The association between betaine and choline intakes and the plasma concentrations of homocysteine in women

Abstract

Background: Elevated total homocysteine (tHcy), a risk factor for many chronic diseases, can be remethylated to methionine by folate. Alternatively, tHcy can be metabolized by other 1-carbon nutrients, ie, betaine and its precursor, choline.

Objective: We aimed to assess the association between the dietary intakes of betaine and choline and the concentration of tHcy.

Design: We conducted a cross-sectional analysis in 1477 women by using linear regression models to predict mean fasting tHcy by intakes of of betaine and choline.

Results: tHcy was 8% lower in the highest quintile of total betaine + choline intake than in the lowest quintile, even after control for folate intake (P for trend = 0.07). Neither choline nor betaine intake individually was significantly associated with tHcy. Choline from 2 choline-containing compounds, glycerophosphocholine and phosphocholine, was inversely associated with tHcy. These inverse associations were more pronounced in women with folate intake < 400 mug/d than in those with intakes >or=400 microg/d (P for interaction = 0.03 for phosphocholine) and in moderate alcohol drinkers (>or=15 g/d) than in nondrinkers or light drinkers (<15 g/d) (P for interaction = 0.02 for glycerophosphocholine and 0.04 for phosphocholine). The strongest dose response was seen in women with a low-methyl diet (high alcohol and low folate intake) (P for interaction = 0.002 for glycerophosphocholine and 0.001 for phosphocholine).

Conclusions: Total choline + betaine intake was inversely associated with tHcy, as was choline from 2 water-soluble choline-containing compounds. Remethylation of tHcy may be more dependent on the betaine pathway when methyl sources are low as a result of either inadequate folate intake or heavier alcohol consumption.

FIGURE 1

Homocysteine remethylation by the folate and betaine pathways. THF, tetrahydrofolate; MTHFR, methylenetetrahydrofolate reductase; MTR, methionine synthase reductase; BHMT, betaine-homocysteine methyltransferase; DMG, dimethylglycine. Dietary folate can be converted into THF, which is metabolized by the MTHFR enzyme into 5,10-MTHF. In this form, folate can serve as a methyl donor to homocysteine by the MTR enzyme and its cofactor vitamin B-12. In this process, methionine is formed and 5,10-MTHF is metabolized back to THF, which may reenter the metabolic cycle. Betaine, which is obtained directly in the diet or through oxidation of dietary choline, can remethylate homocysteine with the BHMT enzyme, forming DMG as a byproduct.

FIGURE 2

Adjusted mean plasma total homocysteine (tHcy) among 1477 women according to quintiles of energy-adjusted glycerophosphocholine and phosphocholine intake by methyl diet status (◆, high-methyl diet: 0 g/d alcohol + ≥400 μg/d folate; n = 227; ■, intermediate-methyl diet, n = 1126; ▲, low-methyl diet: ≥15 g/d alcohol + < 400 μg/d folate; n = 82). Mean tHcy values were calculated by linear regression models adjusted for age, smoking status, menopausal status, laboratory batch, coffee, total calories, and intakes of methionine and riboflavin. The SEs of mean tHcy within quintiles of glycerophosphocholine intake ranged from 0.4 to 0.6 for a high-methyl diet, from 0.2 to 0.3 for an intermediate-methyl diet, and from 1.3 to 2.8 for a low-methyl diet. The SEs of mean tHcy within quintiles of phosphocholine intake ranged from 0.4 to 0.6 for a high-methyl diet, from 0.2 to 0.4 for an intermediate-methyl diet, and from 1.0 to 3.0 for a low-methyl diet. Methyl diet status (in 3 categories) × glycerophosphocholine (continuous variable using median of quintiles) interaction, P = 0.002. Methyl diet status (in 3 categories) × phosphocholine (continuous variable using median of quintiles) interaction, P = 0.001. *Significantly different from the first quintile of the choline-containing compound within the low-methyl diet group based on linear regression models, P < 0.05 (Wald test).