Vitamin B12 Supplementation and NT-proBNP Levels in COPD Patients: A Secondary Analysis of a Randomized and Controlled Study in Rehabilitation.

Fernanda Viana Paulin,Leandro Steinhorst Goelzer,Paulo De Tarso Müller

doi:10.3389/fnins.2020.00740

Fernanda Viana Paulin, Leandro Steinhorst Goelzer + Show 1 more

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https://doi.org/10.3389/fnins.2020.00740

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Abstract

PurposeThere is evidence of complex interaction between vitamin B12 (vB12) level, hyperhomocysteinemia (HyCy), and natriuretic peptide secretion. Exercise training could also modulate such interaction. In this secondary analysis of a Randomized Clinical Trial performed in a chronic obstructive pulmonary disease (COPD) rehabilitation setting, our primary objective was to investigate the interaction between vB12 supplementation, exercise training, and changes in NT-proBNP levels after 8 weeks of intervention. Secondary objectives were to explore the correlations between acute changes in NT-proBNP levels with (i) acute exercise and (ii) oxygen uptake (V’O2) kinetics during rest-to-exercise transition.MethodsThirty-two subjects with COPD were randomized into four groups: Rehabilitation+vB12 (n = 8), Rehabilitation (n = 8), vB12 (n = 8), or Maltodextrin(n = 8). They were evaluated at baseline and after 8 weeks, during resting and immediately after maximal exercise constant work-rate tests (CWTs, Tlim), for NT-proBNP plasmatic levels.ResultsAfter interaction analysis, the supplementation with vB12 significantly changed the time course of NT-proBNP responses during treatment (p = 0.048). However, the final analysis could not support a significant change in NT-proBNP levels owing to high-intensity constant work-rate exercise (p-value > 0.05). There was a statistically significant correlation between V’O2 time constant and ΔNT-proBNP values (Tlim – rest) at baseline (p = 0.049) and 2 months later (p = 0.015), considering all subjects (n = 32).ConclusionWe conclude that vB12 supplementation could modulate NT-proBNP secretion. Moreover, possibly, the slower the initial V’O2 adjustments toward a steady-state during rest-to-exercise transitions, the more severe the ventricular chamber volume/pressure stress recruitment, expressed through higher NT-proBNP secretion in subjects with larger V’O2 time constants, despite unchanged final acute exercise-induced neurohormone secretion.

Highlights

In a recent Randomized Controlled Trial (RCT), we showed a slight but significant increase in maximal exercise tolerance (Tlim) in patients with chronic obstructive pulmonary disease (COPD) supplemented with vitamin B12 during physical training, but without effects on oxygen uptake (V’O2) kinetics beyond training alone (Paulin et al, 2017)
Individuals with COPD are at risk of vitamin B12 deficiency (Solomon, 2016) and hyperhomocysteinemia (HyCy) (Seemungal et al, 2007; Fimognari et al, 2009)
Normal levels of vitamin B12 do not rule out the possibility of cobalamin deficiency, and low-normal levels (200–300 pg/mL), when associated with risk factors for increased oxidative stress, demonstrate metabolic evidence of deficiency, with high levels of HyCy or methylmalonic acid (MMA), since this vitamin is inactivated by oxidation (Solomon, 2016)

Summary

Introduction

MATERIALS AND METHODSIn a recent Randomized Controlled Trial (RCT), we showed a slight but significant increase in maximal exercise tolerance (Tlim) in patients with chronic obstructive pulmonary disease (COPD) supplemented with vitamin B12 during physical training, but without effects on oxygen uptake (V’O2) kinetics beyond training alone (Paulin et al, 2017). HyCy is linked to numerous cardiovascular alteration (Ganguly and Alam, 2015) including histological changes in the heart (Piquereau et al, 2017), impaired global and segmental cardiac contractility (Kaya et al, 2014), or increased N-terminalpro-B-type natriuretic peptide (NT-proBNP) secretion (Herrmann et al, 2007; Guéant Rodriguez et al, 2013). This prepropeptide is synthesized and stored as a high molecular weight mass propeptide from both the atria and ventricles, and released mainly under pressure/volume overload of the cardiac chambers, after cleavage of the active form of BNP, inducing natriuresis and vasodilatation (Calzetta et al, 2016). An experimental study was negative for cardiac morphological alterations during HyCy induction (Taban-Shomal et al, 2009)

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