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Advanced age as a risk factor for folate-associated functional cobalamin deficiency.
J Am Geriatr Soc. 2013 Apr; 61(4):577-82.JA

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23521545

Citation

Solomon, Lawrence R.. "Advanced Age as a Risk Factor for Folate-associated Functional Cobalamin Deficiency." Journal of the American Geriatrics Society, vol. 61, no. 4, 2013, pp. 577-82.
Solomon LR. Advanced age as a risk factor for folate-associated functional cobalamin deficiency. J Am Geriatr Soc. 2013;61(4):577-82.
Solomon, L. R. (2013). Advanced age as a risk factor for folate-associated functional cobalamin deficiency. Journal of the American Geriatrics Society, 61(4), 577-82. https://doi.org/10.1111/jgs.12155
Solomon LR. Advanced Age as a Risk Factor for Folate-associated Functional Cobalamin Deficiency. J Am Geriatr Soc. 2013;61(4):577-82. PubMed PMID: 23521545.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Advanced age as a risk factor for folate-associated functional cobalamin deficiency. A1 - Solomon,Lawrence R, Y1 - 2013/03/21/ PY - 2013/3/26/entrez PY - 2013/3/26/pubmed PY - 2013/6/19/medline SP - 577 EP - 82 JF - Journal of the American Geriatrics Society JO - J Am Geriatr Soc VL - 61 IS - 4 N2 - 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. SN - 1532-5415 UR - https://www.unboundmedicine.com/medline/citation/23521545/Advanced_age_as_a_risk_factor_for_folate_associated_functional_cobalamin_deficiency_ L2 - https://doi.org/10.1111/jgs.12155 DB - PRIME DP - Unbound Medicine ER -