Mold, Dr. Cheney and ME/CFS

[slayadragon]

PEM and C4a

I've been puzzling over the topic of C4a and thought I'd put some comments here.

First, Dr. Shoemaker's beliefs (which, to my understanding, have not been published in a peer-reviewed journal yet).

Dr. S says that C3a and C4a tend to be correlated with acute toxic mold exposures in non-CFS patients. If you can get these patients out of a moldy environment, their C3a and C4a (complement) levels go down to normal.

In CFS patients, that doesn't happen. He states in Mold Warriors that C3a remains stubbornly up. (That seems to be the case for C4a, which he doesn't discuss in MW. It seems to be much more correlated with toxic mold exposures than C3a though, he says now.)

Dr. S makes it seem in MW that C3a (and presumably C4a) are staying elevated for no apparent reason. That would be consistent with the idea that all kinds of things are causing inflammation in the CFS patient, not just mold.

HOWEVER, this is where my little trip down the rabbit hole has the potential of providing useful testable information.

Some of us pursuing extreme mold avoidance have found that insofar as we keep our exposures low, we are able to get those complement measures down to normal. (What I need to do is to arrange to get a draw before and then after a small exposure, to show that only a small amount of exposure indeed is needed to cause the elevation.)

It thus seems that in our case, C4a is not being driven by "general inflammation" or the system doing things randomly. It's in response to tiny bits of mold exposures.

This is hardly an unprecedented concept. It's exactly what happens in (say) peanut allergies, which is the metaphor that Erik's been using ever since 1998 when he first proposed the "extreme avoidance" concept to Dr. Peterson.

Similarly, those exercise studies (above) make it seem like CFSers are just generally inflamed. They observe C4a going up after exercise and staying up, and attribute the post-exertional malaise to it.

That's not our experience though. We experience the PEM not from exercise alone, but from exercise in combination with toxic mold. We've yet to find any other substance or any other variable that causes PEM, if toxic mold is taken out of the equation.

And as the authors suggest, there doesn't have to be any exercise in order to cause the problem (Erik's "no-exertional malaise" concept). They report C4a being elevated to begin with; it just gets worse with exercise.

I'd like to be able to say, "Yes, there are all kinds of things that cause inflammation in CFS, and mold is just one." That doesn't seem to be what's happening though. Underlying Lyme infections or XMRV infections or herpes virus infections or emotional stress or other sorts of chemicals don't, in our experience, interfere with the ability to exercise without PEM. Just the mold.

Moreover, the ability to exercise without PEM seems to occur almost immediately after getting free of the mold. Most of the improvements from mold avoidance take time. But with the PEM, it happens almost immediately. Based on our experience, if a CFSer can really get clear, it's possible for the ability to exercise to come back within a day or two, sometimes even within a couple of hours. Depending on the overall weakened state of the body and decreased muscle capabilities, exercise ABILITY may still be limited. But in that case, it's not inflammation driven and the PEM concept won't apply.

It's very hard for people to get that free of mold toxicity though. But the fact that some CFSers can engage in a perplexingly large amount of exercise at odd times without negative effects is consistent with this.

Going back to the title of this thread....I heard recently that stem cell patients in Cheney's studies had a certain inflammatory marker (that will remain unnamed but that is relevant to this post) go down. Dr. C apparently attributes this to general inflammation going down. Insofar as all his patients are like me, I would attribute it to their being able to "hold their mold" better.

Maybe this seems a small distinction, but I'm not so sure. If their C4a was initially really high because they were in a moldy environment and the stem cell made them more able to handle the moldy environment and all other mold exposures permanently, that would be great.

But our observations and Shoemaker's hypotheses suggest that the longer that normal people stay in moldy environments, the worse their health gets. If that's the case, wouldn't you expect a stem cell patient who went back to a really moldy house to eventually relapse?

In that case, wouldn't it make sense to take a look at the house and at least do some basic remediation so that the place isn't a Sick Building?

Certainly, remediation isn't cheap. It might even cost more than the $20k stem cell transplant.

But even if the stem cell transplants have the potential of allowing people's systems to withstand this crap, getting multiple transplants done seems like it would have the potential to really add up.

Maybe a stem cell transplant plus moderate avoidance (meaning simply not living in a really moldy place) would equal full wellness, not just the ten or twenty point improvements on the Karnofsky Performance Status index that Cheney's patients are reporting.

I asked Jen on another thread to give speculate on how exactly the stem cells might be influencing C4a or other issues of relevance to CFSers. Maybe she or others will do so here.

Thoughts please? This feels to me like maybe it's an important issue for us.

Best, Lisa

 

[richvank]

Hi, Lisa.

I just want to note that Ray Stricker and Ritchie Shoemaker have also studied C3a and C4a in Lyme disease. Stricker's paper is about chronic Lyme, and Shoemaker's is about acute Lyme. See below.

Best regards,

Rich

Scand J Immunol. 2009 Jan;69(1):64-9.
Complement split products c3a and c4a in chronic lyme disease.

Stricker RB, Savely VR, Motanya NC, Giclas PC.

International Lyme and Associated Diseases Society, Bethesda, MD, USA. rstricker@usmamed.com
Abstract

Complement split products C3a and C4a are reportedly elevated in patients with acute Lyme disease. We have now examined these immunologic markers in patients with chronic Lyme disease compared to appropriate disease controls. The study population consisted of 29 healthy controls, 445 patients with chronic Lyme disease, 11 patients with systemic lupus erythematosus (SLE) and six patients with AIDS. The Lyme disease patients were divided according to predominant musculoskeletal symptoms (324 patients) or predominant neurologic symptoms (121 patients). C3a and C4a levels were measured by radioimmunoassay. All patients with chronic Lyme disease and AIDS had normal C3a levels compared to controls, whereas patients with SLE had significantly increased levels of this marker. Patients with predominant musculoskeletal symptoms of Lyme disease and AIDS patients had significantly increased levels of C4a compared to either controls, patients with predominant neurologic symptoms of Lyme disease or SLE patients. Response to antibiotic therapy in chronic Lyme disease was associated with a significant decrease in the C4a level, whereas lack of response was associated with a significant increase in this marker. In contrast, AIDS patients had persistently increased C4a levels despite antiretroviral therapy. Lyme patients with positive single-photon emission computed tomographic (SPECT) scans had significantly lower C4a levels compared to Lyme patients with normal SPECT scan results. Patients with predominant musculoskeletal symptoms of Lyme disease have normal C3a and increased C4a levels. This pattern differs from the increase in both markers seen in acute Lyme disease, and C4a changes correlate with the response to therapy in chronic Lyme disease. C4a appears to be a valuable immunologic marker in patients with persistent symptoms of Lyme disease.

PMID: 19140878 [PubMed - indexed for MEDLINE]


Int Arch Allergy Immunol. 2008;146(3):255-61. Epub 2008 Feb 13.
Complement split products C3a and C4a are early markers of acute lyme disease in tick bite patients in the United States.

Shoemaker RC, Giclas PC, Crowder C, House D, Glovsky MM.

Center for Research on Biotoxin Associated Illnesses, Pocomoke, Md., USA.
Abstract

BACKGROUND: Current laboratory markers do not readily detect acute Lyme disease. We assessed the utility of complement and its split products as markers of Lyme disease in patients shortly after a tick bite. METHODS: Thirty-one consecutive acute Lyme disease patients, 14 with and 17 without erythema migrans (EM) skin rash, seen by a physician within 96 h of a tick bite were matched with 24 consecutive tick bite patients without Lyme disease symptoms and 46 healthy control subjects. Complement and split products measured included factor B, Bb, C4, C3c, C3a(des Arg), C4a(des Arg), C1q- and C3d-containing immune complexes, and C2. RESULTS: C2, C4, C3 and factor B levels were within normal ranges in all groups. C3a and C4a levels were significantly higher in acute Lyme disease patients than in tick bite and healthy control groups (both p < 0.001). All acute Lyme disease patients, regardless of EM, had elevated levels of C3a or C4a. Few tick bite controls had elevated levels of C3a (2/20) or C4a (5/24) and only 1 of the healthy control subjects had elevated C3a (0/46) or C4a (1/32). CONCLUSIONS: These findings suggest that C3a and C4a may be useful markers of Lyme disease in patients seen shortly after tick bite, even in those without EM. (c) 2008 S. Karger AG, Basel

PMID: 18270493 [PubMed - indexed for MEDLINE]

 

[Mark]

On day I will get to reading this whole thread and there will no doubt be a great deal I will want to comment on. But the first thing to say is that clearly I have found "my cluster" here with slayadragon, my subgroup of ME/CFS/MCS/WTF, and it's quite extraordinary for me to finally come across somebody who's saying exactly the same things I want to say. There are a few others of us on the mold and MCS threads now actually, But Lisa's comment rings truest I think from what I've seen.

Lisa's point, in the first post on this thread, about people getting better through mold avoidance, and other people who don't get better, is potentially very contentious of course. My own feeling on this is that we have to approach the problem through definition of subgroups, and that we can do that through this community based approach, as indeed we are doing, of course. We are all mixed up together and we need to gravitate towards those we identify with most and separate ourselves out so that we can start making sense of things.

I noticed a comment by Gerwyn about there being no evidence base for Lisa's comments, and I hope that this hasn't remained contentious. My intuition says that the point about there being no evidence is to say: we are patients with an experience forming a series of hypotheses based on our common experience, and that it is then for scientists to test these hypotheses, and then we may or may not have our evidence. So the frontier between the two groups need not be contentious, because somehow you have to generate ideas in order to test them, and both halves are needed, so I find it strange that these two camps see themselves as being at war when in reality they are ultimately co-operating. The best and strongest ideas that arise out of the mold subgroup will eventually demand testing, and then maybe there will be evidence. So there's no reason to be taking sides.

I have one guess about identifying these subgroups, and that is to say that when I trace back my own illness, athlete's foot and some other fungal infection problems were one of the first things that happened, and since then, mold has always been a feature and the one that's yielded the clearest results on treatment. Whereas people with a viral onset and who keep catching colds tend to be the sort of people I've had big flames from and who I have to be careful what I say for risk of causing offence. I think this has to suggest that we are a different subgroup and that's it, and the arguments are pointless.

That said I do still strongly suspect that XMRV lies behind all these subgroups and it's basically a question of site integration (where in the DNA the retrovirus gets inserted) - which part of your immune system was knocked out, in other words. I expect that's pretty obvious and somebody has probably already made the point, but just in case...

One final note before bed: when I first came across XMRV and started googling to find out about the outbreak history, I of course quickly came across Incline Valley, and was interested to do some google searches for certain terms. So I searched for incline valley and various combinations of mold, fungus etc. As I recall I found very little concrete, except a few key posts, but there was one quite remarkable account observing that in the area there was a notorious and weird kind of mold in the air, seasonally, and especially so in an extreme way at the time during the season when the outbreak happened, and that it was really noticeable to people with sensitivities who returned there, and made them very ill. I'm sorry I can't recall any of these accounts or where I found them, and that's a pretty scratchy account I've just given, but anyway I remember my conclusion that the mold seemed like a very probable cause of the outbreak to me. XMRV can perhaps infect certain mold, just as viruses can.

Mold management may not be as crucial for everyone as it is for us, but I suspect it's a useful thing for everyone to address anyway, and as I say, I do suspect XMRV or perhaps another strain or other retrovirus, lies behind IBS etc as well - there's no evidence on that either way yet, of course, which means: all the more reason to test and get the evidence.

Anyway that's all I have time for now, but I will obviously get back to this because this is obviously my subgroup.

 

[slayadragon]

C4, Musculoskeletal vs. Neurological Lyme

These are really interesting articles, Rich.

I'm a little puzzled about something. Maybe if I summarize, someone can fill me in.

The Shoemaker et al study suggests that C4a is highly elevated in patients who have just acquired acute Lyme disease after getting a tick bite. They suggest that (presumably since conventional ELISA/Western Blot testing is so inaccurate), this could be a good diagnostic marker for physicians to use.

The Stricker et al study suggests that C4a is tends to be elevated in chronic Lyme with predominantly "musculoskeletal symptoms" and in AIDS. It is not elevated in chronic Lyme with predominantly "neurological symptoms" or in Lupus.

Consistent with that is the finding that Lyme patients with a positive SPECT (showing evidence of changes in the brain apparently due to the Lyme) had lower levels of C4a than those patients with a normal SPECT (showing no evidence that the brain had been changed by the Lyme).

The study also looked at responses to antibiotics. In those subjects who "responded" to antibiotics (apparently with a decrease in symptoms), the C4a did go down. In subjects that did not respond, the C4a did not go down. (Actually what it says is "whereas lack of response was associated with a significant increase in this marker," which almost suggests to me that there was a die-off like effect where the level got higher. I'd have to read the whole paper to check.)

AIDS patients did not have their C4a levels improve as a result of antiretrovirals.

What puzzles me a bit are the findings about musculoskeletal Lyme vs. neurological Lyme. I'm aware that the first cases of Lyme were mostly "physical" (e.g. like arthritis), but was under the impression that it had become much more neurological in most patients in recent years. Certainly that seems to be the case with those Lyme patients who also meet the criteria for CFS (regardless of whether we're using Fukuda or Canadian Criteria definition).

But if CFS patients tend to have elevated C4a (as the exercise studies suggest), and Lyme/CFS patients are primarily neurological (which seems clear), then it's surprising that the neurological ones wouldn't have come up with elevated C4a.

Does anyone have any thoughts about why that might be?

I find it interesting to see that the antiretroviral drugs did not help AIDS patients to get the C4a levels down. Do AIDS patients get PEM, does anyone know?

Thanks for any insights or further questions that folks can provide.

Best, Lisa

 

[slayadragon]

Oh, look, here's the whole article, in the event anyone wants to join me in reading it. Otherwise I will summarize when finished.

http://www3.interscience.wiley.com/cgi-bin/fulltext/121576238/PDFSTART

 

[slayadragon]

C4a and Lyme

Reading that whole paper did turn out to be really helpful. I learned a lot from it.

It does indeed say that C4a increased as a result of treatment with antibiotics in the Lyme patients who did not improve. I would guess that most LLMD's would say that the patients were not on the drug for long enough, and that if they'd continued to take it for a number of years, the C4a levels eventually would go down.

The summary of the article is below. It's hard to find much info out there about C4a, so it will be good to keep it here for reference.

What I find interesting is the suggestion that C4a is not associated with neurological inflammation. It more seems to be associated with physical inflammation, of the sort experienced by CFSers in post-exertional malaise (or "no-exertional malaise").

What I have found is that overcoming the PEM is a pretty low bar in terms of my efforts to achieve wellness. If I'm not avoiding toxic mold successfully, my ability to exercise is non-existent and my PEM if I force myself to do so is profound. But if I "merely" avoid mold scrupulously for a few days, I have no problems exercising without PEM. I can do so quite consistently and predictably. So can Erik, which is why he was able to make it to the top of Mt Whitney every August for 10 years in a row.

The neurological inflammation is much more difficult for me to get under control. This affects both cognition and emotions, but also just being "present" in the world. I think it's clearly related to the mold, since if I get a big mold hit it gets infinitely worse. But even the most careful mold avoidance doesn't resolve it completely.

The Valcyte actually does seem to have helped that. And not being as reactive to the mold has helped keep the neurological inflammation from flaring as much as I try to navigate a world where toxic mold is ubiquitous. But it feels like the neurological inflammation is still there, underlying everything that I do.

I wonder what "measure" it is that the "neurological" Lyme is causing to be inflamed. Apparently it's something other than C4a.

(Dr. Shoemaker actually has said, to my understanding, that C4a tends to be a more specific marker for chronic mold toxicity than chronic Lyme. So the idea that addressing just mold fixes C4a altogether, and also allows exercise issues to be resolved, makes some sense in that context.)

And I would bet a large amount of money that whatever that inflammatory "thing" is, it needs both Lyme toxin and mold toxin to really go haywire. It's not an additive effect, in my experience. The two toxins seem to work synergistically. I once said, subjectively, that it was like the mold was inflaming my brain and the Lyme was pouring salt into it. Based on what I know of the effects of satratoxin and of Lyme toxin, this might even be almost literally true.

I wonder what that neurological inflammatory marker would be. Any thoughts?

I guess I could try antibiotics (on their own or as part of the Marshall Protocol) next. I will say that chipping away at this stuff is becoming a bit tedious, but collecting as much information as I can from the rabbit hole seems to have the potential of being of value anyway.

Best, Lisa

*

Discussion

C3a, C4a and C5a have been designated as anaphylatoxins. Recent studies, however, have cast doubt on the role of C4a as an anaphylatoxin, and the function of this molecule is presently unclear.

Whereas C4a is generated by the classical or the lectin complement activation pathway, C3a is generated by the classical, alternative and lectin pathways. C5a, which is a product of the terminal pathway of complement activation, has a very short half-life that makes it difficult to measure in routine blood samples.

In contrast, C4a levels are selectively increased in adult insulin-dependent diabetes mellitus, while C3a and C4a are reportedly increased in normal pregnancy, active SLE requiring immunosuppressive therapy and other forms of vasculitis.

C4a was also found to be increased in a model of CFS.

Of note, C3a appears to play a significant role in central nervous system inflammation associated with ischaemic stroke and substrachnoid haemmorhage, while C4a appears to have only a minor role in brain inflammation. The reason for this discrepancy is unclear, but it may reflect decreased constituitive production of the parent C4 compound or a diminished response to cytokines such as interferon gamma in brain tissue.

In contrast to C4a, an increase in C3a was only seen in patients with active SLE. As stated previously, increased C3a correlates with active autoimmunity, and this immunologic marker may help to distinguish chronic autoimmune pathology from persistent tick borne infection. As increased C4a was also found in patients with AIDS and to a variable degree in patients with SLE, this marker by itself would not be sufficient to diagnose chronic Lyme disease. In the absence of a positive AIDS test or autoimmune serology and the presence of significant musuloskeletal symptoms, the pattern of normal C3a and increased C4a appears to correlate with the presence of chronic tick-borne disease.

Sorensen et al demonstrated that C4a is increased in patients with CFS following exertional challenge. Chronic fatigue and fibromyalgia are prominent symptoms of chronic Lyme disease, and there appears to be significant overlap in these clinical syndromes.

It is noteworthy that patients with predominant neurologic symptoms of Lyme disease had normal levels of C4a despite the presence of chronic fatigue in most of these patients. A comparison between chronic fatigue patients who are seronegative for Lyme disease and seropositive Lyme patients would be of interest to help distinguish these disease entities.

It is unclear why C4a but not C3a is increased in patients with predominant musculoskeletal symptoms of chronic Lyme disease. The pattern suggests that chronic infection with B. burgdorferi is associated with activation of the classical complement pathway rather than the alternative and lectin pathways.

Support for this hypothesis comes from in vitro studies showing that the Lyme spirochete activates complement via both the classical and alternative pathways, but the spirochetes are capable of inactivating the alternative pathway, thereby allowing the infection to persist. Alternatively, increased C4a with normal C3a may reflect the inhibition of immune precipitation rather than solubilization of immune complexes in chronic Lyme disease. Thus, elevated C4a may be a marker of a failed immune response against the Lyme spirochete. Conversely return of this complement component to normal suggests clearance of the organism by antibiotic therapy.

C4a does not appear to play a significant role in inflammation of the central nervous system. This may explain why patients with predominant neurological symptoms of chronic Lyme disease have relatively normal levels of this complement split product. The difference in C4a levels associated with positive or negative SPECT scan results is intriguing. One explanation is that predominant neurological symptoms may reflect generalized inflammation rather than direct brain involvement in some patients with concomiitant musculoskeletal symptoms. Alternatively, increased C4a may be associated with inflammation in peripheral nerves rather than the central nervous system in chronic Lyme disease. We have observed elevated levels of C4a in patients with Lyme-associated motor neuron disease that resumbles ALS. In this condition, however, the increase in C4a may reflect the involvement of both upper and lower motor neurons. The interaction between nervous system inflammation and complement activation requires further study.

 

[jenbooks]

Hi Lisa...you've drawn me back into your thread...
I think the questions you pose on complement and stem cells and mold are really fascinating.
I don't have any easy answers.
The way I see stem cell therapy without ablation (without wiping out the immune system to create "space" for the new stem cells to completely repopulate) is that it is more akin to the way stem cells are being used to repair tissue, as in cardiac damage (I know there are animal studies that indicate good tissue repair, and I believe there are some human trials now taking place). So I think of the immune system as a kind of mobile "tissue". The stem cells can provide lots of new troops to repair lots of things. One person on CFS Experimental mentioned her hiatal hernia repairing rather quickly after her first placental stem cell treatment. Other things sucessively repaired over time with successive treatments. One could intuit, that perhaps the cells go to where the body most needs them, first. That part of the body might be signalling the loudest with inflammatory markers etc (sort of like a cut signals to platelets to rush to the site of the wound immediately).

However, because the immune system is not being wiped out and rebooted, I am not quite sure how it is having such remarkable results in some. It looks like a reboot. And sometimes the corrupted phenotype--the sick person--seems to be partly a really bad information loop that perpetuates itself on the part of the immune system. Thus they found that a certain type of chemo could sometimes cure aplastic anemia--by basically rebooting the immune system, so it stopped turning on itself and destroying its red blood cells. Whatever had initially triggered the aplastic anemia, I don't know, but the body apparently could not shut down its response. But when wiped out and rebooted, the immune system righted itself. It ran information "correctly."

So maybe this is partially happening by the flow of new information, in large #'s, in stem cell treatments. Those uncorrupted stem cells are signaling, "Hey body, THIS is the correct way to do it, the correct information, don't listen to that corrupted information loop set into motion by X pathogen..." There's enough of that, and enough good new fresh life in the cells, to, it seems, put one back into the profound somnolence and healing ability of a little baby. Babies sleep a lot, and grow a lot. And stem cell recipients sleep a lot, and heal a lot, which is a sort of "growth' I suppose.

These are completely unschooled suppositions as I haven't studied it at all.

Anyway, to continue on with the metaphor, it's almost as if the immune/neurological systems experienced a hostile takeover, and eventually, got so used to it, the system functions as an automaton under the new hostile regime. And it becomes the new norm. And then it's harder to break free because the immune/neuro system is used to it. It will automatically generate inflammation, whether complement or other markers, at the slightest trigger.

If you re-set it back to health, and a healthy response, theoretically you could "hold the mold" better. But I agree with you, too little is known, and the risk too great, to knowingly expose yourself to *anything* that could make you sick again. Which is why as Mark notes the subset of us who are "moldies" along with everything else, need to be really vigilant, if possible. It's not always or even often, possible, for most.

 

[floydguy]

I'd also like to point out that Shoemaker considers TGF Beta to be as important these days as the C4a measurement. I am curious to hear what people think of TGF beta as it relates to C4a and other markers.

http://www.cambridgebiomedical.com/media/PDFLibrary/TechBrief_TGF-b1TB-050.pdf

 

[Jenny]

I've been thinking about this mould issue for some time, as I'm usually better in hot, dry climates. But one of my main relapse triggers is a change of temperature from warm to colder and I've had periods of being in damp, musty environments and been completely well.

Anyway, some are implying on this thread that it's relatively simple, though expensive, to get your house tested for mould. How on earth would one do that in the UK?

Jenny

 

[slayadragon]

Dr. Mary Beth Short-Ray, Mold Testing/Remediation, "Suicide Season"

Hi Jenny,

I don't know if by "a change of temperature from warm to colder" you're talking about what happens on a particular day, or a seasonal change.

If the latter, many of us "Moldies" find that we do much worse in winter than in warmer months. I'm going to put a comment of Erik's on this topic below.

Damp musty environments don't necessarily have substantial amounts of toxic mold in them. We're only concerned with the poisonous species of mold, and perhaps in particular Stachybotrys.

My own observations makes me think that if a building doesn't have drywall in it, the likelihood that it will be at least vaguely tolerable for me even if it smells musty is pretty good. This is consistent with the idea that Stachy is finicky in its growing conditions, generally needing a lot of water and some easily digestible cellulose. The use of "paper" to cover up plumbing pipes was a disaster waiting to happen, from that perspective.

Buildings without any drywall (in original construction or renovations) are increasingly uncommon in the U.S. Maybe they're more common in England?

In any case, as discussed above, the outside air in England seems to be an issue. Maybe Mark will tell us more about that. The story of people feeling great when they go to places like Greece or the Caribbean and then relapsing when they return to England is absolutely classic.

Not everywhere with damp air is bad, btw. I felt great in Carmel, California, which is right on the ocean. I would suspect that there are certain places in England that are on the sea that might feel okay too (as a result of the fresh breezes and/or negative ions), but I have no concept of where they might be.

Oddly, the only place I felt good in England when I spent a summer there many years ago was in Stratford-upon-Avon. Things may have changed since then though. It may have been that it was more in the countryside. Also, this was an old cob inn from the 1500s, and it may not have had any drywall renovations in it. Anyway, there may be scattered okay places in England, but good luck finding them if you're not already unmasked enough to identify this stuff when you come across it.

Here are some thoughts on mold testing and remediation. However, keep in mind that CFSers' mold reactivity tends to be so high that "ordinary" standards do not apply. When I was at my most reactive, I got sick from the spores sticking to my hair after 30 seconds in a moldy building or from washed clothing that had once been in my moldy house. So even if no mold whatsoever is growing in a place does not mean that moving into it is going to effect any sort of a "cure."

However, the point of this thread is the idea that CFSers can use addressing mold as "leverage" to help other treatments to work better. Moving to a place that is ordinarily okay may not improve wellness in itself, but it may keep CFSers from further declines and give them a stronger base to benefit from other approaches.

A number of people from England have told me that they've had a hard time finding remediation professionals. I thus was glad to run into one guy who seemed to me reasonable on the internet. I can't vouch for him, but it's a start. Here's his information.

Jeff Charlton
www.999team.org
London
07990 500 999

The ERMI (described in one of my posts above) is a test that people can do themselves. Following is Dr. Mary Beth Short-Ray's site, where it can be ordered:

http://www.toxic-black-mold-syndrome.com/Black-Mold-Testing.html

Note that I'm ONLY suggesting that the ERMI conceivably could be helpful. I would not recommend that you try any of the other environmental testing products on that site.

Here's some background on Dr. Mary (a D.O.), so that folks can have a better idea of how to interpret her comments and experiences.

Her own initial exposure to Stachy ("Toxic Black Mold") was in her workplace. Air tests came up with horrific levels of the mold.

She also found some mold in her own home. This was identified on a tape lift as Aspergillus, though (as I mentioned in the testing post above) this does not mean that other molds also weren't present. She attempted remediation of this mold.

I met her in Ann Arbor a year later. Her reactivity at the point was so high that she was living with her baby in her car, had concluded that she couldn't work in her office (which I found to be, like most doctors' offices, somewhat but not severely contaminated), and was spending as much time as possible in the local library and the local Panera because every other place was intolerable.

Apparently she never got "masked" enough to the mold to put her down into full-fledged CFS. She was fading fast though.

She found more mold growing in her basement, but a tape lift suggested that it again was Aspergillus.

Her husband was rapidly losing patience with the whole thing.

Erik and I spent some time talking with her about our experiences and her situation. She ended up moving to the coast of Florida (I think near Jacksonville). (It seems like Florida should be terrible for toxic mold because of the humidity, but Erik found it to be not too bad during a trip there. The bright sun and ocean breezes seem to help.) The last time I corresponded with her, she was working in a tolerable office and doing a lot better.

Shortly after first getting sick, Dr. Mary wrote a book that is basically a summary of Dr. Shoemaker's "Mold Warriors" but written at a level that mold victims and CFSers can easily comprehend. I highly recommend it as a starting point for anyone interested in the topic.

The title is "Surviving Toxic Black Mold Syndrome."

I think the medical information in the book is good.

However, the do-it-yourself remediation tips in the book are awful! Clearly they didn't work for Dr. Mary herself, and they could be dangerous or deadly for CFSers to attempt. I've seen CFSers get really sick from attempting their own remediations, and Erik has seen a number of people (including some who weren't already especially sick) die from doing this.

So PLEASE don't follow Dr. Mary's instructions on the remediation.

Other than the ERMI, I don't think people should consider any of the testing products on her site either. (If you really want a tape lift, I'd suggest MouldWorks.)

Dr. Mary is in a general practice at present, but I think she would see mold patients if they want to visit her there. She thus could be an option for people who want to get Dr. Shoemaker's lab panel and prescriptions.

Just please ignore the remediation suggestions in her book.

Best, Lisa

*

I refer to October through January as "Suicide Season."

When the winter storms start unleashing the plumes in late October, the ambient badness seems to exert a depressing influence on nearly everyone. It seems to peak right around the Christmas holidays.

Yeah, I know. Everyone blames the Christmas blech on the "stress" of shopping, relatives, etc.

But the more you look at the peculiar lack of a real solid emotional stimulus to really correlate to just how much people lose it this time of year, I think you'll agree.

There is a generalized neurotoxin shift the puts the edge on everyone and it shows,
if you know what you're looking for. And it appears to me that every year, it gets just a bit worse.

By the end of January, sometime in February, it seems to start easing up.

-Erik (2008)

*

October through March are the months when I used to want to shoot myself, before I discovered that I could escape that seasonal downturn completely by mold avoidance.

So I called it "Suicide Season,” which is how I felt, but not quite so politically correct as "The November Factor.”

http://www.pediatricnetwork.org/lyndonvillenews/jean/novemberfactor.htm

-Erik (2010)

 

[slayadragon]

TGF Beta, C4a, Antiretrovirals

Dr. Jamie Deckoff-Jones is a physician with CFS/whatever who is taking a few antiretroviral drugs to treat her XMRV. I think she's been on the drugs for a couple of months.

Here is a comment about her TGF Beta and C4a responses. Perhaps they will be useful in our discussion.

Lisa

*

I ended up stopping tenofovir after five days. The symptoms that I experienced when I added the tenofovir were more consistent with a flare of my disease than anything to do with the known toxicity profile of the drug. In addition I had repeated my TGF beta-1 (the only potential marker I've ever found of my disease) and C4a which was high normal at baseline. TGF beta-1 was still astronomically high and C4a shot way up, on AZT/raltegravir, even though I didn't feel worse when the labs were drawn. Shortly after that draw, I started to feel and function much better, then plateaued until I started the tenofovir. Repeat TGF beta-1 and C4a from just prior to starting tenofovir are pending. By the way, I am having safety labs every two weeks (blood count and metabolic panel).

http://treatingxmrv.blogspot.com/2010/05/speculation-about-drug-reaction.html

 

[lono]

1. I think it's important to keep in mind that a high reading from a biomarker like C4a doesn't give us a road map to exactly what's wrong. So for example, C4a has been shown to be elevated in Lyme patients, a subset of people who have had exposure to water-damaged buildings, and multiple sclerosis (and those are just the ones we know about - it's only within the last several years that it's been generally studied/considered in relation to the conditions mentioned).

One other thing about C4a I wanted to note. In the Nijs paper I referenced in #119 (where they concluded that, "the level of complement C4a following submaximal exercise was identified as a clinically important biomarker in people with ME/CFS") it looked like the CFS/ME folks who they tested didn't initially have high C4a levels. My recollection is that the average was around 2,000 or so (which is in the normal range), but 24 hours after exercise in increase in C4a also corresponded with an increase in fatigue and pain.

However there are a number of CFSers (including me) who seem to have permanently elevated C4a levels.

2. I'm also hoping that some other people will weigh in regarding TGF Beta-1, which floydguy mentioned in posting #128. I've had it tested and (at least for now) my levels are normal, but I've heard about a number of CFSers who have elevated levels (and I know that the Whittemore Peterson Institute is also quite interested in TGF-B). Anyone else had this tested?

 

[slayadragon]

Inflammatory Markers

The idea that C4a is associated with physical rather than neurological inflammation was a real breakthrough for me.

Does anyone know what kinds of effects TGF Beta is associated with?

Are there any markers that tend to be associated in particular with neurological inflammation?

What kinds of markers do the Lyme Literate MD's look for, does anyone know?

Iono, you say that you have chronically elevated C4a but normal TGF Beta. What kinds of CFS symptoms are (and are not) major problems for you?

Figuring out how all these different inflammation-producing factors work together to lead to this disease is one of the top questions on my list. I'm glad we're discussing it.

Lisa

 

[sarahg]

Ok bear with me, my brain is nearly gone at the moment. This is an interesting discussion. I am another who has had consistently high c4a levels. (ooh the papers are right on the desk!- last test about 2 months ago...14,000 ng/ml...reference range of 0-2830) after a bit of research and talking to my doctor it seemed this was either because of catastrophically high levels of hhv-6, parvovirus b-19, and ebv...or that I had a chronic lyme infection that wasn't behaving enough for the tests to be anything but inconclusive. I've had mold issues since I was a child so the mold aspect is an interesting one that I hadn't come across in relation to the c4a.

So about 3 weeks ago I got bit by a tick and am in the throes of actute lyme disease at the moment. I'm thankfully tolerating the antibiotics, but still not rid of the neurological manifestations that have sprung up.

Anyway, I am curious to see what my c4a levels will do in response to this new insult. I am seeing my specialist the day after tomorrow and trying to formulate a more coordinated response to this, but I think he will also give me the order sheet to get the igenex tests redone in a few weeks and retest the c4a levels. I mean, I doubt they would come down if I find myself with very neurological-ish lyme, but I wonder if there will be some sort of change.


ETA just learned the results are actually above 14,000 ng/dl but that is the upper threshold of the test, there is no way of knowing how much higher they actually are. Apparently the test used to be different but they have changed the way they conduct it so after that level there is no way of knowing how much higher it is. Be aware of this if you get this test. It's probably cheaper for them, but not very helpful when you're trying to see if the levels have gone down at all.

 

[floydguy]

C4a & TGF Beta Symptoms

My frustration is that I struggle with matching up symptoms and labs. My C4a bounces around from a low of about 4,000 to a high of 32,000+. But I don't usually have much in the way of physical issues (PEM). TGF Beta the last few times has been 10,000 - 23,000. Many of my symptoms are neurological and hormonal - body dysregulation (freezing cold), extremely poor circulation. I have the constant flu like achiness. I struggle telling the difference between low and high values.

For me what's most important is summer/hot sunny weather (hotter the better) and being in a "clean" environment. For some reason ventilation - steady clean breeze - is helpful. Otherwise, I can actually feel the inflammation building in my head.

Out of curiosity has anyone taken Provigil or Adderol or something similar for brain fog/concentration issues? Has this helped?

For me none of the gobs of antibiotics that I took when being treated for Lyme helped reduce symptoms.

Here is a Lyme Doc who has mentioned C4a in his diagnostic process. I don't think he mentions TGF Beta. Aside from Shoemaker I've only heard it mentioned in regards to CFS (Cheney & Mikovits).

http://lymemd.blogspot.com/

Check out November 9, 2009 post. He looks at CD57, C4a, CIC, CRP among others....

 

[Rockt]

"I'd like to be able to say, "Yes, there are all kinds of things that cause inflammation in CFS, and mold is just one." That doesn't seem to be what's happening though. Underlying Lyme infections or XMRV infections or herpes virus infections or emotional stress or other sorts of chemicals don't, in our experience, interfere with the ability to exercise without PEM. Just the mold.

Moreover, the ability to exercise without PEM seems to occur almost immediately after getting free of the mold. Most of the improvements from mold avoidance take time. But with the PEM, it happens almost immediately. Based on our experience, if a CFSer can really get clear, it's possible for the ability to exercise to come back within a day or two, sometimes even within a couple of hours. Depending on the overall weakened state of the body and decreased muscle capabilities, exercise ABILITY may still be limited. But in that case, it's not inflammation driven and the PEM concept won't apply.

It's very hard for people to get that free of mold toxicity though. But the fact that some CFSers can engage in a perplexingly large amount of exercise at odd times without negative effects is consistent with this."


Sorry, I couldn't read the whole thread, (my symptoms are primarily cognitive in nautre), but... are you saying that if one can get clear of mold, they can exercise without PEM? How does one go about getting clear of mold, or even know if mold is a problem, (though if mold is the only cause of PEM, I must be effected by it - I live in an old house)? If I could exercise, my whole world would open up.

 

[Jenny]

Hi Jenny,

I don't know if by "a change of temperature from warm to colder" you're talking about what happens on a particular day, or a seasonal change.

If the latter, many of us "Moldies" find that we do much worse in winter than in warmer months. I'm going to put a comment of Erik's on this topic below.

Hi Lisa

What often triggers a long relapse is simply getting chilled. For example, I went to a party in a marquee last October and it was freezing. Within a few days I was in a relapse that still has me bedridden most of the time. But in general I'm better in the summer, particularly when the temperature is consistently more than 22 degrees.

Thanks for the link for the London mould inspectors. Overall, I think mould is a possible factor for me, but unlikely. I don't usually improve when I go away, and I was mostly recovered in the 1990s, though living in the same house as I was when I first became ill.

I have a long list of things to try - mould avoidance is on it, but I'm trying other things first that seem to stand more chance of success with less outlay and effort.

Jenny

 

[slayadragon]

Using Mold Avoidance as Leverage

Hi Rock,

That excerpt makes it sound like I'm saying that all CFSers would be able to exercise if they weren't getting mold exposure, and that mold avoidance is a magic cure. Neither of these things is true.

A number of people with classic severe CFS have found that "merely" by avoiding toxic mold, they can exercise vigorously without PEM. Whether that would hold for any other CFSers other than ourselves, I cannot say.

The extent to which these individuals have had to attend to the presence of toxic mold in the environment in order to obtain this gain is really large. It's not just a matter of moving to a building where there's no mold growing. Very small amounts of mycotoxins (mold toxins) can set off the response. For instance, at my most reactive, the amount of mold that clung to my hair after a 30-second visit to a moldy building would make me increasingly sick until I washed it out.

This is apparently similar to how people with severe peanut allergies respond when they get exposed to even tiny amounts of peanuts. They don't have to eat a peanut butter sandwich to get affected. Just a tiny bit of peanut oil or a tiny bit of peanut "dust" breathed in can do it. That's why foods now carry labels that say "this product is from a factory that processes peanuts"....so that people with peanut allergies know to avoid it.

Since such tiny amounts of toxin can cause the response, care needs to be taken in terms of all aspects of our lives. Because mycotoxins can be in the outside air (especially in cities where there are a lot of bad buildings or in certain places where it grows outside), that puts a limit on where we can live and remain wholly well. Contaminated objects in the environment (such as bedding) can have an effect. Going briefly into a bad building and then not decontaminating afterwards (washing hair and changing clothing) can be enough. Just living in a building without any mold growing in it is just a start.

Obviously controlling for all these factors is extremely difficult. It's not something that I am encouraging people to jump into lightly.

I'm discussing it on this thread for a couple of reasons.

First, I'm increasingly of the belief that the reason that many CFSers don't benefit from the treatments that dedicated doctors and researchers are making available is not because the treatments themselves are useless but because their systems are too overwhelmed with toxic mold exposures to be able to use those treatments effectively.

Toxic mold is not the only factor that contributes to CFSers' illnesses. Our illnesses seem to be a stew of all kinds of bad stuff---viruses, Lyme, other bacteria, candida, mercury, other toxins, hormonal dysfunctions, brain injuries.

Effectively addressing any of these things seems like it has the potential of getting at the core issues of CFS---e.g. getting inflammation under control, increasing system strength, improving mitochondrial function. All of these things are tied together.

The problem is that a high percentage of CFSers are so debilitated that they can't address any of these things effectively. Die-off responses are a major impediment to the effective treatment of Lyme. Jose Montoya, who started off treating CFS patients aggressively with Valcyte, more recently concluded that this is counterproductive and is being much more conservative in the amounts he prescribes. Many CFSers can't treat candida without getting really sick. We've seen already that drugs that could conceivably address XMRV cannot be easily tolerated by at least many CFSers. Many patients starting Rich van K's methylation protocol cannot tolerate even the tiniest doses of those supplements.

So what we have is a bunch of patients who know that they have a huge variety of problems but cannot treat any of them. What's then left to do is the approach that Dr. Cheney is now advocating. In large part, this involves reducing stress on the system. Avoid foods that create sensitivities or that are hard to process. Don't take most drugs. Don't do too much. Support the system with proper nutrition and supplements.

I don't have any problem with any of these things. I don't even have any problem with Amygdala Retraining or other ways of helping people to address their emotional stress levels. Certainly, it's stressful to have CFS, stress is not without physical consequence, and we need all the help we can get.

The problem that I have is that many of the very same people who are sitting around worrying about flecks of gluten in their diet and who are attempting to make themselves more serene than Buddhist monks, or who are enduring excruciatingly painful experiences trying to get viruses or Lyme under control, are doing so without having put even one second's worth of thought into the topic of toxic mold.

Even if it weren't for my experiences and the experiences of other CFSers in achieving recovery just from avoiding mold, this would make no sense.

As we've discussed on this thread, there is no doubt in the literature at this point that toxic mold is dangerous. Living in a moldy place has the ability to make well people sick in and of itself. It affects the immune system, causes inflammation, causes decreases in the presence of available reduced glutathione, and causes neurological problems. The idea that CFSers---who clearly have all those problems---would be especially harmed by its presence should not be that hard to accept.

And yet, almost universally, the presence of toxic mold has been overlooked.

Just looking at this logically, it would make sense that one of the first things that a CFS doctor would want to do during a consultation with a new patient is to consider whether toxic mold could contributing to the problem. A simple ERMI test would be a good start. If all kinds of other "stressors" are being discussed, it doesn't make sense for this one to be left out.

I've yet to hear ANY CFS doctor propose this as part of an interview though. I'm not sure why. My best guess is that they're afraid that patients won't want to move out of their homes and thus don't want to open up the whole can of worms. "What you're suggesting would lose me all my patients," one doctor (who believes my recovery story and admits that many of his patients appear to be "Moldies") told me at one point.

So here we have doctors who are not suggesting that mold could be an issue because they're afraid that patients are not going to be happy at being told that they should do something about it. And of course, we have patients who don't believe that they need to do anything about mold because their doctors aren't suggesting it. This makes for less contentious office visits, but if I'm right and mold IS an issue, it means that a lot of people are shooting themselves in the foot in terms of their potential to get well.

Here I'm not talking about "extreme avoidance" of the sort that I am doing, and that has restored my exercise ability. I'm just talking about not living in an ordinarily moldy building. If every CFSer got the ERMI done and addressed any problems (by moving or remediation) to the point that the ERMI was okay, that would be a really good first step. The number of people who would get markedly better just from that would be pretty small, but it would be a good stepping stone toward avoiding further declines and maximizing the effects of other treatments.

Certainly, people with peanut allergies don't want to get ANY exposures. But even if they had to continue to fly on airplanes where peanuts were served, I would guess that they probably would want to minimize the number of peanut butter sandwiches that they consumed.

When I was in my own moldy house, I was unable to tolerate any treatments for this disease. Tiny doses of antibiotics and antivirals made me extremely ill, and I didn't recover from those experiments for months after I stopped the drugs. I got sick enough on Rich's supplements that I was included in the "adverse effects" section of his papers. Candida was out of control no matter what I did to address it. And though I was fanatical in terms of my attention to food sensitivities, rarely did anything other than rest in bed, and took a whole bunch of supportive supplements, my health just kept declining.

Throughout my 12-year illness, I tried every single treatment I could find for this illness. Some of them helped a little, but in general my health just kept going down. It only stopped going down after I got away from the mold.

I didn't have to pursue "extreme avoidance" to experience improvements. Just moving out of my house and putting aside the stuff from the house was enough to allow me to make really big gains.

And after I made those gains, a lot of the treatments that I hadn't been able to use before (like Rich's supplements, antivirals, antibiotics and things to address candida) became tolerable and beneficial to me.

This is what I mean by leverage. Regardless of whether mold is a "cause" of this disease, decreasing exposures is an option for CFSers regardless of how debilitated their bodies are. Many people never are going to be able to attack Lyme, viruses or methylation defects head on, if that's where they start. Reducing mold exposures is a place where they can at least start.

Obviously, addressing one's environment can be difficult and expensive. Some say that the emotional stress is not worth it. I would encourage those individuals to look at the literature involving the physical effects of emotional stress vs. the physical effects of toxic mold exposures and make their own conclusions about which is worse.

It's my observation that a very high percentage of people with CFS are hyperreactive to mold and that a bizarrely high percentage of them are living in extraordinarily moldy environments. I don't have peer-reviewed published evidence that this is the case, and (unless either CFS doctors and/or CFS patients start to look into whether mold indeed is a particular issue in this disease) I don't anticipate having them available right away. But even if we take the info that we already know (e.g. the effects that toxic mold has on the system and doctors' insistence that addressing these same issues is important in CFS), looking at the mold seems a sensible and prudent thing to do for those who have any interest whatsoever in maximizing their own health.

My other goal is to try to use the experiences of those who have achieved spectacular and specific improvements in wellness (such as the ability to exercise) as a way of providing information about the nature of this disease to those researchers and doctors who might benefit from knowing more. Not everyone is going to want to pursue mold avoidance to the extent that I have. I understand that. But the information about what DOES happen if you can avoid this stuff to a large enough amount is informative in terms of the role that it plays, just as knowing that people get sick from the peanut exposures rather than something else is a good first step in allowing researchers to attempt to treat that problem.

Best, Lisa

 

[slayadragon]

TGF Beta

In keeping with the theme of this thread, here is a quote about TGF Beta from Dr. Cheney's web site.

>It is interesting that T-cell activation is such as big part of CFS and hence TGF Beta-1 activation in response to T-cell activation. Yet, there is little true autoimmune disease seen in CFS as distinct from autoantibody formation without organ destruction which is more common. Do you suppose TGF Beta-1 activation is the reason for such low autoimmune disease or despite it as there is some other reason?

*

Here is an exchange between Dr. Cheney and Dr. Mikovits:

Cheney: A lot of [CFS] patients, if you investigate their immune system, there’s evidence of significant activation of the immune system of almost any parameter that you look at, particularly cytokine elevations of various kinds and evidence of TGF beta 1 activations. Suggesting the immune system is really activated and there’s kind of a counter response trying to tone it down. Is immune activation, which we almost see universally by cytokine markers, consistent with XMRV infection?

Mikovits: Well yes, and every other retroviral infection, absolutely. Again, it goes unchecked, so the immune system is trying to do it’s job, clear the virus, keep the virus down, and when the virus goes unchecked, it causes the kind of things we discussed with elevated T cells as the problem. So in the face of chronic inflammation you develop immune deficiency.

*

And here is a comment from that same interview that the envelope of XMRV might be serving as a neurotoxin itself.

Cheney: There’s a lot of brain involvement in CFS and it comes in the form of neurocognitive complaints; it comes in the form of neuro-behavioral shifts; it comes in the form of abnormal MRI scans that are typically non-specific but abnormal; it comes in the form of subtle neurological findings on exams such as hyper-reflexia and disturbances of the vestibular apparatus. So my question is, do you think XMRV could be causing neurological problems like this?

Judy: Oh absolutely, and again we go back to other retroviruses, HTLV-1, in addition to leukemia that it is causative for, has associated with it a disease called HTVL-1 associated myelopathy, where it is a myelopathy type disease. The patients stagger, can’t walk, end up in wheelchairs, and it is related directly to viral load but they don’t understand all of the mechanisms. Importantly, in XMRV family members in animals the envelope protein actually is a neurotoxin, so parts of the viruses by themselves, without all the infectious replicating virus, can cause neurotoxicity. We are actually investigating the envelope protein of this virus as potentially a neurotoxin.

 

[Cloud]

Lisa....thank you for all the great information. I have a question....You mention "setting your things aside" when moving into a mold free environment. Does it not rid clothes, blankets, etc. of Mold to be washed and dried?