Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, United Kingdom.
J Nutr. 2021 Dec 3;151(12):3738-3745. doi: 10.1093/jn/nxab280.
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.
血清维生素 B-12 水平低、血清叶酸水平高的个体，其血浆中甲基丙二酸（MMA）浓度较高。目前尚不清楚叶酸（FA）是否会导致 MMA 增加。
我们旨在确定补充 FA 对血清维生素 B-12 水平较低或边缘状态的人群血浆 MMA 浓度的影响。
我们进行了一项多中心、双盲、安慰剂对照、随机临床试验，在参与 FoLATED（叶酸增强治疗-评估抑郁症）试验的接受抗抑郁药物治疗的中年患者中，口服 FA（5mg/d，持续 12 周）。纳入的参与者被定义为血清维生素 B-12“低”（维生素 B-12≥150 且<220ng/L）或“边缘”（维生素 B-12≥220 且<280ng/L）。本亚研究的主要结局为第 12 周时的 MMA。采用混合效应线性回归，并使用调整后的平均差（aMD）进行报告。
共有 177 名参与者（85 名随机分配至安慰剂组，92 名分配至 FA 组），平均年龄为 46.2±11.8 岁，112 名（63.3%）为女性。MMA 分析包括 135 名参与者，aMD 为-0.01（95%CI：-0.06，0.04；P=0.71）。166 名参与者检测了血清叶酸，补充组的叶酸增加；aMD 为 21.6μg/L（95%CI：8.13，25.02μg/L；P<0.001）。117 名参与者评估了 RBC 叶酸，补充组的 RBC 叶酸也增加；aMD 为 461μg/L（95%CI：387，535μg/L；P<0.001）。
在血清维生素 B-12 为 150-280ng/L 的个体中，FA 补充会导致血清和 RBC 叶酸增加，但不会改变血浆 MMA 浓度。我们不能排除在老年人或血清维生素 B-12<150ng/L 的人群中产生的影响。先前报道的关联可能是由于维生素 B-12 状态受损对叶酸代谢的影响。该试验在 www.isrctn.com 上注册，编号为 ISRCTN37558856。
