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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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Flow Diagram of Participant Progress through Study 3
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pmed-0020135-g004: Flow Diagram of Participant Progress through Study 3

Mentions: The primary endpoints of this study were plasma homocysteine concentrations and vascular function. Blood lipid measurements were planned before the study took place, but power analysis was based on changes in the primary endpoint vascular function, and not on changes in blood lipids. The original study protocol of this study can be found in Protocol S1, and the trial was registered at clinicaltrials.gov under identifier NCT00102843. The study was conducted at the division of Human Nutrition, Wageningen University (Wageningen, the Netherlands). The local medical ethics committee approved the protocol, and all volunteers gave their written informed consent. Volunteers were recruited from June to September 2002. Eligible volunteers were healthy as assessed by routine medical screening and a general health questionnaire, had plasma total homocysteine concentrations below 26 μmol/l, had no history of CVD; and had not used vitamin B supplements more than once a week in the 3 mo before entering the study. Out of the eligible participants, the 40 participants (23 males and 17 females, age 50–70 y) with the highest plasma total homocysteine concentrations (range 10.2 to 21.7 μmol/l) were included in this placebo-controlled, double-blind cross-over trial (Figure 4). Participants were randomly assigned to one out of six treatment orders, and they received each of the following supplements for 6 wk, with a 6-wk wash out in between: (a) 6 g/d of betaine (BUFA), (b) 0.8 mg/d of folic acid, or (c) placebo. A person not further involved in the study assigned codes to the study treatments, and randomly allocated the selected participants to one out of six treatment orders, according to a computer-generated randomization list, and kept the key in a sealed envelope. The participants and all others involved in this study were unaware of treatment allocation. The principal investigator performed unblinding of the treatment allocation after the study had ended and laboratory analyses were complete. The study supplements were dissolved in water and ingested twice per day, one half of the daily dose after breakfast and the other half after the evening meal. During the study participants were not allowed to consume supplements containing B vitamins, antioxidant vitamins (A, beta-carotene, C, and E), or omega-3 fatty acids/fish oil supplements.


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)

Flow Diagram of Participant Progress through Study 3
© Copyright Policy
Related In: Results  -  Collection

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

pmed-0020135-g004: Flow Diagram of Participant Progress through Study 3
Mentions: The primary endpoints of this study were plasma homocysteine concentrations and vascular function. Blood lipid measurements were planned before the study took place, but power analysis was based on changes in the primary endpoint vascular function, and not on changes in blood lipids. The original study protocol of this study can be found in Protocol S1, and the trial was registered at clinicaltrials.gov under identifier NCT00102843. The study was conducted at the division of Human Nutrition, Wageningen University (Wageningen, the Netherlands). The local medical ethics committee approved the protocol, and all volunteers gave their written informed consent. Volunteers were recruited from June to September 2002. Eligible volunteers were healthy as assessed by routine medical screening and a general health questionnaire, had plasma total homocysteine concentrations below 26 μmol/l, had no history of CVD; and had not used vitamin B supplements more than once a week in the 3 mo before entering the study. Out of the eligible participants, the 40 participants (23 males and 17 females, age 50–70 y) with the highest plasma total homocysteine concentrations (range 10.2 to 21.7 μmol/l) were included in this placebo-controlled, double-blind cross-over trial (Figure 4). Participants were randomly assigned to one out of six treatment orders, and they received each of the following supplements for 6 wk, with a 6-wk wash out in between: (a) 6 g/d of betaine (BUFA), (b) 0.8 mg/d of folic acid, or (c) placebo. A person not further involved in the study assigned codes to the study treatments, and randomly allocated the selected participants to one out of six treatment orders, according to a computer-generated randomization list, and kept the key in a sealed envelope. The participants and all others involved in this study were unaware of treatment allocation. The principal investigator performed unblinding of the treatment allocation after the study had ended and laboratory analyses were complete. The study supplements were dissolved in water and ingested twice per day, one half of the daily dose after breakfast and the other half after the evening meal. During the study participants were not allowed to consume supplements containing B vitamins, antioxidant vitamins (A, beta-carotene, C, and E), or omega-3 fatty acids/fish oil supplements.

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