 Large daily doses of B vitamins may protect vulnerable populations from the brain shrinkage and memory loss associated with Alzheimer's disease, according to a study conducted by researchers from Oxford University and published in the journal Proceedings of the National Academy of Sciences in May. The new findings came from a reanalysis of data originally collected in 2010 from 271 older adults suffering from mild cognitive impairment, a form of memory loss considered a potential precursor to Alzheimer's disease. Although the brain naturally shrinks as we get older (about 0.5 percent per year), in people with mild cognitive impairment this shrinkage takes place twice as fast as usual. In Alzheimer's patients, shrinkage takes place four times as fast as usual. The researchers assigned participants to take either a placebo pill or a high daily dose of three B vitamins - folic acid (0.8 mg), vitamin B6 (20 mg) and vitamin B12 (0.5 mg) - over the course of two years. They found that memory loss halted in those who took the B vitamins, but not in those who took the placebo. The vitamins also slowed brain shrinkage by 50 percent compared to the placebo, but only in patients with higher-than-normal blood levels of the amino acid homocysteine. The homocysteine connection In healthy humans, homocysteine levels are low because the amino acid is quickly transformed into other substances, including the memory-regulating chemical acetylcholine. Researchers have long known that in Alzheimer's patients, homocysteine levels tend to be high and acetylcholine levels tend to be low. Because B vitamins appear to play a role in converting homocysteine into acetylcholine, researchers had wondered if the vitamins might help stem the development of Alzheimer's. Researchers remain unsure whether it is high levels of homocysteine, low levels of acetylcholine, or some other factor that leads to the development of Alzheimer's. Whatever the case, however, the 2010 study was the first to directly showed that increasing B vitamin levels might have a clinical effect. 'B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline,' the researchers wrote. New analysis strengthens findings One of the weaknesses of the original analysis, however, was that researchers could not prove that the observed improvements in memory were related to the decreased rate of brain shrinkage. In the new study, researchers conducted a more advanced analysis of the original data and found that the effect of the B vitamins was actually much greater than they had in initially thought: Among those taking the vitamins, brain shrinkage was reduced by an astonishing 90 percent, not just 50 percent. 'I've never seen results from brain scans showing this level of protection,' said brain imaging expert Paul Thompson, who heads the world's largest brain scan database at the UCLA School of Medicine 's Imaging Genetics Center. 'We study the brain effects of all sorts of lifestyle changes - alcohol reduction, exercising more, learning to handle stress, weight loss - and a good result would be a 25 percent reduction in shrinkage.' Notably, the new analysis also found that the B vitamins had the greatest protective benefit in the very areas of the brain that are most affected by Alzheimer's, including regions responsible for learning, memory and the organization of thoughts. The analysis also showed that the reduction in this damage was indeed directly responsible for halting participants' memory loss. 'The study needs to be repeated because there's a lot to learn about why homocysteine is damaging and whether lowering it can stop people with memory problems progressing to Alzheimer's,' said Thompson, who was not involved in the study. 'But if the results survive retesting, homocysteine level could be a useful biomarker for Alzheimer's risk.' 