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European journal of clinical nutrition 03/2011; 65(6):771; author reply 772. · 3.07 Impact Factor
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ABSTRACT: Betaine is an osmolyte that when catabolised decreases plasma total homocysteine. A betaine-rich meal has acute effects similar to a supplement, but the effects of a longer-term increase in dietary betaine intake need clarification. We compared the effects of two weeks of dietary and supplementary betaine on plasma betaine and homocysteine concentrations both fasting and after a methionine load.
In a randomized crossover study, 8 healthy males (22-36 y) consumed either a betaine-rich diet ( approximately 800 mg/day) or a betaine supplement (0.5 g twice daily) for 14 days. Fasting blood samples were collected on day -5, -1 (pre-treatment) 0, 2, 6, 9, 13 (treatment), 14 and 18 (post-treatment). Post-methionine load blood samples were collected on day -5, 0, 6 and 13, while 24h urine samples were collected on day -5, 0, 6, 13 and 14. Plasma betaine, dimethylglycine, homocysteine and urine betaine, dimethylglycine and creatinine concentrations were measured. Plasma betaine concentrations significantly increased for both treatments compared to pre-treatment values (P<0.001). Fasting homocysteine levels were minimally affected. Both treatments reduced post-methionine load homocysteine and this effect tended to be greater following a betaine-rich diet (P=0.108). Small increases in urinary betaine excretion were observed following both treatments ( approximately 1.5% of supplement; approximately 1.3% of dietary betaine). Most was attributable to increased excretion of betaine as dimethylglycine.
Supplemental or dietary betaine similarly increase circulating betaine concentrations and attenuate the post-methionine load rise in homocysteine concentrations.
Nutrition, metabolism, and cardiovascular diseases: NMCD 04/2009; 19(11):767-73. · 3.52 Impact Factor
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ABSTRACT: Tissue betaine is an intracellular osmolyte that also provides a store of labile methyl groups. Despite these important biological roles, there are few data regarding tissue betaine content. We measured the betaine concentration of plasma and various tissues (brain, heart, lungs, liver, kidney, spleen, intestine, reproductive tissues, skeletal muscle and skin) in male and female rats and assessed whether there were any gender-specific differences in betaine content or distribution and whether there was any relationship between tissue accumulation and plasma levels. Betaine was highest in the liver and kidney with values ranging from 1.6 to 9.5 mmol/l and 2.0 to 5.4 mmol/l, respectively. Plasma betaine concentrations were significantly lower than tissue levels except in the brain (? 25 % of plasma) and skeletal muscle (similar to plasma). Regression analysis of the combined male and female data revealed a significant plasma-related accumulation of betaine in the heart, skin and skeletal muscle, while the lung, liver, kidney, spleen, and intestine showed significant plasma-related and plasma-independent accumulations of betaine. The betaine content of the skin, liver and kidney was not significantly different between males and females, but in plasma and all tissues analyzed it was significantly higher in males (P<0.01).
Physiological research / Academia Scientiarum Bohemoslovaca 01/2009; 58(3):403-10. · 1.55 Impact Factor
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ABSTRACT: To determine whether trigonelline contributes to the effect of coffee on homocysteine (Hcy).
This was a randomised crossover study. Subjects consumed 50 mg trigonelline, 5 g of instant coffee (approximately 50 mg trigonelline) or water, consumed as a single dose in 100 ml, with 1 week between each treatment. Blood samples were drawn fasting and hourly for 8 h. Urine samples were collected pretreatment and every 2 h for 8 h.
Christchurch Clinical Studies Trust, Christchurch, New Zealand.
Eight healthy male subjects.
Instant coffee raised plasma Hcy concentrations compared with water (P=0.019) and trigonelline (P=0.037). Plasma Hcy concentrations were not different between water and trigonelline treatments (P=0.789). The change in plasma Hcy concentration was higher (mean+/-s.e.) 4 h (0.7+/-0.2 micromol/l, P=0.006), 5 h (0.7+/-0.2 micromol/l, P=0.013) and 7 h (0.7+/-0.2 micromol/l, P=0.024) following coffee consumption. Urinary glycine betaine excretion was increased by coffee but not by trigonelline.
Ingestion of instant coffee acutely elevated plasma Hcy; however, trigonelline is not responsible for this rise.
Supported by the Health Research Council, the Canterbury Medical Foundation, the Foundation of Research, Science and Technology.
European Journal of Clinical Nutrition 10/2004; 58(9):1253-6. · 2.46 Impact Factor
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ABSTRACT: Glycine betaine and trimethylamine-N-oxide counteract urea denaturation in solutions containing urea and the methylamine in the mole ratio of 2:1. Near infra-red difference spectra (water spectrum subtracted) of solutions containing both urea with either glycine betaine or trimethylamine-N-oxide can be predicted from the spectra of the single solutes, with r(2)>0.999 both using the spectrum from 1200 to 2100 nm (where most absorbance is attributable to hydrogen bonding) and using an extended range 1000 to 2500 nm, which includes solute specific bands. Thus urea and the kosmotropes appear to interact with water independently and the counteraction cannot be attributed to specific interactions between them. The spectrum of aqueous glycine betaine can be predicted from tetramethylammonium and formate ions (r(2)=0.998), suggesting that independent interactions of the quaternary amine, and of the carboxyl function, with water are dominant. The exceptional properties of glycine betaine do not arise from specific intramolecular interactions between the charged groups.
Biochimica et Biophysica Acta 10/2001; 1528(2-3):135-40. · 4.66 Impact Factor
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ABSTRACT: Hyperhomocysteinemia is a risk factor for atherosclerosis that is common in chronic renal failure (CRF), but its cause is unknown. Homocysteine metabolism is linked to betaine-homocysteine methyl transferase (BHMT), a zinc metalloenzyme that converts glycine betaine (GB) to N,N dimethylglycine (DMG). DMG is a known feedback inhibitor of BHMT. We postulated that DMG might accumulate in CRF and contribute to hyperhomocysteinemia by inhibiting BHMT activity.
Plasma and urine concentrations of GB and DMG were measured in 33 dialysis patients (15 continuous ambulatory peritoneal dialysis and 18 hemodialysis), 33 patients with CRF, and 33 age-matched controls. Concentrations of fasting plasma total homocysteine (tHcy), red cell and serum folate, vitamins B(6) and B(12), serum zinc, and routine biochemistry were also measured. Groups were compared, and determinants of plasma tHcy were identified by correlations and stepwise linear regression.
Plasma DMG increased as renal function declined and was twofold to threefold elevated in dialysis patients. Plasma GB did not differ between groups. The fractional excretion of GB (FE(GB)) was increased tenfold, and FED(MG) was doubled in CRF patients compared with controls. Plasma tHcy correlated positively with plasma DMG, the plasma DMG:GB ratio, plasma creatinine, and FE(GB) and negatively with serum folate, zinc, and plasma GB. In the multiple regression model, only plasma creatinine, plasma DMG, or the DMG:GB ratio was independent predictors of tHcy.
DMG accumulates in CRF and independently predicts plasma tHcy concentrations. These findings suggest that reduced BHMT activity is important in the pathogenesis of hyperhomocysteinemia in CRF.
Kidney International 07/2001; 59(6):2267-72. · 6.61 Impact Factor
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ABSTRACT: Diabetes mellitus subjects, type 1 and type 2, have increased glycine betaine excretion compared to normal subjects that correlated with plasma glucose and HbA(1C) concentrations. The current study was undertaken to determine whether elevated glucose concentration directly increases glycine betaine excretion in an animal model. Non-pregnant female Coopworth sheep received an intravenous glucose load (12.5,25 and 50% w/v; rate 200 ml/h) for 6 h followed by a 12 h physiological saline washout (0.9% w/v). Plasma and urine samples were analyzed for glycine betaine and glucose. Urine volumes and osmolality were also measured. Using the non-parametric Kruskal Wallis analysis of variance test we found no difference in glycine betaine excretion between glucose loaded and saline infused control animals (P=0.861). However, a significant negative correlation (r=-0.28, P<0.001) was observed between urine osmolality and glycine betaine excretion independent of treatment. We conclude that acute elevations of plasma glucose concentrations did not result in increased glycine betaine excretion and is therefore unlikely to be directly responsible for elevated glycine betaine excretion observed in diabetes mellitus subjects.
Diabetes Research and Clinical Practice 06/2001; 52(3):165-9. · 2.75 Impact Factor
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ABSTRACT: It has long been recognised that some individuals produce urine that is inhibitory to uropathogens. This may be partly explained by inhibitors. Several inhibitors have been identified in urine including urea and organic acids. Bacteria adapt to high osmolarity by activating osmoregulated betaine porters and accumulating organic osmolytes intracellularly. The preferred substrate is glycine betaine, which is present in urine, and promotes rapid growth by balancing osmotic forces and stabilising macromolecular structures against the toxicity of urea and low pH. Other dietary betaines such as trigonelline may also be taken but enhance urea toxicity. The importance of such compounds in vivo is unknown.
International Journal of Antimicrobial Agents 06/1999; 11(3-4):293-6. · 4.13 Impact Factor
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ABSTRACT: The hydrophilic betaines, deanol betaine, triethanol betaine, diethanolthetin and methylethanolthetin, and also thioxanium betaine and citrulline betaine, were accumulated by Escherichia coli. All betaines tested had significant osmoprotective activity for E. coli and, with the exception of citrulline betaine and diethanolthetin, also demonstrated urea protection. Staphylococcus aureus accumulated only methylethanolthetin, deanol betaine and thioxanium betaine: the first two had an osmoprotective effect but conferred no urea protection. Diethanolthetin and thioxanium betaine significantly decreased urea tolerance for S. aureus.
Antonie van Leeuwenhoek 05/1999; 75(3):183-9. · 2.09 Impact Factor
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ABSTRACT: In an ambulatory population of diabetic subjects (Type 1 and Type 2), the urine excretion of the renal osmolyte, glycine betaine, was compared to known markers of glycemic control, renal dysfunction and to the excretion of related betaines, including trigonelline, proline betaine, carnitine and acetyl-carnitine. Of the 85 subjects, 20 patients had urine glycine betaine concentrations above the reference range for normal subjects. Plasma glycine betaine concentrations were within reference ranges for normal subjects. Patients with elevated glycine betaine excretion tended to have lower plasma glycine betaine concentrations, but this did not reach statistical significance. One way analysis of variance found excretion is independent of treatment, duration of diagnosed diabetes, blood pressure and body mass index (BMI). An association between glycine betaine excretion and glycemic control was observed with statistically significant correlations occurring with both plasma glucose (r = 0.43, P < 0.001) and glycated haemoglobin (HbA1c) (r = 0.35, P < 0.005). The excretion of carnitine, acetyl-carnitine and proline betaine were related to glycine betaine excretion (r = 0.49, P < 0.001; r = 0.40, P < 0.001; r = 0.27, P < 0.05, respectively). Urine carnitine and acetyl-carnitine concentrations were also related to plasma glucose concentrations (r = 0.30, P < 0.01). Increased urine retinol binding protein concentrations (RBP), a marker of proximal tubular dysfunction, correlated with elevated urine glycine betaine excretion and plasma HbA1c (r = 0.28, P < 0.01). These results suggest poor glycemic control is associated with the increase in urine glycine betaine, carnitine, acetyl-carnitine and RBP excretion in diabetic patients. However, < 50% of the observed increase in glycine betaine excretion has been accounted for by the variables measured, suggesting other unidentified processes may also be involved.
Diabetes Research and Clinical Practice 03/1999; 43(2):91-9. · 2.75 Impact Factor
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ABSTRACT: Betaines were evaluated as potential antistaphylococcal agents for urinary tract infections. Staphylococcus aureus accumulated all tested betaines except trigonelline. S. aureus transport systems were less sensitive to carbon chain length than those of Escherichia coli. Betaines were accumulated in the absence of osmotic stress, and 10-fold more in hyperosmotic medium. Most betaines increased the osmotolerance of S. aureus in defined minimal medium. Unlike E. coli, S. aureus did not significantly accumulate a second betaine in the presence of glycine betaine. Betaines are less likely to be useful in treating staphylococcal than E. coli urinary infections.
FEMS Microbiology Letters 04/1998; 160(1):25-30. · 2.04 Impact Factor
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ABSTRACT: Escherichia coli was used as a model system to evaluate a range of betaines for their ability to protect against salt and urea stresses. Betaine structure determined the salt and urea protective effects. Dimethylthetin conferred salt protection similar to glycine betaine, whereas dimethylsulfoniopropionate (DMSP) was less effective than either glycine betaine or dimethylthetin, but similar to propionobetaine (its nitrogen analogue). Hydrophobic alpha-substituents altered salt tolerance. Valine betaine with an aliphatic side group conferred salt tolerance similar to glycine betaine. Betaines containing phenyl groups (phenylglycine, phenylalanine and N-phenylglycine betaines) did not confer salt protection, growth being similar to, or less than the control (no betaine). Hydrophobic groups decreased the ability to protect against urea stresses; valine betaine conferred poor urea tolerance. The addition of an hydroxyl group increased the ability of a betaine to protect against urea denaturation. Proline betaine, an effective salt protector, conferred poor urea tolerance. Increasing the charge separation in the betaine molecule decreased the ability to confer urea tolerance. Thiolanium, pyridinium and triethylglycine betaines, with larger cationic functions, conferred no urea tolerance to E. coli.
Biochimica et Biophysica Acta 01/1997; 1291(3):189-94. · 4.66 Impact Factor
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ABSTRACT: The regulation of intracellular concentrations of organic solutes, including glycine betaine, is an important adaptive response to osmotic stress for Escherichia coli. The clinical significance of glycine betaine to uropathogens is not clear. Clinical isolates of E. coli, Klebsiella pneumoniae, Enterobacter species, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, S. saprophyticus, and Enterococcus faecalis accumulated glycine betaine from hyperosmotic media. The addition of glycine betaine to hyperosmotic minimal medium accelerated the growth rates of all species tested except P. mirabilis. However, when clinical strains of E. coli were transferred from urine with low osmolality to hyperosmotic urine, there was no slowing of the growth rate. There was no difference in growth rates of E. coli isolates from acute pyelonephritis, cystitis, and asymptomatic bacteriuria nor from fecal isolates. The ability to accumulate osmolytes, although it may be a factor in the adaptation to hypertonic environments, was not related to virulence.
Journal of Laboratory and Clinical Medicine 11/1996; 128(4):417-22. · 2.62 Impact Factor
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Nephron 02/1996; 74(1):1-10. · 13.26 Impact Factor
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ABSTRACT: Intracellular accumulation of different betaines was compared in osmotically stressed Madin Darby canine kidney (MDCK) cells to model the betaine accumulation specificity of the mammalian inner medulla and to show how this accumulation differed from that of bacteria. All betaines accumulated less than glycine betaine. Arsenobetaine (the arsenic analogue of glycine betaine) accumulated to 12% of the glycine betaine levels and the sulphur analogue dimethylthetin accumulated to >80%. Most substituted glycine betaine analogues accumulated to 2-5% of intracellular glycine betaine concentrations, however, serine betaine accumulated to <0.5% of glycine betaine levels. Inhibition studies to distinguish the betaine ports were performed by the addition of proline. Butyrobetaine and carnitine accumulation was not proline sensitive, whereas that of other betaines was. As with glycine betaine, the accumulation of propionobetaine and dimethylthetin was proline sensitive and osmoregulated. Pyridinium betaine was accumulated by both proline-sensitive and -insensitive systems, with a small increase under osmotic stress. High concentrations (10 times that of glycine betaine) of the dietary betaines proline betaine and trigonelline inhibited total betaine accumulation. Because alpha-substituted betaines are accumulated by bacteria and not by MDCK cells, these betaines may be the basis for design of antimicrobial agents.
Biochemistry and Cell Biology 02/1996; 74(2):283-7. · 2.67 Impact Factor
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ABSTRACT: Escherichia coli was grown in hyperosmotic media containing both glycine betaine and one other betaine. E. coli K-12 derivative WG439 (putP- proP- proU-) did not accumulate any of 15 betaines. Strains WG445 (putP- proP- proU+), WG443 (putP- proP+ proU-) and the control strains all accumulated less betaine, (CH3)3N(+)-(CH2)n-COO-, when n was greater than 1. Accumulation was not detectable when n = 5. Both L- and D-isomers of alpha-substituted betaines were accumulated by both strains WG443 and WG445, the D-isomers more slowly. Hydroxylated alpha-substituted betaines were accumulated relatively more through the osmoregulated transport protein ProU than through ProP. In actively growing cultures glycine betaine appeared to be the preferred substrate for accumulation, but the proportion of the second accumulated betaine increased as cultures approached stationary phase.
Biochimica et Biophysica Acta 09/1995; 1245(1):116-20. · 4.66 Impact Factor
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ABSTRACT: The cells of the inner medulla of the mammalian kidney accumulate high concentrations of nonurea organic osmolytes. The organic osmolytes found in the kidney include glycine betaine and sorbitol. This study was designed to measure changes in the urinary excretion of glycine betaine and sorbitol and the plasma concentration of glycine betaine in response to an acute water load (20 ml/kg) or acute water deprivation in young healthy males. In response to a water load the urinary excretion of glycine betaine and sorbitol increased parallel with or shortly after urinary urea excretion. The increase in urinary urea and sorbitol excretions preceded maximum minute volume, whereas peak glycine betaine excretion was closely related to maximum urine minute volume. Subsequently, urea, sorbitol, and glycine betaine excretion rates returned to baseline. In contrast, during water deprivation no change in glycine betaine, sorbitol, and urea urinary excretions occurred during the study period. Plasma glycine betaine concentration was stable during both diuresis and antidiuresis. We conclude that the organic osmolytes glycine betaine and sorbitol are components of a physiological and dynamic system in response to an acute water diuresis.
The American journal of physiology 03/1995; 268(2 Pt 2):F227-33.
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ABSTRACT: In normal human plasma the concentrations of the renal osmolyte, glycine betaine, are usually between 20 and 70 mumol/l, in adult males (median 44 mumol/l) higher than in females (34 mumol/l). Concentrations are lower in renal disease (median 28 mumol/l) and normal in diabetes. Urinary excretion of glycine betaine shows no sex difference and is frequently elevated both in renal disease and in diabetes (medians: normal, 6.2, renal 12.3 and diabetes, 39.7 mmol/mol creatinine). The elevation in diabetes does not strongly correlate with known renal disease, nor with either urinary microalbumin or plasma creatinine. There is no correlation with glycated haemoglobin. The positive correlation with the excretions of another renal osmolyte, sorbitol, was highly significant in diabetic subjects. In the diabetic group there was also a significant negative correlation between plasma glycine betaine and urine microalbumin.
Clinica Chimica Acta 11/1994; 230(1):69-79. · 2.54 Impact Factor
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ABSTRACT: In healthy human subjects, glycine betaine concentrations in the blood plasma are normally between 20 and 60 mumol/l, adult males tending to have higher concentrations than females. Proline betaine concentrations are more variable, ranging from undetectable to about 50 mumol/l. Both betaines are present in urine. Whereas the urinary excretion of proline betaine reflects plasma concentrations, with high clearance rates, there is no correlation between plasma and urine glycine betaine concentrations. The apparent clearance rates are low (usually less than 5%). The proline betaine content of human kidney tissue is less than 0.1% of the glycine betaine content, and this is true also of rabbit tissue despite high concentrations of both betaines in rabbit circulation and urine. These data suggest that glycine betaine, but not proline betaine, is important in human and other mammalian biochemistry.
Biochimica et Biophysica Acta 09/1994; 1200(3):259-64. · 4.66 Impact Factor
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ABSTRACT: Naturally occurring betaines, especially glycine betaine and proline betaine, were accumulated by Escherichia coli from urine. In synthetic hyperosmotic medium, with an homologous series of added betaines, (CH3)3N(+)-(CH2)n-COO-, osmoprotective activity and intracellular accumulation decreased monotonically as n increased from 1 to 5. In contrast, alpha-substituted glycine betaines were accumulated in a similar manner to glycine betaine, but with different osmoprotective activities. Arsenobetaine, with a quaternary arsonium group, was also accumulated but amino acids which can become negatively charged in a chemically basic environment were not.
FEMS Microbiology Letters 08/1994; 120(1-2):125-31. · 2.04 Impact Factor
