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Better Health News and Comment

High Homocysteine Linked to Poor Memory
By Jeremy Appleton, ND

Healthnotes Newswire —A high level of homocysteine in the blood has been linked with poor memory among Americans over 60 years old, according to data from the third National Health and Nutrition Examination Survey (NHANES III), published in this month’s American Journal of Clinical Nutrition.1

Over 10,000 volunteers had their blood levels of homocysteine and folate measured, and also took part in word-recall and paragraph-recall tests of cognitive (thinking and memory) function. Researchers found two significant trends: first, the higher the levels of homocysteine in the blood, the poorer the recall; second, the lower the level of folate in the blood, the poorer the recall. Folate is the form of folic acid that circulates in the blood; along with vitamins B12 and B6, folate keeps homocysteine at safe levels.

What is Homocysteine?

Homocysteine is an amino acid (a building block of protein). It is a toxic chemical that is not meant to accumulate unchecked in the body. Rather, homocysteine needs to be transformed into safer amino acids, like methionine and cysteine. Elevated homocysteine levels in the plasma portion of the blood are caused, at least in part, by metabolic problems that can be inherited or can result from nutritional deficiencies. In healthy people, homocysteine levels should be low.

Elevated blood levels of homocysteine are now a widely accepted risk factor for atherosclerosis, coronary heart disease, and stroke.2 Homocysteine elevations have also been associated with an increased risk of Alzheimer’s disease,3 4 while higher blood levels of B vitamins (like folate) appear to be protective.5 The now famous “Nun Study,” published last year in the American Journal of Clinical Nutrition, found that low blood levels of folic acid are related to a relatively high risk of Alzheimer’s disease–related brain degeneration.6

Does Homocysteine Impair Memory?

The common finding of high homocysteine levels in stroke and in Alzheimer’s disease suggests that homocysteine may be the common link between these two causes of age-related memory impairment.7 8 Byproducts of homocysteine metabolism could be directly toxic to the brain and nerve tissue,9 and thus may be directly responsible for the memory deficits observed in this study. However, other explanations for the association between high homocysteine and poor memory must also be considered.

The researchers excluded people who had had a stroke, so any association between high homocysteine and poor recall cannot be explained by stroke-related brain damage. However, it is still possible that the subjects with high homocysteine were the ones with more advanced cerebral atherosclerosis (hardening and blockage of the arteries supplying the brain) and that their memory impairment was the result of reduced blood flow to the brain.

Folic Acid: The Missing Link?

Another possibility is that the low folate status observed in participants with poor recall could have impaired the function of folate-dependent neurotransmitters (chemical messengers in the brain).10 11 In this case, high homocysteine may simply have been a marker for low folate. However, the researchers found a link between high homocysteine and poorer recall that was independent of folate status, suggesting a more direct effect of homocysteine on mental status.

Nonetheless, of all the B vitamins, folic acid supplementation has been shown to lower homocysteine levels the most for the average person.12 Given the results of the new study, older Americans seeking to preserve their cognitive function may wish to consult their doctor about supplementing their diet with additional folic acid.

1. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey. Am J Clin Nutr 2001;73:927–33.
2. Christen WG, Ajani UA, Glynn RJ, Hennekens CH. Blood levels of homocysteine and increased risks of cardiovascular disease. Arch Intern Med 2000;160:422–34.
3. Nilsson K, Gustafson L, Faldt R, et al. Hyperhomocysteinaemia—a common finding in a psychogeriatric population. Eur J Clin Invest 1996;26:853–9.
4. Lehmann M, Gottfries CG, Regland B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dement Geriatr Cogn Disord 1999;10:12–20.
5. Riggs KM, Spiro A 3rd, Tucker K, Rush D. Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 1996;63:306–14.
6. Snowdon DA, Tully CL, Smith CD, et al. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Am J Clin Nutr 2000;71:993–8.
7. Miller JW. Homocysteine and Alzheimer’s disease. Nutr Rev 1999;57:126–9.
8. Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998;49:31–62.
9. Clarke R, Smith AD, Jobst KA, et al. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55:1449–55.
10. Rosenberg IH, Miller JW. Nutritional factors in physical and cognitive functions of elderly people. Am J Clin Nutr 1992;55(6 Suppl):1237S–43S.
11. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137–52.
12. Stein JH, McBride PE. Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology, screening, and treatment. Arch Intern Med 1998;158:1301–6.

Jeremy Appleton, ND, is a licensed naturopathic physician, writer, and educator in the field of evidence-based complementary and alternative medicine. Dr. Appleton is Chair of Nutrition at the National College of Naturopathic Medicine and Senior Science Editor at Healthnotes.


Information presented at is for educational purposes only; statements about products and health conditions have not been evaluated by the U.S. Food & Drug Administration. Copyright ©2007 Inc.