Maybe you’ve walked down the supplement aisle of your local pharmacy and noticed a recurring ingredient, or skimmed through the health section of a cosmopolitan magazine, or your favourite influencer mentions it time and time again, so what could this not-so-mystical ingredient be? You may have guessed it, magnesium. That’s right, so why does this commonly found mineral attract the hype and attention that it does? Let’s find out.

The basis of the role of all nutrients in the human body is essentially to catalyse all the chemical reactions necessary to sustain life. Hundreds of these reactions take place within our cells at any given moment and without the necessary co-factors to drive this complex chain of events, humans can’t function optimally, if at all. Every single one of these nutrients exists within certain ratios within the human body, some being far more abundant than others. Magnesium just so happens to be the second most abundant intracellular cation, just behind potassium, in the human body, and for good reason too; It plays functional roles in over 600 enzymatic reactions and is critical in processes pertaining to the muscles, heart, and brain (de Baaij, et al. 2015). 

Let’s focus on the most critical roles that magnesium plays in the human body, which include;

• Energy production and nucleic acid synthesis
  • RNA and DNA synthesis
  • ATP (adenosine triphosphate) production from adenosine diphosphate (ADP) and inorganic phosphate
  • Oxidative phosphorylation
  • Glycolysis
• Enzymatic activity 
  • Protein synthesis and muscle contraction
  • Nerve function
  • Blood glucose control and hormone receptor binding
  • Blood pressure regulation and cardiac excitability (Schwalfenberg & Genuis, 2017)

Enzyme activity

Magnesium-dependent enzymes are involved in the regulation of glycolysis, beta-oxidation, Krebs cycle, and active transport of ions.  The formation, storage, and usage of high-energy compounds is dependent on enzymes that are activated by magnesium. In fact, magnesium is compartmentalized in the nuclei, mitochondria, and endo/sarcoplasmic reticulum within cells, so it is clear just how important this mineral is in cellular activity relating to energy and genetic activity (Kolte et al., 2014). In particular, adenosine triphosphate, the central energy molecule, requires magnesium for it to function in any reaction. Magnesium also modulates enzymes involved in oxidative phosphorylation, a critical reaction that forms adenosine triphosphate from the flow of electrons within the mitochondria (Pasternak et al., 2010). Mg²⁺ is an essential component of DNA replication, RNA transcription, amino acid synthesis, and protein formation as enzymes required for these processes are magnesium dependent, such as topisomerases, helicases, exonucleases, protein kinases, cyclases, and large groups of ATPases (de Baaij et al., 2015).

Magnesium and the heart

Given magnesium’s important role in muscular activity, as all enzymes that utilize or synthesize muscle ATP require magnesium (Barbagallo et al, 2021), it would be safe to say that it would also oversee critical functions pertaining to the most energy-intensive muscle in the human body, the heart. Magnesium has been shown to promote vasodilation, reduce vascular resistance and improve systemic blood flow. It promotes vasodilation, partly, by neutralizing negative charges in cell membranes, which stabilises excitable membranes and antagonises calcium current in excitable cells. Magnesium also stimulates the production of prostacyclin, a hormone produced in the endothelium which promotes vasodilation alongside nitric oxide. However, it pays to mention the importance of magnesium’s counter-mineral, calcium, as extracellular calcium stimulates nitric oxide synthesis (Kolte et al., 2014).   

The regulation of calcium flow in the myocardium essentially protects the heart from cell toxicity and calcium overload. Additionally, magnesium is necessary for the function of the sodium/potassium pump, which controls intracellular potassium flow during the action potential of the heartbeat. This effect explains why magnesium can prevent and manage cardiac arrythmias (Fiorentini et al., 2021). Magnesium also exerts it’s cardioprotective effects by conserving cellular ATP, thereby preserving energy-dependent cellular processes and by reducing myo-cardial oxygen consumption through lowering heart rate, contractility, systemic afterload and mitigating catecholamine-induced elevated oxygen demand (Kolte et al., 2014).  

Magnesium and the brain

Magnesium forms part of the coenzyme responsible for the conversion of tryptophan to serotonin, this may partly explain the anxiolytic and antidepressant effect that magnesium has been shown to have in management of depression and anxiety (Schwalfenberg & Genuis, 2017). Another proponent of magnesium’s antidepressant is due to its interaction with the NMDA receptor. NMDA receptors are activated by glutamate, an excitatory neurotransmitter that can cause oxidative stress in the brain if its production is up-regulated. Magnesium works by blocking NMDA receptors, inhibiting glutamate from presynaptic neurons to bind to NMDA receptors, which prevents hyperexcitability of neurons (Fiorentini et al., 2021). Additionally, magnesium is also a GABA agonist, which is an inhibitory neurotransmitter that not only has a relaxing effect but prevents neuronal hyperexcitability by influencing membrane potential to hyperpolarize neuronal cells, resulting in the block of NMDA receptors (de Baaij et al., 2015). 

Variables that deplete magnesium and most prevalent signs of deficiency 

To see if you may need to increase your intake or supplement with magnesium, you should be aware of the common variables that drive magnesium usage and depletion. These include;

• Reduced food intake of dietary sources of magnesium, including whole grains, green-pigmented fruits and vegetables
• Food processing, cooking and boiling, which diminishes magnesium content in food
• Reduced gastrointestinal absorption caused by diarrhoea/vomiting or inflammatory bowel diseases, vitamin D deficiency, and medications that interfere with magnesium absorption such as proton pump inhibitors
• Excessive sweating and stress 
• Increased renal loss from alcohol/drugs such as diuretics (Schwalfenberg & Genuis, 2017)

Furthermore, learning to spot the common signs of magnesium deficiency will help you become aware of when to increase your intake. Even though clinical deficiency signs can be completely absent, the signs include;

• Non-specific signs; fatigue, dizziness, light-headedness, headache, muscle aches (myalgia) and cramps 
• Generalised muscular weakness, tics/tremors (in severe deficiency)
• Cardiac arrythmias, hypertension
• Neuro-emotional manifestations, including depression, anxiety, agitation, seizures, and psychosis (Barbagallo et al., 2021)

Magnesium in the diet and supplementing guidelines

Magnesium is generally well-distributed in food, however, soil degradation, food refining, cooking and boiling can drastically reduce the bioavailable magnesium in food. Additionally, the idea that chlorophyll-containing foods are a source of magnesium is correct but the acidity of gastric acid rapidly degrades chlorophyll and the total amount of chlorophyll-bound magnesium present in most leafy green vegetables only amounts to up to 10% of total magnesium. Refining flour, rice, starch and sugar can reduce the magnesium content between 80 and 99% (Fiorentini et al., 2021). Additionally, phytic acid, a naturally occurring chelator found in nuts, seeds, and grains can inhibit the absorption of magnesium, as well as calcium, iron and zinc. However, phytate content in food can be reducing by soaking in water overnight. Keep in mind what the recommended dietary intake for magnesium varies from age groups and between men and women. Men who are 14 years old or older should consume between 400-420 mgs of magnesium per day whereas women who are 14 years and older should consume between 300-360 mgs per day (National institutes of health, n.d).

With this being said, foods naturally high in magnesium (per 100 grams) include;

• Hemp seeds (700mg)
• Pumpkin seeds (535 mg)
• Flax seeds (392 mg)
• Brazil nuts (376 mg)
• Whole wheat bread (46 mg)
• Baked potato (43 mg)
• Boiled spinach (78mg in ½ cup)
• Avocado (44 mg in 1 cup cubed)
• Yoghurt (42 mg in 235 ml) (Schwalfenberg & Genuis, 2017) 

When supplementing magnesium, it is important to consider the form of magnesium salt present in highest concentration in the supplement you are taking. Different salts of magnesium will have varying rates of bioavailability as well as different therapeutic applications. It is evident that organic formulations of magnesium are better absorbed than inorganic ones. Additionally, magnesium formulations that used capsules with enteric coating or extended-release formulation have also been shown to have higher bioavailability than magnesium formulations with the same salts that did not use the same technology (Pardo et al, 2021). 

Here is a list of magnesium salts used in supplement formulas and their therapeutic applications;

• Magnesium hydroxide and oxide (both are poorly bioavailable but are used in laxative formulas and as antacids)
• Magnesium chloride, aspartate, and lactate (higher and similar bioavailability)
• Magnesium citrate (one of the highest rates of absorption as it is more soluble)
• Magnesium orotate (cardiac applications, used in heart failure)
• Magnesium glycinate and taurinate (used in mental health applications, anxiety, depression, insomnia) (Schwalfenberg & Genuis, 2017) 

In conclusion, magnesium is a cornerstone component of health that is all too commonly overlooked. It is evident why this mineral is so widely mentioned in all domains of health media and I believe everyone should pay close attention to what they are eating to ensure they consume the recommended intake of magnesium. It is also safe to say that having a magnesium supplement readily available in your pantry will be an investment that will pay itself off in spades, especially during times of stress. 

References

Barbagallo, M., Veronese, N. & Dominguez, L. (2021). Magnesium in aging, health and diseases. Nutrients, 13(2), 463. https://doi.org/10.3390/nu13020463

de Baaij, J., Hoenderop, J., & Bindels, R. (2015). Magnesium in man: implications for health and disease. Physiological reviews, 95(1), 1-46. https://doi.org/10.1152/physrev.00012.2014

Fiorentini, D., Cappadone, C., Farrugia, G., & Prata, C. (2021). Magnesium: biochemistry, nutrition, detection, and social impact of diseases linked to its deficiency. Nutrients, 13(4), 1136. https://doi.org/10.3390/nu13041136

Kolte, D., Vijayaraghavan, K., Khera, S., Sica, D.A., & Frishman, W.H. (2014). Role of magnesium in cardiovascular diseases. Cardiology in review, 22(4), 182-92. https://doi.org/10.1097/crd.0000000000000003

National institutes of health. (n.d). Magnesium: fact sheet for professionals. https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/

Pardo, R.M., Vilar, G.E., Martin, M.S.I & Martin, C.A.M. (2021). Bioavailability of magnesium food supplements: a systematic review. Nutrition, 89, 111294. https://doi.org/10.1016/j.nut.2021.111294

Pasternak, K., Kocot, J., & Horecka, A. (2010). Biochemistry of magnesium. Journal of elementology, 15(3), 601-616. https://www.researchgate.net/profile/Joanna-Kocot-2/publication/273127001_Biochemistry_of_magnesium/links/579c616708ae80bf6ea46101/Biochemistry-of-magnesium.pdf

Schwalfenberg, G.K. & Genuis, S.J. (2017). The importance of magnesium in clinical healthcare. Scientifica, 2017. https://doi.org/10.1155/2017/4179326