Wednesday September 14 2011
The trial used very high doses of vitamin B
“A daily 10p vitamin pill could prevent millions of people being struck down by Alzheimer’s disease,” the Daily Express has today reported. In a front-page story the newspaper said that vitamin B can help protect the brain from dementia, as demonstrated in new research that looked at whether high doses of vitamin B could help elderly people with mild memory problems.
The news is based on results presented at this week’s British Science Festival, where scientists have been discussing two sets of results from a recent study on high-dose vitamin B in people with mild cognitive impairment, or MCI. MCI can be an early symptom of Alzheimer’s disease. The research found that, in a small number of tests, those taking vitamin B showed improvements compared with those taking a placebo (dummy) drug. Previous results published last September had shown that people taking vitamin B experienced 30% less brain atrophy (shrinkage) than those taking a placebo.
While its results look promising, this small, well-conducted study does not show that vitamin B can help prevent dementia. However, it suggests that high doses of the vitamin may help some people with MCI, which sometimes develops into dementia. A larger trial is required to explore the possible role of the vitamin in slowing progression to dementia.
This trial used very high doses of vitamin B that could not be obtained from a normal diet or standard supplements. High doses of any vitamin supplement may be harmful and the researchers warn that they can increase the risk of other conditions such as cancer. People wishing to use vitamin B supplements, particularly at doses over the recommended daily allowance (RDA), should consult their GP before doing so.
Where did the story come from?
The study was carried out by researchers from the University of Oxford and the University of Oslo, Norway. It was funded by various UK organisations, including the Charles Wolfson Charitable Trust, the Medical Research Council and Alzheimer’s Research UK.
The results from this research have so far been presented in two different research papers focusing on different types of results. The first set of results, on brain shrinkage, was published in the journal PLoS One and covered by Behind the Headlines in September 2010. The latest set of results was published in the peer-reviewed International Journal of Geriatric Psychiatry in July 2011. The results are currently in the news because they are being presented at the British Science Festival.
Newspaper coverage of this research has tended to be overly optimistic about the study’s findings. For example, the Daily Express described vitamin B supplements as a “Pill to beat Alzheimer’s”. The Express also listed some “natural ways to beat dementia”, which include eating meat, fish and vegetables. This information is misleading, as none of these foods has been found to prevent dementia. While the foods listed in the Express can be dietary sources of vitamin B, the amount of vitamin B in the pills used in this study was extremely high, and the study’s authors have been quoted as saying that they should be considered to be medicines rather than regular vitamin supplements.
What kind of research was this?
The researchers point out that MCI affects about 5 million people in the US and 14 million in Europe. About half of all those with MCI will develop dementia within five years of being diagnosed, and there is an urgent need to identify ways of slowing cognitive decline in this population.
The researchers say that low levels of B vitamins are associated with cognitive impairment and that the probable biological pathway for this is raised blood levels of homocysteine, a protein that some studies have found to be more abundant in people with Alzheimer’s disease. Blood levels of homocysteine are a risk factor for vascular disease and are known to increase with age.
The study was a double blind randomised controlled trial to explore whether large doses of folic acid, vitamin B6 and vitamin B12 could be of benefit in elderly people with mild cognitive impairment. The first results of this trial, published last year, examined the outcome of brain atrophy (shrinkage), while this newest study looked at whether these doses of vitamins had any effect on mental and clinical decline. The previous analysis found that high levels of vitamin B supplements could slow the rate of atrophy by 30% compared with a placebo drug. The effect of this treatment was greater in those with higher baseline levels of homocysteine.
What did the research involve?
Between April 2004 and November 2006 researchers recruited 271 people aged 70 and over, specifying that they should have a diagnosis of MCI defined using specific criteria. These include concerns about memory that did not interfere with daily living and pre-specified scores on cognitive scales assessing word recall and fluency. The study excluded people with existing dementia, people with cancer and those who were already taking certain B vitamins. Five of the original 271 did not start the study.
Of the remaining volunteers, 133 were randomly assigned to receive high-dose vitamin B pills (0.8mg folic acid, 0.5mg vitamin B12 and 20mg vitamin B6) and 133 were assigned a placebo pill during the two-year period. The trial was double blinded, which means that the participants and all the staff directly involved in the study were unaware which pills were being received. This is important as it eliminates potential biases associated with knowledge of whether someone was taking the treatment or a placebo. The tablets were taken for a period of two years.
In the earlier publication, the researchers presented results from 168 participants who had their blood levels of homocysteine measured and underwent MRI scans at the start and end of the study to assess brain atrophy. In their latest research paper the authors describe the associations between taking B vitamins and various aspects of cognitive function, measured using neuropsychological tests given at the start of the study, on five occasions during the follow-up period and at the end of the study. These included:
- tests of orientation
- tests of memory
- tests of attention and language
- tests of verbal learning
- the CLOX test, which measures ability to plan and execute a task
- a questionnaire for someone close to the participant on whether they have seen any cognitive changes
- a clinical dementia rating (a validated scale to assess the severity of dementia)
The researchers analysed these results to find out if treatment had any effect on mental function, taking into account other factors that might also affect cognition, such as age, sex and education. They were also interested in whether the B vitamins were having an effect in those who had high levels of homocysteine (linked to low vitamin B levels). To look at this, they did a further subgroup analysis. In this they tested if the results were affected if they took into account the participants’ blood homocysteine levels.
What were the basic results?
Of the 266 people who started the study, 223 (83.8%) completed it. The researchers found that:
- At the end of the study homocysteine levels were on average 30% lower in the group taking B vitamins than in those taking placebo.
- Overall, treatment with B vitamins had no effect on most cognitive tests.
- In the CLOX test, people taking B vitamins had a 30% higher chance of getting the correct answer than those taking the placebo.
- Among the 50% of people with the highest homocysteine levels at the start of the study, those taking B vitamins did significantly better in several tests than those taking placebo.
- Among the quarter of people with the highest homocysteine levels at the start of the study those who took B vitamins did better in the test assessing clinical dementia scores than those taking the placebo.
How did the researchers interpret the results?
Researchers say that B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular those with elevated homocysteine levels. They say that the results of one test suggested a “reversal of early cognitive impairment” in some of those with MCI.
Further trials are needed, say the researchers, to determine if this treatment can slow or prevent the progression of MCI to dementia.
In this well-conducted trial, researchers found that high-dose B vitamins appeared to have benefit in a number of mental tests for those people with MCI who had raised homocysteine levels. However, as the researchers point out, the study had some limitations, including the relatively small size of the trial and also the relatively modest size of the effect (the cognitive improvements seen). Also, the study was not set up primarily to assess the possible effect of vitamin B on cognitive function, as the first part of this study looked at brain atrophy.
While this study has presented intriguing results, a larger trial is now needed to assess whether high doses of vitamin B could slow down progression to dementia.
This trial used very high doses of vitamin B that could not be obtained from a normal diet or standard supplements. High doses of any vitamin supplement may be harmful, and people wishing to use vitamin B supplements, particularly at doses over the recommended daily allowance (RDA), should consult their GP before doing so.