Magnesium Absorption

Surprising Facts About Magnesium Absorption

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In a 40 year long career, Charles never met an athlete that was not magnesium deficient when they first came to see him. So, if you are dealing with the athletic population or are exercising yourself, it is fair to say that you should pay extra attention to your magnesium absorption and intake.

Magnesium Relevance in Health

Magnesium belongs to the category of the major minerals, these are also called macro-minerals. They differ from trace minerals by their abundance in the body. Trace minerals are also called micro-minerals or, for extra confusion, micro-elements, thank you science! [1] The major minerals in order of abundance are calcium, phosphorus, potassium, sodium, chloride and magnesium [1.] Magnesium is the second most abundant cation in the body right after potassium.

The human body’s magnesium content makes up about 20mmol/kg of fat free tissue. [6]  This translates into 24-25g of magnesium for your average 70kg male. Number will be slightly higher in people with more muscle mass and less body fat, but it won’t be a linear deviation since about 50% of total body magnesium is located in the bones. Bone mass, even if it varies between sedentary and active individuals, varies to a lesser extent than soft tissues. [2] In comparison, calcium is 42x more abundant in the human body. [7] Which might be the reason calcium always gets all the love!

But what does a macro-mineral do?

The short answer is A LOT! The longer answer is that macro minerals:

  • provide the medium essential for normal cellular activity
  • determine the osmotic properties of body fluids
  • impart hardness to bones and teeth
  • function as obligatory cofactors [1]

Note: Cofactors, mostly metal ions or coenzymes, are inorganic and organic chemicals that assist enzymes during the catalysis of reactions. These are to be distinguished from coenzymes which are non-protein organic molecules that are mostly derivatives of vitamins soluble in water by phosphorylation. [5]

You have probably heard that magnesium acts as a co-factor in 300+ enzymatic reactions. Well, that is outdated, and flat out wrong. That number dates back to 1968. Now, that number is more reliably estimated at 700 to 800. [3,4,5] Magnesium is involved in more than 80% of the metabolic functions [16].

Knowledge is an ever evolving process and there are MANY things science does not know for sure yet! The take home message here is that magnesium is vital to health and function, in so many ways, that we are still counting!

Magnesium Foods

Magnesium is an essential nutrient. This means that magnesium is required for normal physiological function. It also means that it cannot be synthesized in the body, either at all, or in sufficient quantities. Magnesium must therefore be obtained from a dietary source.

The RDA recommendations for magnesium vary with age and sex. Within the 19 to 30 year old bracket, males need 400 mg and females need 310 mg of magnesium per day. For those 31 years old and older, males need 420 mg and females need 320 mg of magnesium daily [1] It is now estimated that 60% of adults do not achieve dietary intake recommendations[16].

You should know better than just following the RDA, as Charles used to say, these numbers are like the minimum wage, do you want to survive or actually thrive? On a side note, magnesium toxicity is a thing, but you are safe as long you don’t add another 350mg/day from supplements and medicine on top of whatever you get from foods. [20]

The burning question becomes, where can I find magnesium?

Well, about everywhere … it is the 8th most abundant mineral in the earth’s crust. But before you start wondering whether or not parmesan is a great dressing for a rock salad… let’s look at what digestible options are out there.

Surprisingly about 10% of our magnesium intake comes from the water we drink. [6,7] Tap, mineral, and bottled waters can be sources of magnesium. The amount of magnesium varies by source and brand, substantially. It can range from 1 mg/L to more than 120 mg/L) [8].

Apart from water, green vegetables are one of the best sources of magnesium. The key word being green, green as in rich in chlorophyll. As you may know the core of the chlorophyll molecule is magnesium, exactly in the same way that iron is at the center of hemoglobin molecules [9]. Nuts and seeds are also very good sources. Cereals are rich sources of magnesium as well. Further down the scale, intermediate levels of magnesium are available in fruits, fish, and meat. And, lastly, dairy products provide a very small amount of magnesium. [6,10]

So, magnesium for all intents and purposes, is ubiquitous in food. And yet, the majority of the population in Western countries consume less than the recommended amount of magnesium. [6]

How is that even possible?

Magnesium deficiency

This is actually a modern problem and due to reduced nutrient content in foods. There are two main reasons for that.

One of the obvious reasons is food processing. The Western diet contains more refined grains and processed food. Estimates are that 80–90% of Mg2+ is lost during food processing. [3] This is relevant for cereals, grains and also the all time favorite in the fitness community, nut butters. Water is also very often demineralized, which takes most magnesium out of it.

The second problem stems from the soil used for agriculture, which is becoming increasingly deficient in essential minerals. [11] Over the last 60 years the Mg2+ content in fruit and vegetables decreased by 80–90%. [11] Charles was fond of recalling a gem he got from Dr Rakowski. Rakowski explained to him that it takes 17 elements to grow a healthy plant, but today’s most used fertilizers contain only three. So it raises question about whether the the nutrient charts are of any value anymore.

Magnesium Losses – Physiological and Otherwise

It is estimated that under normal conditions, renal elimination removes approximately 100 mg of Mg2+ per day. These are what we call physiological losses. [12] Losses via sweat are generally low, but intense exercise can ramp up the losses.

When we deviate from what is normal, several issues can alter magnesium status. Here are a few reasons why you might have issues with magnesium deficiency. Gastrointestinal malabsorption and loss, severe or prolonged chronic diarrhea, increased renal loss, congenital or acquired renal magnesium wasting, excessive lactation, heat, prolonged exercise, severe burns, cardiopulmonary bypass surgery, and chronic alcoholism.

There are also a couple endocrine causes:
Primary and secondary hyperaldosteronism
Hungry bone syndrome
Syndrome of inappropriate anti-diuretic hormone hypersecretion

Of special interest is magnesium renal loss that comes with diabetes. What happens is that the extra glucose in the urine pulls magnesium away with it. It often results in magnesium depletion, the severity of which depends on the amount of glucose that is excreted. [13] Metabolic acidosis also impairs renal conservation of magnesium [14].

Finally, medication is a huge player in magnesium loss. Certain types of drugs, such as diuretics, epidermal growth factor receptor inhibitors, calcineurin inhibitors, and proton pump inhibitors also cause magnesium loss. [3]

Mechanisms of Magnesium Intestinal Absorption

Unlike other minerals, magnesium can be absorbed along the entire length of the gastrointestinal tract. However, different segments contribute unequally to the overall absorption of dietary magnesium. The majority of magnesium is absorbed in the distal portion of the small intestine. [16] Magnesium intestinal absorption ranges from 20 to 80% which is a huge span, on average 30-50% of ingested magnesium gets absorbed. 

Passive Transport

The major pathway that usually accounts for about 80-90% of overall magnesium absorption is a non-saturable paracellular passive pathway. This means that magnesium passes in between the cells of the gut lining, namely the enterocytes.

This passive pathway is responsible for bulk absorption of magnesium. It depends on an electrochemical gradient and a solvent drag that exist between the lumen and the blood. This is why at higher intestinal concentrations this passive pathway predominates. 

This pathway also depends on tight junction permeability. And more specifically on a family of molecules named claudins which control said permeability. It is an area under investigation and it appears that certain claudins (claudins 2,7,12) can facilitate transport by creating selective transport complexes while others inhibit transport by sealing the tight junctions (claudins 1,3,4,5).   

Active Transport

The other pathway is a saturable transcellular active pathway, where magnesium goes through the enterocytes via special channels. This pathway usually accounts for 10-20% of overall magnesium absorption.

This pathway is responsible for the fine-tuning of magnesium absorption. It prevails at low magnesium intestinal concentrations. It can bump magnesium absorption up to 80% when necessary if intestinal magnesium is low and the passive transports are rendered inefficient.

Basically, magnesium enters the cell through specialized channels and is then effluxed, that is taken out of the cell, through a Na+/Mg2+ exchanger. These channels are of special interest to research. They have been called “chemzymes” [18] since they act as both enzymes and channels and have very interesting properties that make them specific to magnesium peculiarities. They belong to the family of Transient Receptor Potential Channel Melastatin: the famous TRPM6 and TRMP7. And are constituted of channel and enzyme domains which are a very rare feature unique amongst ion channels. Research is still working on the question of active magnesium absorption and other mediators are under scrutiny. About two dozen magnesium transporters such as IMM, Mrs2, SLC41A3, SLC41A1 and APC/SCaMC (either confirmed or putative) are bring studied.[18]

Bioavailability of Magnesium

Mg salts that are poorly soluble in water have an opportunity to become water soluble upon reaction with the acid of the stomach. This facilitates absorption of Mg in the small intestine.

Magnesium is an interesting character and it is quite unique amongst other cations such as potassium and calcium. When hydrated, magnesium grabs a double layer hydration shell. The first layer is very tightly bound and consists of six water molecules, the second layer is relatively tightly bound and is made up of 12–14 water molecules. Hence the magnesium molecule grows 400x larger than its ionic form, that is its dehydrated form. To put it to scale, calcium only gets 4 times bigger when hydrated. This poses quite the challenge when it comes to transport since transporters will need to recognize the hydrated magnesium and remove the hydration shell which strongly interacts with the ion to deliver magnesium trough the membrane. Therefore magnesium is unable to pass small ion channels. [19,16]

But bioavailability is not only about managing hydration status, since other variables factor in, as we will see in part 2 of this article.

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[1] Advanced Nutrition and Human Metabolism 6th edition. by Sareen S. Gropper (Author), Jack L. Smith (Author)

[2] Sports Nutrition2nd Edition by Ronald J. Maughan (Editor)

[3] Magnesium in man: implications for health and disease, de Baaij JH, Hoenderop JG, Bindels RJ.

[4] The Essential Nutrient Magnesium – Key To Mitochondrial Atp Production And Much More, by Andrea Rosanoff, PhD 

[5] The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Caspi R1, Altman T, Dreher K, Fulcher CA, Subhraveti P, Keseler IM, Kothari A, Krummenacker M, Latendresse M, Mueller LA, Ong Q, Paley S, Pujar A, Shearer AG, Travers M, Weerasinghe D, Zhang P, Karp PD.

[6] Magnesium and Human Health: Perspectives and Research Directions, by Abdullah M. Al Alawi, Sandawana William Majoni, and HenrikFalhammar

[7] Magnesium in Drinking Water and Ischemic Heart Disease Arthur Marx and Raymond R. Neutra

[8] Comparison of the mineral content of tap water and bottled waters. Azoulay A, Garzon P, Eisenberg MJ.

[9] Understanding chlorophylls: Central magnesium ion and phytyl as structural determinants. Leszek Fiedor a, Agnieszka Kania b, Beata Myśliwa-Kurdziel a, Łukasz Orzeł b, Grażyna Stochel b

[10] Magnesium basics by Wilhelm Jahnen-Dechent and Markus Ketteler

[11] Magnesium and Human Health: Perspectives and Research Directions, by Abdullah M. Al Alawi, Sandawana William Majoni, and Henrik Falhammar

[12] Intestinal Absorption and Factors Influencing Bioavailability of Magnesium-An Update, Jan Philipp Schuchardt and Andreas Hahn

[13] Diabetes mellitus and electrolyte disorders, George Liamis, Evangelos Liberopoulos, Fotios Barkas, and Moses Elisaf

[14] Magnesium: Nutrition and Homoeostasis, by Jürgen Vormann

[15] Intestinal Absorption and Factors Influencing Bioavailability of Magnesium-An Update, Jan Philipp Schuchardt and Andreas Hahn

[16] Challenges in the Diagnosis of Magnesium Status by Jayme L. Workinger, Robert. P. Doyle and Jonathan Bortz 

[17] Mg2+ Homeostasis: The Mg2+nificent TRPM Chanzymes by Craig Montell

[18] Magnesium Extravaganza: A Critical Compendium of Current Research into Cellular Mg2+ Transporters Other than TRPM6/7 Martin Kolisek, Gerhard Sponder, Ivana Pilchova, Michal Cibulka, Zuzana Tatarkova, Tanja Werner, and Peter Racay

[19] Magnesium chemistry and biochemistry, Michael E. Maguire, James A. Cowan

[20] Magnesium or Mg2+ Lecture, SNPed Lecture, by Dr. Christy Williamson and Dr. Jessica Pizano