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J Am Geriatr Soc. 2013 Apr;61(4):577-82. doi: 10.1111/jgs.12155. Epub 2013 Mar 21.

Advanced age as a risk factor for folate-associated functional cobalamin deficiency.

Author information

  • 1Section of Palliative Care, Department of Medicine, School of Medicine, Yale University, New Haven, CT 06520, USA. lawrence.solomon@yale.edu

Abstract

OBJECTIVES:

To determine whether high serum folate levels contribute to metabolite changes in elderly subjects with normal cobalamin levels.

DESIGN:

Case series.

SETTING:

Outpatient clinic at a university-based staff model health maintenance organization.

PARTICIPANTS:

Two hundred thirty-three ambulatory individuals without diabetes mellitus with normal renal function and normal cobalamin levels evaluated for cobalamin deficiency.

MEASUREMENTS:

Cobalamin, serum folate, methylmalonic acid (MMA), and homocysteine.

RESULTS:

Older individuals (≥60) with low-normal cobalamin levels (201-300 pg/mL) had higher MMA and lower homocysteine levels when serum folate levels were high (>20 ng/mL) than when serum folate levels were normal (P < .02), but serum folate levels within the normal range were not a determinant of either metabolite. In younger subjects with low-normal cobalamin levels, high serum folate levels were not associated with significant differences in either metabolite. At mid-normal cobalamin levels (301-600 pg/mL), high serum folate levels were associated with lower homocysteine levels in older adults (P < .001) but not with differences in MMA in either age group. Cobalamin therapy decreased or normalized MMA and homocysteine in 89% or more of participants even at pretherapy cobalamin levels greater than 600 pg/mL.

CONCLUSION:

High serum folate levels are associated with higher MMA levels when cobalamin levels are low-normal, and this effect is age dependent, not progressive within the normal serum folate range (suggesting a threshold effect), and reversed by cobalamin therapy. Because MMA may be neurotoxic, these findings suggest caution in the use of folic acid supplements in elderly adults.

© 2013, Copyright the Author Journal compilation © 2013, The American Geriatrics Society.

PMID:
23521545
[PubMed - indexed for MEDLINE]
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