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Article Summary: After listening to the AutismOne lecture by Chris Shade, I was excited about continuing the work on detoxification covered in AGA – Diet – Detox and GSH Detox Protocol. In particular, Chris mentions a novel approach to helping folks that are just really sensitive – have bad reactions to most treatments. Given that I know a few people like this along with being somewhat sensitive myself, it was an interesting journey to dig in a bit on the suggestions he offered. What follows are some insightful and helpful suggestions along with supportive documentation and recommended dosages for people that struggle taking on board supplements of any type. October 26, 2015

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Chris Shade – AutismOne Media

In June 2015, Chris Shade gave an AutismOne Media talk regarding detoxification that I found intriguing. In particular, he talked about how to work with folks that are particularly sensitive to supplements and medications. The suggestion was that the reason those with chronic fatigue syndrome (CFS or ME/CFS), fibromyalgia (FMS), multiple chemical sensitivity (MCS), post-traumatic stress disorder (PTSD), and chronic inflammatory response syndrome (CIRS) may be having a hard time getting better had to do with blocked detoxification.

In brief, Chris contends that the reason some struggle to get better has to do with a detoxification “transcription factor” called NF-E2-related factor-2 (Nrf2) being blocked. Nrf2 upregulates detoxification and antioxidant genes. When Nrf2 is blocked, the glutathione (GSH) detoxification pathway that is so important for removing toxins stops working – see AGA-Diet-Detox: Phase II. This is a big problem.

In brief, Chris’s approach to clearing this block begins by using liposomal GABA with L-Theanine to calm down anxiety producing Glutamate activity in the brain followed by liposomal Diindolemethane (DIM) in high doses to lift Nrf2 blocks. Once the Nrf2 blocks are removed, he slowly ramps up detoxification.

The reason this video drew me in was because I’ve worked with a couple of people that are just super sensitive. Also, I have sensitivities to food, certain supplements, most probiotics, and have to limit oxidative therapies like ozone and oxygen. The fact that mold among other factors can block Nrf2 made it all the more interesting. Given that I’d just finished writing two articles about detoxification, researching Chris’s approach seemed like a good next step to take. As I dug into the various points Chris made, I learned a lot more about the importance of lipids for mitochondria repair, methylation for treating anxiety and lifting Nrf2 blocks, additional ways to help rebuild the Extracellular Matrix (ECM), and so on.

With that introduction, let’s get started. I’ll begin with the show notes I took and then dive into what I learned as I examined the various steps to getting detoxification working as outlined by Chris.

Christopher Shade – AutismOne Show Notes

AutismOne Media – Christopher Shade

• When inflammation is elevated, the body is producing oxidants to try and kill off offending pathogen(s). Since detoxification is primarily an anti-oxidant process, when inflammation is high then detoxification will necessarily be lower resulting in the body hanging onto toxins. 00:08:00
• Transport proteins pull toxins into the liver from both the ECM and blood while other proteins move the toxins out into the bile. Liver blockage leads to colestasis, where bile cannot flow from the liver to the duodenum. This then produces problems in the small intestines wherein toxins are not cleared well. 00:30:00
• Leaky gut in the small intestine is caused by glyphsate. On top of this, GMO gluten (see Dr. Zack Bush and read about Redox) results in a lot of inflammatory endotoxins (lipopolysaccharides). Lipopolysaccharides (LPS) are cell wall fragments produced by bad gut flora. Due to leaky gut, these endotoxins are then able to get into the blood and stimulate an inflammatory response. Endotoxins can also come from root canals, alcohol, chronic sinusitis, and urinary infections. They stimulate a strong gut inflammation that can dramatically diminish the entire detoxification system by 60%. When this happens, movement of toxins through the liver is hampered. The body responds by shunting toxins originally destined for the liver over to the kidneys via the MRP3 pathway. This can then lead to overloading the kidneys. To make matters worse, if mercury is present in combination with endotoxins, then transporters in the proximal tubules in the kidneys will be damaged further hampering detoxification. 00:36:00

  Concurrent Inflammation As A Determinant Of Susceptibility To Toxicity From Xenobiotic Agents
  Augmentation Of Mercury-Induced Nephrotoxicity By Endotoxin In The Mouse
  Synergistic Destruction: How Vaccines and GMOs Converge to Fuel Autism and Neurodegenerative Conditions

• Along with the polyphenolics as discussed in GSH Detox Protocol to upregulate Phase II, sulfur compounds like R-Lipoic Acid can also be used. In comparison to polyphenolics like Haritaki, sulfur compounds are very strong because they create more free-radical damage and subsequently produce a stronger detoxification response. Although, sulfur compounds aren’t as well tolerated in general, they do have the added benefit of stimulating mitochondria production and efficiency. Plant and sulfur compounds produce oxidant cascades that turn on the Nrf2 anti-oxidant Glutathione (GSH) detoxification switch. Contrary to mainstream understanding, they are not “chelators” or anti-oxidants! Rather, they upregulate detoxification. Make sure to take enough molybdenum and B12 with sulfur compounds like Lipoic Acid as some people with CBS mutations will build up sulfites. Molybdenum helps to oxidize and clear sulfites so the person doesn’t become toxic with them. Chris speculates that those that herx using sulfur compounds may actually be overloaded with sulfites. 00:47:00
• Unusual therapies like ozonated GSH injected in the blood triggers Nrf2 upregulation. This happens because the body interprets the damaged GSH as a stress signal and responds by increasing detoxification. In fact, DMPS and DMSA also have pro-oxidative qualities that may also increase GSH detoxification. In part, this may be why people that use these chelators get benefit. 00:56:00
• NF-E2-related factor-2 (Nrf2) is a protein that regulates an array of detoxifying and antioxidant defense genes in the liver. Nrf2 is often blocked epigenetically most often by mold – but also in neoplastic diseases like prostate cancer. For example, scientists found that Glutathione-S-Transferase (GST) was shutoff in prostate tumors suggesting the tumors formed, not because of toxins, but because the body lost the ability to synthesize GST and other detoxification enzymes. As a consequence, Chris speculates that the reasons tumors form is due to toxins becoming trapped in the tissue due to blocked detoxification. Chris also speculates that some viruses like Epstein Barr can cause epigenetic down-regulation of detoxification. Related to this, the herpes virus can be sprayed with liposomal GSH and it will stop the skin outbreak. This all suggests mold, neoplastic diseases, and viruses all have the ability to shutdown the GSH pathway as a way of creating a more habitable environment for themselves. 1:00:00
• Chris sites a study about Ochratoxin produced by Aspergillus mold and how it shuts down detoxification by blocking Nrf2. Both mold and mercury are cleared by Nrf2 pathways. 1:04:00
  Reduction In Antioxidant Defenses May Contribute To Ochratoxin A Toxicity & Carcinogenicity
• Lipoic Acid is often used to clear liver damage – see Dr. Burton Berkson. However, giving folks Lipoic Acid that are Nrf2 impaired will cause them to become very sick as they won’t be able to clear the toxins that are liberated. When Nrf2 is shut down, Lipoic Acid acts as a major pro-oxidant. Since mold shuts down Nrf2 and consequently GSH enzyme production, you must first get detoxification going before giving Lipoic Acid to moldy folks. Likewise, ozone and oxygen therapies will just make moldy people with impaired Nrf2 sicker as they can’t clear the oxidative damage. On the flip side, when Nrf2 is working, oxidative therapies upregulate Glutathione (GSH), Superoxide Dismutase (SOD), and detoxification in general. 1:05:00
• Mitochondria membranes are critical to ATP energy production. If the membrane is damaged by inadequate phospholipids, then you’ll get very little ATP (energy) and a lot of free-radical damage. Other membranes within the cell like the endoplasmic reticulum, responsible for making proteins and lipid (hormone) formation, are also dependent on phospholipids. Healthy membranes of all types throughout the body are essential in facilitating movement of nutrients and clearing of toxins. When Chris loaded up on his version of phosphatidylcholine, he got a flood of testosterone and felt great. 00:32:00, 1:07:00
  Phosphatidyl Choline (PC)
  Designs for Health Phosphatidyl Choline 40% Powder
• Protocol for Blocked Patients 1:15:00
• Dr. Martin Palls is the expert on the Nitric Oxide (NO) and Peroxynitrite (ONOO) free-radical cascade that can happen in MCS causing inflammatory neurotoxicity. This happens when the glutamate receptors become hyper-stimulated. The neurotransmitter Glutamate stimulates the sympathetic nervous system while the neurotransmitter GABA counters Glutamate by stimulating the parasympathetic nervous system. Too much Glutamate (like from mercury toxicity) results in anxiety. Over expression of Glutamate “fries the brain”. Palls tries to solve this by up-regulating Nrf2 but Chris believes this won’t work because Nrf2 is likely blocked. Chris speculates that people that go “crazy” taking even small amounts of supplements and treatments have this issue. Chris likes to settle down the brain with liposomal GABA combined with L-Theanine. This dampens down reactivity so neuro-inflammatory patients can take much higher doses of remedies beginning with Diindolemethane (DIM). If it was legal, he’d use Cannabidiol as it’s very good at calming. Liposomal glutathione (GSH) is also calming and the next best legal alternative to Cannabidiol. 1:09:00, 1:27:00
• In terms of a treatment protocol, Chris sites studies that show Diindolemethane (DIM) reverses epigenetic Nrf2 blocks on prostate cancer cells. As a result, he also believes DIM works for mold and other hyper-sensitive patients with Nrf2 blocks. Chris mentions treating a sensitive Lyme patient with liposomal DIM and GABA followed by GSH and eventually Lipoic Acid by slowly increasing doses over the course of as little as one day. This is uncommon with most taking a couple months but it does offer some credence to this approach. Chris’s liposomal DIM has a 200% better uptake than capsules. He recommends 20mg twice daily of his liposomal product. Generally, you only need to take DIM for 2-3 months to lift Nrf2 blocks. In Biotoxin Journey – Sulfation I wrote, “You can get Diindolemethane (DIM), a sulfur containing molecule found in cruciferous vegetables, and Indole 3 Carbinol (IC3) supplements. In conversions with Dave Asprey, Dave commented that DIM and IC3 promote beneficial metabolism of estrogen for folks that are estrogen dominant by turning on Sulfation pathways often shut down by mold. At that time, Dave was taking IC3.” In other words, Chris and Dave seem to be thinking along the same lines. 1:13:00
• Chris likes Quintessential 0.9 for alkalizing the Extracellular Matrix (ECM) and his liposomal Vitamin C (without Lipoic Acid until later) to build the fibroblast cells in the ECM matrix along with enhancing Phase I liver detoxification through quenching free-radicals. Chris says you can also just add sodium bicarbonate (baking soda) to drinking water to help normalize/alkalize the ECM pH. An alternative is to drink Gerol Steiner alkalizing water. Fiji and Voltic mineral water are also alkalizing bottled waters that have silica too to help remove aluminum and organize the ECM. Aluminum poisons the ECM. Incidentally, energy medicine and acupuncture work through the ECM. 1:15:00, 1:25:00
  Quintessential Bioterrain Restore 0.9
• Chris likes using liposomal forms of supplements that are very small (50-100 nanometers) because they’re readily absorbed instead of having to go through the gut and have special energetic qualities. Pure phosphatidylcholine (PC) made from either soy or sunflower is close to 92% PC and can be used interchangeably as it does not contain impurities. Raw lecithin is about 10-15% PC. Raw Soy lecithin has estrogens and should be avoided. 1:17:00
• When the time comes to up-regulate Nrf2 for enhanced detoxification, you need B-complexes and GSH onboard before introducing other up-regulators like Lipoic Acid (Chris’s favorite), polyphenols like Haritaki, and sulfur compounds. GSH by itself will help clear metals, chemicals, and balance TH1-TH2 immunity. Make sure to start slowly using GSH with sensitive people and only add in stronger up-regulators like Lipoic Acid later on. 1:30:00
• Drainage is important. Liver and gallbladder drainage is improved with bitters like Gentian, Dandelion and Milk Thistle. Kidney drainage is improved with herbs like Solidago, Corn Silk, and Juniper. Myrrh (Chris’s favorite), Burdock, Dandelion, and Echinacea are good for blood clearing. Sensitive patients must start with homeopathic solutions of drainage remedies like the PEKANA Big Three Basic Detoxification & Drainage Kit from BioResource. 1:31:00
• Binders like charcoal, CSM, Welchol, Chitosan, chlorella, and IMD are essential. Once scoop of IMD is equivalent to 100 chlorella tablets. For sensitive people, start with weaker binders as IMD will “open the floodgates”. 1:33:00

Protocol for Blocked Patients

1. GABA
2. DIM
3. ECM
4. Phospholipids
• How to Repair Mitochondria with Lipids Show Notes
5. CoQ10 & the Rest
• Drainage Bitters
• Binders – clay, charcoal, zeolite, chlorella, and chitosan. Chris says Chitosan is the “virtually identical” to Welchol. Don’t use Intestinal Metal Detoxification (IMD) until later as it can “shake the tree”. Make sure to heal the gut as much as possible as an inflamed gut significantly blocks liver detoxification. Quantifying Your Mercury Burden and Detoxification
• Crank It Up – Later, you can add in Nrf2 up-regulators, anti-inflammatory supplements, and drainage remedies. Haritaki and Chris’s ClearWay CoFactors turns up Nrf2. Liposomal C with Lipoic Acid and Liposomal EDTA are very strong Nrf2 upregulators. Make sure to add molybdenum for those with CBS mutations.
6. Helping the Unusually Sensitive Patient Show Notes

GABA

As mentioned in the Show Notes, GABA is important because it calms down neuro-inflammation. Without GABA’s calming effect, sensitive patients can find it very difficult to stick to any treatment due to the excitatory states induced by excess Glutamate. Can you say intense anxiety for no apparent reason?

According to Dr. Martin Pall, high Glutamate levels are a result of toxic levels of pesticides, insecticides, mercury, biotoxins, hydrogen sulphide, and carbon monoxoide. These toxins over stimulate the Nitric Oxide (NO) and Peroxynitrite (ONOO) cycles. This in turn leads to excitatory states due to excesses of Glutamate. GABA is one way to quench this fire.

More specifically, Glutamate is an important and helpful excitatory brain neurotransmitter. It makes us sit up and pay attention. However, it’s known that when Nitric Oxide (NO) levels become too high, Glutamate and Peroxynitrite (ONOO) levels in the brain rise. Excessive levels of Glutamate and ONOO in turn lead to over sensitized Glutamate receptors called N-methyl-D-aspartate (NMDA).

NMDA Glutamate receptors are found in brain neurons, the spinal cord, and the peripheral nervous system. Not surprisingly, higher levels of Glutamate and over sensitized glutamate receptors cause a person to be more sensitive to pain, anxious, restless, and to have difficulty focusing. You can read more about this dynamic in Nitric Oxide, Superoxide & Peroxynitrite.

Lower Glutamate
8 Important Roles of Glutamate
Glutamate – One More Piece in the Chronic Fatigue Syndrome

So what causes the NO/ONOO cycle to spin too fast? I found three points of view. The first comes from Dr. Martin Pall who argues that the reason for an over active NO/ONOO cycle, and consequently neuro-excitatory symptoms from Glutamate, has to due with lack luster Nrf2 activity. Nrf2 is an important protein inside our cells that when triggered combines with our DNA to produce antioxidants like glutathione (GSH), superoxide dismutase (SOD), and others. These antioxidants help to dampen the NO/ONOO cycle.

Nitric Oxide, Superoxide & Peroxynitrite

Dr. Pall’s protocol consists of recommendations that either reduce NO/ONOO levels or stimulate Nrf2 activation. To lower ONOO levels that are a result of high NO levels, Dr. Pall recommends 5-MTHF, high dose Vitamin C, B4P, and FIR saunas. When it comes to stimulating Nrf2 activity, zinc, curcumin, tocopherols, milk thistle, green tea, and others are recommended. In addition, D-ribose, VIP, reduced GSH, and a diet that includes olives, sweet potatoes (especially purple), tomatoes, dark leafy vegetables, and oils from fatty fish, are also helpful.

When I stand back and look at Dr. Pall’s approach, most of the recommendations are fairly easy and safe to implement. You can read specific protocol details in How Can We Cure NO/ONOO- Cycle Diseases. The exception is B4P supplementation. This B vitamin can cause trouble for some. In BH4 Supplementation, Dr. Lynch recommends supplementing with precursors to B4P instead of B4P and then only after getting other methyl cycles working to prevent crashing from B4P. Along with decreasing inflammation, infections, and ammonia levels, Dr. Lynch recommends adding methylfolate, iron, Vitamin C, magnesium, B6 and others to repair BH4 levels.

The second position related to high NO/ONOO levels comes from Chris Shade who agrees with Dr. Pall that excess Glutamate levels are a problem but disagrees as to the cause. Chris sites studies that show Nrf2 gets blocked by mold, neoplastic diseases, and viruses. When Nrf2 is blocked, important antioxidants including Glutathione (GSH) don’t get made. When the GSH pathway is shutdown, NO/ONOO levels rise that then produces excess Glutamate. Chris’ recommendation is to use GABA to counter the excitatory Glutamate so that sensitive people can tolerate higher doses of DIM to turn Nrf2 back on. We’ll talk about DIM a bit later.

GABA production depends on the active form of B6 (P5P), glutamine (not to be confused with Glutamate), magnesium, and is boosted by zinc and taurine. B6 can get depleted from excessive oxidative stress or chronic infections. In Could It Be B-6 Deficiency?, the authors site birth control pills, Hydralazine, Hydrazide, and Tartrazine, along with Pyrrole Disorder as reasons for a B6 deficiency. Interestingly, Pyrrole Disorder relates to the use of Round-Up as discussed in AGA – Diet – Detox – Phase I, as well as, tying in with the work of Dr. Walsh. Dr. Walsh regularly tests for Pyrrole Disorder. The more I read, the more all the pieces end up being inter-related. Getting tested for B6 levels for those that suffer from anxiety and the like seems to make good sense. I was.

Chris Shade recommends his Liposomal GABA with L-Theanine . Since poor nutrient absorption from gut inflammation is common in chronic illness, taking a high quality liposome that is directly absorbed into the blood stream by holding it in your mouth makes sense. As most know, liposomes are much more potent too. I purchased a bottle of PurXpressions Liposomal GABA and see mild but significant benefit in its use. It helps with sleep and does seem to cause me to chill out a bit more. However, I’m probably not the best person to judge this as I don’t have much anxiety now-a-days. I’ve also had good luck taking 1,000mg of NOW Foods Gaba with 200mg of NOW Foods L-Theanine. Chris recommends 250mg of his liposomal GABA. Given that most liposomes are five times stronger compared to supplements that go through the G.I. tract, (5×250)= 1,250mg and this is roughly equal to what I’ve taken in pill form.

The third point of view regarding high NO/ONOO levels driving excessive Glutamate comes from Rich Von Konynenburg. In Possible Causes Of Methylation Cycle Block, Rich argues that physical stressors deplete glutathione (GSH). Since GSH protects B12, a lack of B12 results that then slows the methylation cycle. This partial methylation block further reduces GSH production and also results in higher levels of NO. When NO rises, so does ONOO along with Glutamate.

Along the lines of B12, it’s interesting to read studies showing B12 depletion from mold and other studies showing that taking mega-doses of B12 quenches NO levels resulting in diminished inflammation. It’s all interrelated. Rich has seen high-dose B12 taken with active folate lift methylation cycle and glutathione blocks.

Regarding optimal levels, in the study Vitamin B12: Vital Nutrient for Good Health, the authors suggest that the American B12 deficiency threshold of 200 pg/mL is way too low. The optimal range of 1100-1300 pg/mL dramatically reduces psychiatric symptoms including Alzheimer’s. In AGA – Diet – Detox – Methylation, I outline Rich’s Simplified Approach For Lifting Methylation Blocks wherein a total of 2,250mcg of B12 is recommended. This is in comparison to the RDA for B12 of 2.4mcg. I’m guessing you could say that 2,250mcg qualifies as a “mega dose”.

Impedance on Vitamin B12 in Chronic Toxigenic Mold Exposures
Supra-Therapeutic Doses of Cobalamin in the Treatment of Systemic Inflammatory Response Syndrome

For a related aside, there is a surprising amount of overlap between Chronic Inflammatory Response Syndrome (CIRS) symptoms and those associated with Glutathione (GSH) deficiency. Looking at Expectations When Glutathione Is Depleted, low ATP energy output, heart dysfunction, Th2 immune system dominance, along with ACTH and ADH imbalances all fall under both headings. Clearly, GSH is important.

In addition, as I did more reading about methylation, B12, and active folate (folinic acid), I invariably came across the work of Dr. William Walsh. Dr. Walsh is an expert in treating mental illness including repairing methylation. He uses around 15 different “nutrients” that include zinc, copper, folic acid, methionine, B6, glutathione, anti-oxidants, and others. What I appreciate about his work is that he’s been in this field for decades and has collected records on over 3 million patients including the methylation status of over 30,000 patients.

By trial and error, he’s figured out what works. Now I know that lately it’s all about getting your genetic variations (SNPs) mapped through 23andme so that approaches used by the likes of Dr. Ben Lynch and Dr. Amy Yasko, along with analyses by geneticgenie and Sterling’s App can be employed. However, if you listen to Dr. Lynch, he clearly states that methylation is only one part of the puzzle and that you have to marry symptoms with genetic SNPs before being able to formulate a plan. He’s adamant about not trying to fix every deviant enzyme in a person’s genome.

So Dr. Walsh takes this same approach but from an even bigger perspective. Given that there are over 10 million genetic mutations (SNPs) that have been identified, along with the fact that every person has over 1,000 of these SNPs, Dr. Walsh takes a more functional approach. For example, many people assume that if you have the MTHFR SNP then you’re necessarily under-methylated wherein the addition of methyl groups is recommended. However, Dr. Walsh has found that this is not always the case. What Dr. Walsh has found is that it’s impossible to only look at a handful of genetic variations (SNPs) and somehow conclude what the overall effect on methylation of the 1,000 or so SNPs people have.

Instead, Dr. Walsh has learned through clinical experience that using whole blood histamine or the SAMe/SAH ratio are much better ways to determine overall methylation status. So we know that the overall methylation status is important. If you’re under-methylated then nutrients like Methionine and SAMe will help. If you’re over-methylated, then folic acid is very beneficial. Assuming that a person with the MTHFR SNP is under methylated and giving them Methionine or SAMe is going to make them worse if their overall methylation status already has too many methyl groups. This clinical insight into methylation status is just one of many that Dr. Walsh “brings to the table” in order to determine what nutrients will help a person.

Nutrigenomics – MTHFR

By the way, I know there are folks that argue Dr. Walsh is “old school” and that he doesn’t even know the differences between nutrients like folic acid and folinic acid. However, he has stated that folinic acid is converted to folic acid after one methylation cycle and that’s why it doesn’t have the desired effect. Having said this, clearly Dr. Lynch and Dr. Yasko are making new discoveries and helping folks too. For me, the bottom line is Dr. Walsh has a ton of data and clinical experience proving what he does works. I’ll leave it to the up-and-coming methylation experts figure out why.

Based upon what I’ve learned, at some point I plan on being seen by a Dr. Walsh trained physician. Direct HealthCare Access offers a Metabolic Panel & Clinical Consultation for $435 as of October 2015. The Panel includes the four most telling tests consistent with the work of Dr. Walsh along with a consultation with Dr. Albert Mensah at Mensah Medical. Dr. Mensah was trained by Dr. Walsh and is located in Chicago, Illinois. For a point of reference, I called his office and found out that an office visit costs over $800, not including tests. You have to submit to insurance separately with the paperwork they provide. Although I was told that seeing Dr. Mensah in person would help him to select the appropriate tests, as opposed to the four most common tests in the panel, I just don’t know that it’s worth the extra expense.

When I reflect on the high levels of anxiety I experienced, I wish I knew about GABA back then. Furthermore, based upon Sterling’s analysis of my 23andme data, I have several GAD SNPs that are associated with an inability to produce enough GABA to counter excess Glutamate. This in combination with the understanding that excess levels of NO/ONOO result in neuro-excitatory states due to high Glutamate levels all gives credence for my following Chris Shade’s recommendation to take GABA to help with anxiety when it shows up.

When it comes down to it, CIRS really hammers a person’s mental health. In A Volumetric NM Study Using Neuroquant, the authors write, “Having TGFB 1, VEGF and MMP9 changing rapidly with exposure and re-exposure suggests that the BBB permeability will fluctuate as the inflammatory elements of CIRS-WDB change, creating the potential for ongoing fluctuations in neuropsychiatric symptoms.” This doesn’t even touch on the swelling and atrophy of various portions of the brain that occurs with CIRS along with the neurological symptoms these brain changes produce. When it comes down to it, being able to quiet down psych symptoms goes a long way toward helping a person stick with a therapeutic program – not to mention the much appreciated peace of mind.

Is it any wonder that many end up taking psychotropic drugs like Lamotrigine (Lamictal), Clozaril (Clozapine), and Olazapine (Zyprexa)? Interestingly, from my cursory research, all of these medications work to either reduce Glutamate levels or NMDA Glutamate receptor sensitivity. Sometimes the situation is so bad that it makes sense for some to take these types of drugs just to get through it. If you go this route, make sure to very slowly wean yourself off once your CIRS labs are improved while under the supervision of a “shrink”.

So although there are at least three competing theories related to why NO/ONOO levels are too high, much of advice for remedying this physiology is typically included in any good health recovery protocol. More specifically, supporting methylation, taking liposomal C and liposomal GSH (see GSH Detox Protocol), along with supplementing with vitamin E, milk thistle, D-ribose, zinc and curcumin just make good sense for many reasons – not the least of which is the fact that they’ll help reduce excitatory states due to excess Glutamate per Dr. Pall. To that, the addition of liposomal GABA to help calm anxiety appears to have solid support. A month or two after taking GABA, Chris’s approach of adding in liposomal DIM to remove any Nrf2 blocks seems like a nice addition to Dr. Pall and Rich’s approach (see the discussion below). DIM should unblock GSH detox and subsequently bring down neuro-excitation from high levels of NO/ONOO/Glutamate. Personally, I also plan on seeing a Dr. Walsh trained physician to determine my overall methyl status in order to better tweak Rich’s Simplified Protocol. Also, since I have a CBS mutation, I plan on adding in molybdenum to make sure I’m able to oxidize any excess sulfites that result from taking GSH and Alpha-Lipoic Acid (ALA) as both of these are sulfur based.

DIM

I’ve already mentioned Chris Shade’s approach to using Diindolemethane (DIM) to reverse epigenetic Nrf2 blocks as the second step in helping folks with blocked detox. The first step was the use of GABA to counter excitatory Glutamate levels until Nrf2 is working again. So now let’s get into a few details.

The nutrient DIM comes from the brassica family of plants that includes cabbage, broccoli, bok choy, Brussels sprouts, cauliflower, kale, kohlrabi, and the like. In the AutismOne video, Chris says that his liposomal DIM has a “200 fold better absorption than regular DIM”. If we’re to take him literally, this works out to 200 times better or 10,000%! This sounds like an extraordinary uptake rate as typically liposomes are absorbed at a rate of 5 times over pills. Chris goes on to recommend 20mg (2mL or 4 pumps) twice daily of his liposomal product.

If we run the math, 20mg of PurExpressions DIM works out to 4000mg of products like Source Naturals DIM twice daily. At 100mg of DIM per capsule, that’s 40 capsules a day! Alternatively, each bottle of PurExpressions DIM contains 50mL. Eight pumps a day uses 4mL so there are (50/4)= 25 days worth in a bottle.

My take-away from this is that it takes high doses of DIM for 2-3 months to lift Nrf2 blocks. I’ve ordered two bottles of PurExpressions DIM to give it a try and I like the facts that it’s super potent and by-passes the gut. Given that DIM is sulfur based, I’ll be sure to take molybdenum and B12 especially since I have a few CBS mutations including C699T.

Phytochemicals from Cruciferous Vegetables, Epigenetics, and Prostate Cancer Prevention
Diindolylmethane But Not Indole-3-Carbinol Activates Nrf2

ECM

In GSH Detox Protocol – PreTox – Increase Drainage, I discuss the importance of clearing the space between the cells and tissues, called the Extra Cellular Matrix (ECM). Toxins are transported across the ECM on their way to the liver, gut, and kidneys. Having a well balanced ECM is important to detoxification and creates a healthful environment that triggers positive epigenetic switches in cells. Related to CIRS, in A Volumetric NM Study Using Neuroquant, Dr. Shoemaker writes “Disruption of the BBB (Blood Brain Barrier) from hypoxia (low VEGF) results in increased permeability involving the rearrangement of tight junctions with disrupted continuity, gapping and increased extra-cellular matrix (ECM) destruction due to increased MMP9 … Neuroglial-secreted MMP9 controls the composition of the extracellular matrix (ECM).” In other words, Chronic Inflammatory Response Syndrome (CIRS) isn’t good for the ECM.

In addition to Quintessential 0.9, BioPure Matrix Electrolytes, and Celtic Sea Salt discussed in GSH Detox Protocol – PreTox – Increase Drainage, Chris offers a few other suggestions to repair the ECM. To start, he recommends his PurXpressions Liposomal C. In relation to the ECM, Vitamin C helps build fibroblast cells that then in turn create the ECM matrix. If you decide to add in liposomal C, make sure to initially use liposomal C without R-Lipoic Acid (R-LA). According to Chris, R-LA will seriously upregulate detoxification and if you haven’t cleared detox blocks, you’re going to get sick from a toxin overload. Personally, I make my own liposomal C and take the equivalent of 10 grams daily – see Updated 3-Cup Liposomal C Recipe or Liposomal Vitamin C.

Chris also mentions the inexpensive approach of adding sodium bicarbonate (baking soda) to drinking water to help normalize/alkalize the ECM pH. Dr. Sirus has written extensively on the use and benefit of baking soda in Sodium Bicarbonate – Second Edition. He recommends using urine pH strips to guide dosage. Personally, I’ve read conflicting views on this sort of approach and if I decided to add baking soda to drinking water I’d use the strips to help me put the pH of the water somewhere in the 7.4 or slightly higher. So if you decide to take baking soda orally, make sure to do some reading on the subject.

My preferred method is to add baking soda to bath water as mentioned in Detoxification: Safe, Effective and Without a Healing Crisis. I sleep better and feel calmer after these baths. I’ll leave it up to the reader to Google for specifics but soaking in a tub with 1/2 cup of baking soda for 10-20 minutes twice weekly is a common recommendation. Chris goes on to mention Gerol Steiner, Fiji and Voltic bottled water as being alkalizing. Fiji and Voltic mineral water also have silica to help remove aluminum and help organize the ECM.

Phospholipids

Chris’s Phospholipid supplementation recommendation peaked my curiosity given that it was mentioned in the context of ATP energy production. I’m sure most people are aware that mitochondria are small entities (organelles) found within our white blood cells that are responsible for making energy out of glucose and oxygen. Dr. Shoemaker mentions that the reason folks with CIRS get badly fatigued after even moderate exercise has to do with the low oxygen levels resulting from low VEGF levels – see What is Biotoxin Illness. When there isn’t enough oxygen, the mitochondria just can’t make much energy.

This makes sense, but I can tell you that my VEGF levels were normal, and yet fatigue is a big issue that I’m still working through. So it seems like it’s more than just oxygen levels that’s involved. The question that naturally arose was “does mold damage cell membranes”? Well, if you’ve done some reading on my site, you’ll know that mold increases levels of inflammatory cytokines. Furthermore, there are numerous studies that show inflammatory cytokines increase Reactive Oxygen Species (ROS) levels that then in turn damage cell membranes. Given the importance of moving electrons across their membranes via the Electron Transport System, healthy mitochondria membranes are essential for ATP energy production.

Pro-inflammatory Cytokines Increase Reactive Oxygen Species
Mold Elicits Atopic Dermatitis by Reactive Oxygen Species

In addition, Chris mentions that phospholipids are also important for the overall health of all cell membranes – not just mitochondria. We know from Liver Detoxification that toxins have to be moved across cell membranes and transported to the gut, liver, and kidneys. Just like with mitochondria, if the cell membranes are damaged, moving toxins out and nutrients into the cells becomes more difficult. So OK, cell membrane health is important but what are phospholipids and does taking phospholipids help?

Phospholipids are specialized fat molecules that are used to construct cell membranes. However, not all lipids are created equal. Chris’s QuickSilver Pure PC contains the lipid Phosphatidylcholine (PC) and is described as “most predominant phospholipid building block of animal and plant cell membranes”. In searching for sources on Amazon, I came across products like Swanson Sunflower Lecithin that contains 25% PC. This is not to be confused with less expensive products that contain Choline bitartrate. Unlike PC, Choline bitartrate can not cross the blood-brain barrier and needs to be augmented with Acetyl-L-Carnitine (ALCAR).

Advanced Guide to Choline in Nootropic Stacks

25% PC Dosage Guidelines

• 1,250-1,800mg for liver disorders – three times daily with meals
• 1,800-3,250 mg for lowering cholesterol – three times daily with meals
• 18,000-36,000 mg for Alzheimer’s and bipolar depression – one time daily with meal
  Woodlands Healing Research Center – Phosphatidylcholine

So that information all seemed well and good until I listened to How to Repair Mitochondria with Lipid Replacement. In this podcast, research scientist, Professor Garth Nicolson PhD, describes not only the benefits of lipid supplementation but the importance of getting the right kinds of lipids and to make sure they’re undamaged. In other words, while supplementing with PC is a reasonable approach, the specifically designed lipid mix in Allergy Research Group – NT Factors Energy Lipid Powder was clearly the way to go. My show notes of this podcast follow.

How to Repair Mitochondria with Lipid Replacement Show Notes

Episode 29 – Professor Garth Nicolson PhD

• Mitochondria are found only in white blood cells and create the energy of the body. Mitochondria use the oxygen we breathe along with the electron transport system to produce this energy. When the mitochondria are damaged, we become fatigued. Damage to the lipid membrane of mitochondria is the most common form of damage. When this membrane is damaged, the mitochondria are unable to develop a charge across their membrane making it difficult to produce high-energy electrons.
• Reactive Oxygen Species (ROS) damage mitochondria cell membranes. Infections from viruses and bacteria, along with chronic illness, aging, over work, and toxic exposures cause an increase in ROS. Furthermore, mold can also increase ROS.
• Repairing the mitochondria can have wide reaching positive effects beyond improved energy since all body functions rely on the energy from mitochondria. For example, some people have been able to restore endocrine health (adrenal fatigue) simply by repairing the mitochondria. In general, healthy mitochondria are important to recovering from any illness. This is a result of the accelerated repair of damaged membranes but also by providing more ATP energy.
• Lipids are important not only to mitochondria membranes, but to the membranes of all the cells in the body. Glycerophospholipids are the main lipid used in cell membranes. Plasmalogens, Phosphatidates, Phosphatidylcholines, and other phospholipids are all Glycerophospholipids. Many of the lipids you can buy are ineffective either because they have oxidative damage from poor handling or they are of the wrong type. Consuming damaged lipids can cause problems because the body takes many of these in and tries to use them. Professor Nicolson has consulted with Nutritional Therapeutics that makes NTFactor and Researched Nutritionals that makes ATP Fuel. 23:00, 41:00
• People that are old or sick for any number of reasons can’t keep up with membrane damage and this is one example when taking lipids can help. Another example is people with chemical exposures. Taking extra lipids can help clear toxins because many of these chemicals get trapped in fat. The lipids soak up these fat-loving (hydrophobic) chemical molecules. This is a slow but effective process.
• FIR saunas can help bring out hydrophobic chemicals and this is enhanced with lipid supplementation.
• Lipid replacement reduces detoxification symptoms including those associated with cancer therapy. This is a result of repairing damaged cells. As a result, cytokine levels are lowered. Also, lipid supplementation can lower homocysteine levels and bad cholesterol levels. Taking NTFactor the day after chemo treatment dramatically reduces side-effects of fatigue, nausea, etc.
• It takes between 10 days to 3 months before the maximum benefit from lipid replacement is seen. Stopping lipid replacement results in a return of symptoms unless the underlying cause is addressed.
• There are no known adverse side-effects with lipids. Some patients take several grams per day.
• Professor Garth mentioned looking for products at NTFactor and his website, The Institute for Molecular Medicine, for additional studies. 53:30

On Research Nutritionals website, we learn about the effectiveness and dosage of NT Energy Factor. People with moderate to severe fatigue experienced a 40% reduction of symptoms within eight weeks. As mentioned in the Show Notes, additional benefit may be had up to three months after starting lipid replacement. The study started participants on 2 tablets of NT Factor Energy with each meal for the first two months, and then reduced this to 1 tablet with each meal.

Personally, I’m taking Allergy Research Group – NT Factors Energy Lipid Powder because it’s less expensive. According to my calculations, 3/8th of a teaspoon of the lipid powder should roughly equal the NTFactor found in two NT Factor Energy tablets. This means there are 80 servings in a 150g container of NTFactor lipid powder at a cost of $51 – as of October 2015. I prefer taking my NTFactor lipids separately and add in other supplements as opposed to using ATP Fuel.

The Science Behind NT Factor

CoQ10 & the Rest

Well, the last piece I’m going to touch on in this article is Coenzyme Q10 (CoQ10). I’m sure you’ve all heard about the importance of supplementing with CoQ10 for folks taking Statins to lower cholesterol. What’s important to this conversation is that CoQ10 supports mitochondria function. In addition, it has the added benefit of not upregulating detoxification, so it may be taken by those that are working on clearing detox blocks.

Coenzyme Q10 Increases Brain Mitochondrial
“…to help repair mitochondria without stimulating detoxification. “Coenzyme Q10 is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes.”
Clinical Aspects of Coenzyme Q10: An Update
“The latest findings highlight the beneficial role of coenzyme Q10 as coadjuvant in the treatment of syndromes, characterized by impaired mitochondrial bioenergetics and increased oxidative stress…”

Switching topics to “drainage”, getting the kidneys, liver, and gallbladder to “drain” well (move toxin laden fluids) is important. For the liver and gallbladder, Chris mentions bitters like Gentian, Dandelion and Milk Thistle. Kidney drainage is improved with herbs like Solidago, Corn Silk, and Juniper. Myrrh (Chris’s favorite), Burdock, Dandelion, and Echinacea are good for blood clearing. Sensitive patients must start with homeopathic solutions of drainage remedies like the PEKANA Big Three Basic Detoxification & Drainage Kit from BioResource. The QuickSilver website suggests this Liver Detox regimen. In addition, we all know the benefits of organic coffee enemas in helping to clear the liver and move bile.

So that’s it. I’m wrapping up this article. For those with blocked detox, start very slowly with GABA to calm neuro-excitation and then follow with DIM to remove Nrf2 blocks. Along the way, support the ECM and consider taking PC with CoQ10 for mitochondria health. When the time comes to up-regulate Nrf2 for enhanced detoxification, make sure to get B-complexes and GSH onboard before taking up-regulators like Lipoic Acid (Chris’s favorite), polyphenols like Haritaki, and sulfur compounds. Don’t foget, if you have CBS SNPs, look at supplementing molybdenum with sulfur compounds.

Helping the Unusually Sensitive Patient to Heal Show Notes

The Cutting Edge of Health and Wellness – Wayne Anderson, ND – September 18, 2015

• The show focuses on treating “sensitive” patients. They begin by making distinctions between sensitive versus toxic. Sensitive people react quicker to smaller doses of compounds. They have more frequent side-effects to drugs and herbals. They have less neurological symptoms like brain fog and chronic pain than the toxic person. They’re more sensitive to foods. They’re more active but crash easier than the toxic person. They can exercise for longer periods compared to toxic people. Sensitive people will react almost immediately when exposed (headache, dizzy) but will recovery fairly quickly. Toxic people are more “dull and flat”. When toxic folks are exposed, they’re slow to recognize trouble and it takes 2-3 days to recover.
• Dr. Nathan mentions he’s working with Dr. Robert Naviaux, M.D. using a Metabolomics assay to help distinguish between these two types of patients.
  For Scientists At UC San Diego, The Effort To Conquer Autism Is Personal
  “A professor in the departments of Medicine, Pediatrics and Pathology, Naviaux is a highly regarded authority on mitochondria—the tiny power plants in all cells, whose dysfunction can result in an alarming array of metabolic diseases.”
  Metabolic Features of the Cell Danger Response
  “The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes…”
• To prevent overload, sensitive patients should be given less treatment. When certain metabolites like histamine are in excess or the enzyme Diamine Oxidase (DAO) that breaks down histamine is low, the sensitive patient will react more. Note: High histamine is related to under-methylation and consequently the ability to detox and repair. 9:00
• People that absorb oxalates tend to be more sensitive. People that have high porphyrins are more sensitive. Also, those with internal oxidative stress from metabolic imbalance are more sensitive.
  Oxalates: Test Implications for Yeast & Heavy Metals
• An example is Mast Cell Degranulation Disorder that causes the cells of the gut to release histamine at the slightest provocation including even drinking water for some. These people bloat after eating and can only eat a few foods. 13:00
• Anderson believes many sensitive patients have overwhelmed livers – clogged ducts, low P450 enzymes, toxic chemicals, etc. An overloaded liver causes the gallbladder to become sluggish. He focuses on using drainage remedies to help the liver and gallbladder detoxify. He also works on the gut as it is often inflamed from histamine, bad bacteria, etc. along with clearing the spleen, lymph system, and kidneys. The net effect of toxin overload is that these patients become “waste recyclers” that often spiral down over time. Often, it’s best to start getting these organs working better before trying to kill pathogens.
• Dr. Nathan believes that when you treat patients, it “knocks off toxins” that make the person worse. Consequently, it’s really important to focus on detoxification along with killing pathogens. 23:00
• Anderson believes infections like Lyme can trigger other issues like porphyria. In fact, chlamydia pneumoniae is often associated with Lyme. Killing Lyme also kills chlamydia pneumoniae causing a release of porphyrins. When this happens, the die-off reaction doesn’t last a couple days but instead lingers on for weeks.
• Heavy metals block methylation resulting in a build-up of toxins in the cells. 27:00
• The unusual symptoms often are the most telling in terms of treatment. Doctors need to take thorough histories. 44:00
• When it’s not clear what’s driving symptoms, the gut is a good place to start including looking for parasites. Dr. Anderson says 60-80% of his patients have parasites. 52:00
• Dr. Nathan says mold is the most common sensitizer with the second most common being Lyme along with Bartonella and Babesia co-infections. Bartonella and mold toxins present the same and are often both found in patients.
• Trying to treat an infection in sensitive patients too aggressively makes it harder for the immune system to find balance and can cause more harm than good.

Detox Series

1. AGA – Diet – Detox
2. GSH Detox Protocol
3. Blocked Detox