brand logo

Am Fam Physician. 2006;74(10):1777-1780

Clinical Question: Does supplementation with folate, vitamin B12, and vitamin B6 to reduce homocysteine levels have a beneficial effect on cognition in older adults?

Setting: Population-based

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: Observational studies have found an association between higher levels of serum homocysteine and Alzheimer's disease and cognitive impairment. However, it is not clear whether this association is causal or whether lowering homocysteine levels improves cognition. In this trial, community-dwelling, healthy adults older than 65 years with a plasma homocysteine level of at least 1.76 mg per L (13.0 μmol per L) were recruited. The authors excluded those with impaired renal function, known cognitive impairment, those taking folate or B vitamins, and those taking medications that might interfere with folate metabolism.

After an extensive battery of baseline cognitive tests, 276 patients were randomly assigned to receive 1,000 mcg folate, 500 mcg vitamin B12 (cobalamin), and 10 mg vitamin B6 (pyridoxine) daily or matching placebo. The patients underwent cognitive testing after one and two years. Of the 138 who began the study in each group, 126 in the placebo group and 127 in the treatment group had data available for analysis. The mean age of participants was 73 years, and 44 percent were women (37 percent in the vitamin group, 52 percent in the placebo group;P = .02).

The vitamins had the expected effect on homocysteine levels, reducing them approximately 2.16 to 1.62 mg per L (16.0 to 12.0 μmol per L) in the treatment group during the two-year study. The homocysteine levels did not change in the placebo group. Neither group demonstrated improvement in cognition. The average score on the Wechsler Paragraph Recall test was worse in the vitamin group, although this difference disappeared after adjustment for sex and education. The vitamin group also did worse on the Reitan Trail Making Test, a difference that persisted after adjustment for sex and education.

Bottom Line: There is no evidence from this well-designed study that vitamin supplementation to lower homocysteine levels has any beneficial effect on cognition. Although cognition actually appeared to worsen with the use of vitamins in one of the tests, this may be a false finding given the large number of comparisons made by the researchers. (Level of evidence: 1b)

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see https://www.essentialevidenceplus.com/Home/Loe?show=Sort.

To subscribe to a free podcast of these and other POEMs that appear in AFP, search in iTunes for “POEM of the Week” or go to http://goo.gl/3niWXb.

This series is coordinated by Natasha J. Pyzocha, DO, contributing editor.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.

Continue Reading


More in AFP

Copyright © 2006 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.