Hyperhomocysteinemia Induced by Guanidinoacetic Acid Is Effectively Suppressed by Choline and Betaine in Rats

Setoue, Minoru; Ohuchi, Seiya; Morita, Tatsuya; Sugiyama, Kimio

doi:10.1271/bbb.70791

Cited by 36 publications

(31 citation statements)

References 39 publications

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“…It appears unlikely that the limited effect of betaine is solely due to the supplementation level of betaine. We previously demonstrated that guanidinoacetic acid-induced hyperhomocysteinemia was almost completely suppressed by betaine supplementation at a level of 0.34% (12) and that choline deprivation-induced hyperhomocysteinemia was completely suppressed by betaine supplementation at a level of 0.28% (5). Therefore, the 1% supplementation level of betaine used in the present study appears to be relatively high, although a dose-response experiment is needed to confirm the effect of betaine.…”

Section: Discussionmentioning

confidence: 54%

“…Results of a number of studies on the plasma homocysteine-lowering effect of betaine in human subjects have been reported ( 6 , 7 ). The effects of betaine in hyperhomocysteinemic animal models have also been reported (8)(9)(10)(11)(12). The efficacy of betaine is based on the mechanism by which the compound increases hepatic betaine concentration and BHMT activity ( 13 ) and thereby stimulates homocysteine removal by the betaine-BHMT system.…”

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confidence: 95%

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Effects of Betaine Supplementation and Choline Deficiency on Folate Deficiency-Induced Hyperhomocysteinemia in Rats

Liu

Morita

et al. 2012

J Nutr Sci Vitaminol

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Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 95%

Effects of Betaine Supplementation and Choline Deficiency on Folate Deficiency-Induced Hyperhomocysteinemia in Rats

Liu

Morita

et al. 2012

J Nutr Sci Vitaminol

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“…After collecting the blood, the whole liver was quickly removed, rinsed in ice-cold saline, blotted on filter paper, cut into three portions, weighed, quickly frozen in liquid nitrogen, and stored at Ϫ 80˚C until needed for analyses. Homogenization of the liver and centrifugation of the homogenate were conducted according to the methods described previously ( 27 ).…”

Section: Methodsmentioning

confidence: 99%

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

Kawakami

Ohuchi

Morita

et al. 2009

J Nutr Sci Vitaminol

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Summary Rats were fed diets with and without 0.5% L -cysteine supplement for 14 d or shorter periods to clarify the mechanism by which dietary cysteine elicits its hypohomocysteinemic effect. Cysteine supplementation significantly decreased plasma homocysteine concentration with an increase in plasma cysteine concentration in rats fed 10% casein diet (10C) or 15% soybean protein diet (15S) but not in rats fed 25% casein diet (25C) or 25% soybean protein diet. Cysteine supplementation also significantly suppressed hyperhomocysteinemia induced by choline-deprived 10C with an increase in plasma cysteine concentration but not that induced by 25C ϩ 0.65% methionine or 25C ϩ 0.4% guanidinoacetic acid. Hepatic S -adenosylmethionine (SAM) and homocysteine concentrations were significantly decreased by cysteine supplementation of 15S. These decreases in plasma homocysteine concentration and hepatic SAM and homocysteine concentrations due to cysteine supplementation disappeared when 15S was fortified with 0.3% methionine. The plasma homocysteine concentration significantly decreased with an increase in plasma cysteine concentration only 1 d after diet change from 15S to cysteine-supplemented 15S, while hepatic cystathionine ␤ -synthase and betaine-homocysteine S -methyltransferase activities were not altered. Unlike cysteine, cysteic acid and 2-mercaptoethylamine did not decrease plasma homocysteine concentration. These results indicate that cysteine markedly decreases plasma homocysteine concentration only when added to diets low in both protein and methionine levels and suggest that increased plasma cysteine concentration and decreased flow of methionine toward homocysteine formation, but not alteration of homocysteine-metabolizing enzyme activities, are associated with the hypohomocysteinemic effect of cysteine. Key Words hypohomocysteinemic effect, cysteine, homocysteine, low protein diet, low methionine diet Homocysteine is an intermediate in the metabolism of methionine (Fig. 1) ( 1 ), but a number of studies have suggested that an elevated plasma homocysteine concentration is an independent risk factor for cardiovascular disease ( 2 -4 ). It is thought that elevated plasma homocysteine concentrations cause arterial damage by several mechanisms, e.g., endothelial cell injury, platelet activation, and increased oxidizability of low-density lipoproteins ( 4 ). In humans, the normal range of plasma homocysteine concentration is 5 to 15 M , and a 5-M increase in the concentration of this amino acid is associated with a 60-80% increased risk of coronary heart disease ( 3 ). The plasma homocysteine concentration is affected by various factors, such as nutritional, physiological, hormonal, pharmacological, lifestyle, disease, and genetic factors ( 2 -4 ). Of these factors, genetic and nutritional factors are thought to have a greater influence on plasma homocysteine concentration. Many studies have been conducted in humans to investigate the effect of dietary treatments on plasma homocysteine concentration. However, studie...

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“…It has been reported that a highmethionine diet decreased the liver betaine level. 19,20) Furthermore, Liu et al have reported that the hepatic betaine concentration was improved, but only slightly, by folate supplementation under low casein and choline deficient conditions. 21) Under our dietary conditions, in which methionine was supplemented and folate was fortified, we propose that the increase of 5-MTHF in the liver was mainly responsible for the amelioration of hyperhomocysteinemia although further study is needed to confirm this.…”

Section: Involvement Of 5-methyltetrahydrofolate In the Amelioration mentioning

confidence: 99%

Involvement of 5-Methyltetrahydrofolate in the Amelioration of Hyperhomocysteinemia Caused by Vitamin B<sub>6</sub> Deficiency and <small>L</small>-Methionine Supplementation

Yamamoto

Isa

Nakagawa

et al. 2013

Bioscience, Biotechnology, and Biochemistry

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Hyperhomocysteinemia Induced by Guanidinoacetic Acid Is Effectively Suppressed by Choline and Betaine in Rats

Cited by 36 publications

References 39 publications

Effects of Betaine Supplementation and Choline Deficiency on Folate Deficiency-Induced Hyperhomocysteinemia in Rats

Effects of Betaine Supplementation and Choline Deficiency on Folate Deficiency-Induced Hyperhomocysteinemia in Rats

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

Involvement of 5-Methyltetrahydrofolate in the Amelioration of Hyperhomocysteinemia Caused by Vitamin B<sub>6</sub> Deficiency and <small>L</small>-Methionine Supplementation

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