Vitamin B(12) Supplementation and NT-proBNP Levels in COPD Patients: A Secondary Analysis of a Randomized and Controlled Study in Rehabilitation

PURPOSE: There is evidence of complex interaction between vitamin B(12) (vB(12)) 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 vB(12) 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’O(2)) kinetics during rest-to-exercise transition. METHODS: Thirty-two subjects with COPD were randomized into four groups: Rehabilitation+vB(12) (n = 8), Rehabilitation (n = 8), vB(12) (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. RESULTS: After interaction analysis, the supplementation with vB(12) 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’O(2) 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). CONCLUSION: We conclude that vB(12) supplementation could modulate NT-proBNP secretion. Moreover, possibly, the slower the initial V’O(2) 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’O(2) time constants, despite unchanged final acute exercise-induced neurohormone secretion.