Saturday, February 4, 2012

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.

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.


  1. As someone who had irregular and painful menstrual cycles, I don't feel aunt flow coming anymore since supplementing with Mg. I have next to zero pain that time of the month. It's even good for sleep. Mg can do a lot, just not everything.

  2. yes, it can do a lot, but it also is unlikely to do much on it's own. It seems to me that people with these sorts of chronic illnesses generally need to be doing a whole lot more changes with diet and lifestyle etc...magnesium is likely to be part of the picture but not the least not long-term.

    Also, antidepressant treatment for pain can backfire...some people getting quite a lot worse as a result.

  3. Hi Emily,what is your view of The Guaifenesin Protocol
    I ask because a number of people in NZ use this, and my old boss found it tranformed his life after he was diagnosed with fibro.

    On another I have spoken to a local fibro group a few times, and my observation is that many have an appalling diet. The foods at the conferences was chosen by the group, and is full of refined grains and sugar.

    @zombie, my cramps went completely with a combo of paleo, omega 3 and magnesium

  4. while people are talking cramp relief stories...I've pretty much cured my endometriosis, but I can't say what exactly helped as I've been on an evolution of dietary experimentation for a few years...

    I too eat paleo at this point...I found that Pine Bark helped markedly and I also do lots of omega 3 and magnesium :-)

    I"m still chronically ill, but the endo is not causing me problems's one less thing...

    @junlianne, yes I've found that most people who are very ill eat atrociously...I didn't ever ..which is why cleaning up my diet hasn't been so hard for me, but the fact is when people are really ill changing diet can feel like one more choices are so tied up with ones sense of self...and junk food, all too often is comfort when sick. I am grateful I never ate much junk...I just needed to clean up my diet, but I wasn't eating a ton of processed food to begin with...

  5. @julianne, only thing I could find on pubmed was this study, which mentions it peripherally and apparently folks in California have tried it as well:

    The reasoning on the site you linked seems a bit wacky. Mucinex is not looked upon very favorably in academic medicine, for other reasons (it doesn't seem to be a very good mucolytic)

  6. Hi Emily,

    Thank you for an interesting post. I hope everyone won't assume that people with fibromyalgia or myofascial pain syndrome automatically eat a poor diet. I have supplemented with 250mg mag for years to try to reduce my restless leg syndrome. Just over three years ago I began eating a no grain (now eat small amounts of rice) and about 75-100gms of carbs per day. The first result was that my allergies went away. Perhaps because of that, or the dietary changes, my sleep apnea was diagnosed as having disappeared, which felt like a miracle to me. My diet is not paleo, as I eat cheese, chocolate and ice cream. Mostly real foods, no gluten. Insulin resistance seems to have resolved also, according to the glucose meter, though only postprandial (not FBS).

    Regardless, I still have significant trigger point pain that I can't understand how to keep to a minimum. Sometimes it is worse than others - yesterday I played golf and I felt like I got hit by a truck the rest of the day. This does not always happen. Today I played again and much less pain. I have no idea why, as today I carried my bag and yesterday I rolled it.

    I have decent sleep hygiene but don't sleep well and most people would consider my job fairly stressful. I would love to figure out a way to reduce the body pain and reduce the trigger point knots. Magnesium just hasn't done it, though going gluten free seems to have helped. Paul J wrote about antibiotic treatment and the Road Back Foundation - but there is very little science on whether the pain is caused by infection and it is hard to find a doc that will prescribe antibiotics for pain.

    I will say I do take two drugs to help me sleep at night. Without the intervention, I don't think I could do the work required for my job (public speaking, extensive travel and trade press interviews often).

    1. I would highly recommend topical magnesium oil as an alternative to oral supplementation as it is better absorbed and very well tolerated. Mark Sisson of Mark's Daily Apple turned me onto it (and this blog too :) )
      You could also look up the book and/or website of Dr. Sircus, the author of Transdermal Magnesium Therapy.

      As always, thank you Emily for another wonderful post.

      Foggy dude

  7. Getting not enough magnesium is often due to not eating enough leafy greens. Maybe we should put that somewhere on the supplement pill boxes.

  8. in one of the last robb wolf podcasts chris kresser talks quite extensively about fibro and his undesrtanding of the mechanisms behind it (glutathione depletion, broken folate/b12/methylation cycle, etc). certainly fits into my experience. NAC,R-LA, ALC, Mg orothate (shuttles the Mg right into the cell), B12 complex, D3, and fixing SIBO and leaky gut are among the fundamentals and very powerful when treaing fibro. basic rule: if it protects or enhances glutahdione or mitochondrial function, it will help.

  9. Nick, I think most people assume nearly everyone eats a poor diet! In my experience (lumping together all sorts of illnesses, fibromyalgia, autoimmune, depressive disorders, etc. and noting that most people are unwilling to change diet) some people's symptoms are affected not at all by diet, some have terrific improvement, and most have modest to moderate improvement.

    Henk - 10 cups of raw spinach will net you 230 mg of magnesium. While leafy greens have great nutritional bang for the calories, unless you are a raw vegan with a vitamix you will have a hard time getting all your vitamins and minerals from them. Concentrated veggie sources are nuts, seeds, dried figs and dates, and whole grains (even when phytic acid is considered for the nuts, seeds, and grains). Shellfish and organ meats are the best meat sources, though 100 grams of most meat will net you about the same as a cup of raw spinach, more or less. Mineral water is another source, but you have to drink a lot. I'm 100% in favor of getting nutrition from food, but magnesium is a tough one. Magnesium I have to say is one of the very few things I supplement on a regular basis.

  10. @Nick,
    I should make the statement I made wasn't meant to sound like a slur against the chronically ill (I realize it sort of does) and indeed I too am chornically ill or people with was more a statement about people in general...and the chronically ill are also people in general...people in general eat really poorly. I'm sorry it came out sounding like I might have been painting all the chronically ill the was not my intention but I certainly see why it sounded like that. I"m sorry.

    The fact is many of the chronically ill become very motivated to get well and make big I've done too...and end up eating very well and being uber conscious about these issues.

    As long as we live in the toxic environment that we live in with convenience foods and convenient living though, the chronically ill, like everyone else in society are subject to bad food, bad air, bad water etc until they make changes...of course our whole society needs to move in that direction.

  11. Slightly off the topic...but my endocrinologist, who exclusively treats hypothyroidism, says that of the many patients who come in the door with fibromyalgia diagnoses, most no longer complain of it after he stabilizes them on a combined T4/T3 hypothyroidism treatment (with a T3/T4 dose ratio much higher than that used by conventional medicine--0!--but only a fraction of that contained in the pig thyroid extract, e.g. Armour, favored by many holistic docs).

    He says the same is true of adrenal fatigue, plus depression, anxiety, and other psychiatric diagnoses, and a great many other complaints. He speculates that many of these problems, to a significant degree, are consequences of improperly treated or untreated hypothyroidism (some of it subclinical in that it would not necessarily be diagnosed by TSH or other lab work but responds beautifully to hormone supplementation). At the least, thyroid replacement including optimal amounts of T3 (neither not enough nor too much) seems to do an awful lot of good for these problems, whatever their causes. Infertility is another example.

    He also has told me that he finds it interesting that psychiatry, a branch of medicine with substantial experience using T3, seems largely afraid to employ it in the face of endocrinology's T4-only religion, when it would help so many of the patients at small fractions of the doses that have been safely used for decades. It doesn't help that the clinical trials always use, in his view, hugely supra-physiological T3 doses, e.g. 10x what he has found in practice to be optimal. Try that with insulin and see how good that therapy fares in a diabetes clinical trial! All the dead bodies would be a bit of a problem for future funding.

    As an evolutionary aside on T4-only doctrine, he sometimes asks the faithful adherents why the healthy thyroid gland would make T3 if it wasn't needed. He has yet to get an answer.

  12. Hi William -- of course one question to ask is why are there so many people walking around hypothyroid?? I have used T3, though not extensively, in my practice. I find it works best in people diagnosed hypothyroid already on T4 (hmmm, wonder why? :-). I also find that if I use the psych doses (25-50 mcg) people almost always get side effects and become hyperthyroid within a few months. I've had much better luck with 2.5 or 5 or 10 mcg combined with lowering the dose of T4 a bit (going from 150 mcg to 125, for example). A couple of times I've had some wrangles with endocrinologists but mention "it's for psychiatric indications" and they often get scared and back off. Technically speaking T3 in particular is supposed to have a serotonin effect that t4 does not (that doesn't really make sense to me as T4 should become T3 but that's what the papers say) . In these cases I try to keep the TSH on the low end of the normal range. It has been particularly helpful in lifting residual fatigue and depression symptoms. I don't recall it ever helping fibromyalgia symptoms but my N may not be large enough.

  13. "the latest review in Hungarian about sleep disorders"

    A Magyaroknak is kell alludni.

    "Mineral water is another source"

    Yeah, I wish we got Mg in our water, but no, we get fluoride.

    If I'm not mistaken, amitryptyline is a neurotrophic tyrosine kinase agonist, too. No great surprise, since it hath all the finesse of a mace.

  14. Strake -- not wrong. That's the finesse of all the antidepressants, I'm afraid.

  15. i have fibro and my magnesium was .5 (1.5-2.2 range)
    i never had inflammation.

    some drugs to treat fibro actually cause mg wasting.

    i agree with other posters that it's more complicated, altho a multi-mineral and epsom salt bath won't hurt. you definitely sleep better.

  16. @ Gianna

    No worries, I didn't take it personally, but I do think many of the commenters in the paleosphere tend to think the answers to most problems are very prosaic and they often don't apply critical thinking to the issues (including me). In fact, if IBS, fibromylagia, obesity or brain disorders were simple we would likely understand how to treat them with better results. One thing I like about Emily is that she states up front that much of what she muses upon is hypothesis, but is yet to be scientifically proven. It is truly amazing how many times very, very smart people accept something that seems logical to only find out under scrutiny that correlation did not equal causation.

    "In my experience..." has led mankind down many blind alleys!

    @ Emily

    Interesting take on fibromylgia by one doc (now deceased, and no, I don't think that means anything with regard to his hypothesis):

  17. oh also have to add to my story

    i believe what caused my mg wasting was drinking a LOT OF water, green tea, carbonated water etc. i have pots and low blood pressure so i am always drinking water, now i drink salt water. anyhoo. also popping too many ibuprofen over the years. im not even sure why i was popping it because it wasn't working! these things feed into a vicious cycle.


    Yes, my endocrinologist says that hypothyroid people who've been on standard T4 only treatment generally feel fantastic for a while when given T3 at high doses. They're starved for T3 and feel great while repleting. But before too long they get overdosed on T3 and start to feel lousy again. They need the T3 dose lowered to physiological levels, which he has found to be only about 1.2% of the appropriate T4 dose for most people (it does vary). Your example of 2.5 mcg T3 with 125 mcg of T4 isn't too far from that.

    This is why thyroid extract, e.g. Armour, has such mixed record. At 20% T3, it works wonders for repleting T3 but patients eventually wind up overdosed on T3 and consequently their long term T4 stores deplete as TSH gets badly suppressed. They get addicted, in a sense, to the short-acting T3 since they have grossly inadequate long term T4 stores to draw upon and therefore are badly dependent upon constant T3 provision. He has to carefully wean them from the T3 overdose while repleting T4, which he says can be very difficult.

    The well meaning holistic docs who favor "natural" (pig) thyroid extract don't seem to understand this. What's natural for a pig thyroid does not seem to work very well for humans taking an oral medication. We are not pigs, and besides that T3 and T4 are differentially absorbed in the GI tract and probably handled differently in the liver. This process bears little relation to a pig's thyroid injecting hormones directly into its circulation.

    "A couple of times I've had some wrangles with endocrinologists but mention 'it's for psychiatric indications' and they often get scared and back off."

    Good plan, since I think you can't argue with endocrinologists! The T4-only gospel is not much open to question. My doc's been trying to get other endos to try--just try!--his methods and see if the patients don't in fact get better from all manner of complaints, psychiatric and otherwise, that hypothyroids are so well known for. No takers yet. He points out that patients vote with their feet: he's had many come to him from the big shot endos at the Harvard teaching hospitals, but few if any go the other way. They know what makes them feel better.

    If you're interested, he has a book coming out about all this:

    His earlier book is good, too, but he has refined his methods significantly since it was written.

    Based on my own experiences, and that of others I've sent his way, I really do believe that T3, at the right dose for true bioidentical hormone replacement, has incredible potential in medicine, and not just mental health and fibromyalgia. A hypothyroid friend of mine just had her disabling dry eye clear up 75% just by adding T3 to her T4 regime. As my doc says, if your thyroid's broke, you're broke!

    Related to the thyroid-fibromyalgia connection is the other big promising idea I'm aware of: iodine repletion. Quite a bit on iodine and fibromyalgia here:

    All a bit off your post topic, I know. Sorry, but promising ideas for natural approaches to fibromyalgia and much else of interest on this blog, so related enough I hope. Until someone patents their own high dollar designer T3 or iodine, however, getting the medical world to try such things out may be tough.

  19. @Emily
    Reverse t3? This can be an effect of excessive T4, so it stands to reason adding small amounts of T3 while decreasing T4 in hypothyroid pts presenting with depression/fatigue will help. TSH may be okay and T4 may be okay (or not) but T3 is reverse type which opposes thyroid. Euthyroid sick syndrome.
    Just goes to show poor hypothyroid people are one of those diseases that medicine does a mangle job of treating well, similar to obesity, diabetes, or any chronic non-infectious disease really.
    It's good that there are some doctors educated enough to help patients, making up for the general ignorance of others. Will never forget being told by endocrinologist within a few minutes: "I have another patient with your symptoms/like you, and have not been able to help". Really, you've never heard of PCOS? You're an endocrinologist? That's sort of scary.

  20. @WilliamS
    I find your ideas very interesting. I wonder if T3 can help post obese individuals? Our thyroid problems are downstream relative/absolute hypoleptinemia, and are therefore entirely physiologic, but I had always wondered if a dab of t3 can transform my dilapidated metabolism in a similar fashion as 0.04mg/kg recombinant human leptin, a very low dose protocol. I have been afraid to pursue this because of scare mongering pertaining to thyroid hormone.

    I have also suspected the conventional idea that excess iodine is a problem is wrong, and think many hypothyroid issues are complicated by too little. Sure we have iodized salt, but few people cook anymore and salt food, most people are living on chips and takeout and candy none of which is iodized salt. I do think part of the increased incidence of thyroid issues are related to malnutrition and low iodine, that which is not a straightforward immune system rebellion.

  21. I think the increase in thyroid incidence is a part of increase in autoimmune deceases since most hypo are diagnosed with the Hashimodo type.
    @William, I thought when I changed my Synthyroid on Aamour and finally learned how normal people feel, all my thyroid worries were over, but your post says "not yet". I feel like a deflated balloon in a spirit sense. Should I run and find a decent endo, or there are things to watch that indicate a trouble and there is a chance that Armour works?

  22. I wonder if I would benefit from T3 and feel more energy. I take T4 and my free T3 is 0.84 ng/ml (ref. range 0.80 - 2.00 ng/ml)

  23. Woo, I'm pretty sure if you asked my doc your question about T3 he'd say the only way to know is to try. That reflects the "functional" approach reflected in the title of his upcoming book. No one knows enough to confidently predict such things for a given individual.

    I think the T3 doses he uses are probably safe since they are small fractions of doses that have been used very safely for decades. However, bear in mind that his use of T3 is specifically intended for *hypothyroid* people who need hormone replacement. The wrinkle is that hypothyroidism, in milder forms at least, is not reliably diagnosable with any existing lab work. That's why new patients of his with signs and symptoms consistent with hypothyroidism are offered a trial of T4 even if labs appear "normal." It's safe and either the patient feels better or not. Many times, people have gotten dramatically better when other docs refused to treat them due to "normal" labs. He asks how he could possibly know where a given patient's body wants to be in the very wide "normal" ranges. The only way to find out is to experiment a bit.

    But using T3 outside of hypothyroidism would, I think, be well beyond anything he has done or advocated.

    As for iodine, I am convinced enough to be on 50 mg of Iodoral. It's allowed me to reduce my thyroid meds by almost half. None of my docs have ever seen or heard of anyone recovering that much, apparently, from Hashimotos. It's interesting

    I'm not absolutely sure doses that high are safe long term, but the benefits to me (and many others) are undeniable, and due to sky high bromide toxicity on iodine loading tests, I'll take my chances at least until I eliminate that bromide. It may be that widespread toxic halide exposure, including bromine, explains why we might need iodine supplementation at higher doses than provided by even seaweed-rich natural diets.

    As you may know, the docs with the most iodine experience do seem to believe that iodine deficiency underlies much hypothyroidism, and hyperthyroidism, and much else including breast cancer.

  24. Galina, don't despair. If you wind up overdosed on T3 (you'll have to base this on how you feel), you can always reduce the T3 dose. Even though my doc has found that most people do best on a T3 dose about 1.2% of their T4 dose, it does vary quite a bit. A few people, he says, seem to thrive on 100% Armour thyroid extract, at 20% T3, and a few seem to do great on the conventional T4-only regime. Unknown biochemical differences between us presumably explain such variation.

    One problem is finding a way to get the appropriate lower T3 dose if you need it. He uses compounded meds to provide the desired T3 dose (from pharmaceutical T3 or thyroid extract) in time-release form, since T3 is so short acting. I know some people without access to that use small amounts of pharmaceutical T3 in divided doses through the day instead.

    His book will explain everything he's learned, and there's always the hope of finding an open-minded doc willing to try his methods. It's not easy, though, in the current climate. Most seem afraid to depart too much from the standard of care, even if they realize it may not be very good. I don't quite know what I'll do myself when he retires! I do believe there are docs out there willing to experiment within reason (this blog is proof of that); just may be a project to find them.

    Also, bear in mind that many people say they do great long term on 100% thyroid extract meds such as Armour. My doc has told me that might be due to self-selection, i.e., the people coming to him are the ones who have failed other approaches, almost always T4-only conventional care but often also thyroid extract meds prescribed by holistic docs. His experience could be a bit skewed by that. Another reason he advocates careful experimentation and avoidance of doctrinaire attitudes.

  25. … because there are no definitive biomarkers [in FMS] …
    You should look into the gene-expression studies (with a aerobic exercise challenge) done by Kathleen and Alan Light. Their work may not be ready for clinical application, but there are measurable differences between patients and controls. And their sample size with regards to CFS (both patients and controls) seems large enough, alas but it lacks a bit on the FMS side.

    I made two posts about two lectures by Alan:

    Alan Light 2007 Lecture: The Physiology of Chronic Pain and Fatigue

    Alan Light 2011 Lecture: Gene Expression Biomarkers for Chronic Fatigue & Fibromyalgia Syndromes

    The mostly focus on CFS, but they do look into FMS as well. There is a interesting newer study where they compared CFS and MS patients.


    Unfortunately, this is a very sensible position.

    My personal n-1 anecdote (which isn't worth more than $0.02, I'm afraid) is a mixed but net positive one. First of all, I am not sure if I have FMS, CFS or something else. So the usability is a bit dampened. And secondly, after initial success with Paleo, I thought I could test other things as well. I stumbled upon cphnhelp, thought they have answers to everything (MS? It is cp! CFS? It is cp! FMS? It is cpn!) They advertise a protocol with high amounts of VitD and NAC, and do not have the scruples you voiced in that quote above. Suffice to say that VitD and NAC did more harm that good – and anybody talking about "die off" and having only a couple of anecdotes is most likely a qauck.

    So even with these caveats, here is my n-1: Paleo helped me get rid of my depression and anxiety (I blame wheat). It helped me get rid of part of my skin problems (I blame milk-products, as acne flares up when I eat milk-products every now and then). It temporarily improved my CFS/FMS (or whatever they are) symptoms. Unfortunatetly my journey into VitD/NAC/Quackland did make my CFS/FMS symptoms much worse and tainted my n-1.

    And one more observation: While I had little problems with IBS or some such, the "Chinese" or "Asian" food we have here gave me the runs.

    I would dearly like to see proper studies done with regards to a Paleo diet intervention in various diseases, something like Terry Wahls is doing in MS. But I wouldn't be surprised if food is only one etiologic component. Wolfgang Lutz reported of a stroke risk during a rapid transition from Standard Western Diet to his "bread free" diet – this alone would be counter to the "first do no harm" dogma you have. :-) We need to take the anecdotes and make proper studies based on them.

    1. Due to my n=1 I am very bias toward Paleo diet because it addressed an unbelievably long list of health issues in my case. My doctor is surprised that I don't need an asthma medication, cream for eczema,have no more seasonal flues or urinary tract infections last 4 years, no symptoms of premenopause, especially mood-swings, no leg edema (I was prescribed deuretic for that). He is also surprised I didn't regained the lost weight. The irony is I started the diet to cure migraines and loose weight. Migraines are much better but not gone, some weight is lost, but I am not really thin (size 12).

  27. Two more things:

    I think Bill Lands has good data on the hole Omega-3/-6 affair (alas, he is a terrible presenter of what he gathered…)

    I was trying to make a few points at Nikolay's blog with regards to the scientific process and giving nutritional advice with regards to illnesses like T2DM – but Nikolay wants to live out his adherence to anarchistic theory and seems hellbent on proving "the man" wrong, that he has no problem with post-modern relativism. Sigh. But I don't see the point of arguing there and maybe I am wrong person to do so anyway…

  28. Tony - Yes, I am adverse to making specific recommendations other than I think a paleo-style diet (Archevore or PHD), reasonable exercise, stress reduction and sleep hygiene will be beneficial for people in general and will not be likely to cause harm. When you get more specific, things become much more cloudy. Some people tolerate more carbohydrate or more fruit or more whatever. For me, "reasonable exercise" is crossfit 3X a week plus other low intensity work (hiking, cleaning, etc). There will obviously be a different prescription for a 70 y/o with arthritis or a 20 y/o athlete. The studies are tough. They aren't done in such a way, often, that will provide answers to the real question. A perfect example was the statin meta analysis from my last post. It gave us relative risk numbers when what we actually need to make a viable clinical decision is absolute risk and sex-specific adverse event risk.

    All, re: thyroid. There is a robust clinical literature for using T3 for depression in psychiatry, not only a host of older studies, but even up to the very large STAR-D trial where it did well (or at least as well as anything else, and better than most) as an adjunctive treatment. I can't speak to the use of T3 for hypothyroidism alone because I am not up on the literature. My clinical experience seems to match what @WilliamS's endo has found, which is interesting.

  29. Ok, one more thought re T4/T3:

    I have seen a study ( showing that T4/T3 is secreted via bile into the gut. And I remember somehow sketchy reading that a part of the T4 is turned into T3 (via some bacteria that lives there). Afterwards, both T4/T3 get reabsorbed. Don't know how much secretion/conversion/absorption happens in gut (or how solid the study was). Another one for the gut-connection list.

    While I think the gut-connection is underrated by most medical people, the few "pushing" it do overrate it a bit…

    What I can't get a handle on is the whole rT3 thing. How much do we know about rT3? The mainstream endocrinology seems to ignore it totally, while it seems to me that mostly the fringe embraces it.

  30. Dear Emily, I'm responding to this blog but the one that I really read that was so fascinating was your blog about Folic acid. I wanted to run some facts by you. I have simple partial seizures for which I take Lamictal.

    The last several months I've been having strange neuropathy symptoms and increased anxiety. They ran a test on my blood and found everything was pretty normal (in fact it was all very healthy) except for my folic acid. My level of folic acid was 88 ng/mL. My neuro was surprised. She said she'd never seen levels that high.

    I know this blog isn't to dianose, but in your studies have you every heard of high levels of folic acid causing neuropathy in an otherwise very healthy person? I'd like to take the information to my neuro.

  31. Lamictal interferes with the conversion of Folic acid to dimethylfolate. Thus on lamictal you can have high Folic acid levels. I read one paper stating that high Folic acid levels are thought to interfere with the uptake of the neuroactive form, methylfolate, into the CNS. One could presumably avoid foods and vitamins supplemented with Folic acid (leafy greens and beans and whatever rich in natural "folate" which is the dimethylfolate, should be okay) and then take supplemental methylfolate. Also, having some B vitamins out of whack can upset the others as well. Make sure your B12 is greater than 400.

  32. Hi,
    something that came to mind after reading the comments: Dr. Myhill in UK who has had trouble with the licensing board who recommends high Mg intake and 'stoneage diet'
    (sorry, I don't know tinyurl).

  33. As someone who has been diagnosed with fibromyalgia, my feeling is the following. Its just another way of saying you in conflict. No doubt eventually it has physical causes, eg your magnesium or mercury goes down or whatever, but that for me is a sign, or what adds to the problem. Essentially the body cannot handle its stress load and breaks down. I would treat it as any depression or anxiety disorder. Simplify the diet, less sugar, less meat, etc, more natural foods. A light exercise regimen, swimming is probably the best. This helps with many things, mood elevation, will release some endorphins,etc. A good multivitamin and omega 3s just to top up any thing that has become deficient. Taking and anti depressent/sleeping tablet, and go see a therapist.

    Its a long process, and you need to be committed. Emily if i may ask, have you thought of doing a study on TRE and fibromylagia and depression? Sounds like a great idea to me.

  34. About Fibromylagia and Chronic Fatige:

    Chris Kresser has some interesting information about causes, research, labtests and treatment for his patients.
    It is on Robb Wolf's Podcast 117 (you can download a transcript)

    "So number one is that chronic stressors deplete glutathione, the reduced form of glutathione, and that leads to oxidative stress; and when there's oxidative stress, toxins will accumulate because we're not able to get rid of them. Those toxins interfere with the protection and the intracellular metabolism of vitamin B12. So when you get a functional deficiency of B12 and those accumulated toxins react with a lot of the B12 that's in the body and they make it inactive as I described earlier.
    And then a lack of sufficient B12 establishes the block, basically blocks that methylation cycle by messing with methionine synthase and then sulfur metabolism becomes totally disregulated. And when sulfur metabolism doesn't work, glutathione will become depleted because
    glutathione is an end product of sulfur metabolism.
    So then you're in a really nasty vicious cycle where low glutathione leads to destruction of B12 and inactivation of B12, which in turn leads to even further reduced glutathione levels. And then you get sulfur metabolites
    draining excessively into the transsulfuration pathway and then getting excreted, and that further depletes methionine. Then you get folate draining from the cells into the blood via the methyl trap mechanism and
    you're just stuck in this really bad vicious cycle and that's why chronic fatigue is a chronic condition.

    There's a way that you can figure out if this is happening to you, and there's a test called the Methylation Pathways Panel. It's offered by Health Diagnostics Research in the US and by I think the European Laboratory of Nutrients in
    Europe and a scan lab in Europe. I've ordered it for eople in Europe and in the US. You have to be a ractitioner to order it so you have to find someone who can order it for you. There's also organic acids testing from places like Metametrix in Geneva, and there you'd be testing for urinary methylmalonic acid. If that's high,
    that means active B12 is low. Fromino-glutamic acid or Figlu, if that's high, then that suggested active folates are low; and then pyroglutamic acid, if that's out of range, then glutathione is depleted.
    And then there is the MTHFR or methylenetetrahydrofolate reductase mutation panel, DNA panel from Spector Cell, and that will test for mutations, genetic mutations that cause problems in the metabolism of folate and homocysteine; and if you have the mutation, you're way, way more likely to be suffering from this problem that I described.
    In terms of treatment, it's fairly involved -- I'll have to maybe talk about it another time or I'm going to be writing about it more and talking about it on my show. But it involves active B12, active forms of folate, phosphatidylserine or phosphatidylcholine and some other nutrients that support the methylation cycle. So anyone out there who is suffering from chronic fatigue or thinks they may be suffering from chronic fatigue or
    fibromyalgia, you can search for glutathione depletion and methylation block and you'll be able to find a lot of information."

  35. "The studies are tough."

    Yes, I know. And we certainly are not in a position to conduct such studies. Nor are we the ones responsible that such such studies haven't been done. But still, a quote I grew quite fond of recently brings it to the point:
    "The plural of anecdote is not data and even the most intuitively obvious medical beliefs must be tested"

    I think most deviations from the SAD will be helpful for *most* people, whether it is Archeovore, PHD, Sisson's Primal, Lutz's "Bread Free", Kwasniewski's "Optimal Diet", Atkin's diet or the countless others. And most people will not experience adverse events. Most. Most certainly not all. In that context, just look at statins! Some people say, looking at the numbers gathered by the studies, that total mortality stays the same with statins – less people die from heart related problems, more from other problems. And the absolute number of people dieing is really small! You don't see this in small sample sizes, especially if you have drop outs you don't follow up.

    I think most deviations from the SAD will bring down mortality, but that needs to be tested.

    The other thing, we simply don't know all pathogenic processes involved when eating SAD. For example, I don't know how solid the research is and how strong the effect is, but there seems to be some indiction that gluten exorphines act as opioids. So basically when dropping wheat and other grains, it is an abrupt discontinuation/separation or a decrease in dosage of the intake of a an opiod. In other words: withdrawal. Different people react differently to wheat and the SAD (after all, not all people suffer from depression and anxiety) and people might react differently to withdrawal.

    We need this tested.

    These might be theoretical problems (and scaremongering by me). Or these might not be theoretical problems.

    We need this tested. Tested for each disease, I am afraid. We need to know: Is there an overall beneficial effect? (I guess yes) And are there risks for some? (I guess yes)

    If a drug or a treatment, that is used in disease A, is going to be tested in disease B, it first needs to be asserted if it is safe in disease B, before the efficiency can be tested in disease B. Medical science had to learn this the hard way, I guess, and we shouldn't ignore it. It may be overkill, but we won't know if we don't test it.

    Sorry to repeat myself. We need this tested.

  36. I want to ask how our adrenal glands fit into all this.

    I had celiac and systemic inflammation which was resolved by paleo diet but later developed fibro symptoms following long overload of stress which resulted in the classic cluster of "adrenal exhaustion" symptoms (orthostatic hypotension, low temp, circadian rhythm messed up, and very low 24-hour salivary cortisol levels). For me the fibro symptoms came with the adrenal symptoms, though my thyroid levels tested normal.

    I have topical hydrocortisone (low dose) I take on and off which seems to help with the pain (I don't apply it where it hurts -- the idea is to give the adrenals a break). I've had a cold the last week and taking guaifenisen and I think it's helping with the pain too. I have taken mag supplements and epsom salts baths for a couple of years and they don't seem to help a whole lot with the pain, though maybe they make it better than it otherwise would be.

    I've been told by my doc here that giving thyroid medication to someone with adrenal trouble may further weaken the adrenals and that you have to get the adrenals functioning better first.

    Any thoughts on how the adrenal glands fit into this picture of impaired methylation, hypothyroid, fibro, etc etc? Is some of the pain accounted for by build up of lactic acid that the body lacks the capacity to get rid of?

  37. I tried to keep on point with your discussion of t3 and t4, but I am fairly uninformed about thyroid problems. My mother had a goiter for many years after which she was dx with low thyroid. My test results always come back in the normal range but right on the border line of normal/low and have for over 25 yrs. I have been unable to get a dr to treat me as having an inactive thyroid. How in the world do you get someone to pay attention and at least try synthroid or something to help. I feel my energy waning on a daily basis, not periodically changing. Yes, I have FM, CFS, Osteoarthritis (Mobic the only one I can tolerate) of which more than one dr has told me is the most severe case they have ever seen, dysthymia (do take Prozac and Remeron). Degenerative Disc Disease, Spondylosis, have had a lower fusion on L4, L5 and tailbone, but damage too extensive to allow a fusion in my neck (would need a 13 to 15 in bar fused from base of my skull to center of my back). These are just the biggest problems. Have had Epstein Barre, Mono and a few other viruses for good measure. They shot horses still don't they? So how do I go about getting a dr to treat the thyroid issue?

  38. Forgot to add I am one of the lucky ones who does take Mucinex 1200 mg twice daily (guaifinesin protocol). It has helped me immeasurably. If I run out or cannot afford to take them for more than a few days every massage therapist I have used in the past 12 yrs has noticed a marked decline in my body and muscle tissue, lumps become huge instead of just small.

  39. I have fibro, take Lyrica for it, also acid reflux, take Pariat for that, have been taking Eurthromyacin for motility and to decrease diarrhea have been told by gastroenterologist to avoid magnesium.. is this why I am depressed??

  40. A useful online database of magnesium content of foods for those who prefer dietary magnesium to supplements:


