Homocysteine is a metabolite of the essential amino acid methionine which can build up in cells and plasma if nutrition quality is low. High concentrations of plasma homocysteine are linked to an increased risk of cardiovascular disease and dementia, because elevated homocysteine can damage the endothelial lining of blood vessels. Folate, vitamin B12 and vitamin B6 are able to reduce cellular and plasma levels of homocysteine because they act as co-factors for enzymes that metabolise homocysteine back to methionine (methionine transferase: requires vitamin B12 and folate) or to cystathionine (cystathionine β-synthase: required vitamin B6). Homocysteine can also be metabolised back to methionine using an alternative pathway that involved the transfer of a methyl group from the compound betaine, via the enzyme betaine methyl transferase. However, little is known about the effects of betaine intake, and its precursor choline, on plasma levels of homocysteine.
Researchers1 have investigated the associations between betaine-plus-choline intake and plasma levels of homocysteine under both fasting conditions and following a methionine load. Intakes of choline-plus-betaine were assessed in 2732 healthy volunteers using food-frequency questionnaires and homocysteine concentrations in plasma were assessed via a blood sample. Subjects were assessed before and after mandatory folate fortification of flour (1996). The results showed that higher intakes of choline-plus-betaine were inversely associated with fasting and post-methionine load plasma homocysteine concentrations. Those in the top quintile of choline-plus-betaine intake had mean plasma homocysteine concentrations of 24.1 µmol/L, compared to 25 µmol/L in the lowest quintile of intake. When plasma folate and vitamin B12 concentrations were taken into account, betaine and choline was only inversely associated with homocysteine concentrations with the lowest intakes of the vitamins.
These results are interesting because they suggest that higher intakes of betaine are inversely associated with plasma homocysteine levels and that this inverse association also applies to the betaine precursor, choline. Post folate fortification, the inverse association was not observed, suggesting that the folate was effective at lowering the homocysteine concentrations in plasma. These results support previous findings that show beneficial effects of folate, vitamin B6, vitamin B12 and betaine on plasma homocysteine concentrations. The inverse association between betaine and choline with plasma homocysteine was particularly strong in those subjects that consumed alcohol and had low folate plasma concentrations. Rats fed a folate diet show reductions in liver choline levels, which suggests that in the absence of available folate, choline and betaine are used to metabolise homocysteine. Beets and spinach are rich sources of betaine.
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