Magnesium and Connective Tissue

John Libbey Eurotext – Magnesium Research – Magnesium and connective tissue | March 2003

This extremely technical article explains why and how magnesium is essential to connective tissue, The original article contains far more detail, but left me flummoxed.

The cells which constitute tissue of vertebrates are in charge of the synthesis and remodelling during the life of the four extracellular macromolecules contained in the connective tissue.

  • Magnesium stimulates collagen synthesis expressed by fibroblasts in culture.
  • Magnesium inhibits prolyl and lysyl hydroxylases and could be considered as antifibrotic.
  • Magnesium is associated with elastin and plays a protective role in maintaining the extensibility of elastin.
  • Magnesium associated proteoglycans in cartilage prevent the swelling and degradation of this tissue.
  • Magnesium regulates the functional activity of integrins.  

This non exhaustive list of some properties linked to magnesium makes it a potential leader in physiological and pathological situations which occur at the level of the connective tissue and also at the level of the matrix associated cells.

Magnesium and connective tissue

Magnesium (Mg2+) is the fourth most abundant cation and the second most abundant intracellular cation in vertebrates. The normal adult total Mg2+ content is estimated at 25g (for 70 kg body weight) of which about 53% is found in bone

Magnesium plays an essential role in a wide range of biological processes and is crucial for life. Mg2+ is essential for many enzymatic reactions and develops two interactions

(1) Mg2+ binds to the substrate thereby forming a complex with which the enzyme interacts, for example enzymes that utilize ATP do so with Mg ATP, and

(2) Mg2+ binds to the enzyme and plays an allosteric activator role

Furthermore Mg is critical for some cellular functions such as DNA transcription and protein synthesis

Extracellular matrix is a complex integrated system responsible for the biological and mechanical properties of our tissues. The extracellular matrix is in constant remodelling and tissue homeostasis is a dynamic process involving a balance between protein synthesis and degradation

Cells, which constitute the tissues of vertebrates, are in charge of the synthesis and renewal of the four extracellular macromolecules which compose the connective tissue:

  1. two fibrillar components, collagens and elastin and
  2. two other families of macromolecules which do not belong to the fibrillar component, namely proteoglycans and structural glycoproteins.

Collagens and magnesium

The connective tissue exists in a wide variety of specialized forms; the most abundant and ubiquitous element of the extracellular matrix is the collagen family.

Among this family, the classical fibrous collagens (types I, II, III, and V) are found in greatest amounts and type I collagen is quantitatively the most important [6]. The biosynthesis of the collagen molecule is a complex process with intra and extracellular phases.

It has been shown that ascorbic acid stimulates collagen synthesis in dermal fibroblasts by increasing the rate of collagen gene transcription, but unfortunately experiments involving the use of ascorbic acid require daily supplementation of this molecule [10] due to its instability

Proteoglycans and magnesium

The collagen fibers form a network which appears to be formed by individual fibers interacting with neighboring fibers via other matrix constituents

The cartilage is a highly specialized connective tissue, essentially avascular, the main matrix components are type II collagen and large aggregating proteoglycans (aggrecan), not binding covalently to hyaluronic acid and forming a macromolecular complex with a relative mass exceeding 3 106kDa

Thus we can propose that magnesium maintains the structure and function of the cartilage.

Elastin and magnesium

Elastic recoil is a critical property of several tissues and organs; such as lungs, aorta, and skin... Elastic fibers are found in the extracellular matrix of the connective tissue providing elasticity and resilience to tissue which have the ability to deform repetitively and reversibly.

Elastic fibers are made of two major components: elastin and microfibrils [20]. Deposition of tropoelastin (soluble elastin) into the extracellular space occurs at specific sites on the cell surface, then tropoelastin is incorporated into the forming elastic fiber. Before elastin deposition into the extracellular space, microfibrils are secreted

It has been reported that Mg2+ is associated with the elastin core of elastic fibers and not with the associated microfibrils

Elastin degradation is extensive in many physiological processes such as growth, wound healing, and tissue remodeling

Mg2+ plays a protective role in maintaining the extensibility of elastin

So it appears that Mg 2+ is active in maintaining the structure and mechanical properties of elastic fibers and it is also actively involved in elastic fiber elastolysis.

This non exhaustive list of some properties linked to magnesium make it a potential leader in physiological and pathological situation, which occur at the level of the connective tissue macromolecular components and also at the level of the matrix associated cells.


Magnesium (Mg2+) one of the most abundant cations in vertebrates was shown to be involved in fundamental cellular functions such as adhesion migration and also in protein synthesis

Interestingly Mg2+ is associated with elastin and collagen, two fibrillar components of the extracellular matrix, and also with non fibrillar macromolecules namely proteoglycans and glycoproteins

The cells which constitute the connective tissue are in constant dialogue with the extracellular matrix components.

Due to Mg2+ functions with cells and on extracellular macromolecule structuring, Mg2+ can be considered a pivotal actor in tissue homeostasis.  


4 thoughts on “Magnesium and Connective Tissue

  1. Jan Groh

    I’m so glad you posted this. I am pretty sure my diagnostic geneticist must have seen this somehow before I saw her on Valentine’s Day 2012 in my wheelchair when I got diagnosed finally at 44.9 with HEDS. (I went from walking to wheelchair in 3 weeks in January 2012 suddenly, oof! But hey at least I finally got diagnosed with something besides depression!)

    I knew there was no “cure” since it’s genetic, and I will always write faulty collagen (whatever the cause). But when I asked her what my best strategy was, she said “Vitamin C helps form procollagen, that is, to lay in new collagen and magnesium helps build smooth muscle fiber”. And while still faulty, the more the merrier.

    I literally got some at the store on the way home that day with my friend’s help and started on 1000/day and haven’t looked back. (I’m now on 6000/day and holding, I’m lucky I can take cheap corn based OTC Vitamin C. Others might try sago palm based from Twin Labs, or tart cherry juice. Another friend has done even better with intramuscular C shots. Painful but very effective she says. EDS does look a lot like scurvy if you think about it after all. But I digress.)

    It took me 3 months to start walking again, but I did, and I just sold my power chair and put my manual chair in storage last week, 4 years later. Go me! (And Vitamin C.) And Dr. Heidi Collins has written at length on the benefits of magnesium in EDS patients also as you may know. (On my resources page at

    I admit I’m supplementing several other cofactors and the Cusack Protocol ( too now – all of which are helping me not look back and need very few pain pills anymore. I still have one Lofstrand crutch to ditch, but I think its days are numbered too if I can just tighten up my right leg socket a touch more.

    Cheers – Jan(droid) 3.0 (better, faster, stronger! At least than in 2012!)

    Liked by 1 person

    1. Zyp Czyk Post author

      Wow, Jan, this is great information! I was taking a few grams of VitC daily for years, but then stopped since I didn’t think it helped with anything. (Money problems made me stop all supplements that weren’t clearly helping)

      I’m still trying to figure out what magnesium does to me. I think I’m the only one on the planet who gets constipated from it – everyone else says it un-constipates! I thought it could replace MiraLax, but nope, I have to keep it.

      Do you take VitC in tablets, capsules, or powder? The powder is SO much less expensive I used that in the past. I always try to get my supplements in capsules, so I can be sure I’ll be able to digest it and also get the effect sooner.

      I’m taking 2x 400mg magnesium, morning and night. How about you?

      Your progress is indeed near miraculous, so I’m interested in the details of what you’re doing.


      1. teeks55

        I take magnesium glycinate, as this formulation is supposed to be the most absorbable magnesium for the body. I really like it, not only because of all the great stuff it does for my body…..but it also gives a wonderful sense of relaxation and calmness. I call it “xanax without a prescription”. I do take pharmaceutical grade mag. glycinate, that is compounded by my pharmacy. I highly recommend it to anyone with fibromyalgia, or chronic pain of any kind as well as those with anxiety. If you have a local compounding pharmacy available, get it there. It will be the freshest and highest quality.

        Liked by 1 person

        1. Zyp Czyk Post author

          This is very interesting to me, as I could definitely use a muscle relaxant like this sometimes.

          My problem is that magnesium causes me constipation!

          I’ve tried different brands of different formulations of magnesium and they all plug me up, even though it’s supposed to have the opposite effect. I do take MiraLax daily now and the magnesium only partially “undoes” its effects, so it’s tolerable.

          I thought maybe my body would acclimate, but it hasn’t in weeks. I sure wish I had even a clue why my body reacts so strangely and what that might mean.

          I taking Life Extension brand magnesium and they are usually one of the best, but the glycinate form is listed last. The next bottle I bought has the citrate and aspartate forms, so who knows how that will work on me.

          How much does your compounded mag cost? What’s the dose? Do they make tablets or capsules or…?

          From all I’ve read, magnesium would be very beneficial for me, but this constipation issue is problematic. Maybe the pharmacist would be able to figure that out.



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