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High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial
Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, Bottiglieri T, Jin S et al.. JAMA, 2008-10-01
Topic: Amyloid, tau and blood-test diagnosis
Context Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline. Objective To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. Design, setting, and patients A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States. Intervention Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months. Main outcome measure Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Results A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P Conclusion This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD. Trial registration clinicaltrials.gov Identifier: NCT00056225.
Key findings
- Results A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication.
Why it matters
This trial tested high-dose folate, vitamin B6, and vitamin B12 supplementation in 409 individuals with mild to moderate Alzheimer disease and normal levels of these vitamins and homocysteine. The provided text does not report whether the supplements affected cognitive decline.
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Study details
- Participants340
- Evidence strengthHigh
How this study scored 78/100
Published in a top-tier journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 340 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 6 / 7 | Cited 560 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 28.0 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 5 / 6 | Cited 29.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 28 other studies in this library |
| Still being cited | 3 / 4 | Cited 64 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Paul S. S Aisen: h-index 87 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18854539) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 78 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Aisen, P. S., Schneider, L. S., Sano, M., Diaz-Arrastia, R., van Dyck, C. H., Weiner, M. F., et al. (2008). High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. https://doi.org/10.1001/jama.300.15.1774
Vancouver
Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008. doi:10.1001/jama.300.15.1774. PMID: 18854539.
BibTeX
@article{aisen2008-18854539,
author = {Aisen, P. S. and Schneider, L. S. and Sano, M. and Diaz-Arrastia, R. and van Dyck, C. H. and Weiner, M. F. and Bottiglieri, T. and Jin, S. and others},
title = {{High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial}},
journal = {JAMA},
year = {2008},
doi = {10.1001/jama.300.15.1774},
pmid = {18854539},
url = {https://doi.org/10.1001/jama.300.15.1774}
}
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