Monthly Archives: December 2017

Biotoxin XIV: Fixing TGF-beta 1

 

Biotoxin XIV: Fixing TGF-Beta1

References: Shoemaker ProtocolScienceWikipediaSci Rep 2017,

We are almost at the end of our Biotoxin Treatment Pathway. Fixing TGF-beta 1 is next to last. If your level is over 2380, you need to fix it. And fix it you can. What is it that TGF-beta 1 does? It’s a member of superfamily of cytokines in that it has myriad functions. It plays a key roll in cellular differentiation, proliferation, and finally apoptosis. Many cells secrete it and respond to it, so our understanding of it is just getting started. We do see it act badly in Marfan’s syndrome where folks are super stretchy and bendy and have a “wingspan” greater than their height. They often die from burst aortic aneurysms, caused by too much TGF-beta 1. In fact, someone whose wingspan is greater than their height is very likely to have an elevated TGFb1. Hmmm. Might you measure yours? If you have an autoimmune disease, know your wingspan, and your TGFb1, as fixing your mold illness may revert your BT illness. Cool, huh!
Levels of 5000 and below usually aren’t too sick but over 10,000 and you are almost certain to have some identifiable effect. Lung, joint, brain are common victims. For example, in the brain we know that glial cells put out Glial Fibrillatory Acidic Protein, that inhibits cell growth and axonal connections. In lungs we suspect that at many as 50% of adults developing new asthma are doing so from biotoxin illness with ‘TGF-beta 1 playing a leading roll.

TGF beta 1 drives the development of imbalance between T-regulatory CD4+CD25++ cells and TH-17 cells. This might be at the heart of autoimmunity. T-regulatory cells help prevent autoimmunity – the body attacking itself. In some with biotoxin illness, T-regulatory cells are improperly changed into pathogenic effector T-cells by TH-17 cells. The next effect is an endless positive feedback look driving more TGF beta 1. We can now measure CD4+CD25++ and CD4+CD25++127lo/- cells as one method of getting to the heart of this imbalance. Can you imagine if this works out to have a major impact on ALL autoimmune disease. That would be so amazing!

How do you fix it? Actually, it’s easy….well, sort of. Cozaar, or Losartan, yes – a high blood pressure mediation lowers TGFbeta 1. If it is above 2380, and particularly if T-regulatory CD4+CD25++ combo cell levels are less than 18, you need to be on Losartan. 25 mg twice a day will do most adults, but if blood pressure doesn’t drop too much, 50 mg a day will push it even faster. For how long? Until you are better. Not years, weeks. Maybe months. Provided you are out of the biotoxin environment and not being reignited with new inflammation. For those whose blood pressure is too low, VIP spray also works. (Next week).

What is it that Losartan does? Remember, you asked: here goes: “EXP3179, but not losartan and EXP3174, dose-dependently inhibited (P<0.05) phorbol myristate acetate and insulin-stimulated NADPH oxidase activity. EXP3179 also inhibited phorbol myristate acetate-induced NADPH oxidase in endothelial cells. In addition, EXP3179 inhibited (P<0.05) both phorbol myristate acetate-stimulated p47phox translocation from cytosol to membranes and protein kinase C activity.” Did you get that? I didn’t either till I read it three times. Remember, EXP3179 does it, not Losartan. But it does lower TGF-beta 1. Aren’t you relieved! Stupid little high blood pressure medicine, works wonders on TGFb1.

WWW.What will work for me. I’m seeing tons of folks with CIRS and mold illness with TGFb1 over 10,000. My highest has been 28,000 something and that person answered 29 symptoms on Shoemaker’s symptom list. Mostly they said their brain just didn’t work. Can you imagine the wonder I feel to see folks getting better from a mystery illness that heretofore went not only unrecognized, but blamed on the victim?  It’s like a Christmas present.

 

Pop Quiz:

1.     TGFb1 is ….?                                                                    Answer: a peptide cytokine that has regulatory properties for cell growth and differential, and eventually cell death. It plays a key role in facilitating autoimmune disease.

2.     It needs treatment to lower it when…?                       Answer If you feel sick and have levels over 2380,

3.     The best way to lower it is with a drug called…..?     Answer: Losartan

4.     How long do you have to treat for?                             Answer: until better with normal TGFb1, which might be a couple of weeks or months. Or VIP

5.     If you are “double jointed” and can bend your fingers back to your wrist or scratch the middle of our back easily, you might first want to measure what?                   Answer: Your wingspan, then your TGFb1.

 

 

 

Biotoxin XIII: Fixing C4a

References: Jr Aller Clin ImmunSelfHacked.comSeminar Immunopath,

If you hadn’t heard of C3a last week, you don’t know about C4a either. It’s another member of the complement system, that basic process that kills invading bacteria with nonspecific chemicals. The complement system is a cascade like multiplying dominoes that rapidly magnify your immune response. C4a is an activationanaphylatoxin that can rapidly ramp up trouble. It’s one step up from C3a. . There are three pathways of complement activation, but mold illness tends to use the MBL (mannose binding lectin) pathway. This pathway is designed to recognize specific shapes, mannose and n-acetylglucoseamine in particular. When MBL sees those shapes, it turns on the heavy duty MBL Associated Serine Proteinases – or MASPS. There are several MASPs but MASP-2 is the wicked one that keeps making more C4a. C4a only lasts a few seconds, but MASP-2 keeps turning it on. Turn off MASP-2 and the whole show stops. Did you get that?
One of the peculiar effects of C4a is that it blocks the assembly of “multimer’s” that allow blood clotting. With a blasting off cascade of higher C4a, your blood becomes anti-coagulated and mold folks start having nosebleeds like crazy. Fortunately, ddavp works on helping assemble multimers and works like a little charm at stopping nose bleeds. You learn to carry your ddavp with you.
If C4a is elevated, you get cognitive dysfunction, increased smooth muscle contraction, blood vessels leaking fluid, release of chemotactic factors followed by capillary hypoperfusion and low tissue oxygen. It’s normal range is 0-2830 but you will see folks with levels of 18,000, rising higher and higher after each exposure. The average level of C4a in CIRS or biotoxin illness is at least 10,000, but it’s not uncommon to have 20,000 on the second exposure, 50,000 the third, 150,000 the fourth and too high to measure on the fifth. The phrase “sicker, quicker” really applies here and C4a becomes one of the cardinal tools to see how sick someone is. For folks with re-exposure to a toxic environment, C4a will explode the first day as a strong marker of immediate toxicity. (Leptin rises on day 2 and MMP9 rises on 2-3 and TGF-beta 1 will vary depending on your genetic variability.) You have about 5 minutes in a “toxic” environment before you start activating C4a and 10 minutes is your maximum time before you better get out.

C4a makes such a dramatic decrease in blood flow to brains that you can measure the toxic effect of mold illness on MRI scans on your brain where computer algorithms can generate a test called NeuroQuant. It is all computer managed so doesn’t take a radiologist to read, so costs less (or should). C4a has such an effect on brains, it’s not a far reach to understand Bredesen’s claim that 500,000 Americans are developing Alzheimer’s because of this inflammatory effect.
What is the most effective way to lower C4a? Turn off MASP-2. What does that the best? Erythopoeitin. “Epo”. So called Procrit is used extensively in America for cancer patients with low blood counts. It boosts their ability to make more blood. But it also blocks the MASP-2 nightmare in its tracks. Now that’s handy. It’s also tricky. In fact, so tricky that there is a lot of pushback to using EPO for this and regulatory bodies don’t like it much. (Beyond the scope of this note.)
How can I summarize all this confusing stuff? Forget the confusion. The simple facts for you to remember is that you have 10 minutes to get out of a bad place if you are mold sensitive. If you are a nosebleed victim, you need to carry DDAVP around with you. If you know your C4a, you can have a sense of how serious your mold illness is: 10,000 is awful, 2100 is ok, 180,000 is “I gotta get outta here”. Erythropoetin is a miracle worker at allowing your energy level to return, your brain to fix and your nosebleeds to get better, but you may not be able to get it.

And then there is VIP. Like the Lone Ranger riding the rescue, VIP can work to resolve high C4a when you can’t use EPO. The nasal spray of VIP fixes elevated C4a like a charm. It’s much safer than epo, and much easier to give.

How does all this fit together? It’s complex but then again, simple. All the cytokines and inflammogens are all on the same team and pushing in the same direction. So, they are all linked and all work together to make the same mess, or the symphony. Shoemaker references Beethoven’s 9th when everything is working well. Folks with mold illness, have everything working badly. If you had heard me on the bassoon in10th grade, trying to play Peter and the Wolf, that’s what happens in mold illness. It all goes badly.

www.What Will Work for me. I’m in a quandary finding a reliable place to measure c4a. We are working on it. I have some folks who tell me they are fatigued all the time and have nosebleeds and don’t know why. Our local labs can’t do C4a yet. Most folks reading this blog will be in places where it can’t be measured yet. As more doctors learn this method, they will develop more demand for it. Someday it will be as important a test for you to know as your cholesterol, as least if you want to know why your memory is slipping, your joints ache, you are tired after walking up stairs…..

 

Pop Quiz

1.      C4a is part of the complement cascade the complements your good looks? T or F                   Answer: Pardon the tongue in cheek. This system of complement is your basic innate immune system that generates the inflammation that nonspecifically attacks invading bacteria, punching a hole in their walls and killing them.

2.     In biotoxin illness, what gets messy that keeps C4a so elevated?                                                    Answer: Your MASP-2 protein gets elevated and keeps generating new C4a endlessly. You can measure C4a

3.      What is the best way to turn off MASP-2?                                                                                          Answer: Erythropoietin or EPO or branded as Procrit. But VIP is probably just as good, and much easier and safer.

4.     You can show the damage of biotoxin illness on your brain with a radiology test called what?     Answer: Neuroquant, 15 minutes in an MRI, if you can get it.

5.     How much time do you have if you sit down at a wedding in a moldy church before your C4a fires off?        Answer: 5 minutes

 

Biotoxin XII: Cleaning up C3a

References: Surviving Mold, Mold Warriors, p 396Jr of Immunology,

Ever heard of C3a? Bet you hadn’t. Ever heard of statins? Sure. That’s where statins work. And C3a is the heart of biotoxin illness. It is the nexus of the complement system. The complement system is the cascade of inflammation that fires off when your body sees and recognizes an outside invader. We have made the analogy of biotoxin setting off the 911 alarm system in your community with sirens blaring everywhere. C3a is the volume of the siren.

You can look at a diagram of the C3a activation system. and you see that the production of C3a is the first summary action. And uniquely, it plays in role in starting the inflammatory process, and then in modulating and reigning it in. Shoemaker has discovered that C3a is like the gift that keeps on giving in mold illness. When folks get sick, it’s C3a and C4a that go up right away. In Lyme disease, C3a is a unique marker for early Lyme and can skyrocket with two days of infected Lyme bite. The same happens with acute mold exposure. C3a rises as soon as within 4 hours of exposure to mold. In folks with the genetic HLA biotype for susceptibility to Lyme, the C3a doesn’t go back to normal with the proper antibiotics. In folks with a normal HLA genotype, their C3a goes back to normal. That explains the Lyme riddle of why some folks never get better with continued antibiotic.

What’s going on in mold with high C3a? The complement system continues to be activated. Low grade inflammation of the innate (lizard) system keeps happening and the involved person keeps feeling ill. What ever organ appears to be affected continues to be affected. For those with plaque developing in their brain, they keep developing plaque. For those getting asthma, they keep getting worse. For those getting coronary artery disease, they keep getting worse. C3a is the attack dog of the innate immune system, and it continues to rot you out from the inside.

Now, along comes a unique cure. Guess what lowers C3a and puts it to bed? Guess what resolves the inflammation and cures C3a, provided the mold exposure is gone? A high dose statin. For a month. Yes. A statin. Imagine, is this why statins work? You can search the internet and see lots of odd links, but Shoemaker has seen the clinical evidence of coronary artery disease and “cholesterol” normalizing with C3a normalizing. Now, you need to start CoQ10 at least a week before you start the statin, and push whatever statin you use to its upper limit, and then watch the C3a fall. And with the MMP9 coming down, and the PAI-1 coming to normal mean the illness was cured.

Can you imagine the scope of biotoxin illness if everyone developing coronary artery disease had their HLA typing and their C3a measured. This topic might have broader implications than anyone has imagined yes.

WWW.What will work for me. Well. Measuring C3a is turning out to be quite a challenge. I haven’t figured it out yet in Milwaukee. None of my labs have done it right, so we are in that stage of trying to navigate this journey. Once we can get the wheels greased for the lab evaluation, I have lots of folks pent up waiting to get better. But they only get better when their mold illness is fixed, and that starts with their homes and their workplaces. I got Sporocidin today and the sprayer is coming. I want my basement to smell pristine when I’m done. Sporocidin is the cleaning agent you want to use if you have a “moldy” smelling basement.

 

Pop Quiz

1.      C3a is the common instigating cytokine in the innate immune system? T or F                  Answer: That is about as accurate as you can be

2.      C3a both activates and modulates the innate immune response. T or F                           Answer. Again. Just about right.

3.     In acute mold illness, C3a rises very rapidly? T or F                                                                Answer: Bingo, you can prove it with reexposure.

4.      In Lyme Disease with the dreaded Lyme HLA phenotype, you get better in just two weeks. T or F       Answer: This was my dummy question. If you got this wrong, you didn’t read the column and skipped to the pop quiz. False.

5.     And you can cure high C3a, and in fact MUST cure high C3a, with what?                           Answer: High dose statins for a month, after meticulous removal from exposure.

 

Biotoxin XI: Cleaning up VEGF and Getting Your Energy Back

References: Mold Warriors, p 93 by Ritchie Shoemaker, Surviving Mold – BerndtsonJr Physiology,

Fatigue is a cardinal symptom of the Chronic Inflammatory Response Syndrome, CIRS. Biotoxin Illness. Folks just feel tired. And this unpacks the third layer of biotoxin illness. Layer one is the nonspecific inflammation set off by the innate immune system and all the resultant cytokines streaming all over your body, wreaking havoc and causing weird symptoms. Layer two is the resultant disruption of the leptin, MSH, ADH and VIP systems in the hypothalamus and pituitary. Now we get to layer three, the disruption of blood flow by damage to the VEGF system.

VEGF is Vascular Endothelial Growth Factor. It’s the internal hormone your body uses to make more tiny capillaries to bring in more blood, usually in response to low oxygen and signs of anaerobic stress. It’s getting a lot of press recently in cancer care because cancers need a lot of blood flow to survive, so blocking their ability to create new blood vessels slows down cancers.

The cytokine storm caused by biotoxins acts differently. The lining cells of capillaries can both send off cytokines, calling for help, and respond to them by making “glue” for white cells to stick to. If you have an infection invading you, that works well. The lining cells call for help, the white cells show up and can stick to the glue and the white cells can then kill the bugs. That works. In biotoxin illness, the cytokines are everywhere and nowhere. All the blood vessels get choked up with white cells looking for invaders they can’t find. And VEGF that is meant to now surge to allow new blood vessel formation instead tanks. No VEGF. No new blood vessels. No better blood flow. Horrible consequences.
What do you see? Fatigue. Not short term fatigue. Days worth after every exertion. Go out for two hours and spend two days in bed. It can start with, “Why am I so tired all the time?” and end up with, “I can’t get out of bed.” No kidding. And you can prove it physiologically. Take someone with CIRS and send them to the hospital for a pulmonary stress test to measure their oxygen consumption and their anaerobic threshold. In 10 minutes you will find a robust, buff looking 35 year old testing like an 85 year old with congestive heart failure. When you can’t deliver enough oxygen to your tissue to burn fuel, you start burning glucose into lactate without oxygen. That’s your anaerobic threshold. In heart failure it’s the heart that’s failing. In CIRS, it’s the capillaries that are plugged and VEGF that’s failing. But no one believes a buff 35 year old isn’t just faking it. So we add insult to injury.

That damage actually can go deeper. Your body gets so desperate for fuel that it turns to burning up protein to make new glucose, leading to protein wasting. The cycle of dysfunction can get pretty deep, explaining why it takes so long to recover.

Can I fix VEGF? Actually. You can. And remarkably easily. Flood your system with the building blocks for all the anti-inflammatory cytokines. Fish oil. Get yourself on 2.4 grams of EPA and 1.8 grams of DHA per day – or 4 grams of high quality fish oil. Daily. Add pioglitizone (Actos). Combine that with a very low amylose diet so that you reduce your PPAR competition. (Remember last week where we gave a nod to the competition between amylose containing foods and inflammation. By avoiding amylose and taking pioglitizone, you let your own body lower than inflammatory response that comes along with anything that induces insulin. If you want a deep dive into the Common Soil Hypothesis – you can get all wrapped up in inflammation versus metabolism). What you need to know is that you can chill out VGEF with lots of fish oil and no amylose.

If that fails, Shoemaker noted that folks with low VGEF felt better at high altitude. Follow that reasoning and humans put out more red cell production stimulation with a hormone called erythropoietin when at high altitude with low oxygen. So called “epo” or branded as PROCRIT, you can turn off VEGF with a course of low dose erythropoietin when fish oil fails. Given in low doses over a month, you can again play gene therapy with erythropoietin and walk away with a normal VEGF in just a month. You can reset your genes and your VEGF in a month. What happens to your pulmonary anaerobic threshold? You guessed it. Returns to normal in the twinkling of an eye. Gene therapy, all aimed at your primitive lizard level immune system, works.  (This is very controversial because of Procrit’s black box FDA warning and used mostly in cancer patients.  For the vast majority, stick with the fish oil and low amylose diet)

www.What Will Work for Me. I’ve been slugging away at my fish oil for years knowing that it basically was good for me. The Lyon Heart Study showed that a gram a day reduced mortality more than statins, so I’ve done it for years. Now I know the biological basis for it. If you can sort out the complexity of the common soil idea, you understand that the precedent for inflammation is dysfunctional glucose metabolism. Biotoxin illness highlights it in blazing headlines. You can’t get out of bed. And now you can. We can fix you!

 

Pop Quiz

 

  1. Low VEGF is a common finding in biotoxin illness? T or F                             Answer: True. So common, it is one of the necessary separate steps in repair.
  2. The main symptom of low VEGF is?                                                                  Answer: Fatigue. Deep, bone chilling fatigue. As much as two days in bed after any exercise fatigue
  3. The fatigue is caused by?                                                                                    Answer: plugged capillaries with low flow blood and lowered oxygen delivery caused by low VEGF.
  4. The easiest way to fix low VEGF is?                                                                   Answer: Start with high dose fish oil and low amylose diet combined with pioglitizone. With a lot of care, you may need a round of low dose erythropoietin.
  5. (Extra Credit) The common soil hypothesis refers to?                                   Answer: the intersection in biology of inflammation and metabolism of glucose. They both seem to stem from a common evolutionary source, so confound each other with their overlap. They aren’t quite distinct and separated, so high glucose ends up with inflammation. An aspirin overdose (anti-inflammatory) ends up with low blood sugar. Etc.