Magnesium is essential, which means that it must be obtained through food and cannot be produced by the body itself.  An adult's body contains approximately 24 to 28 g of magnesium. 50-70% of this is stored in the bones (bound to hydroxyapatite; partially mobilizable in the event of magnesium deficiency) and 25-30% in the muscles and soft tissue (intracellular).

Relative proportions of magnesium in the total magnesium of our body:

serum erythrocytes connective tissue muscle Bone Plasma concentration: Ionized Mg: Erythrocytic Mg:

0.3% 0.5% 19.3% 27% 52.9% 0.85 mmol/l 0.5–0.65 mmol/l 1.65–2.73 mmol/l

Magnesium intake:

20-30% of the magnesium ingested from food is absorbed by the body. This occurs both through active transport (via the ion channel TRPM6) and through passive diffusion. The absorption rate is influenced primarily by the type of magnesium compound. For example, magnesium bisglycinate, citrate or lactate are more bioavailable than magnesium oxide or magnesium sulfate.

Studies show that the best absorption with single doses of <200 mg elemental magnesium takes place.

Magnesium elimination:

Magnesium is excreted primarily through the kidneys, but also through sweat. renal magnesium elimination at about 100 mg/day. Excretion is increased by alcohol and large amounts of protein.

Magnesium effects:

Magnesium is involved in almost all metabolic processes:

• Energy metabolism (e.g. ATP is bound intracellularly to magnesium) à Figure below
• neuromuscular excitation transmission (reduces excitability)
• muscle function
• protein, DNA and RNA synthesis
• Contributes to cell membrane permeability and stability at the cellular level via the cross-linking of phospholipids
• Has central importance for the control of glucose metabolism
• Regulation of many cardiac functions (e.g. contraction (negative inotropic effect), myocardial metabolism, cardiac performance, stabilization of cardiac rhythm
• Biological calcium antagonist

Importance of magnesium in energy metabolism:

Cofactor in over 300 enzyme systems (2), e.g.

• acetyl-CoA synthetase
• 5'-nucleotidase
• phosphoryl kinase
• Phosphoribosylpyrophosphate transferase
• phosphoglucomutase
• Na+-K+-ATP-ase (activity of the Na-K pump!)
• Ca++ transport ATPase of the sarcoplasmic reticulum
• H+-ATPases of the mitochondrial membrane (seethere)
• adenylate cyclase
• myosin ATPase
• hexokinase
• phosphofructokinase
• phosphoglycerate kinase
• enolase
• pyruvate kinase

Glucose metabolism (central importance):

• reduces diabetes incidence
• improves insulin sensitivity
• stimulates insulin receptors
• increases activity of pyruvate kinase,
• cofactor in glucose transport and glycogen synthesis

Biological calcium antagonist:

• Prevention of excessive calcium influx (protection of heart muscle cells)
• modulation of intracellular calcium action
• Activation of calcium ATP-ase (stabilizes excitation potential of heart/skeletal muscle cells)
• Influence on potassium channels or Na/K-ATP-ase (muscles, heart muscle, nerve cells)
  • Mg closes K channels in cells and increases K intracellularly
  • reduction of muscle contractions and vascular tone
  • But also: calcium-like effects (synergism)

Involvement in cardiac functions, such as:

• regulation of contractile proteins
• transport of Ca++ (via sarcoplasmic reticulum)
• co-factor of ATPase activities
• Influence of Ca++ binding and Ca transport in membranes and intracellular organelles
• metabolic regulation of energy-dependent cytoplasmic and mitochondrial metabolic pathways
• Influence on the contractility of the heart muscle fibers (has a negative inotropic effect)
• influencing hormone-receptor interactions
• regulation of electrolyte transport and content
• influencing resting and action potentials
• change in the electromechanical coupling
• Inhibition of calcium-induced NTM release at presynaptic membranes (reduction of stress hormones and excitability -> cf. heart)
• reduction of cardiac O2 consumption
• Improvement of myocardial metabolism, cardiac output, vascular tone
• Protection against cardiac arrhythmias (inhibits conduction at the AV node, improves recovery time at the sinus node)

Magnesium indications:

• urolithiasis
• diabetes mellitus
• heart diseases (e.g. tachycardia, hypertension)
• Cor pulmonale
• asthma
• pregnancy eclampsia
• cramps
• stress

Magnesium deficiency & possible causes:

Magnesium deficiency is associated with a large number of chronic diseases, such as Alzheimer's, type 2 diabetes, high blood pressure, cardiovascular disease, migraines and ADHD. In the USA, it is assumed that 50% of the population is undersupplied with magnesium. In Germany, according to a study from 2001, almost 34% have suboptimal magnesium levels in their blood.

Possible causes of magnesium deficiency are:

• Reduced intake (diet, alcoholism, absorption disorders)
• pregnancy and breastfeeding
• Intensive sports
• stress
• Increased excretion (in kidney disease, diabetes, alcohol consumption, hyperaldosteronism, diuretics, digitalis, aminoglycosides, etc.))
• Inhibition of magnesium absorption by tetracyclines and antacids

magnesium deficiency symptoms (Source: Internists’ Congress 2008, Wiesbaden):

• Neuromuscular hyperexcitability (muscle cramps up to tetany, headache)
• Increased lactate levels (see sports)
• confusion, depression
• Insomnia, difficulty concentrating, fatigue
• disturbances of the mineral balance
• Gastrointestinal hyperexcitability
• Cardiac hyperexcitability (arrhythmia, AP, hypertension)
• immune disorders
  
  

Magnesium deposits:

• In almost all foods
• But usually only low concentrations
• Low magnesium content in staple foods
• Preferably found in whole grain products

• People with an average diet consume about 200 mg of magnesium per day through their diet

Magnesium-rich foods

• Wheat bran: 600mg magnesium in 100g
• Sunflower seeds: 420mg in 100g
• Soy flour: 245mg in 100g
• Wheat germ: 120-130mg in 50g
• Barley, rice (unpolished): 160mg in 100g
• Walnuts, almonds, peanuts, hazelnuts: 65-90mg in 50g
• whole wheat bread: 90mg in 100g
• Lentils: 75mg in 100g
• Oatmeal: 70mg in 50g
• magnesium-rich mineral waters: 80-120mg in 0.2 l
• Spinach: 60mg in 100g

Magnesium interactions with other micronutrients

calcium

• Magnesium is a calcium antagonist, but also synergism (e.g. in tetany: Ca or Mg work!):
• Magnesium is important for calcium metabolism:
  • Magnesium deficiency (PTH decrease) leads to hypocalcemia
    (in case of Ca ↓, give Ca + Mg together in a ratio of 2:1 – 3:1)
  • Magnesium competes with calcium for oxalate anion and lowers oxalate ions (concentration in urine: Reducing the risk of calcium oxalate stones)

potassium

• Magnesium deficiency (PTH decrease) leads to potassium deficiency
• Magnesium influences the transmembrane movement of potassium
• Potassium improves magnesium absorption in the intestine

Interactions of magnesium with medications

Several medications can affect magnesium levels. Here are some examples (see Magnesium Fact Sheet for Health Professionals, National Institutes of Health):

• Diuretics, which are prescribed to lower blood pressure, for example, often lead to increased magnesium excretion in the urine and thus to a deficiency if magnesium is not taken as a dietary supplement.
• Proton pump inhibitors (PPIs; also known as “acid blockers”/“stomach protectors”), such as omeprazole or lansoprazole, can lead to a magnesium deficiency if used over a long period of time. In 25% of those affected, even taking magnesium did not help to increase magnesium levels when the PPI was continued. Only stopping the medication was able to increase magnesium levels again.
• Conversely, magnesium can also affect the absorption and effect of some medications - it can inhibit the absorption of bisphosphonates used to treat osteoporosis, for example - so magnesium supplementation should always be discussed with your doctor. Often, it is sufficient to take the supplement at least 2 hours after taking the medication.
• Magnesium can also form insoluble complexes with some antibiotics, such as tetracyclines (Declomycin®), doxycycline (Vibramycin®) and fluoroquinolone antibiotics (ciprofloxacin (Cipro®) and levofloxacin (Levaquin®)). Therefore, these antibiotics should be taken at least 2 hours before or 4-6 hours after magnesium supplementation.

Current studies on the therapeutic use of magnesium

Magnesium for insulin resistance & type 2 diabetes

Insulin resistance is a precursor to type 2 diabetes. Muscle and liver cells no longer fully absorb blood sugar, so that it is increasingly converted to fat and stored. Magnesium could prevent this process (cf. Rosanoff A, et al, Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutrition Reviews, 2012 Mar;70(3):153-64 (4) Schimatschek HF and Rempis R, Prevalence of hypomagnesemia in an unselected German population of 16,000 individuals, Magnesium Research, 2001 Dec;14).

In addition, the increased insulin levels associated with insulin resistance lead to increased magnesium loss in the urine, which further reduces magnesium levels. Magnesium supplementation can improve this condition (cf. Wang J, et al, Dietary magnesium intake improves insulin resistance among non-diabetic individuals with metabolic syndrome participating in a dietary trial, Nutrients, 2013 Sep 27;5(10):3910-9.; Mooren FC, et al, Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects - a double-blind, placebo-controlled, randomized trial, Diabetes, Obesity & Metabolism, 2011 Mar;13(3):281-4.; Guerrero-Romero F, et al, Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial, Diabetes & Metabolism, 2004 Jun;30(3):253-8).

In a 2003 study, magnesium supplementation led to reduced insulin resistance and also to a decrease in blood sugar levels (see Rodríguez-Morán M and Guerrero-Romero F, Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial, Diabetes Care, 2003 Apr;26(4):1147-52.).

A meta-study from 2011 shows how a magnesium deficiency increases the risk of diabetes (cf. Dong JY, et al, Magnesium intake and risk of type 2 diabetes: meta-analysis of prospective cohort studies, Diabetes Care, 2011 Sep;34(9):2116-22.; Hruby A, et al, Higher magnesium intake reduces risk of impaired glucose and insulin metabolism and progression from prediabetes to diabetes in middle-aged americans, Diabetes Care, 2014 Feb;37(2):419-27).

Furthermore, a 2010 study of more than 4,000 people over 20 years showed that those with the highest magnesium intake had a 47% lower risk of diabetes (see Kim DJ, et al, Magnesium intake in relation to systemic inflammation, insulin resistance, and the incidence of diabetes, Diabetes Care, 2010 Dec;33(12):2604-10).

In a randomized double-blind study, participants with low magnesium levels and type 2 diabetes were given 50 ml of a magnesium chloride solution daily for 4 months. In addition to the fact that magnesium levels recovered, insulin sensitivity, blood sugar levels and long-term blood sugar (HbA1c) also improved (see Rodríguez-Morán M and Guerrero-Romero F, Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial, Diabetes Care, 2003 Apr;26(4):1147-52).

Magnesium for cardiovascular diseases

Low magnesium levels promote the development of high blood pressure and lipid metabolism disorders (high cholesterol and triglyceride levels). According to a meta-study from 2017, high blood pressure can be positively influenced by taking magnesium. The magnesium dose administered was 365-450 mg/day of pure magnesium and led to a reduction in both systolic (by 4.18 mmHg) and diastolic (by 2.27 mmHg) blood pressure (cf. Dibaba DT, et al, The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials, The American Journal of Clinical 2017 Sep;106(3):921-929).

The lower the magnesium level, the higher the risk of so-called “window shopping disease” – a vascular disease of the legs. According to a study from 2009, taking magnesium improves the condition of the vessels (see Hatzistavri LS, et al, Oral magnesium supplementation reduces ambulatory blood pressure in patients with mild hypertension, American Journal of Hypertension, 2009 Oct;22(10):1070-5.; Kawano Y, et al, Effects of magnesium supplementation in hypertensive patients: assessment by office, home, and ambulatory blood pressures, Hypertension, 199 8 Aug;32(2):260-5; Kass LS, et al, A pilot study on the effects of magnesium supplementation with high and low habitual dietary magnesium intake on resting and recovery from aerobic and resistance exercise and systolic blood pressure, Journal of Sports Science & Medicine, 2013 Mar 1;12(1):144-50.; Guerrero-Romero F and Rodríguez-Morán M, The effect of lowering blood pressure by magnesium Supplementation in diabetic hypertensive adults with low serum magnesium levels: a randomized, double-blind, placebo-controlled clinical trial, Journal of Human Hypertension, 2009 Apr;23(4):245-51.).

In normal doses, magnesium only lowers high blood pressure, whereas healthy blood pressure is not lowered any further (cf. Lee S, et al, Effects of oral magnesium supplementation on insulin sensitivity and blood pressure in normo-magnesemic nondiabetic overweight Korean adults, Nutrition, Metabolism, and Cardiovascular Diseases, 2009 Dec;19(11):781-8.).

Magnesium activates vitamin D

A February 2018 review in The Journal of the American Osteopathic Association confirmed that vitamin D cannot be metabolized if there is not enough magnesium available at the same time. If there is a magnesium deficiency, vitamin D is stored but remains inactive.

Magnesium influences vitamin D metabolism in three ways:

• Magnesium is involved in the activation of vitamin D, which means that only with magnesium can the enzymes that convert vitamin D into its active form become active.
• Vitamin D requires certain transport molecules that would remain inactive without magnesium.
• Parathyroid hormone, a hormone produced by the parathyroid glands, is involved in regulating vitamin D metabolism. Parathyroid hormone, in turn, is highly dependent on magnesium levels.

Magnesium in Autoimmune Diseases

Magnesium can also be helpful in autoimmune diseases such as Hashimoto's. A 2018 study discovered that low magnesium levels are associated with an increased risk of Hashimoto's and hypothyroidism (see Wang K, et al. Severely low serum magnesium is associated with increased risks of positive anti-thyroglobulin antibody and hypothyroidism: A cross-sectional study, Scientific Reports, 2018 Jul 2;8(1):9904).

Magnesium has an anti-inflammatory effect

Chronic inflammatory processes are considered to be the cause of many chronic diseases (cf. Nielsen FH, Effects of magnesium depletion on inflammation in chronic disease, Current Opinion in Clinical Nutrition and Metabolic Care., 2014 Nov;17(6):525-30.; Barbagallo M and Dominguez LJ, Magnesium and aging, Current Pharmaceutical Design, 2010;16(7):832-9.; Nielsen FH, Magnesium, inflammation, and obesity in chronic disease, Nutrition Reviews, 2010 Jun;68(6):333-40.).

Even in children, it has been shown that low magnesium levels are associated with increased inflammation levels (sensitive CRP). At the same time, the children had higher blood sugar, insulin and blood lipid levels  (cf. Rodríguez-Morán M and Guerrero-Romero M, Serum magnesium and C-reactive protein levels, Archives of Disease in Childhood, 2008 Aug;93(8):676-80.).

Magnesium intake can reduce inflammatory markers – both in the elderly and in overweight people, as well as in people with pre-diabetes (cf. Nielsen FH, et al, Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep, Magnesium Research, 2010 Dec;23(4):158-68; Chacko SA, et al, Magnesium supplementation, metabolic and inflammatory markers, and global genomic and proteomic profiling: a randomized, double-blind, controlled, crossover trial in overweight individuals, The American Journal of Clinical Nutrition, 2011 Feb;93(2):463-73.; Simental-Mendía LE, et al, Oral magnesium supplementation decreases C-reactive protein levels in subjects with prediabetes and hypomagnesemia: a clinical randomized double-blind placebocontrolled trial, Archives of Medical Research, 2014 May;45(4):32530.).

Magnesium prevents migraines

Many migraine patients suffer from a magnesium deficiency (see Mauskop A and Varughese J, Why all migraine patients should be treated with magnesium, Journal of Neural Transmission, 2012 May;119(5):575-9.).

Migraines can be treated with magnesium – not only preventively, but also when migraines have already manifested (cf. Wang F, et al, Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial, Headache, 2003 Jun;43(6):601-10.; Köseoglu E, The effects of magnesium prophylaxis in migraine without aura, Magnesium Research, 2008 Jun;21(2):101-8.).

In a 2015 study, patients with acute migraine attacks were given 1 g of magnesium sulfate and the control group was given the usual medication, consisting of metoclopramide (for nausea/vomiting) and dexamethasone (cortisone). It was shown that the magnesium was able to relieve the attack better than the migraine medication (see Shahrami A, et al, Comparison of therapeutic effects of magnesium sulfate vs.dexamethasone/metoclopramide on alleviating acute migraine headache, The Journal of Emergency Medicine, 2015 Jan;48(1):69-76.).

But a change in diet with increased consumption of magnesium-rich foods can also help reduce migraine symptoms in the long term  (cf. Teigen L and Boes CJ, An evidence-based review of oral magnesium supplementation in the preventive treatment of migraine, Cephalalgia, 2015 Sep;35(10):912-22).

Magnesium for Premenstrual Syndrome

Magnesium can also be helpful in PMS in doses of 200 mg daily. In a study, there was no improvement in the first cycle of taking the drug, but from the second cycle onwards the symptoms improved (cf. Facchinetti F, et al, Oral magnesium successfully relieves premenstrual mood changes, Obstetrics and Gynecology, 1991 Aug;78(2):177-81.; Walker AF, et al, Magnesium supplementation alleviates premenstrual symptoms of fluid retention, Journal of Women's Health, 1998 Nov ;7(9):1157-65).

Magnesium against depression

Magnesium also plays an important role in brain metabolism. Low magnesium levels are associated with an increased risk of depression (see Serefko A, et al, Magnesium in depression, Pharmacological Reports, 2013;65(3):547-54.; Tarleton EK and Littenberg B, Magnesium intake and depression in adults, Journal of the American Board of Family Medicine, Mar-Apr 2015;28(2):249-56.).

A 2015 study of 8,800 people found that those with the lowest magnesium levels had a 22% higher risk of depression. Experts suspect that the low magnesium content of today's diet is an important reason for depression and other mental disorders (see . Eby G and Eby K, Rapid recovery from major depression using magnesium treatment, Medical Hypotheses, 2006;67(2):362-70).

In one study, for example, depressed adults were given 450 mg of magnesium daily. The effect was as good as that of an antidepressant (see Barragán-Rodríguez L, et al, Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial, Magnesium Research, 2008 Dec;21(4):218-23.).

Magnesium in Sports

Since magnesium is involved in cellular energy production in the mitochondria and in the transport of blood sugar to the muscles, a good magnesium supply leads to better performance in sports. At the same time, the magnesium requirement increases by 10-20% during training compared to the resting state (see. Chen HY, et al, Magnesium enhances exercise performance via increasing glucose availability in the blood, muscle, and brain during exercise, PLoS One, 2014 Jan 20;9(1)).

According to studies from 2006, 2012 and 2014, supplementing with magnesium improves physical performance in older people and in people with chronic diseases (see do Amaral AF, et al, The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients, Clinics, 2012;67(6):615-22.; Pokan R, et al, Oral magnesium therapy, exercise heart rate, exercise tolerance, and myocardial function in coronary artery disease patients, British Journal of Sports Medicine, 2006 Sep;40(9):773-8.; Veronese N, et al, Effect of oral magnesium supplementation on physical performance in healthy elderly women involved in a weekly exercise program: a randomized controlled trial, The American Journal of Clinical Nutrition, 2014 Sep;100(3):974-81).

Based on a study from 2015, magnesium is considered to be performance-enhancing in athletes even if there was no previous magnesium deficiency (see Mirela Vasilescu, Magnesium supplementation in top athletes - effects and recommendations, March 2015, Medicina Sportiva. Journal of the Romanian Sports Medicine Society).

It was previously assumed that taking magnesium was only effective if there was a magnesium deficiency. However, this was refuted for the first time in a study from 1998: volleyball players took 250 mg of magnesium per day, which improved their jumping power and arm movements, among other things. In another study from the same year, triathletes took magnesium for four weeks and subsequently had better swimming, cycling and running times. In addition, their insulin and stress hormone levels fell (cf. Golf SW, et al, On the significance of magnesium in extreme physical stress, Cardiovascular Drugs and Therapy, 1998 Sep;12 Suppl 2:197-202.).