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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., (Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25OHD) concentrations and Staphylococcus aureus nasal carriage; however, clinical trials of vitamin D supplementation are lacking. To assess the effect of vitamin D3 supplementation on persistent S. aureus nasal carriage we conducted a randomized, double-blind, placebo-controlled trial among 322 healthy adults. Participants were given an oral dose of either 200 000 IU vitamin D3 for each of 2 months, followed by 100 000 IU monthly or placebo in an identical dosing regimen, for a total of 18 months. Nasal swabs for S. aureus culture and serum for 25OHD measurement were obtained at baseline, 6, 12 and 18 months of study. The mean baseline concentration of 25OHD was 72 nM (SD 22 nM). Vitamin D3 supplementation increased 25OHD levels which were maintained at >120 nM throughout the study. Nasal colonization by S. aureus was found in 31% of participants at baseline. Persistent carriage, defined as those that had positive S. aureus nasal cultures for all post-baseline swabs, occurred in 20% of the participants but vitamin D3 supplementation was not associated with a reduction in persistent carriage (OR = 1.39, 95% CI 0.63-3.06). Risk factor analysis showed that only gender was significantly associated with carriage, where women were less likely to be carriers than men (relative risk 0.83, 95% CI 0.54-0.99). Serum 25OHD concentrations were not associated with the risk of carriage. In conclusion, monthly administration of 100 000 IU of vitamin D3 did not reduce persistent S. aureus nasal carriage., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Background and Aims: 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., Methods and Results: 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., Conclusions: Supplemental or dietary betaine similarly increase circulating betaine concentrations and attenuate the post-methionine load rise in homocysteine concentrations.

Choline is an essential nutrient which is difficult to measure because it has no native absorbance or fluorescence and only relatively unreactive functional groups. The method described here uses the reaction of the hydroxyl group on choline with 1-naphthyl isocyanate to form a stable cationic aromatic urethane that can be measured by high performance liquid chromatography (HPLC) on a cation exchange column, followed by fluorescence detection. The sample was directly added to acetonitrile and mixed with magnesium oxide and 1-naphthyl isocyanate. The 1-naphthylurethane choline derivative was separated by HPLC using a strong cation exchange column with a tetramethylammonium glycolate buffer in the mobile phase, and measured by fluorescence detection. The recoveries from blood plasma were over 94%. In this study an internal standard was not used, and quantification was achieved by calibration using standards containing known choline concentrations. The within batch and between batch coefficients of variation (CVs) were below 6%. The response was linear over the biological range investigated (8.9-58.9 micromol L(-1), r2=0.998). This is a technically simple method that can be carried out with an inexpensive HPLC system with fluorescence detection. It has sufficient sensitivity to measure choline in biological materials such as human plasma, and is suitable for processing batches of samples.

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.

Glycine betaine supplementation lowers homocysteine levels in homocystinuria and in chronic renal failure patients through methylation catalysed by betaine-homocysteine methyltransferase (BHMT). The aim of this study was to determine the effect of glycine betaine analogues on homocysteine metabolism in Lewis rats. Glycine betaine, proline betaine, trigonelline, dimethylsulfoniopropionate (DMSP) or dimethylthetin (1.5 mmoles) was subcutaneously administered to rats fed a low betaine diet. The effect of each betaine on total plasma homocysteine and urinary and plasma betaine concentrations was monitored for 24h following administration. Baseline plasma homocysteine was 8.5 +/- micromol/l (S.E.M., n=44) and compared to controls concentrations decreased following glycine betaine (0.8+/-0.4 micromol/l, P = 0.064), DMSP (1.0+/-0.5 micromol/l, P = 0.041) and dimethylthetin (1.5 +/- 0.7micromol/l, P = 0.033) treatment, while concentrations increased following proline betaine (2.24 +/-0.7micromol/l, P = 0.002) and trigonelline (1.6 +/-0.3 micromol/l, P < 0.001) treatment. The effect of glycine betaine, DMSP and dimethylthetin on circulating homocysteine concentrations was thought to be mediated by BHMT in vivo. This hypothesis was supported by the finding that circulating glycine betaine concentrations increased following DMSP and dimethylthetin treatment. Proline betaine and trigonelline appeared to be poor BHMT substrates, being largely excreted in the urine unchanged, yet increased circulating homocysteine levels. This suggests they are inhibitors of BHMT. Urinary excretion of glycine betaine increased following treatment with all betaines, suggesting that the resorption of glycine betaine in the kidney was inhibited. The study shows that glycine betaine analogues have multiple effects on homocysteine metabolism (250).