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The clinical significance of betaine,an osmolyte with a key role in methyl group metabolism
Authors:Michael Lever  Sandy Slow
Institution:1. Department of Obstetrics & Gynecology, St. Michael''s Hospital & University of Toronto, Toronto, ON, Canada;2. Department of Obstetrics and Gynecology, Assuta Ashdod University Hospital, Ashdod, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel;3. The Keenan Research Center for Biomedical Science of St. Michael''s Hospital, Toronto, Ontario, Canada;4. Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada;5. Department of Medicine, University of Toronto, Toronto, Ontario, Canada;6. Division of Nutritional Sciences, College of Human Ecology, Cornell University, Ithaca, NY;7. Freelance statistics consultant, Toronto, Ontario, Canada;8. Research Institute, the Hospital for Sick Children;9. The Division of Gastroenterology, Department of Medicine, St. Michael''s Hospital, Toronto, Ontario, Canada
Abstract: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 μmol/L and in men 25–75 μmol/L. Plasma dimethylglycine is typically < 10 μmol/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.
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