Betaine Other names: Betaine hydrochloride Trimethylglycine

Betaine was shown to lower plasma homocysteine levels in the three types of homocystinuria, i.e. CBS deficiency; MTHFR deficiency and cbl defect. The extent of this effect was dependent on the absolute degree of hyperhomocysteinemia, being higher in severe hyperhomocysteinemia.

Pharmacodynamic effects

Betaine acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. As a result, plasma levels of homocysteine should decrease in these patients, to 20-30 % of pre-treatment levels.

Betaine has also been shown to increase plasma methionine and S-adenosyl methionine (SAM) levels in patients with MTHFR deficiency and cbl defects. In CBS-deficient patients without dietary restriction of methionine, excessive accumulation of methionine has been observed.

Betaine supplementation was shown to improve the metabolic abnormalities in the cerebrospinal fluid of patients with homocystinuria.

The pharmacokinetic data of homocystinuric patients on long-term betaine supplementation are very similar to those of healthy volunteers. This demonstrates that differences in betaine kinetics are most probably due to betaine depletion in untreated homocystinuria and are only meaningful for the initial treatment.

Absorption

The absolute bioavailability of betaine has not been determined. In healthy adult volunteers (age between 21 to 49 years), after a single oral dose of betaine anhydrous (50 mg/kg), absorption was rapid (t_max = 0.9 ± 0.3 hours and a C_max = 0.9 ± 0.2 mM).

After a repeated dose regimen of 100 mg/kg/day for 5 days, the absorption kinetics did not change.

Distribution

Betaine anhydrous was rapidly distributed into a relatively large volume (V/F = 1.3 l/kg).

After a repeated dose regiment of 100 mg/kg/day for 5 days, the distribution half life was prolonged significantly (up to 36 h), indicating saturable transport and redistribution processes.

Biotransformation

Betaine is a methyl group donor.

Elimination

With a slow elimination rate (mean half life = 14 h, mean total body clearance, CL/F, = 84 ml/h/kg), renal clearance is negligible (5% of total body clearance), assuming 100% bioavailability.

At high doses, a CNS depressant effect and irritation of the gastrointestinal tract was seen in rats. Long-term carcinogenicity and reproductive toxicity studies have not been conducted on betaine. A standard battery of genotoxicity test reveals no specific hazard for humans.