Low Vitamin B-12 Linked to Risk of Dementia

by | Jul 24, 2008 | 2007, Aging, Alzheimer's Disease, Brain Health, Cognitive Health, Vitamin B12 - Mental

Written by Marcia Egles, MD. Doubling a measure of vitamin B-12 was associated with a 30% slower rate of cognitive decline.

An association between low vitamin B12 status and cognitive decline in older adults is the finding of a ten- year long British study. Vitamin B-12, which is found only in foods of animal origin such as meat, eggs and dairy, is adequately obtained by most young, healthy persons. However, an estimated 10-15% of those over age 60 are deficient in vitamin B-12 (1). Diverse causes can result in a loss of ability to absorb vitamin B-12 from food, even when the diet itself is otherwise nutritious (2). Whereas the absorption of the protein–bound vitamin B-12 found in food can be decreased in the elderly, the absorption of  the crystalline form of B-12 found in supplements and fortified cereals remains generally intact with advancing age (1).

Vitamin B-12 deficiency in its severe forms has long been recognized as a medical disorder characterized by anemia and neurological problems, including dementia. Because vitamin B-12 is well stored in the body, the manifestations of deficiency can take years to surface. That more marginal degrees of B-12 deficiency might be involved in the loss of mental function in the elderly was a consideration of this investigation.

Previous studies have observed a link between elevated homocysteine levels and increased risk of Alzheimer’s dementia (3,4). Homocysteine is an amino acid, elevated levels of which have been associated with heart and  vascular disease. Vitamin B-12 and folate are involved in the metabolism of homocysteine. Several studies have established that B-12 and folate supplements can lower homocysteine levels (2, 5), spurring the hope that B-12 and folate supplementation might curb the development of Alzheimer’s disease. Dementia currently afflicts about 4.5 million people in the United States and many more have cognitive impairment.

This study, a longitudinal cohort study*, followed 1648 Oxford citizens, aged 65-75, from 1995-2005. No mandatory folic acid fortification program was in place for this population. Blood levels of vitamin B-12, holotranscobalamin, total homocysteine, methylmalonic acid (MMA), and folate levels were measured.”  Holotranscobalamin was included in the measurements because it is a more sensitive marker of vitamin B-12 status than is a vitamin B-12 level. MMA was included because it is elevated in vitamin B-12 deficiency.

After statistical adjustment for known risk factors such as vascular disease, the blood levels were compared to measures of mental status. Mental function was assessed by the “Mini Mental Status Examination” at three points over eight years. Research nurses interviewed the participants in their homes. The maximum score on the Mini Mental Status Examination is 30. The baseline average score of the participants was 24.8.

The study found that a doubling in holotranscobalamin concentration, the measure of biologically active vitamin B-12, was associated with a 30% slower rate of cognitive decline. In contrast, cognitive decline was found unrelated to standard vitamin B-12 or folate levels. The researchers explained that holotranscobalamin, MMA and homocysteine are more precise measures of vitamin status than are plain vitamin B-12 or folate levels. A doubling of both homocysteine and MMA levels were each associated with a 50% more rapid cognitive decline.

Clinical trials are necessary to determine whether vitamin B-12 supplementation is effective for maintenance of cognitive function. One such large study, the “B-Vitamin Treatment Collaboration” is currently underway (7).

Source: Clarke, Robert, Jacqueline Birks, Ebba Nexo, Per M. Ueland, Joern Schneede, John Scott, Anne Molloy, and John Grimley Evans. “Low vitamin B-12 status and risk of cognitive decline in older adults.” The American journal of clinical nutrition 86, no. 5 (2007): 1384-1391.

© 2007 American Society for Nutrition

Posted July 24, 2008.

*The observational study of a group of individuals at regular intervals over a relatively long period of time.

References:

  1. Baik HW, Russell RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr. 1999;19:357-377.
  2. Linus Pauling Institute at Oregon State University.
  3. Clarke R, et al.  Folate, vitamin B-12, and serum total homocysteine levels in confirmed Alzheimer disease.  Arch Neurol 1998:55: 1449-55.
  4. Haan MN et al.  Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacremento Area Latino Study on Aging.  Am J Clin Nutr 2007:85:511-7.
  5. Homocysteine Lower Trialists’ Collaboration.  Dose dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials.  Am J Clin Nutr 2005: 82:806-12.
  6. Shane B. Folic acid, vitamin B-12, and vitamin B-6. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483-518.
  7. Clarke R, Armitage JM et al.  B-Vitamin Treatment Trialists’ Collaboration.  Homocysteine-lowering trials for the prevention of cardiovascular events: a review of the design and power of the large randomized trials.  Am Heart J 2006: 151: 282-7.