Magnesium Deficiency and Fibromyalgia

Free the Animal's Richard Nikoley may have no use for government (I recommend the depressing but excellent book, Humanity, A Moral History of the 20th Century to get some measure of the amount of systematic human death and suffering caused by government even recently), but I must say I do appreciate the United States of America hosting the organized repository of online knowledge that is PubMed.

I'm old enough to remember hunting the Stacks in the undergraduate library. Even then we had Wargames-era computerized search engines. Half the time you would get sent to something on microfiche and you would give up. In medical school, Medline, MedlinePlus, Ovid, and LoansomeDoc were still ways to search (and you still had to comb the library for the actual paper journal nearly all of the time). In most cases we would do almost anything to avoid a literature search and generally gave presentations straight from textbooks.

Look at me now. Voluntarily doing literature searches for the purposes of gaining knowledge and stuff.

The Ting Tings:  Hang it Up (right click to open in new tab--VEVO so there's an ad the first time through.  Sorry about that, but I think this song is a new, and it is rockin'.)

Now if the whole shebang could be shifted to PubMed Central and free full text were the norm…well.  I suppose my school (I'm not going to mention the name of it, because we all know what happened the last time) would have to find some other way to pay me for my teaching duties than academic journal access. Maybe money of some kind, a discount on malpractice insurance, a holiday basket, a free MRI or something. But for now I get PubMed's friendly My NCBI to email me automatically and regularly with searches of interest. And then I'm able to plug the search results into my school's online academic access for full text so the emails are not a horrible tease.

Sometimes I get a lot of results for boring articles about rats on ketogenic diets, or the latest review in Hungarian about sleep disorders. Sometimes I hit the veritable Evolutionary Psychiatry jackpot, relatively speaking.

Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?

It's a small study, 60 women with fibromyalgia. Nothing definitive but certainly very interesting. Have I talked about fibromyalgia before? It's a disease characterized mostly by generalized muscle pains and body aches, fatigue, and poor sleep. Like irritable bowel syndrome, a good proportion of the folks I see in my outpatient clinic that I see for anxiety or depressive disorders have been diagnosed with fibromyalgia. I would say men tend to be more on the irritable bowel side while the afflicted women generally have a nice helping of both, in combination with long term anxiety, depression, and often some autoimmune arthritis or skin issues. Fibromyalgia is one of those debilitating conditions that many doctors (and lay people) consider the 21st century version of hysteria, partially because there are no definitive biomarkers, no x-ray findings, it tends to co-occur with depression and anxiety, and it can respond somewhat to certain antidepressants.

My guess is that fibromyalgia is a variant of depressive disorders that is mediated by a poorly regulated stress response combined with broken sleep, oxidative stress, and inflammation. There's very likely a gut microflora connection. I can further speculate that a program of stress reduction, a nutrient-rich, toxin-avoidant diet, sensible exercise and good sleep hygiene will go a long way to help a large percentage of those with fibromyalgia.

The diagnosis of fibromyalgia has become more popular recently because there is a shiny new Drug to treat it, Cymbalta (duloxetine), which is also FDA-approved for major depressive disorder. There are, of course, no studies as far as I know for paleo diets combined with intensive lifestyle interventions for fibromyalgia, so it is madness and pseudoalternative crap medicine to promote that idea on my blog, whereas there is growing literature evidence for Cymbalta (and pregabalin and milnacipram, the other two FDA-approved treatments). Cymbalta is one of the class of second generation mixed norepinephrine and serotonin-reuptake inhibitors. And I would have to say, in my experience working with people, it really does seem to help the annoying, constant aches of fibromyalgia in many. Cymbalta can also cause weight gain, sedation and a host of other irritating antidepressant side effects, and it is expensive.

Of course, the dirty little secret of expensive pharmaceuticals is that there are older, dirt-cheap antidepressants that are equally effective for fibromyalgia, called tricyclic antidepressants (TCAs).  To be perfectly fair, the TCAs are fatal in overdose and cause much more weight gain, sedation, and deal-breaking dry mouth than the second-generation Cymbalta.

But what if there were an even cheaper, easier, less side-effect laden pill or supplement to take for fibromyalgia? How about magnesium? If you like more detail, go read my Psychology Today article, Magnesium and the Brain: The Original Chill Pill. It combines the information from several articles from this blog. To summarize, magnesium deficiency can cause us to be more vulnerable to a poorly regulated stress response, and magnesium is absolutely necessary to metabolize energy efficiently. Many on a Standard American (or whatever) Diet are likely to be at least somewhat magnesium deficient. Since most magnesium is stored within cells and bones, a simple serum level generally won't tell us much. Since we die rather quickly of heart problems if our blood levels are low, our regulatory systems pull out all the stops to make sure our blood levels remain within a certain range, even if our bodies are relatively deficient.

Back to the study. These researchers took 60 women with fibromyalgia and 20 controls.  The patients were randomized into three groups, magnesium citrate 300mg daily, amitriptyline 10mg daily (a TCA), or Mg Citrate + amitriptyline for eight weeks.  Number of tender points and a "tender point index" were assessed.  Serum and red blood cell levels of magnesium were measured and followed.  In addition, all the participants took standard scale questionnaires measuring depression, anxiety, and fibromyalgia symptoms.  All of these measures were taken before and after treatment.

Why magnesium?  The researchers were intrigued by the idea of fibromyalgia being a disease of oxidative stress, and mineral deficiencies are known to predispose folks to oxidative stress.  Magnesium plays a critical role in the various processed turning the food we eat and our fuel stores into energy used by the cells.  It was postulated that muscle cells could be low in magnesium while the blood levels were maintained with normal limits (to preserve the heart), and this low magnesium could cause problems with muscle cells turning fuel into energy, thus fatigue, weakness, and pain.  A previous study showed that 300-600 mg of magnesium malate daily improved the symptoms of fibromyalgia (1).  Another trial used a mix of magnesium supplements (low and high) with similar results to the previous study in the high-dose arm (2).

In the brand new study, here are the results:

...magnesium levels [both serum and red blood cell] were lower [in fibromyalgia patients] than in the control groups and there was a correlation between magnesium and VAS, the number of tender points, tender point index, the FIQ, the Beck depression and anxiety score and clinical symptoms such as fatigue, sleep disorder, headache, numbness and gastric disorders. All of these findings support the fact that magnesium plays an important role in the development of fibromyalgia.

That's pretty impressive.  And here, then, appears to be the third trial showing clinical improvement with magnesium supplementation for fibromyalgia.  The patients who did best were on a combination of magnesium and amitriptyline (the 10mg dose is quite low and would not expect to have much in the way of antidepressant effects).

Before we get too terribly excited, there are studies showing that sleeping medicines alone will help improve symptoms of fibromyalgia, and one of the most consistent reports of people taking magnesium is that sleep is improved.  Similarly, amitriptyline in a 10 or 25mg dose is often used off-label as a prescription sleep aid.  That might explain the improvement all on its own.

But however the magnesium seems to help, that it does could be significant for many.  It certainly seems worth a try, considering the risks and benefits and costs of the FDA approved treatments (pregabalin, duloxetine, and milnacipram) and the multitude of benefits from getting one's magnesium levels up to snuff.  These are not massive doses.  Considering the average diet gives us maybe 250mg daily, adding 300mg daily puts us just a little above the RDA.  Seems sensible enough to me, anyway.