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

Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial

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 (χ2 P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ2 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 (χ2 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) ACTRN1260900048622

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

Legionellosis Caused by Non-Legionella pneumophila Species, with a Focus on Legionella longbeachae

Although known as causes of community-acquired pneumonia and Pontiac fever, the global burden of infection caused by Legionella species other than Legionella pneumophila is under-recognised. Non-L. pneumophila legionellae have a worldwide distribution, although common testing strategies for legionellosis favour detection of L. pneumophila over other Legionella species, leading to an inherent diagnostic bias and under-detection of cases. When systematically tested for in Australia and New Zealand, L. longbeachae was shown to be a leading cause of community-acquired pneumonia. Exposure to potting soils and compost is a particular risk for infection from L. longbeachae, and L. longbeachae may be better adapted to soil and composting plant material than other Legionella species. It is possible that the high rate of L. longbeachae reported in Australia and New Zealand is related to the composition of commercial potting soils which, unlike European products, contain pine bark and sawdust. Genetic studies have demonstrated that the Legionella genomes are highly plastic, with areas of the chromosome showing high levels of recombination as well as horizontal gene transfer both within and between species via plasmids. This, combined with various secretion systems and extensive effector repertoires that enable the bacterium to hijack host cell functions and resources, is instrumental in shaping its pathogenesis, survival and growth. Prevention of legionellosis is hampered by surveillance systems that are compromised by ascertainment bias, which limits commitment to an effective public health response. Current prevention strategies in Australia and New Zealand are directed at individual gardeners who use potting soils and compost. This consists of advice to avoid aerosols generated by the use of potting soils and use masks and gloves, but there is little evidence that this is effective. There is a need to better understand the epidemiology of L. longbeachae and other Legionella species in order to develop effective treatment and preventative strategies globally

Variability of plasma and urine betaine in diabetes mellitus and its relationship to methionine load test responses: an observational study

Abstract Background Since betaine is an osmolyte and methyl donor, and abnormal betaine loss is common in diabetes mellitus (>20% patients), we investigated the relationship between betaine and the post-methionine load rise in homocysteine, in diabetes and control subjects. The post-methionine load test is reported to be both an independent vascular risk factor and a measure of betaine sufficiency. Methods Patients with type 2 diabetes (n = 34) and control subjects (n = 17) were recruited. We measured baseline fasting plasma and 4-hour post-methionine load (L-methionine, 0.1 mg/kg body weight) concentrations of homocysteine, betaine, and the betaine metabolite N,N-dimethylglycine. Baseline urine excretions of betaine, dimethylglycine and glucose were measured on morning urine samples as the ratio to urine creatinine. Statistical determinants of the post-methionine load increase in homocysteine were identified in multiple linear regression models. Results Plasma betaine concentrations and urinary betaine excretions were significantly (p p = 0.00014) and plasma dimethylglycine concentrations (p = 0.039) were also more variable. In diabetes, plasma betaine was a significant negative determinant (p  Conclusions Both high and low plasma betaine concentrations, and high and low urinary betaine excretions, are more prevalent in diabetes. The availability of betaine affects the response in the methionine load test. The benefits of increasing betaine intake should be investigated.</p

SIT1 is a betaine/proline transporter that is activated in mouse eggs after fertilization and functions until the 2-cell stage

Betaine (N,N,N-trimethylglycine) added to culture media is known to substantially improve the development of preimplantation mouse embryos in vitro, and to be imported into 1-cell embryos by a transporter that also accepts proline. Here, we found that the betaine/proline transporter is active in preimplantation mouse embryos only for a short period of development, between the 1- and 2-cell stages. Betaine/proline transport was activated after fertilization, beginning ∼4 hours post-egg activation and reaching a maximum by ∼10 hours. One- and 2-cell embryos contained endogenous betaine, indicating that a likely function for the transporter in vivo is the accumulation or retention of intracellular betaine. The appearance of transport activity after egg activation was independent of protein synthesis, but was reversibly blocked by disruption of the Golgi with brefeldin A. We assessed two candidates for the betaine/proline transporter: SIT1 (IMINO; encoded by Slc6a20a) and PROT (Slc6a7). mRNA from both genes was present in eggs and 1-cell embryos. However, when exogenously expressed in Xenopus oocytes, mouse PROT did not transport betaine and had an inhibition profile different from that of the embryonic transporter. By contrast, exogenously expressed mouse SIT1 transported both betaine and proline and closely resembled the embryonic transporter. A morpholino oligonucleotide designed to block translation of SIT1, when present from the germinal vesicle stage, blocked the appearance of betaine transport activity in parthenogenotes. Thus, SIT1 is likely to be a developmentally restricted betaine transporter in mouse preimplantation embryos that is activated by fertilization

Effect of adjunctive single high-dose vitamin D3 on outcome of community-acquired pneumonia in hospitalised adults: The VIDCAPS randomised controlled trial

Abstract 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

The contrasting relationships between betaine and homocysteine in two clinical cohorts are associated with plasma lipids and drug treatments.

BACKGROUND: Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease. METHODS: The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic. PRINCIPAL FINDINGS: In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = -0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = -0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion. CONCLUSIONS: Betaine excretion correlates with homocysteine in subjects with elevated blood lipids