52) associated with Gln/Gln versus Arg/Arg at BHMT codon 239 have been suggested among three previous studies.…”

Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas

“…Because smoking is known to be associated with compromised folate status, this suggests an increased importance of alternative methyl group donors under folate deficient conditions, which for example has been shown for betaine (42,43) and may also apply to methionine and choline. In addition, smoking has been associated with lower circulating concentrations of vitamin B2 and B6 (44).…”