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

Journal of the American Geriatrics Society (2013-03-26)
Lawrence R Solomon
ABSTRACT

To determine whether high serum folate levels contribute to metabolite changes in elderly subjects with normal cobalamin levels. Case series. Outpatient clinic at a university-based staff model health maintenance organization. Two hundred thirty-three ambulatory individuals without diabetes mellitus with normal renal function and normal cobalamin levels evaluated for cobalamin deficiency. Cobalamin, serum folate, methylmalonic acid (MMA), and homocysteine. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cyanocobalamin, tested according to Ph. Eur.
Sigma-Aldrich
Cyanocobalamin, meets USP testing specifications
Sigma-Aldrich
Cyanocobalamin, SAJ special grade, ≥95.0%
Sigma-Aldrich
Methylmalonic acid, 99%
Supelco
Cyanocobalamin (B12), analytical standard
Supelco
Cyanocobalamin (Vitamin B12) solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Cyanocobalamin, pharmaceutical secondary standard, certified reference material
Sigma-Aldrich
Vitamin B12, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥98%
Sigma-Aldrich
Vitamin B12, ≥98%
Supelco
Methylmalonic acid solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®