Higher folate levels linked to lower Alzheimer's risk

By Stephen Daniells

- Last updated on GMT

Related tags: Folic acid, Alzheimer's disease

An increased intake of folate by diet and supplements may halve the
risk of developing Alzheimer's disease, suggests new research from
the US.

Writing in the Archives of Neurology​, lead author Jose Luchsinger from Columbia University Medical Center, New York, reports that after analyzing the diets of 965 individuals, and then following them for about six years, the highest intake of folate from both dietary and supplements was associated with a significant reduction in the risk of developing Alzheimer's.

Alzheimer's is the most common form of dementia and currently affects over 13 million people worldwide. The direct and indirect cost of Alzheimer care is over $100 bn (€ 81 bn) in the US alone. The direct cost of Alzheimer care in the UK was estimated at £15 bn (€ 22 bn).

By the year 2047, the prevalence of Alzheimer's disease (AD) is expected to quadruple, said Luchsinger in the background information in the article.

For the new study, dietary assessment was performed using 61-item food frequency questionnaires, and the intakes of folate, vitamin B6 and B12 calculated accordingly. The participants had an average age of 75.8 and 70.2 percent were women, 32.6 percent African-American, 45.3 percent Hispanic and 22.1 percent white.

Ninety-eight per cent of these dietary assessments were obtained in 1996 or earlier, before the introduction of mandatory folate fortification of grain - an overwhelming body of evidence linked folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) in infants.

This connection led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid - the synthetic, bioavailable form of folate.

After an average of 6.1 years of follow-up, 192 cases of Alzheimer's disease had been diagnosed. After adjusting for potential confounding factors, like age, sex, ethnicity, cardiovascular history and B6 and B12 intake, Luchsinger and co-workers report that increasing folate intake, from both dietary and supplemental sources, was associated with a significantly reduced risk of Alzheimer's disease (50 per cent risk reduction).

Interestingly, neither dietary folate nor supplements alone were significantly linked to Alzheimer's disease risk; only the two in combination appeared to produce an effect.

Vitamin B12 and B6 levels were not associated with Alzheimer's disease risk, said the researchers.

"We found that higher folate intake was independently related to lower AD risk in a predominantly Hispanic and African American cohort of elderly persons with a high prevalence of vascular risk factors,"​ wrote the researchers.

Higher folate intake was modestly correlated with lower homocysteine levels, "indirectly suggesting that a lower homocysteine level is a potential mechanism for the association between higher folate intake and a lower Alzheimer's disease risk,"​ said the authors.

The link between Alzheimer's and homocysteine involves the accumulation of amyloid proteins in the brains. In vitro​ studies have reported that folate deficiencies and high homocysteine levels may enhance the effects of amyloid-beta, which in turn would indicate an increase in Alzheimer risk factors.

The researchers stress that no definitive conclusion about the role of folate in the development of Alzheimer's disease can be made, since the findings are at odds with previously published studies.

"Thus, the decision to increase folate intake to prevent Alzheimer's disease should await clinical trials,"​ they concluded.

Clive Ballard, director of research for British charity the Alzheimer's Society agreed that a controlled trial is necessary to "determine the full value of this research."

"It is worth noting that follow-up studies within communities are notoriously difficult to interpret because there are other external factors that can influence the results,"​ siad Ballard in a statement.

"These latest findings add weight to growing evidence about the important role that dietary factors can play in preventing Alzheimer's disease,"​ he said.

The B-Vitamin Treatment Trialists' Collaboration​ should soon be better able to address the link between B-vitamins, homocysteine levels, and cognitive function. 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 from 12 large homocysteine-lowering trials.

The study was funded by the National Institutes of Health, the Charles S. Robertson Memorial Gift for research on Alzheimer's disease, the Blanchette Hooker Rockefeller Foundation, and the New York City Council Speaker's Fund for Public Health Research.

Source: Archives of Neurology​ January 2007, Volume 64, Pages 86-92 "Relation of Higher Folate Intake to Lower Risk of Alzheimer Disease in the Elderly"​ Authors: J. Luchsinger, M-X. Tang, J. Miller, R. Green, R. Mayeux

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