Choline supplementation and measures of choline and betaine status: a randomised, controlled trial in postmenopausal women

Abstract

Choline is an essential nutrient and can also be obtained by de novo synthesis via an oestrogen responsive pathway. Choline can be oxidised to the methyl donor betaine, with short-term supplementation reported to lower plasma total homocysteine (tHcy); however, the effects of longer-term choline supplementation are less clear. We investigated the effect of choline supplementation on plasma concentrations of free choline, betaine and tHcy and B-vitamin status in postmenopausal women, a group more susceptible to low choline status. We also assessed whether supplementation altered plasma lipid profiles. In this randomised, double-blinded, placebo-controlled study, forty-two healthy postmenopausal women received 1 g choline per d (as choline bitartrate), or an identical placebo supplement with their habitual diet. Fasting blood samples were collected at baseline, week 6 and week 12. Administration of choline increased median choline and betaine concentrations in plasma, with significant effects evident after 6 weeks of supplementation (P,0·001) and remaining significant at 12 weeks (P,0·001); no effect was observed on folate status or on plasma lipids. Choline supplementation induced a median (25th, 75th percentile) change in plasma tHcy concentration at week 6 of 20·9 (21·6, 0·2) mmol, a change which, when compared to that observed in the placebo group 0·6 (2 0·4, 1·9) mmol, approached statistical significance (P¼ 0·058). Choline supplementation at a dose of 1 g/d significantly increases the circulating concentration of free choline, and can also significantly increase the concentration of the methyl donor, betaine, thereby potentially enhancing the betaine -homocysteine methyltransferase-mediated remethylation of tHcy. This trial was registered at http://www.controlled-trials.com/ISRCTN82708510.

Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults,

“…Higher betaine concentrations were associated with a favorable risk-factor profile, and higher choline concentrations were associated with an unfavorable risk-factor profile (8). Plasma choline and betaine concentrations were comparable with those previously reported (8,(19)(20)(21)(22). Compared with the overall US population aged $65 y, the NAME population has a higher percentage of women, more college graduates, higher prevalences of diabetes and hypertension, and higher reported current alcohol consumption and cigarette use (23).…”

The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway

“…The flow of methyl groups via the BHMT pathway is not dependent on folate or vitamin B12, but there are several cross-talk mechanisms between the BHMT and the folate pathways. Choline has been shown to indirectly support homocysteine methylation [15]. One study of postmenopausal women showed that choline supplementation increased plasma betaine levels and slightly lowered plasma levels of total homocysteine (tHcy) after six weeks (median change, −0.9 vs. +0.6 μmol/L in the placebo group: p = 0.058) and 12 weeks [15].…”

“…Choline has been shown to indirectly support homocysteine methylation [15]. One study of postmenopausal women showed that choline supplementation increased plasma betaine levels and slightly lowered plasma levels of total homocysteine (tHcy) after six weeks (median change, −0.9 vs. +0.6 μmol/L in the placebo group: p = 0.058) and 12 weeks [15]. Sex- and age-related differences in choline requirements and blood levels have been reported.…”

Role of fatty acids and micronutrients in healthy ageing: a systematic review of randomised controlled trials set in the context of European dietary surveys of older adults

“…The findings from a 4-month RCT showed that women taking 20 lg HyD had significantly (À5.7 mmHg) lower blood pressure (P = 0.0002) (77) . In relation to choline supplementation, a 12-week trial recruiting 42 post-menopausal women found that 1 g of choline daily led to reduction in plasma homocysteine levels that approached statistical significance (P = 0.058) (86) . Finally, a 3-year follow-up study comprising 388 healthy adults showed that those with a history of coronary artery disease receiving 500 lg of phylloquinine daily had 6% less progression compared to those taking a standard multivitamin (P = 0.04) (74) .…”