Betaine and secondary events in an acute coronary syndrome cohort.

BACKGROUND: Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients. METHODS: Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days. PRINCIPAL FINDINGS: The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002). CONCLUSIONS: Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk.

Plasma lipids and betaine are related in an acute coronary syndrome cohort.

BACKGROUND: Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is associated with elevations in plasma lipids. We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these. METHODOLOGY: Fasting plasma samples were collected from 531 subjects (and urine samples from 415) 4 months after hospitalization for an acute coronary syndrome episode. In this cross-sectional study, plasma betaine and dimethylglycine concentrations and urine excretions were compared with plasma lipid concentrations. Subgroup comparisons were made for gender, with and without diabetes mellitus, and for drug treatment. PRINCIPAL FINDINGS: Plasma betaine negatively correlated with triglyceride (Spearman's r(s) = -0.22, p<0.0001) and non-high-density lipoprotein cholesterol (r(s) = -0.27, p<0.0001). Plasma betaine was a predictor of BMI (p<0.05) and plasma non-high-density lipoprotein cholesterol and triglyceride (p<0.001) independently of gender, age and the presence of diabetes. Using data grouped by plasma betaine decile, increasing plasma betaine was linearly related to decreases in BMI (p = 0.008) and plasma non-HDL cholesterol (p = 0.002). In a non-linear relationship betaine was negatively associated with elevated plasma triglycerides (p = 0.004) only for plasma betaine >45 µmol/L. Subjects taking statins had higher plasma betaine concentrations (p<0.001). Subjects treated with a fibrate had lower plasma betaine (p = 0.003) possibly caused by elevated urine betaine loss (p<0.001). The ratio of coenzyme Q to non-high-density lipoprotein cholesterol was higher in subjects with higher plasma betaine, and in subjects taking a statin. CONCLUSION: Low plasma betaine concentrations correlated with an unfavourable lipid profile. Betaine deficiency may be common in the study population. Controlled clinical trials of betaine supplementation should be conducted in appropriate populations to determine whether correction affects cardiovascular risk.

Plasma and urine betaine and dimethylglycine variation in healthy young male subjects.

OBJECTIVES: We aimed to compare the individuality (within subject consistency) of plasma and urine betaine and N,N-dimethylglycine. DESIGN AND METHODS: In two separate groups of 8 males (ages 19 to 40), plasma (10) and urine (6) samples were collected either over a single day or over an 8 week period. The individuality of the betaine and N,N-dimethylglycine plasma concentrations and excretions were estimated by one-way repeated measures analysis of variance. The reliability coefficients and indices of individuality were calculated. The between-subject variation in the study population was compared with that in a normal population (n=192 for plasma, 205 for urine). RESULTS: Plasma betaine concentrations were significantly different between subjects over 24 h and 8 weeks (p<0.00001). Plasma dimethylglycine concentrations were different over 24 h. Urine betaine and dimethylglycine excretions were different in both (p<0.0001). Betaine was more individual than dimethylglycine in both plasma and urine. Compared with a normal healthy population, the between-subject variation in plasma betaine was less (p<0.001) in the study group, but similar for dimethylglycine and for urine betaine. CONCLUSIONS: Plasma betaine and urinary betaine excretions are more individual than dimethylglycine. Plasma and urine betaine are highly individual in the general population.

Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects.

BACKGROUND: Betaine comes from the diet and from choline, and it is associated with vascular disease in some patient groups. Betaine supplementation lowers plasma total homocysteine. OBJECTIVE: We compared the acute effects of dietary and supplementary betaine and choline on plasma betaine and homocysteine under standard conditions and after a methionine load. DESIGN: In a randomized crossover study, 8 healthy men (19-40 y) consumed a betaine supplement (approximately 500 mg), high-betaine meal (approximately 517 mg), choline supplement (500 mg), high-choline meal (approximately 564 mg), high-betaine and -choline meal (approximately 517 mg betaine, approximately 622 mg choline), or a low-betaine and -choline control meal under standard conditions or postmethionine load. Plasma betaine, dimethylglycine, and homocysteine concentrations were measured hourly for 8 h and at 24 h after treatment. RESULTS: Dietary and supplementary betaine raised plasma betaine concentrations relative to control (P < 0.001) under standard conditions. This was not associated with raised plasma dimethylglycine concentration, and no significant betaine appeared in the urine. A small increase in dimethylglycine excretion was observed when either betaine or choline was supplied (P = 0.011 and < 0.001). Small decreases in plasma homocysteine 6 h after ingestion under standard conditions (P < or = 0.05) were detected after a high-betaine meal and after a high-betaine and high-choline meal. Dietary betaine and choline and betaine supplementation attenuated the increase in plasma homocysteine at both 4 and 6 h after a methionine load (P < or = 0.001). CONCLUSIONS: Dietary betaine and supplementary betaine acutely increase plasma betaine, and they and choline attenuate the postmethionine load rise in homocysteine concentrations.

Effects of orange juice and proline betaine on glycine betaine and homocysteine in healthy male subjects.

BACKGROUND: Proline betaine (PB), a glycine betaine (GB) analogue found in citrus foods, increases urinary GB loss and plasma total homocysteine (tHcy) concentrations in rats. Its presence in human plasma is associated with increased GB excretion. AIM: To compare the effects of dietary levels of PB on GB excretion, and on plasma tHcy and GB concentrations in healthy volunteers. METHODS: In a randomized crossover study, eight healthy males (18-50 years) ingested either 750 mL orange juice (containing 0.545 g PB), a PB supplement (0.545 g PB dissolved in 750 mL apple juice), or 750 mL apple juice (control). Plasma PB, GB and tHcy, and urine PB, GB and creatinine concentrations were measured hourly for 6 h and at 24 h post-treatment. RESULTS: Plasma tHcy concentrations were not increased (relative to control) following ingestion of either orange juice or PB supplement. Both treatments produced a significant increase in plasma PB concentrations (P < 0.001), this effect being greater following orange juice compared with PB supplement (P < 0.05, 1-2 h). Urinary excretion of PB was greater than the control following both orange juice (P < 0.001) and PB supplement (P < 0.001), from 2 to 24 h post-treatment. This increase in PB excretion was significantly greater following orange juice compared with PB supplement with higher peak excretion (Cmax difference, P = 0.008). GB excretion was significantly greater following ingestion of orange juice compared with PB in apple juice (P = 0.007) and apple juice control (P < 0.001) in the first 2 h post-ingestion. CONCLUSIONS: PB administered in dietary doses had little effect on plasma tHcy concentrations in healthy humans. Ingestion of PB in orange juice compared with PB alone resulted in greater increases in the urinary excretion of PB and GB.