This post is not meant to be comprehensive. The point of this post is to discuss some (not all) of the “root causes” of mold sickness.
Some of this is discussed by Shoemaker and some of it is completely new. Even if you don’t feel you have a mold problem, you can benefit from this post.
- About CIRS, Mold Illness and Chronic Lyme
- Testing for CIRS
- CIRS/Mold and SOCS3
- CIRS, Hypoxia and Low NAD+/SIRT1
- Get Help With Test Resuts
- SIRT1, The Circadian Rhythm, and CIRS
- Hypoxia and Mold Illness
- Why Do People With CIRS/Mold Illness Suffer From Hypoxia?
- CIRS and Low Acetylcholine
- Mold and Weight Gain
- Why Do Mold People Get Fat and Other CFS People Get Thin?
- Probiotics May Help with Mold
- The Takeaway: What To Do?
- Irregular MSH Levels?
About CIRS, Mold Illness and Chronic Lyme
New research from nature points to fungal infections as a cause of Alzheimer’s, after every patient they tested, were found to have fungal infections (R).
People often try to give a name to the disease that they have because they feel that it will give their suffering credibility among their family and peers. They also believe that if they have the name of the disease, they can research it more.
The problem is that these health issues have no fixed boundaries. Everyone’s immune system is different and the toxin that caused the illness can be different.
Chronic Inflammatory Response Syndrome or CIRS is a condition coined by Dr. Ritchie Shoemaker that encompasses a wide range of health issues that can be triggered by a toxin.
There’s often a cluster of events that take place, but not always.
ACTH is actually protective, which is why when it falls, the condition usually gets worse.
Mold sufferers seem to do uniquely well with cholestyramine (disclaimer: not for personal use), which binds to the mold and other toxins.
Chronic lyme or what I’d prefer to call post-lyme sickness has somewhat different markers and characteristics.
But the common denominator between “chronic lyme” and mold illness is that both were triggered by a toxin and result in an immune system that’s imbalanced – weak in some ways and overactive in others.
Testing for CIRS
There are a number of tests that you can do to differentiate what kind of inflammation you’re having, which will be important in identifying the root cause.
Some of the test that will identify mold illness include:
- VCS test – tests for mold problems,
- Transforming Growth Factor Beta1 (TGFb1) -Will help you determine if you have a biotoxin issue and if you are actively being exposed… needs to be shipped frozen. Normal Range: <2380 pg/ml (R).
- Complement C4a – Will help you determine if you have a biotoxin issue and if you are actively being exposed… This will necessitate a different protocol…it needs to be processed fairly quickly, no significant lag time during the processing period. Normal Range: 0-2830 ng/ml (R).
- MSH – This is an anti-microbial and anti-fungal and can easily be increased by sun and MSH analogs. normal range: 35-81 (R),
- VIP – VIP is an anti-inflammatory and you can easily increase it naturally and with VIP. In healthy controls, a median VIP-serum level of 42.44 +/- 2.540 pg/ml (range, 12.9-98.5 pg/ml) was found (R)….Normal range: 23-63 (R).
CIRS/Mold and SOCS3
Here’s a part of the immune system related to mold that I haven’t heard Shoemaker discuss: “suppressor of cytokine signaling 3” or SOCS3.
It’s hard to know how big of a role SOCS3 plays in people with mold issues, but elevated SOCS3 seems to play some role in CIRS.
SOCS3 deserves closer attention because this is the most likely cause of leptin resistance in mold illness.
SOCS3 is a mixed bag. It restrains some kinds of inflammation (inhibits Th17 dominance), but it increases most other kinds (R). I’m going to discuss mainly the bad, but it has a lot of good aspects as well.
Like TGF-beta, SOCS3 is one of those things that depend on the cellular milieu and the issues you’re dealing with and can’t be put into a good or bad category.
SOCS3 can be increased directly or indirectly from toxins.
SOCS3 may also increase directly from mold rather than simply indirectly from the cytokine storm since mycobacteria (found in mold) stimulates SOCS3 (R).
So mold and mycobacteria can increase SOCS3 by direct and indirect ways.
So Mold—>cytokines and higher SOCS3 (directly and indirectly)—>leptin resistance—>less of an ability to make MSH and VIP—>more inflammation, circadian disruption—>more leptin resistance, etc…
SOCS3 and Th2 Dominance
I’ve noticed mold warriors were Th2 dominant. My previous explanation was that Th2 dominant people were more likely to become sensitive to mold.
In addition, TGF-beta is also a Th2 dominant cytokine and is elevated in mold illness. So TGF and SOCS3 skew the immune system to a Th2 dominant profile.
I never understood why in my observations Th2 dominant people were more likely to be overweight. SOCS3 explains this link since SOCS3 causes Th2 dominance and leptin resistance.
SOCS3 and SIRT1
Too little SIRT1 activity contributes to mold problems in a significant way.
So if you have good levels/high activity of SIRT1, you have lower SOCS3, lower leptin resistance, and therefore higher MSH.
CIRS, Hypoxia and Low NAD+/SIRT1
When you have low oxygen (hypoxia), your mitochondria don’t work as well and for good reason. Oxygen needs to be there to accept electrons in the mitochondria. When you have low oxygen, it can’t accept electrons, so your body wants to slow mitochondrial function down.
When you have low oxygen, your body responds by slowing the conversion of NADH to NAD+ (less oxidation). Therefore, you have a buildup of NADH and a relative reduction of NAD+.
The more NAD+ levels increase, the more SIRT1 is active (on the other hand, Nicotinamide blocks SIRT1 activity) (R).
When you have high NAD+ levels, it means you likely have been using your energy up and have a negative energy balance – you’re expending more calories than you’re consuming. It also likely means you’re well oxygenated.
Low NAD+ is called “pseudohypoxia,” because the body sets in motion some of the same responses to low NAD+ that’s caused by low oxygen, even if you have adequate oxygen levels.
The Importance of NAD+
So the less NAD+ you have, the less you will repair your DNA when it’s damaged.
I’ve noticed in CIRS clients (and other people who I would suspect to have low NAD+ levels) burn easily from the sun. This indicates low MSH and/or low NAD+.
Fatigue, low physical and mental energy are also signs of lower NAD+/SIRT1.
Levels of NAD+ largely control the “redox potential” because NAD+ has the ability to acquire electrons.
The higher the redox potential of the cell, the better the mitochondria work and the more it can fight infections and function the way a cell is supposed to function.
NAD+ levels also control mitochondrial function, as it’s needed to safely move electrons through the mitochondria (R).
Lower levels of NAD+ reduce mitochondrial function, with fewer energy-rich ATP molecules being produced, and fewer mitochondria produced (R).
NAD+ and the Immune System
People with CIRS commonly have infections that they can’t get rid of and chronic inflammation.
Increasing NAD+ in animal models reverses autoimmune disease through various means, which demonstrates that low NAD+ is one cause of a deregulated immune system and why autoimmune conditions often coexist with chronic mold issues. This works mainly by increasing an anti-inflammatory variety of Th1 and Th17 cells (which are usually bad, but NAD+ changes them to increase TGF-b and IL-10). So NAD+ levels can turn Th1 dominance from being bad to being good (R).
Just like we saw with SOCS3 and TGF-beta, the cellular environment can take something good and make it bad and vice versa.
SIRT1 is important for the immune system to clear pathogens in part via MHC II activation. Hypoxia or low oxygen prevents MHC II from activating by decreasing SIRT1 activity (oxLDL also decreased SIRT1 in macrophages) (R).
NAD+ (and by extension SIRT1) seems like one of those molecules that creates an optimal and balanced environment for your immune system to fight infections, while also dampening inflammation.
What Affects NAD+ Levels
Having low oxygen in your cells also results in higher NADH and lower NAD+.
Blood sugar dose-dependently worsens (increases) your NADH/NAD+ ratio in the same way as low oxygen. When you combine excess carbs/sugar and low oxygen, you become fatigued.
This is one of the most significant reasons why sugar/carbs make people with mold issues feel worse.
In fact, you might feel worse after eating anything because eating decreases NAD+ levels and fasting increases it. Of course, inflammation will also make you fatigued by shutting orexin down.
On the other hand, some people do worse in the short term because skipping meals cause hypoglycemia and when I was in a bad state, I’d feel like crap if I skipped meals. And then I’d eat a meal and crash because there weren’t enough energy-related molecules (ATP levels) in my lateral hypothalamus from fasting, which results in the shutting down of orexin down.
Alcohol has a host of other negative effects, but they don’t explain the rapidity by which people feel worse from it. NAD+ explains the almost instant effects in CIRS people.
When rats were given Niacinamide to increase NAD+ levels, the negative changes caused by amphetamines were reduced (R).
So we see that lower levels of NAD+ will decrease brain energy and dopamine, and people will start to need amphetamines to keep up. This happened to a mold client of mine who started to use amphetamines a bit before the mold crash hit because of attention problems. But what this really reveals were low NAD+ levels that started to cause brain changes that were partially reversed by amphetamines. However, the root cause (lower NAD+) wasn’t addressed and it was only time before an exposure to mold caused some kind of crash. And if mold exposure didn’t do it, some other biotoxin would have.
Saunas are also considered a panacea and have been a part of every historical culture. We think it’s because we’re sweating out toxins, and that might have something to do with it, but saunas and heat shocks also increase NAD+ levels (R).
However, some fermentation byproducts cause problems in mold/histamine intolerance and Th2 dominant people.
Get Help With Test Resuts
If you’re confused by all this information about CIRS, Lab Test Analyzer is your digital health advisor that helps you understand your lab tests and makes recommendations based on your results.
SIRT1, The Circadian Rhythm, and CIRS
The enzyme that makes NAD+ (NAMPT) is under circadian control (R). When your circadian rhythm isn’t working, NAD+ levels are not regulated properly and that means SIRT1 (and SIRT3) isn’t either regulated properly since NAD+ is needed to activate SIRT1&3.
Not taking care of your circadian rhythm properly is also a root cause of mold problems.
This is why all people with mold issues that I’ve seen have a messed up circadian rhythm.
Lower levels of SIRT1 combined with an imbalanced hormonal and immune system (often caused by stress, lack of sun, mitochondrial dysfunction, circadian dysregulation, HLA genes) causes your system go haywire when exposed to mold.
Now SIRT1 is important for ALL CFS sufferers, but mold people have high SOCS3 as an additional cause and reduced SIRT1 is a significant cause of this.
SIRT1 powerfully reverses leptin resistance (R), which is a problem in mold sufferers (hence, the weight gain).
SIRT1 (and PGC-1a) also make you more sensitive to T3 (R), which is also a problem in CIRS – indicated by the fact that people feel cold and have symptoms of low T3 (symptoms that are worse than their numbers reveal).
Hypoxia and Mold Illness
Hypoxia will decrease NAD+ levels, SIRT1, and mitochondrial function.
We need superoxide/free radicals to defend against infections and oxygen is needed to create superoxide.
Hypoxia also caused less activation of MHC-II, which lowers our ability to clear pathogens.
Low oxygen or hypoxia causes VEGF, TGF-beta, and SOCS3 to increase, which are characteristic of mold illness.
When the immune system environment is off, TGF-beta is inflammatory and damaging rather than anti-inflammatory.
It’s no wonder that my girlfriend does so well with hyperbaric oxygen therapy. Pressure and oxygen result in increased oxygen delivery to cells.
In addition, pressure helps create EZ water around cellular proteins, which “energize” your cells.
Why Do People With CIRS/Mold Illness Suffer From Hypoxia?
There are 4 reasons specific to why CIRS/mold sufferers have low oxygen or hypoxia.
1) Low oxygen is caused in part by cytokines, which prevent oxygen from reaching the tissues from capillaries. Mold/CIRS people have higher cytokines.
2) Low oxygen is also caused by a sympathetic or fight or flight system that is in overdrive. This causes more shallow breaths. Mold/CIRS people always have an overactive sympathetic system, which is evident by the number of breaths per a minute and cortisol levels. CIRS/mold people almost always have more than 10 breaths per a minute and usually high CRH/ACTH/cortisol.
3) Almost all mold people have lower blood pressure. Oxygen is transported through the blood and when you have low blood pressure, not enough blood goes to the brain.
Remember, you need force to pump blood against gravity and when you stand gravity is against you. You need good blood flow to get enough blood to the brain to deliver oxygen.
There are many reasons for low blood pressure, but here’s one significant mechanism in CIRS:
Inflammation and cytokines increase iNOS, which produces large quantities of Nitric Oxide (as opposed to eNOS and nNOS) (R).
Very high levels of uncontrolled nitric oxide through increased iNOS decreases smooth muscle contractions by the heart and lead to lower blood pressure (R).
Nitric oxide from iNOS is more systemic rather than localized where you need increased blood, which is how eNOS and nNOS work.
nNOS is important in long-term potentiation and hence is likely to be important in memory and learning. nNOS is also important for gut flow and sexual arousal in males and females. CIRS/Mold people have memory problems, gut flow issues and decreased libido (R). Given the inflammatory environment, CIRS people likely have higher iNOS and lower nNOS and eNOS.
So you have lower blood pressure to pump blood to the brain, but you also have less localized oxygen delivery in the brain, the capillaries, and neurons, where you need it most.
Hypoxia locally in the brain is why mold/CIRS sufferers have so many cognitive problems. Indeed, my girlfriend does well with hyperbaric therapy and aerobic exercise in large part because these bring blood flow to the brain.
4) What I realized in mold clients in general is that they have lower levels of hemoglobin and red blood cells from their blood tests, which result in reduced oxygen transport/delivery. This is because SOCS3 also happens to decrease red blood cells and hemoglobin (R, R2).
TGF-b also suppresses red blood cells (R), so it makes sense that CIRS people have lower RBCs and hemoglobin.
Shoemaker wants to say that hypoxia is a result of mold illness. I want to say that the relationship is bidirectional and that hypoxia (and pseudohypoxia) is a central cause of elevated cytokine levels as well as a consequence of them.
CIRS and Low Acetylcholine
CIRS people are likely to exhibit a mix of the following list of symptoms that almost exactly match symptoms from anticholinergic drugs.
This is why CIRS people tend to do better with cholinergics.
When I recommended a CIRS client take some nicotine (a strong cholinergic), all of her symptoms diminished almost instantly. She said her visual symptoms rapidly improved. This CIRS patient also does well with caffeine, which also has cholinergic properties.
Other cytokines like IL-1 induces the enzyme that breaks down acetylcholine (acetylcholinesterase) and also increases the enzyme’s activity, thus promoting a cholinergic deficit. In addition, IL-1 directly inhibits acetylcholine release from neurons (R).
Interestingly, some fungi (such as Mycetismus) have anticholinergic properties, which means the effects could simply be directly from mycotoxins or other neurotoxins.
I recently had a client whose issues came about after botox injections. Botulinum toxin A has anti-cholinergic properties (inhibits acetylcholine release) and they’re even investigating whether to use it as an anticholinergic drug (R).
I bring this up because botox can cause the same symptoms as experienced by biotoxin people.
Now not all neurotoxins cause anticholinergic effects. In addition, people have different pre-disease levels of acetylcholine. These factors may explain why some people don’t get the full range of symptoms or get them to a lesser degree.
Interestingly, acetylcholine has been shown, in moths, to inhibit candida biofilm formation (R). This means that acetylcholine may do more than decrease inflammation – it could be anti-fungal as well.
Symptoms of anticholinergic drugs (ripped from Wikipedia):
- Poor coordination
- Increased body temperature (although inflammation causes lower thyroid hormones, which should diminish this symptom for some).
- Sensitivity to bright light (photophobia) – from pupil dilation.
- Loss of focusing ability blurred vision
- Increased heart rate
- Tendency to be easily startled
- Diminished bowel movement (decreases motility via the vagus nerve)
- Increased intraocular pressure
- Euphoria or dysphoria
- Respiratory depression
- Memory problems
- Inability to concentrate
- Wandering thoughts; inability to sustain a train of thought
- Mental confusion (brain fog)
- Muscle jerking/twitches
- Unusual sensitivity to sudden sounds
- Illogical thinking
- Visual disturbances
- Periodic flashes of light
- Periodic changes in visual field
- Visual snow
- Restricted or “tunnel vision”
- Visual, auditory, or other sensory hallucinations
- Warping or waving of surfaces and edges
- Textured surfaces
- “Dancing” lines; “spiders”, insects; form constants
- Lifelike objects indistinguishable from reality
- Hallucinated presence of people not actually there
- Orthostatic hypotension (sudden dropping of systolic blood pressure when standing up suddenly).
- Rarely: seizures, coma, and death
- Urinary retention,
- Decreased mucus production in the nose and throat; consequent dry, sore throat
- Dry-mouth with possible acceleration of dental caries
A common mnemonic for the main features of anticholinergic syndrome is the following:
- Blind as a bat (dilated pupils)
- Red as a beet (vasodilation/flushing)
- Hot as a hare (hyperthermia)
- Dry as a bone (dry skin)
- Mad as a hatter (hallucinations/agitation)
- Bloated as a Toad (ileus, urinary retention)
- And the heart runs alone (tachycardia)
Mold and Weight Gain
Another reason why mold warriors lose muscle and increase fat is because MSH causes fatty acids to be burned in your muscles for energy (R). Low MSH will cause less fatty acids to be burned in your muscles, which should result in more fat and less muscle.
Leptin resistance can increase fat cells and insulin resistance in muscle cells can decrease muscle mass.
Higher cortisol from an overactive HPA axis and high ACTH also can add some pounds in CIRS sufferers.
Chronic oxidative stress and inflammation often lower free T3 and metabolism, which may contribute minorly to weight gain.
Last, cytokines can’t explain an increase in fat, but it can explain muscle wasting.
Why Do Mold People Get Fat and Other CFS People Get Thin?
Both leptin and insulin regulate POMC neurons and AgRP neurons at multiple levels(R).
When AgRP neurons are active, weight gain results (R). These neurons are overactive in the overweight people.
AgRP is controlled by the protein (transcription factor) FoxO1. FoxO1 also regulates the expression of carboxypeptidase E, which is necessary for increasing α-melanocyte-stimulating hormone (via processing POMC). (R)
Mold warriors have enough POMC release, which is indicated by higher ACTH, yet they have lower MSH. It must be then that they have lower levels of carboxypeptidase E(R).
Phosphorylated FOXO1 probably doesn’t produce the enzyme (carboxypeptidase E) needed to make MSH, so you have low MSH.
Both leptin and insulin act on POMC neurons to increase sympathetic activity to adipose tissues and to promote the browning of white fat (R).
Probiotics May Help with Mold
The Takeaway: What To Do?
This regimen has been getting positive results. There are many other things you can do, but this is already overwhelming.
You’re welcome to try other tips mentioned in this post, but here are some of my favorites:
- Lectin avoidance diet
- Sun….to increase MSH, kill infections, utilize oxygen better, increase nitric oxide, rebalance immune system (with UVA, UVB, infrared and red light) and improve mitochondrial function. You need to get at least 1 hour of full body sun. You can do a half hour in the morning and afternoon. Getting the sun between 6-10 and 5-7 will get you the most infrared in the summer time. You want more infrared and less UV, but both are needed. In the winter you want the sun between 11 AM-2 PM to get more UV. Also getting the sun when it rises is important to reset your circadian rhythm. Take with 8 mg of Astaxanthin to protect you from radiation in the summer – especially if you have low NAD+ levels (because NAD+ protects your from UV).
- Exercise increases VIP (R), MSH (R, R2, R3) and blood flow….6 young men who exercised had their VIP increase markedly (from an average of 1.8 to 22.3) during 3 hours of mild bicycle exercise (R). Other studies confirm that exercise increases VIP (R).
- Fasting – During 59 hours of fasting, VIP increased from 3.6 to 10.2. Fasting also increases NAD+ levels (R).
- Stress reduction – Psychological stress increases TGF in primates (R, R2) and in the rat hippocampus (R). Psychological stress increases TGF-beta through catecholamines (epinephrine, norepinephrine, and dopamine) (R). Stress neurotransmitters can increase MMP-9 (R).
- Taking care of your Circadian Rhythm –Read my post on how to take care of your circadian rhythm.
- Cold exposure – cold showers, Cold Vest, Cryohelmet/Ice Helmet. Cold increases SIRT1, ADH, cyclic AMP (and therefore MSH), T3, fatty acid burning and mitochondrial function.
- Fish for DHA. If you can’t eat seafood supplements are better than nothing….Fish oil. I take fish oil with the meals that don’t contain seafood.
- Oxygen – with an Oxygen Concentrator and breathing exercises with this Breathing Exerciser. Oxygen will increase NAD+, mitochondrial function and help combat infections. HBOT is obviously ideal, but it’s really expensive. Hyperbaric is great if you can get your hands on it.
- Ketosis/β-hydroxybutyrate (R) – to increase NAD+ and improve mitochondrial function.
- ICES increases oxygenation to tissues – ICES® DigiCeutical® A9a Model System. Use the code SAVE50 to get 50$ 0ff….Both I and my GF noticed benefits from this.
- Infrared – Infrared will improve mitochondrial function, increase NAD+, decrease inflammation
- Infrared Sauna – increases NAD+, increases Vasopressin/ADH, EZ, gets out toxins.
- Nicotine gum – increases VIP (R, R2, R3), acetylcholine and decreases cytokines.
- Alpha GPC
- Huperzine A
- Resveratrol – to increase SIRT1…Needs to be combined for synergistic effect (R).
- Glycine – to increase VIP (R).
- Nicotinamide Riboside – Niagen NAD (IHERB) – to increase SIRT1
- Forskolin (IHERB)
- Curcumin increase SIRT1, activate the vitamin D receptor, decrease cytokines and rebalance the immune system. Curcumin has so many other benefits that are beyond the scope of this post.
- EGCG/Tea – to increase SIRT1 and modulate the immune system.
- Grape Seed Extract (R).
- Kelp Powder (IHERB) – to increase SIRT1 and as a source of iodine.
- Oxaloacetate – to increase NAD+ and mitochondrial function
- Increase MSH
- Chitosan-micro (IHERB) – as a binder
- Activated Charcoal
- Pregnenolone if no sleep issues
- Clay (IHERB)
- L. rhamnosus GG binds to mold toxins in the gut and reduce cellular damage (R).
Cholestyramine (CSM) (pure, with no sugar) disclaimer: not for personal use
Irregular MSH Levels?
If you have not yet tested your MSH levels, I recommend that you ask your doctor to do it. If you already have your blood test results and you’re not sure what to make of them, you need to check out Lab Test Analyzer. It does all the heavy lifting for you. No need to do thousands of hours of research on what to make of your various blood tests.
People don’t realize that their blood test results contain a gold mine of information that’s waiting to be unearthed. Unfortunately, not everyone has the time nor the inclination to sift through dozens of research papers.
It’s super-simple, so that even if you don’t have any background in science, you will understand what your results mean and what you can do to get them in the optimal range.
Lab Test Analyzer gives you up-to-date scientific information about your lab results. In addition, you will get both lifestyle tips and natural solutions to help you optimize your health. You can also rely on our science-based Optimal Ranges to prevent potential health issues and maximize your overall well-being.
All of the content is backed by science and researched by a team of PhDs, professors, and scientists.
We’re all unique, so we deserve solutions that treat us that way.
The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.
HOW WOULD YOU RATE THIS ARTICLE?