The meta-analysis study, published last year in the American Journal of Clinical Nutrition (AJCN), collected data from 11 large trials using a total of 22,000 participants. It aimed to determine whether using B vitamins to lower plasma homocysteine – a risk factor for Alzheimer’s – could prevent the disease.
The researchers concluded that although allocation of vitamin B lowered homocysteine levels by 26–28%, there was no significant effect on individual cognitive domains, global cognitive function or cognitive ageing.
Dr Robert Clarke of Oxford University, who led the work, stated at the time: “Our study draws a line under the debate: B vitamins don’t reduce cognitive decline as we age. Taking folic acid and vitamin B-12 is sadly not going to prevent Alzheimer’s disease.”
However, Dr Peter Garrard of the Cardiovascular and Cell Sciences Research Institute at St George’s University of London has now said that this statement was “inaccurate and misleading” and that it could have a negative impact on public health policy-making and research.
Flaws in the study
Two separate letters were addressed to the AJCN from Dr Garrard and David Smith of Oxford University, outlining several serious flaws in the researchers’ methods.
The claimed flaws included: “1) reliance on data from trials of vascular disease prevention rather than dementia; 2) the use of the Mini Mental State Examination (MMSE), which is designed to detect dementia but is unsuitable for assessing small changes in cognitively normal people; and 3) the absence of any cognitive decline in untreated patients, rendering the whole study irrelevant to the question of clinical benefits in cognitive impairment or dementia.”
Letter of response
Clarke et al sent a letter to the editor of the AJCN in defence of their methodology, claiming that the results were still valid.
“Our meta-analysis is a careful analysis of all available data. We have acknowledged its potential limitations, but unless substantial additional data emerge, the null results of the present meta-analysis provide the best summary of the evidence.”
Regarding Garrard’s criticism on using inappropriate data in their analysis, they responded: “We followed standard ‘‘best practice’’ for conducting meta-analyses by including all available results from all large trials. We avoided placing undue emphasis on data-dependent subgroup analyses, by restricting these analyses to pre-specified subgroups.”
They also said that the MMSE had been widely used in landmark observational studies of dementia, and that its limitations were duly acknowledged in their original study.
According to the Alzheimer’s Society: “The MMSE can be used to assess changes in a person who has already been diagnosed with dementia. It can help to give an indication of how severe a person's symptoms are and how quickly their dementia is progressing.”
Dr Clare Walton, research manager of the Alzheimer’s Society, said:
“There have been conflicting reports about whether vitamin B supplements might be able to slow down memory decline or the development of Alzheimer’s disease and this has led to confusion from public and patients about whether to take them. Combining the results of several studies, this meta-analysis finds no convincing evidence that taking vitamin B can improve memory or prevent dementia.
“Based on the existing evidence, Alzheimer’s Society wouldn’t recommend that people begin vitamin B supplements if they are worried about their memory. However, we would still encourage more clinical trials to determine if there is a benefit in taking vitamin B for people already with dementia."
Upon publication of the Oxford University study, Hugh Perry, chair of the Medical Research Council's Neurosciences and Mental Health Board, said: “Science progresses through testing and re-testing previous research and sometimes overturning existing theories. Health advice always needs to be based on the best available data from the largest possible studies and this is even more important when the findings have implications for what we do or don’t eat and drink.”
Source: American Journal of Clinical Nutrition
First published June 25, 2014, pp 657–66, doi: 10.3945/ajcn.113.0763492014
Title: "Effects of homocysteine lowering with B vitamins on cognitive aging: Meta-analysis of 11 trials with cognitive data on 22,000 individuals"
Authors: Robert Clarke et al.
Letter of response published Feb 2015, pp 416-7, doi: 10.3945/ajcn.114.100941