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Fibromyalgia

5 Hours Continuing Education

Carolyn McMakin, M.A.,D.C.

Private Practice
Portland, Oregon

My Personal Hypothesis

When you put together all of the features of Fibromyalgia and all of the things that are effective in its treatment a certain group of amino acids becomes prominent.  They are the branch chain or neutral amino acids, tryptophane, tyrosine, leucine, and isoleucine.  They are all found in reduced levels in FMS patients.

These branch chain amino acids are all transported in the gut by the same amino transport molecule. There are four different amino acid transport molecules in the small intestine, one each for acidic, basic, branch chain, and proline has its own. It is a sodium co-transport system susceptible, according to Guyton, to disturbance by toxicity.  When you "clean up" the gut in some patients - their FMS symptoms go down.  The hypoallergenic diet, detox program, and antioxidant supplements would reduce intestinal inflammation and improve function of the transport proteins.

Leucine:
Each of the four types of thyroid hormone receptor has a "leucine zipper"- 10 leucine molecules in a row-right in the middle of the thyroid hormone binding domain.  If leucine is not available, reproduction of the receptors would stop, resulting in a reduced number, or there can be a frame shift in the RNA molecule and the receptors may be made incorrectly.
Tryptophane:
Serotonin is made from tryptophane.  If you supplement 5-hydroxy tryptophane, which, because of its positive charge, would use a different protein carrier molecule, patients improve.  Supplementing tryptophane doesn't seem to help.  If tryptophane levels were low because it was being used up in liver de-tox reactions then tryptophane supplementation should help. This suggests that the transport system is the problem.
Leucine/isoleucine:
Oxytocin seems to be effective in certain patients.  Oxytocin is only 10 amino acids long and there are only two essential amino acids in it, leucine and isoleucine.
Tyrosine:
Tyrosine is a precursor to epinephrine, nor epinephrine, and dopamine which are reduced in FMS patients.

Electro-acupuncture seems to work well.  If you think of protein molecules, such as the amino acid transport molecules, as existing in a certain thermodynamically stable configuration, which can shift to a different configuration when an electromagnetic current is applied along a specific axis, it provides a model as to how electro acupuncture might work. The transient elevation of endorphins may also be helpful, but doesn't explain the long-term improvement seen with electro-acupuncture.

The ragged red fibers seen in FMS could be caused by scavenging of the muscle tissue for essential amino acids unavailable through transport.

Guaifenesin is the only therapeutic agent that doesn't fit this model, but we're not really sure how it works.  The Uric acid reduction hypothesis begs the question of why uric acid is elevated in the first place, or how Uric acid elevation influences the amino acid deficiencies and other problems seen in FMS.  Guaifenesin has been reported to improve brain function and minimize damage following a stroke.  The mechanism isn't understood and there are obviously some features of Guaifenesin's actions we don't understand.

The problem in Fibromyalgia may be either in the transport, utilization or conversion of amino acids.  The transport proteins seem to me to be the most likely problem, but no one has done studies to evaluate them yet.

Dr. I John Russell at University of Texas has a similar hypothesis, and has explained the difficulties associated with verifying the hypothesis.  Radioactive tagging of amino acids to study transport is too toxic for patients, and unethical since it makes them radioactive for life.  Studying amino acid metabolic byproducts, as suggested to me by Dr.Jeffrey Bland, still leaves the basic questions of transport unanswered. If the body were scavenging the amino acids from muscle tissue the amino acid excretion products would be the same as if they were ingested.  Tissue culture study of amino acid transport would accomplish the study goal but arranging for a GI tissue sample from a living or deceased Fibromyalgia donor patient would require some persistence and good luck.

Stress, emotional trauma, or physical trauma such as surgery or an auto accident, cause a rise in serum cortisol.  In creases in cortisol cause thinning of the intestinal lining and reduction in protein production as well as a reduction in TSH and a shift from beta stimulatory receptors to alpha receptors. (Guyton).  If the increase in cortisol lasts long enough the thinning it causes in the gut lining and the reduction in protein synthesis could be responsible for a shift in the transport proteins.  This mechanism could explain the posttraumatic and emotional stress cases of FMS.  The cases of gradual onset FMS could be caused by genetic susceptibility and borderline function of the amino acid transport proteins complicated by modern diet and chronic exposure to low level toxicity in the food, air, water, and dental fillings.  Guyton states that the amino acid transport molecules are susceptible to inactivation by toxicity.  This mechanism would explain the cases that arise following some chronic or acute toxic exposure.

The "amino acid transport" model is the only model I can find which accommodates and explains the various causes of FMS, its features and treatments.  Any comments or corrections would be most appreciated.


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