Category Archives: 26. Biotoxin Illness

Leptin Resistance and Inflammation

Leptin Resistance and Inflammation

References: Am Jr Coll CardVitamin HormonesCurr Immunol ReviewCell,

Leptin is the hormone that has several important functions. One is that it is secreted when your fat cells say they are full. It is a feedback loop that tells you that you have had enough to eat, so stop. Fine and dandy. But like everything else in your body, there are layers and layers of delicate complexity far exceeding the first layer of functionality. Another layer is that it essentially mediates the release of fat from fat cells, making it the guardian of your energy stores. When all is well and working properly, your leptin level falls when you don’t have food and your fat cells open up and share their calories. Women have more leptin than men. As a general rule, gaining weight results in a higher leptin level which should result in your feeling full and not eating. Something strange happens, however, when you get inflamed.
The fly in the ointment here is that there is an intersection between metabolism and inflammation. The leptin receptor in your hypothalamus appears to be a critical link. It turns the Proopiomelanocortin system and has you produce melanocortin. MSH. MSH is a potent down-regulator of appetite. With a nice high MSH, you don’t feel like eating. Low MSH, you don’t have a feedback loop. And just what happens with inflammation? Leptin plays a role in that it has a critical effect on innate and adaptive immune response. It promotes the secretion of cytokines like IL-6 and Tumor Necrosis Factor, and there you have it. It sets up the link between metabolism and inflammation. What you see is a dramatic dysregulation of inflammation in folks who become overweight, and thereby establishing the first step in increasing risk for Alzheimer’s, heart disease, cancer, autoimmune disease and just about everything else that ails us. The “Common Soil Hypothesis” is the concept that metabolism and inflammation came from the same source in evolution, way, way back. Here again, we see that nexus and it makes for problems.

What you see happen is as follows. Folks with inflammation, like low-grade mold exposure, have low MSH and high cytokines that damage the leptin receptor in the hypothalamus. Leptin drifts higher in response, trying to bring about control of calorie balance. The person gains weight. Leptin goes higher, but the receptor is damaged and the higher leptin then mediates more inflammation. Around and around you go. If you feel overweight and have chronic pain or chronic fatigue, you likely fit this model. Forget trying to lose weight until you lower your leptin.

How can you lower your leptin most effectively? I suspect the fast mimicking diet will do so, but that is not yet proven. The one good study that shows regeneration of the pancreas beta cell used mice with a genetic defect in their leptin receptor, so they couldn’t be used to proven leptin repair. Right now we can use pioglitizone (ACTOS) which is an old fashioned diabetes drug that has lots of side effects when used for too long, but is dandy at lowering leptin and MMP-9, two mold effects.

Can we reduce leptin with our own lifestyle? Well, quite a lot. If you focus on several key items, you can guide your leptin lower. Keep your daily sleep cycle to a regular pattern. That plays into your POMC system being played every day at the same time. Avoid sugar. Increase fat in your diet. Cut down on your evening meal and increase your daytime eating, making for at least 12 hours of fasting each night. Exercise. Sleep at least 8 hours, starting with at least 3 hours of no food before bed. Consider training yourself to enjoy a cold shower, particularly if you get a nice hot sauna just before. (The Finns had it right.)

WWW.What will work for me. I’m fascinated with leptin and mold illness. I keep seeing women in particular with not only high leptins but super high leptins levels. Just about every one of them has had low MSH levels, meaning some sort of mold or biotoxin exposure. Throw in stress, sugar, lack of exercise, lousy sleep and we make for a perfect storm to elevate leptin, and keep everyone overweight and inflamed.

 

Pop Quiz.

  1. Leptin helps you make MSH which suppresses your appetite. T or F                Answer: Almost right but backward. LACK of leptin results in hight MSH, and then weight loss and lack of appetite.
  2. Inflammation turns on leptin. T or F                                                                      Answer: I’m into backward today. It makes for leptin resistance, which then elevates leptin.
  3. Name a few means by which you can lower your leptin with lifestyle changes. Answer: Regular schedule, exercise, sleep, 12 hours of fasting, weight loss, less sugar….
  4. Leptin allows the release of MSH. What does MSH do?                                     Answer: It’s a potent appetite down-regulator.
  5. The cause of fibromyalgia is likely?                                                                    Answer…….. /biotoxin illness leading to damaged leptin receptors.

 

 

Biotoxin XV: VIP – The Magic Bullet


 Biotoxin XV: VIP The Final Magic Bullet

References: Surviving MoldBiotoxin JourneyInternal Medicine Review,

100%. Did you catch that? Everyone with mold illness, following the 11 step program Shoemaker has put together, will find relief. Well, almost everyone. Some folks who have been sick for years have deeply imbedded patterns and may need to be on VIP for a long time, but nevertheless, Shoemaker has found that his program returns (almost) everyone back to much higher levels of functioning, if not complete cure. The limitations are more on getting to a completely clean environment free from biotoxin after a life time of training their immune system to be “sicker, quicker”. Remember, it’s not quantity that sets off the innate immune system, it’s just the first domino that sets off the storm.
Well, explain what VIP does. What is it first of all. Vasoactive Intestinal Peptide was discovered as being active in the gut, hence its name. But its most profound effects are more likely in the brain.

The sequence of events is as follows. You live in a moldy home, or work in a moldy workplace. The ceiling has black spots below the AC unit upstairs. You breathe in the mycotoxins. (They are TINY: if botulism toxin weighs 150,000 daltons, T-2 toxin weight 466). They set off the “cloud” of cytokines of your innate immune system: the fire alarm. The cytokines attach themselves to the Leptin Receptor in your brain which is the gateway to secrete MSH, VIP and ADP. First, you stop making MSH. With a mucked up VIP receptor, your whole POMC system goes down. You stop making beta-endorphin and you start to hurt all over. Your energy tanks. You gain weight. You are tired.
VIP dropping shortly follows. About 98% of folks with chronic fatigue syndrome have low VIP. It is a regulatory neuropeptide that acts in the hypothalamic suprachiasmatic nucleus. Does that sound like a mouthful? It appears to have a profound effect on Cyclic AMP which is a second tier messenger. But other than that loosy-goosey explanation, we haven’t a clue how it really works. And it just doesn’t work if you skip any steps in the 11 step program. But if you have done the other 11 steps, it becomes a secret super weapon. It works in minutes.

The sorts of things you can measure are almost immediate improvement in the pulmonary artery pressure. That means blood is flowing much faster, immediately. Breathing is easier. “Asthma” suddenly feels ok. That means energy perks up, right away. In two hours your fizz is back. In two days you feel like you were never sick. For those folks with joint stiffness, 10 minutes and you are feeling more limber. This is a real magic wand.

The protocol is to take it as a nose spray 4 times a day for 30 days; then twice a day for 30 days; then daily for 30 days; then off 30 for days.

Unless: you have any of the following: ERMI > 2 at home/work/school, your VCS (Visual Contrast test) still positive, still have MARCoNS in your nose, MMP9, PAI-1, leptin still high, Untreated C3a, C4a, TGF beta-1 still hanging around.

This is really cool. We have a final step that fixes things that is measurable, repeatable, explainable. I have met one person who flunked VIP, albeit they did feel a little better.

www.what will work for me. I’m eager to get experience of using it. Again, it will be a new modality in this town so getting a pharmacy to make it right might be a challenge. Getting insurance to pay for it. Well, dream on. But there are work-arounds for all those things. In the meantime, I’m still working on my own basement. My ERMI was 4 and I’m determined to get it down. When I see someone with a -6 ERMI, I’m jealous. They lived on the 16th floor of a pristine, new condo building. Lucky devils.

 

Pop Quiz

 

  1. Where was VIP discovered?                                                       Answer: as a regulatory peptide in the gut, hence the name, Vasoactive Intestinal Peptide.
  2. Where else does it work?                                                           Answer: very definitely in the brain – in the suprachiasmatic nucleus, to be exact – and many others.
  3. What does it do?                                                                          Answer: We haven’t a clue. It has effects on a secondary messenger inside cells called c-AMP but other than that, we are clueless. It just fixes everything like a magic wand.
  4. What makes it not work?                                                            Answer: anything in the previous 11 steps that weren’t fixed first. Still living in a toxic environment with an ERMI score over 2, still having MARCONs in the nose, still having elevated cytokines, etc etc.
  5. How quickly does it work?                                                           Answer: Minutes. And can be tapered over 3-6 months to off, provided the person doesn’t go back into their dangerous place.

 

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.

 

Biotoxin Part X: Putting Cytokines back in Order – One by One – MMP-9 First


References: www.survivingmold.comBiochem Biophy Res CommMol Med Rep

CIRS (Biotoxin Illness) or Chronic Inflammatory Response Syndrome sets off a host of cytokines. We are a long way from understanding the complexity of all the interactions that occur, but we are beginning to understand preliminary methods of how to manipulate them and fix them. Remember, CIRS is really a firestorm being set off in your innate immune system – your lizard level built in, non specific, immune system that creates inflammation but isn’t focused and precise. The folks who get sick with CIRS are the ones who can’t mount the next level of response and sit there mired in the continued process of hyper alarm with no relief. To bring relief, we want to start disconnecting and calming down all the sources of dysfunction.
Specifically: you get “invaded” or exposed to biotoxins (the musty smelling basement, the ancient church choir closet, the leaking school roof). These toxins are fat soluble and circulate throughout your body. In your fat tissue, fat cells take them up and don’t like it. They put out a host of cytokines that circulate all over asking for your adaptive system to come and clean them up. You can’t “see” the biotoxin because your immune system is “blind” – you have a high risk HLA type – 25% of us all. The circulating cytokines damage your hypothalamic leptin receptor and MSH, VIP and ADH all get damaged. You feel chronic pain, fatigue, and 31 other odd symptoms. You are off to the races with biotoxin illness.

That’s where MMP9 sits. It is the mediator of the cytokine chorus. If it is elevated, you have a biotoxin burden. MMP9 is not a cytokine, it is a protein enzyme that facilitates the entry to biotoxins into the sub-intimal space. This is the part of tissue beyond the basement membrane of blood vessels. Your blood vessel’s intimal membrane is the last barrier protecting your cells from invading damage. It’s the “gristle” of dense, gooey connective tissue that the blood vessel cells sit on and typically is impenetrable. MMP9 penetrates it. Penetrating it is a huge step, and a dangerous one. Once you have penetrated the basement membrane the inflammatory cytokines get into your brain, your lungs, your muscles, your joints. In the brain, MMP9 can help make plaque that looks like MS, and even shows up on MRI scans. In your lungs, you can cough endlessly and look like asthma, often being misdiagnosed (as much as 50% of kids?). In your joints, it looks like arthritis. Can you see the scope of what can happen once you open the gates and high MMP9 lets the cytokines get in? It’s a runaway train with no conductor.

How to reign it in? Well, this is what is fascinating and unique. Ritchie Shoemaker had the genius to look at the bench research on cytokines and chase down a new idea. The thiazolidinediones class of diabetes drugs (Actos as an example) turn on genes as their method of action. In fact, ACTOS lowers MMP9 (and TNF, leptin, and PAI-1)after biotoxins cause it/them to be elevated. And in a couple of weeks, we will also learn in increase VEGF. Actos (pioglitizone) is the gift that keeps on giving. It activates the PPAR-gamma class of nuclear receptors. It is that PPAR system you are trying to activate with Actos, as that is what lowers the MMP9. And you can overwhelm it and ruin the effect if you force insulin to rise rapidly be eating foods with lots of freely available glucose. The food form of glucose that gets into you the fastest is called amylose. It’s in all grains, all root vegetables, bananas. The only folks who need to be wary of Actos are the really skinny folks with low leptin who need to get on enough fat to raise their leptin level first. Then, Actos will work and their MMP9 level will come down.

Sounds complicated? Actually, it’s not. Actos, combined with a low amylose diet is a fantastically simple form of gene therapy that works with anyone with a high MMP9. We can’t see what’s happening at the cellular level, but you can imagine that by muscling the MMP9 down, the circulating cytokines can’t get in to cause their damage. If you have cleaned out the biotoxin, now you need to clean up the mess they made. And MMP9 is the first layer.
Again, simple. Amylose free diet, frequent small meals, pioglitizone, 45 mg a day.

WWW.What will work for me. I’m just thrilled with this simple concept. I have already tried it on dozens of folks and sure enough, they start to feel better, start to lose weight, get their headaches in control, feel less fatigue. If you are someone who is overweight and simply can’t lose the weight and feel achy and sore, it’s likely you have biotoxin mediated high leptin and high MMP9. It’s not you that is to blame, it’s the biotoxin. Get your MMP9 down!

Pop Quiz

  1. MMP9 is a cytokine. T or F                                                                          Answer. Wake up, sleepy. Read the blog again. It’s a protein enzyme.  It dissolves connective tissue and allows inflammatory cytokines access to the tissue beneath the membrane.
  2. What does MMP9 do?                                                                                 Answer: It dissolves the gooey, gristle that is the foundation of connective tissue lining blood vessels, allowing biotoxins to penetrate from inside the blood vessel into brains, joints, lungs etc.
  3. MMP9 is a handy marker of biotoxin illness. T or F                                Answer: That’s it in a nutshell. And it should be under 332. Many labs say normal includes a higher range than that because there are so many people with elevated MMP9 that are then included in the normal population. Well people have levels below 332.
  4. The best way to lower MMP9 is with?                                                       Answer: gene therapy using pioglitizone (Actos) combined with a low Amylose diet.
  5. What is amylose?                                                                                          Answer: the form of glucose plants use to store glucose that is the most easily digested (you have amylase in your saliva and start breaking it down as you chew) found in root vegetables, all grains, bananas. Eating amylose with Actos undermines the gene therapy of lowering MMP9.

 

 

 

Biotoxin IX: Peeing Like a Racehorse

 References: Surviving MoldBiotoxin Journey

How often do you take a leak? Four to five times a day? Once at night? Or have you gotten used to urinating every hour? Twenty times a day? Do you get up more than twice at night? Do you feel thirsty all the time? Even more mysterious, do you have a lot of static shocks?

If so, these are all they symptoms of biotoxin illness affecting the pituitary gland. Once your understand it and you learn how to fix it, you breathe a sigh of relief. You cancel your scheduled prostate surgery. You decline to go to the Gyn doctor for bladder sling surgery. You weren’t getting old, you are biotoxin affected. And this symptom may be one of the only prominent ones you have. To really be fixed, you have to go back to the source and get rid of your exposure to biotoxin (usually mold).

Here is what is going on. Your brain has a meter that measures the concentration of your blood – the number of particles in it. That’s called your osmolality. It is tightly regulated in a very narrow range. When you drink a lot of water, your total “concentration” of ions, or osmolality falls. Every membrane of every cell in your body depends on that concentration being reliably consistent. If it is falling, you protect yourself by NOT secreting your regulatory hormone called ADH or anti-diuretic hormone. ADH acts by telling your kidney to hang on to water. (Anti Diuretic means it stops you forming urine.) Without ADH, your rapidly start to let go of all that extra water you just drank.

Vice versa, if you are dehydrated, your ADH goes way up and your kidneys promptly stop excreting out any liquid and start to concentrate your urine. You get the feeling of thirst and seek water to drink. That brings your concentration back into line. This is a very elegant system and works in a very tight range.

Biotoxins upset that applecart. For any given osmolality, your secretion of ADH is just a bit short, so you pee out more free water than you intended to. The concentration of your blood, your osmolality, rises. You feel thirsty and drink more to catch up. But it’s the lack of ADH comes first. You are drinking to keep up, and not always accomplishing it. Your blood concentration, or osmolality, rises, maybe not out of the normal range, but too high for the ADH level you are making. 60% of biotoxin damaged folks have this symptom.

This is where it gets weird. Your sweat glands are designed to help out. They can excrete a tiny amount of salt when your blood is too concentrated. If your kidneys won’t hang onto free water, your sweat glands try to make up for it by getting rid of extra salt.. Your skin gets to have a slight layer of salt on its surface. Salt is a great conductor of electricity. You become a walking battery. You touch anything with any charge on it, and you readily accept it, or transmit it. Little sparks fly off of you. No kidding! For those whom this affects, this can be a royal pain. You find yourself turning off switches with your elbow, not shaking hangs, avoiding wool clothing.

And you get a headache from hell. Your brain takes great exception to this slightly over concentrated blood and complains loudly. You may have blood tests that are hardly abnormal, but not matched. For a given osmolality, you need a certain ADH, and you come up short. The biotoxin has short circuited your measurement device in your hypothalamus/pituitary. You can go to every headache clinic in America and not come up with an answer.

How to fix this? That’s the next step in the biotoxin pathway. A simple, inexpensive analog to ADH called DDAVP, used for years to help kids stop bedwetting, helps you stop peeing every twenty minutes too. A dose of 0.2 mg once a day to every other day for a 10-30 period might just shake you back into shape, provided you have gotten rid of the biotoxin. It’s too easy a fix not to jump on. There are several regimens for DDAVP, which we will get to in future weeks too. Coming up is how DDAVP fixes some nosebleeds.  (There are some potential side effects: if you don’t get rid of water, you may get edema and gain weight with that.)

WWW.What will work for me. This is such a weird symptom, few folks notice it on their own, thinking instead that they are just getting old. It can be one of the symptoms that sneaks up on you when you aren’t horribly damaged yet by the biotoxin. Take warning. Get the biotoxin cleaned up or avoided before you get sicker.

 

Pop Quiz

  1. When your blood gets too concentrated you feel thirsty and drink plain water? T or F    Answer: TRUE
  2. The hormone that helps with your dehydration is called?                   Answer: ANTI-diuretic hormone or ADH. It is against you leaking out too much liquid
  3. What is the defect caused in biotoxin illness?                                        Answer: too little ADH for any given concentration of blood.
  4. The main symptom of that is?                                                                   Answer: too frequent urination.
  5. How often does this happen?                                                                    Answer 60% of the time in biotoxin illness
  6. And way do these folks have unusually frequent static shocks?         Answer: their sweat glands excrete a bit of extra salt, trying to help with the salt imbalance. This makes their skin a good electrical conductor, resulting in unusual skin conductivity.

 

 

 

Biotoxin VIII: Absent Androgens

References:  Surviving Mold,  Jr Sex Medicine,

How many men do you know who say they are low on energy? And how many ads do you see touting the claim that they are “low T” and suggesting they get on more testosterone? Are you a bit skeptical that that may be the case? You should be, because many of those men, if not most, are Biotoxin Refugees, not “Gonadal Insufficiency” as modern medicine defines them.   They can get fixed by going upstream, in the majority of situations, to the root cause.   So just how does that happen?   Explain that “root cause”.  (First: Definition –  Biotoxin Refugee: they are sick from biotoxins and no one recognizes it and calls them crazy.  They are medically homeless and fleeing from a pervasive enemy.)

Here’s the skinny explanation. We are now in the phase of explaining the next layer of biotoxin illness, the hypothalamic and pituitary damage that arises from biotoxin’s effect on MSH (melanocyte stimulating hormone), VIP (vasoactive intestinal peptide), ADH (anti-diuretic hormone) and all the rest.   To recap, you inhale the biotoxin. That comes from the breakdown products of “black mold” which is code word for a complex mix of molds, bacteria, actinomycetes etc  . When the mid winter sun is angling across your room, you can see tiny bits of dust floating in the air. You breathe that in.   That floating stuff is what turns into the dust bunnies under your bed, and contains the substrates of biotoxin illness. The biotoxins all share a similar structure that makes them incredibly fat-soluble and damages cells by mucking up their energy production and DNA messaging. Your innate immune system recognizes them as foreign and sets off fire alarms in the form of “cytokines”, calling 911. But your adaptive system, the higher order immune system that makes antibodies and T-cells doesn’t “see” or “recognize” biotoxins in 25% of us. Those are the folks who get in trouble. The biotoxin sets off your bodies 911 system, and your adaptive system doesn’t know what to do. You flounder. That floundering takes the shape of downshifting POMC endocrine system: the 11 hormones made from one protein substrate. When you downshift 11 different hormones, you are going to have a broad array of dysfunction. No wonder hormone production takes a hit.

That’s the upstream skinny. So simply giving testosterone circumvents the real problem. Of course, folks feel better and function better for a short period of time. And then it fades. A higher dose of T then reboots the problem and your pituitary responds by making less and less LH, the hormone that drives T production. And it fades again. You have now accomplished a further down-regulation of your hypothalamus; the same place the biotoxin down regulated. And all the complex interplays of LH and pituitary/hypothalamic balance get forced out of balance.

We can’t get close to understanding all the interactions of our pituitary/hypothalamic hormones yet. Thinking that Testosterone replacement will fix our waning libido is true, only so far. There are several dozen other functions of T that aren’t so easily measured or experienced. I want to live long enough for the research to emerge that clarifies them all. As an example, STEP 11, 4 weeks from now will tell you how VIP normalizes MSH, lowers TGF-beta1 and raises VGEF. VIP is called Vasoactive Intestinal Peptide, but it does so much more, it’s hard to describe. Its name implies that it is involved just in the gut, because that is where it was first discovered. But its most important function is likely it’s balancing the POMC system, and bringing the orchestra of the hypothalamic opera into tune.

So, what specifically is being mucked up with androgens? Part of the explanation is around the enzyme aromatase. This enzyme is the last step of estrogen production, which is turning testosterone into estrogen. Aromatase gets up regulated in biotoxin illness. Testosterone disappears into estrogen. Giving more T results in more Estrogen until you get to the root problem.   The solution is not more T, it’s DHEA, the precursor to T. Most folks in their 40s and 50s have very low DHEA the precursor hormone to T and E. Giving that doesn’t seem to disrupt the whole system, and allows your body to proceed with balancing its hormones as it sees fit. We need to know more. That’s coming. Sooner would be better.

WWW.What will work for me. Well, I’ve now checked MSH and TGF-beta 1 in a handful of my clients with low T, and sure enough, they have all been low and all report basements that smell “musty”.   I’m not sure we can explain the whole story to them yet, but I’m certain this is a more satisfying track.

 

Pop Quiz

  1. We need testosterone for more than libido. T or F                                    Answer. Immune function is on the list and that may be part of the dysfunctional damage of biotoxins.

 

  1. Biotoxin refugees are?                                                                                     Answer: Folks with low energy, diffuse pain, lousy sexual function, diarrhea, trouble concentrating, mind fog…….(all the 31 symptoms of biotoxin illness) and no one wants to give them the time of day because the current medical model hasn’t learned biotoxin illness yet, so they are “homeless”.

 

  1. Replacing Testosterone is fraught with risk because?                             Answer: the enzyme aromatase is already up-regulated by biotoxins, and further exacerbated with extra T. Aromatase makes more estrogen from the T. So the T/E ratio gets all out of whack. The human body likes proper balance.

 

  1. The best way to fix low T is:   a) Replace it,   b) Give Clomiphene, c) Fix the biotoxin problem, d) Give DHEA e)   All of the above                                                                 Answer: Probably C needs to be number 1.   You do that by d). Your may use b) now and then.   Stay tuned, more to learn.

 

  1. Giving T without measuring MSH may be jumping the gun. T or F     Answer: Bingo, that’s this week’s take-home.

BioToxin VII: The Gluten Connection

References: NatureImmunityClinical and Devel ImmunSurviving Mold,

How many folks do you know who are gluten sensitive? You hear some people scoff at the idea but you also know quite a few folks that say they just feel better when they are off gluten. They don’t have celiac disease, at last most don’t. So, what’s up? Would you be surprised if you heard that biotoxins set off your innate immune response, and that sets up for the production of TH-17 immune cells, that tip you in the balance towards autoimmune disease? And gluten does that!
Step 4 in Shoemaker’s Surviving Mold Pathway is to get off of gluten/amylose for at least 3 months if you have antibodies to Gluten. This is the next phase of the Shoemaker protocol: sequentially and progressively cleaning up all the sources of persistent inflammation. And actually, he calls for you being off amylose. Amylose is about 30% of most white carbs. It is composed of long strings of glucose hooked together at the 1,4 positions on the glucose molecule, making for a long, linear chain. Amylopectin is the other component of most starches. It is branched and less dense in formation. Plants can store more energy as amylose. Curiously, it’s structure also binds iodine avidly, making for a dark color indicating the presence of amylose with iodine.
This is where future research is going to have a rich source of discovery. We don’t know all the details yet. What we do see is that lowered MSH (melanocyte stimulating hormone) and elevated TGF-beta 1 leads to unbalanced TH17 immune cells. These are the regulatory cells that march you down the path to autoimmune disease. And oddly enough, we see antibodies to gluten like IGg and IgA antibodies to gluten in biotoxin disease. That’s what leads you to step 4.

Get off of anything that stimulates inflammation. It’s not just wheat, it’s all amylose products like potatoes and rice too. All white carbs.

Now, your brain, your gut and your immune system all make a team, a triad. When you have inflammation in your gut, your brain doesn’t feel so good either. Biotoxins are setting off cytokines all over your body that are then blocking the leptin receptor in your brain, lowering your MSH. Without MSH to direct your immune system, your gut gets dysfunctional. Autoimmunity emerges.  Gluten wasn’t the first step, mold biotoxin set the table.

You thought your gluten sensitivity was set off by the changes made to wheat back in the 1950s when we tripled it’s chromosomes. I thought that. May not be the sole problem The underlying dynamic may be that your innate immune system is goofy because of biotoxins from molds. And you are in the 25-30% of folks sensitive to those biotoxins. If you live and work in clean environments, you might not ever feel the effects. You can eat bread and potatoes all day long. But add in biotoxins and your genetic susceptibility takes over.

We have tantalizing clues that this is what’s happening. Rock solid proof awaits. We do know that Hashimoto’s gets better with wheat avoidance. We do know that Crohns and Sjogren’s appear to be sensitive. Stay tuned.

WWW.What will work for me. I don’t eat much wheat anymore. We just don’t buy bread or potatoes. It becomes a lifestyle thing. Shoemaker asks the same as Functional medicine with wheat, 3 months without any. Now, that’s hard. For those who are sensitive, the rewards are there. I can’t wait for more science to figure out this connection more fully.

 

Pop Quiz

  1. Gluten irritates your gut and sets off autoimmune disease? T or F                          Answer: We used to say this was true. We now think that biotoxins lower your MSH that then makes your immune system unable to protect your gut. That’s the nuance.
  2. To have an effective challenge of being gluten free, you need to be off for how long? Answer: Three months
  3. If I put a drop of iodine into a cup of hot water with rice flour in it, it will instantly turn black, making for a great magic trick? T or F                                                  Answer: True. Amylose binds iodine avidly. It’s kind of fun. You can complete the trick with a tablespoon of green tea after your iodine turns the water black – if you want to really have fun with food chemistry tricks. Poof, clear again. Try it.
  4. Turning off amylose sensitivity is the first step in fixing the inflamed body, once biotoxin is removed from your body and your MARCoNs are cleaned up. T or F               Answer: That’s it. Now we embark on tackling all the sources of inflammation and calming your hot body down.
  5. Biotoxin illness spreads its trouble much further afield than I ever imagined. T or F                Answer: Just wait till we get to hormones! True, true, true.