Search

Primary findings from a recent study reported that magnesium supplementation significantly reduced stress in severely stressed subjects with low magnesemia, and additional vitamin B6 enhanced this effect. The mechanism by which combining magnesium and vitamin B6 leads to reduced stress in these subjects remains to be elucidated. This secondary analysis investigated the impact of magnesium and vitamin B6 supplementation and perceived stress on erythrocyte magnesium levels, as a marker of body magnesium status. This was a secondary analysis from an 8-week randomized controlled trial comparing oral magnesium (300 mg) and magnesium-vitamin B6 (300 mg + 30 mg) supplementation. Stress level and erythrocyte magnesium level at baseline, and change in erythrocyte magnesium and serum vitamin B6 levels at weeks 4 and 8, were analyzed. Overall, 264 subjects were randomized to treatment and had evaluable Depression Anxiety Stress Scale scores (132 in each treatment arm). At baseline, stress scores, and mean serum magnesium, erythrocyte magnesium, and serum vitamin B6 concentrations were similar between arms. Although not significant between groups, a significant increase over time in erythrocyte magnesium levels was observed in the subgroup of subjects with low baseline erythrocyte magnesium levels (<1.6 mmol/L) following treatment with magnesium and magnesium-vitamin B6 (week 4:0.21 mmol/L [95% confidence interval (CI), 0.10 to 0.31], p = 0.0003; and 0.13 mmol/L [95% CI, 0.02 to 0.23], p = 0.0233, respectively). Change from baseline in circulating vitamin B6 levels at weeks 4 and 8 in the magnesium-vitamin B6 supplemented group (314.96 nmol/L [95%CI, 294.61 to 335.31]) was significantly different (p < 0.0001) compared with the magnesium supplemented group (-0.39 nmol/L [95% CI, -20.73 to 19.94]). Magnesium alone and magnesium-vitamin B6 provided statistically significant increases in erythrocyte magnesium in subjects with low magnesium status (<1.6mmol/L). Vitamin B6 supplementation did not further increase magnesium levels.

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., Competing Interests: 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.

This study was conducted to determine whether the daily consumption for 84 days of tyrosol and hydroxytyrosol, the main olive oil phenolic compounds, and olive oil mill wastewater (OMWW), a byproduct of olive oil production, rich in micronutrients, may improve bone loss in ovariectomized rats (an experimental model of postmenopausal osteoporosis) and in ovariectomized rats with granulomatosis inflammation (a model set up for senile osteoporosis). As expected, an induced chronic inflammation provoked further bone loss at total, metaphyseal, and diaphyseal sites in ovariectomized rats. Tyrosol and hydroxytyrosol prevented this osteopenia by increasing bone formation ( p < 0.05), probably because of their antioxidant properties. The two doses of OMWW extracts had the same protective effect on bone ( p < 0.05), whereas OMWW did not reverse established osteopenia. In conclusion, polyphenol consumption seems to be an interesting way to prevent bone loss.