The results of several research studies suggest that consuming adequate amounts of folic acid and vitamins B6 and B12 throughout one's lifetime may play a key role in reducing the risk of developing Alzheimer's disease and other types of dementia in later years.
It is known that the strongest determinant of blood homocysteine levels (unless there is an overriding genetic defect of some major consequence) is one's nutritional status of folic acid, vitamin B6 and vitamin B12, as will be discussed below. These same B vitamins are also involved in the synthesis of important neurotransmitters that are required for cognition and other brain functions.
The average intake of folic acid is only about half of the 400 mcg that experts indicate should be taken daily for otherwise healthy individuals. A significant number of people over the age of 60 don't efficiently absorb vitamin B12 from food sources, due to age-related changes in their digestive tracts. As such, many authorities encourage consumers to ingest more dark green vegetables, beans and fortified grains to acquire more folic acid, and more fortified cereals to help acquire additional vitamin B12. The Tufts University Health & Nutrition Letter also suggests that taking a daily multiple vitamin and mineral taken daily is another way to ensure that patients achieve a more optimal intake of these B vitamins, which may be a simple, but important measure to prevent changes in brain function related to the development of Alzheimer's and dementia.1
The notion that deterioration in mental capacities is a natural part of the aging process has been challenged by a number of recent research studies that indicate that vitamin and mineral status may be significant factors in modifying a person's risk of developing Alzheimer's and other types of cognitive impairment and dementia.
In March 1996, Dr. Riggs and associates published results from a study in The American Journal of Clinical Nutrition, that findings indicated that older individuals with low blood concentrations of vitamin B12, B6, and the B vitamin known as folic acid had the poorest scores of brain function measured by a battery of cognitive tests.2
In previous studies, clinical deficiencies of B vitamins have been implicated in brain-related disorders, including reversible dementia (vitamin B12 and possibly folate), depression (folate), and electrophysiological dysfunction, including convulsions (vitamin B6).3-5 In healthy older adults, blood levels of B vitamins usually considered to be in the normal range were associated with poorer scores on tests of delayed recall, abstract reasoning, and selective attention.6,7 There is also good evidence that deficiencies of folic acid and vitamins B12 and B6 increase with age, and are common in older adults.8,9
Thus, there is growing support for the premise that optimal B vitamin status can prevent, slow or reverse the deterioration in memory and other mental capacities important to the quality of life of older individuals.
The "Normative Aging" study involved 70 male subjects, aged 54-81 years. It revealed that blood levels of vitamin B12 and folic acid appear to be related to cognitive performance in a different manner than vitamin B6 blood levels. Low blood levels of vitamin B12 and folic acid were associated with deficits in spatial copying. Higher blood levels of vitamin B6 were associated with better performance on two tests of memory.2
Another interesting finding was that nearly half of the subjects in this study had low blood levels of vitamin B6 (<30 umol/L).2,10 This is extremely important, because B vitamins are known to participate in brain chemistry and physiology. Vitamins B12 and folic acid are required as coenzymes in the synthesis of the neurotransmitters serotonin and the catecholamines (adrenaline, norepinephrine). They are also required for the production of S-adenosylme-thionine, which has antidepressant properties.11-13 Vitamin B12 deficiency may also result in de-insulation of nerve fibers (demyelination), which produces a constellation of neurological symptoms.5 Vitamin B6 is a cofactor in the production of other brain chemicals (neurotransmitters), including dopamine, norepinephrine, serotonin, GABA, and taurine.14
Also, higher blood levels of homocysteine often result from subnormal intakes of folic acid, vitamin B12 and vitamin B6. This is because these vitamins are required to recycle homocysteine to other amino acids such as methionine and cystathionine.15 High blood levels of homocysteine are associated with increased risk of cardiovascular, cerebrovascular (narrowed arteries in the brain), and peripheral vascular disease (narrowed blood vessels in the arms, hands, legs and feet).16 Narrowed arteries in the brain (cerebrovascular disease) have been shown to be associated with decrements in psychomotor speed and on tests measuring fluid and visual abilities.17-21
Such cognitive dysfunction, therefore, may stem from high levels of homocysteine. As previously stated, vitamins B6, B12 and especially folic acid are key nutrients that prevent and reverse high blood levels of homocysteine.
In the Normative Aging study, subjects with high levels of homocysteine performed, on average, like patients with mild Alzheimer's. They also exhibited difficulty in copying the most complex spatial figures. For example, few subjects in the highest 25th percentile of homocysteine concentrations completed the cube (22 percent) and tapered box (17 percent) figure tests correctly. By comparison, these figures are mastered by 50 percent of school children by the age of 13 years. Subjects with the lowest blood homocysteine levels demonstrated the best results on these tests.2
Taken together, the body of evidence continues to support the contention that B vitamin nutritional status is crucial to the development and preservation of mental capacities throughout one's lifetime. The sad reality is that many midlife and older members of society have poor dietary intake and nutritional status of various B vitamins (vitamin B6, folic acid, etc.). By all counts, it appears that health practitioners should encourage patients to pay attention to foods that are rich sources of these, and to continue to emphasize the multitude of benefits available from the daily use of a well-formulated multiple vitamin and mineral supplement.
Finally, health practitioners should be aware that other nutritional supplements have also been shown to improve mental faculties and cognition in older subjects. These include huperzine A; CDP-choline; bacopa monnieri; dimethylaminoethanol (DMAE); ginkgo biloba; vitamins E and C; phosphatidylserine; and acetyl-L carnitine. Additional information on these brain nutrients and the physiological mechanisms through which they restore and/or preserve mental capacities will be discussed in future articles in this column. As nutrition and supplementation have been shown to influence the development and progression of Alzheimer's disease and age-related cognitive impairment (conditions that are expected to affect many millions of Americans as the Baby-Boomer generation heads into the over-50 age bracket), health practitioners should be well informed as to the evidence-based natural interventions that have been shown to prevent or improve these serious, and increasingly prevalent, threats to one's quality of life.
- B vitamins for staving off Alzheimer's disease. Tufts University Health & Nutrition Letter Jan 1999;16(11): p1, 2/3p.
- Riggs K. et al. Relations of vitamin B12, vitamin B6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am. J. Clin. Nutr 1996;63:306-14.
- Martin DC. B12 and folate deficiency dementia. Clin Geriatr Med 1988;4:841-52.
- Abou-Saleh MT, Coppen A. The biology of folate in depression: implications for nutritional hypotheses of the psychoses. J Psychiatr Res 1986;20:91-101.
- Sauberlich HE. Relationship of vitamin B6, vitamin B12, and folate to neurological and neuropsychiatric disorders. In: Bendich A, Butterworth CE Jr, eds. Micronutrients in Health and in Disease Prevention. New York: Marcel Dekker, Inc, 1991:187-218.
- Bohnen N, Jolles J, Degenaar CP. Lower blood levels of vitamin B12 are related to decreased performance of healthy subjects in the Stroop Color-Word Test. Neurosci Res Commun 1992;11:53-6.
- Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA 1983;249:2917-21.
- Joosten E, van den Berg A, Riezler R, et al. Metabolic evidence that deficiencies of vitamin B12 (cobalamin), folate, and vitamin B6 occur commonly in elderly people. Am J Clin Nutr 1993;58:468-76.
- Lindenbaum J, Rosenberg IH, Wilson PWF, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr 1994;60:2-11.
- Leklem JE. Vitamin B6: a status report. J Nutr 1990;120:1503-7.
- Carney MWP, Toone BK, Reynolds EH. S-Adenosylmethionine and affective disorder. Am J Med 1987;83(suppl 5A):104-6.
- Levitt AJ, Joffe RT. Folate, vitamin B12, and life course of depressive illness. Biol Psychiatry 1989;25:867-72.
- Shane B, Stokstad ELR, Vitamin B12 folate interrelationships. Annu Rev Nutr 1985;5:115-41.
- Dakshinamurti K, Paulose CS, Siow YL. Neurobiology of pyridoxine. In: Reynolds RD, Leklem JE, eds. Vitamin B6: Its Role in Health and Disease. New York: Alan R Liss, Inc, 1985;99-121.
- Selhub J, Jacques PJ, Wilson PWF, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in the elderly. JAMA 1993;270:2693-8.
- Jacques PJ, Riggs KM. B vitamins as risk factors for age-related diseases. In: Rosenberg IH, ed. Nutritional Assessment of Elderly Populations: Measure and Function. New York: Raven Press, 1995.
- Berg S. Psychological functioning in 70 and 75-year-old people. Acta Psychiatr Scand 1980;Suppl 288:1-47.
- Botwinick J, Storandt M. Memory, Related Functions and Age. Springfield, IL: Charles C Thomas, 1974.
- Hertzog C, Schaie KW, Gribbin K. Cardiovascular disease and changes in intellectual functioning from middle to old age. J Gerontol 1978;33:872-83.
- Rinn WE. Mental decline in normal aging: a review. J Geriatr Psychiatry Neurol 1988;1:144-58.
- Spieth W. Slowness of task performance and cardiovascular disease. In: Welford AT, Birren JE, eds. Behavior, Aging and the Nervous System. Springfield, IL: Charles C Thomas, 1965:366-400.
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