by Dr. Sarah Myhill
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.
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 ATP (adenosine triphosphate) via a process called oxidative phosphorylation. This process requires oxygen, is extremely efficient and the way in which the vast majority of energy is produced for the vast majority of time.
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 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 mitochondrial production of energy (aerobic) to glycolysis (very inefficient 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.
For some reason (see below) this does not seem to happen in fibromyalgia and the sufferer is completely pole axed by inability to move, ongoing lactic acid burn 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 and, 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 What are the reasons why people should switch into glycolysis rather than oxidative phosphorylation?
1. 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 handout - causes of CFS, mitochondrial failure and mitochondrial function test) 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), poor antioxidant status (so mitochondria are damaged by biochemical activity), poor hormonal control (poor levels of thyroid or adrenal hormones) and so on.
2. 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 were 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 with 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.
3. 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 requires the muscle itself to contract. Thanks to a serious 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 it is 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 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.
Implications for Treatment
1. Treatment of mitochondrial failure as per handout. My experience so far is that this works reliably well, but it takes moths to respond, not weeks, but improvement is sustained month on month. What gets in the way is allergy - that is to say tolerating the supplements.
2. 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. Eating sugar provides immediate substrate for glycolysis.
3. 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. 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!
4. 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. There is one antioxidant which has been trialled in horses with good results called astaxanthin and the dose for humans would be 4mg daily.
5. Possible suggestions for the future. Allow me to digress for a moment. It has been known from work done by Otto Warburg in 1930 that the difference between cancer cells and normal cells is that cancer cells can only function on glycolysis as their energy source, whilst normal cells function on mitochondria. It has been thought up until recently that this was a secondary effect of cells becoming cancerous. However, it now looks very much as though this is the primary effect that is to say this is a cause of cancer. The problem with cells switching to glycolysis is that it is mitochondria which control survival of the whole cell because they activate apoptosis, which is the mechanism by which normal cells self destruct. When cells switch mitochondria off, they become immortal and this is, of course, the basis of cancer.
Therefore, this is one possible basis for treating cancer and indeed has already been shown to be an effective treatment. By using a drug, namely dichloroacetate (DCA), cells can be switched from glycolysis and back to normal mitochondrial function (this of course pre-supposes the existence of healthy mitochondria!). In cancer, the switch from mitochondria to glycolysis is probably caused by some sort of genetic damage. By feeding tumour cells DCA, glycolysis is switched off, mitochondrial function is switched on, mitochondria recognises that the cell is damaged and causes it to self-destruct. Therefore this is an extremely cheap and effective way of treating all cancers, whatever that cancer may be.
However, it strikes me that this could also be a useful way of switching people back from glycolysis to normal aerobic respiration. It may well be that part of the problems in fibromyalgia and chronic fatigue syndrome is that metabolism gets in a rut. It literally gets used to glycolysis because that is the route that it has been switched into for reasons above. Once the mitochondrial lesion has been repaired, we then need a switch to kick people back into oxidative phosphorylation instead of a tendency to lapse into glycolysis. Remember that from an evolutionary point of view, glycolysis is a more primitive and therefore possibly more desirable root because it has been longer established.
So this is a possible therapeutic avenue if all the above interventions do not have an impact in fibromyalgia. The only problem is that this drug is only available on a named patient basis and the only compounding pharmacy that can supply is College Pharmacy. It is all rather expensive! So far I have not tried this for anyone! John McLaren Howard is also developing his ideas on mitochondrial function by looking at mitochondrial membranes and this may have implications for treatment.