Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients.
BACKGROUND
Elevated serum homocysteine levels have been associated with the development of Alzheimer's dementia (AD). The combined use of a mecobalamin capsule preparation, which contains vitamin B12 0.5 mg with an active methyl base, and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen.


OBJECTIVE
The aim of this study was to determine whether oral multivitamin supplementation containing vitamins B6 and B12 and folic acid would improve cognitive function and reduce serum homocysteine levels in patients with mild to moderate AD.


METHODS
This randomized, double-blind, placebocontrolled trial was conducted at En Chu Kong Hospital, Taipei, Taiwan. Male and female patients aged >50 years with mild to moderate AD and normal folic acid and vitamin B12 concentrations were enrolled. All patients received treatment with an acetylcholinesterase inhibitor and were randomized to receive add-on mecobalamin (B12) 500 mg + multivitamin supplement, or placebos, PO QD for 26 weeks. The multivitamin contained pyridoxine (B6) 5 mg, folic acid 1 mg, and other vitamins and iron. Serum homocysteine level was measured and cognitive tests were conducted at baseline and after 26 weeks. The primary efficacy outcome was change in cognition, measured as the change in score from baseline to week 26 on the Alzheimer's Disease Assessment Scale 11-item Cognition subscale. Secondary efficacy outcomes included changes in function in performance of activities of daily living (ADLs) and concentrations of homocysteine, B12, and folic acid. Tolerability was assessed by comparing the 2 study groups with respect to physical examination findings, including changes in vital signs, laboratory test abnormalities, concomitant medication use, and compliance of study medication was assessed using an interview with the patient's caregiver, as well as the monitoring of adverse events (AEs) throughout the study.


RESULTS
Eighty-nine patients (45 men, 44 women; all Taiwanese; mean [SD] age, 75 [7.3] years) were enrolled and randomized. Overall, there were no significant differences in cognition or ADL function scores between the 2 groups. At week 26, the mean (SD) between-group difference in serum homocysteine concentration versus placebo was -2.25 (2.85) micromol/L (P = 0.008), and the mean serum concentrations of vitamin B12 and folic acid were significantly higher (but within normal range) in the multivitamin group compared with placebo (., +536.9 [694.4] pg/mL [P < 0.001] and +13.84 ng/mL [11.17] [P = 0.012] at 26 weeks, respectively). The 2 most common AEs were muscle pain (11.1% and 6.8%) and insomnia (8.9% and 9.1%) in the multivitamin and placebo groups, respectively.


CONCLUSIONS
In this population of patients with mild to moderate AD in Taiwan, a multivitamin supplement containing vitamins B(6) and B(12) and folic acid for 26 weeks decreased homocysteine concentrations. No statistically significant beneficial effects on cognition or ADL function were found between multivitamin and placebo at 26 weeks.
Department of Neurology, En Chu Kong Hospital, San-shia, Taipei, Taiwan. sunyu@ms4.hinet.net
Yu
Y
Sun
Chien-Jung
CJ
Lu
Kuo-Liong
KL
Chien
Sien-Tsong
ST
Chen
Rong-Chi
RC
Chen
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D044466:Asian People; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D013624:Taiwan; D014805:Vitamin B 12 / Q000627:therapeutic use*; D025101:Vitamin B 6 / Q000627:therapeutic use*; D014803:Vitamin B Complex / Q000627:therapeutic use*
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D006710:Homocysteine; D014803:Vitamin B Complex; D025101:Vitamin B 6; D000077265:Donepezil; D005492:Folic Acid; D014805:Vitamin B 12