Print Friendly, PDF & Email

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).

Screenshot 2016-05-04 17.30.03

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.



Conditions With Elevated C4a

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

C4A and Mold Illness


It’s been observed that C4A levels can be increased in people with Lyme disease (R).

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

C4A and Lyme Disease


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


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

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.


1 Star2 Stars3 Stars4 Stars5 Stars (5 votes, average: 4.80 out of 5)


  • Hillary Anderson

    I have a really elevated ochratoxinn level (53) and checked my C4a which was 2520. The ranges for normal seem pretty crazy. Can you please put that level is a meaningful perspective? I have symptoms of constant allergies, vision issues, my eyes burn, urinary frequency and urgency. I feel sure all this is related to biotoxin Illness.

  • Pat

    Quick comment on this, won’t go into my whole health history, but was one of the first documented cases of borrelia miyamotoi here on the east coast. Unfortunately it took a few years to test for it but I’ve now had positive pcr, nanotrap, and antibody results for it.

    In relation to c4a, mine has been elevated all along, presumably from the miyamotoi infection, in the range of 7000-10000. I had a good period of about 9 months where I was able to get back to 85% health, but unfortunately didn’t test the c4a to see if it fell in relation. In the past 4 weeks for whatever reason I’ve gone back down hill and tested c4a last week, value was at 7000.

    So it most definitely raises with infections, including miyamotoi and presumably other spirochete infections. I’m trying to figure out next steps as I don’t want to go back on antibiotics. But next time I feel good will definitely test to see if it fell.

    With those of levels above 15000 or so be wary of the lab draw and their technique. There is a huge problem with the quest facilities not drawing/transporting correctly which can veg quickly and easily falsely elevate levels to ridiculous numbers.

  • Sam12587

    Very interesting. What direction can we go to dig further on this subject or address the deeper? Are there foods or supplements we research?

    I was exposed to mold Saturday(it’s Wed now) when removing a broken appliance (didn’t expect based on symptoms) & within 24 hours became severely ill with a pneumonia diagnosis with 48-72 hours. Am on Doxycycline & Prednisone now & trying figure out if this infection mold what I can do to kill it. The medical people keep trying to tell me it’s the flu & their ears are dead to my voice, I had to fight for what I;m on however there has been prob about a 30-40% reduction in illness with the pain completely gone since I started the meds.
    I am taking garlic & vitamins strategically spaced between the prescriptions. I’m not asking for med advice, just data to try to figure out if I should do/take more or wait a few days. Mold scares me as I have a history of resp issues.

  • Teri saviano

    I purchased a grade II medical device registered with FDA and used by NASA. Developed and manufactured in Liechtenstein Germany the BEMER , which I am now a distributor for is a pulsed electronic magnetic frequencies I have it in my home it’s costly $6000 but I did not care. I have severe pain in my right foot my right hip and my right arm within three days the pain was gone my C4a levels in July 2016 with 21,479. After using the unit for four months my C4 a level was 1050 this unit has saved my life my inflammation is gone down I lost 12 pounds and I no longer have pain. You can contact me at

  • hoggle

    Why didn’t you explain low c4a?

  • Jay

    Are there any ways to lower c4a levels with supplements or medication? I know Actos is supposed to help, anything else that might be safer?

  • Valerie Mirakaj

    Dr. Kristine Gedroic in Morristown, nj helps with mold toxicity. Expensive, but can do it.

  • Lori Wobser

    Hello. I had a Complement 4A Level test done. the results are: 18,851 ng/mL I had this test done in April and still have not received a response explaining if I should be alarmed. to me this looks extremely high. Could you please explain this to me.

  • Pilar Olave

    I was exposed to a prolonged chemical substance and my C4a was taking after that. It came back extremely high ,elevated. Dr. Told me he had never seen such an elevated amount of inflammation in his 40 years as a Doctor in any patient. He did say this was caused by the toxin from the prolonged exposure to this chemical. Is it possible that besides mold toxins, chemical toxins can also elevate C4a levels? Thank you

  • Erik Johnson

    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.

  • 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.

    1. Joseph M. Cohen

      Yes, possibly. Be wary of the docs with lyme goggles.

    2. Dr. Soszka

      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?

    3. 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.

  • Leo


    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?


    1. Joseph M. Cohen

      I agree

  • 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.

    1. 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.

  • 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!

    1. Joseph M. Cohen

      Yes, I do look at labs and those numbers are alarming

  • 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?

    1. Greg

      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)…

      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

      1. Joseph M. Cohen


    2. 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.

      1. Greg

        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.

  • Leo

    What do you recommen to lower c4a?

    1. Joseph M. Cohen

      You need to probe what it’s elevated from….Toxins, infections? Fix underlying cause.

  • 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!

  • Leave a Reply

    Your email address will not be published. Required fields are marked *