Magnesium the forgotten cation:

By Dr. M. Kyu Chung

Magnesium is a mineral/electrolyte that is often ignored and forgotten by many physicians. Even the comprehensive metabolic profile (CMP) that is part of the routine blood analysis does not include this electrolyte in its analysis. In sharing some examples from my clinical experience, I hope to demonstrate how simple supplementation with magnesium can make a positive impact in a variety of symptoms and conditions.

Low magnesium contributing to cardiovascular conditions:

Low magnesium and intractable angina:

45-year-old female presented to our office complaining of frequent chest pain from intractable frequent angina. She was referred to our center by her cardiologist because she was not responding to medication management. Recently she had been mistakenly diagnosed with severe triple vessel coronary artery stenosis and given a triple coronary bypass. Shortly after surgery, she continued to have the same multiple episodes of angina and a repeat catheterization revealed that her original coronary vessels were completely normal and the bypass graft had all occluded (presumably because the original native vessels were open and shunted the blood flow away from the graft, resulting in poor flow, collapse, and occlusion of the graft vessels).  The cardiologist to their chagrin realized retroactively that the original findings of stenosis were a result of the vessels being narrowed by spasm of the vessel and not due to actual coronary artery hardening and stenosis. On the very first visit, she had been using nitroglycerin SL often and was poorly responsive to medical therapy. Autonomic Response Testing (A.R.T.) revealed that her magnesium level was very low, and a red cell magnesium level was drawn which supported the diagnosis. All her chest pains disappeared after administering and replenishing her magnesium.

Low magnesium and atrial fibrillation:

60-year-old male with a history of paroxysmal atrial fibrillation presented to our office. He was being evaluated by a cardiologist and cardiac ablation was going to be scheduled. A.R.T. revealed low magnesium. His episodes of atrial fibrillation subsided with magnesium supplementation and his ablation was canceled. [1],[2]

Low magnesium and poorly controlled blood pressure:

I have had cases of patients whose primary care doctor wanted to keep adding more anti-hypertensives those patients labeled “labile HTN”. Their fluctuating high blood pressures resolved immediately with intravenous magnesium followed by aggressive oral supplementation. They then remained stable on a lesser dose and/or on a lower number of HTN medications. I have used intravenous magnesium in many patients who present with acutely high blood pressure, and nearly all respond quite nicely by a normalization or reduction of their blood pressure.

Two factors may explain why low magnesium might contribute to heart attacks and strokes. In basic science studies, magnesium is known to cause relaxation of the smooth muscles that surround the arteries, and low magnesium can cause spasm and constriction of the smooth muscles that surround the arteries. (I have used magnesium successfully in many patients who suffer from frequent muscle cramps). Also, magnesium has been shown to reduce the tendency for the blood to clot by reducing excess platelet activation.[3] Many strokes and heart attacks are a result of acute constriction and clotting of the arteries to the heart and brain.

Low magnesium contributing to infertility:

35-year-old female with a history of 4 miscarriages near the end of her first trimester undergoing conventional infertility treatment. She was in process of IVF with six embryos waiting for transplantation and complaining of severe anxiety and feeling “stressed out”.  On her first visit she appeared extremely anxious and A.R.T revealed severe Magnesium deficiency along with Vitamin D and Iodine deficiency. She was given IV Magnesium Sulfate, oral mg glycinate, Vitamin D and Iodine supplementation and instruction to do Epsom salt baths 3/week for two weeks. Follow-up one month later revealed a much calmer patient who noted marked improvement in energy and sleep. Follow-up two months later, she became pregnant “naturally” without IVF. She then carried the pregnancy to full term and delivered a healthy son. Zarean et al in a randomized trial with magnesium showed a significant reduction in pregnancy complications.[4] Currently magnesium supplementation for pregnancy is through prenatal vitamins alone. From my experience, this is inadequate.

Low magnesium and severe anxiety and depression:

50-year cardiologist was brought to us by his wife. He had a history of worsening anxiety and depression, now failing three different anti-depressants, and beginning to miss work several days at a time. A.R.T. revealed an exceptionally low magnesium level. He was given Magnesium Sulfate intravenously slow push two days in a row. His depression improved markedly in those two days, and he was able to return to work. He continued to do very well on oral supplementation until one year later when he started to have a recurrence of his depression. A.R.T again revealed low magnesium, and the patient admitted that he became inconsistent with his magnesium supplements. He recovered after only one IV dose of magnesium, and Epsom salt baths and has continued to be well for the past year with consistent oral magnesium supplementation.

Apparently, we are not the only ones advocating I.V. magnesium for depression.[5] In the past, I would have given anxiolytics/anti-depressant medications to these same patients who experience depression and anxiety with panic attacks, poor sleep, and feelings of chronic stress. Now I have been able to help resolve a significant number of these individuals with simple magnesium supplementation along with other non-drug therapies. Moabedi et al reported a systematic review of seven clinical trials with a total sample size of 325 individuals with ages ranging from 20 to 60 years on average. Their meta-analysis showed a significant decline in depression scores due to intervention with magnesium supplements.[6]

A few additional diagnoses that may benefit from magnesium supplementation:

• Low magnesium in diabetes:

Pooled analyses of 24 randomized controlled trials with 1,325 Type 2 diabetic individuals revealed that subjects who received magnesium supplementation had statistically significant reductions in fasting plasma glucose, glycated hemoglobin (HgbA1C), systolic blood pressure and diastolic blood pressure, with WMD values of –0.20 mM (95% CI: –0.30, –0.09), –0.22% (95% CI: –0.41, –0.03), –7.69 mmHg (95% CI: –11.71, –3.66) and –2.71 mmHg (95% CI: –4.02, –1.40), respectively.[7] Yet another reason why studies show a correlation of lower all-cause mortality in individuals with higher magnesium intake.[8]

• Low magnesium in osteoporosis:

Low serum magnesium has been demonstrated to be associated with low bone density in pre- and postmenopausal women[9],[10] and magnesium intake is found to be positively correlated with a greater bone mineral density in both men and women.[11] Furthermore, magnesium supplements have been shown to improve Bone Mineral Density (BMD) in osteoporotic women. [12],[13]

• Low magnesium in asthma:

I have seen magnesium relieve acute asthma on numerous occasions. Intravenous magnesium is being increasingly recognized as a useful treatment in E.R.s for the treatment of acute severe asthma. [14] Unfortunately, this is not usually carried over to the outpatient setting as a regular preventive treatment of asthma. There are very few if any studies using magnesium to prevent asthma attacks. Clinically, through A.R.T., we routinely find low magnesium in patients with poorly controlled asthma and have found magnesium supplementation extremely important in the prevention of asthma attacks and in reducing the need for chronic asthma medications.

• Magnesium and pre-eclampsia/eclampsia:

A nationally recognized female runner recently died of a pregnancy complication called “Eclampsia”.  This condition often is treated with high dose intravenous magnesium when a pregnant patient shows severe signs which include marked elevated blood pressure called “pre-eclampsia. A recent meta-analysis concludes that intravenous magnesium sulfate for treatment of preeclampsia can reduce the risk of eclampsia by 50% [15].

• Magnesium in immunity:

Low Magnesium has been shown to adversely affect the immune system and increase inflammatory markers. [16],[17] Most chronic illnesses are associated with an increase in inflammation. [18]

• Magnesium and Cancer:

Magnesium has multiple roles in supporting normal immunity. Numerous studies show low magnesium intake correlating with higher risk of various cancers (liver, pancreatic, lung, colorectal, breast), and greater inflammatory conditions. [19]

Discussion:

Magnesium has multiple beneficial effects on over 600 different enzymes in the body. It is used in over 300 different enzyme catalytic actions. [20]It is an essential nutrient in every system of the body.

Reffemann et al. showed that subjects with a  lower Mg (++) ≤0.73 mmol/l level were at significantly higher risk for all-cause deaths (10.95 death per 1000 person years), and higher risk of cardiovascular deaths (3.44 deaths per 1000 person years) in comparison to subjects with higher Mg (++) concentrations (1.45 deaths from all-cause per 1000 person years, 1.53 deaths from cardiovascular cause per 1000 person. That is to say that the individuals with the highest magnesium levels had 1.45/10.95=0.13 times less deaths; a whopping 87% reduction in overall deaths.  They had 1.53/3.44 = .44 less cardiovascular deaths.  [21] Unfortunately, these are correlational studies and not randomized controlled studies. If a drug came out that could produce these kinds of statistics, it would be hailed as a miracle drug and considered to become a multibillion-dollar drug.

Why is magnesium underappreciated by doctors?

Magnesium is an intracellular cation. It is stored inside the cells. Only 0.3% of magnesium is found in the blood. When intake becomes suboptimal, the body pulls magnesium out of the cells into the bloodstream to restore blood levels. Hence serum magnesium levels are often within normal limits even in the face of depleted body magnesium and are a poor reflection of actual body levels of magnesium. Doctors are often unaware of this fact and order serum levels and are content when they come back within normal limits. Red cell magnesium levels previously were thought to be better than serum magnesium levels as a reflection of the overall body levels. Unfortunately, even red cell magnesium levels can underestimate magnesium deficiency. Without a reliable way for average doctors to assess magnesium levels by laboratory methods, doctors rarely diagnose this deficiency.

On numerous occasions we have seen patients with normal serum levels of magnesium test positive for low levels using A.R.T. These patients had dramatic improvement in their symptoms when given magnesium.

Low magnesium in our diet.

In the United States, it is estimated that the prevalence of inadequate magnesium intake for adults is about 64% among males and 67% among females; among individuals aged more than 71 years, the figure rises to 81% and 82% for males and females, respectively. [22]   

Magnesium is generally found in the following foods: whole grains, nuts, leafy vegetables.  Even those who seem to have adequate amounts of vegetables can sometimes have low body levels of magnesium because commercial farming methods are thought to deplete the soil of important minerals including magnesium. It is estimated that as much as 50% of Americans have an inadequate magnesium intake.

Most studies related to magnesium are correlational studies and given that blood tests are a poor indicator of magnesium status, most average physicians do not proactively supplement their patients. We have found that Autonomic Response Testing can be considerably useful in helping to decide when to supplement. Until better laboratory tests are available, the clinician must decide clinically when it is appropriate to supplement a patient.

In conclusion:

Clinically we find magnesium supplementation is needed for more than 50% of new patients when assessing with A.R.T. Given the marked safety of giving a few hundred milligrams of magnesium, it may be worthwhile to give an empiric trial of magnesium in patients who have the following conditions: hypertension, anxiety, insomnia, depression, heart disease, atrial fibrillation, asthma, unstable angina, infertility, excess inflammation.

[1] Miller S, Crystal E, Garfinkle M, Lau C, Lashevsky I, Connolly S J. Effects of magnesium on atrial fibrillation after cardiac surgery: a meta-analysis. Heart. 2005 May;91 (5):618–23.

[2] Piotrowski Alexandria A, Kalus James S. Magnesium for the treatment and prevention of atrial tachyarrhythmias. Pharmacotherapy. 2004 Jul;24 (7):879–95.

[3] Ravn H. Et al. Magnesium inhibits platelet activity–an infusion study in healthy volunteers. Thromb Haemost 1996 Jun;75(6):939-44.

[4] Zarean, E, Tarjan, A. Effect of Magnesium Supplement on Pregnancy Outcomes: A Randomized Control Trial, Adv Biomed Res, 2017 Aug 31:6:109.

[5] Eby, G, Eby, K. Rapid recovery from major depression using magnesium treatment. Med Hypotheses, 2006;67(2):362-70

[6] Moabedi, M; Aliakbari, M; Magnesium supplementation beneficially affects depression in adults with depressive disorder: a systematic review and meta-analysis of randomized clinical trials.

[7] Xu, L, Li, X, Wang, X, Xu, M. Effects of magnesium supplementation on improving hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes: A pooled analysis of 24 randomized controlled trials. Front Nutr. 2022; 9: 1020327.

[8] Reffelmann, T, et al; Low serum magnesium concentrations predict cardiovascular and all-cause mortality, Atherosclerosis, 2011 Nov;219(1):280-4.

[9] . Castiglioni S., Cazzaniga A., Albisetti W., Maier J. A. Magnesium and osteoporosis: current state of knowledge and future research directions. Nutrients. 2013;5(8):3022–3033. doi: 10.3390/nu5083022.

[10]  Saito N., Tabata N., Saito S., et al. Bone mineral density, serum albumin and serum magnesium. Journal of the American College of Nutrition. 2004;23(6):701S–703S. doi: 10.1080/07315724.2004.10719412.

[11]  Tucker K. L., Hannan M. T., Chen H., Cupples L. A., Wilson P. W. F., Kiel D. P. Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. The American Journal of Clinical Nutrition.

[12] Tranquilli A. L., Lucino E., Garzetti G. G., Romanini C. Calcium, phosphorus, and magnesium intakes correlate with bone mineral content in postmenopausal women. Gynecological Endocrinology. 1994;8(1):55–58. doi: 10.3109/09513599409028459.

[13] Orchard T. S., Larson J. C., Alghothani N., et al. Magnesium intake, bone mineral density, and fractures: results from the Women’s Health Initiative Observational Study. The American Journal of Clinical Nutrition. 2014;99(4):926–933.

[14] Kew K. M., Kirtchuk L., Michell C. I. Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department. Cochrane Database of Systematic Reviews. 2014

[15] McDonald S. D., Lutsiv O., Dzaja N., Duley L. A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use. International Journal of Gynecology & Obstetrics. 2012;118(2):90–96. doi: 10.1016/j.ijgo.2012.01.028. 

[16] Weglicki WB, Phillips TM, Freedman AM, Cassidy MM, Dickens BF. Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin. Mol Cell Biochem. 1992;110(2):169–173.

[17]  Chacko SA, Song Y, Nathan L, Tinker L, de Boer IH, Tylavsky F, et al. Relations of dietary magnesium intake to biomarkers of inflammation and endothelial dysfunction in an ethnically diverse cohort of postmenopausal women. Diabetes Care. 2010;33(2):304–310. doi: 10.2337/dc09-1402.

[18] Katsanos AH, Kyriakidi K, Karassa FB, Politis D, Skamnelos A, Christodoulou DK, Katsanos KH. Biomarker Development in Chronic Inflammatory Diseases. Biomarkers for Endometriosis. 2017 Sep 23:41–75. doi: 10.1007/978-3-319-59856-7_3. PMCID: PMC7122305.

[19] Ashique, S. Et al, A narrative review on the role of magnesium in immune regulation, inflammation, infectious diseases, and cancer, J Health Popul Nutr. 2023 Jul 27;42(1):74. doi: 10.1186/s41043-023-00423-0.

[20] Fiorentini D, Cappadone C, Farruggia G, Prata C. Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency. Nutrients. 2021 Mar 30;13(4):1136. doi: 10.3390/nu13041136. PMID: 33808247; PMCID: PMC8065437.

[21] Reffelmann, T, et al; Low serum magnesium concentrations predict cardiovascular and all-cause mortality, Atherosclerosis, 2011 Nov;219(1):280-4.

[22] Moshfegh A, Goldman J, Cleveland L (2005) What we eat in America, NHANES 2001–2002: Usual nutrient intakes from food compared to Dietary Reference Intakes: US Department of Agriculture, Agricultural Research Service. pp. 1–56.