Breaking The Vicious Cycle Of Stress With Magnesium And Vitamin B6 Supplementation

In today’s world, stress seems to be an inevitable part of modern life. However, for some people, stress can have a particularly negative effect on their lives, behavior, and relationships. Stress may also be a predecessor for physical and mental health problems.

Magnesium is a mineral in the body that plays an essential role in a large number of biological processes (1),­ including stress responses, and is found in large quantities throughout the body, however, levels of magnesium in the blood are tightly controlled, primarily by absorption within the intestine and excretion via the kidneys (2). Hormones released during periods of stress can trigger magnesium to be released from cells. In turn, this magnesium is then excreted in the urine, and, as a consequence, magnesium levels in the blood decrease (3,4). Subsequently, low concentrations of magnesium in the blood trigger the release of stress hormones, creating a vicious cycle of reduced resistance to stress and decreased magnesium levels (5,6).

Magnesium is naturally present in a number of foods; however, most diets today provide insufficient magnesium which is below recommended amounts. Thus, people who are deficient in magnesium may benefit from additional supplementation. Indeed, supplemental magnesium has been shown in clinical trials to improve markers and symptoms of stress, such as insomnia and decreased serum cortisol concentrations, a hormone released in response to stress (7–9). High doses of vitamin B6 may also have therapeutic benefits in people with stress (10). Vitamin B6 can alter the levels of the brain neurotransmitters serotonin and GABA (gamma-aminobutyric acid), which are involved with depression and anxiety, and have been shown to lower blood pressure and reduce the impact of certain stress hormones (10).

Magne B6® is a dietary supplement and includes a combination of magnesium (300 mg) and vitamin B6 (30 mg). Magne B6® is currently indicated for the prevention and treatment of magnesium deficiency and associated symptoms (including fatigue, mild anxiety, and nervousness) (11).

For the first time, a clinical trial has compared the anti-stress effects of supplementation with magnesium alone or magnesium combined with vitamin B6 (Magne B6®). In total, 264 adults with moderate to extremely severe stress and who had low blood magnesium took part in the trial. Half of the enrolled participants took a magnesium and vitamin B6 supplement (Magne B6®) with every meal (three meals per day), whilst the other half took magnesium alone. Stress levels were measured using the validated self-assessment questionnaire “DASS-42” (Depression Anxiety Stress Scale).

Following 8 weeks of supplementation, stress was reduced in both groups; by 45% in those taking the magnesium and vitamin B6 supplement and by 42% in those taking magnesium alone, with improvements in stress levels reported by participants in both groups by week 4 of the trial.

Participants who had severe to extremely severe stress at the start of the trial seemed to benefit more following the magnesium and vitamin B6 combination compared with participants who took magnesium alone. In these participants, those who took the combination showed a 24% greater reduction in stress than magnesium alone after 8 weeks. Furthermore, magnesium combined with vitamin B6 appeared to reduce stress faster than magnesium alone in participants with severe to extremely severe stress. In fact, in participants with severe to extremely severe stress who took magnesium and vitamin B6 supplementation, a reduction in stress was recorded by week 4 that was only seen by week 8 in their counterparts taking magnesium alone.

Overall, magnesium and vitamin B6 supplementation was well tolerated, with very few side effects reported. Diarrhea was one of the most frequent side effects experienced by participants in this trial. However, diarrhea only became severe for one participant (who was taking the magnesium-only supplement).

Thus, although stress may seem like an unavoidable burden, this trial has added further evidence that for stressed individuals who are low in magnesium, supplementation with magnesium and vitamin B6 may help to break the vicious cycle of depleted magnesium and reduced resistance to stress. For the first time, this trial provides clinical evidence that severely stressed individuals could benefit from taking a combined magnesium and vitamin B6 supplementation, however, studies of longer duration are needed to confirm how stress may be relieved in the long term.

These findings are described in the article entitled Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial, recently published in the journal PLoS ONE (PLoS ONE (2018) e0208454). This work was conducted by Etienne Pouteau, Marmar Kabir-Ahmadi and Lionel Noah from Sanofi; Andre Mazur, Gisele Pickering and Claude Dubray from the University of Clermont Auvergne; Louise Dye from the University of Leeds and Juliane Hellhammer from Contract Research Organisation Daacro.Medical writing support was provided by Rachel Cicchelli, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, and was funded by Sanofi-Aventis Groupe, Gentilly, France, in accordance with Good Publications Practice (GPP3) guidelines (


  1. de Baaij J.H., Hoenderop J.G., Bindels R.J. (2015). Magnesium in man: implications for health and disease. Physiol Rev, Vol. 95, p. 1–46.
  2. de Baaij J.H., Hoenderop J.G., Bindels R.J. (2012). Regulation of magnesium balance: lessons learned from human genetic disease. Clin Kidney J, 5(Suppl 1): i15–i24
  3. Seelig M.S. (1994). Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review). J Am Coll Nutr, Vol. 13, p. 429–446.
  4. Whyte K.F., Addis G.J., Whitesmith R., et al (1987). Adrenergic control of plasma magnesium in man. Clinical Science, Vol. 72, p. 135–138.
  5. Cuciureanu M.D., Vink R. (2015). Magnesium and Stress. In: Vink R. (ed) Magnesium in the Central Nervous System. University of Adelaide Press, Adelaide, South Australia, p. 251–268.
  6. Murck H. (2002). Magnesium and affective disorders. Nutr Neurosci, Vol. 5, p. 375–389.
  7. Verster J.C., Palagini L., Mackus M., et al (2018). Insomnia and stress: associations with mental resilience and mood. Sleep, Vol. 41, p. A162.
  8. Abbasi B., Kimiagar M., Sadeghniiat K., et al (2012). The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. J Res Med Sci, Vol. 17, p. 1161–1169.
  9. Zogovic D., Pesic V., Dmitrasinovic G., et al (2014). Pituitary-gonadal, pituitaryadrenocortical hormones and IL-6 levels following long-term magnesium supplementation in male students. J Med Biochem, Vol. 33, p. 291–298.
  10. McCarty M.F. (2000). High-dose pyridoxine as an ’anti-stress’ strategy. Med Hypotheses, Vol. 54, p. 803–807.
  11. Sanofi (2019). Magne B6 Summary of Product Characteristics. Sanofi.

About The Author

Etienne Pouteau

Etienne Pouteau is a research scientist and the Global Medical Head for Nutritionals at Sanofi.

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