Improved Body Weight and Biochemistry

Lu et al (2008). "Effects of betaine on body weight and biochemical index of obese rats fed high-fat diet." Acta Nutr Sinica 30(3): 311-5.

This study, published in Chinese, compared rats fed for 8 weeks on these diets:

- control
- high fat (HF)
- HF plus low betaine (15 mg/kg bwt) (HF/LB)
- HF plus medium betaine (30 mg/kg bwt) (HF/MB)
- HF plus high betaine (60 mg/kg bwt) (HF/HB)

Results for weight compared to control showed:

- HF diet led to greatest weight gain (i.e. 14% greater body weight at 8 weeks)
- HF/HB diet led to slowest weight gain (i.e. 7% greater body weight at 8 weeks)

Results for blood markers showed:

HF diet compared to control led to:

- higher fasting glucose and insulin
- higher malonaldehyde (MDA - marker of oxidative stress) and lower total antioxidant capacity (TAOC)
- lower HDL and higher LDL cholesterol
- higher free fatty acids (FFA)
- unchanged total cholesterol and triglyerides (TG)

Compared to HF diet:

- HF/HB diet led to improved blood glucose, MDA, TG and FFA
- HF/LB diet led to improved blood insulin, MDA and TAOC

Effect of Betaine on GAA-induced homocysteinemia

Setoue et al (2008). "Hyperhomocysteinemia induced by guanidinoacetic acid is effectively suppressed by choline and betaine in rats." Biosci Biotechnol Biochem 72(7): 1696-703.

Guanidinoacetic acid (GAA), a precursor of creatine:

- raised plasma homocysteine
- raised liver homocysteine and s-adenosylhomocysteine (SAH)
- lowered liver s-adenosylmethionine (SAM)

Betaine and choline significantly suppressed these effects.

Betaine Reverses IR and NAFLD

Borgschulte et al (2008). "Betaine Treatment Reverses Insulin Resistance and Fatty Liver Disease Without Reducing Oxidative Stress or Endoplasmic Reticulum Stress in An Animal Model of NAFLD." Gastroenterology 134(4): A414.

Compared to a control diet, a high fat diet led to increased:

- body weight
- plasma insulin and homocysteine
- liver injury
- oxidative and endoplasmic reticulum stress

Addition of betaine (1.5%) to the high fat diet reduced:

- body weight
- plasma insulin and homocysteine
- liver injury

Papers 2004-7:

Erman et al (2004). "Betaine or taurine administration prevents fibrosis and lipid peroxidation induced by rat liver by ethanol plus carbon tetrachloride intoxication." Amino Acids 27(2): 199-205.

Balkan et al (2004). "The effect of betaine treatment on triglyceride levels and oxidative stress in the liver of ethanol-treated guinea pigs." Exp Toxicol Pathol 55(6): 505-9.

Balkan et al (2005). "The effect of taurine or betaine pretreatment on hepatotoxicity and prooxidant status induced by lipopolysaccharide treatment in the liver of rats." Eur J Gastroenterol Hepatol 17(9): 917-21.

Kharbanda et al (2005). "A Comparison of the Effects of Betaine and S-Adenosylmethionine on Ethanol-Induced Changes in Methionine Metabolism and Steatosis in Rat Hepatocytes." J. Nutr. 135(3): 519-524.

Kharbanda et al (2005). "Role of elevated S-adenosylhomocysteine in rat hepatocyte apoptosis: Protection by betaine." Biochem Pharmacol 70: 1883-90.

Kim et al (2005). "Effect of betaine supplementation on changes in hepatic metabolism of sulfur-containing amino acids and experimental cholestasis induced by alpha-naphthylisothiocyanate." Food Chem Toxicol 43(5): 663-70.

Trappoliere et al (2005). "The treatment of NAFLD." Eur Rev Med Pharmacol Sci 9(5): 299-304.

Samara et al (2006). "Betaine resolves severe alcohol-induced hepatitis and steatosis following liver transplantation." Dig Dis Sci 51(7): 1226-9.

Duong et al (2006). "S-Adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro." Hepatology 43(4): 796-806.

Hanje et al (2006). "The use of selected nutrition supplements and complementary and alternative medicine in liver disease." Nutr Clin Pract 21(3): 255-72.

Kaplowitz and Ji (2006). "Unfolding new mechanisms of alcoholic liver disease in the endoplasmic reticulum." J Gastroenterol Hepatol 21 Suppl 3: S7-9.

Liu et al (2006). "Betaine modulates high carbohydrate diet-induced fatty liver in mice." Faseb J 20(4): A183.

Sparks et al (2006). "Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine-homocysteine S-methyltransferase." Biochem J 395(2): 363-71.

Chang et al (2006). "Therapy of NAFLD: Antioxidants and Cytoprotective Agents." J Clin Gastroenterol 40 Suppl 1: S51-60.

Kaplowitz et al (2007). "Endoplasmic reticulum stress and liver injury." Semin Liver Dis 27(4): 367-77.

Kharbanda et al (2007). "Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway." J Hepatol 46(2): 314-21.

Purohit et al (2007). "Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a symposium." Am J Clin Nutr 86(1): 14-24.

Song et al (2007). "Involvement of AMP-activated protein kinase in beneficial effects of betaine on high-sucrose diet-induced hepatic steatosis." Am J Physiol Gastrointest Liver Physiol 293(4): G894-902.

Song et al (2008). "Inhibition of adiponectin production by homocysteine: a potential mechanism for alcoholic liver disease." Hepatology 47(3): 867-79.

Ji (2008). "Dissection of endoplasmic reticulum stress signaling in alcoholic and non-alcoholic liver injury." J Gastroenterol Hepatol 23 Suppl 1: S16-24.

Kim et al (2008). "Alleviation of acute ethanol-induced liver injury and impaired metabolomics of S-containing substances by betaine supplementation." Biochemical and Biophysical Research Communications 368(4): 893-898.

Mato et al (2008). "Methionine Metabolism and Liver Disease." Annual Review of Nutrition 28: 273-93.

Strength and Power

Maresh et al (2007). "The Effects of Betaine Supplementation on Strength and Power Performance" Med Sci Sports Exerc 39(5 Suppl): S101.

This study found that ingestion of betaine over 2 weeks led to increased power, force and maintenance as measured in:

- vertical jump power
- isometric squat force
- isometric bench press
- bench throw power

There were no differences in bench press repetitions, number of squat repetitions, and jump squat power.

Athletic Performance in the Heat

Armstrong et al (2008). "Influence of betaine consumption on strenuous running and sprinting in a hot environment." J Strength Cond Res 22(3): 851-60.

Investigators found a trend towards longer sprint time until exhaustion when betaine was present in either a sports beverage or in flavored water compared to placebo.

Papers 2004-7:

Millard-Stafford et al (2005). "Fluid replacement in the heat - effects of betaine." Med Sci Sports Exerc 37(5): S28.

Cancer Treatment Hypothesis

Jellinek (2008). "The need for a multi-level biochemical approach to defeat cancer that will also support the host." Medical Hypotheses 71(4): 515-526.

The author suggests a multi-level, simultaneous biochemical approach to treating key elements of cancer (metastasis, tumor growth and immunity) and that betaine should be a component to help prevent tumor growth. For studies to confirm the proposal, the overall expected result is that a combined administration of all agents cited here will outperform any single agent considered so far for anticancer treatment.

Papers 2004-7:

Cho et al (2007). "Dietary Choline and Betaine and the Risk of Distal Colorectal Adenoma in Women." J. Natl. Cancer Inst.: 1224-31.

Cho et al (2007). "Nutrients involved in one-carbon metabolism and risk of breast cancer among premenopausal women." Cancer Epidemiol Biomarkers Prev 16(12): 2787-90.

Ziegler and Lim (2007). "One-Carbon Metabolism, Colorectal Carcinogenesis, Chemoprevention with Caution." J. Natl. Cancer Inst. 99(16): 1214-5.

Xu et al (2007). "A functional 19-base pair deletion polymorphism of dihydrofolate reductase (DHFR) and risk of breast cancer in multivitamin users." Am J Clin Nutr 85(4): 1098-102.

Xu et al (2008). "Choline metabolism and risk of breast cancer in a population-based study." Faseb J 22(6): 2045-52.

Betaine Metabolism and Distribution

A couple of studies investigating the intake and distribution of betaine in tissues:

Clow et al (2008) "Elevated tissue betaine content in developing rats are due to dietary betaine, not synthesis"

Increase in tissue betaine reflects high dietary betaine and not a change in endogenous betaine synthesis.

Slow et al (2008) "Plasma Dependent and Independent Accumulation of Betaine in Male and Female Rat Tissues"

The authors measured the betaine concentration of plasma and various tissues (brain, heart, lungs, liver, kidney, spleen, intestine, reproductive tissues, skeletal muscle and skin) in male and female rats. Some of the findings were:

- betaine was highest in the liver and kidney
- plasma betaine concentrations were significantly lower than tissue levels except in the brain and skeletal muscle
- there was significant plasma-related accumulation of betaine in the heart, skin and skeletal muscle, while the lung, liver, kidney, spleen, and intestine showed significant plasma-related and plasma-independent accumulations of betaine.