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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLAs) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient.
|Proper name(s)||Common name(s)||Source material(s)|
1-Carboxy-N,N,N-trimethylmethanaminium inner salt (Moffat et al. 2014; O'Neil et al. 2006)
(Carboxymethyl)trimethylammonium hydroxide inner salt (Martindale 2014; O'Neil et al. 2006)
1-Carboxy-N,N,N-trimethylmethanaminium chloride (O'Neil et al. 2006)
(Carboxymethyl)trimethylammonium chloride (O'Neil et al. 2006)
Statement(s) to the effect of
Helps to support liver function (Kempson et al. 2014; Obeid 2013; Ueland 2011; Lever and Slow 2010; Purohit et al. 2007; Pajares and Perez-Sala 2006; Craig 2004; Patrick 2002; Barak et al. 1996).
Helps to support digestion / Digestive aid (DNP 2014; Moffat et al. 2014; O'Neil et al. 2006)
|Betaine||500||4000||Schwab et al. 2011; Atkinson et al. 2008|
|Betaine hydrochloride||650 mg; not to exceed 1000 mg per single dose||3500||Allen Jr. 2014; Moffat et al. 2014; Atkinson et al. 2008|
|Betaine hydrochloride||180 mg; not to exceed 1000 mg per single dose||3500||Allen Jr. 2014; Moffat et al. 2014|
Directions for use
Take with food/meal (Allen Jr. 2014; Moffat et al. 2014).
If you are pregnant or breastfeeding, consult a health care practitioner prior to use.
If you have a peptic ulcer or excess stomach acid, consult a health care practitioner prior to use (Hendler and Rorvik 2008; O'Neil et al. 2006).
If you have high cholesterol, consult a health care practitioner prior to use (Olthof et al. 2005; Swab et al. 2002).
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Craig SAS. Betaine in human nutrition. American Journal of Clinical Nutrition 2004;80:539-549.
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Lever M. Slow S. The clinical significance of betaine, an osmolytes with a key role in methyl group metabolism. Clinical Biochemistry 2010;43:732-744.
Martindale 2014: Sweetman SC, editor. Martindale: The Complete Drug Reference [Internet] London (GB): Pharmaceutical Press; Copyright 1933-2014. [Accessed 2014 July 03].
Moffat AC, Osselton MD, Widdop B, Watts J (Editors). Clarke's analysis of drugs and poisons. Pharmaceutical Press. Royal Pharmaceutical Society. 2014. [Accessed 2014 July 03].
Obeid R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients 2013;5:3481-3495.
Olthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB. Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in health humans. PLoS Medicine 2005;2(5):e135.
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Pajares MA, Perez-Sala D. Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? Cellular and Molecular Life Sciences 2006;63:2792-2803.
Patrick L. Nonalcoholic Fatty Liver Disease: Relationship to Insulin Sensitivity and Oxidative Stress. Treatment Approaches Using Vitamin E, Magnesium, and Betaine. Alternative Medicine Review 2002;7(4):276-291.
Purohit V, Abdelmalek MF, Barve S, Benevenga NJ, Halsted CH, Kaplowitz N, Kharbanda KK, Liu Q-Y, Lu SC, McClain CJ, Swanson C, Zakhari S. Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a symposium. Americal Journal of Clinical Nutrition 2007;86:14-24.
Swab U, Alfthan G, Aro A, Uusitupa M. Long-term effect of betaine on risk factors associated with the metabolic syndrome in healthy subjects. European Journal of Clinical Nutrition 2011; 65:70-76.
Swab U, Torronen A, Toppinen L, Alfthan G, Saarinen M, Aro A, Uusitupa M. Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. American Journal of Clinical Nutrition 2002;76:961-967.
Ueland MP. Choline and betaine in health and disease. Journal of Inherited Metabolic Disease 2011;34:3-15.
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Abdelmalek MF, Angulo A, Jorgensen RA, Sylvestre PB, Lindor KD. Betaine, a promising new agent for patients with non-alcoholic steatohepatitis: results of a pilot study. American Journal of Gastroenterology 2001;96(9):2711-2717.
Abdelmalek MF, Sanderson SO, Angulo P, Soldevila-Pico C, Liu C, Peter J, Keach J, Cave M, Chen T, McClain CJ, Lindor KD. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepatology 2009;50:1818-1826.
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AMA 2010. Homocysteine, Folic Acid and Cardiovascular Disease.. American Heart Association [Accessed 2014 July 11].
Atkinson W, Slow S, Elmslie J, Lever M, Chambers ST, George PM. Dietary and supplementary betaine: Effects on betaine and homocysteine concentrations in males. Nutrition, Metabolism & Cardiovascular Diseases 2009;19:767-773.
Bellis HE. Process for making aqeous betaine solutions. United States Patent 1997;5,696,287.
Bidulescu A, Chambless LE, Siega-Riz AM, Zeisel SH, Heiss G. Usual choline and betaine dietary intake and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. BMC Cardiovascular Disorders 2007;7:20.
del Favero S, Roschel H, Artioli G, Ugrinowitsch C, Tricoli V, Costa A, Barroso R, Negrelli AL, Otaduy MC, da Costa Leite C, Lancha-Junior AH, Gualano B. Creatine but not Betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids 2012;42:2299-2305.
Edsall JT. Raman spectra of amino acids and related compounds. VI. Sarcosine, ethanolamine, choline, betaine and betaine derivatives. Journal of the Americal Chemical Society1943;66:1767-1770.
Diekman EF, de Koning TJ, Verhoeven-Duif NM, Rovers MM, van Hasselt PM. Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency. JAMA Neurology 2014;71(2):188-194.
Eussen SJPM, Ueland PM, Clarke R, Blom HJ, Hoefnagels WHL, van Staveren WA, Groot LCPGM. The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people. British Journal of Nutrition 2007;98:960-968.
Filipowicz M, Bernsmeier C, Terracciano L, Duong FHT, Heim MH. S-Adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse. PLoS One 2010;5(11):e15492.
Gahl WA, Bernardini I, Chen S, Kurtz D, Horvath K. The effect of oral betaine on vertebral body bone density in pyridoxine-non-responsive homocystinuria. Journal of inherited Metabolic Disease 1988;11:291-298.
Glaze DG, Percy AK, Motil KJ, Lane JB, Isaacs JS, Schultz RJ, Barrish JO, Neul JL, O'Brien WE, Smith EO. A Study of the treatment of Rett syndrome with folate and betaine. Journal of Child Neurology 2009;25(5):551-556
Hoffman JR, Ratamess NA, Kang J, Gonzalez AM, Beller NA, Craig SAS. Effect of 15 days of betaine ingestion on concentric and eccentric force outputs during isokinetic exercise. Journal of Strength and Conditioning Research 2011;25(8):2235-2241.
Hoffman JR, Ratamess NA, Kang J, Rashti SL, Faigenbaum AD. Effect of betaine supplementation on power performance and fatigue. Journal of the International Society of Sports Nutrition 2009;6:7.
Holm PI, Bleie O, Ueland PM, Lien EA, Refsum H, Nordrehaug JE, Nygard O. Betaine as a determinant of postmethionine load total plasma homocysteine before and after B-vitamins supplementation. Arteriosclerosis, Thrombosis, and Vascular Biology 2004;24:301-307.
Innis SM, Hasman D. Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis. Journal of Nutrition 2006;136:2226-2231.
Lawson-Yuen A, Levy HL. The use of betaine in the treatment of elevated homocysteine. Molecular Genetics and Metabolism 2006;88:201-207.
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Lever M, Atkinson W, Slow S, Chambers ST, George PM. Plasma and urine betaine and dimethylglycine variation in healthy young male subjects. Clinical Biochemistry 2009;42:706-712.
Lever M, George PM, Slow S, Elmslie JL, Scott RS, Richards AM, Fink JN, Chambers ST. Fibrates may cause an abnormal urinary betaine loss which is associated with elevations in plasma homocysteine. Cardiovascular Drugs and Therapy 2009;23:395-401.
McGregor DO, Dellow WJ, Robson RA, Lever M, George PM, Chambers ST. Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure. Kidney International 2002;61:1040-1046.
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Olthof MR, van Vliet T, Boelsma E, Verthoef P. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. Journal of Nutrition 2003;133:4135-4138.
Olthof MR, Verhoef P. Effects of betaine intake on plasma homocysteine concentrations and consequences for health. Current Drug Metabolism 2005;6:15-22.
Peters SU, Bird LM, Kimonis V, Glaze DG, Shinawi LM, Bichell TJ, Barbieri-Welge R, Nespeca M, Anselm I, Waisbren S, Sanborn E, Sun Q, O'Brien WE, Beaudet AL, Bacino CA. Double-blind therapeutic trial in angelman syndrome using betaine and folic acid. American Journal of Medical Genetics Part A;2010;152A:1994-2001.
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Price RK, Keaveney EM, Hamill LL, Wallace JMW, Ward M, Ueland PM, McNulty H, Strain JJ, Parker MJ, Welch RW. Consumption of wheat aleurone-rich foods increases fasting plasma betaine and modestly decreases fasting homocysteine and LDL-cholesterol in adults. Journal of Nutrition 2010;140:2153-2157.
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Swab U, Torronen A, Meririnne E, Saarinen M, Alfthan G, Aro A, Uusitupa M. Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans. Journal of Nutrition 2006;136:34-38.
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