FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, November 9, 2017

MAGNESIUM

by Carolyn Dean, MD, ND

(OMNS Nov 9, 2017) Even though I've spent the last 20 years focused on one mineral, magnesium, it's made me a generalist, not a specialist, because magnesium does so much for the body. Most people are deficient in magnesium. So I've listed below the top 10 facts and 12 functions associated with magnesium. There are several contraindications to magnesium therapy, but most often withholding it is unwise. Moreover, in magnesium-deficient individuals, high dose vitamin D can cause their magnesium levels to be further depleted. The large number of magnesium deficiency diseases (more than 60) makes it difficult for doctors to diagnose their true cause .[1]

Sixty-five conditions associated with magnesium deficiency

According to the FDA, I am not permitted to say that magnesium can treat diseases. Doing so pushes magnesium into the drug category because the FDA (a non-medical body) says that only drugs can treat disease. However, I contend that magnesium deficiency is constantly being misdiagnosed as many different diseases, so I am merely suggesting that people treat their magnesium deficiency. Using high doses of magnesium (600-1200 mg elemental magnesium per day) for migraines, high blood pressure, angina, diabetes, high cholesterol, muscle cramps and spasms, nerve tingling and burning, is far less invasive than immediately prescribing drugs. I've observed thousands of people using therapeutic doses of a non-laxative form of magnesium with tremendous success.

Why do doctors know so little about magnesium deficiency and mistake it for many other diseases?

1. Magnesium deficiency is massively pervasive, affecting 70-80% of the population.
2. In medical school we learned nothing about essential nutrients, even though every biochemical reaction in the body is facilitated by mineral and vitamin cofactors.
3. Many agricultural lands are quite depleted of magnesium, and it's a rare farmer who replaces magnesium and other minerals using rock dust.
4. The serum magnesium blood test is an inaccurate measure of magnesium in the body, which is why magnesium is not even on a standard electrolyte panel. In a review paper, Long and Romani wanted to "advocate for the necessity of identifying easy and reproducible methods to assess serum and cellular magnesium levels and to identify magnesium deficiency in order to alleviate related pathological conditions." They acknowledged that serum magnesium is a "poor predictor of tissue magnesium content and availability."[2]

The top 10 magnesium facts

1. Magnesium is necessary for the proper functioning of 700-800 enzyme systems in the body - that's why it is implicated in scores of symptoms and 65 health conditions.
2. Most people in the USA, 70-80 percent, are magnesium deficient.
3. Excess calcium in the diet depletes magnesium in the body, and many people take too much calcium, either as supplements, in fortified foods or dairy products.
4. Magnesium is often very deficient in the soil and in the food supply, especially in "modern" processed foods, so it must be supplemented.
5. Many forms of magnesium supplements cause a laxative effect, which prevents them from being taken in a therapeutic dose to relieve magnesium deficiency and its symptoms. However it is possible to use liquid magnesium chloride, a non-laxative form of magnesium that can be taken in therapeutic dosages.
6. Magnesium deficiency can cause mitochondrial dysfunction. ATP (adenosine triphosphate) energy molecules are made in the mitochondria via the Krebs cycle. Six of the 8 steps in that cycle depend on adequate levels of magnesium.
7. To help you identify magnesium needs, I've listed "100 Factors Related to Magnesium Deficiency." [3]
8. The Serum Magnesium test is inaccurate, but is still the standard test used in hospitals, clinics and in most clinical trials, and it doesn't even appear on a standard electrolyte panel. A helpful and more accurate test, Magnesium RBC, must be used in conjunction with your clinical symptoms. But the definitive Ionized Magnesium Blood Test is not available to the public.
9. Magnesium deficiency is a major factor in chronic disease - diabetes, heart disease, high blood pressure, high cholesterol, migraines, IBS, and heartburn. Moreover, the drugs used to treat all these conditions deplete magnesium, often making symptoms worse. Yet the FDA tells me that if I say magnesium can help treat these magnesium deficiency conditions, that makes magnesium a drug that has to undergo expensive drug testing!
10. Telomeres (the DNA sequence at the ends of the chromosomes) hold the key to aging, as does magnesium, which prevents telomeres from deteriorating.

The 12 functions of magnesium

Getting more technical, here are twelve crucial functions of magnesium that appear in a textbook on magnesium in a chapter called "Divalent Cation Metabolism: Magnesium." [4,5] There will be some overlap with the Top Ten Magnesium Facts that help to explain the amazing features of this mineral.

1. Energy: The most important function of magnesium is assisting in the creation of energy in the trillions of cells making up our body. Magnesium is a cofactor in the production of ATP (adenosine triphosphate) via ATP synthase. ATP, the molecule that transfers energy, is manufactured in the mitochondria and it must be bound to a magnesium ion (MgATP) in order to be biologically active. Each human cell contains 1,000-2,000 mitochondria. ATP is made in each one through a series of 8 steps called the Krebs cycle. What's remarkable about magnesium is that it is necessary for 6 of those 8 steps. In this cycle, magnesium is a modulator of oxidative phosphorylation during which electrons are transferred from electron donors to electron acceptors such as oxygen in redox reactions, using magnesium as a cofactor. These redox reactions, called electron transport chains, form a series of protein complexes within the cell's mitochondria that release energy by generating ATP.
2. Transporters and Pumps: ATP has many other functions besides being a source of energy. ATP is required by many transporters ("transmembrane ATPases") that import molecules necessary for cell metabolism and export toxins and wastes across cell membranes. A hydrogen-potassium ATPase creates the gastric proton pump, which acidifies the contents of the stomach. Many other pumps and transporters are directed by ATPases with magnesium as a necessary cofactor.
3. Membrane Stabilizer: Magnesium is an important membrane-stabilizing agent. Stabilization decreases excessive excitation of nerves and contraction of muscle cell membranes.
4. Protein Production: Magnesium is required for the structural integrity of numerous body proteins. To date, over 3,700 magnesium receptor sites have been found on human proteins!
5. RNA & DNA: Magnesium is required for the structural integrity of nucleic acids. Consequently, magnesium is a requirement for the production of RNA and DNA.
6. GTP: Magnesium is a cofactor for the enzyme guanosine triphosphatase (GTPase). This enzyme has many functions: (a) signal transduction, or "switching on" specific receptor proteins located on cell membranes and transmitting that signal to trigger taste, smell, and perception of light; (b) protein biosynthesis; (c) control and differentiation of cell division; (d) translocation of proteins through cell membranes; and (e) transport of vesicles within the cell and assembly of vesicle coats.
7. Phospholipase C: Magnesium is a cofactor for the enzyme phospholipase C, which is a class of enzymes that split phospholipids at the phosphate group. These enzymes define signal transduction pathways. The most important one allows calcium to enter cells.
8. Adenylate and Guanylate cyclase: Magnesium is a cofactor for the enzyme adenylate cyclase. This enzyme converts ATP to cyclic AMP (cAMP) and pyrophosphate. Cyclic AMP is used for intracellular signal transduction of the effects of hormones like glucagon and adrenaline into cells because the hormones can't pass through cell membranes. Cyclic AMP is involved in the activation of protein kinases and regulates the effects of adrenaline and glucagon. It also binds to and regulates the function of ion channels or gateways into the cell.
   
   Magnesium is also a cofactor for the enzyme guanylate cyclase. This enzyme synthesizes cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP) keeping cGMP-gated ion channels open, allowing calcium to enter the cell. Cyclic GMP is an important second messenger that transmits the message across cell membranes from peptide hormones and nitric oxide, and it can also function in hormone signaling. It can trigger changes requiring protein synthesis. In smooth muscle, cGMP is the signal for relaxation, which can regulate vascular and airway tone, insulin secretion, and peristalsis.
9. 700-800 Enzyme Processes: Magnesium is a required cofactor for the activity of hundreds of enzyme processes. The authors of "Magnesium in Man: Implications for Health and Disease" assure us that the number of magnesium enzymatic reactions is more than 600.[6] Andrea Rosanoff, PhD, says, "While it was estimated in 1968 that magnesium was a required cofactor for over 300 enzyme processes, that number is now more reliably estimated at 700 to 800." [7]
10. Regulates Ion Channels: Magnesium is a direct regulator of ion channels, most notably via the other key electrolytes potassium, calcium and sodium. Magnesium is intimately involved in potassium transport. Magnesium and potassium depletion cause similar damaging effects on the heart. Furthermore, it is impossible to overcome potassium deficiency without replacing magnesium. That's why hospitals often seem to have such a difficult time finding the right electrolyte balance of sodium, potassium, calcium, and chloride: they ignore magnesium and do not routinely measure it in their electrolyte panels and when they do test for it, they use the inaccurate serum magnesium test.
    
    Magnesium is intimately involved with calcium channels. I have written about magnesium guarding the ion channels that allow calcium to enter and leave the cell, orchestrating the exact amount of calcium that's required to cause a muscle or nerve cell to contract and then flushing that extra calcium out to prevent excessive contraction.[1] Thus, magnesium is a natural calcium channel blocker. But instead of using magnesium to modify the effect of calcium on body physiology, medical practice often insists on using calcium-channel-blocking drugs that have many side effects . . . including magnesium deficiency.
11. Intracellular Signaling: Magnesium is an important intracellular signaling molecule itself. While I've mentioned signaling several times; the role of cell signaling cannot be underestimated. Without intracellular communication the cells of the body would not be able to function at all.
12. Nerve and Muscle Function: Magnesium is intimately involved in efficient nerve conduction. Although calcium is vital for proper nervous system function, too much calcium is dangerous. Excess calcium is pro-inflammatory and can excite nerves to the point of cell death. Magnesium helps cells to regulate calcium levels. Magnesium is intimately involved in efficient muscle function. The mechanisms are varied and include oxygen uptake, electrolyte balance, and energy production. Magnesium is important for properly functioning muscles, allowing calcium to cause muscle contraction and then pushing calcium out of the muscle cells to allow the relaxation phase.[8] In the same way that nerve cells can be "excited to death," muscle cells stimulated by too much calcium can go into uncontrollable spasms or cramps, resulting in tissue damage such as occurs in a heart attack.

How to get therapeutic amounts of magnesium without the laxative effect

1. Avoid the highly laxative magnesium oxide. It's only 4 % absorbed; the rest attracts water and is eliminated via the bowel.

2. Apply transdermal magnesium lotion and/or take Epsom salts baths -- as often as needed, or every few days.

3. Mix liquid magnesium chloride or magnesium citrate powder in your drinking water or juice and sip throughout the day. The taste will be strong but you can add flavored stevia or a natural sweetener.

4. Take 1 tablespoon of psyllium seed powder in 8 oz of water once or twice a day (1 hour away from meals or supplements) to bulk up the stool and prevent diarrhea.

Contraindications to magnesium therapy

1. Kidney failure. With kidney failure there is an inability to clear magnesium from the kidneys.
2. Myasthenia gravis. Intravenous administration could accentuate muscle relaxation and collapse the respiratory muscles.
3. Excessively slow heart rate. Slow heart rates can be made even slower, as magnesium relaxes the heart. Slow heart rates may require an artificial pacemaker.
4. Bowel obstruction. A major route of elimination for unabsorbed oral magnesium is through the bowel. Someone with bowel obstruction should be hospitalized.

Magnesium is required to convert vitamin D to its active form

Vitamin D is the new popular supplement but it's being prescribed in huge doses. What is not widely known is that vitamin D requires magnesium in order to be transformed into its active form. Further, very high levels of vitamin D can deplete magnesium levels. The relationship between vitamin D and magnesium is crucial and has been ignored by many doctors.[9] It is important to make sure you are taking enough magnesium before supplementing with vitamin D. You can do that by following your magnesium RBC levels and targeting an optimum of 6.0-6.5 mg/dL.

Vitamin D is converted to 25-hydoxyvitamin D in the liver and 1,25(OH)2D in the kidneys and other organs as needed. The 1,25(OH)2D metabolite of vitamin D is actually a hormone required by many sites throughout the body. The average range for 25-hydroxy vitamin D (25(OH)D) is from 10.0 to 40.0 ng/mL, but with supplements the levels can range to 70 ng/mL or higher. However, optimum levels of vitamin D are more toward 40 ng/mL, not the high end. The average levels of 25-hydroxyvitamin D vary with skin color because dark skin attenuates formation of vitamin D. At higher latitudes, light skin has evolved to collect meager UVB light rays in order to generate some vitamin D.[10] In the USA, the average level for African Americans is near 16 ng/mL, Hispanics near 21 ng/ml, and whites near 26 ng/mL. Therefore, most people can benefit by taking vitamin D supplements along with magnesium supplements.

The paper "Magnesium, Vitamin D Status and Mortality" in BMC Medicine displays a detailed flow chart of vitamin D metabolism, which shows that magnesium is required in 8 crucial steps.[11] This is vital information for every doctor prescribing vitamin D and every person taking vitamin D. The investigators said, "Our preliminary findings indicate it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status. The associations between serum 25(OH)D and risk of mortality may be modified by the intake level of magnesium."

It will be obvious from the above that I consider magnesium one of the most important essential nutrients in the body and it should be included in every health treatment protocol. Yet it is often the most deficient and neglected mineral. I urge everyone to read more about magnesium and reconsider your intake of this miraculous mineral.

(Carolyn Dean, MD, ND has been a member of the editorial board of the Orthomolecular Medicine News Service since its third issue in 2005. She offers voluntary disclosure that she has a commercial interest in ReMag, a brand of liquid magnesium chloride. Dr. Dean is the author of The Magnesium Miracle. Her radio shows are archived at www.drcarolyndeanlive.com .)

References:

1. Dean C. The Magnesium Miracle. 2nd Ed., Ballantine Books, 2017, ISBN-13: 978-0399594441.

2. Long S, Romani AM. Role of cellular magnesium in human diseases. Austin J Nutr Food Sci. 2014;2(10): 1051. http://austinpublishinggroup.com/nutrition-food-sciences/fulltext/ajnfs-v2-id1051.php

3. Dean C. 100 Factors Related to Magnesium Deficiency. https://drcarolyndean.com/2010/06/gauging-magnesium-deficiency-symptoms/

4. McCarthy JT, Kumar R, "Divalent cation metabolism: magnesium," in Schrier R (series ed.), The Atlas of Diseases of the Kidney, Blackwell, Oxfordshire, 1999.

5. Heaton FW, "Role of magnesium in enzyme systems," in Siegel H (ed.), Metal Ions in Biologic Systems, Marcel Dekker, New York, 1990.

6. de Baaij, JHF. et. al. Magnesium in man: Implications for health and disease. Physiological Reviews. Jan 1, 2015 Vol. 95 no. 1, 1-46. http://physrev.physiology.org/content/95/1/1.long

7. Rosanoff A. The Essential Nutrient Magnesium - Key to Mitochondrial ATP Production and Much More (2009). https://www.prohealth.com/library/print.cfm?libid=14606.

8. Abraham GE, Flechas JD, "Management of fibromyalgia: rationale for the use of magnesium and malic acid." J Nutr Med, vol. 3, pp. 49-59, 1992. https://www.ncbi.nlm.nih.gov/pubmed/8587088

9. Reddy P1, Edwards LR. Magnesium supplementation in vitamin D deficiency. Am J Ther. 2017 May 3. https://www.ncbi.nlm.nih.gov/pubmed/28471760

10. Jablonski NG, Chaplin G. The evolution of human skin coloration. J Hum Evol. 2000 Jul;39(1):57-106. https://www.ncbi.nlm.nih.gov/pubmed/10896812

11. Deng et al. Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III. BMC Medicine 2013. 11:187. https://www.ncbi.nlm.nih.gov/pubmed/23981518

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