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Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans.

Olthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB - PLoS Med. (2005)

Bottom Line: Previous studies of phosphatidylcholine and blood lipids showed no clear effect.Thus the effect of phosphatidylcholine supplementation on blood lipids remains inconclusive, but is probably not large.Folic acid supplementation does not seem to affect blood lipids and therefore remains the preferred treatment for lowering of blood homocysteine concentrations.

View Article: PubMed Central - PubMed

Affiliation: Wageningen Centre for Food Sciences, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands. margreet.olthof@wur.nl

ABSTRACT

Background: Betaine (trimethylglycine) lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals are lacking. Such an effect on cholesterol would counteract any favourable effect on homocysteine. We therefore investigated the effect of betaine, of its precursor choline in the form of phosphatidylcholine, and of the classical homocysteine-lowering vitamin folic acid on blood lipid concentrations in healthy humans.

Methods and findings: We measured blood lipids in four placebo-controlled, randomised intervention studies that examined the effect of betaine (three studies, n = 151), folic acid (two studies, n = 75), and phosphatidylcholine (one study, n = 26) on plasma homocysteine concentrations. We combined blood lipid data from the individual studies and calculated a weighted mean change in blood lipid concentrations relative to placebo. Betaine supplementation (6 g/d) for 6 wk increased blood LDL cholesterol concentrations by 0.36 mmol/l (95% confidence interval: 0.25-0.46), and triacylglycerol concentrations by 0.14 mmol/l (0.04-0.23) relative to placebo. The ratio of total to HDL cholesterol increased by 0.23 (0.14-0.32). Concentrations of HDL cholesterol were not affected. Doses of betaine lower than 6 g/d also raised LDL cholesterol, but these changes were not statistically significant. Further, the effect of betaine on LDL cholesterol was already evident after 2 wk of intervention. Phosphatidylcholine supplementation (providing approximately 2.6 g/d of choline) for 2 wk increased triacylglycerol concentrations by 0.14 mmol/l (0.06-0.21), but did not affect cholesterol concentrations. Folic acid supplementation (0.8 mg/d) had no effect on lipid concentrations.

Conclusions: Betaine supplementation increased blood LDL cholesterol and triacylglycerol concentrations in healthy humans, which agrees with the limited previous data. The adverse effects on blood lipids may undo the potential benefits for cardiovascular health of betaine supplementation through homocysteine lowering. In our study phosphatidylcholine supplementation slightly increased triacylglycerol concentrations in healthy humans. Previous studies of phosphatidylcholine and blood lipids showed no clear effect. Thus the effect of phosphatidylcholine supplementation on blood lipids remains inconclusive, but is probably not large. Folic acid supplementation does not seem to affect blood lipids and therefore remains the preferred treatment for lowering of blood homocysteine concentrations.

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Related in: MedlinePlus

Role of Folic Acid, Choline, and Betaine in Homocysteine Metabolism and in Phosphatidylcholine MetabolismPhosphatidylcholine is necessary for synthesis of VLDL, which exports lipids from the liver.
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getmorefigures.php?uid=PMC1140947&req=5

pmed-0020135-g001: Role of Folic Acid, Choline, and Betaine in Homocysteine Metabolism and in Phosphatidylcholine MetabolismPhosphatidylcholine is necessary for synthesis of VLDL, which exports lipids from the liver.

Mentions: Increases in blood lipid concentrations due to betaine or choline supplementation might offset the potential beneficial effects of their homocysteine-lowering properties. Folic acid is the most commonly used homocysteine-lowering agent. The betaine remethylation and folic acid remethylation pathways are interrelated (Figure 1), so effects of folic acid supplementation on lipid metabolism cannot be excluded [18].


Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans.

Olthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB - PLoS Med. (2005)

Role of Folic Acid, Choline, and Betaine in Homocysteine Metabolism and in Phosphatidylcholine MetabolismPhosphatidylcholine is necessary for synthesis of VLDL, which exports lipids from the liver.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1140947&req=5

pmed-0020135-g001: Role of Folic Acid, Choline, and Betaine in Homocysteine Metabolism and in Phosphatidylcholine MetabolismPhosphatidylcholine is necessary for synthesis of VLDL, which exports lipids from the liver.
Mentions: Increases in blood lipid concentrations due to betaine or choline supplementation might offset the potential beneficial effects of their homocysteine-lowering properties. Folic acid is the most commonly used homocysteine-lowering agent. The betaine remethylation and folic acid remethylation pathways are interrelated (Figure 1), so effects of folic acid supplementation on lipid metabolism cannot be excluded [18].

Bottom Line: Previous studies of phosphatidylcholine and blood lipids showed no clear effect.Thus the effect of phosphatidylcholine supplementation on blood lipids remains inconclusive, but is probably not large.Folic acid supplementation does not seem to affect blood lipids and therefore remains the preferred treatment for lowering of blood homocysteine concentrations.

View Article: PubMed Central - PubMed

Affiliation: Wageningen Centre for Food Sciences, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands. margreet.olthof@wur.nl

ABSTRACT

Background: Betaine (trimethylglycine) lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals are lacking. Such an effect on cholesterol would counteract any favourable effect on homocysteine. We therefore investigated the effect of betaine, of its precursor choline in the form of phosphatidylcholine, and of the classical homocysteine-lowering vitamin folic acid on blood lipid concentrations in healthy humans.

Methods and findings: We measured blood lipids in four placebo-controlled, randomised intervention studies that examined the effect of betaine (three studies, n = 151), folic acid (two studies, n = 75), and phosphatidylcholine (one study, n = 26) on plasma homocysteine concentrations. We combined blood lipid data from the individual studies and calculated a weighted mean change in blood lipid concentrations relative to placebo. Betaine supplementation (6 g/d) for 6 wk increased blood LDL cholesterol concentrations by 0.36 mmol/l (95% confidence interval: 0.25-0.46), and triacylglycerol concentrations by 0.14 mmol/l (0.04-0.23) relative to placebo. The ratio of total to HDL cholesterol increased by 0.23 (0.14-0.32). Concentrations of HDL cholesterol were not affected. Doses of betaine lower than 6 g/d also raised LDL cholesterol, but these changes were not statistically significant. Further, the effect of betaine on LDL cholesterol was already evident after 2 wk of intervention. Phosphatidylcholine supplementation (providing approximately 2.6 g/d of choline) for 2 wk increased triacylglycerol concentrations by 0.14 mmol/l (0.06-0.21), but did not affect cholesterol concentrations. Folic acid supplementation (0.8 mg/d) had no effect on lipid concentrations.

Conclusions: Betaine supplementation increased blood LDL cholesterol and triacylglycerol concentrations in healthy humans, which agrees with the limited previous data. The adverse effects on blood lipids may undo the potential benefits for cardiovascular health of betaine supplementation through homocysteine lowering. In our study phosphatidylcholine supplementation slightly increased triacylglycerol concentrations in healthy humans. Previous studies of phosphatidylcholine and blood lipids showed no clear effect. Thus the effect of phosphatidylcholine supplementation on blood lipids remains inconclusive, but is probably not large. Folic acid supplementation does not seem to affect blood lipids and therefore remains the preferred treatment for lowering of blood homocysteine concentrations.

Show MeSH
Related in: MedlinePlus