Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial

PLoS One. 2018 Dec 18;13(12):e0208454. doi: 10.1371/journal.pone.0208454. eCollection 2018.

Abstract

Introduction: Animal and clinical studies suggest complementary effects of magnesium and high-dose pyridoxine (vitamin B6) on stress reduction. This is the first randomized trial evaluating the effects of combined magnesium and vitamin B6 supplementation on stress in a stressed population with low magnesemia using a validated measure of perceived stress.

Methods: In this Phase IV, investigator-blinded trial (EudraCT: 2015-003749-24), healthy adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 and serum magnesium concentration 0.45 mmol/L-0.85 mmol/L, were randomized 1:1 to magnesium-vitamin B6 combination (Magne B6 [Mg-vitamin B6]; daily dose 300 mg and 30 mg, respectively) or magnesium alone (Magnespasmyl [Mg]; daily dose 300 mg). Outcomes included change in DASS-42 stress subscale score from baseline to Week 8 (primary endpoint) and Week 4, and incidence of adverse events (AEs).

Results: In the modified intention-to-treat analysis (N = 264 subjects), both treatment arms substantially reduced DASS-42 stress subscale score from baseline to Week 8 (Mg-vitamin B6, 44.9%; Mg 42.4%); no statistical difference between arms was observed (p>0.05). An interaction (p = 0.0097) between baseline stress level and treatment warranted subgroup analysis (as per statistical plan); adults with severe/extremely severe stress (DASS-42 stress subscale score ≥25; N = 162) had a 24% greater improvement with Mg-vitamin B6 versus Mg at Week 8 (3.16 points, 95% CI 0.50 to 5.82, p = 0.0203). Consistent results were observed in the per protocol analysis and at Week 4. Overall, 12.1% of Mg-vitamin B6 treated and 17.4% of Mg-treated subjects experienced AEs potentially treatment related.

Conclusions: These findings suggest oral Mg supplementation alleviated stress in healthy adults with low magnesemia and the addition of vitamin B6 to Mg was not superior to Mg supplementation alone. With regard to subjects with severe/extremely severe stress, this study provides clinical support for greater benefit of Mg combined with vitamin B6.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Dietary Supplements
  • Drug Therapy, Combination
  • Female
  • France
  • Healthy Volunteers
  • Humans
  • Intention to Treat Analysis
  • Magnesium / administration & dosage*
  • Magnesium / blood*
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Single-Blind Method
  • Stress, Psychological / blood
  • Stress, Psychological / complications
  • Stress, Psychological / diet therapy*
  • Stress, Psychological / pathology
  • Treatment Outcome
  • Vitamin B 6 / administration & dosage*
  • Young Adult

Substances

  • Vitamin B 6
  • Magnesium

Grant support

The study was funded by Sanofi-Aventis Groupe, Gentilly, France, the manufacturer of MagneB6. The Sanofi-Aventis Groupe took an active a role in all aspects of this study, including the design, data collection and analysis, decision to publish, and the preparation of the manuscript. JH was employed by Daacro, a private contract research and saliva analysis laboratory during this study. Daacro did not play any role in funding the study design, data collection, decision to publish, or preparation of the manuscript, however, research materials and the laboratory premises were used to analyse saliva samples for this study. Daacro provided support in the form of a salary for JH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of JH is articulated in the ‘author contributions’ section.