RESUMO
Patients hospitalised with community acquired pneumonia (CAP) have low peripheral blood vitamin C concentrations and limited antioxidant capacity. The feasibility of a trial of vitamin C supplementation to improve patient outcomes was assessed. Participants with moderate and severe CAP (CURB-65 ≥ 2) on intravenous antimicrobial treatment were randomised to either intravenous vitamin C (2.5 g 8 hourly) or placebo before switching to oral intervention (1 g tds) for 7 days when they were prescribed oral antimicrobial therapy. Of 344 patients screened 75 (22%) were randomised and analysed. The median age was 76 years, and 43 (57%) were male. In each group, one serious adverse event that was potentially intervention related occurred, and one subject discontinued treatment. Vitamin C concentrations were 226 µmol/L in the vitamin C group and 19 µmol/L in the placebo group (p < 0.001) after 3 intravneous doses. There were no signficant differences between the vitamin C and placebo groups for death within 28 days (0 vs. 2; p = 0.49), median length of stay (69 vs. 121 h; p = 0.07), time to clinical stability (22 vs. 49 h; p = 0.08), or readmission within 30 days (1 vs. 4; p = 0.22). The vitamin C doses given were safe, well tolerated and saturating. A randomised controlled trial to assess the efficacy of vitamin C in patients with CAP would require 932 participants (CURB-65 ≥ 2) to observe a difference in mortality and 200 participants to observe a difference with a composite endpoint such as mortality plus discharge after 7 days in hospital. These studies are feasible in a multicentre setting.
Assuntos
Ácido Ascórbico , Pneumonia , Adulto , Humanos , Masculino , Idoso , Feminino , Ácido Ascórbico/uso terapêutico , Estudos de Viabilidade , Pneumonia/tratamento farmacológico , Vitaminas , Infusões IntravenosasRESUMO
OBJECTIVES: Supplementation provides the best means of improving vitamin D status; however, individual responses vary partly owing to genetics. The aim of this study was to determine whether 28 single nucleotide polymorphisms (SNPs) in six key vitamin D pathway genes (GC, DHCR7, CYP2 R1, CYP24 A1, CYP27 B1, VDR) were associated with differences in response to supplementation. METHODS: Participants (N = 313; n = 160 vitamin D, n = 153 placebo) were part of VIDARIS (Vitamin D and Acute Respiratory Infections Study), a double-blind, randomized controlled trial involving oral monthly supplementation of either vitamin D3 (200 000 IU each for the first 2 mo, thereafter 100 000 IU monthly) or placebo for 18 mo. Circulating 25-hydroxyvitamin D (25[OH]D) concentrations at baseline and 2, 6, 12, and 18 mo, and vitamin D binding protein (Gc-globulin) and calculated free 25(OH)D concentrations at baseline and 2 mo were obtained. Multiple regression was used to model associations between genetic variants and 25(OH)D, Gc-globulin, and free 25(OH)D concentrations. RESULTS: SNPs within GC, CYP2 R1, and CYP27 B1 were associated with 25(OH)D concentrations following supplementation. However, only two GC gene SNPs (rs2282679, rs1155563) were significant after adjustment for multiple testing. This effect disappeared after more than 2 mo of supplementation. None of the SNPs were significantly associated with Gc-globulin concentrations; however, there was a significant interaction with one SNP in DHCR7 (rs12785878), which was associated with reduced free 25(OH)D concentrations in the supplemented arm. CONCLUSION: Only variants of GC were associated with 25(OH)D concentrations after supplementation. This effect was modest and disappeared after >2 mo of supplementation, suggesting it may be time/dose-dependent and saturable.
Assuntos
Colecalciferol , Deficiência de Vitamina D , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Vitamina D , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/genética , Proteína de Ligação a Vitamina D/genéticaRESUMO
Low vitamin D status is associated with increased risk of pneumonia, greater disease severity and poorer outcome. However, no trials have examined the effect of adjunctive vitamin D therapy on outcomes in adults with community-acquired pneumonia (CAP). We conducted a randomised, double-blind, placebo-controlled trial examining the effects of adjunctive vitamin D in adults hospitalised with CAP. Participants were randomised to either a single oral dose of 200,000 IU vitamin D3 or placebo. The primary outcome was the complete resolution of chest radiograph infiltrate at 6 weeks post-study treatment. Secondary outcomes included length of hospital stay, intensive care admission and return to normal activity. Only participants who completed the study or died within the 6 week period were included in the analysis (n = 60 vitamin D, n = 57 placebo). Adjunctive vitamin D did not have any effect on the primary outcome (OR 0.78, 95% CI 0.31 to 1.86, p = 0.548). However, there was evidence it increased the complete resolution of pneumonia in participants with baseline vitamin D levels <25 nmol/L (OR 17.0, 95% CI 1.40-549.45, P = 0.043), but this did not reach statistical significance using exact methods (OR 13.0, 95%CI 0.7-960.4, P = 0.083). There were no significant effects for any secondary outcome.
Assuntos
Colecalciferol/administração & dosagem , Colecalciferol/uso terapêutico , Pneumonia/tratamento farmacológico , Adulto , Idoso , Colecalciferol/metabolismo , Infecções Comunitárias Adquiridas/tratamento farmacológico , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Efeito Placebo , Vitamina D/administração & dosagem , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/administração & dosagemRESUMO
OBJECTIVE: To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. DESIGN: Opportunistic addition to an established randomised double blind placebo controlled trial. SETTING: Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. PARTICIPANTS: 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. INTERVENTION: Participants were randomised to receive an oral dose of either 200,000 IU vitamin D3 monthly for two months then 100,000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. MAIN OUTCOME MEASURE: This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of "psychological" adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. RESULTS: 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ(2) P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ(2) P=0.03). The number of psychological adverse events-such as fatigue, stress, anxiety, and insomnia-that participants reported at their usual monthly appointments was significantly higher after the earthquake (χ(2) P=0.007) but did not differ between treatment groups. CONCLUSION: In this trial, vitamin D supplementation did not reduce the adverse impact of earthquakes in healthy adults. Trial registration Australian New Zealand Clinical Trials Registry (anzctr.org.au) ACTRN12609000486224.
Assuntos
Ansiedade/prevenção & controle , Colecalciferol/uso terapêutico , Terremotos , Fadiga/prevenção & controle , Distúrbios do Início e da Manutenção do Sono/prevenção & controle , Vitaminas/uso terapêutico , Administração Oral , Adulto , Idoso , Ansiedade/etiologia , Suplementos Nutricionais , Método Duplo-Cego , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Inquéritos e Questionários , Fatores de Tempo , Falha de TratamentoRESUMO
BACKGROUND: Cross-sectional data suggest that bezafibrate increases betaine excretion in dyslipidemic patients. OBJECTIVE: We aimed to demonstrate that fenofibrate induces increased betaine excretion in normal subjects and explore whether other 1-carbon metabolites and osmolytes are similarly affected. METHODS: Urine was collected from 26 healthy adults before and after treatment with fenofibrate (145 mg/day for 6 weeks). Excretions of betaine, N,N-dimethylglycine, free choline, myo-inositol, taurine, trimethylamine-N-oxide, carnitine, and acetylcarnitine were measured by liquid chromatography with mass spectrometric detection. RESULTS: Fenofibrate increased the median betaine excretion from 7.5 to 25.8 mmol/mole creatinine (median increase 3-fold), P < .001. The median increase in N,N-dimethylglycine excretion was 2-fold (P < .001). Median choline excretion increased 12% (significant, P = .029). Participants with higher initial excretions tended to have larger increases (P < .001 in all 3 cases). Fenofibrate did not significantly change the median excretions of myo-inositol, taurine, trimethylamine-N-oxide, and carnitine. The excretion of acetylcarnitine decreased 4-fold on treatment, with no correlation between the baseline and after-treatment excretions. Changes in all urine components tested, except trimethylamine-N-oxide, positively correlated with changes in betaine excretion even when the median excretions before and after were not significantly different. CONCLUSIONS: Fibrates increase betaine, and to a lesser extent N,N-dimethylglycine and choline, excretion. Other osmolytes are not elevated. Because the increase in betaine excretion depends on the baseline excretion, large increases in excretion in the metabolic syndrome and diabetes (where baseline excretions are high) could be expected. Replacement with betaine supplements may be considered.
Assuntos
Betaína/urina , Dislipidemias/tratamento farmacológico , Fenofibrato/administração & dosagem , Hipolipemiantes/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Colina/urina , Cromatografia Líquida , Feminino , Fenofibrato/efeitos adversos , Humanos , Hipolipemiantes/efeitos adversos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Sarcosina/análogos & derivados , Sarcosina/urinaRESUMO
PURPOSE: Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes? METHODS: Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate (n = 32). These samples were compared with participants matched for age and gender and not on a fibrate (comparator group, n = 64). Betaine, related metabolites, and osmolytes were measured in plasma and urine samples from these 96 participants. RESULTS: Median urinary betaine excretion in those on bezafibrate was 5-fold higher than in the comparator group (p < 0.001), itself 3.5-fold higher than the median reported for healthy populations. In the bezafibrate group, median dimethylglycine excretion was higher (9-fold, p < 0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and glycerophosphorylcholine, were not significantly different between groups. Some participants excreted more betaine than usual dietary intakes. Several betaine fractional clearances were >100 %. Betaine excretion correlated with excretions of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the excretion of choline and N,N-dimethylglycine, but it was inconclusive whether these relationships were affected by bezafibrate therapy. CONCLUSIONS: Increased urinary betaine excretions in type 2 diabetes are further increased by fibrate treatment, sometimes to more than their dietary intake. Concurrent betaine supplementation may be beneficial.
Assuntos
Betaína/urina , Bezafibrato/efeitos adversos , Colina/urina , Diabetes Mellitus Tipo 2/urina , Hipolipemiantes/efeitos adversos , Sarcosina/análogos & derivados , Adulto , Idoso , Betaína/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Glicerilfosforilcolina/urina , Homocisteína/sangue , Humanos , Inositol/urina , Masculino , Pessoa de Meia-Idade , Sarcosina/urina , Taurina/urina , Adulto JovemRESUMO
Previous randomized controlled trials of vitamin D supplementation and blood pressure (BP) mainly have given vitamin D for short periods (<6 months) or at low doses (400 IU per day). This study aims to determine whether long-term high-dose vitamin D taken for 18 months lowers BP. Adults were recruited from a healthcare organization or university into a double-blind controlled trial and randomized to receive either vitamin D3 200 000 IU for 2 months followed by 100 000 IU monthly up to 18 months (n=161) or placebo (n=161). BP was measured at baseline, 5, and 18 months. Subjects had a mean (SD) age of 47.6 (9.7) years, 75% were women, and 94% were of European ancestry (white). Mean (SD) 25-hydroxyvitamin D3 changed from 73 (22) nmol/L at baseline to 124 (28) nmol/L at 18 months in the vitamin D group, and from 71 (22) nmol/L to 56 (22) nmol/L in the placebo group. Mean BP was similar for the vitamin D and placebo groups at baseline (123.4/76.3 versus 122.6/75.6 mm Hg; respectively). The mean change (95% confidence interval) in BP at 18 months minus baseline in the vitamin D group compared with placebo group was -0.6 (-2.8 to 1.6) mm Hg for systolic (P=0.61) and 0.5 (-1.1, 2.2) mm Hg for diastolic (P=0.53). Long-term vitamin D supplementation, which increased mean 25-hydroxyvitamin D3 concentration >100 nmol/L for 18 months, had no effect on systolic or diastolic BP in predominantly white, healthy adults without severe vitamin D deficiency. Beneficial effects on BP cannot be ruled out for other populations.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Adolescente , Adulto , Idoso , Pressão Sanguínea/fisiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem , Adulto JovemRESUMO
Betaine (N,N,N-trimethylglycine) has previously been shown to function in cell volume homeostasis in early mouse embryos and also to be a key donor to the methyl pool in the blastocyst. A betaine transporter (SLC6A20A or SIT1) has been shown to be activated after fertilization, but there is no saturable betaine uptake in mouse oocytes or eggs. Unexpectedly, the same high level of betaine is present in mature metaphase II (MII) eggs as is found in one-cell embryos despite the lack of transport in oocytes or eggs. Significant saturable betaine transport is, however, present in intact cumulus-oocyte complexes (COCs). This transport system has an affinity for betaine of â¼227 µM. The inhibition profile indicates that betaine transport by COCs could be completely blocked by methionine, proline, leucine, lysine, and arginine, and transport is dependent on Na(+) but not Cl(-). This is consistent with transport by a y+L-type amino acid transport system. Both transcripts and protein of one y+L isoform, SLC7A6 (y+LAT2), are present in COCs, with little or no expression in isolated germinal vesicle (GV)-stage oocytes, MII eggs, or one-cell embryos. Betaine accumulated by COCs is transferred into the enclosed GV oocyte, which requires functional gap junctions. Thus, at least a portion of the endogenous betaine in MII eggs could be derived from transport into cumulus cells and subsequent transfer into the enclosed oocyte before gap junction closure during meiotic maturation. The oocyte-derived betaine then could be regulated and supplemented by the SIT1 transporter that arises in the embryo after fertilization.
Assuntos
Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Betaína/metabolismo , Blastocisto/metabolismo , Células do Cúmulo/metabolismo , Oócitos/metabolismo , Aminoácidos/metabolismo , Animais , Betaína/farmacocinética , Transporte Biológico/fisiologia , Blastocisto/citologia , Proteínas de Transporte/metabolismo , Células do Cúmulo/citologia , Feminino , Fertilização/fisiologia , Proteínas da Membrana Plasmática de Transporte de GABA , Junções Comunicantes/metabolismo , Íons/metabolismo , Camundongos , Camundongos Endogâmicos , Oócitos/citologia , Gravidez , TrítioRESUMO
CONTEXT: Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25-OHD) levels and incidence of upper respiratory tract infections (URTIs). However, results of clinical trials of vitamin D supplementation have been inconclusive. OBJECTIVE: To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch, New Zealand. INTERVENTION: Participants were randomly assigned to receive an initial dose of 200,000 IU oral vitamin D3, then 200,000 IU 1 month later, then 100,000 IU monthly (n = 161), or placebo administered in an identical dosing regimen (n = 161), for a total of 18 months. MAIN OUTCOME MEASURES: The primary end point was number of URTI episodes. Secondary end points were duration of URTI episodes, severity of URTI episodes, and number of days of missed work due to URTI episodes. RESULTS: The mean baseline 25-OHD level of participants was 29 (SD, 9) ng/mL. Vitamin D supplementation resulted in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study. There were 593 URTI episodes in the vitamin D group and 611 in the placebo group, with no statistically significant differences in the number of URTIs per participant (mean, 3.7 per person in the vitamin D group and 3.8 per person in the placebo group; risk ratio, 0.97; 95% CI, 0.85-1.11), number of days of missed work as a result of URTIs (mean, 0.76 days in each group; risk ratio, 1.03; 95% CI, 0.81-1.30), duration of symptoms per episode (mean, 12 days in each group; risk ratio, 0.96; 95% CI, 0.73-1.25), or severity of URTI episodes. These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels. CONCLUSION: In this trial, monthly administration of 100,000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12609000486224.
Assuntos
Colecalciferol/uso terapêutico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Vitaminas/uso terapêutico , Absenteísmo , Administração Oral , Adulto , Método Duplo-Cego , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Risco , Índice de Gravidade de Doença , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
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 (pâ=â0.0046, pâ=â0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (pâ=â0.014), and the top quintile plasma betaine with heart failure (pâ=â0.043), 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 (pâ=â0.004, <0.001), heart failure (pâ=â0.027, 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 (pâ=â0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (pâ=â0.002). 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.
Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/urina , Betaína/sangue , Betaína/urina , Insuficiência Cardíaca/etiologia , Infarto do Miocárdio/etiologia , Idoso , Idoso de 80 Anos ou mais , Betaína/metabolismo , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/urina , Homocisteína/sangue , Humanos , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/urina , Nova Zelândia , Fatores de Risco , Sarcosina/análogos & derivados , Sarcosina/sangueRESUMO
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)â=â-0.22, p<0.0001) and non-high-density lipoprotein cholesterol (r(s)â=â-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 (pâ=â0.008) and plasma non-HDL cholesterol (pâ=â0.002). In a non-linear relationship betaine was negatively associated with elevated plasma triglycerides (pâ=â0.004) 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 (pâ=â0.003) 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.
Assuntos
Síndrome Coronariana Aguda/sangue , Betaína/sangue , Lipídeos/sangue , Síndrome Coronariana Aguda/urina , Idoso , Idoso de 80 Anos ou mais , Betaína/metabolismo , Betaína/urina , Estudos de Coortes , Complicações do Diabetes/sangue , Complicações do Diabetes/urina , Suplementos Nutricionais , Feminino , Humanos , Hipolipemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Sarcosina/análogos & derivados , Sarcosina/sangue , Sarcosina/metabolismoRESUMO
Betaine is an essential osmolyte and source of methyl groups and comes from either the diet or by the oxidation of choline. Its metabolism methylates homocysteine to methionine, also producing N,N-dimethylglycine. Betaine insufficiency is associated with the metabolic syndrome, lipid disorders and diabetes, and may have a role in vascular and other diseases. Betaine is important in development, from the pre-implantation embryo to infancy. Betaine supplementation improves animal and poultry health, but the effect of long-term supplementation on humans is not known, though reports that it improves athletic performance will stimulate further studies. Subsets of the population that may benefit from betaine supplementation could be identified by the laboratory, in particular those who excessively lose betaine through the urine. Plasma betaine is highly individual, in women typically 20-60 micromol/L and in men 25-75 micromol/L. Plasma dimethylglycine is typically <10 micromol/L. Urine betaine excretion is minimal, even following a large betaine dose. It is constant, highly individual and normally <35 mmol/mole creatinine. The preferred method of betaine measurement is by LC-MS/MS, which is rapid and capable of automation. Slower HPLC methods give comparable results. Proton NMR spectrometry is another option but caution is needed to avoid confusion with trimethylamine-N-oxide.
Assuntos
Betaína/análise , Betaína/uso terapêutico , Suplementos Nutricionais , Feminino , Fármacos Gastrointestinais , Humanos , Masculino , Metabolismo , Metilação , GravidezRESUMO
PURPOSE: Betaine is an osmolyte, supplies methyl groups, and controls plasma homocysteine. Abnormal urinary loss of betaine is common in patients with the metabolic syndrome or diabetes mellitus. These patients are often treated with fibrates which alter renal function and raise plasma homocysteine concentrations. We suggest there is a connection between fibrate treatment and betaine excretion. METHODS: We identified 32 fibrate-treated patients in several studies (total of 740 subjects) and compared the betaine excretion by these with the excretion by other patients, both in the separate studies and in the combined group. We investigated the correlation of betaine excretion with homocysteine in these groups. RESULTS: Patients taking bezafibrate had higher betaine excretion than patients not taking fibrates, p < 0.00001 in some studies with n < 10. Of 32 patients taking bezafibrate, 20 had abnormal (>97.5 %-ile) betaine excretion. Plasma homocysteine correlated positively with betaine excretion in male patients with lipid disorders who were not taking fibrate (n = 68, p = 0.043), but the relationship was stronger if patients taking bezafibrate were included (n = 76, p < 0.00001). In elderly (>65 years) subjects with hypertension there was a similar correlation (n = 19, p = 0.047), which was stronger when a subject taking bezafibrate was included (n = 20, p = 0.013). CONCLUSIONS: Abnormal betaine excretion is common in patients treated with bezafibrate. Bezafibrate appears to exacerbate betaine loss, which will cause a rise in plasma homocysteine. Betaine supplementation could be considered in conjunction with fibrate therapy.
Assuntos
Betaína/urina , Ácido Clofíbrico/efeitos adversos , Homocisteína/sangue , Hipolipemiantes/efeitos adversos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/urina , Idoso , Ácido Clofíbrico/uso terapêutico , Estudos de Coortes , Complicações do Diabetes/sangue , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/urina , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Masculino , S-Adenosilmetionina/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/urinaRESUMO
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.
Assuntos
Betaína/sangue , Betaína/urina , Sarcosina/análogos & derivados , Adulto , Betaína/administração & dosagem , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais , Feminino , Humanos , Masculino , Sarcosina/administração & dosagem , Sarcosina/sangue , Sarcosina/urina , Fatores de Tempo , Adulto JovemRESUMO
Choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (BHMT) are 2 enzymes involved in choline oxidation. BHMT is expressed at high levels in rat liver and its expression is regulated by dietary Met and choline. BHMT is also found in rat kidney, albeit in substantially lower amounts, but it is not known whether kidney BHMT expression is regulated by dietary Met or choline. Similarly, CHDH activity is highest in the liver and kidney, but the regulation of its expression by diet has not been thoroughly investigated. Sprague Dawley rats ( approximately 50 g) were fed, for 9 d in 2 x 3 factorial design (n = 8), an l-amino acid-defined diet varying in l-Met (0.125, 0.3, or 0.8%) and choline (0 or 25 mmol/kg diet). Liver and kidney BHMT and CHDH were assessed using enzymatic, Western blot, and real-time PCR analyses. Liver samples were also fixed for histological analysis. Liver BHMT activity was 1.3-fold higher in rats fed the Met deficient diet containing choline, which was reflected in corresponding increases in mRNA content and immunodetectable protein. Independent of dietary choline, supplemental Met increased hepatic BHMT activity approximately 30%. Kidney BHMT and liver CHDH expression were refractory to these diets. Some degree of fatty liver developed in all rats fed a choline-devoid diet, indicating that supplemental Met cannot completely compensate for the lack of dietary choline in growing rats.
Assuntos
Betaína-Homocisteína S-Metiltransferase/genética , Colina Desidrogenase/genética , Colina/administração & dosagem , Rim/enzimologia , Fígado/enzimologia , Metionina/administração & dosagem , Animais , Dieta , Regulação da Expressão Gênica/efeitos dos fármacos , Lipídeos/análise , Fígado/química , Fígado/crescimento & desenvolvimento , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Aumento de Peso/efeitos dos fármacosRESUMO
OBJECTIVE: To determine whether daily dimethylglycine supplementation affects plasma homocysteine concentrations. DESIGN AND METHODS: A randomized, blinded, crossover design was used. Seven pre-dialysis chronic renal failure patients consumed 400 mg of dimethylglycine or placebo daily for 28 days. Fasting blood samples and 12-h urine samples were collected at baseline and at the end of each treatment period for analysis. RESULTS: No significant differences were observed in plasma homocysteine (P = 0.624), glycine betaine (P = 0.452) and methionine (P = 0.457) concentrations between dimethylglycine and placebo treatments. CONCLUSION: Daily supplementation with dimethylglycine does not affect plasma homocysteine.