Magnesium & Vitamin B6 Benefits on Mental Health
Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults:
Post-hoc analysis of a randomized controlled trial
Advances in understanding the neurobiology of stress have demonstrated an interplay between disturbances in biochemical processes and physical and mental symptoms. The protective biological responses that occur in response to stressors (allostasis) usually involve activation of neural, neuroendocrine, and neuroendocrine-immune mechanisms. However, over long periods of time, allostatic overload can occur, resulting in mood disorders, chronic illness, and reduced quality of life. Furthermore, components of the allostatic system have been associated with depression- and anxiety-like behaviors. Since the cumulative effect of daily stress has been linked to symptoms of anxiety and depression up to 10 years later, it follows that chronic stress, anxiety, and depression could be viewed as a continuum of the same condition.
Magnesium status has been shown to be linked to anxiety, depression, and mood changes. During periods of stress, catecholamines and corticosteroids are released; prolonged release of these stress-associated hormones then causes a progressive loss of magnesium from body stores. Since low magnesium status results in further release of catecholamines and corticosteroids a positive feedback loop that exacerbates magnesium depletion is created.
As magnesium is an enzymatic cofactor in over 600 biochemical reactions, a magnesium deficiency could affect allostatic regulation in multiple ways. Magnesium influences the activity of the hypothalamic-pituitary-adrenal axis, which instigates various responses to cope with stress demands. Magnesium also reduces central adrenocorticotrophic hormone and peripheral (cortisol) endocrine responses, thereby decreasing anxiety. Additionally, magnesium may help reduce presynaptic glutamate release and glutamatergic activity that has been implicated in fear, anxiety, and panic responses.
Magnesium levels have also been linked with general health and QoL; a retrospective study (n = 81) showed that the higher magnesium levels were associated with improved QoL scores in all 10 categories of the Short Form-36 Health Survey (SF-36) measuring QoL and health. Magnesium supplementation is therefore of interest not only as a potential aid to coping with stress but also as a treatment for anxiety and depression. However, to date, no evidence has shown that magnesium supplementation can result in improved QoL.
Pyridoxine (vitamin B6) plays an important role in numerous physiological processes. It acts as a cofactor in over 100 enzymatic reactions, including in the synthesis of neurotransmitters such as gamma-aminobutyric acid, serotonin, and dopamine. In addition to modulating neurobiological mechanisms associated with mood disorders such as depression and anxiety, vitamin B6 may have other stress-reducing properties, including hypotensive effects, and may reduce the physiological consequences of corticosteroid release.
Inadequate intake of vitamin B6 has recently been linked to an increased risk of anxiety and depression in a cross-sectional study of over 3,000 individuals. Furthermore, vitamin B6 supplementation has demonstrated beneficial effects on emotional symptoms, such as reducing irritability, depression, and tiredness. Vitamin B6 may also modulate magnesium levels, with some evidence showing increased circulating and tissue magnesium concentrations following high-dose vitamin B6 supplementation. As both vitamin B6 and magnesium modulate neurobiological mechanisms, it has been hypothesized that they may have a synergistic effect.
Magnesium status and vitamin B6 intake have been linked to mental health and/or quality of life (QoL).
In an 8-week Phase IV randomized controlled study in individuals with low magnesemia and severe/extremely severe stress but who were otherwise healthy, greater stress reduction was achieved with magnesium combined with vitamin B6 than with magnesium alone.
We present a previously unreported secondary analysis of the effect of magnesium, with and without vitamin B6, on depression, anxiety, and QoL.
Adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 were randomized 1:1 to magnesium + vitamin B6 combination (Magne B6®; daily dose 300 and 30 mg, respectively) or magnesium alone (Magnespasmyl®; daily dose 300 mg).
Outcomes included changes from baseline in DASS-42 depression and anxiety scores, and QoL (Short Form-36 Health Survey). DASS-42 anxiety and depression scores significantly improved from baseline to week 8 with both treatments, particularly during the first 4 weeks.
Improvement in QoL continued over 8 weeks!
Participants' perceived capacity for physical activity in daily life showed greater improvement with magnesium + vitamin B6 than magnesium alone (Week 4).
In conclusion, magnesium supplementation, with or without vitamin B6, could provide a meaningful clinical benefit in daily life for individuals with stress and low magnesemia.