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Muscle Pain in Chronic Fatigue Syndrome (ME/CFS) – Causes and Treatment

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Disuse, disrupted energy supply to muscles, magnesium deficiency, inflammation and poor antioxidant status, underactive thyroid, hypoglycemia – all are causes of general muscle pain that can be identified and helped in patients with ME/CFS.

Chronic fatigue syndrome (ME/CFS) is a symptom which may have many causes. The causes of chronic fatigue syndrome are often the same as the causes of muscle pain, and so these two symptoms are often found together. It is not that one causes the other, simply that they have a common underlying cause.

In considering any patient with muscle pain, the first question to ask is whether it is generalized muscle pain or local muscle pain. This is simply because generalized muscle pain will have a general cause, whereas localized muscle pain will have a local cause such as nerve pressure or physical damage.

This article is about generalized muscle pain.

The key to any diagnosis is to identify something that can be treated and corrected. When I see a patient with muscle pain, I am trying to think of the underlying mechanism which is causing that muscle pain, which will thereby give a clue to treatment. The sort of causes I am thinking of, and I am quite sure this is not an exhaustive list, in order of importance are as follows:

Disuse Pain

A major cause of muscle pain is disuse. This needs a little explanation. The heart is responsible for pumping blood away from the heart to the body, and of course much of the body is made up of muscles. The muscles themselves are largely responsible for pumping blood back to the heart. This occurs because when muscles contract they squeeze the blood out of them and a series of valves in our veins ensure the blood can only go in one direction; that is, back to the heart. When the muscles are at work and indeed even at rest they are making energy (in order that they can work), and the process of energy making inevitably creates toxins and free radicals.

This muscle pump also does another job; that is, it physically squeezes these toxins out of the muscles and into the blood stream where they can be detoxified and carried away.

Problems arise when the muscles stop being used.

Toxins tend to build up in the muscles, even when the muscles are at rest, and if they get to a critical level they will cause pain. The muscle’s response to pain is to go into spasm. When the muscle is in spasm, blood cannot get into it. Neither can it get out of it, and toxins build up even more quickly. So suddenly one is in a vicious cycle of muscle spasm causing toxic stress which causes more muscle spasm.

The pain from muscle spasm can be extremely severe. For example labor pains, renal colic, and biliary colic from gallstones are all muscle spasm pain. The majority of low back pain problems are also due to muscle spasm.

This, therefore, explains the benefit of many therapies such as massage, because without the muscles having to work at all they are physically squeezed, which stimulates the blood circulation and so toxins in the muscle are squeezed out.

If you watch any animal after it has lain down and slept or rested for some time, they invariably get up and stretch. This stretch passes through the body like a wave and every single muscle is contracted – this physically squeezes out the toxins which have built up during sleep or rest. This is then followed by exercise as the animal gets into its daily routine. Compare this with humans who sleep long hours at night and on rising often do not bother to stretch, let alone take any exercise.

The commonest group of muscles that are affected like this are the core muscles of the back and pelvis.

Indeed, I suspect this mechanism explains the majority of low back pains, which are often triggered by a very minor incident such as twisting awkwardly or reaching up to pick something off a shelf or whatever. Such a minor movement would not be sufficient to cause structural damage, but sometimes it is the last straw which triggers one into the vicious cycle of toxic build up and muscle spasm.

In the acute phase, therefore, anything which can be done to improve blood flow such as heat and massage is extremely helpful. This also explains why wearing a corset is so helpful, because very minor exertions greatly improve the pressure in the muscle and therefore toxins are squeezed out very efficiently. However, in the long term corsets weaken core muscles and should not be used as a long term panacea.

So the key to avoid these sorts of muscle pains and spasms is to make sure you go through a regular daily routine of stretching and gentle exercise. Just a few minutes a day suffices to help most people, and there are many regimens available such as Pilates and yoga.

This also explains why traditional advice of bed rest for acute backs actually makes the situation very much worse.

Energy Supply to Muscles

For muscles to work they need energy. Interestingly, they also need energy to relax as well as to contract.

I now see chronic fatigue syndrome as a symptom of "mitochondrial failure." Mitochondria are the little engines which power every cell in the body, and if they cannot deliver energy to the cell, then that cell will go slow. Energy is supplied to the cell by mitochondria in the form of ATP (adenosine triphosphate), which releases its energy when it is converted to ADP (adenosine diphosphate). ADP is then recycled in mitochondria back to ATP.

CFS patients are slow recyclers.

If a normal person recycles ATP every 10 seconds, perhaps [a top athlete] recycles every 5 seconds, CFS sufferers may recycle every 60 seconds! So I can do in 10 seconds what the athlete can do in 5 seconds, but that task would take a CFS sufferer 60 seconds!

However, if the CFS patient pushes himself too hard, ATP production cannot keep up and so the body switches into anaerobic metabolism whereby a small amount of ATP can be made from converting glucose into lactic acid. [Anaerobic metabolism occurs when insufficient oxygen is available for the needed muscular energy production, as in a short burst of high activity.]

However, lactic acid quickly builds up in muscle, which causes pain. Everybody has experienced this sort of pain. If somebody asked me to sprint 100 meters, then by the end of that my muscles would be aching, heavy and dead because of lactic acid that has built up. So if patients get this type of muscle symptom then I am thinking about poor energy supply by mitochondria.

This, of course, is the central problem in chronic fatigue syndrome and wants to be treated as per my routine work-up for all patients with chronic fatigue with respect to diet, micronutrients, sleep, pacing and so on.

However, I am coming to the view that some sufferers are “metabolically dyslexic.”

That is to say, they cannot make the necessary enzymes for mitochondria to work well simply from diet and supplements – they can have all the letters of the alphabet but they cannot make the words! As they cannot make their own Coenzyme Q10, D-ribose, or whatever, then these have to be supplied directly. We can test for levels of some of these essential nutrients, but some have to be supplied.

So far, my clinical experience is that the two most helpful nutrients for muscle pain are magnesium (take as much as possible without getting diarrhea – but some do require magnesium by injection) and D-ribose (5 grams taken three times daily).

Poor energy supply from mitochondria not only affects local metabolism in muscles, causing a rapid build up of lactic acid, but also affects the muscle of the heart. Indeed, many symptoms of chronic fatigue syndrome are caused by poor cardiac output secondary to cardiac muscle failure, secondary to mitochondrial failure.

This low cardiac output alone can cause muscle pain. This is because the body has to look after the important organs first – and blood is directed largely to the kidneys, liver and gut and diverted away from less essential areas like skin, muscle and joints.

So patients with poor circulation, cold hands, cold feet, intolerance of hot weather (because they cannot lose heat through their skin) and muscle pain (particularly when associated with chest pains), may indeed be suffering from low cardiac output. Very often they have low blood pressure and feel much worse standing up than lying down.

[For more about this, see Dr. Myhill’s article, “CFS as Heart Failure Secondary to Mitochondrial Malfunction.” For those interested in the test mentioned in that article, see “Mitochondrial Function Profile Test – Practical Information for Non-UK Residents.”]

Magnesium Deficiency

To understand this, a little knowledge of how muscles work is useful. Think of muscle fibers working like lots of little men in a rowing boat, all with oars and all working together. In order to make muscles contract, they dip their oars into the water and pull themselves along. For muscles to relax, the oars need to come out of the water.

  • Muscle contraction is calcium dependent,
  • And muscle relaxation is magnesium dependent.

So, for the oars to come out of the water they need magnesium, and if this is not present, the oars get stuck in the water and will snap off. The magnesium deficient patient – every time he stretches or relaxes his muscles – will cause muscle damage, and this results in pain.

Accordingly, if I see patients who get muscle pain as a result of exercise, then I would first think of magnesium deficiency.

I would want to measure levels by doing an intracellular red cell magnesium (a serum magnesium would be a useless test) and correct levels possibly with oral supplements, possibly Epsom salts baths (magnesium can be absorbed through the skin), possibly with magnesium by nebulizer; but the only way I can guarantee to get levels up is magnesium by injection. [To quote Dr. Paul Cheney, "Magnesium, like potassium, is pumped into the cell, so normally there’s a higher concentration inside the cell than there is in the blood. And that pump mechanism may not work very well in people with CFS, so their magnesium levels can be normal in the blood and low in the cell.”]


In some ways the body is not very clever. The immune system can only react to things in one way, and that is with inflammation. Inflammation is designed to kill viruses, bacteria and parasites, and to do this the immune system has to release nasty toxic substances which kill these bugs. These are called cytokines (cell killers), leukotrienes, interferons, superoxides, nitric oxide, and other such free radicals. Unfortunately these substances are rather indiscriminate and not only kill bugs, but also damage the body.

So inflammation is very much a two-edged sword, with the ability to do great good and great harm.

Inflammation in the muscles causes muscle pain. Typically this muscle pain is worse in the morning and improves as the day progresses. Sometimes tests show up muscle inflammation, either because of a raised ESR [erythrocyte sedimentation rate], a raised plasma viscosity or a raised C-reactive protein, or raised levels of muscle enzymes such as CPK [all indicators of inflammation].

Inflammation in muscles therefore obviously can be caused by chronic infections, but it can also be caused by autoimmunity and by allergy. The clinical clue to this is a symptom of being worse in the morning.

Tests to eliminate infection and/or autoimmunity can be helpful. Tests for allergy can be unreliable and initially I would suggest an elimination diet based on foods which are not commonly allergens. I favor the “StoneAge Diet,” based on meat, fish, nuts, seed, vegetables, fruit and water.

Poor Antioxidant Status

All cellular processes, in particular creating energy, will produce free radicals. If you produce a fire you will make smoke. Free radicals to the chemist are molecules with an unpaired electron – this makes them very unstable, highly reactive – and as a result they tend to stick on to anything that comes to hand. This may be cell membrane, cell organelles, DNA, or whatever.

In doing so they cause damage, and if the damage is extensive this can trigger an inflammatory process with release of nasty toxic substances which cause even more damage.

Happily the body has evolved an excellent antioxidant system which mops up these free radicals before they have time to do serious damage.

The body makes use of anything which is available, and:

  • Many vegetables, nuts and fruit contain natural antioxidants.
  • The best known antioxidants are vitamins A, C, E and selenium,
  • But the body also makes its own antioxidants such as superoxide dismutase and glutathione peroxidase.
  • Other vitamins in high doses also have antioxidant effects, in particular vitamin B3 and vitamin B12.
  • Melatonin, which is the natural sleep hormone, has important antioxidant action.

Therefore, one can see that a deficiency of any of these substances could cause muscle pain because of free radical damage. I routinely use B12 injections in my CFS patients and there is often a beneficial effect on muscle pain because of the ability of B12 to scavenge nitric oxide.

Also, I often measure levels of superoxide dismutase (SODase) and commonly find deficiencies in chronic fatigue syndrome. This can be corrected by supplements of copper, manganese, and zinc [required for SODase synthesis]. Glutathione peroxidase requires amino acids and selenium for its synthesis – hence the importance of a high protein diet. [See also Dr. Myhill’s article on Antioxidants.]

Hormonal Effects

…The symptoms of underactive thyroid can often present with muscle pain. In fatigue syndromes there is a general suppression of the hypothalamic-pituitary-adrenal axis, and one tends to see low normal levels of hormones across the board (thyroid hormones, adrenal hormones, melatonin, growth hormone and so on).

To assess thyroid function one needs a blood test to measure a TSH, a free T4 and a free T3. Very often in patients with fatigue, I see low free T4s and low free T3s – and patients feel very much better when they are running high normal free T4s and free T3s, albeit with a slightly suppressed TSH. [TSH – thyroid stimulating hormone, made by the pituitary, commands the thyroid gland to increase production of T4 and T3. T4 is thyroxine, from which the main active thyroid hormone, T3, can be made. TSH is suppressed when T4 & T3 levels are sufficient, and vice-versa.]

If mitochondria are the engines of a car, then the thyroid gland is the accelerator pedal. If it is stuck at 20 miles an hour then the poor patient cannot go any faster.

I have seen cases of muscle pain improving when DHEA levels are corrected – there is a simple test available just requiring a saliva sample, and the usual maintenance dose is 25mg daily. [DHEA – dehydroepiandrosterone – is a steroid hormone produced by the adrenal gland.]


Yudkin et al. explains all in the Lancet May 2005! ["‘Vasocrine’ signalling from perivascular fat: A mechanism linking insulin resistance to vascular disease."] Too much sugar in blood vessels going to muscles is very damaging to muscles. The control of the blood supply to muscles is by a tiny collar of fat which wraps itself round tiny arteries (arterioles). If the blood sugar rises, this collar of fat releases a cytokine which makes the arteriole contract. This has the metabolically desirable effect of preventing too much sugar getting to muscle and damaging it. However, it also has the undesirable effect of impairing the blood supply to the muscle, so the muscle cannot work properly.

Also, the cytokine released by the fat causes inflammation and damages the arteriole wall. And don’t forget in CFS we see high levels of cytokines! Indeed, this is probably the basis of high blood pressure and arterial disease. The general presumption is that these cytokines come from immune activity as a result of viral or toxic stress. But they could be produced by fat cells as a result of too much carbohydrate in the diet!

The treatment of hypoglycemia is to do a diet based on foods of low glycemic index – namely meat, fish, eggs, oils, nuts, seeds and vegetables. Care should be taken with grains, root vegetables, sugar and fruits, which are high GI foods. [See also “Hypoglycemia (low blood sygar) – a problem for many Chronic Fatigue Syndrome and Fibromyalgia patients, but treatable.”]

Treatment of Muscle Pain

I have tried to explain some of the mechanisms by which muscle pain is produced. However, some of these mechanisms also have common causes. For example magnesium deficiency will cause muscle pain because:

  • Muscles are unable to relax without causing damage,
  • Because magnesium is the spark plug which fires the engine, i.e. the mitochondria in every cell,
  • Because magnesium deficiency pre-disposes to allergies, and
  • Magnesium is also required in the manufacture of thyroid hormones.

So really, treatment of muscle pain should be as per my treatment for chronic fatigue syndrome:

1. Start off with the basic essentials with respect to diet, micronutrients, sleep, and pacing, and this addresses many of the underlying problems.

2. Then one can move on to the more esoteric treatments such as magnesium, B12, correcting thyroid and adrenal status, looking for specific deficiencies of vitamin B3, superoxide dismutase, Coenzyme Q10, specific vitamins and minerals and essential fatty acids.

What I have not discussed above, but what is also a major cause of muscle pain, is mitochondrial damage by toxins such as pesticides, heavy metals, volatile organic compounds and foreign bodies such as silicone. These all cause muscle pain because of direct damage to mitochondria, and need to be dealt with by doing a good detox sweating regimen.

I find myself most often caught out by patients who are multiply intolerant of foods, who have undiagnosed multiple chemical sensitivity or mould allergy. If the muscle pain does not settle from the above interventions, this can be because one cannot break the vicious cycle of allergy, inflammation, and micronutrient deficiency.

Sometimes one just has to revert to medication to try to tackle some of the underlying pain and inflammation, and then this gives the body a chance to respond to the diet and supplements.

The medical profession likes to use non-steroidal antiinflammatories [such as aspirin or ibuprofen] and Cox II inhibitors [such as Celebrex]… The trouble with these is that they all cause leaky gut and therefore increase any tendency to allergy or autoimmunity. In addition, nearly 20% of patients taking these drugs will develop bleeding from the gut, and a small proportion can go on to get gut strictures.

So I am really not a fan of using these drugs, but there are some excellent herbal alternatives which seem relatively free from side effects which are well worth trying. The ones that I most commonly recommend are:

  • Willow bark tablets – 120mg daily
  • Green tea – the polyphenyls in green tea have powerful anti-inflammatory effects and are cox II inhibitors
  • Ginger – this inhibits both cox II and leukotriene synthesis as well as inhibiting the metabolism of arachidonic acid. I suggest using up to 1000mg of fresh ginger root daily. Indeed chewing fresh ginger root is an excellent treatment for gum disease and dental plaque!

There are many other herbal preparations which are said to be anti-inflammatory, but I do not have experience of using them, so I cannot comment.…

* Dr. Sarah Myhill, MD, is an internationally recognized, UK-based ME/CFS specialist focused on preventive healthcare, nutrition, and patient education. This material is reproduced here with permission of the author from pp. 128-133 of Dr. Myhill’s 193-page book, Diagnosing and Treating Chronic Fatigue Syndrome, which is offered free online in pdf format at her patient-information website (http://www.drmyhill.co.uk). R Sarah Myhill Limited, Registered in England and Wales: Reg. No. 4545198

Note: This information has not been evaluated by the FDA. It is generic and is not meant to prevent, diagnose, treat or cure any illness, condition, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

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One thought on “Muscle Pain in Chronic Fatigue Syndrome (ME/CFS) – Causes and Treatment”

  1. charming says:

    Just a yesterday I seen my physician and it looks like he been reading up on fibromyalgia because he ordered all kind of blood work and x-rays to make sure I am getting the proper care and diagnoses. There are certain things mentioned in this article that made me think of all the blood work I’ve taken like thyroid 3rd generation test , some kind of DNA test I think its the sickle cell test and rhematoid and CBC and a complete lipid panel.

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