Plasma Methylmalonic Acid Concentration in Folic Acid-Supplemented Depressed Patients with Low or Marginal Vitamin B-12: A Randomized Trial.
folic acid
metabolism
methylmalonic acid
public health
vitamin B-12
Journal
The Journal of nutrition
ISSN: 1541-6100
Titre abrégé: J Nutr
Pays: United States
ID NLM: 0404243
Informations de publication
Date de publication:
03 12 2021
03 12 2021
Historique:
received:
25
02
2021
revised:
29
03
2021
accepted:
02
08
2021
pubmed:
13
9
2021
medline:
17
2
2022
entrez:
12
9
2021
Statut:
ppublish
Résumé
Individuals with low serum vitamin B-12 and high serum folate have higher plasma concentrations of methylmalonic acid (MMA). Whether folic acid (FA) causes an increase in MMA is not known. We aimed to determine the impact of FA supplementation on plasma MMA concentration in people with low or marginal serum vitamin B-12. We conducted a multicenter double-blind placebo-controlled randomized trial of oral FA (5 mg/d for 12 wk) in middle-aged patients treated with antidepressant medication participating in the FoLATED (Folate Augmentation of Treatment-Evaluation for Depression) trial. Participants defined as having "low" serum vitamin B-12 (vitamin B-12 ≥150 and <220 ng/L) or "marginal" serum vitamin B-12 (vitamin B-12 ≥ 220 and <280 ng/L) were included. The primary outcome of this substudy was MMA at week 12. A mixed-effects linear regression was fitted and reported using the adjusted mean difference (aMD). A total of 177 participants were included (85 randomly assigned to placebo and 92 to FA); the mean ± SD age was 46.2 ± 11.8 y, and 112 (63.3%) were female. The MMA analysis included 135 participants and the aMD was -0.01 (95% CI: -0.06, 0.04; P = 0.71). Serum folate was measured on 166 participants and increased in the supplementation group; the aMD was 21.6 μg/L (95% CI: 8.13, 25.02 μg/L; P < 0.001). A total of 117 participants were assessed for RBC folate, which also increased in the supplementation group; the aMD was 461 μg/L (95% CI: 387, 535 μg/L; P < 0.001). Supplementation of FA leads to an increase of serum and RBC folate, but does not change plasma MMA concentration in individuals with serum vitamin B-12 between 150 and 280 ng/L. We cannot exclude effects in older people or those with serum vitamin B-12 <150 ng/L. Previously reported associations may arise from effects of impaired vitamin B-12 status on folate metabolism.This trial was registered at www.isrctn.com as ISRCTN37558856.
Sections du résumé
BACKGROUND
Individuals with low serum vitamin B-12 and high serum folate have higher plasma concentrations of methylmalonic acid (MMA). Whether folic acid (FA) causes an increase in MMA is not known.
OBJECTIVES
We aimed to determine the impact of FA supplementation on plasma MMA concentration in people with low or marginal serum vitamin B-12.
METHODS
We conducted a multicenter double-blind placebo-controlled randomized trial of oral FA (5 mg/d for 12 wk) in middle-aged patients treated with antidepressant medication participating in the FoLATED (Folate Augmentation of Treatment-Evaluation for Depression) trial. Participants defined as having "low" serum vitamin B-12 (vitamin B-12 ≥150 and <220 ng/L) or "marginal" serum vitamin B-12 (vitamin B-12 ≥ 220 and <280 ng/L) were included. The primary outcome of this substudy was MMA at week 12. A mixed-effects linear regression was fitted and reported using the adjusted mean difference (aMD).
RESULTS
A total of 177 participants were included (85 randomly assigned to placebo and 92 to FA); the mean ± SD age was 46.2 ± 11.8 y, and 112 (63.3%) were female. The MMA analysis included 135 participants and the aMD was -0.01 (95% CI: -0.06, 0.04; P = 0.71). Serum folate was measured on 166 participants and increased in the supplementation group; the aMD was 21.6 μg/L (95% CI: 8.13, 25.02 μg/L; P < 0.001). A total of 117 participants were assessed for RBC folate, which also increased in the supplementation group; the aMD was 461 μg/L (95% CI: 387, 535 μg/L; P < 0.001).
CONCLUSIONS
Supplementation of FA leads to an increase of serum and RBC folate, but does not change plasma MMA concentration in individuals with serum vitamin B-12 between 150 and 280 ng/L. We cannot exclude effects in older people or those with serum vitamin B-12 <150 ng/L. Previously reported associations may arise from effects of impaired vitamin B-12 status on folate metabolism.This trial was registered at www.isrctn.com as ISRCTN37558856.
Identifiants
pubmed: 34510193
pii: S0022-3166(22)00435-7
doi: 10.1093/jn/nxab280
pmc: PMC8643600
doi:
Substances chimiques
Vitamins
0
Homocysteine
0LVT1QZ0BA
Methylmalonic Acid
8LL8S712J7
Folic Acid
935E97BOY8
Vitamin B 12
P6YC3EG204
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3738-3745Investigateurs
Rhiannon Whitaker
(R)
Joshua Pink
(J)
Seren Roberts
(S)
Clare Wilkinson
(C)
Dyfrig Hughes
(D)
Emma Betson
(E)
Diana Carr
(D)
Andrea Jorgenson
(A)
Munir Pirmohamed
(M)
Nevyn Williams
(N)
Helen Lewis
(H)
Keith Lloyd
(K)
Yvonne Sylvesture
(Y)
Richard Tranter
(R)
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.
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