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Intro to C4A (Complement Component 4 A) and Its Role in CFS, Mold, and Histamine Intolerance

Information is sparse on C4a, but I’ve tried to gather what there is.  C4a is often elevated in chronic inflammation.

Intro to C4a

C4A is part of a “complement” group. The term complement means it is able to kill bacteria and contributes to immune defenses. However, if there are too many compliments, it can cause tissue damage and trigger an allergic reaction.

C4A is an activation protein, which means it also activates the other complement proteins to increase in level (R).

The C3a, C4a, and C5a components are referred to as anaphylatoxins (R, R2): they cause smooth muscle contraction, histamine release from mast cells, and enhanced vessel permeability (R).

They also mediate inflammation and the generation of free radicals (R).

C4a activates Neutrophils, which increases inflammation and free radicals (R).

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What Increases C4a?

There are three general pathways by which the body increases C4a: The Alternative Pathway, The Lectin Pathway, and The Classical Pathway.

These pathways are activated by infections, which include bacteria, fungi, viruses, and parasites.  Immunoglobulins (IgG, IgM) and CRP can also increase C4a (they can be high in infections).  The body often detects infections by the toxins that they give off, so toxins may also increase C4a.

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Conditions With Elevated C4a

C4A appears to be an immune marker (has increased levels) in the following disorders:

  • Lyme Disease (R, R2)
  • CFS (R), CIRS (R)
  • Psoriasis (R)
  • Eczema (R)
  • Antiphospholipid syndrome (R)
  • Lupus (R) and higher C3a (R)….According to one study, lower C4a contributes to lupus (R).
  • AIDS (R)
  • Schizophrenia (R)
  • Acute pancreatitis (R)

C4A and Mold Illness

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It’s been observed that C4A levels can be increased in people who come into contact with mold (R), or people with Lyme disease (R).

C4A levels may be decreased with mold avoidance (anecdotal) and antibiotic treatments (R).

C4A and Lyme Disease

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Some researchers are looking at C3A and C4A levels to diagnose lyme disease (R).

One must realize, however, that C3A and C4A and general markers, and will never be able to diagnose lyme disease specifically (see images above).

C4A and CFS (Chronic Fatigue Syndrome)

One study found that C4a goes up after exercise in people with CFS (R).

A case study found that a CFS patient felt better after their C4a normalized (R).

C4A and Histamine Intolerance

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Many people who believe they have histamine intolerance have high C4a because this activates mast cells.

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Comments

  1. http://amzn.to/2jWmX5y

    Mold Warriors by Dr Ritchie Shoemaker
    Gateway Press 2005

    Chapt. 23
    Mold at Ground Zero for CFS

    History Doesn’t Remember the Names of the Critics

    The history of Chronic Fatigue Syndrome (CFS) begins in Incline Village, Nevada in 1985. In the medical history of CFS, each of the concepts applies–failed theories and failed criticism.
    One victim, Erik Johnson, told everyone who would listen that mold was a cause of CFS. He came up with his theory at the wrong time in the politics of medical opinion, as a unknown viral cause was blamed instead. Johnson tried repeatedly to get the attention of leading CFS researchers then and now to look at what he knew about mold sensitivity. None of the heralded CFS researchers would listen.
    Twenty years passed before Erik’s mold opinions were vindicated.
    Erik remains bitter that his correct insights about mold and CFS were ignored for 20 years. But like so many people in medical history who were right but ignored, he must be content that his ideas are now validated. We will have many more years of clinical research to follow 2005, beginning by educating the “CFS establishment.” That will take swimming upstream against the CDC once again but Mold Warriors will offer a new set of ideas and data for the Chronic Fatigue Syndrome experts.
    That is, if they read it.

  2. Mary Beth

    Do you think an elevated C4A level (9,000) could be caused by Candida alone? My doc is treating mine as indicative of Lyme. My Lyme tests (Igenix Lab) came back negative for Lyme. I have been on several months of antibiotics for Lyme and feel a bit better. Just wondering if perhaps what I have is Candida and not Lyme. Thank you most sincerely for your help.

    • I’ve had patients with elevated C4a who were negative for Lyme Disease, but were positive for mold exposure in one case and CFS in the other. C3a is more likely to be elevated in Candida. Did you have this tested as well?

    • Michelle

      The antibiotics will almost certainly cause Candida. I had breast implants removed. The inflammation, CFS, and RA, symptoms almost disappeared immediately. I had these tests done, and found my C4a High. I hope it was from a UTI that I had just prior to testing. I feel much better, but foreign objects in the body cause a lot of damage.

  3. Leo

    Joe,

    This is an important subject. And I’m sure you have a ton going on, this article would benefit from expanding. Maybe time to hire some additional (qualified) writters?

    L

  4. The Walking Dead (literally)

    All you need to know? that’s a bit pompous isn’t it? More accurate would be, A Primer. But I do like your attempt to simplify a complex subject, that is still poorly understood. If it weren’t for Shoemaker, I don’t think modern medicine would even be attempting to employ it yet. He kind of catapulted breaking science, into treatment options. So give the guy some credit. Hardly any Dr even knows about this stuff, even twenty years later. I’m a patient, I know how lacking Modern Medicine is in this respect. (Here, take these Antidepressants. Everything will be fine. Since I, your Dr, don’t have to live with what my ignorance is costing you. Namely, Your Life.) I know it all too well! I saw 50+ doctors who weren’t shy about letting me know how mental I was, for having an illness they had no clue about. But that did’t stop any of them from charging an arm and a leg, then prescribing treatment; no matter how poorly conceived it was. (Shoemaker took both arms and legs in charges, but he also had concrete answers, and a plan that wasn’t thought up for him by Merck.)

    I am certainly no devout follower of Shoemaker. He used me for data, then abandoned me, like thousands of us. But I have never met a more methodical or rigid scientist. Yes, his personality sucks. But without him, no one would even be thinking of Biotoxins today. He single handidly changed the landscape in diagnostic and treatment for chronic illness. If you’re honest, I doubt you would either Dr Cohen. So you might want to lighten up on him? He has intimate knowledge of it, because he suffers with it. (Most Hotel rooms are not safe places for us Mold Hoards, and he has traveled the World at high cost to his health, to push awareness. It’s safer for us to live in a tent.) If you really know anything about this illness, you know it can drive weight crazy. The best thing is to go is Paleo, but few people possess that discipline. I agree he has huge gaps in his treatment knowledge. Like applying Methylation Analysis and Treatment would help people, but I think Joe hit it. He doesn’t want to dilute the science with stuff his peers might reject on a technicality. Anyone going to an American Dr knows most are ego-maniacal with a license to steal. More interested in showing (off to/or up) their peers, than truly furthering science. I hear some of that in your tone too.

    I got sick in January 2000; I was finally diagnosed in 2008, and have mostly suffered since too. I think because people just don’t want to work together. I am what Shoemaker calls one of the two or three Dreaded Genotypes, and I have resolved myself to dying before professionals get this worked out. It would be nice to see knowledgeable people work together, to save all of us they can? It’s funny, I know a lot of people trying to kill themselves with drugs or alcohol, prescriptions too. Here I am sick, desperately clinging to life. Pretty ironic. Sometimes I think, I’m actually the one who’s insane? Maybe when Mother Nature wants to recycle your body, you should just let her do it? I can’t decide? It costs too much to be sick, I know that. There use to be a philosophy in our culture to help the poor and weak. I know, my grandfather was a Dr. He got paid what his patients could afford. Now the sick are exploited.

    I think at some point Drs are going to have to acknowledge what Dr Dietrich Klinghardt already understands. That once you live around the Fungi long enough, and it does it’s tweaking to your immune system. It goes from being exogenous, to endogenous. To my knowledge Shoemaker isn’t there yet. Then your Biotoxins are auto-generated, and you have a more deadly issue. I don’t know anyone who knows how to remove it, once it gets established endogenously. I could sure use someone who understands that; or better yet? How to get it back on your outsides.

    • Steven

      “All you need to know” got me to read the article which was helpful. We aren’t paying for his work but I certainly appreciate it. That said he can be as pompous as he wants.

  5. Kimberley

    Do you ever look at labs? My 10 year old daughter’s C4A came back at 52,261 and her Histamine levels 24.9. Candida/yeast came back in mold plates. IGA antibody low. Nasal culture- negative. High lymphocytes and Eosinophils. Follow up appt not until June. Are these numbers are alarming and what are your recommended next steps? Do you agree with the cholestrymaine treatment for a young girl? Thank you!

  6. Joe,

    I always look forward to reading your articles. You do a nice job digging into the material and present helpful insights. Regarding quantifying the relationship between mold and C4a as “anecdotal”, you may want to look at the graph in the study below showing that those exposed to moldy buildings had high C4a about 72% of the time.

    Neurotoxicology and Teratology
    http://www.survivingmold.com/docs/NTT_NQ_PDF_06_17_2014.PDF

    • Joseph M. Cohen

      Thanks, I put it up. Still iffy about that reference.

      Do you have a study where he breaks down average C4a levels of cases vs controls? Did he look at C4a before mold exposure and after mold exposure?

      • I think I get where you’re coming from. It’s one of the reasons I like reading your material. Namely, it’s important to look at quality data whenever possible and really try to understand what that data is saying.

        Regarding your question, it would take some digging to put together what Dr. Shoemaker has written regarding C4a and mold. Unfortunately, I don’t have the time right now. I did remember seeing that graph on page 30 of Neurotoxicology and Teratology listing several biomarkers used in Shoemaker’s protocol – including C4a. In addition, the fact that C4a is included in his protocol, because it was found to be statistically significant, is also telling.

        Are You Moldy – Diagnosing Mold Illness Using Labwork
        http://biotoxinjourney.com/areyoumoldy/#Labwork

        Anyway, my main point (besides conveying my respect for your work) is that I think of the word “anecdotal” when I read personal accounts of folks that tried various therapies. In the case of C4a, we have Dr. Shoemaker’s data from thousands of patients along with numerous doctors following his protocol saying that C4a is significant in diagnosing and treating mold. Thanks again for your work.

        • Joseph M. Cohen

          It’s just that his data is sometimes contradicted by other researchers. For example, he thinks that CFS is mainly caused by mold and MSH is low in CIRS, and he gives some ridiculous reference ranges. Whereas other researchers found MSH was higher in CFS.

          Then he says stress is not more likely in CIRS, sun is dangerous, activated charcoal doesn’t help anyone, etc…

          There’s a lot of examples of him being inaccurate and other situations where his experience goes against mine.

          I used to trust his data, but he’s got a serious bias against anything that’s not prescription or that he didn’t figure out. He’s got a reality distortion field.

          What this means is that I am skeptical of his stuff if it’s not backed by studies (and preferably by other people).

          He’s seriously obese, with a serious diet/lifestyle related illness and he’s mocking diet, sun, circadian rhythms, all of which will actually help his condition.

          He might have an MD next to his name, but be skeptical of someone giving medical advice who can’t take care of their own health.

          But I still think he’s made some good contributions to the CFS/chronic inflammation field, and I try to take the good stuff from him.

          • I like what you’ve written. It speaks to the challenges anyone must face when trying to decide how best to take care of their health. I think that’s why we both like supportive data.

            Regarding being skeptical, I’d go one step further and say be skeptical of anyone’s advice. We all have “skeleton in our closets” that color our view. It’s inevitable; it’s life. The trick, as you’ve said, is to try to take the good stuff and marvel at the wonderment of it all whenever possible.

            One point is clear, the guy is very smart. I sometimes wonder if the reason he takes such a hard line on unconventional treatments is that he knows full well the insurance and medical industry will use any “weakness” to discredit all his hard work. Even if that’s not the case and he’s just a knucklehead when it comes to alternative therapies, it still works in our favor because he’s establishing a foothold against an entrenched system that throws away people that can’t get better with the standard course of antibiotics.

            Be well.

      • I ran across this data doing other reading today. See page 4, wherein controls had C4a levels around 1,800 while cases were around 9,000.

        VIP Corrects Chronic Inflammatory Response Syndrome (CIRS)…
        http://www.survivingmold.com/docs/VIP_published_3_2013.pdf

        You may also want to look at the Sequential Activation of Innate Immune Elements (SAIIE) protocol used to legally prove that a particular building is the cause of mold illness. One key marker is a rapid rise in C4a upon re-exposure to mold toxins.

        SAIIE meets ERMI
        https://www.survivingmold.com/docs/SAIIE_MEETS_ERMI_IAHCE_6_08_FINAL.MCH.pdf

  7. jacob

    Hi Joe, great post. I know this is kind off topic, but I’d ask you for a post about man’s libido, the mainstream medicine just relate low libido to low testosterone, but there are ton of people with libido issues and perfect hormones. Thanks!

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