Literature reviewBetaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis
Introduction
Homocysteine is a sulfur-containing amino acid formed during the metabolism of methionine. Homocysteine can be converted back to methionine using the enzyme methionine synthase, a vitamin B-12 and folate–dependent reaction, or the enzyme betaine-homocysteine methyltransferase (BHMT), a betaine (trimethylglycine)–dependent reaction. Betaine donates methyl groups to homocysteine, which in turn is metabolized back to methionine. In the liver, BHMT catalyzes up to 50% of homocysteine metabolism.1
Betaine is found naturally in most living organisms and is formed in cells as an oxidation product of choline and can be obtained externally from foods such as spinach, beets, and wheat products. An inverse association between dietary betaine intakes and homocysteine concentrations has been observed in the sixth examination of the Framingham Offspring Study.2 As well, low plasma betaine concentrations have been shown to be related to an unfavorable cardiovascular risk profile3 and an increased risk of secondary heart failure and acute myocardial infarction.4 Plasma homocysteine concentration has been associated with cardiovascular disease and stroke,5 as elevated homocysteine promotes atherosclerosis and stroke through increased oxidant stress, impaired endothelial functions, and induction of thrombosis.6 Plasma homocysteine concentrations are usually around 8 to 10 μmol/L, with the 95th percentile at approximately 15 μmol/L.7 Elevated plasma levels of homocysteine greater than 15 μmol/L are present in 5% of the general population and in as many as 50% of those with cardiovascular disease and stroke.6
Supplementation with betaine decreases plasma homocysteine concentrations substantially in patients with hyperhomocystinemia.8 Studies in healthy volunteers show that 6 g/d of betaine lowers plasma homocysteine concentrations by 5% to 20%.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 The purpose of this study was to perform a meta-analysis of randomized placebo-controlled trials that used daily betaine supplementation to identify the range in betaine's effects on lowering homocysteine.
Section snippets
Selection of studies
A comprehensive MEDLINE literature search was performed to locate relevant randomized controlled trials published between 1966 and August 2012. The following headings were combined using the following Boolean operation: (“betaine” OR “trimethylglycine”) AND “homocysteine.” The search was restricted to key terms located in the title/abstract and was also restricted to studies published in English-language journals. Only full-length original journal articles were considered. No attempt was made
Participant characteristics and study designs
Participant and study design characteristics for the 5 randomized controlled trials included in the meta-analysis are presented in Table 1. Collectively, the 5 trials that were conducted between 2002 and 2010 included a total of 206 participants (124 in the betaine group and 119 in the control group). All of the trials were conducted in adults, with an age range of 27 to 59 years. Women were the majority in 3 of the 5 trials, with the pooled population being made up of 60.2% women. Four trials
Discussion
This meta-analysis shows that supplementation of betaine at 4 to 6 g/d significantly lowers plasma homocysteine concentration in healthy adults by 1.23 μmol/L or 11.8% of baseline values. A reduction in plasma homocysteine of 5 μmol/L is estimated to reduce the risk of cardiovascular disease by 20% to 30% and stroke by 40% to 60%.22 Based on this current meta-analysis, a person who consumes 4 to 6 g/d of betaine would have a 1.23-μmol/L lower plasma homocysteine concentration with an estimated
Conclusion
This meta-analysis shows that betaine supplementation of 4 to 6 g/d significantly lowers plasma homocysteine concentration in healthy adults by 1.23 μmol/L or 11.8% of baseline values. As new evidence continues to confirm that plasma homocysteine is a cause of cardiovascular disease, these results suggest that betaine could be used effectively to lower plasma homocysteine levels, which may potentially lead to a reduction in the risk of cardiovascular disease and stroke. However, there are few
Funding sources and potential conflicts of interest
No funding sources or conflicts of interest were reported for this study.
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