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Health See other Health Articles Title: Vitamin B and Cognition Supplementation with vitamin B for 2 years did not affect cognitive performance in elderly people with raised homocysteine levels, according to a new randomized placebo-controlled trial. However, the participants involved in the trial had normal cognitive function that did not decline over the 2-year study period in the placebo group, making it difficult to show a benefit of intervention. They also had good levels of vitamin B at baseline. The study, published online November 12 in Neurology, was conducted by a team of Dutch researchers led by Nikita L. van der Zwaluw, PhD, from Wageningen University, the Netherlands. They note that high homocysteine levels are thought to be toxic to neurons and have been associated with cognitive decline and dementia. Vitamin B12 and folic acid are involved in the metabolism of homocysteine, and deficiencies of these vitamins may result in the build-up of homocysteine, which may, in turn, negatively influence cognitive performance. Thus, there is interest in establishing whether supplementation with B vitamins helps preserve cognitive function. "In our study vitamin B supplementation caused homocysteine to fall significantly to normal levels. But despite this, there was no improvement in cognition as measured in four domains," coauthor Rosalie Dhonukshe-Rutten, PhD, also from Wageningen University, commented to Medscape Medical News. "We saw a very small effect on global cognition which was statistically significant but this was not clinically relevant," she said. "This could just be chance. When you do many different tests, there is always the possibility that one will be significant just with the play of chance." What were they expecting to show? Dr David Smith But upon reviewing the study for Medscape Medical News, Professor David Smith, FMedSci, founding director of the Oxford Project to Investigate Memory and Ageing, United Kingdom, who is also researching the role of B vitamins in cognition, said, "As there was no cognitive decline in the placebo group, what were they expecting to show? "It has never been suggested that vitamin B would improve cognition in people with normal brain function," he said. "We are trying to establish whether it could delay decline. As there was no decline in the placebo group then it is impossible to show this." Professor Smith suggested that the study would have been better to include a population with mild cognitive impairment at baseline. "These patients would likely show further decline over the next few years, so then there would be something to work on." Dr Dhonukshe-Rutten acknowledged Professor Smith's comments and agrees that a study in patients with mild cognitive impairment is needed. She also points out that MRI of the brain would be useful to depict early brain abnormalities associated with cognitive decline that might occur before clinical signs. She explained that for this study they recruited elderly patients (average age, 74 years) with raised levels of homocysteine under the expectation that they would have low vitamin B levels and would demonstrate some degree of cognitive decline on follow-up. "But it turned out that actually they had good vitamin B status and high levels of cognitive function — in the normal range — which did not decline significantly over the 2-year follow-up," she said. "We just happened to enroll a very strong healthy population. In such a population, it would take a longer follow-up period to see a decline in age-related cognitive function in the placebo group." She noted that only about 10% to 15% of the participants had a low vitamin B status. "And they did decline slightly less with vitamin B supplementation. But numbers are too small to make any meaningful interpretation of this." For the study, 2919 elderly individuals with homocysteine levels of 12 to 50 ¼mol/L were randomly assigned to 400 ¼g folic acid and 500 ¼g vitamin B12 (B-vitamin group) or placebo. Both tablets contained 15 mg vitamin D3. Results showed that after 2 years, homocysteine concentrations decreased by 5.0 ¼mol/L in the B-vitamin group and 1.3 ¼mol/L in the placebo group. Cognitive domain scores did not differ over time between the two groups. Mini-Mental State Examination score decreased by 0.1 in the B-vitamin group and 0.3 in the placebo group (P = .05). No Benefit in a Healthy Population Dr Dhonukshe-Rutten says the study does demonstrate that vitamin B supplementation has no benefit on cognition in a healthy population of cognitively normal elderly people with good vitamin B status at baseline. But Professor Smith believes the study was underpowered to allow this conclusion. "They need a much longer follow-up and a larger population to make a statement like that," he said. Dr Dhonukshe-Rutten agreed that it would have been better to follow the participants for longer, but "you have to think about logistics. Other studies of nutritional supplements have shown effects on cognition in a 2-year period." Professor Smith has previously conducted a smaller study in which supplementation with B vitamins was associated with a slowing of cognitive decline in patients who had mild cognitive impairment at baseline. "We would like to do a larger trial to confirm these results, but the publication of studies like this one suggesting no effect of vitamin B is making it difficult to secure funding, even though they have been conducted in a different population," he told Medscape Medical News. "If our preliminary results turn out to be true we might be able to prevent about 20% of Alzheimer's cases. It is thought that 22% of Alzheimer's cases may be caused by raised homocysteine levels. Vitamin B supplementation of these patients therefore could have a huge effect," he added. The study was supported by the Netherlands Organization for Health Research and Development, the Dutch Dairy Association, MCO Health, Netherlands Consortium Healthy Aging, Dutch Ministry of Economic Affairs, Agriculture and Innovation, Wageningen University, VU University Medical Center, and Erasmus Medical Center, all based in the Netherlands. Neurology. Published online November 12, 2014. Abstract Editors' Recommendations No Effect of Multivitamins on Cognition Low Vitamin B12 Tied to Brain Atrophy, Cognitive Impairment B-Vitamin Supplements May Slow Brain Atrophy in MCI Post Comment Private Reply Ignore Thread
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