Plasma methylmalonic acid concentration in folic acid supplemented depressed patients with low or marginal vitamin B-12: a randomized trial

TY - JOUR

T1 - Plasma methylmalonic acid concentration in folic acid supplemented depressed patients with low or marginal vitamin B-12: a randomized trial

AU - Carter, Ben

AU - Zenasni, Zohra

AU - Moat, Stuart

AU - Hudson, Peter

AU - Russell, Ian

AU - McCaddon, Andrew

PY - 2021/7/30

Y1 - 2021/7/30

N2 - 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. Objective: 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/day for 12 weeks) in middle-aged patients treated with anti-depressant medication participating in the FoLATED trial, (Clinical Trial Number ISRCTN37558856). Participants defined with ‘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 sub-study was MMA at week 12. A mixed-effects linear regression was fitted and reported with an adjusted mean difference (aMD). Results: A total of 177 participants were included (85 randomized to placebo and 92 to Folic Acid), the mean age (SD) was 46.2 (11.8) years, and 112 (63.3%) were female. The MMA analysis included 135 participants and the aMD = -0.01 (95% CI, -0.06, 0.04; p= 0.71). Serum folate was measured on 166 participants and the aMD = 21.6 μg/L (95% C, 8.13, 25.02; p<0.001) and 117 participants were assessed for red cell folate and the aMD = 461.29 μg/L (95 % CI, 387.48, 535.09; p<0.001). Conclusions: Supplementation of FA leads to an increase of serum and red cell 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 below 150 ng/L. Previously reported associations may arise from effects of impaired vitamin B-12 status on folate metabolism.

AB - 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. Objective: 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/day for 12 weeks) in middle-aged patients treated with anti-depressant medication participating in the FoLATED trial, (Clinical Trial Number ISRCTN37558856). Participants defined with ‘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 sub-study was MMA at week 12. A mixed-effects linear regression was fitted and reported with an adjusted mean difference (aMD). Results: A total of 177 participants were included (85 randomized to placebo and 92 to Folic Acid), the mean age (SD) was 46.2 (11.8) years, and 112 (63.3%) were female. The MMA analysis included 135 participants and the aMD = -0.01 (95% CI, -0.06, 0.04; p= 0.71). Serum folate was measured on 166 participants and the aMD = 21.6 μg/L (95% C, 8.13, 25.02; p<0.001) and 117 participants were assessed for red cell folate and the aMD = 461.29 μg/L (95 % CI, 387.48, 535.09; p<0.001). Conclusions: Supplementation of FA leads to an increase of serum and red cell 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 below 150 ng/L. Previously reported associations may arise from effects of impaired vitamin B-12 status on folate metabolism.

KW - Folic acid

KW - Vitamin B-12

KW - Methylmalonic acid

KW - Metabolism, Public Health

M3 - Article

SN - 0022-3166

JO - Journal of Nutrition

JF - Journal of Nutrition

ER -