An open-label, 24-week pilot study of the methyl donor betaine in Alzheimer disease patients.

We investigated the safety and tolerability of betaine in patients with Alzheimer disease (AD). Betaine is an alternative methyl donor, distinct from the folate-and cobalamin-dependent conversion pathway between homocysteine and methionine. Betaine has been used successfully to reduce homocysteine levels in homocystinuria. The rationale for betaine in AD was to decrease serum homocysteine levels and to increase brain methionone and S-adenosylmethionine, both of which might delay disease progression. Hyperhomocysteinemia is a possible risk factor for AD. Eight patients with probable mild AD (7 men; mean age, 69.6 years; mean Mini-Mental State Exam score, 23.7) received oral betaine (3 g twice daily) for 24 weeks. All patients were on donepezil 10 mg/day for at least 3 months before entry and throughout the study. One patient suffered a myocardial infarction and withdrew after 6 weeks. Another patient, who completed the trial, experienced diarrhea and prostatitis. Four of the 7 patients who completed the trial were rated on the Clinician's Global Impression of Change as worse after 24 weeks. On the cognitive portion of the AD Assessment Scale, 2 patients worsened by at least five points over 24 weeks, whereas the others had changes in scores of no more than two points either way. Six of 8 patients tolerated betaine for 24 weeks without difficulty. Several patients worsened over 24 weeks, but as a pilot study without a control group, efficacy measurements cannot be interpreted. The current study provides a basis for pursuing larger controlled trials with betaine in AD. The homocysteine to S-adenosylmethionine pathway is of interest in AD therapeutics.