Title
Effect of homocysteine-lowering nutrients on blood lipids: Results from four randomised, placebo-controlled studies in healthy humans
Author
Olthof, M.R.
van Vliet, T.
Verhoef, P.
Zock, P.L.
Katan, M.B.
TNO Kwaliteit van Leven
Publication year
2005
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. © 2005 Olthof et al.
Subject
Biology
Biomedical Research
betaine
folic acid
high density lipoprotein cholesterol
homocysteine
lipid
low density lipoprotein cholesterol
phosphatidylcholine
placebo
protein inhibitor
triacylglycerol
adult
calculation
confidence interval
controlled study
diet supplementation
female
lipid blood level
male
time series analysis
vitamin supplementation
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http://resolver.tudelft.nl/uuid:f503be42-47d7-47b3-a5da-924a310972fd
DOI
https://doi.org/10.1371/journal.pmed.0020135
TNO identifier
238609
ISSN
1549-1277
Source
PLoS Medicine, 2 (5), 0446-0456
Document type
article