Insufficient evidence of the efficacy of thiamine for people with Alzheimer's disease

Preclinical and laboratory studies show an effect of thiamine on the release and breakdown of acetylcholine. Some intellectual functions, including attention and memory, are influenced by neurons which release acetylcholine. Cholinergic function is impaired in Alzheimer's disease. It has therefore been hypothesized that thiamine may be beneficial in Alzheimer's disease. Biochemical abnormalities in thiamine-dependent enzymes have been found in the brains of patients with Alzheimer's disease. The three included randomized controlled trials totaled less than 50 participants and insufficient detail in the results did not allow combination of the data. Thus the review found no evidence of the efficacy of thiamine for people with Alzheimer's disease.

Authors' conclusions: 

It is not possible to draw any conclusions from this review. The number of people included in the studies is less than 50 and the reported results are inadequate.

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Background: 

Vitamin B1 (thiamine) deficiency plays an important role in Wernicke-Korsakoff syndrome. This is a form of brain damage occurring in long-term alcoholics who rely mainly on alcohol for nutrition. The acute syndrome (Wernicke's encephalopathy) is normally reversible. Progression to the profound amnestic syndrome (Korsakoff's psychosis) can be averted by a timely injection of a large dose of thiamine. There have been suggestions that thiamine may have a beneficial effect in Alzheimer's disease.

Objectives: 

The objective of this systematic review is to evaluate the efficacy of thiamine for people with Alzheimer's disease.

Search strategy: 

The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 12 February 2003 using the terms thiamin*, vitamin-B1, B1, "Vitmain B1". This Register is regularly updated with records from all major health care databases (MEDLINE, EMBASE, CINAHL, PsycINFO) and many trials databases.

In addition the reviewers searched bibliographies of published reviews and conference proceedings and contacted pharmaceutical companies and trial investigators to obtain additional data.

Selection criteria: 

All unconfounded, double-blind, randomized trials in which treatment with thiamine was administered for more than a day and compared with placebo in patients with dementia of the Alzheimer's type.

Data collection and analysis: 

Two reviewers extracted the data independently by and estimated the odds ratios (95% CI) or the average differences (95% CI).

Main results: 

Three studies were included. The two cross-over studies did not report results from the first phase. It was not possible to pool any results for a meta-analysis. Nolan 1991 reports results that show no evidence of an effect on MMSE at 3, 6, 9 and 12 months for thiamine compared with placebo for those who completed the trial. Meador 1993a noted that 3/8 on thiamine compared with 6/9 on placebo were worse as measured on the ADAS-Cog at 3 months compared with baseline, but the difference is not statistically significant.

Blass 1988 and Nolan 1991 reported that no significant side-effects were noted during the study, and Meador 1993a did not mention side-effects. Blass 1998 noted that 5/16 and Nolan 1991 that 5/15 did not complete the study, but neither mentioned the groups to which these people belonged.