A metabolic disturbance caused by a lack of three B vitamins (folate, B12 and B6) reduces the number and density of small blood vessels (capillaries) in the brain and causes problems with thinking and memory in mice, researchers at Tufts University report.
"Mice fed a diet lacking these three vitamins showed a clear decline in spatial learning and memory compared with healthy mice," says Professor Troen. The deficiency also raised blood levels of homocysteine sevenfold. Homocysteine is made when the body breaks down methionine, and these B vitamins are needed to turn it back into methionine, keeping its level down.
Earlier studies had linked high homocysteine with a greater risk of mental decline, but hadn't proved that homocysteine itself is to blame. "Based on these results, we propose that a lack of these vitamins causes a metabolic disorder, shown by high homocysteine, together with poor blood vessel function in the brain," Professor Troen says.
The team divided the mice into three groups for 10 weeks: a normal diet with methionine and the B vitamins, and two diets that raised homocysteine in different ways, one rich in methionine and the other lacking the B vitamins. They measured B vitamins and homocysteine in the blood, examined the brain and its blood vessels, and tested movement, memory, spatial learning and thinking.
The B-vitamin-deficient mice had more difficulty with the tests and took longer than the normal mice. Their slower responses went with higher homocysteine and shorter capillaries, especially in the hippocampus, a memory centre of the brain. Apart from the blood vessel changes, the brain looked normal, with no sign of the scarring (gliosis) that usually goes with nerve degeneration.
The study helps explain how blood vessel disease of the brain develops, and so how it might be treated before irreversible nerve damage occurs.
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