Epidemiological studies have reported that high levels of the amino acid homocysteine are associated with suspected or confirmed dementia. Indeed, the Framingham study reported that people with homocysteine levels above 14 micromoles per litre of serum had twice the risk of dementia.

This has led to the hypothesis that by lowering circulating levels of homocysteine by B vitamin supplements, the risk and occurrence of dementia could be reduced.

A new case of dementia is diagnosed every seven seconds, according to a paper published in December in The Lancet, which is equivalent to 4.6m new cases each year.

By 2040 the number of people with dementia is predicted to rise to 81.1m, from 24.3m today.

The double-blind, placebo-controlled, clinical trial, published in the New England Journal of Medicine (Vol. 354, pp. 2764-2772), randomly assigned 276 healthy volunteers with high plasma homocysteine (13 micromoles per litre or more) to a daily supplement of B vitamins containing 1000 micrograms of folate, 500 micrograms of B12, and 10 milligrams of B6 (Merck Eprova), or a placebo.

After two years the researchers, from the University of Otago, found that homocysteine levels in the supplemented group had fallen by an average 4.36 micromoles per litre compared to placebo group.

Plasma folate levels also increased by 250 per cent, while plasma B12 levels increased by almost 100 per cent after two years.

Compliance was good, with a reported 215 people taking at least 95 per cent of the capsules.

A battery of cognitive tests, including the Mini-Mental State Examination, was taken by the subjects at baseline, after one year, and at the end of the two years.

The researchers found that, despite lowering the homocysteine levels of the subjects, no significant difference between the scores on the cognitive tests was observed for the B vitamin supplemented group, with respect to the placebo group.

“The results of our trial do not support the hypothesis that homocysteine lowering with folate, vitamins B12, and B6 improves cognitive performance in healthy older people,” concluded lead author Jennifer McMahon.

In an accompanying editorial however Robert Clarke from the University of Oxford said: “Since the trial included too few participants, the duration was too short, and cognitive-function scores in controls remained intact throughout the trial, it lacked the statistical power to refute the homocysteine hypothesis of dementia.”

This point was noted by the researchers from New Zealand: “We cannot rule out the possibility of a benefit with long-term [supplementation].”

The B-Vitamin Treatment Trialists' Collaboration should soon be better able to address the link between B-vitamins, homocysteine levels, and cognitive function, said Clarke.

“The effects of three to seven years of treatment with B vitamins on cognitive function should eventually be available on about 20,000 of the 50,000 participants with previous cardiovascular or renal disease in the 12 large homocysteine-lowering trials for the prevention of cardiovascular events,” said Clarke.

Dr Clarke also said that vitamin B12 is a more important determinant of high homocysteine levels in people over 70 than folate, and that future studies should focus on dietary supplementation of 1000 micrograms of B12 in elderly people to investigate cognitive decline.