Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.
While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.
Abromine, alpha-earleine, betaine, betaine glucuronate, BetaPureTM, Cystadane®, glycine, glycine betaine, glycocoll betaine, glycylbetaine, hydroxide, inner salt, lycine, oxyneurine, TMG, trimethylammonioacetate trimethylbetaine, trimethylglycine, trimethylglycocoll.
Note: This monograph covers betaine anhydrous, which should not be confused with betaine hydrochloride.
Betaine is found in most microorganisms, plants, and marine animals. Its main physiologic functions are to protect cells under stress and as a source of methyl groups needed for many biochemical pathways. Betaine is also found naturally in many foods and is most highly concentrated in beets, spinach, grain, and shellfish.
Betaine supplementation has historically been used in the treatment of homocysteinuria due to genetic deficiencies in the cystathione beta synthase and methylenetetrahydrofolate reductase genes.
Betaine supplementation may reduce circulating levels of homocysteine, a potential risk factor for heart disease, stroke, cancer, and Alzheimer's disease.
Betaine supplementation has been thought to improve hepatic steatosis, from both alcoholic and nonalcoholic etiologies. While many animal studies have provided plausible mechanisms, data from human studies are limited.
Betaine in the form of cocamidopropylbetaine has been identified as a cause of contact allergy in some skin care products. In this same form, betaine has been studied as a potential replacement for sodium lauryl sulfate in toothpastes to reduce dry mouth, ulcers, and other mucosal irritations.
Since the 1980s, betaine has been used as a treatment option for subjects who have homocystenuria, due to a genetic defect in the cystathione beta-synthase (CBS) gene. Pyridoxine (vitamin B6) was beneficial in only 50% of CBS patients, and betaine was a therapeutic option for homocysteine reduction in these unresponsive patients. Benefit was also seen among pyridoxine-responsive patients.
Early anecdotal reports showed that among CBS variants, treatment with betaine, in addition to B6 and methionine restriction, prevented or delayed clinical complications of the disease, including cardiovascular disease before age 30.
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Cardiovascular disease (in homocysteinuric patients)
Homocystinuria is a severe form of hyperhomocysteinemia caused by genetic defects in homocysteine-metabolizing genes, most commonly the cystathionine beta-synthase (CBS) gene. Patients with severely elevated homocysteine due to a genetic deficiency can use betaine treatment, in combination with other vitamins and diet restrictions, to reduce the risk of vascular events. Further studies are needed to determine whether betaine supplementation can lower cardiovascular risk within the general population.
Overall, betaine supplementation has shown significant reductions in both fasting and postmethionine load homocysteine. However, additional studies are needed to make a strong recommendation.
Hyperhomocysteinemia (in chronic renal failure patients)
Hyperhomocysteinemia is a complication found in 80% of end-stage renal failure patients and may contribute to the progression of atherosclerosis among these patients. The effect of betaine supplementation on reducing homocysteine concentrations within this population has only been studied in addition to folic acid. Additional study investigating betaine alone is needed to make a firm recommendation.
Betaine raises S-adenosylmethionine (SAM) levels that may in turn play a role in decreasing hepatic steatosis. Additional studies are needed to confirm these results.
Limited evidence from human trials suggests betaine supplementation increases total cholesterol, LDL cholesterol, and triglycerides, which may offset any benefit in CHD risk received through homocysteine lowering. However, the increase in cholesterol is relatively small. More study is warranted to confirm these results.
There is currently insufficient available evidence supporting betaine for weight loss.
*Key to grades:A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.
Alzheimer's disease, angina (chest pain), appetite stimulant, arthritis, asthma, atherosclerosis (hardening of the arteries), cognitive improvement, congestive heart failure (CHF), digestion enhancement, dyspnea (shortness of breath), erectile dysfunction, fatigue, high blood sugar/glucose intolerance, hormone related problems, immune stimulation, kidney function, libido (improvement), memory improvement, physical endurance.
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Adults (18 years and older)
Currently, there has been no recommended daily allowance (RDA) set by the United States Food and Nutrition Board for betaine. Manufacturers recommend that betaine powder be dissolved in water, juice, milk, or formula prior to administration and be administered in two doses of 3 grams each. For cardiovascular disease (hyperhomocysteinemics), 2-15 grams daily for up to 17 years has been used. For hyperhomocysteinemia, 1-6 grams daily of betaine for up to six weeks has been used. For nonalcoholic steatohepatitis, Cystadane® up to 20g daily for up to one year has been used.
Children (younger than 18 years)
In children, 250 milligrams per kilogram daily in children 6-14 years-old with cystathionine beta-synthase deficiency for three to six months has been used.
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Avoid in individuals with a known allergy or hypersensitivity to betaine anhydrous or cocamidopropylbetaine, a form of betaine.
Side Effects and Warnings
In the majority of clinical trials among healthy volunteers and renal disease patients, no adverse effects have been reported. In other studies, reported adverse effects are primarily gastrointestinal, such as diarrhea, stomach upset, gastrointestinal irritation, and nausea. However, these transitory events were not severe enough to require discontinuation of betaine use during clinical trials.
Betaine may also cause mental changes or body odor. Use cautiously in patients with psychiatric conditions.
Use cautiously in patients with renal disease or who are obese, as betaine may increase total cholesterol, LDL, HDL, and triglyceride levels when it is taken with folic acid and vitamin B6.
Pregnancy and Breastfeeding
Betaine is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence.
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.
Interactions with Drugs
Although not well studied in humans, betaine supplementation may lower homocysteine concentrations that are elevated by alcohol use.
Patients with renal disease may experience increases in total cholesterol, LDL, HDL, and triglycerides when betaine is taken with folic acid and vitamin B6. Betaine may increase total cholesterol and LDL cholesterol in obese patients. Caution is advised in patients with high cholesterol or those taking cholesterol-lowering medications.
Interactions with Herbs and Dietary Supplements
Patients with renal disease may experience increases in total cholesterol, LDL, HDL, and triglycerides when betaine is taken with folic acid and vitamin B6. Betaine may increase total cholesterol and LDL cholesterol in obese patients. Caution is advised in patients with high cholesterol or those taking cholesterol-lowering herbs or supplements, such as red yeast rice.
This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
Abdelmalek MF, Angulo P, Jorgensen RA, et al. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am.J.Gastroenterol. 2001;96(9):2711-2717. View Abstract
Alfthan G, Tapani K, Nissinen K, et al. The effect of low doses of betaine on plasma homocysteine in healthy volunteers. Br.J.Nutr. 2004;92(4):665-669. View Abstract
Brattstrom L, Wilcken DE, Ohrvik J, et al. Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 12-8-1998;98(23):2520-2526. View Abstract
Craig SA. Betaine in human nutrition. Am.J.Clin.Nutr. 2004;80(3):539-549. View Abstract
Holm PI, Ueland PM, Vollset SE, et al. Betaine and folate status as cooperative determinants of plasma homocysteine in humans. Arterioscler.Thromb.Vasc.Biol 2005;25(2):379-385. View Abstract
Kelly TL, Neaga OR, Schwahn BC, et al. Infertility in 5,10-methylenetetrahydrofolate reductase (MTHFR)-deficient male mice is partially alleviated by lifetime dietary betaine supplementation. Biol Reprod 2005;72(3):667-677. View Abstract
Kharbanda KK, Rogers DD, Mailliard ME, et al. A comparison of the effects of betaine and S-adenosylmethionine on ethanol-induced changes in methionine metabolism and steatosis in rat hepatocytes. J Nutr 2005;135(3):519-524. View Abstract
McGregor, D. O., Dellow, W. J., Robson, R. A., Lever, M., George, P. M., and Chambers, S. T. Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure. Kidney Int. 2002;61(3):1040-1046. View Abstract
Miglio F, Rovati LC, Santoro A, et al. Efficacy and safety of oral betaine glucuronate in non-alcoholic steatohepatitis. A double-blind, randomized, parallel-group, placebo-controlled prospective clinical study. Arzneimittelforschung. 2000;50(8):722-727. View Abstract
Olthof MR, van Vliet T, Boelsma E, et al. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J.Nutr. 2003;133(12):4135-4138. View Abstract
Olthof MR, van Vliet T, Verhoef P, et al. Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans. PLoS.Med 2005;2(5):e135. View Abstract
Schwab U, Torronen A, Meririnne E, et al. Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans. J Nutr 2006;136(1):34-38. View Abstract
Schwab U, Torronen A, Toppinen L, et al. Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am.J.Clin.Nutr. 2002;76(5):961-967. View Abstract
van Guldener C, Janssen MJ, Lambert J, et al. Folic acid treatment of hyperhomocysteinemia in peritoneal dialysis patients: no change in endothelial function after long-term therapy. Perit.Dial.Int 1998;18(3):282-289. View Abstract
Zeisel SH, Mar MH, Howe JC, et al. Concentrations of choline-containing compounds and betaine in common foods. J.Nutr. 2003;133(5):1302-1307. View Abstract
Copyright © 2013 Natural Standard (www.naturalstandard.com)
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
March 22, 2017