Fibromyalgia: The vicious cycle of contributing factors part: 1

Discussion in 'Fibromyalgia Main Forum' started by RadioFM, Dec 2, 2014.

  1. RadioFM

    RadioFM Active Member

    Multi-Systemic Infections mechanism may be driving the immune response in Fibromyalgia?

    "Oxidative stress plays a dual role in infections. Free radicals protect against invading microorganisms, and they can also cause tissue damage during the resulting inflammation. In the process of infection, there is generation of reactive species by myeloperoxidase, NADPH oxidase, and nitric oxide synthase."

    See more here:

    Dr. Martin Pall's NO/ONOO Hypothesis
    is a comprehensive explanation of how cellular oxidative stress illnesses mechanisms that control pathogens don't turn off in Fibromyalgia.

    " He suggests that the elevated Nitric Oxide and Peroxynitrite levels in these conditions is a shared root cause or factor, which is also comorbid in a large number of other well-accepted diseases, for example viral related illnesses, allergies and autoimmune conditions. This might also explain how some sufferers of one of these conditions may develop multiple instances of other inflammatory conditions concurrently, as they share a root driver. Autoimmune diseases such as Lupus and Rheumatoid Arthritis, are reported to have elevated iNOS activityand peroxynitrite, NF-kB and cytokine elevation at the sites of the autoimmune-related inflammation. These factors shall be examined in this article."

    "In these illnesses, short term stressors such as viral or bacterial infection, physical or psychological trauma or exposure to various toxic chemicals are thought to raise the Nitric Oxide (oxidant) levels in the body, exaccerbating their symptoms. The elevated Nitric Oxide levels react with Superoxide in the body, a byproduct of a number of bodily processes, to form the very harmful rogue oxidative species Peroxynitrite. The formation of Peroxynitrite causes a wide variety of oxidative damage to the body, particularly to mitochondrial enzymes, membranes and also hemoglobin, as well as destroying the protective antioxidant enzyme Superoxide Dismutase (SOD) (and other mechanisms for stimulating Superoxide production), thereby allowing Superoxide levels to build up, causing more of the Nitric Oxide to react with this Superoxide, thereby perpetuating or worsening the condition by producing more Peroxynitrite."

    See more here: Nitric Oxide Cycle, Superoxide and Peroxynitrite

    If NO-synthases
    is making to much NO and depleting BH4. This can Lead to increased peroxynitrite. BH4 is also required to convert ammonia to urea in the Urea cycle. This domino effect may be a risk factor driving the hyperactive cytokine immune response seen in FM.

    Please reviewhow oxidative stress can impacted BH4 below.

    MTHFR.Net Dr Ben Lynch, Quote:

    "There are ways to increase BH4 safely – without supplementing directly with biopterin."

    "The biggest gains in increasing biopterin are:"

    "decreasing inflammation"
    " decreasing infections"

    – "both of these decrease neopterin which in turn increases biopterin formation"

    "When neopterin is elevated, biopterin typically is decreased."

    "decreasing ammonia levels"
    "adding methylfolate, iron, vitamin C, magnesium, b6 and others."

    "It is always best to support a cycle with the necessary precursors rather than supplementing directly with the end product." BH4 supplement for a1298c? - MTHFR.Net

    Elevated Nitric Oxide & Oxidative stress

    Dr. Jay Davidson NO ONOO Cycle

    The NO/ONOO-Cycle, a New Disease Paradigm, by Martin L. Pall

    • Ammonia - Neuro-Antitox II This ammonia-induced glutamine accumulation may cause dysfunction of astrocytes that leads to impairment.
    Last edited: Jan 16, 2015
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  2. RadioFM

    RadioFM Active Member

  3. Sherpa_

    Sherpa_ Member

    I have identified several different causes of my own "fibromyalgia" muscle pain.

    Different imbalances can cause physical pain. Listening to your body to find out what it's missing and correcting the balance will remove the fibromyalgia symptoms quickly. Here are some imbalances to look out for:

    • Lack of electrolytes (low potassium cramps, etc. Can be fixed with a drink like Emergen-C Electro Mix or Optimal Electrolyte)
    • Lack of magnesium (transdermal magnesium oil massage can soothe if this is reason for flare)
    • Low levels of thyroid hormone (need more iodine & selenium or thyroid glandular. methylation supplements improve my thyroid function)
    • Low levels of glycogen in muscles (Sometimes muscles ache after heavy physical exertion, and it can be corrected by eating a snack or meal higher in carbs)
    • ATP bankruptcy (if I've really over done it physically, 5 grams of d-ribose will 'hotwire' the energy synthesis cycle and remove muscle pain. May require several doses over a day or two.)
    • Inflammation from allergies, GLUTEN, delayed onset food intolerances, bad fats, etc. (Do an elimination diet and find out what causes you to flare. Then stop eating it!)
    For my "wired" insomnia that often comes with fibromyalgia, I have found that taking sublingual B6 will usually put me right to sleep. I suspect its caused by Pyroluria.
    Last edited: Dec 8, 2014
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  4. RadioFM

    RadioFM Active Member

    "Polymicrobial"/Lyme Disease, Do You Have It?

    Co-infection and non-Lyme MSIDS

    In Lyme disease concurrent infections frequently occur. The clinical and pathological impact of co-infections was first recognized in the 1990th, i.e. approximately ten years after the discovery of Lyme disease. Their pathological synergism can exacerbate Lyme disease or induce similar disease manifestations. Co-infecting agents can be transmitted together with Borrelia burgdorferi by tick bite resulting in multiple infections but a fraction of co-infections occur independently of tick bite. Clinically relevant co-infections are caused by Bartonella species, Yersinia enterocolitica, Chlamydophila pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae. In contrast to the USA, human granulocytic anaplasmosis (HGA) and babesiosis are not of major importance in Europe. Infections caused by these pathogens in patients not infected by Borrelia burgdorferi can result in clinical symptoms similar to those occurring in Lyme disease. This applies particularly to infections caused by Bartonella henselae, Yersinia enterocolitica, and Mycoplasma pneumoniae. Chlamydia trachomatis primarily causes polyarthritis. Chlamydophila pneumoniae not only causes arthritis but also affects the nervous system and the heart, which renders the differential diagnosis difficult. The diagnosis is even more complex when co-infections occur in association with Lyme disease." Suppl 1: Chronic Lyme Disease and Co-infections ...

    Chlamydia Mycoplasma FM Connection?

    Dr. Wilmore Webley on Chlamydia Pneumoniae & Biofilms

    Beta Interferon Is Produced by Chlamydia trachomatis-Infected Fibroblast-Like Synoviocytes and Inhibits Gamma Interferon-Induced HLA-DR Expression

    "Infection of fibroblast-like synovial cells with Chlamydia trachomatis (serotype D strain IC Cal 8) in culture induced the secretion of beta interferon (IFN-β). Chlamydial infection inhibited IFN-γ-induced expression of HLA-DR antigen in the cells. Addition of IFN-β antibody directly to infected cultures mitigated HLA-DR inhibition, suggesting involvement of produced IFN-β. "

    See more here:

    Autoimmune Disease: The Infection Connection with Dr. Nikolas Hedberg,
    Last edited: Mar 18, 2015
    Nanie46 likes this.
  5. Sherpa_

    Sherpa_ Member

    Great information!

    I don't doubt that I have some multi-systemic infections. I am currently working on killing parasites that I am infested with and after they are done I will test for & tackle the smaller, microscopic infections!

    I have been following Radio's posts and I have had really significant improvement in my overall energy and wellness from some of these ideas!

    Yesterday I went to a picnic party at the park here in Florida and I found myself enjoying a game of frisbee, dancing and socializing without even thinking of fatigue or malaise.

    What has really helped:
    • Lipid Replacement Therapy - NT Factor powder 2x a day (this stuff is potent, start LOW - like 1/8th - teaspoon and build up)
    • Antioxidant / polyphenol support with organic green tea
    • pyroluria support - Zinc + B6 makes me feel like a different, much more relaxed person
    • increased DHA intake
    • tannin foods and supplements (pueple potatoes & blackberries, blueberries & Tanalbit)
    • low dose methylation support with Yasko's All-in-One Multivitamin, sublingual B12 and methylfolate
    RadioFM likes this.
  6. RadioFM

    RadioFM Active Member

    The NO/ONOO-Cycle, Review:

    "Raised Superoxide levels through physical or mental overexertion can also trigger increased inflammation by reacting with Nitric Oxide as well as burning up our mitochondrial enzymes and membranes, impairing mitochondrial function. The increased inflammation also makes it harder for the mitochondria to repair effectively, creating slow recovery periods from overexertion, even when the patient rests for days or weeks at a time."

    "Pall argues that therapy should focus on down-regulating the NO/ONOO- cycle biochemistry rather than on treating symptoms. He has recommended that nutritional/mineral support and individual and full-spectrum antioxidant preparations that together may assist in down-regulating this NO/ONOO- cycle mechanism are to be considered a sensible approach as part of an overall treatment programme."

    "The intensity of the Nitric Oxide and Peroxynitrite cycle does appear to vary in the patients of the above cases, but it does appear to be a factor in the overall illness of each respective person to some degree. It may be a primary driver or cause in one patient, and play a secondary part compared to other primary causes, e.g. heavy metal toxicity, in the next patient. In some phases of an illness, inflammation can play a smaller part secondary to other factors, and in other phases it may play the dominant role. Symptoms of inflammation vary, depending on where exactly in the body the inflammation is and what the exact nature of it is. Nervous system aberrations and cognitive disability ('brain fog') often point to excessive inflammation and/or excitotoxicity in the brain."

    Please see more below:

    Nitric Oxide Cycle, Superoxide and Peroxynitrite

    Nitric Oxide
    Nitric Oxide Synthesis
    Physiological (Beneficial) Pathways of Nitric Oxide
    Pathological (Detrimental) Pathways of Nitric Oxide
    Causes of Elevated Nitric Oxide Levels
    Prolonged or Repetitive Immune Activation
    Hyper-Excitement of NMDA Receptors
    Hyper-Excitement of Vanilloid Receptors
    Hyper-Excitment of Muscarnic Acetylcholine Receptors
    Stress or Psychological Trauma
    Physical Trauma
    Ionising Radiation Exposure
    Pre-Existing Autoimmune Disease or Inflammatory Condition
    Genetic Predisposition to Elevated Nitric Oxide Levels
    Low Tissue Oxygenation and Capillary Budding
    Psychological Stress or Trauma
    Too Low Nitric Oxide Levels? David Whitlock's Hypothesis
    Formation of Superoxide
    Genetic Predisposition to Elevated Superoxide Levels
    Superoxide Dismutase (SOD)
    Formation of Peoxynitrite
    Other Reactive Nitration Species (ROS) formed from Peroxynitrite
    Pathological (Detrimental) Pathways of Peroxynitrite
    Antioxidant Protection against Peroxynitrite
    Balance between Free Radicals and Antioxidants
    Dr Martin Pall's Peroxynitrite Protocol
    Preventative Measures
    Treatment Protocol
    Dr Paul Cheney's Peroxynitrite Protocol
    Methods of reducing elevated Peroxynitrite levels
    Methods of Reducing Elevated Peroxynitrite & Superoxide Levels
    Methods of Blocking Nitric Oxide Production
    Other Methods
    General Comments on Dr Paul Cheney's Hypothesis on Peroxynitrite
    Other Protocols
    Dr Jacob Teitelbaum's Peroxynitrite Protocol
    Dr Gareth Nicolson's Peroxynitrite Protocol
    Dr Neboysa Petrovic's Peroxynitrite Protocol
    Markers and Tests for Peroxynitrite

    Last edited: Jan 4, 2015
  7. pilot408

    pilot408 Member

    It really would be best for you to speak with your doctor about this. He, obviously, doesn't feel that you situation is dire enough to warrant an immediate appointment.

    What I can tell you, however, is that if your C-peptide levels are low, then the beta cells (islets of Langerhans) of your pancreas are producing a reduced amount of insulin. This does point towards concerns of diabetes, and may require further testing.

    I had a C-Peptide test done and the doctor called and told me my levels were low and on more than one occasion has said that my blood sugar is abnormally high. He scheduled me for an appointment. But does this mean I have diabetes.
  8. RadioFM

    RadioFM Active Member

    Hey pilot408,

    I think you may have posted in the wrong forum...

  9. Sherpa_

    Sherpa_ Member

    Really interesting information about Nitric Oxide,Peroxynitrite and SOD.

    Very timely, this information is helping me out as I feel like this is a major stiumbling block I might be experiencing right now. I was trying to raise my dose of methylfolate from 100 to 200mcg, but got inflammation and agitation side effects.

    Dr. Ben Lynch says that if you have a SOD deficiency or mutation, there is a good chance you will experience side effects with methylfolate.

    Solution: The best way to support SOD is to make sure your red blood cell levels of manganese, zinc and copper are in the normal ranges. If they are and you have a SOD snp, then you may need to supplement SOD directly. SOD requires advanced delivery technology for good oral absorbtion."Gilisodin" is SOD cannelouple extract bonded onto wheat protein to get it through the digestive. "Extramel" a gluten-free, high-SOD French melon extract encapsulated in palm oil.
    RadioFM likes this.
  10. RadioFM

    RadioFM Active Member


    Intracellular infections can stimulate reactive oxygen species. SOD serves as a key antioxidant needed to protect cell from superoxide toxicity. SOD insufficiencies can have a major impact on cellular metabolism.

    Eicosanoids may be another possible contributing factors to consider. When cells are damaged by oxidation, eicosanoids are formed from arachidonic acid. These eicosanoids can also trigger the inflammatory response as well.

    Another way to mitigated this pathway is to have a understanding of the Arginine/Lysine ratio in foods.

    Why does this matter?

    Arginine drives the NO/ONOO- cycle.

    Seafood diet may have the best Arginine/Lysine ratio, also DHA may be very beneficial.

    See more here:

    Last edited: Mar 18, 2015
  11. tdog333

    tdog333 Member

    Great Thread, I think a key step is improving quality of sleep any way possible. It seems that most people with CFS/FM are always lacking in a deep or restful sleep, once I focused on this things got a bit better.

    One trigger for me is low electrolytes as you mentioned above as well. Most people are chronically dehydrated even if they don't realize it. I start getting muscle spasms very quickly if I don't drink enough water and supplement.
    The lipid replacement therapy is also key. We need to heal ourselves on the cellular level as soon as possible. PQQ has also been helpful in term of biogenesis of new mitochondria. Most of these infections work through oxidative damage so we need as much help controlling inflammation through diet and supplements as possible.

    Good post, great work so far:)
  12. Sherpa_

    Sherpa_ Member

    What form and doses of Lipid Replacement Therapy did you do? I am using NT Factor EnergyLipids powder. Started at 1/8 tsp 2x a day. Been at 1/4 tsp 2x a day. I just bumped up from 1/4 tsp (1.25 grams) to 1.5 grams and I feel a big lift in energy. I think I need more and may work up to the 'loading dose' of 2.5 grams suggested on the package for 1 to 2 months.

    Can you tell us more about your experience with PQQ? What kind of doses, side effects? Do you take it with methylation supplements like B12 / methylfolate?
  13. tdog333

    tdog333 Member

    I probably did 1/2 a teaspoon twice a day for about 3 months. I haven't taken it since i recovered from CFS though. I think PQQ was key. I felt way more energy after taking it for a couple of weeks. I took it for 2-3 months. PQQ and equilibrant were game changers for me. If i took it too close to bed time I would get some insomnia, no other sides besides that. I took it with methylation supplements yes. I've been on 2.4mg methylfolate and 5mg methylb12 a day for the past 9 months now. (i am also +/+ C677T and both COMT+/+)
    Last edited: Jan 14, 2015
    RadioFM likes this.
  14. RadioFM

    RadioFM Active Member

    How Can We Restore Cellular Integrity?
    Lipid replacement therapy supplementation is designed to improve mitochondrial function in people with chronic illnesses and multiple chronic infections.

    "Clinical trials have shown that NT Factor® can actually support the repair of damaged cell membranes – in effect reducing the cells’ biological age and restoring mitochondrial ability to generate energy."

    The most important factors in healing the body:

    • Detoxification
    • Immune modulation
    • Cellular integrity
    • Cellular fluidity

    Mitochondria Support:

    Please review links below:

  15. RadioFM

    RadioFM Active Member

    Oxidative stress plays a dual role in infections. Free radicals protect against invading microorganisms, and they can also cause tissue damage during the resulting inflammation.

    In this process of chronic infections, there is reactive species by Myeloperoxidase.


    Could elevated Myeloperoxidase be driving the oxidized inflammatory response in FM?

    Please review link

    Myeloperoxidase: molecular mechanisms of action and their relevance to human health and disease.


    "Myeloperoxidase (MPO) is a heme-containing peroxidase abundantly expressed in neutrophils and to a lesser extent in monocytes. Enzymatically active MPO, together with hydrogen peroxide and chloride, produces the powerful oxidant hypochlorous acid and is a key contributor to the oxygen-dependent microbicidal activity of phagocytes. In addition, excessive generation of MPO-derived oxidants has been linked to tissue damage in many diseases, especially those characterized by acute or chronic inflammation. It has become increasingly clear that MPO exerts effects that are beyond its oxidative properties. These properties of MPO are, in many cases, independent of its catalytic activity and affect various processes involved in cell signaling and cell-cell interactions and are, as such, capable of modulating inflammatory responses. Given these diverse effects, an increased interest has emerged in the role of MPO and its downstream products in a wide range of inflammatory diseases. In this article, our knowledge pertaining to the biologic role of MPO and its downstream effects and mechanisms of action in health and disease is reviewed and discussed."

    Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention


    "There is considerable interest in the role that mammalian heme peroxidase enzymes, primarily myeloperoxidase, eosinophil peroxidase and lactoperoxidase, may play in a wide range of human pathologies. This has been sparked by rapid developments in our understanding of the basic biochemistry of these enzymes, a greater understanding of the basic chemistry and biochemistry of the oxidants formed by these species, the development of biomarkers that can be used damage induced by these oxidants in vivo, and the recent identification of a number of compounds that show promise as inhibitors of these enzymes. Such compounds offer the possibility of modulating damage in a number of human pathologies. This reviews recent developments in our understanding of the biochemistry of myeloperoxidase, the oxidants that this enzyme generates, and the use of inhibitors to inhibit such damage."

    "MPO protein has little bactericidal effect per se, but enzymatic reaction with H2O2 and halide (Cl−, Br−, I−) or pseudohalide (SCN−) ions generates hypohalous acids: hypochlorous acid (HOCl), hypobromous acid (HOBr), hypoiodous acid (HOI), and hypothiocyanous acid (HOSCN).(911) These oxidants are widely believed to be responsible for much of the anti-bactericidal activity of neutrophils, although other oxidants (including nitric oxide (NO•), peroxynitrite (ONOOH) and H2O2) and enzymatic systems (e.g., peptides, proteases, lysozyme) clearly also play an important role."

    "Although the generation of oxidants by MPO is beneficial in terms of the immune response to invading pathogens, there is considerable evidence that inappropriate stimulation of oxidant formation by this enzyme (wrong place, wrong time, excessive levels) can result in host tissue damage. Thus marked damage to cells and other biological materials (extracellular matrix, biological fluids) has been detected at sites of inflammation (reviewed in (10,12)). This damage has been linked with several human pathologies, and in at least some cases experimental and/or epidemiological evidence is available to suggest that oxidant generation by MPO (and/or other related heme peroxidases, such as eosinophil peroxidase (MPO)) is, at least partially, causal. This evidence for a role for MPO and its oxidants in human disease has been recently reviewed,(10,12) and will not be covered further here."


    "There is now considerable evidence that MPO and other heme peroxidases are enzymes that have both beneficial and damaging actions. These species have a clear beneficial function in terms of killing invading pathogens, but this same enzymatic activity can result in host tissue damage and play a role in a number of important human pathologies. Information and an understanding of the enzymology and mechanisms of action of these enzymes is clearly therefore of major importance, both in terms of enhancing their positive actions in terms of disinfection and improved hygiene, and diminishing their deleterious effects. Recent studies have provided valuable information on the targets and actions of the oxidants generated by these enzymes and their mechanisms of biological damage. Ongoing studies on the control of the halogenation and peroxidase cycles are providing valuable data on new therapeutic strategies to limit oxidant damage to human tissues and it is possible that selective inhibition of these enzymes will have major clinical benefits."

    1. Myeloperoxidase--H2O2--halide system: cytotoxic effect... Cached
      Myeloperoxidase, H2O2, and a halide form a potent antimicrobial and cytotoxic system of the polymorphonuclear leukocyte. A cytotoxic effect of this system on human ...
    2. Oxidation of microbial iron-sulfur centers by the ...
      Myeloperoxidase, H2O2, and a ... The oxidation of iron-sulfur centers in microorganisms by the myeloperoxidase-H2O2-halide system may contribute to the death of ...
    Last edited: Mar 18, 2015
  16. RadioFM

    RadioFM Active Member

    Inhibitors of MPO

    "Azide has been used traditionally as an MPO inhibitor, but 4-aminobenzoic acid hydrazide (4-ABH) is a more specific inhibitor of MPO. "

    4-Aminobenzoic acid (also known as para-aminobenzoic acid or PABA because the number 4 carbon in the benzene ring is also known as the para position) is an organic compound with the formula H2NC6H4CO2H. PABA, a white-grey crystalline substance, is only slightly soluble in water. It consists of a benzene ring substituted with an amino group and a carboxyl group.
    Last edited: Mar 17, 2015
  17. RadioFM

    RadioFM Active Member


    Could MPO be a marker of inflammation and oxidative stress in FM?

    "MPO activity can be measured in blood and tissues by spectrophotometric assays using hydrogen peroxide and o-dianisidine dihydrochloride as substrates. In addition, MPO content can be measured in neutrophils as an index of degranulation with the Coulter counter and flow cytometry and circulating MPO by ELISA. Very recently, commercial methods allowing low-cost and high-volume measurements have been proposed. The introduction of these methods of measurement might make MPO a new and useful cardiac biomarker."

    Other related testing below:

    Anti-neutrophil cytoplasmic antibody?

    Myeloperoxidase Antibodies, IgG, Serum? and Interpretive/80389
    Last edited: Mar 18, 2015
  18. RadioFM

    RadioFM Active Member