Fibromyalgia - possible causes and implications for treatment
Fibromyalgia is just a symptom - it just means pain in the muscles. It occurs very commonly with chronic fatigue syndrome because I suspect the underlying causes are similar.
How energy is produced in cells
All cells require energy in order to work. There are two ways that they can get their energy. Normally energy is supplied to cells by mitochondria (little organelles within cells), which supply energy in the form of Adenosine Triphosphate (ATP) via a process called Oxidative Phosphorylation. This process requires oxygen, is extremely efficient and is the way in which the vast majority of energy is produced for the vast majority of time. You might enjoy watching a very interesing presentation on oxidative phosphorylation published on the website of Purdue University, Indiana. (Details in External Links below)
The second way in which cells can get energy is through Glycolysis. From an evolutionary point of view this is a very much more primitive way of supplying energy. It does not require oxygen, it just needs sugar. It is extremely inefficient and the result of glycolysis is the production of large amounts of lactic acid. All athletes recognise the moment when they switch from aerobic metabolism (requiring oxygen) via mitochondria to anaerobic metabolism (glycolysis) resulting in a build up of lactic acid. It is this build up of lactic acid that causes the pain, heaviness, feeling of exhaustion, deadened muscles, and 'muscles will not work or go any faster' sensation.
I am also interested in this idea because in horses there is a condition known as azoturia (tying up), which does not have an obvious human parallel. I suspect, however, that this parallel is fibromyalgia. This condition occurs in some susceptible horses when there is a huge build up of lactic acid in their muscles which causes extremely severe muscle damage, massive amounts of pain and distress and in severe acute cases the horse can die from it.
So what goes wrong in fibromyalgia?
I suspect that in fibromyalgia there is an inappropriate switch from aerobic mitochondrial production of energy (via oxidative phosphorylation) to glycolysis (very inefficient anaerobic production of energy, not requiring oxygen, but with a large build up of lactic acid). Lactic acid in the short term causes immediate muscle pain. Normally this is remedied by the person slowing down or stopping because of that pain, cells switch back into aerobic metabolism and the lactic acid is quickly cleared away and got rid of. All athletes know that when they stop running the horrible painful sensation in their legs will be gone within a few seconds or minutes.
This does not happen in fibromyalgia because the sufferer can't make ATP quickly enough to shunt lactic acid back to acetate (via the Cori Cycle Please see Wikipedia entry on the Cori Cycle) and the sufferer is completely pole axed by ongoing lactic acid burn with inability to move and possibly secondary damage from lactic acid which, for example, is good at breaking down the collagen matrix which holds cells together. That is to say, the lactic acid may cause microscopic muscle tears, which would present as local areas of soreness and would trigger a process of healing and repair by the immune system. There would also be excessive release of free radicals as the immune system repairs. This may well cause further muscle damage in people with poor antioxidant system. This is a disease amplifying process. Some sufferers find B12 helpful, possibly because it is acting as a scavenger of free radicals.
So why this switch into glycolysis?
- The most obvious reason for this of course is mitochondrial failure, which I believe is a major cause of chronic fatigue syndrome.
- If mitochondria cannot supply sufficient energy to cells, cells will switch into glycolysis with a resultant build up of lactic acid. In the heart, this switch into anaerobic metabolism because of mitochondrial failure will present with angina (chest pain). There are many causes of mitochondrial failure (see CFS - The Central Cause: Mitochondrial Failure and Mitochondrial Function Profile) such as lack of nutrients for mitochondria to work (D-ribose, magnesium, Vitamin B3, co-enzyme Q10 and acetyl L-carnitine), toxic stress (which is blocking oxidative phosphorylation, or blocking translocator protein function. Please see Wikipedia entry on Translocator proteins), poor antioxidant status (so mitochondria are damaged by biochemical activity), poor hormonal control (poor levels of thyroid or adrenal hormones) and so on.
- Lack of oxygen to muscles.
- There was a fascinating paper in the Lancet recently by John Yudkin explaining how a high carbohydrate diet could cause high blood pressure. He demonstrated that high levels of sugar in the blood are very damaging to muscles and the body compensates for this by shutting down the blood supply to muscles when blood sugar levels are running too high. Whilst this protects muscles from damage by sugar, it restricts oxygen supply to that muscle. Therefore, one can see how if that muscle was asked to suddenly work quite hard, it would rapidly switch into glycolysis (because that muscle had very little oxygen supply available) which in turn would result in the production of lactic acid. Therefore, I suspect high carbohydrate or high sugar diets are a risk factor for fibromyalgia. In horses with azoturia, a high carbohydrate diet is a known risk factor. Please see Professor Yudkin's profile and full details of all his published paper - Professor Yudkin's profile at UCL
- Exercise - too much or too little!
- Muscles are extremely dynamic organs. Blood is obviously supplied to them by the heart. However, for blood to come out of muscles. the muscle is required to contract itself. Thanks to a series of valves within veins, when muscles contract they squeeze the blood out of themselves, then as they relax the muscles fill with blood from the heart and then as they contract, the blood is pumped out of them again. Indeed, during exercise it is this alternate muscle contraction and relaxation that is largely responsible for the circulation of blood through the muscle. That is to say, the muscles like being worked - it is essential for good blood supply and this contraction-relaxation cycle is also essential to move out and excrete toxins (such as lactic acid), which inevitably build up in muscles when they are being used. The problem for people with fatigue syndromes is that they do not have sufficient energy to exercise their muscles and therefore bring an adequate blood supply to their muscles and this alone causes muscle problems. This is compounded in severe CFS, where cardiac output is poor, because of mitochondrial failure in heart muscle! For example, if there is too much build up of toxins in muscle, the reflex response of that muscle is to go into spasm. If that muscle goes into spasm and remains in spasm (i.e. a cramp), then the circulation is further impaired and there is a sudden and quick build up of toxic metabolites, which causes more pain and spasm. This is exactly what happens in horses with azoturia (hence its other name 'tying up'). There is so much muscle spasm and pain that the horse is literally unable to move and there is a huge amount of tissue damage going on. Obviously, humans do not push themselves to the extremes that horses do and so we do not see this same acute clinical picture, but I suspect the underlying biochemistry is the same.
- The Cori Cycle
- In converting glucose to lactic acid, 2 molecules of ATP are produced. To get rid of lactic acid it has to be converted back to glucose, but this requires 6 molecules of ATP. When energy in the form of ATP is in such short supply, lactic acid 'hangs around much longer' in the body and is therefore much more damaging. This explains "atypical chest pain" seen in ME patients. They experience lactic acid burn of the heart muscle which is called angina. But because it takes a long time for the lactic acid to clear, the pain is much more persistent than angina due to poor blood supply.
Implications for Treatment
- Treatment of mitochondrial failure (Please see CFS - The Central Cause: Mitochondrial Failure)
- My experience so far is that this works reliably well, but that it takes months to respond, rather than weeks. However, improvement is sustained month on month. To achieve this one has to take the necessary supplements, not let the fermenting gut get in the way (ie good absorption) and, where blockage is a feature of the tests, do the necessary detoxification regimes (see Detoxification - an overview )
- Eat a low carbohydrate low sugar diet.
- Most calories should come from protein, fat and complex carbohydrates requiring gut fermentation by probiotics - these ferment carbohydrates into short chain fatty acids which are the desirable fuel for mitochondria.
- The muscle problem.
- There is a fine balance to be judged here! When the muscle is in acute spasm and in pain, the worst thing you can possibly do is to exercise it because it will simply make everything much worse. A common cause of acute muscle spasm and pain is Allergic muscles. However, the muscle does require blood circulation in order to heal and repair and this can be encouraged by muscle relaxants (such as diazepam), improving trace mineral status (imbalance of magnesium, calcium, sodium and potassium can cause a tendency to cramp and muscle spasm), heat (to improve blood supply), and ideally massage or toning tables. The idea here is that the muscle is gently and rhythmically squashed, which therefore improves the circulation of the muscle, but without the muscle having to do any work. Painkillers may be helpful because the body's response to pain is muscle spasm.
- However, if the muscle feels completely fine and is not painful at all then it should be exercised gently on a daily basis. Obviously, the more exercise one can tolerate the better, but as soon as it switches into pain, you must stop or you simply make the situation much worse. Gentle daily use of the muscles, therefore, improves the circulation and helps the muscle to clear toxic metabolites which trigger the above problems. This may be why yoga or Pilates exercises are often helpful in fibromyalgia. However, do not use painkillers to allow exercise - this may make things much worse!
- Improve antioxidant status.
- As soon as muscle starts to become painful and release toxic metabolites, there is secondary muscle damage by free radicals. Having good antioxidant status helps protect against this secondary damage. The obvious antioxidants to measure which I check on a regular basis are Co-enzyme Q10, glutathione peroxidase, and superoxide dismutase. See Antioxidants.
- Iodine deficiency. This may present with fibromyalgia. See Iodine - what is the correct daily dose?
- Allergic muscles
- Muscle Stiffness
- CFS - The Central Cause: Mitochondrial Failure
- Detoxification - an overview
Oxidative Phosphorylation. Online presentation published by the Department of Chemistry, College of Science at Purdue University, Indiana, USA.
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