Homocystinuria — The Effects of Betaine in the Treatment of Patients Not Responsive to Pyridoxine

Abstract

The treatment of homocystinuria that is not responsive to pyridoxine is not usually biochemically or clinically successful, and vascular, ocular, and skeletal complications commonly supervene. Persistent marked homocysteinemia appears to be the most important biochemical disturbance leading to these complications. Ten patients with cystathionine beta-synthase deficiency that was not responsive to pyridoxine and one patient with homocystinuria due to a defect in cobalamin metabolism were treated with 6 g daily of betaine added to conventional therapy, to improve homocysteine remethylation. All patients had a substantial decrease in plasma total homocysteine levels (P less than 0.001) and an increase in total cysteine levels (P less than 0.001). Changes in plasma methionine concentrations were variable. Fasting levels of plasma amino acids became normal in two patients, and in six there was immediate clinical improvement. There were no unwanted effects. We conclude that treatment of homocystinuria that is not responsive to pyridoxine and of disorders of homocysteine remethylation should include betaine in adequate doses to ensure maximum lowering of elevated plasma homocysteine levels.

The association of homocysteine and coronary artery disease

“…Supplementation with betaine, starting at 3 g twice a day, is experimental and has yielded conflicting results, but can be used in very highrisk patients. 79,80 Once the patient is within goal range, a fasting tHcy can be repeated on a yearly basis. 9…”

Long-term effect of betaine on risk factors associated with the metabolic syndrome in healthy subjects

“…In humans, there is little safety data regarding the use of betaine in healthy individuals. In hyperhomocysteinemic patients, betaine is used to lower plasma homocysteine concentrations (Wilcken et al, 1983;Singh et al, 2004), which is suggested to be an independent risk factor for coronary heart disease (El-Khairy et al, 1999;Chambers et al, 2000;Humphrey et al, 2008). Hyperhomocysteinemia is also associated with hyperinsulinemia and insulin resistance, which in turn increases the risk of cardiovascular diseases (Meigs et al, 2001).…”

Betaine treatment of cystathionine β-synthase-deficient homocystinuria; does it work and can it be improved?

“…Wilcken et al reported on the effects of betaine supplementation (6 g per day) in 10 patients with pyridoxine-nonresponsive HCU in conjunction with pyridoxine (100 mg/day) and folic acid (5 mg/day). 21 Six of these patients were also on a protein-restricted diet. All of these patients showed a substantial reduction in total free Hcy as a consequence of betaine supplementation with the average plasma level dropping from 57 µmol/L prior to treatment to 6 µmol/L during treatment.…”

“…The average decrease in plasma Hcy concentration is reported to be between 74% and 92% following doses of 6-20 g day −1 of betaine. 42,43 However, some studies have found no clinical benefit using 6 g day A number of limited trials have been performed to investigate these aspects of betaine therapy, but these have typically been limited by relatively short study durations and/or the use of normal volunteers rather than HCU patients who are likely to have different responses to the application of betaine. [45][46][47] Some investigators have tried to model the effects of HCU for studying betaine dosing by using a methionine-loading strategy but again, the time course of this kind of analysis is not suitable for detecting possible metabolic adaption induced in long-term betaine therapy.…”