GcMAF (Gc protein macrophage activation factor) is an immune-regulating compound from Europe that may have benefit for those of us struggling with immune system health. It has been used in HIV and cancer for several years. More recently, doctors and researchers have been considering GcMAF for use in patients with illnesses that most of us will recognize.

From gcmaf.eu, "In its role of immune system regulator, research shows GcMAF can reverse other diseases that attack the immune system like Autism, CFS, XMRV, Lyme disease, Aids, HIV, Fibromyalgia (all of which we've begun to have success with ourselves), osteoporosis, Hodgkin’s, Lupus, MS, Parkinson’s, various bacterial and viral infections and various types of Immune dysfunction."

I first heard about GcMAF almost a year ago. At the same time, I had first learned about "nagalase", a blood test that is used to in part determine whether or not one might be a candidate for GcMAF therapy. Nagalase is an enzyme that prevents Vitamin D receptors (VDR) from being activated on the surface of the macrophage. As a result, macrophages are not "activated" and our immune systems are not able to properly respond to invaders.

Here are some points that I have learned thus far on GcMAF:

  • GcMAF has reportedly been tested more for safety, purity, etc. than other human blood products.
  • Macrophages are cultured, destroyed, and the GcMAF receptors are purified.
  • Treatment is via injection 1x/week for 8-20 weeks. Dose is titrated initially to avoid exacerbation or Herx responses as much as possible.
  • A commonly used dose is .25ml once weekly (a 2.2 ml vial should last 8 injections).
  • The primary test used in looking at whether or not GcMAF may be a reasonable intervention is nagalase.
  • Nagalase inactivates macrophages.
  • I personally would NEVER consider this option without having a baseline nagalase test. Normal is < 0.95. Mine was 2.9.
  • The practitioner I worked with suggested that 2.9 was in the range of someone with HIV or cancer in terms of the impact on the immune system. I'd like to hear from others in the Lyme community as you get test results as well to see if there is a pattern of elevated nagalase in those with Lyme disease. Whether or not Lyme itself has anything to do with nagalase elevation is something I have not been able to find anything on. We certainly all have underlying viral co-factors that are likely in play as well, but I suspect that Borrelia may also play a role in nagalase elevation.
  • In healthy college students, a nagalase 0.4 is not uncommon (the lower the better).
  • At 2.9, my practitioner was surprised that I did not have more cognitive deficits such as memory loss and other cognitive issues.
  • It has been suggested that ongoing antimicrobial therapy without a working immune system is like leaving the house with the door wide open inviting burglars in. By using GcMAF to activate macrophages, nagalase drops, and one may regain a functional immune system. The door is then closed to further invaders and we may no longer serve as a microbe hotel.
  • Maintenance therapy should not be needed once the immune system is once again properly functioning.
  • Activated macrophages only remain active for 7 days so any negative responses are generally short-lived. That said, some people do have strong inflammatory responses that are not believed to be typical die-off reactions.
  • It has been indicated that in some cases, other medications may be needed in order to manage the inflammatory response. This is another reason that one needs to be working closely with a knowledgeable practitioner before considering GcMAF in my opinion. In the CFS and GcMAF world, this more severe form of a die-off reaction is called IRIS.
  • VDR genetics do not seem to play a role in predicting response as earlier thought according to one practitioner that I have spoken with. That said, Vitamin D levels do correlate with the positive response rate of GcMAF. Thus, Vitamin D supplementation may be required in order to optimize outcome.
  • Other than die-off reactions or activation of symptoms (inflammation), no other side effects are generally expected.
  • Nagalase should be monitored every 1-2 months while on treatment to determine the required duration of the therapy. Target nagalase after treatment would be 0.4 to 0.6.
  • Elevated nagalase has a profound detrimental effect on the immune system. Elevated nagalase is often presumed to be related to microbes of viral origin or cancer. Viruses that are nagalase producers open the door to chronic infections.
  • Hemagglutinin contains nagalase and is also found in flagella of some bacteria so it could also be the case that some bacteria may produce nagalase.
  • Parents with ASD children also often have elevated nagalase.
  • A practitioner I spoke with likened Lyme disease to a "peat moss fire" burning below the surface. Activating macrophages should help to deal with the fire.
  • GcMAF should be helpful in dealing with other infections that are not of viral origin; for example, Borrelia, Bartonella, and other infections commonly associated with Tick-Borne Infections (TBIs). GcMAF is active against many cancers and many different kinds of microbes.
  • Neopterin is another test that is sometimes used as an indicator of immune suppression. As macrophages become activated, neopterin may rise and later fall. If one is in the normal range for neopterin and has an immune-related illness, this could be an indication that the immune system is suppressed and not responding appropriately.
  • People with autoimmune conditions can generally use GcMAF. However, GcMAF may be contraindicated in people with Multiple Sclerosis.
  • Reduction in nagalase is generally seen early in the course of treatment; within the first 3-6 weeks. In some studies, nagalase dropped by over 50% in less than six weeks.
  • Cancer patients may initially feel as bad on GcMAF as they do on chemotherapy, but often feel much better after the first month.
  • Anti-inflammatories may limited the effect of GcMAF.
  • Enzymes and biofilm-reducing supplements may have a negative impact on GcMAF therapy and may be best avoided. It is still too early to know what the impact may be, but one practitioner I spoke with feels that it is best to avoid these.
  • One should not be on any immune-suppressing agents while on GcMAF as the immune system must be partially functional in order to respond appropriately to the treatment.
  • A common pattern is to see elevated lymphocytes, high nagalase, and low NK cells. Once nagalase drops, it may be the case that NK cell function could be positively impacted. CD57 is a type of NK cell. It is too early to know if this proves to be true, but it is one of the things I'm quite interested in.
In November 2011, I listened to a presentation by Dr. Kenny de Meirleir on GcMAF. This video is an absolute must-watch if you are considering GcMAF. You can find it here. A few of my takeaways from watching this presentation include:
  • With compromised immune activation, increased nagalase cuts off the conversion to GcMAF - result is a deglycosylated Gc protein that cannot activate macrophages.
  • If you have increased nagalase, you have less GcMAF and your Gc protein is not effectively transferred into GcMAF.
  • Nagalase is part of the gp120 enzyme in HIV. HERV's or other viruses active in cells may produce nagalase.
  • Several intestinal bacteria are producers of nagalase. Editor's Note: I found this connection to be quite interesting; the gut is big.
  • Similar to HIV, CFS patients have many infections and reactivate endogenous herpes viruses - EBV, CMV, HHV-6, HSV-1, as well as Herpes 7.
  • Healthy controls have very low nagalase enzyme activity. Normal people do have some, but it should be very low. There is a clear difference in those with pathology.
  • 395 CFS/ME patients - average nagalase in Kenny de Meirleir study was 1.72 with range of 0.28 to 4.0. Controls had < 0.69 with range of 0.35 to 0.68. Only 12/395 had normal nagalase levels resulting in 97% having increased nagalase activity.
  • Dr. Cheney did a small study of 50 patients. Average nagalase was 3.0 with range of 0.8 to 6.7. He has a much sicker patient population than de Meirleir.
  • Origin of nagalase in CFS may be: retrovirus?, herpes viruses, intestinal bacteria, HERVs.
  • Find Lipopolysaccharides (LPS) in the blood from gram negative intestinal bacteria (less so from gram positive bacteria). High LPS suggests increased intestinal permeability or leaky gut syndrome.LPS is one of the most immunogenic substances in the body. Extremely ill and moderately ill patients have increased circulating LPS and thus leaky gut syndrome.
  • Altered intestinal flora and changes in gut permeability may be a major factor in this entire clinical picture.
  • GVDR-Fok1 and GVDR-Bsm1 polymorphisms in CFS - response to GcMAF is dependent on the VDR gene polymorphism. VDR is involved in skeletal metabolism, modulation of immune response, and regulation of cell proliferation and differentiation. Many CFS patients have osteoporosis. Editor's Note: The VDR connection to GcMAF efficacy seems to be an ongoing topic of debate.
  • In 185 patients looking at VDR genetics, FF/bb is a higher responder. Ff/Bb is a moderate responder, and Ff/BB is a low responder. de Meirleir takes VDR genetics into account when giving and dosing GcMAF.
  • Africans are higher responders and Norwegians and Scandanavians are lower responders.
  • GcMAF and LPS activate macrophages. Majority of CFS patients have increased bacterial transfection from gut to blood. GcMAF stimulates macrophages through a different mechanism than LPS without the negative effects of LPS. LPS and GcMAF cannot stimulate macrophages simultaneously - it is one or the other. Affinity of macrophages for GcMAF is higher than for LPS. GcMAF will induce a "good" phagocytosis without the bad IL-1 and TNF-alpha release. "Bad" macrophage activation by LPS is diminished by the competitive action of GcMAF in the macrophages.
  • de Meirleir uses 100 nanogram (1/10,000 of an mg) in 1ml serum. Editor's Note: This is different than GcMAF.eu potency which is 100ng in .25ml
  • Can be done IV or SC once per week at dose of 25-100ng per week. The Dose depends on how activated the immune system is and the VDR genetics. If a patient is a low responder genetically and has low activation of complement in the immune system, the dose might be 100ng per week. Otherwise, much lower dosages may be used. Treatment duration is 5-40 weeks with 15 week being the average.
  • Symptoms such as fatigue, sleep quality, pain, neurocognitive function, recovery/less payback, digestive problems, and orthostatic intolerance improved in over 50%. Of 108 patients, 68 of these had noticeable improvement. Of these, 44 of the 68 had decrease in fatigue.
  • Risks - GcMAF is natural and normal people produce it. T-cell activation in patients with a Th1 -> Th2/Th17 shift could in theory develop or increase auto-immunity. That said, it has not happened once in his cases. He did have a few people that developed autoimmune thyroid conditions; but that is not uncommon in the normal patient group that he sees.
  • Patients with increased TGF-b1, high IL-6, high ANA, and thyroid antibodies are temporarily excluded.
  • Overstimulation with GcMAF can lead to IRIS - immune reconstitution inflammatory syndrome. IRIS has been seen in the past in HIV. In HIV, this is rarely discussed given the severity of the condition they are treating. IRIS occurs when the immune system is heavily damaged by viruses other co-infections are present. The immune cells start to regenerate and the immune system produces an exaggerated response to the co-infections. It is not the GcMAF itself but the result of significant co-infections. IRIS has been replicated in mice.
  • 20-30% of GcMAF CFS patients experience IRIS. It is more common in those with co-infections and in those with activated T-cells or a low number of T cells.
  • de Meirleir monitors IRIS with C4a, cytokines, CD25, and HLADR+.
  • Attempts to prevent IRIS with a broad screen for fungal, viral, intracellular bacteria, and parasites.
  • Start with a low dose and titrate up slowly. In 7 patients that had IRIS, de Meirleir found active Babesia.
Video

 

Current Status

To learn about my personal experience and response to GcMAF, visit my GcMAF Log page.

Nagalase Testing

Health Diagnostics and Research Institute
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Web site: http://www.europeanlaboratory.nl/

The cost of testing is about $65.

Resources

There are numerous resources on GcMAF available. Rather than try to go into great detail here, as I am still learning about GcMAF myself, I have provided some additional resources below that have significant information on GcMAF.

If you have experience with GcMAF, I'd appreciate hearing from you. If you have additions or corrections to the information here or additional information that I should share here, please Contact Me.

Note: I am not an expert on GcMAF therapy. This information is being provided to share my personal experience with this option only. All medical decisions should be discussed with your doctor.


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