They observed that mice fed a diet deficient in folate, B12 and B6 had reduced brain capillary length and density – vascular changes that caused cognitive dysfunction.
"Metabolic impairments induced by a diet deficient in three B-vitamins – folate, B12 and B6 – caused cognitive dysfunction and reductions in brain capillary length and density in our mouse model," said lead researcher, Aron Troen, PhD. "The vascular changes occurred in the absence of neurotoxic or degenerative changes."
“Mice fed a diet deficient in folate and vitamins B12 and B6 demonstrated significant deficits in spatial learning and memory compared with normal mice.”
The B-deficient mice also developed homocysteine levels seven times greater than those in the control group. Homocysteine is produced when the dietary protein methionine breaks down and has been linked with learning impairment.
B vitamins such as folate, vitamin B12, and vitamin B6 are required to convert homocysteine back to methionine.
Despite these findings, published in the August 26, 2008 issue of Proceedings of the National Academy of Sciences, Troen said further research was required into the links between elevated homocysteine levels and learning retardation.
“It has not been determined that homocysteine is directly responsible,” he said. “Based on the findings of our study, we theorise that a deficiency of B-vitamins induces a metabolic disorder that manifests with high homocysteine, as well as cerebral microvascular dysfunction.”
Irwin Rosenberg, MD, director of the Nutrition and Neurocognition Laboratory at the Human Nutrition Research Center on Aging , said of the study: “The elevated levels of homocysteine that were associated with vascular cognitive impairment in the mice in our study are comparable to the levels that are associated in older adults with an increased risk for Alzheimer’s disease and cerebrovascular disease, the latter of which manifests with conditions such as stroke and atherosclerosis. These findings may indicate that microvascular changes mediate the association between high homocysteine levels and human age-related cognitive decline.”
The researchers from the Jean Mayer USDA HNRCA at Tufts University measured the metabolic, cognitive, and microvascular effects of B-vitamin deficiency.
The mice were divided into three groups and fed different diets for 10 weeks. The control group were fed a normal diet containing B vitamins and methionine while two other groups were fed B-vitamin deficient diets designed to induce high homocysteine levels via separate metabolic mechanisms.
Blood concentrations of B-vitamins and homocysteine were measure and brain anatomy and vasculature were assessed.
The mice completed tests such as holding on to a wire and walking a beam as well as spatial learning and memory with the Morris water maze - a test commonly used to assess rodent cognitive function.
“It took longer, on average, for the B-vitamin-deficient mice to manoeuvre the water maze, compared with controls,” says Troen. “Longer latencies were associated with higher plasma homocysteine levels and shorter capillaries, particularly in the brain region called the hippocampus. Despite the vascular changes, the brain anatomy appeared normal, and there was no evidence of a cellular proliferation process called gliosis, which typically accompanies neurodegeneration.”
Proceedings of the National Academy of Sciences.
2008 (Aug. 26); 105 (34): 12474-12479.
“B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice”
Authors: Troen AM, Shea-Budgell M, Shukitt-Hale B, Smith DE, Selhub J, Rosenberg IH.