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Source : Dari Publikasi Medscape
Vitamin B12 May Protect Against Brain Volume Loss in Older People
September 12, 2008 — Individuals who had higher vitamin B12 levels were 6 times less likely to experience brain-volume loss, a new study shows. The results are published in the September 9 issue of Neurology.
Researchers say the findings should encourage further investigation of low vitamin B12 status as a modifiable cause of brain atrophy and subsequent cognitive impairment in the elderly.
"Clinicians should rethink what they consider normal vitamin B12 levels," senior author A. David Smith, DPhil, from the University of Oxford, told Medscape Neurology & Neurosurgery. "They may want to reconsider the current cutoffs that we use, because they may be too low."
Dr. Smith points out that according to the Institute of Medicine, in healthy individuals, no adverse effects have been associated with excess vitamin B12 intake from supplements or foods such as meat, fish, fortified cereals, milk, and others.
Vitamin B12 Deficiency a Public Health Problem
In the August issue of the American Journal of Clinical Nutrition, experts debated whether the mandatory fortification of foods with vitamin B12 would be beneficial (Refsum H, Smith AD. Am J Clin Nutr. 2008;88:253-254). Dr. Smith weighed in on the issue and in an editorial concluded that much work remains to be done.
"We must remember that evidence of benefit and of lack of harm is always needed before introducing mandatory population-level exposures to nutrients," he wrote.
Dr. Smith pointed to a number of concerns, including a lack of data, issues pertaining to potential malabsorption in the elderly, and observational studies suggesting a link between vitamin B12 and an increased risk for cancer.
During an interview, Dr. Smith pointed out that many unknowns remain about what adverse effects may be associated with excessive amounts of vitamin B12. But, he noted, "We know that an oral dose of 1 mg of vitamin B12 will likely result in just 1% of absorption."
Vitamin B12 deficiency is a public health problem, especially among the elderly, who tend to have lower rates of absorption, so more vitamin B12 intake could help reverse this problem, Dr. Smith said.
Dr. Smith's group, led by Anna Vogiatzoglou, from the University of Oxford, conducted a prospective study of 107 community-dwelling volunteers aged 61 to 87 years without cognitive impairment at enrollment. They examined the relationship between markers of vitamin B12 status and brain-volume loss per year over a 5-year period in this elderly population.
The researchers assessed participants yearly by clinical examination, magnetic resonance imaging scans, and cognitive tests. They collected blood at baseline to measure plasma vitamin B12, transcobalamin, holotranscobalamin, methylmalonic acid, total homocysteine, and serum folate.
They found the decrease in brain volume was greater among those with lower vitamin B12 and holotranscobalamin levels. The decrease in brain volume was also greater among those with higher plasma total homocysteine and methylmalonic acid levels at baseline.
Linear regression analysis showed that associations with vitamin B12 and holotranscobalamin remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, apolipoprotein E ε4 status, total homocysteine, and folate.
The researchers used the upper tertile (for the vitamins) and the lower tertile (for the metabolites) as references in logistic regression analysis and adjusted for covariates.
Vitamin B12 in the bottom tertile (<308 pmol/L) was associated with increased rate of brain-volume loss. The association was similar for low levels of holotranscobalamin (<54 pmol/L).
Risk for Brain Volume Loss Associated with Lowest vs Highest Levels of Vitamin B12 and Holotranscobalamin
Level Odds Ratio (95% CI)
Vitamin B12 6.17 (1.25 – 30.47)
Holotranscobalamin 5.99 (1.21 – 29.81)
Low transcobalamin saturation was also associated with brain-volume loss, but the researchers found no association with high levels of methylmalonic acid, high total homocysteine, or low levels of folate.
"The major finding of this study is that at baseline, vitamin B12 status across the normal range is associated with brain atrophy at follow-up," write the researchers.
Vitamin B12 Status Potential Early Marker of Brain Atrophy
Dr. Smith's team points to a number of strengths of their study, including its prospective design with a relatively long follow-up period and its population-based setting.
The group also points to a number of limitations to the study, including the relatively small sample size and the fact that they did not investigate whether the loss in brain volume is focal or diffuse. Also, a total of 41 of the 148 participants did not have a second brain scan.
They conclude, "These findings suggest that plasma vitamin B12 status may be an early marker of brain atrophy and thus a potentially important modifiable risk factor for cognitive decline in the elderly."
The researchers have disclosed no relevant financial relationships.
Neurology. 2008;71:826-832. Abstract