Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated peripheral nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of vitamin B-12 status

Abstract

Background: It is uncertain whether vitamin B-12 supplementation can improve neurophysiologic function in asymptomatic elderly with low vitamin B-12 status or whether folate status affects responses to vitamin B-12 supplementation. Objective: We assessed the effects of a single intramuscular injection of 10 mg vitamin B-12 (which also contained 100 mg vitamin B-6 and 100 mg vitamin B-1) on vitamin B-12 status and neurophysiologic function in elderly community-dwelling Chileans with low serum vitamin B-12 concentrations who were consuming bread fortified with folic acid. Design: A pretreatment and posttreatment study was conducted in 51 participants (median 6 SD age: 73 6 3 y; women: 47%) with serum vitamin B-12 concentrations ,120 pmol/L at screening. Vitamin B-12 status was defined by combining vitamin B-12, plasma total homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin into one variable [combined indicator of vitamin B-12 status (cB-12)]. The response to treatment was assessed by measuring cB-12 and neurophysiologic variables at baseline and 4 mo after treatment. Results: Treatment increased serum vitamin B-12, holotranscobalamin, and cB-12 (P , 0.001) and reduced plasma tHcy and serum MMA (P , 0.001). Treatment produced consistent improvements in conduction in myelinated peripheral nerves; the sensory latency of both the left and right sural nerves improved on the basis of faster median conduction times of 3.1 and 3.0 ms and 3.3 and 3.4 ms, respectively (P , 0.0001). A total of 10 sensory potentials were newly observed in sural nerves after treatment. Participants with high serum folate at baseline (above the median, $33.9 nmol/L) had less improvement in cB-12 (P , 0.001) than did individuals whose serum folate was less than the median concentration (i.e., with a concentration ,33.9 nmol/L). Conclusion: Asymptomatic Chilean elderly with poor vitamin B-12 status displayed improved conductivity in myelinated peripheral nerves after vitamin B-12 treatment and an interaction with folate status, which was detected only with the use of cB-12. This trial was registered at www.controlled-trials.com as ISRCTN02694183.Am J Clin Nutr 2016;103:250-7.

Transcobalamin 776C→G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake

“…The odds of neuropathy were significantly higher for GG genotypes than for CC genotypes when folate intakes were .2 times the Recommended Dietary Allowance (.800 mg/d) but not when the folate intakes were #800 mg/d. These results have been supported by a recent study on vitamin B-12 supplementation of elderly individuals who were deficient in the vitamin, in which the improvement of vitamin B-12 status after supplementation was impaired by high serum folate status (29). Both natural folate and synthetic folic acid from fortified foods and supplements contributed to total folate intake in our population.…”

Vitamin B12 deficiency from the perspective of a practicing hematologist

“…Increasingly, holoTC measurement is being used for clinical assessment of B 12 status, either singly 3,76,77 or in combination with the total serum B 12 with or without measurement of the metabolites MMA and Hcy. [78][79][80] In addition, holoTC levels also reflect B 12 absorptive capacity.…”

Laboratory assessment of folate (vitamin B9) status

“…Likewise, Morris et al found that a combination of high serum folate and poor B 12 status in elderly people predicted faster cognitive decline than normal folate with poor B 12 status 17. In a study of the elderly in Chile, where a higher mandatory dose of folic acid is added to flour (220 µg/100 g) compared with the USA (80 µg/100 g), >26% of subjects had high serum folate (≥45.3 nmol/L), and a weaker biochemical response to a single B 12 injection was observed than in those with serum folate ≥33.9 nmol/L 20. Moreover, some researchers suggest that the daily upper tolerable limit for folic acid of 1 mg/day is set too high as adverse neurological effects have been observed from long-term exposure to folic acid at doses of 0.5–1 mg in the presence of B 12 deficiency 21.…”