Wednesday October 15 2008
The Times reports that Alzheimer’s patients are “wasting their time” taking vitamin B supplements in an attempt to slow the progress of the disease. It says the new research has demonstrated that the supplements actually make very little difference to the decline of mental functions, contrary to what previous studies have suggested.
This was a large, well-designed trial which provides evidence that taking vitamin B as part of a multivitamin supplement has no effect on brain function (or cognition for people with Alzheimer’s disease) when compared with a placebo. Previous research has shown that high doses of vitamin B supplements can reduce levels of homocysteine, a chemical thought to play a role in the development of Alzheimer’s. This new study found that despite this, vitamin B supplements do not actually slow the decline of mental functions associated with Alzheimer’s.
Based on the results of this study, Alzheimer’s patients who have normal levels of vitamin B in the body can be reasonably sure that additional vitamin B supplementation makes little difference to the course of the disease.
Where did the story come from?
Dr Paul Aisen of University of California, and colleagues from other academic institutions across the US, carried out this research. Some authors had affiliations with a large number of pharmaceutical companies, some of whom provided financial support and medications used in this trial. The study was published in the peer-reviewed Journal of the American Medical Association.
What kind of scientific study was this?
This was a “double-blind randomised controlled trial”, which aimed to investigate the safety of taking vitamin B supplements for the treatment of Alzheimer’s, and whether it had any effect upon the rate of cognitive decline.
In previous research it has been suggested that B vitamins may influence levels of homocysteine, a chemical thought to be involved in the changes that occur in the brains of Alzheimer’s sufferers. While previous studies have shown that certain B vitamins may reduce homocysteine levels, they have not demonstrated any effect on cognitive ability.
The current trial was a multicentre study across forty sites, following 409 medically stable people with ‘probable Alzheimer’s’, assessed using the “Mini-Mental State Examination”. Participants had Mini-Mental scores between 14 and 26 and were aged over 50 years, with an average age of 76 years.
They excluded those people who had vitamin B or folate levels below the normal range, those with kidney impairment, or those who had used anti-Parkinsonian medications, investigational treatments for Alzheimer’s, sedatives or drugs with significant anticholinergic effects, within the past two months. Stable use of cholinesterase inhibitors, memantamine and multivitamins was allowed.
People were randomised to receive a daily multivitamin tablet, containing 5mg folic acid, 1mg of vitamin B12 and 25mg vitamins B6 (240 people), or an identical placebo (169 people). The treatment period lasted for 18 months, and subjects were seen on a tri-monthly basis during this period, when they would receive physical and blood test examinations, and receive a new supply of their medication. As a “double-blind” study, both participants and their medical carers underwent testing to ensure that they remained unaware of which treatment they were receiving.
The main outcome that the researchers examined was a change in score on the cognitive subscale of the 70-point Alzheimer Disease Assessment Scale (ADAS-cog, including memory, attention, coordination and language assessment) at 18 months. A significant benefit was defined as a 25% decline in score compared with the placebo group. They also tested for a decline in blood homocysteine levels. In their assessment they accounted for other variables that could affect either homocysteine levels or rate of cognitive decline.
What were the results of the study?
Eighty-four percent of the 409 randomised subjects completed the full 18-month study, with no difference in rate of drop-out between treatment and placebo groups. Almost all of those randomised were included in the analysis (three subjects who had missing data were excluded).
As the researchers expected, vitamin levels increased significantly more in the treatment group compared with the placebo group during the course of the study. Homocysteine levels also decreased significantly more in the treatment group (by 9%) compared to the placebo group (1%). The main study outcome, the rate of change of cognitive ability (measured using the ADAS-cog score) found no significant difference between the groups. Over the time period all scores increased rather than declined; by 0.372 points in the treatment group and 0.401 points in the placebo group. There was also no difference in change in Mini-Mental score, or other neuropsychiatric scales or assessments of daily living.
Of adverse treatment events, depression occurred significantly more often in the treatment group (28% prevalence versus 18% in the placebo group). Tests of blinding indicated that it had been adequately maintained in both groups throughout the study.
What interpretations did the researchers draw from these results?
The researchers concluded that high-dose vitamin B supplements do not slow cognitive decline in individuals with mild-moderate Alzheimer’s disease.
What does the NHS Knowledge Service make of this study?
This was a well-designed randomised control trial with regular assessments, long duration of follow-up and high completion rates in both treatment and placebo groups. It was a large trial, and as such, it provides evidence that taking vitamin B as part of a multivitamin supplement has no effect on function and cognition in Alzheimer’s disease when compared with a placebo. Additionally, as the authors acknowledge, further research should investigate the possible effects of vitamin B levels on depression.
Other points to note:
- This study only included people with normal vitamin B and folate levels. Vitamin B, and its eight various forms, is essential to human health, and cognition results may have been different and more pronounced if supplementation had been given in people who were deficient. No conclusions can be drawn upon the effects of supplementation in people who have levels below normal.
- The trial did demonstrate that the supplement reduced homocysteine levels. Therefore if homocysteine levels do effect the pathological processes involved in Alzheimer’s, it is possible that low vitamin B and high homocysteine may have an effect on cognition.
- The diagnosis of Alzheimer’s was only ‘probable’ and made by Mini-Mental examination. Alzheimer’s is characterised by progressive problems with memory, speech and language, understanding, recognition (of things or faces) and difficulty carrying out normal daily tasks. And, importantly, it is a diagnosis of exclusion where no other medical or psychiatric cause can be identified. Therefore, based on the study report alone, it cannot be concluded that all of the people in this study actually fulfilled a diagnosis of Alzheimer’s.
The study was powered, meaning that sufficient numbers of people were recruited to the trial to be able to detect a (25%) reduction in the rate of cognitive decline. Based on the results of this well-conducted research, Alzheimer’s patients and their carers can be reasonably sure that taking these vitamins makes little difference to the course of this disease.