December 30, 2007

Cognitive Function - Folic Acid and Vitamin B12 Deficiency and Homocysteine

Epidemiologist Martha Morris and biochemist Jacob Selhub examine graphical evidence of the interaction between vitamin B12 status and folate status in relation to cognitive test results. Photo courtesy of the USDA, ARS

Folic Acid and Vitamin B12 Deficiency - Cognitive Function, Mental Deterioration, Alzheimer’s and Dementia Linked to High Homocysteine Levels.

Findings from a broad range of studies show significant relationships between cognitive function and intakes of various nutrients, including long-chain polyunsaturated fatty acids, antioxidant vitamins, and folate and vitamin B12. (Proc Nutr Soc. 2001 Feb;60(1):135-43).

In cross-sectional studies, elevated plasma homocysteine levels have been associated with poor cognition and dementia. An increased plasma homocysteine level is a strong, independent risk factor for the development of dementia and Alzheimer's disease. (N Engl J Med 2002; 346: 476-483)

Elderly people are a vulnerable population group to specific nutrient deficiencies such as vitamin B12 and folic acid, which are closely related to mental functions deterioration, especially of cognitive functions. Elderly were at risk of deficiency for both vitamins and age and mental function were associated with this risk. (Invest Clin. 2005 Mar;46(1):53-63).

Scientists from the National Institute of Aging believe folic acid may help prevent Alzheimer's disease. They say it may control a substance in the brain known to cause damage to nerve cells. The researchers found that mice on a diet deficient in folic acid had higher levels of the amino acid homocysteine. They believe the high levels of homocysteine damage the DNA of the nerve cells. (Journal of Neuroscience, 2002;22:1752-1762).

Doctors in the US analysed data on the diets of 579 people aged 60 or over from the Baltimore Longitudinal Study of Aging to identify the relationship between dietary factors and Alzheimer's disease risk. The researchers found those who consumed at least the recommended daily amount of 400 micrograms of folic acid had a 55% reduced risk of going on to develop Alzheimer's compared to those consuming under that amount. (BBC NEWS 15/8/2005).

Several researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston, Massachusetts, are looking into whether elevated blood levels of the amino acid homocysteine are involved in cognitive decline-and if so, how.

Folate Fortification

Folate is one of the B vitamins that affect the balance of homocysteine levels. A link between high blood folate levels and relatively lower homocysteine levels has long been known.

Epidemiologists Paul Jacques and Martha Morris, biochemist Jacob Selhub, and ARS-funded physician Irwin H. Rosenberg recently completed a study of the interrelationships among the B vitamins and cognitive function in this age of folate fortification.

B vitamins are involved in the synthesis of chemicals crucial to brain function. Scientists have long known that being seriously deficient in vitamin B12 leads to impaired cognitive function due to neurological complications. The researchers used a combination of blood markers to classify subjects’ vitamin B12 ranking.

Morris, who led the study, found that among people aged 60 and older, those with high blood levels of folate and normal, or adequate, vitamin B12 status scored high on cognitive function tests. These seniors were given a test that required response speed, in addition to attentiveness, visual-spatial skills, associative learning, and memory.

But what about those who had low vitamin B12 blood levels—a status that is common among seniors due to the poorer gastrointestinal conditions that come with aging? Low vitamin B12 status was linked with lower scores on cognitive tests.

“The people with high folate and low B12 status were more likely to exhibit both cognitive impairment and anemia than those with normal folate and low B12 status,” says Jacques.

The researchers recommend that future studies examine the implications of having high folate status due to fortification and too little vitamin B12 due to aging.

Population researcher Katherine L. Tucker is focusing on vitamins and cognition in a series of community-based studies.

In the Normative Aging Study, a longitudinal study of originally healthy men in the Boston area, she and colleagues found that those with the best B-vitamin status at the start, or baseline, had little change in their cognitive-function test scores. But test scores went down significantly in the men with the lowest baseline B-vitamin status and highest homocysteine concentrations.

Rosenberg and Tucker are also working with another high-risk group: homebound elderly. “The Nutrition, Aging, and Memory in Elders, or NAME, study is designed to look at the relationships among levels of several nutrients and subsequent cognitive function,” says Tucker.

“We are studying folate, vitamin B6, vitamin B12, vitamin C, and vitamin E intakes among this population, along with each individual’s cognitive functioning,” she says. The data generated may be useful in developing dietary strategies and supplementation targets to help the elderly maintain their cognitive function.

These and future studies are essential to determining whether-and to what extent-nutritional factors can be used to prevent cognitive impairment as we age.

Related articles:

Cinnamon Improves Cognitive Function


Proc Nutr Soc. 2001 Feb;60(1):135-43.

N Engl J Med 2002; 346: 476-483.

Invest Clin. 2005 Mar;46(1):53-63

Journal of Neuroscience, 2002;22:1752-1762.

BBC NEWS 15/8/2005.

Rosalie Marion Bliss, Agricultural Research Service Information Staff, USDA, Agricultural Research Service News & Events. 14/11/2007.
Used with permission. Photo courtesy of the USDA, ARS.

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