Simply Magnesium: Part 1

Magnesium is the 4th most abundant mineral in the body and is vital for health and resilience. Magnesium is stored in the body mainly in the bones, muscles and other cells and is required for the many different and diverse metabolic, physiological and psychological functions. Understanding magnesium’s central role in the structure and function of cells, tissues and organs throughout the body will help you to optimise your own health.[1]

Magnesium and Energy Production

Magnesium is required for the production and structure of the Adenosine Triphosphate (ATP) molecule in cells throughout the body. ATP provides energy for all basic bodily processes ranging from processing and transporting nutrients, to making enzymes, and activating cellular pumps so that important substances and metabolic waste can move in and out of the cell. The sodium-potassium ATPase pump, for example, is the mechanism by which nerve cells carry signals, and is also fundamental to maintaining the balance and flow of electrolytes (namely sodium and potassium, calcium and magnesium) across the cell membrane. Without this electrolyte exchange, cells cannot maintain a sufficient pH, electrical charge or electrolyte for many important metabolic activities.

Magnesium and Detoxification

Detoxification processes also require ATP to function so without enough magnesium, reduced production of ATP, reduced cellular function and build up of cellular and tissue toxicity may affect health.

Magnesium also plays an important role in production of glutathione, an intracellular thiol compound that is regarded as a very valuable cell protector via its direct effects on quenching free radicals and DNA damaging oxidative stressors.[2] In fact, lowered glutathione levels have been observed in several disease conditions[3], so supporting magnesium levels may help this key antioxidant system.[4]

Magnesium and Muscle Health

Muscle tissue functions through opposing actions requiring different minerals; calcium helps muscles to contract, and magnesium helps muscle tissue to relax. Muscle tissue usually contains more calcium than magnesium, but a relative deficiency of magnesium in muscle tissues can contribute to cramps and spasms, as the muscle is unable to relax from its contracted state.

Studies show that magnesium may be greatly beneficial to conditions that involve muscle cramps and spasms such as chronic back pain, leg cramps and evenIBS; after all the digestive tract is made up of different tissue types including smooth muscle. Constrictions in the muscle, nerve and connective tissue cells may contribute not only to muscle spasms, but also to poor postural alignment, as the skeletal structure is misaligned.

The uterus is also comprised of smooth muscle tissue. Monthly variations of oestrogen and progesterone levels in women influence magnesium levels, which may explain why for some women deficient in magnesium, the menstrual cycle is often accompanied by abdominal cramping, including “Mittelschmerz” (mid-cycle cramping) – one-sided, lower abdominal pain associated with ovulation around 14 days before the menstrual cycle.

Magnesium and Cardiovascular Health

A recent study suggested that subclinical magnesium deficiency is the principal driver of cardiovascular disease and amounted to a public health crisis.[5]

Magnesium deficiency can also cause contractions in the arterial walls, which contain smooth muscle tissue. In some people, this may lead to high blood pressure[6]; oral magnesium has been demonstrated to help to decrease high blood pressure.[7]

Blood vessel constriction may also contribute to headachesand migraines, where the blood vessels in the head and neck are constricted.[8] In one study, magnesium supplements reduced migraine occurrence and symptoms.[9]

Reduced levels of magnesium can also contribute to circulatory problems in other parts of the body, such in Raynaud’s syndrome, where the extremities become very cold and pale due to extreme vasoconstriction of the peripheral blood vessels.[10]

Coronary arteries also contain smooth muscle tissue, and so need calcium to contract and magnesium to relax. These tiny blood vessels, around 3mm or less in diameter, depend on magnesium to relax and dilate the muscle tissue so that oxygen-rich blood can nourish the heart tissue itself. The correct balance of magnesium and calcium is also required to regulate the heartbeat; supplementing with magnesium has been shown to be beneficial in the management of arrhythmia.[11]

Magnesium deficiency has been shown to increase platelet aggregation, which contributes to the kind of clotting seen in heart attacks, pulmonary embolism and strokes.[12]

An early pathological sign of magnesium deficiency is degradation of elastin in the sub-endothelial tissue layer of the arteries, the part of the lining, which lies next to the smooth muscle. When this happens, the artery walls lose their elasticity, and inflammation occurs. Current research around heart disease proposes that cholesterol and calcium concentrates in the area of damage in the arterial wall as a plaque to protect the damaged tissue. These plaques are rigid, however, and so not a good long-term solution, hardening the arteries and creating the condition known as atherosclerosis, which ultimately leads to weakening and blockage of the arteries creating angina pain and heart disease.[13]

Magnesium and Bone Health

Many people reach for calcium supplements to support bone health, perhaps with some Vitamin D to aid absorption. But just as important, if not more so, are the levels of magnesium in the body; magnesium is part of the ATP producing cycles to provide energy for bone formation, helps calcium to be laid down in the bone in the form of calcium phosphate crystals (along with other nutrients that support bone structure including boron and silicon) and helps calcium absorption in the small intestines in the first place.[14]

Magnesium and Brain Health

Magnesium and calcium play an essential role in nerve signalling in the central and peripheral nervous systems. Neurotransmitters in the brain also use magnesium and calcium, as well as zinc, to stimulate and regulate electrical activity; for example, magnesium is a natural calcium antagonist and can block the N-methyl-D-aspartate receptor helps to regulate certain signalling pathways in the brain and nervous system. Calcium-rich brain cells can fire excessively, which depletes ATP levels, and sometimes lead to seizures, or even cell death. Magnesium lowers the threshold for those seizures, and may reduce the likelihood that they will happen.[15]

Magnesium is required for the production of serotonin and dopamine has been linked to conditions such as depression, anxiety and panic attacks[16], as well as Parkinson’s Disease and ADHD.[17]^,[18],[19] Recent studies also show the link between magnesium deficiency and alterations in gut bacteria levels, which lead to depressive like behaviour.[20]

Recent studies have demonstrated that the brain, serum and ionized magnesium levels are decreased in Alzheimer’s Disease (AD) patients; however, the exact role of magnesium in AD pathogenesis remains unclear. In mice a chronic reduction in dietary magnesium impairs memory[21], and the treatment of dementia patients with nutritional magnesium improves memory.[22]^,[23] Magnesium depletion, particularly in the hippocampus, appears to represent an important pathogenic factor in AD.[24] 

Magnesium also plays an important role in detoxifying cells from heavy metals, not least though production of glutathione.[25] However, heavy metals compete with magnesium for uptake in the small intestine and the nervous system so may contribute to magnesium deficiency[26] providing a potential links between heavy metals and conditions including AD, Multiple Sclerosis (MS)and Attention Deficit Hyperactivity Disorder (ADHD).

Magnesium and Stress

Prolonged stress in any form, including stressful jobs, repeated heavy exercise or adrenaline sports, “burning the candle at both ends”, running on empty, all these deplete magnesium levels by putting a strain on the adrenal glands for stress hormone production and regulation of fluids in the body by the adrenal hormone aldosterone.

Additionally, magnesium is a co-factor for the hormones, prostaglandins and enzymes required to service the adrenals (alongside zinc, essential fatty acids, Vitamin C, Vitamin E, B vitamins and amino acids), Adrenal depletion also impacts other parts of the endocrine system including the thyroid gland (i.e. the Hypothalamic-pituitary-adrenal (HPA) axis). Magnesium deficiency is therefore caused by, and contributes to, physical and psychological stress-related symptoms within the body.[27]

Magnesium and Blood Sugar Balance

Magnesium plays a crucial role in glucose and insulin metabolism, mainly through its impact on tyrosine kinase activity of the insulin receptor. Magnesium may also affect phosphorylase b kinase enzyme activity by releasing glucose-1-phosphate from glycogen. In addition, magnesium may directly affect glucose transporter protein activity 4 (GLUT4), and help to regulate glucose translocation into the cell.[28]

Diabetes mellitus, both type-1 and type-2, are among the most common causes of magnesium deficiency[29] which include poor oral intake, increased renal loss and the chronic diarrhoea associated with autonomic neuropathy.

A recent meta-analysis of 13 prospective cohort studies involving 536,318 participants and 24,516 cases detected a significant inverse association between magnesium intake and risk of type 2 diabetes.[30] If magnesium supplementation affects insulin sensitivity in patients with diabetes mellitus, it may also improve insulin sensitivity in obese individuals who are at risk of type 2 diabetes mellitus. 

Magnesium and Women’s Health

Oestrogen and progesterone affect magnesium levels, and this is relevant for both menstruating women and women going through menopause.[31] There have been a number of studies showing magnesium to be therapeutic due to its ability to relax muscles and blood vessel walls, and also to reduce PGF2 alpha, a prostaglandin that stimulates contraction of the uterine muscle. Supplementing with magnesium and Vitamin B6 has been shown to reduce symptoms of PMS including breast pain, nervous tension, headaches and mood swings, perhaps because of its effect on serotonin levels.[32]^,[33]

Magnesium requirements increase during pregnancy, labour and breastfeeding, as the developing baby requires magnesium for its own ATP production, manufacture of enzymes and hormones, prostaglandins and to maintain its own electrolyte balance during the production of its own healthy cells. The mother needs increased magnesium intake to provide for all of this, and also to service her own increased levels of hormones, prostaglandins, enzymes and ATP, as well as increased uterine and breast tissue. Magnesium will also be required for muscle relation during labour.

Magnesium sulfate also still remains the most frequently used agent in the management of pre-eclampsia and eclampsia, a disorder of pregnancy characterised by hypertension, proteinuria, often accompanied by pathological oedema. Magnesium is the drug of choice to prevent convulsions in eclampsia.[34]

In conclusion, magnesium is an essential electrolyte for living organisms and magnesium deficiency is associated with a variety of diseases. By supporting magnesium levels through the diet, improving absorption and also by bioavailable supplementation may provide a route to supporting health in a variety of ways.

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Refrences

1. Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015 Sep 23;7(9):8199-226. doi: 10.3390/nu7095388. Full paper
2. Sen,CK. Nutritional biochemistry of cellular glutathione. Nutri Biochem, vol 8, 12 660-672. 1997.View Abstract
3. Gul M, Kutay FZ, Temocin S, Hanninen O. Cellular and clinical implications of glutathione. Indian J Exp Biol. 2000 Jul;38(7):625-34 No Abstract
4. Kidd PM. Glutathione: Systemic protectant against oxidative and free radical damage. Altern Med Rev 1997;1:155-176 View Full Paper
5. DiNicolantonio JJ, O’Keefe JH, Wilson W Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis Open Heart 2018 View Full Paper
6. Kisters, K.; Gröber, U. Lowered magnesium in hypertension. Hypertension 2013, 62, e19. Full paper
7. Rosanoff, A.; Plesset, M.R. Oral magnesium supplements decrease high blood pressure (SBP > 155 mm Hg) in hypertensive subjects on anti-hypertensive medications: A targeted meta-analysis. Magnes. Res. 2013, 26, 93–99 Full paper
8. Assarzadegan F, Asgarzadeh S, Hatamabadi HR, Shahrami A, Tabatabaey A, Asgarzadeh M. Serum concentration of magnesium as an independent risk factor in migraine attacks: a matched case-control study and review of the literature. Int Clin Psychopharmacol. 2016 May 2. View Abstract
9. Chiu HY, Yeh TH, Huang YC, Chen PY. Effects of Intravenous and Oral Magnesium on Reducing Migraine: A Meta-analysis of Randomized Controlled Trials. Pain Physician. 2016 Jan;19(1):E97-112. View Abstract
10. J. Leppert et al (1994)  The Concentration of Magnesium in Erythrocytes in Female Patients with Primary Raynaud’s Phenomenon; Fluctuation with the Time of Year. Angiology 45: 4 View abstract
11. Shah, N.C.; Shah, J.G.; Li, Z.; Jiang, X.C.; Altura, B.T.; Altura, B.M. Short-term magnesium deficiency downregulates telomerase, upregulates neutral sphingomyelinase and induces oxidative DNA damage in cardiovascular tissues: relevance to atherogenesis, cardiovascular diseases and aging. Int. J. Clin. Exp. Med. 2014, 7, 497–514 Full paper
12. Altura, B.M.; Altura, B.T. Magnesium and cardiovascular biology: An important link between cardiovascular risk factors and atherogenesis. Cell. Mol. Biol. Res.1995, 41, 347–359 View abstract
13. Zmysłowski and Szterk (2017) Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols. Lipids in Health and Disease (2017) 16:188 Full paper
14. Castiglioni, S.; Cazzaniga, A.; Albisetti, W.; Maier, J.A. Magnesium and osteoporosis: Current state of knowledge and future research directions. Nutrients 2013, 5, 3022–3033 Full paper
15. Becky Biqi Chen et al (2016) Seizures Related to Hypomagnesemia: A Case Series and Review of the Literature Child Neurology Open Volume 3: 1-6 Full paper
16. Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015 Sep 23;7(9):8199-226. doi: 10.3390/nu7095388. Full paper
17. Nogovitsina, O.R.; Levitina, E.V. Diagnostic value of examination of the magnesium homeostasis in children with attention deficit syndrome with hyperactivity. Klin. Lab. Diagn. 2005, 5, 17–19 View abstract
18. Mousain-Bosc, M.; Roche, M.; Rapin, J.; Bali, J.P. Magnesium VitB6 intake reduces central nervous system hyperexcitability in children. J. Am. Coll Nutr.2004, 23, 545S–548S View abstract
19. Mousain-Bosc, M.; Roche, M.; Polge, A.; Pradal-Prat, D.; Rapin, J.; Bali, J.P. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders. Magnes. Res. 2006, 19, 46–52 Full paper
20. Winther G, Pyndt Jørgensen BM, Elfving B, Nielsen DS, Kihl P, Lund S, Sørensen DB, Wegener G. Dietary magnesium deficiency alters gut microbiota and leads to depressive-like behaviour. Acta Neuropsychiatr. 2015 Feb 18:1-9. View Abstract
21. Bardgett, M.E.; Schultheis, P.J.; McGill, D.L.; Richmond, R.E.; Wagge, J.R. Magnesium deficiency impairs fear conditioning in mice. Brain Res. 2005, 1038, 100–106 View abstract
22. Barbagallo, M.; Belvedere, M.; Di Bella, G.; Dominguez, L.J. Altered ionized magnesium levels in mild-to-moderate Alzheimer’s disease. Magnes. Res. 2011, 24, S115–S121 Full paper
23. Cherbuin, N.; Kumar, R.; Sachdev, P.S.; Anstey, K.J. Dietary Mineral Intake and Risk of Mild Cognitive Impairment: The PATH through Life Project. Front. Aging Neurosci. 2014 Full paper
24. Andrási, E.; Igaz, S.; Molnár, Z.; Makó, S. Disturbances of magnesium concentrations in various brain areas in Alzheimer’s disease. Magnes. Res. 2000, 13, 189–196 View abstract
25. Kidd PM. Glutathione: Systemic protectant against oxidative and free radical damage. Altern Med Rev 1997;1:155-176 View Full Paper
26. Soldatović Det al (1998) Contribution to interaction between magnesium and toxic metals: the effect of prolonged cadmium intoxication on magnesium metabolism in rabbits. Magnes Res. Dec;11(4):283-8. View Abstract
27. Neil Bernard Boyle (2017) The Effects of Magnesium Supplementation on Subjective Anxiety and Stress—A Systematic Review. Nutrients 2017, 9, 429 Full paper
28. Guerrero-Romero, F.; Simental-Mendía , L.E.; Hernández-Ronquillo, G.; Rodriguez-Morán, M. Oral magnesium supplementation improves glycaemic status in subjects with prediabetes and hypomagnesaemia: A double-blind placebo-controlled randomized trial. Diabetes Metab. 2015, 41, 202–207 View abstract
29. Ramadass, S.; Basu, S.; Srinivasan, A.R. Serum magnesium levels as an indicator of status of Diabetes Mellitus type 2. Diabetes Metab. Syndr. 2015, 9, 42–45 View abstract
30. Dong, J.Y.; Xun, P.; He, K.; Qin, L.Q. Magnesium intake and risk of type 2 diabetes: Meta-analysis of prospective cohort studies. Diabetes Care 2011, 34, 2116–2122 Full paper
31. Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015 Sep 23;7(9):8199-226. doi: 10.3390/nu7095388. Full paper
32. Nahid Fathizadeh, et al (2010) Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome Iran J Nurs Midwifery Res. 2010 Dec; 15(Suppl1): 401–405 Full paper
33. Ebrahimi, E.; Khayati Motlagh, S.; Nemati, S.; Tavakoli, Z. Effects of magnesium and vitamin B6 on the severity of premenstrual syndrome symptoms. J. Caring Sci. 2012, 1, 183–189 Full paper
34. Altman, D.; Carroli, G.; Duley, L.; Farrell, B.; Moodley, J.; Neilson, J.; Smith, D. Magpie Trial Collaboration Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomised placebo-controlled trial. Lancet 2002, 359, 1877–1890 View abstract