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Diagnostic Performances of Urinary Methylmalonic Acid/Creatinine Ratio in Vitamin B12 Deficiency.

ABSTRACT: Sole measurement of plasma vitamin B12 is no longer enough to identify vitamin B12 (B12) deficiency. When plasma vitamin B12 is in the low-normal range, especially between 201 and 350 ng/L, B12 deficiency should be assessed by measurements of plasma homocysteine and/or plasma methylmalonic acid (MMA). However, these biomarkers also accumulate during renal impairment, leading to a decreased specificity for B12 deficiency. In such cases, urinary methylmalonic acid/creatinine ratio (uMMA/C) could be of interest, due to the stable urinary excretion of MMA. The objectives were to evaluate the influence of renal impairment on uMMA/C compared to plasma homocysteine and plasma methylmalonic acid, and to determine the diagnostic performances of uMMA/C in the diagnosis of B12 deficiency. We prospectively studied 127 patients with a plasma B12 between 201 and 350 ng/L. We noticed that uMMA/C was not dependent on renal function (p = 0.34), contrary to plasma homocysteine and plasma methylmalonic acid. uMMA/C showed a perspective diagnostic performance (AUC 0.71 [95% CI: 0.62-0.80]) and the threshold of 1.45 umol/mmol presented a high degree of specificity (87.9% [95% CI: 72.0-98.9]). In conclusion, uMMA/C is a promising biomarker to assess vitamin B12 status in doubtful cases, notably during renal impairment.

SUBMITTER: Supakul S

PROVIDER: S-EPMC7466029 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Diagnostic Performances of Urinary Methylmalonic Acid/Creatinine Ratio in Vitamin B12 Deficiency.

Supakul Sopak S Chabrun Floris F Genebrier Steve S N'Guyen Maximilien M Valarche Guillaume G Derieppe Arthur A Villoteau Adeline A Lacombe Valentin V Urbanski Geoffrey G

Journal of clinical medicine 20200722 8

Sole measurement of plasma vitamin B12 is no longer enough to identify vitamin B12 (B12) deficiency. When plasma vitamin B12 is in the low-normal range, especially between 201 and 350 ng/L, B12 deficiency should be assessed by measurements of plasma homocysteine and/or plasma methylmalonic acid (MMA). However, these biomarkers also accumulate during renal impairment, leading to a decreased specificity for B12 deficiency. In such cases, urinary methylmalonic acid/creatinine ratio (uMMA/C) could b ...[more]

PMID: 32707915

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Project description:BackgroundThe inconsistent relationship between Vitamin B12 (B12), methylmalonic acid (MMA, marker of B12 deficiency) and mortality was poorly understood, especially in patients with coronary heart disease (CHD). This study aims to investigate the association of serum MMA, and B12-related biomarkers (serum level, dietary intake, supplement use, and sensibility to B12) with all-cause and cardiovascular mortality in adults with CHD.MethodsThe data of this study were from a subcohort within the US National Health and Nutrition Examination Survey (NHANES). We included adults with preexisting CHD with serum MMA and B12, and dietary B12 intake measurements at recruitment. All participants were followed up until 31 December 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CI of mortality risk.ResultsOverall, 1755 individuals (weighted mean [SE] age, 65.2 [0.5] years; 1047 men [weighted 58.5%]) with CHD were included, with geometric mean levels of serum MMA 182.4 nmol/L, serum B12 494.5 pg/ml, and dietary B12 intake 4.42 mg/day, and percentage of B12 supplements use 39.1%. During a median follow-up of 7.92 years, 980 patients died. Serum B12 concentration, dietary B12 intake and supplements use were not significantly associated with mortality risk (each p ≥ 0.388). In contrast, individuals in the top tertile of MMA had multivariable-adjusted HRs (95% CIs) of 1.70 (1.31-2.20) for all-cause mortality, and 2.00 (1.39-2.89) for cardiovascular mortality (both p trend < 0.001) compared to those in the bottom tertile of MMA. MMA-related mortality risk was particularly higher among participants with sufficient serum B12 (p < 0.001). CHD patients with increased levels of both MMA and B12 had a doubled mortality risk compared to those with lower MMA and B12 (p < 0.001).ConclusionMMA accumulation but not serum or dietary vitamin B12 was associated with increased cardiovascular mortality risk among patients with CHD. This paradox may be related to decreased response to vitamin B12.

Dataset Information

Diagnostic Performances of Urinary Methylmalonic Acid/Creatinine Ratio in Vitamin B12 Deficiency.

Publications

Diagnostic Performances of Urinary Methylmalonic Acid/Creatinine Ratio in Vitamin B12 Deficiency.

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