Betaine overcomes perturbations caused by choline deficiency

Rats were fed either a standard (25%) casein or soybean protein diet, however both diets were choline-deprived. The study found that:

- Hyperhomocysteinemia induced by choline deprivation was effectively suppressed by choline, betaine or methionine supplementation.

- Hepatic SAM:SAH ratio was improved.

They concluded that this might be a useful model for investigating the role of betaine in the regulation of plasma homocysteine concentration.

Setoue et al (2008). "Choline deprivation induces hyperhomocysteinemia in rats fed low methionine diets." J Nutr Sci Vitaminol (Tokyo) 54(6): 483-90.

Betaine reduces oxidative stress and inflammation

This study investigated the effects of betaine on the inflammatory process and the oxidative stress in rats with nonalcoholic steatohepatitis (NASH) using control, model, low and high dose betaine groups. Except control group, all rats were fed with high fat diet containing propylthioracil (PTU), a fatty liver-inducing drug, to construct NASH model, and those in low (200 mg/kg) and high (400 mg/kg) dose group received betaine solution intragastric gavage.

Compared with control group, model group rats had:

- increased liver damage
- enhanced expression of tumor necrosis factor-α (TNF-α), inflammatory factor interferon-γ (IEN-γ), and cytochrome-related factor CYP2E1 mRNA in liver
- decreased expression of IL-10 mRNA
- increased levels of malonaldehyde (MDA) and nitrogen monoxide (NO) in liver
- no significant change in cytochrome-related factor CYP3A2

Compared with that in the model group, high and low dose betaine groups had:

- less liver damage
- attenuated expression of TNF-α, TEN-γ, CYP2E1 and CYP3A2 mRNA in liver
- enhanced expression of IL-10 mRNA
- decreased levels of MDA and NO in liver

There was a significant difference in the above parameters between the two betaine treatment groups. Betaine has protective effects on liver injury in rats induced by a high fat diet. The mechanisms may involve improvement in oxidative stress and suppressed expression of inflammatory factors.

Zhang et al (2008). "Effects of betaine on oxidative stress and inflammatory factors in rats with nonalcoholic steatohepatitis." Wuhan Daxue Xuebao (Yixue Ban) 29(5): 587-91.

Betaine alleviates perturbations of a high fat diet

Male rats were provided with a standard liquid diet, a high-fat liquid diet (HF), or a HF diet supplemented with betaine (1%) for 3 wk.

HF diet intake:

- elevated hepatic triglyceride and serum tumor necrosis factor (TNF)
- reduced antioxidant capacity of liver cytosol against hydroxyl and peroxyl radicals
- decreased hepatic S-adenosylmethionine (SAM) and glutathione (GSH)
- increased hypotaurine and taurine concentrations
- depressed methionine adenosyltransferase (MAT) activity
- elevated activity and concentration of cysteine dioxygenase and GSH S-transferase

Betaine supplementation of the HF diet:

- inhibited hepatic fat accumulation and serum TNF elevation
- prevented the decrease in cytosolic antioxidant capacity
- induced MAT activity and concentration
- increased hepatic SAM and GSH
- depressed elevation of hypotaurine and taurine

The results indicate that the metabolism of S-containing substances is significantly disturbed by the HF diet, suggesting a causal role of impairment of hepatic transsulfuration reactions in NAFLD. Betaine supplementation protects the liver from nonalcoholic steatosis and oxidative stress most probably via its effects on the transsulfuration reactions.

Kwon et al (2009). "Impaired Sulfur-Amino Acid Metabolism and Oxidative Stress in Nonalcoholic Fatty Liver Are Alleviated by Betaine Supplementation in Rats." J. Nutr. 139(1): 63-68.

Review: Current status of therapy in NAFLD

This article discusses some of the basic understanding of non alcoholic fatty liver disease (NAFLD), reviews the currently tested therapies (including betaine), some novel therapies, and potential future therapeutic options.

McNear and Harrison (2009). "Review: Current status of therapy in nonalcoholic fatty liver disease." Therapeutic Advances in Gastroenterology 2(1): 29-43.