Summary  :

1. Magnesium Is a Cofactor for More Than 300 Enzymatic Reactions

2. MS Is Linked with Magnesium Deficiency

3. Magnesium Helps Relieve Stress, Anxiety, and Depression

4. Magnesium Improves  Sleep

5. Low Magnesium Correlates with Fatigue and MS Progression

6. Magnesium Is Very Important for Muscle and Nerve Function

7. Magnesium Promotes the Formation of New Brain Cells

8. The Link Between Magnesium and Neurotransmitters  

9. Magnesium Fights Inflammation,Supports a Healthy  Immune System and Has Antioxidant Qualities

10. Your  Mitochondria Love Magnesium

11. Magnesium and Hormonal Balance  

12. Magnesium Can Prevent and Treat Migraines

13. Magnesium, MS  and Metabolic Syndrome

14. Magnesium May Prolong Your Life

15. Magnesium Deficiency – Causes, Symptoms, Tests and Treatment

 

1. Magnesium Is a Cofactor for More Than 300 Enzymatic Reactions

It may be the fourth  most abundant mineral in the body, but magnesium is the most important mineral for your health in general, and for MS symptoms in particular.  As a cofactor for more than 300 enzymatic reactions, magnesium helps your muscles and nerves function better, keep your bones strong and healthy, improve the metabolism of carbs, proteins, and fats, and keep your heart and blood vessels in great shape. [1] Most of us (almost 70% of North-Americans) don’t get enough magnesium from the diet [2], [3], [4], and this nutrient deficiency had been linked with high blood pressure [5], heart diseases, [6], and type II diabetes[7].

2. Magnesium and MS

Research reveals multiple sclerosis magnesium deficiency link. For example, it was found that people with MS  have a significantly decreased concentration of magnesium in the blood compared with general population [8], [9]. Another multiple sclerosis magnesium deficiency connection was discovered  when the levels of this nutrient were examined in the brain. It appears that people with MS  have  lower levels of magnesium in the brain. Furthermore, the most significant decreased levels  of magnesium  were found in the MS lesions and the  white matter of the central nervous system [10].

3. Magnesium helps relieve stress, anxiety, and depression

Whether you are under physical or mental stress, your body is losing magnesium [11]. A randomized controlled trial suggests that increasing magnesium intake will prevent magnesium deficiency related illnesses such as restlessness, irritability, poor concentration, sleep problems or depression [12].

Another study reveals that the depression, personality changes, confusion, anxiety, and delirium are linked with magnesium deficiency, and the mechanism of action is likely related to the importance of magnesium in the brain biochemistry and its involvement in the production of the neurotransmitters [13].

Both magnesium and depression are associated  with chronic, low-grade inflammation. Luckily, symptoms of depression, anxiety and sleep problems can improve quickly, with results seen as early as one week of magnesium supplementation [14].

Case studies show rapid recovery (within one week) from major depression using 125-300 mg of magnesium (as glycinate and taurinate) with each meal and at bedtime[15]. An increase of intracellular magnesium may, in fact, be one of the reasons why antidepressants work to treat depression [16].

Technical: Magnesium ions regulate calcium ion flow in neuronal calcium channels, thus being involved and  regulate neuronal NO production. In cases of magnesium deficiency, neuronal requirements for magnesium are not achieved, leading to  neuronal damage (which could manifest as depression). Magnesium treatment is suggested  to be effective in treating major depression by improving the intraneuronal magnesium deficits. Magnesium ion neuronal deficits may be caused by various factors such as  stress hormones, excessive calcium in the diet or not enough dietary magnesium [17].

4. Magnesium Improves Sleep

Magnesium helps you sleep like a baby because optimal Mg levels are needed for normal sleep regulation [18]. Supplementation of magnesium helps improve sleep efficiency, the quality and quantity of sleep,  early morning awakening, and improve levels of  melatonin and cortisol [19], [20].

Technical: Magnesium is the natural N-methyl-D-aspartic acid (NMDA) antagonist and GABA agonist, thus playing a key role in the regulation of sleep.

5. Low Magnesium Correlates with Fatigue and MS Progression

Lower levels of magnesium (and folate) in diets are linked with more fatigue in people  with MS [21]. Magnesium, along with calcium and iron could  be related to MS progression, because one study found that people diagnosed  with SPMS had lower intake of these minerals compared with individuals with PPMS and milder forms of MS [22].

6. Magnesium Is Very Important for Muscle and Nerve Function

Magnesium is important to nerve impulse conduction and muscle contractions because this nutrient plays a key role in the active transport of calcium and potassium across cell membranes [1].

It looks  that magnesium supplementation  can improve spasticity and weakness associated with MS, when other therapies (ie. baclofen, tizanidine, physiotherapy) fail [23]. Supplementation with magnesium helps repair damaged nerves and improve the nerve function (in peripheral nerves) [24].

Your brain will be happier and healthier if it has enough magnesium, as this mineral plays a key role in the central nervous system. It protects the membrane of the brain cells, helps improve the blood brain barrier permeability and is involved in many metabolic reactions [25]. Scientists suggest a possible inverse association between magnesium intake and brain tissue damage in MS. Magnesium is neuroprotective.

Technical:  Magnesium is involved in more than 300 metabolic processes i.e.  energy metabolism, membrane stability, protein and DNA synthesis, and inhibition of iNOS (the inducible enzyme nitric oxide synthase). iNOSs had been found in MS lesions, and iNOS increase the NO levels  and  superoxide radicals. These radicals cause oligodendrocyte injury, demyelination, and axonal damage while NO inhibits mitochondrial respiration, Since magnesium inhibits iNOS, it is considered neuroprotective [26].

7.Magnesium Promotes the Formation of New Brain Cells

Magnesium promotes brain repair and rejuvenation , enhanced memory and  synaptic plasticity (in animal models ) [27]. Because it regulates neural stem cell proliferation , magnesium promotes the formation of new healthy brain cells [28].

8.The Link Between Magnesium and Neurotransmitters

Magnesium helps maintain healthy levels of neurotransmitters. MS had been associated with certain neurotransmitter imbalances for example: norepinephrine [29], [30], dopamine  [31], acethylcholine  [32], and serotonin imbalances [33].

Technical: As an essential NMDA receptor modulator, a brain chemical port  that regulates the action of glutamate, magnesium is also very important  for the production of ATP (the source of energy for the cells), and SAM-e, a precursor of some neurotransmitters (i.e.serotonin, dopamine and norepinephrine), fatty acids and oxidants [34].

9. Magnesium Fights Inflammation, Supports a Healthy Immune System and Is an Antioxidant

Magnesium helps your brain and body to fight free radicals, thus having antioxidant qualities. Magnesium deficiency had been linked with increased oxidative stress markers (ie. lipid , protein and DNA oxidative changes).

Technical: There are different mechanisms associated with magnesium deficiency and its involvement in the development of the oxidative stress: systemic reactions such as inflammation and endothelial dysfunction, and  changes at the cellular level (i.e.  mitochondrial dysfunction and excessive fatty acid production [35].

Magnesium has essentially an anti-inflammatory action . Low levels of magnesium  had been linked with inflammation in the whole body [36].

Technical: low levels of magnesium correlate with low grade systemic inflammation,and the release of  proinflammatory  molecules   (i.e. IL-1, IL-6,  (TNF)-α and  higher CRP levels; magnesium also plays a role on inflammatory response pathways like nuclear factor (NF)-κB,  [37], [38].

Magnesium supports a healthy immune system function [39], playing an important role  in both  innate and acquired immune response. [40], [41], [42].

Technical:  Experimental Mg deficiency causes a clinical inflammatory syndrome with leukocyte and macrophage activation, inflammatory cytokines released, and increased  production of free radicals. Hypomagnesemia promotes low-grade inflammation as shown  by increased concentrations of CRP and TNF-α .  Subjects who consume less than 75% of RDA were 1.94 times more likely to have elevated serum CRP levels than consuming above the RDA. Low Mg induces rises in circulating substance P that stimulates systemic inflammatory stress .  Mechanisms explaining  the role of Mg in modulating immune function : Mg enhances iron–transferrin binding, which promotes oxidative stress. Mg decreases the oxidative stress through stabilization of DNA. As a calcium antagonist, magnesium  modulates the intracellular calcium concentration (possible mechanism : priming phagocytic cells,an opening of calcium channels, activation of NMDA receptors, and activation of the renin-angiotensin system ). Mg deficiency causes a systemic stress response through activation of the neuroendocrine axis [36].

10. Your Mitochondria Love Magnesium

Improving the mitochondrial function is crucial for managing MS. One way to make the mitochondria happy and healthy is magnesium supplementation. Magnesium in the mitochondria accounts for one third of total cellular magnesium, playing a key role in the mitochondrial function like ATP synthesis and oxygen detoxification. The more magnesium available to the cell, the more efficient will be mitochondria to produce energy and fight free radicals [43].

11. Magnesium and Hormonal Balance

Magnesium plays a key role in maintaining healthy thyroid and ovarian function and the production of thyroid and steroid hormones.  (other important nutrients include iron, zinc, selenium and coenzyme Q10).

Technical : magnesium-ATP acts in iodine uptake and the heme protein peroxidase is involved in thyroid hormone synthesis. A similar mechanism was found in steroid synthesis. The optimal function of mitochondria will support both thyroid and the ovarian axis [44].

12. Magnesium Can Prevent and Treat Migraines

Migraines may be twice more common in people with MS compared with those without MS. About one third of individuals with MS have history of migraines [47].

Migraines had been associated with magnesium deficiency [45]. A meta analysis of 22 randomized controlled studies found that intravenous magnesium can decrease the migraine attack  and taken in oral (supplement) form can reduce the intensity and frequency of the migraines [46].

13. Magnesium, MS  and Metabolic Syndrome

A systematic review of randomized placebo controlled studies looked at the evidence regarding the benefits of magnesium for treating metabolic syndrome . There is  strong evidence that magnesium supplements can improve  insulin sensitivity, blood sugar levels, triglycerides and HDL- cholesterol levels and blood pressure (all of them are part of  metabolic syndrome), when used for at least four weeks. Treating metabolic reduces the risk of  heart disease and type 2 diabetes [46].

MS progression is linked with reduced mobility and less physical activity, leading to more fatigue, and weakness, thus increasing the risk of metabolic syndrome. Metabolic syndrome can also trigger MS and is considered a poor  prognostic factor [47].

14. Magnesium May  Prolong Your Life

Life expectancy is shortened by  a few months to years  (depending on the study) for someone with MS compared with healthy controls [55], [56]. Luckily, magnesium along and other supplements can help bring back these years to your life. It s not about living longer, but living longer and healthier.

Aging is strongly associated with magnesium deficiency and a chronic shortage of this nutrient is linked with various conditions such as diabetes, metabolic syndrome and altered immune response. Scientists suggest that magnesium deficiency may be one of the links that explain the interaction between oxidative stress, inflammation, and the aging process [48].

Telomeres are segments of DNA at the end of your chromosomes. It is well established now that one way to prevent aging and increase longevity is to lengthen these telomeres.  Increased magnesium consumption (along with other vitamins and minerals) had been found to increase the telomere lengths.  Bottom line : correcting magnesium deficiencies may prolong life [49].

Technical : Magnesium stabilizes DNA, and promotes DNA replication and transcription.  Low magnesium levels accelerate cellular aging by decreasing DNA stability, protein synthesis and mitochondrial function . Telomerase, in binding to short DNA s is dependent on magnesium [49].

15. Magnesium Deficiency – Causes, Symptoms, Tests and Treatment

Reasons why you may have magnesium deficiency include: not eating enough magnesium rich foods, stress, excessive alcohol consumption, certain kidney diseases, some endocrine diseases (i.e. diabetes, metabolic syndrome) and many medications.Taking high doses of vitamin D alone can create magnesium deficiency.  Regular exercise also deplete your body from magnesium [50], [51].

How do you know if you have a shortage of magnesium  ? At the beginning you may experience some   fatigue, weakness, nausea, vomiting or loss of appetite. As this mineral deficiency  worsens, you may feel  numbness, tingling , muscles spasms, cramps and even seizures, changes in personality and abnormal heart rhythms [1]. Note : the above symptoms may be caused by other factors, not just magnesium deficiency .

Magnesium deficiency test : Blood levels of magnesium won’t  give an accurate indication of the magnesium status as  less than 1% of total magnesium is in blood serum.  A better alternative to magnesium deficiency test from the blood  is Magnesium RBC blood test  (which  measures 40 percent of the body’s magnesium). The normal values for this test is 4.2-6.8 mg/dL (ideally  between  6.0-6.5 mg/dL) [1], [53], [54].

Treating magnesium deficiency : Some choose to skip the magnesium deficiency test , and simply add more magnesium to the diet and take supplements. Magnesium supplements are very safe and well tolerated . Keep in mind that you would  get the laxative (the most common side effect) of magnesium before getting the therapeutic effect. Ionic magnesium is the best form absorbed in the body. Epson salt and magnesium oil are also ok. Only 20% of magnesium glycinate is absorbed by the body, but is still a better choice that magnesium oxide ( only 3% absorbed). Ionic magnesium and magnesium glycinate have less laxative effects.

Adding more magnesium rich foods (green leafy vegetables, legumes, nuts, seeds) to your diet is also a good idea ( 30% to 40% of the dietary magnesium consumed is typically absorbed by the body) [53].

References : 

[1] https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/

[2] https://www.ncbi.nlm.nih.gov/pubmed/15930481/

[3]https://www.ncbi.nlm.nih.gov/pubmed/12949381/

[4]https://www.ncbi.nlm.nih.gov/pubmed/17213891/

[5]https://www.ncbi.nlm.nih.gov/pubmed/17145221/

[6]https://www.ncbi.nlm.nih.gov/pubmed/16214452/

[7]https://www.ncbi.nlm.nih.gov/pubmed/14693967/

[8]https://www.ncbi.nlm.nih.gov/pubmed/7572055

[9]https://www.ncbi.nlm.nih.gov/pubmed/27757186

[10]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731789/

[11]https://www.ncbi.nlm.nih.gov/pubmed/26591563

[12]https://www.ncbi.nlm.nih.gov/pubmed/27933574

[13]https://www.ncbi.nlm.nih.gov/pubmed/27910808

[14]http://www.jabfm.org/content/28/2/249.long

[15]https://www.ncbi.nlm.nih.gov/pubmed/16542786

[16]https://www.ncbi.nlm.nih.gov/pubmed/19780403

[17]https://www.ncbi.nlm.nih.gov/pubmed/16542786

[18]https://www.ncbi.nlm.nih.gov/pubmed/11777170,

[19]https://www.ncbi.nlm.nih.gov/pubmed/23853635

[20]https://www.ncbi.nlm.nih.gov/pubmed/21199787

[21]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968354/

[22]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731789/

[23]https://pdfs.semanticscholar.org/8915/d3b6aba14aa51ef63dce234b0534390e514e.pdf

[24]https://www.ncbi.nlm.nih.gov/pubmed/21609904

[25]https://www.ncbi.nlm.nih.gov/pubmed/26591563

[26]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731789/

[27]https://www.ncbi.nlm.nih.gov/pubmed/28280456

[28]https://www.ncbi.nlm.nih.gov/pubmed/26634890

[29]https://www.ncbi.nlm.nih.gov/pubmed/2821365,

[30]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105488/

[31]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357260/

[32]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187809/,

[33]https://www.ncbi.nlm.nih.gov/pubmed/24562640

[34]https://www.ncbi.nlm.nih.gov/pubmed/17229973

[35]https://www.ncbi.nlm.nih.gov/pubmed/27854048

[36]https://www.omicsonline.org/magnesium-influence-on-stress-and-immune-function-in-exercise-2161-0673.1000111.pdf

[37]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127587/

[38]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884513/

[39]https://www.ncbi.nlm.nih.gov/pubmed/26166051

[40]https://www.ncbi.nlm.nih.gov/pubmed/14506478

[41]https://www.ncbi.nlm.nih.gov/pubmed/3075245

[42]http://www.nature.com/ejcn/journal/v57/n10/full/1601689a.html

[43]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669297/#R1

[44]https://www.ncbi.nlm.nih.gov/pubmed/28417080

[47]https://www.ms.org.au/what-is-multiple-sclerosis/symptoms-diagnosis/common-symptoms/headache.aspx

[45]https://www.ncbi.nlm.nih.gov/pubmed/27140442

[46]https://www.ncbi.nlm.nih.gov/pubmed/27834189

[47]https://www.ncbi.nlm.nih.gov/pubmed/27881065

[55]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069023/

[56]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770174/

[48]https://www.ncbi.nlm.nih.gov/pubmed/20388094

[49]https://www.ncbi.nlm.nih.gov/pubmed/2237936

[50]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112180/

[51]https://www.ncbi.nlm.nih.gov/pubmed/18705536

[53]https://drcarolyndeanlive.files.wordpress.com/2016/12/remag-v9-rs-dec14-final.pdf

[54]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586582/