Dr Myhill on Fibromyalgia and Mitochondrial Dysfunction
ProHealth.comby Sarah Myhill, MD*
December 21, 2011
Dr. Sarah Myhill is a UK-based physician with a special interest in fatigue and nutrition. Her pioneering research (“Chronic Fatigue Syndrome and Mitochondrial Dysfunction”)
suggests the cells’ energy generating mitochondria are dysfunctional in
ME/CFS – a situation that can produce various symptom clusters,
including: a) blood flow/vascular abnormalities such as orthostatic
intolerance, b) the widespread pain and sensitization most typical of
fibromyalgia syndrome, and c) fatigue, exhaustion & brain fog. This
information is excerpted with kind permission from (DrMyhill.co.uk).*
_________________
Fibromyalgia – Possible Causes and Implications for Treatment
The word ‘fibromyalgia’ just refers to a symptom - it means pain in the muscles. It occurs very commonly with chronic fatigue syndrome [ME/CFS] 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.
Energy Production Using Oxygen. 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 the vast majority of the time. You might enjoy watching a very interesting presentation on oxidative phosphorylation (which starts with NADH and Ubiquinol CoQ-10) - published on the website of Purdue University, Indiana.
Energy Production Using Sugar. 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 recognize 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 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:
_________________
Fibromyalgia – Possible Causes and Implications for Treatment
The word ‘fibromyalgia’ just refers to a symptom - it means pain in the muscles. It occurs very commonly with chronic fatigue syndrome [ME/CFS] 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.
Energy Production Using Oxygen. 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 the vast majority of the time. You might enjoy watching a very interesting presentation on oxidative phosphorylation (which starts with NADH and Ubiquinol CoQ-10) - published on the website of Purdue University, Indiana.
Energy Production Using Sugar. 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 recognize 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 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 quick enough to shunt lactic acid back to acetate (via the Cori Cycle, aka Lactic Acid Cycle; more on this below).
• 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 and - in people with poor antioxidant system - this is a
disease amplifying process. Some sufferers find vitamin B-12 helpful,
possibly because it is acting as a scavenger of free radicals.
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:
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 (niacin), co-enzyme Q10 and acetyl L-carnitine). [Note: A trial due to start in early 2012 at Columbia University will test the ability of selected nutraceuticals to help manage lactate levels and other aspects of mitochondrial dysfunction in ME/CFS.]
• 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 may be another reason for the switch to glycolysis.
A fascinating paper in the Lancet by John Yudkin explains how a high carbohydrate diet could cause high blood pressure. [As a long-time professor of nutrition and dietetics at the University of London, he was an early advocate of low carb Atkins-type diets]. Dr. Yudkin 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. One can see how if that muscle were 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.
4. The Cori Cycle (aka Lactic Acid Cycle)
A fascinating paper in the Lancet by John Yudkin explains how a high carbohydrate diet could cause high blood pressure. [As a long-time professor of nutrition and dietetics at the University of London, he was an early advocate of low carb Atkins-type diets]. Dr. Yudkin 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. One can see how if that muscle were 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.
4. The Cori Cycle (aka Lactic Acid 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 and is more damaging.
Implications for Treatment
1. Treatment of mitochondrial failure as per handout.
My experience so far is that:
1. Treatment of mitochondrial failure as per handout.
My experience so far is that:
• This works reliably well, though it takes months 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.
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:
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.
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),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.
• 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.
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. [See "A Primer on Antioxidants and Free Radicals."]
There is one antioxidant which has been trialed in horses with good results called astaxanthin, and the dose for humans would be 4mg daily. [See “Astaxanthin – A little-known but power-packed nutrient.”]
5. Iodine deficiency.
This may present with fibromyalgia. [See “Iodine – What is the correct daily dose?”]
