The Role of Magnesium in Fibromyalgia

An investigatory paper by Mark London

I am no longer updating this web page, or responding to questions regarding it.
I also will not give any permission to any company to quote or use this web page.

This web page was the result of my research regarding magnesium, and why it's important not only for the average person, but especially for people with fibromyalgia.  If you aren't interested in reading lots of studies, and are already convinced of magnesium's importance, then just click here to get to my recommendations.  Please note, magnesium is only one of many possible treatments that can help fibromyalgia.  It, by itself, cannot effectively treat it.

Magnesium deficiency is very common in the general US population.  Not only is our daily intake low, but we eat a diet which increases the demand for magnesium.  And unfortunately, urinary magnesium loss can be increased by many factors, both physical and emotional.  Magnesium loss increases in the presence of certain hormones.  Stress can greatly increase magnesium loss. Even loud noises can cause magnesium loss.  One article on the web goes so far as to say that that almost everyone is the United States is at least marginally deficient in magnesium.  So there is an excellent chance that a person with fibromyalgia has a magnesium deficiency.  But since people with fibromyalgia often have high levels of stress, and a disrupted hormonal system, they are more likely to be candidates for magnesium deficiency.  Magnesium utilization is also increased by the presence of estrogen, and this might explain why many women are diagnosed with fibromyalgia after menopause, when estrogen levels would decrease.  Additionally, the sleep disruption which occurs in fibromyalgia might also affect magnesium utilization, as sleep deprivation has been shown to cause lower magnesium levels.

The reason lack of sleep causes a magnesium deficiency is probably due to the lower amounts of growth hormone secretion which occurs due to a sleep disturbance, especially the type that is found in people with fibromyalgia.  Growth hormone is responsible for creating a substance known as IGF-1, or insulin growth factor.  IGF-1 has been found to have many uses by the body.  It's especially known for tissue repair.  However, it can influence intracellular levels of magnesium, as the following studies show:

Also, IGF-1 affects excretion of magnesium by the kidneys:

Magnesium deficiency is therefore one of many problems in people with fibromyalgia which is due to or influenced by the sleep disturbance.  So while it's possible to attain some benefit from taking magnesium, treating any sleep disorder is just as helpful, if not more so.

Magnesium is extremely important to many functions in the body, which is why a deficiency can cause many different symptoms.  It is most widely known for being needed for proper bone formation.  With a deficiency, bones will be soft, and it can play a role in osteoporosis   However, magnesium is also the activating mineral for at least 350 different enzymes in the body, more than any other mineral, so it is crucial for many of the metabolic functions in the body.  Magnesium is necessary for almost all the enzymes that allow the glycolytic and Krebs cycles to turn the sugar and fat we eat into ATP.  Low levels of ATP have commonly been found in people with fibromyalgia, and it is believed that this plays an important role in many of the fibromyalgia symptoms.  Thus, a magnesium deficiency would definitely be a factor in worsening those symptoms.

Magnesium is extremely necessary for proper ATP synthesis, because ATP is stored in the body as a combination of magnesium and ATP, which is known as MgATP.  ATP requires magnesium in order to be stable.  Without magnesium, ATP would easily break down into other components, ADP and inorganic phosphate.

The brain heavily relies ATP for many functions.  In fact, 20% of total body ATP is located in the brain.  Thus, low levels of ATP can diminish brain cognitive functions, a common problem in people with fibromyalgia.

Adequate magnesium is necessary for proper muscle functioning.  Magnesium deficiency promotes excessive muscle tension, leading to muscle spasms, tics, restlessness, and twitches.  This is due to an imbalance of the ratio of calcium to magnesium, as calcium controls contraction, while magnesium controls relaxation.  Plus, in fibromyalgia, changes are seen in the muscles, such as "significantly lower than normal phosphocreatine and ATP levels" and "values for phosphorylation potential ... also were significantly reduced":

But all of these same changes are found also in magnesium deficiencies:

Magnesium may also help Myofascial Pain Syndrome.  According to Devin Starlanyl's web page "Myofascial trigger points can be identified and documented electrophysiologically by characteristic spontaneous electrical activity (SEA).  They may also be identified histologically (which means that the structure of the cells have changed) by contraction knots-- the lumps and bumps we know only too well.  Both of these phenomenon seem to result from excessive release of the neurotransmitter acetylcholine (ACh) from the nerve terminal of the motor endplate (the complex end formation of the nerve)."  But magnesium is well known for being able to inhibit ACh release:

And in fact, intravenous magnesium sulfate is used in emergency situations because of this effect on acetylcholine:

Magnesium is known to regulate or inhibit many nerve receptors, such as NMDA or 5-HT3, which have been considered as sources of certain types of fibromyalgia pain.  Neurontin, for example, is used because inhibits NMDA activity.  Since magnesium also blocks NMDA receptors, studies have used intravenous magnesium therapy to try and treat similar types of neuropathic pain:

And it's because of magnesium's ability to regulate nerve functions that other fibromyalgia symptoms occur.  Migraine headaches, mitral valve prolapse, and Raynaud's phenomenon, all problems commonly found in people with fibromyalgia, are also problems that have been associated with a magnesium deficiency.  Without enough magnesium, nerves fire too easily from even minor stimuli.  Noises will sound excessively loud, lights will seem too bright, emotional reactions will be exaggerated, and the brain will be too stimulated to sleep, all symptoms commonly found in fibromyalgia.  And if the oversensitivity to light and noise reminds you of someone suffering from a hangover, they are one and the same problem, as alcohol is known for decreasing magnesium levels, and magnesium supplementation has been found to relieve hangover symptoms.

Another commonly found condition in fibromyalgia which has nervous related symptoms is reactive hypoglycemia.  Anxiety related symptoms occur after carbohydrate intake, and this is believed to be due to either an excess release of adrenaline, or a higher sensitivity to adrenaline.   In either case, a deficiency of magnesium could be a factor, as magnesium deficiency appears to associated with anxiety and high levels of adrenaline.

Not only that, but magnesium also affects carbohydrate metabolism in a different manner, as a magnesium deficiency appears to create resistance to insulin,  Insulin resistance increases levels of insulin, which may result in  a form of diabetes.  Additionally, insulin resistance by itself can distrupt intracellular magnesium levels, as the following web page explains.

Thus, "insulin resistance and magnesium depletion may result in a vicious cycle of worsening insulin resistance and decrease in intracellular Mg(2+) which may limit the role of magnesium in vital cellular processes."

Magnesium also appears to be able to also affect the nervous system by regulating the release of hormones, which occurs due to many different forms of stress.  However, this hormonal activity is disrupted in fibromyalgia.  Often there is an exaggerated release or high levels of noradrenaline (also known as norepinephrine), as the following studies show:

However, magnesium appears to play a role in regulating noradrenaline levels.  For example, in the following study on mitral valve prolapse, magnesium supplementation not only relieved symptoms, but also reduced the high level of urinary noradrenaline excretion:

And genetically bred mice with low magnesium levels have also been found to have high noradrenaline levels:

And ,as was previously mentioned, sleep deprivation appears to lower magnesium levels.   However, in another study, sleep deprivation was found to raise noradrenaline levels:

Thus, there appears to be a strong link between high noradrenaline levels, and low magnesium levels.  And this imbalance of hormones could play a role in exercise tolerance in fibromyalgia.  High noradrenaline levels are associated with low exercise tolerance.  This might be due to the fact that noradrenaline causes constriction in blood vessels, and this could reduce oxygen flow during exercise.  This is made worse by the lower than normal adrenaline levels in fibromyalgia,  as adrenaline is able to dilate blood vessels in the skeletal muscles and the liver.   However, magnesium is able to relax smooth muscles around blood vessels, and thus has a strong vasodilatory effect, which could counteract the vasoconstriction effect of the hormones.

Related to this is the previously mentioned study of patients that were sleep deprived which resulted in low magnesium levels.  They were also found to have lower levels of exercise tolerance.  But in a subsequeent study, it was found that magnesium supplementation was able to raise that tolerance:

Respiratory problems such as asthma have also been associated with high levels of noradrenaline, and thus magnesium might be of help for those conditions.

A magnesium deficiency also increases levels of substance P, a chemical which has been implicated as being responsible for increased pain levells in FMS.  Several studies, such as the following, show this:

However, even just as important is the fact that this study also shows a rise in inflammatory cytokines.  Cytokines are part of the immune system.  However, raised levels of certain cytokines have been implicated in many health problems and diseases, and some researchers feel that they may be responsible for many of the symptoms of FMS and CFS, as these cytokines play a role in metabolic and many other functions. Sleep deprivation studies also show an increase these cytokines, not surprising since we have shown that sleep deprivation can cause a magnesium deficiency.  The following study showed a significant increase in one of these cytokines, interleukin-6.  This cytokine appears to play a role in the fatigue and other health symptoms that directly result from lack of sleep:

Since a sleep disturbance could cause a rise in these cytokines, and since this study also postulates that these cytokines themselves play a role in regulating sleep, a spiraling effect could occur, as the high levels of these cytokines could cause sleep to be constantly disturbed  Such a circular effect has been proposed for the cause of FMS.

Magnesium is thus involved in many functions in the body, and so it's no wonder that the chemical brain imbalances in fibromyalgia somehow seem connected to processes involving magnesium.  Surprisingly, little is known about magnesium, as compared to other minerals in the body.  So it could be that magnesium even has more effects that we are not yet aware of.  And it's because magnesium is involved in so many processes in the body, that a deficiency has a spiraling effect.  Low magnesium levels causes metabolic functions to decrease, causing further stress on the body, reducing the body's ability to absorb and retain magnesium.  A marginal deficiency could easily be transformed into a more significant problem.  Any stressful event could trigger magnesium loss. So one could postulate that stressful events which trigger fibromyalgia are doing so by creating a high loss of magnesium.  Perhaps people in a fibromyalgia flare could be helped by additional magnesium.

Unfortunately, magnesium deficiency is not easily detected, as serum levels do not reflect the levels of magnesium in tissues.  This is the reason why it is so overlooked and ignored, both by doctors and by studies.  And unfortunately, oral magnesium supplementation can be difficult because of absorption problems.  Digestion and diet play a key role in absorption.  People with fibromyalgia often have conditions like Irritable Bowel Syndrome, gluten intolerance, or other problems that might limit absorption.   Excess amounts of certain substances, such as fructose, may interfere with magnesium absorption.  Phosphate can bind to magnesium in the gut, creating magnesium phosphate, an insoluble salt that can't be utilized.  Many forms of oral magnesium supplements are hard to assimilate.  The most common, magnesium oxide and citrate, happen to be the worst to assimilate, which is why both have a strong laxative effect.  If you suffer from that effect when you take magnesium, it is often not because you are taking too much, but because you are not assimilating it well.  And it may take long term use of supplements before magnesium levels are raised in all the tissues, and for damaged cell functions to be restored.

A magnesium deficiency increases cell membrane permeability, and this condition is believed to lead to a decrease in the intracellular antioxidant system, shown in the following study, one of several in MEDLINE:

Changes in cell membranes and subsequent intracellular imbalance in cells reduces the body's defenses against toxins such as heavy metals.  A long term magnesium deficiency may lead to many other secondary problems that have their own host of symptoms.

A magnesium deficiency causes an increase in intracellular calcium levels, which may lead to calcification and cell death.  And a few more studies for those interested on the effects of a magnesium deficiency on cell disturbances and mitochondria damage:

And if you are still skeptical of the importance of magnesium, I suggest you read the following:  While most symptoms which are directly due to a magnesium deficiency are reversible, magnesium deficiency indirectly causes problems that may not be reversible.  "With a high aluminum diet alone, aluminum content in the nervous system in rats showed no difference with a control group aluminum serum aluminum was high.  However, with an insufficient intake of magnesium the same aluminum load induced an increase in aluminum and calcium concentrations in the nervous system and neurodegeneration with precipitation of insoluble hydroxyapatites."  Combined aluminum intoxication with calcium-magnesium deficiencies is not reversible through physiological oral magnesium supplementation.  And also from that web page: "nervous consequences of magnesium deficiency" ... "are completely reversible since they can be restored to normal with simple oral physiological magnesium supplementation but it should also be pointed out that a prolongation of untreated chronic magnesium deficiency can produce irreversible lesions with histological changes.

Magnesium Supplement Suggestions

If you are considering taking magnesium, I would suggest looking for a form that allows to you start with a low amount, and then slowly increase that dose.  Unabsorbed magnesium will cause a laxative effect, so the amount that you can tolerate will be limited by this effect.  This effect often isn’t seen until a day later, which is why you should only slowly increase the dose.  The RDA for magnesium is 400mg.  If this amount helps any of your symptoms, then you may be helped by taking more than that.  Magnesium is often better absorbed when taken with food.  Also, you can absorb more magnesium, if you take it in small doses, such as some with each meal. This is what I do.  And if possible, you might also want to avoid taking magnesium with foods that are high in phytic acid, such as whole wheat, as this might bind to the magnesium.

Taking magnesium with calcium is often suggested, because the 2 minerals work together in buildling bones.  Another good reason for taking the calcium, is that calcium (especially calcium carbonate) can offset some of the laxative effect from the magnesium.  Traditionally, it's been recommended to take calcium and magnesium in a ratio of 2/1, as that is the ratio of the RDA of calcium and magnesium.  However, magnesium is often poorly absorbed, so many doctors believe the ratio should be closer to 1/1.

Please note that not all forms are the same.  Magnesium oxide is one of the most common, but studies have shown it to be poorly absorbed, due to low solubility.  Studies show that other common forms, such as citrate, chloride, aspartate, are all better absorbed.  However, some people instead recommend chelated forms, believing that they are the best absorbed..  Although in theory this might be true, surprisingly there are no published studies to back up this claim. .

If one brand of magnesium does not work for you, or if you experience a side effect, consider switching to a different brand, as the substance which is combined with the magnesium may be the cause of the side effect.  Many people have found that liquid forms of magnesium help when pills do not help..  This is probably due to increased solubility.  There are various forms of liquid magnesium, i.e. magnesium chloride, gluconate, and citrate.  Magnesium chloride is well absorbed, although the liquid form has to be kept refrigerated.  Liquid gluocate (magonate) contains not only a lot of glucose, but several additives to make it taste better, and also a perservative to keep it from spoiling.  Liquid magnesium citrate is the most common liquid form..  Some people believe that magnesium citrate is not well absorbed, and point to the fact that magnesium citrate is marketed as a laxative.  On the other hand, almost any form of magnesium, taken in excess, will cause a laxative effect.  Magnesium citrate is probably used as a laxative, simply because it's an inexpensive form, and very soluable.

Another form which some people find very useful is the time released version.  Having a steady source of magnesium has been found to help in cases where plain magnesium did not help.  One can do this by taking lots of small doses, especially if one uses a liquid form, but this is inconvenient.  Time released supposedly is absorbed over a 8-10 hour period.  There are 2 available forms, magnesium chloride and magnesium lactate  Two brands are available which contain magnesium chloride, Slow Mag and Pro-Mag.  Slow Mag contains several additives that Pro-Mag does not.  Plus, Slow Mag is enteric coated, which is done to avoid a stomach upset..  However, one study suggests that this may prevent proper absorption.  Pro-Mag is made by Douglas Laboratories, and I personally have had good results with it.  Another good alternative is Mag-Tab.  It contains magnesium lactate, and has been reported by some people to be even better absorbed than the magnesium chloride, possibly because it is released over a longer period of time.  Time released forms are more expensive, so many people recommend a combination of pills and time released, and it may be more effective to combine a slow acting form with a quickly acting form.

Also note that B vitamins are necessary for proper utilization of magnesium.  Some people with fibromyalgia might have B vitamin deficiencies, especially B12.  One study, has shown that homocysteine levels are high in the cerebrospinal fluid, and this indicates low levels of B12 in the brain.  Additionally, homocysteine causes a depletion of intracellular free magnesium:, and according to the following study, only a combination of B6, B12, and folate acid can stop this depletion of magnesium.  Thus, some people with fibromyalgia might benefit from B vitamin supplementation.  (However, certain B12 deficiencies require B12 shots, as some people are unable to orally absorb enough B12.)

In some people, the problem might not be enough magnesium, but instead might be not enough vitamin D, which has an effect on magnesium absorption.  Up until recently, doctors only associated a vitamin D deficiency with weak bones, and they believed that a vitamin D deficiency in young people was rare in countries like the US.  However, both of these beliefs have been proven false.  Not only does it occur in young people, but sometimes a vitamin D deficiency can manifest itself mainly as pain.  Initial symptoms in adults can often appear as vague musculoskeletal pains, muscle weakness, and fatigue, symptoms commonly found in fibromyalgia.   Also, studies on the muscles of vitamin D deficient patients, show a reduction of ATP levels, similar to that of fibromyalgia patients.

In some cases, the deficiency leads to myopathy, with quite severe muscle weakness, especially affecting the legs and ability to walk.  On the other hand, sometimes the symptoms are less severe, in which case it could be easily overlooked in fibromyalgia patients.  In fact, several small studies have shown that at least 40% of patients with fibromyalgia have a vitamin D deficiency.

And while some blood tests can possibly indicate a vitamin D deficiency, often a deficiency can exist without any other biochemical changes.   Thus, the only definite way to tell if you have this problem, is by testing vitamin D levels.  Unfortunately, very few doctors do this.  So It's quite possible that some people who have fibromyalgia, might also have a vitamin D deficiency.  Or perhaps they never had fibromyalgia to begin with.  In the following study from Canada, only 12% of patients referred to rheumatologists with the diagnosis of fibromyalgia, actually had fibromyalgia:

I personally started taking magnesium for spasms and facial tics, only doing so on my own after neurologists simply told me to either get better sleep or take a prescription drug.  The magnesium helped almost immediately, and I then slowly increased the dose to about 225% the RDA (balanced with 100% calcium RDA) At that point, all spasms and tics stopped completely, and they have not returned since starting that dose several years ago.  I doubt any traditional doctor would have been willing to prescribe that much magnesium. The RDA is 400mg, but many people believe this is too low.  Traditionally, it's been recommended to take calcium and magnesium in a ratio of 2/1.  But magnesium is less easily absorbed than calcium, so this ratio may not be valid for a lot of people, and in fact many cal-mag combinations found in health food stores often have additional magnesium.

Magnesium is just one of many helpful remedies and/or supplements for that might be helpful for fibromyalgia.  It's not a cure, but it may be helpful in relieving some of the symptoms. For more information about magnesium, click here to read Sandy Simmons's web page on magnesium.

Copyright (c) 2007
Contents of this article are the property of Mark R. London, MRL@PSFC.MIT.EDU  Contents can be forwarded to other people and posted on the internet, as long as it is forwarded in full.  Contents cannot be used in any way in any other media, without permission of the author.