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Mastering Magnesium

Mastering Magnesium

Magnesium is the fourth most abundant mineral and is essential for good health. Approximately 600 enzymes depend upon its presence in our body in sufficient amounts.1 It affects many cellular functions including the transport of potassium and calcium ions. It modulates signal transduction, energy metabolism and cell proliferation. Magnesium has a huge role in bone mineralization, cardiovascular health and the nervous and neuromuscular systems. It participates in the metabolism of carbohydrates, fats and protein and even plays an important role in immune system function.

About 99% of total body magnesium is located in bone, muscle and non-muscular soft tissue. Of this approximately 50-60% resides on the surface of the bone as a part of hydroxyapatite.2 The remainder is contained in skeletal muscle and soft tissue with just 0.3% of total body magnesium found in serum.3

Magnesium deficiency is not uncommon among the general population. Its intake has decreased over time due to the loss of magnesium during food refining and the change in modern dietary habits. Plant foods are the source of most magnesium intake, especially cereal grains, green vegetables, nuts and pulses. Grains supply the vast majority of dietary magnesium, however in 2011 it was discovered that processing reduces dietary magnesium by 62%.4 The standard diet in the US contains about 50% of the recommended daily allowance and as much as three quarters of the population is estimated to be consuming a magnesium deficient diet.4

Magnesium and Bone Mineralization

Magnesium is one of the main components of bone and is often prescribed for bone growth and regeneration. However it has a complicated connection with osteogenesis. As bone mineralizes there is a complex chemical reaction among calcium phosphate, magnesium and some amino acids which is not well defined yet.5

An appropriate regulation of magnesium is vital for normal bone mineralization. During embryonic development magnesium concentrations increase in the early stages but gradually decrease to a stable state in the late phase. While excessive magnesium can inhibit the crystallization of calcium phosphate, the presence of adequate amounts of magnesium is vital for healthy bone development.5 Magnesium and Calcium are both synergists and antagonists and a balance between these minerals is crucial since increased intake or retention of either one can induce a deficiency in the other.6

Magnesium, Energy and our Body Clock

Circadian clocks are fundamental to our biology by coordinating our behavior and physiology to harmonize with the cycle of day and night. Magnesium is one of the factors that is crucial for cellular circadian timekeeping.7 With magnesium’s essential role as a cofactor for ATP, it has been shown to provide the body with the capacity to progressively tune ATP consumption and metabolic rate to the correct time of day so as not to impact the size of the ATP pool.8 It is able to harmonize our cellular biochemistry and energy consumption throughout the daily cycle to anticipate differing metabolic demands placed on the body.7

Magnesium and the Immune System

Historically, the importance of micronutrients on the immune system and infection was based on vitamin C and several other nutrients. Magnesium isn’t an obvious choice when thinking of immune function, nonetheless it plays an important role. Magnesium is a second messenger in T-Cell activation and contributes to natural killer cell activity. It is a factor in CD8 cells which induce apoptosis and are crucial for responses against intracellular viruses and bacteria.

In people with rare hereditary diseases, such as MAGT1 defects, that cause abnormally low magnesium concentrations, there is an association with the development of recurrent infections including Epstein Barr virus. In fact one study concluded that a higher serum concentration of magnesium has been shown to lower the risk of serious infections during the first year after a kidney transplant.

Magnesium’s importance in immune health can be seen from research into defects in Magnesium transporter 1 (MAGT1) which critically mediates magnesium homeostasis. When MAGT1 is not functional it leads to selective deficiency in both immune and non-immune glycoproteins as well as several critical glycosylation defects in important immune-response proteins. Genes involved in immunity such as CD28, which provide stimulatory signals required for T-Cell activation and survival, cannot be expressed without magnesium.9

Magnesium and the Nervous System

Magnesium is necessary for sufficient brain energy. It aids smooth transmission of communications through the central nervous system and is an important component in the making of serotonin. Its presence is vital for a peaceful nervous system.

 A deficiency of magnesium can give rise to a variety of symptoms. Reduction in cognitive ability and processes, reduced attention span, increased aggression, fatigue and lack of concentration are typical in magnesium deficiency. Other common symptoms include becoming easily irritated, nervousness, fatigue and mood swings.

Glutamate is a powerful excitatory neurotransmitter released by the nerve cells in the brain. It is responsible for sending signals between nerve cells and under normal circumstances plays an important role in learning and memory. Magnesium supports the functioning of N-methyl-D-aspartate (NMDA) receptors which prevents the excitotoxic effect of glutamate. Magnesium participates in the activation of central regulatory mechanisms to control the mediators involved in the stress response.10

Magnesium and Cardiovascular Health

 Cardiovascular disease has been the leading cause of death globally for over 15 years. There is growing evidence to suggest that mild to moderate magnesium deficiency might increase the risk for abnormal cardiac excitation, atherosclerosis, ischemic heart disease and congestive heart failure. Severe magnesium deficiency can cause an increased risk of sudden cardiac death.

Magnesium is important for cellular energy generation. All adenosine triphosphate (ATP) dependent reactions require the presence of magnesium to hydrolyze and transfer phosphate groups. It plays a key role in the regulation of ion channels.  It is through this metabolic pathway that magnesium exerts an effect on cardiac conduction and contraction. Magnesium modulates potassium and calcium channels and sodium-potassium ATPase pumps.

Low magnesium may also increase prothrombotic and proatherogenic states. Higher magnesium has been reported to inhibit both platelet adhesion and aggregation. Magnesium also interferes with the process of vascular calcification by increasing the expression of calcification inhibitors and decreasing the expression of calcification promotors.11

Magnesium and Insulin Regulation

Magnesium is required for insulin signaling and action. A recent analysis observed that high dietary magnesium intake was associated with a 15% lower risk of type 2 diabetes, compared with a lower intake. The most favorable outcome belonging to the group with the highest intake of magnesium and the highest carbohydrate quality diet.12 

Magnesium Absorption

The primary sites of magnesium absorption are the jejunum and ileum. When dietary intake of magnesium is high, absorption is low, however when intake is low, absorption is high.13

Low digestible carbohydrates and oligosaccharides enhance magnesium absorption. Organic acids produced by the catabolism of fermentable low digestive carbohydrates in the transverse, descending and sigmoid colon are a major factor in enhancing magnesium absorption.14 The addition of vitamin B6 improves magnesium absorption as well as its transportation and intracellular storage.15

Measuring Magnesium

An assessment of adequacy or deficiency is very important. In spite of the fact that there are several methods for the measurement of magnesium (ie. blood, plasma/serum, erythrocytes, cerebrospinal fluid, saliva and urine), none of them is regarded as satisfactory.15 Serum magnesium concentration does not reflect the total amount of body magnesium content, since only 0.3% of total body magnesium is found in serum.3

One of the best ways to measure tissue levels of magnesium is through Hair Tissue Mineral Analysis (HTMA). The use of hair has advantages over the testing of other body tissues. For instance, serum concentrations may fluctuate with the time of day or foods eaten prior to testing. Serum magnesium can even fluctuate depending on the drawing technique. The longer the tourniquet is applied, the higher the magnesium rises as a result of tissue hypoxia.

InterClinical Comment

HTMA offers the opportunity to assess magnesium status together with symptomatic conditions. HTMA provides significant additional information, since it exposes the relative relationships of magnesium to other minerals.  An examination of these ratios can be important and tell us more than obtaining the elemental mineral status alone. For example, determining the relationship between calcium and magnesium may reveal the reason behind many health issues such as anxiety, insomnia and more.

References

1 Van Ooijen, G., & O’Neill, J. S. (2016). Intracellular magnesium and the rhythms of life. Cell Cycle, 15(22), 2997–2998. doi:10.1080/15384101.2016.1214030 
2 Elkady, G. A., GabAllah, R. R., Mansour, A. Z. (2017) Magnesium in Intensive Care Unit: A Review. The Egyptian Journal of Hospital Medicine, 68(3), 1497-1504 doi: 10.12816/0039695
3 Uwitonze A, M., Razzaque, M. S. (2018) Role of Magnesium in Vitamin E Activation and Function. The Journal of the American Osteopathic Association, 118(3). doi:10.7556/jaoa.2018.037
4 Rosanoff, A., Kumssa, D.B. (2020) Impact of rising body weight and cereal grain food processing on human magnesium nutrition, Plant Soil. doi.org/10.1007/s11104-020-04483-7
5 Zhang, J., Tang, L., Qi, H., Zhao, Q., Liu, Y., & Zhang, Y. (2019). Dual Function of Magnesium in Bone Biomineralization. Advanced Healthcare Materials, 1901030. doi:10.1002/adhm.201901030 
6 Watts D. Trace Elements and Other Essential Nutrients. 5th ed. Addison, Texas: Writer’s B-L-O-C-K; 1995.
7 Feeney, K. A., Hansen, L. L., Putker, M., Olivares-Yañez, C., Day, J., Eades, L. J., van Ooijen, G. (2016). Daily magnesium fluxes regulate cellular timekeeping and energy balance. Nature, 532(7599), 375–379. doi:10.1038/nature17407 
8 Van Laecke, S., Vermeiren, P., Nagler, E. V., Caluwe, R., De Wilde, M., Van der Vennet, M., Van Biesen, W. (2016). Magnesium and infection risk after kidney transplantation: An observational cohort study. Journal of Infection, 73(1), 8–17. doi:10.1016/j.jinf.2016.04.007 
9 Matsuda-Lennikov, M., et al. (2019) Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune response genes. The Journal of Biological Chemistry, 294, 13638-13656. doi:10.1074/jbc.RA119.008903
10 Antonenko, S. A. (2019) Influence of Magnesium on excitability of neurons of different levels of their organization. Journal of Education Health and Sport. 9(11):314-322. doi:org/10.12775/JEHS.2019.09.11.029
11 Tangvoraphonkchai, K., & Davenport, A. (2018). Magnesium and Cardiovascular Disease. Advances in Chronic Kidney Disease, 25(3), 251–260. doi:10.1053/j.ackd.2018.02.010 
12 Hruby, A., Guasch-Ferré, M., Bhupathiraju, S. N., Manson, J. E., Willett, W. C., McKeown, N. M., & Hu, F. B. (2017). Magnesium Intake, Quality of Carbohydrates, and Risk of Type 2 Diabetes: Results From Three U.S. Cohorts. Diabetes Care, 40(12), 1695–1702. doi:10.2337/dc17-1143 
13 Nielsen, F. H. (2017). Magnesium. Molecular, Genetic, and Nutritional Aspects of Major and Trace Minerals, 307–317. doi:10.1016/b978-0-12-802168-2.00025-7 
14 Vakil, N. (2018). Dietary Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAPs) and Gastrointestinal Disease. Nutrition in Clinical Practice, 33(4), 468–475. doi:10.1002/ncp.10108 
15 Serefko, A., Szopa, A., Wlaź, P., Nowak, G., Radziwoń-Zaleska, M., Skalski, M., & Poleszak, E. (2013). Magnesium in depression. Pharmacological Reports, 65(3), 547–554. doi:10.1016/s1734-1140(13)71032-6 

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