The Fibro Puzzle

Discussion in 'Fibromyalgia and ME & Chronic Fatigue Syndrome' started by Annesse, Nov 13, 2012.

  1. Annesse

    Annesse Member

    I think protease is more involved in ME and FM, but I will be presenting evidence of a lack of DNase1 also. For instance, the low levels of uric acid that that have been found in ME would point directly to DNase1. Uric acid is the final break down product of dietary DNA. If you lacked DNase1 (which digests dietary DNA) you would have lower levels of uric acid.


    Uric acid is a potent scavenger of peroxynitrite ( a powerful oxidant).
  2. Annesse

    Annesse Member


    Both restless legs syndrome (RLS) and fibromyalgia are associated with hypothyroidism.
    http://www.umm.edu/patiented/articles/what_risk_factors_restless_legs_syndr ome_000095_3.htm
    http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001463/?report=printable

    The thyroid hormones, thyroxine and triiodothyronine, are both derived from tyrosine, just as dopamine is. Tyrosine is derived from the essential amino acid phenylalanine. (Phenylalanine>Tyrosine>Dopamine) Just as dopamine breaks down into both of the adrenal hormones, tyrosine breaks down into both of the thyroid hormones.

    So, without the essential amino acid phenylalanine (which fibromyalgia patients lack) you would not be able to produce either of your thyroid hormones, nor would you be able to produce dopamine. This would explain why both fibromyalgia and RLS are associated with hypothyroidism.

    Here are some of the symptoms of hypothyroidism from WebMD.

    Hypothyroidism can cause many different symptoms, such as:
    Feeling tired, weak, or depressed.
    Dry skin and brittle nails.
    Not being able to stand the cold.
    Constipation.
    Memory problems or having trouble thinking clearly.
    Heavy or irregular menstrual periods

  3. IanH

    IanH Active Member

    Which protease(es) are you suggesting? and why?
  4. Annesse

    Annesse Member

    Hi IanH~

    When I use the term "protease", I am referring to the group of enzymes that break down protein. Not a specific protease.


    I also wanted to add that every scientific finding I post for fibromyalgia, I can also post a corresponding one for CFS if anyone would like me to. For instance, CFS patients also lack essential amino acids, such as phenylalanine. Phenylalanine is needed to produce dopamine and both of the adrenal hormones and the thyroid hormones. This would explain the "significant adrenal atrophy" found in CFS in this study.
    http://www.ncbi.nlm.nih.gov/pubmed/10451910

    In addition to significant decreases in phenylalanine, the following study also found that CFS patients lacked the branched-chain amino acids; leucine, isoleucine, and valine. The researchers stated that, "Branched-chain amino acids have anabolic and anti-proteolytic effects on muscle protein.

    These are not isolated findings. The study states that the "majority" of studies have noted reductions in amino acid levels in CFS patients compared to healthy controls. (I have permission to reprint the following information.)

    Hematologic and Urinary Excretion Anomalies in Patients with
    Chronic Fatigue Syndrome
    Niblett, S.H., K.E. King, R.H. Dunstan, P. Clifton-Bligh, L.A. Hoskin, T.K. Roberts, G.R.
    Fulcher, N.R. McGregor, J.C. Dunsmore, H.L. Butt, I. Klienbeg, T.B. Rothkirch. 2007. Exp
    Biol Med 232(8):1041-9.
    http://www.ncbi.nlm.nih.gov/pubmed/17720950

    Fibromyalgia patients were also found lacking the three branched chain
    amino acids (BCAAs) in the study entitled “Serotonergic markers
    and lowered plasma branched-chain-amino acid concentrations in
    fibromyalgia” (Maes, 2000). The patients had significantly lower levels of
    phenylalanine as well. The researchers stated, “Patients with fibromyalgia
    had significantly lower plasma concentrations of the three BCAAs (valine,
    leucine, and isoleucine) and phenylalanine than normal controls. It is
    hypothesized that the relative deficiency in the BCAAs may play a role in
    the pathophysiology of fibromyalgia, since the BCAAs supply energy to
    the muscle and regulate protein synthesis in the muscles.”


  5. IanH

    IanH Active Member

    Serum amino acids, in particular phenylalanine, leucine, isoleucine and tryptophan are lower in ME (as well as in FM) because the energy system is dysfunctional. The citric acid cycle is dysfunctional and glycolysis is malfunctioning. In addition carnitine levels are low, PPAR functioning is low and mitochondrial membrane potential is low, both of which are an indicator of poor fat metabolism.

    This causes energy derivation from proteins, in particular the above amino acids. In simple terms the body, mainly muscle tissue, is deriving more energy than usual from proteins. This, in turn causes low measures of serum amino acids in ME. The high levels of uric acid are due to this excessive reliance on protein derived energy. Where is the evidence that proteases are dysfunctional?

    Michael Maes was partly onto it when he said "It is
    hypothesized that the relative deficiency in the BCAAs may play a role in
    the pathophysiology of fibromyalgia, since the BCAAs supply energy to
    the muscle and regulate protein synthesis in the muscles.” (http://www.ncbi.nlm.nih.gov/pubmed/17720950)

    But that was way back in 2000, since then we have found that the aa deficiency problem is metabolic rather than a transcription problem. Michael was trying to postulate that muscle energy deficits were being caused by a lack of protein as a metabolic source. As you would know, proteins are a last resort for energy except in ME.
  6. Annesse

    Annesse Member

    I disagree Ian. I believe that the mitochondrial dysfunction is due to a lack of the missing essential amino acids .For instance, you mention carnitine levels are low. That is true.Carnitine is essential for the proper functioning of the mitochondria. Carnitine is derived from the essential amino acid methionine. Methionine is one of the essential amino acids found lacking in the previous studies I posted in fibro.


    As with carnitine, the essential amino acid methionine is also needed
    to produce glutathione. Glutathione is an integral part of the body’s detoxification system. It helps the mitochondria avoid or repair damage that would normally lead
    to mitochondrial dysfunction and cell death. Methionine is a precursor for
    cysteine, and cysteine is a precursor for glutathione.

    In addition to carnitine and glutathione, another critical component
    necessary for the proper functioning of the mitochondria is Coenzyme Q10
    (CoQ10). It acts as an essential cofactor to produce adenosine triphosphate
    (ATP), which is the currency of energy in the body. CoQ10 also functions as an antioxidant.

    CoQ10 is a fat-soluble compound synthesized by the body and also
    consumed in the diet. A report from Iowa State University lists beef,
    chicken, pork, and fish as the foods with the highest levels of CoQ10. In
    a healthy person, CoQ10 can be synthesized, but it requires the presence
    of one of two amino acids we have found lacking in CFS and fibromyalgia,
    phenylalanine or tyrosine.

    According to the Linus Pauling Institute’s Micronutrient Information
    Center at Oregon State University, one of the major steps involved in biosynthesis
    of coenzyme Q10 uses either tyrosine or phenylalanine for synthesis
    of the benzoquinone structure (Higdon, 2003).


    Studies show that fibromyalgia and CFS patients lack carnitine, glutathione, and CoQ10.

    Without protease you would not be able to release the essential amino acids that are needed to produce carnitine, glutathione or CoQ10.

    You ask where is the evidence that protease are dysfunctional? I have already shown that protease regulate iron absorption and cellular iron release. Mitochondrial dysfunction would not explain the abnormal iron metabolism found in fibromyalgia.

    Nor would mitochondrial dysfunction explain the comorbidity fibromyalgia has with lupus. DNase1 has been determined to be a causative factor of lupus, not mitochondrial dysfunction. A lack of DNase1 and protease will lead to mitochondrial dysfunction though.

    The other piece of evidence I have presented is that the low levels of uric acid found in fibromyalgia and CFS can be traced directly back to DNase1. Uric acid is the final break down product of dietary DNA and DNase1 breaks down dietary DNA. If you lacked DNase1 you would not be able to digest dietary DNA and therefore, you would have low levels of uric acid. You mentioned Dr. Martin Pall. Here is what he states about uric acid and CFS and fibro:

    "People with these diseases tend to be low in uric acid presumably because of the oxidation of uric acid by peroxynitrite and its breakdown products."

    http://esme-eu.com/supplements/how-can-we-cure-no-onoo-cycle-diseases-approaches-to-curing-chronic-fatigue-syndrome-myalgic-encephalomyelitis-fibromyalgia-multiple-chemical-sensitivity-article314-139.html

    Please be patient. I have only just begun. I will be presenting very definitive evidence that shows the involvement of protease in CFS and fibromyalgia.




    [This Message was Edited on 11/22/2012]
    [This Message was Edited on 11/22/2012]
  7. IanH

    IanH Active Member

    I hope you will be more specific in your identification of "protease" There are so many proteases. Otherwise what you are saying is just a pile of associations without a proper theoretical framework.

    Also mitochondrial dysfunction is ubiquitous in ME but that is not to say that it is the cause of ME. It may well be an effect of upregulated INFalpha and IFNgamma both of which affect mitochondrial function.

    also can you direct me to a study which shows "abnormal" iron metabolism in ME (or FM) but not a hair analysis as they are unreliable.

  8. IanH

    IanH Active Member

    I think your focus has some merit but I think you should look at the kinases not the proteases. In particular PKA and PKC. These are much more likely to be dysfunctional and indeed there is evidence already implicating them in many of the neuro-immune disorders including ME. They are also well linked to the energetics and mitochondrial membrane depolarization, which is not empirically connected to protease function.
  9. Annesse

    Annesse Member

    Hi Ian~

    At a lecture given by Dr. Wood (scientific advisor for the National Fibromyalgia Association) at the Salt Lake City Medical Care Providers Conference he stated that "a growing body of evidence suggests abnormal iron metabolism in FM". A study on this is due to be published soon.

    Here is a link to a discussion of this and other topics covered at the conference.
    http://www.hadit.com/forums/index.php?/topic/39351-answers-being-found-on-cfids-and-fibromyalgia-what-benefits-for-ill-gulf-war-veterans/

    Since protease regulate iron absorption and cellular iron release, a lack of protease would explain the low serum ferritin found in the study I posted. I agree with Dr. Woods though, and I think future studies will show the low serum ferritin is a result of abnormal iron metabolism. This would mean the body is pulling the ferritin from the blood in order to bind the iron in the cell, since it is not being allowed to leave the cell.

    This is just one example of why we shouldn't look at these diseases in simplistic terms and just treat symptoms. A low serum level of iron in FM and ME may very well be due to toxic overload within the cells. So we wouldn't want to ingest more iron in supplement form.


    Here is a study from my book (I have permission to reprint) that shows the connection to higher levels of ferritin in the cells due to "deregulation of intracellular iron homostasis" and cancer.
    Remember, ferritin is a binding protein that is bound to iron to render it harmless. The body tries to protect the cells from iron by pulling in ferritin from the blood.


    Role of ferritin alterations in human breast cancer cells.
    Shpyleva SI, Tryndyak VP, Kovalchuk O, Starlard-Davenport A, Chekhun VF, Beland FA, Pogribny IP.
    SourceDivision of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.

    Abstract
    Breast cancer is the most common malignancy in women. Successful treatment of breast cancer relies on a better understanding of the molecular mechanisms involved in breast cancer initiation and progression. Recent studies have suggested a crucial role of perturbations in ferritin levels and tightly associated with this, the deregulation of intracellular iron homeostasis..."



    The researchers also found that women with breast cancer had levels of ferritin in their breast fluid that were 5X higher than women without cancer.
    [This Message was Edited on 11/23/2012]
  10. Annesse

    Annesse Member

    Fibromyalgia and ME patients have been shown in studies to lack the nutrients necessary for the proper functioning of the mitochrondria. Coenzyme Q10, carnitine, B12 and glutathione are all essential for the mitochrondria.

    CoQ10 acts as an essential cofactor to produce adenosine triphosphate (ATP), which is the currency of energy in the body. CoQ10 also functions as an antioxidant.

    A recent study found that plasma CoQ10 was significantly lower in chronic fatigue syndrome patients than in normal control patients (Maes, 2009).
    It stated, “Up to 44.8% of patients with ME/CFS had values beneath the
    lowest plasma CoQ10 value detected in the normal controls…”

    The following study entitled "Oxidative stress and mitochondrial dysfunction in fibromyalgia" states, "Signs and symptoms associated with muscular alteration and mitochondrial dysfunction, including oxidative stress, have been observed in patients with FM. To this respect, Coenzyme Q10 deficiency, an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant, alters mitochondria function and mitochondrial respiratory complexes organization and leading to increased ROS generation." The study also states that fibromyalgia patients have been shown to have a CoQ10 deficiency in blood mononuclear cells.
    http://www.ncbi.nlm.nih.gov/pubmed/20424583

    The following study found that fibromylagia had significantly lower levels of ATP.

    http://www.ncbi.nlm.nih.gov/pubmed/9506567



    CoQ10 is a fat-soluble compound synthesized by the body and also
    consumed in the diet. A report from Iowa State University lists beef,
    chicken, pork, and fish as the foods with the highest levels of CoQ10. In
    a healthy person, CoQ10 can be synthesized, but it requires the presence
    of one of two amino acids we have found lacking in CFS and fibromyalgia,
    phenylalanine or tyrosine.

    A lack of protease would lead not only to a lack of the essential amino acids necessary to produce CoQ10, but it would also most likely lead to the inability to acquire it in adequate amounts from the diet.

    CoQ10 also protects the mitochondrial membrane from depolarization.

    http://www.ncbi.nlm.nih.gov/pubmed/15934940

    http://www.ncbi.nlm.nih.gov/pubmed/12736273

  11. sunflowergirl

    sunflowergirl Active Member

    I have an appt. friday with a new integrative doctor and I'm going to bring all this information to her.....hoping she can run all the lab tests available and get me on the right road to health.

    And I also thank others who have kindly shared their research. What would we do without this board!
  12. Annesse

    Annesse Member

    You're welcome sunflowergirl. I hope your appt. goes well.

    Another nutrient found lacking in fibromylalgia patients is zinc. The following study found that serum levels of zinc were significantly reduced in fibromyalgia patients.

    http://link.springer.com/article/10.1007%2Fs00296-008-0593-9

    Here is some information on zinc and its functions.
    http://www.nlm.nih.gov/medlineplus/ency/article/002416.htm


    The information states:
    "Fruits and vegetables are not good sources, because the zinc in plant proteins is not as available for use by the body as the zinc from animal proteins. Therefore, low-protein diets and vegetarian diets tend to be low in zinc."

    An inability to break down proteins due to a lack of protease would account for the low levels of zinc found in fibromyalgia.




  13. Annesse

    Annesse Member

    I am having a little trouble remembering where I posted what, so I thought I would just post a link to the the posts I made on the other site and keep them all in one place. If anyone has any questions, you can still post them here.

    http://www.inspire.com/groups/fibromyalgia/discussion/the-fibro-puzzle/