PMID- 30562392 OWN - NLM STAT- MEDLINE DCOM- 20190530 LR - 20231005 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 12 DP - 2018 TI - Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. PG - e0208454 LID - 10.1371/journal.pone.0208454 [doi] LID - e0208454 AB - 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. FAU - Pouteau, Etienne AU - Pouteau E AUID- ORCID: 0000-0002-8254-1892 AD - Nutritionals, Sanofi, Gentilly, France. FAU - Kabir-Ahmadi, Marmar AU - Kabir-Ahmadi M AD - Statistics, Sanofi, Gentilly, France. FAU - Noah, Lionel AU - Noah L AD - Nutritionals, Sanofi, Gentilly, France. FAU - Mazur, Andre AU - Mazur A AD - Unite de Nutrition Humaine, INRA, Universite Clermont Auvergne, Clermont-Ferrand, France. FAU - Dye, Louise AU - Dye L AD - Nutrition and Behaviour Group, School of Psychology, University of Leeds, Leeds, United Kingdom. FAU - Hellhammer, Juliane AU - Hellhammer J AD - Contract Research and Saliva Lab, Daacro, Trier, Germany. FAU - Pickering, Gisele AU - Pickering G AD - Clinical Pharmacology Department, CHU, Universite Clermont Auvergne, Clermont-Ferrand, France. FAU - Dubray, Claude AU - Dubray C AD - Clinical Pharmacology Department, CHU, Universite Clermont Auvergne, Clermont-Ferrand, France. LA - eng PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20181218 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 8059-24-3 (Vitamin B 6) RN - I38ZP9992A (Magnesium) SB - IM MH - Adolescent MH - Adult MH - Dietary Supplements MH - Drug Therapy, Combination MH - Female MH - France MH - Healthy Volunteers MH - Humans MH - Intention to Treat Analysis MH - Magnesium/*administration & dosage/*blood MH - Male MH - Middle Aged MH - Severity of Illness Index MH - Single-Blind Method MH - Stress, Psychological/blood/complications/*diet therapy/pathology MH - Treatment Outcome MH - Vitamin B 6/*administration & dosage MH - Young Adult PMC - PMC6298677 COIS- I have read the journal's policy and the authors of this manuscript have the following competing interests to declare: CD reports no conflict of interest. AM reports consultancy fees from Sanofi, unrelated to this publication. LD has received research funding from Sanofi and consultancy payments unrelated to this publication. JH was employed by Daacro at the time of this study, and has also received consultancy fees and performed saliva analyses for Sanofi, unrelated to this publication. Daacro is a private contract research and saliva analysis laboratory. 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 trial and the company was reimbursed for any time or materials used relating to this study. EP, MK-A and LN are employees of Sanofi. LN was employed by Metabrain Research during the conduction of the trial and the early stages of the development of this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. EDAT- 2018/12/19 06:00 MHDA- 2019/05/31 06:00 PMCR- 2018/12/18 CRDT- 2018/12/19 06:00 PHST- 2018/08/14 00:00 [received] PHST- 2018/11/16 00:00 [accepted] PHST- 2018/12/19 06:00 [entrez] PHST- 2018/12/19 06:00 [pubmed] PHST- 2019/05/31 06:00 [medline] PHST- 2018/12/18 00:00 [pmc-release] AID - PONE-D-18-20818 [pii] AID - 10.1371/journal.pone.0208454 [doi] PST - epublish SO - PLoS One. 2018 Dec 18;13(12):e0208454. doi: 10.1371/journal.pone.0208454. eCollection 2018.