Re: The Role of Magnesium in Fibromyalgia, by Mark London

[Guest guest]

Thanks Bindi,

Good stuff.

Patty

>

> Mark London has an interesting article about magnesium. It is

especially useful for info on its relationship to vitamin D and the

types of magnesium supplements and dosage. One of the brands he

recommends is Mag-Tab, which is a time-released form of magnesium

lactate. I take it.

> Bindi

>

> http://web.mit.edu/london/www/magnesium.html

>

> The Role of Magnesium in Fibromyalgia

> An investigatory paper by Mark London

> Please report any links that are not working to mrl@...

> 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.

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9068914 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9851785 & dopt=Abstract

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9828151 & dopt=Abstract

>

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

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=10381152 & dopt=Abstract

>

> 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 " :

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9506567 & dopt=Abstract

>

> But all of these same changes are found also in magnesium

deficiencies:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=8988330 & dopt=Abstract

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=7847586 & dopt=Abstract

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=8399369 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=2812517 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=10687324 & dopt=Abstract

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9785788 & dopt=Abstract

>

> 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.

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=8861135 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=2532682 & dopt=Abstract

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=10765933 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9070556 & dopt=Abstract

>

> And genetically bred mice with low magnesium levels have also been

found to have high noradrenaline levels:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & llst_uids=7545412 & dopt=Abstract

>

> And ,as was previously mentioned, sleep deprivation appears to

lower magnesium levels. However, in another study, sleep

deprivation was found to raise noradrenaline levels:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=10372697 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9626901 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=1384353 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=10443646 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=10192096 & dopt=Abstract

>

> 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:

>

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9529585 & dopt=Abstract

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=9641824 & dopt=Abstract

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=7738680 & dopt=Abstract

> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=8988330 & dopt=Abstract

>

> And if you are still skeptical of the importance of magnesium, I

suggest you read the following: http://www.mgwater.com/dur30.shtml

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

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.

>

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=12810939

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=11708429

>

> 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:

>

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=12595620

>

> 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 's web

page on magnesium.

>

> Copyright © 2007

> Contents of this article are the property of Mark R. London,

MRL@... 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.

>

> Mark London MRL@...

>