Related Terms

• 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.

Background

• 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.

Scientific Evidence

Tradition/Theory

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.

Dosing

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.

Safety

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.

Allergies

• 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.

Interactions

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.

Author Information

• 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).

References

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.

1. 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

2. 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

3. 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

4. Craig SA. Betaine in human nutrition. Am.J.Clin.Nutr. 2004;80(3):539-549. View Abstract

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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