Workshop Q+A Part 2 - Mitochondria and Toxins

On August 5-7, 2022, GPL Academy hosted the Mitochondria and Toxins: Advanced Strategies & Protocols in Chicago and live-streamed online. The following Q+A is a grouping of responses from the workshop presentations.

The material contained within this article is not intended to replace the services and/or medical advice of a licensed healthcare practitioner, nor is it meant to encourage diagnosis and treatment of disease. It is for educational purposes only. Any application of suggestions set forth in the following portions of this article is at the reader's discretion and sole risk. Implementation or experimentation with any supplements, herbs, dietary changes, medications, and/or lifestyle changes, etc., is done so at your sole risk and responsibility.

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Joseph Pizzorno, N.D.

Joseph Pizzorno, ND is a world-leading authority on science-based natural medicine, a term he coined in 1978 as founding president of Bastyr University. A naturopathic physician, educator, researcher and expert spokesman, he is Editor-in-Chief of PubMed-indexed IMCJ, Chair of Board of IFM, board member of American Herbal Pharmacopeia, and a member of the science boards of the Hecht Foundation, Gateway for Cancer Research and Bioclinic Naturals. Author or co-author of six textbooks and 7 consumer books (Encyclopedia of Natural Medicine, The Toxin Solution), he has been an intellectual, political and academic leader in medicine for four decades.

Q: What was the supplement you recommended when using NAC for a patient?   

A: N-acetylcysteine is readily available from many good companies. I use Natural Factors/Bioclinic Natural since I am a scientific consultant for them. I like adding fiber to help bind the toxins that NAC helps excrete. 

Q: How do you detox arsenic? What nutrients or binders do you use to detox arsenic?  

A: The best detox for arsenic is avoidance. Its half-life is typically 2-4 days, so avoidance is effective. The rate of detox can be increased by consuming dietary folates, not folic acid, and flavonoids such as phloretin.  

Q: What are your thoughts on NAD and Glutathione IV therapy?  

A: IV therapy can be helpful but should only be done by those who are very skilled and when the safer oral interventions are not adequate. Before giving anyone IV glutathione, be sure the blood is cleared of mercury. 

Q: For someone with deletions in glutathione-S-transferase, what is the best way/form to increase GSH?  

A: This is really two different issues. Glutathione-S-transferase uses glutathione, does not produce it. Oral NAC and liposomal glutathione increase GSH. 

Q: With a sulfa allergy which is directly correlated with that deletion, is glutathione supplementation not recommended or cautioned?  

A: I am not aware of sulfa allergy being a contraindication for glutathione. 

Q: Is there any connection between the malate you are speaking about in your lecture and supplements with malate, such as calcium and magnesium malate?  

A: Same molecule. Several minerals have been bound to Krebs cycle intermediates, supposedly to improve absorption and utilization. 

Q: Do you have data on the effects of Metformin on Cplx 1 - causing acidosis?  

A: Yes, Metformin does indeed cause pericellular acidosis. Anything which increases lactic acidosis causes acidosis, such as biguanides (metformin), antiretrovirals, statins, many more. 

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Elena Villanueva, D.C.

Dr. Elena Villanueva, producer and co-host of the 5 Part Series Mental Health Masterclass, the 5 Part Series Inflammation Masterclass, and The Leaky Brain Summit, is an internationally recognized crusader for ending the global chronic illness & mental health crisis by educating both the public and health professionals that mental health & other chronic illnesses are actually a body or brain health issue and not a disease. Elena has been featured on multiple occasions on FOX news, MSN, Healthline, Houston Chronicle, Anxiety and Depression Secrets Docu-Series, and several other documentaries. Dr Villanueva teaches on stages around the globe on evidence-based approaches for finding the underlying causes of chronic illness and brain-related conditions and how to use holistic and 'whole person' approaches to restore brain-related disorders and other chronic diseases.

Q: Do you have any experience with devices such as the NanoVi, to assist with mitochondrial function and proper folding of proteins? 

A: I do not. I do however have experience with bioenergetics and how that shows improvement of mitochondrial function. In fact, a recent study was just completed by a university out of California showing the biological improvements in mitochondrial function and replication with the use of bioenergetics. 

Q: What is your glyphosate protocol? 

A: Glyphosate has a short half-life and is one of the toxins that can leave the body without help of added supplementation. However, the client must discover and stop his/her exposure to the glyphosate for levels to come down. When we detox, our protocols are designed to detox ALL toxins, chemical, myco, and HM’s… this simplifies the protocols (and reduces the costs) for patients/clients and makes them much more compliant and with that compliance you and your patients/clients will see more consistent positive outcomes. 

Q: Are you concerned when toxins don't increase on testing between months 4-6 indicating they are not coming out as much? 

A: Not as much of a concern as it is an indicator that the client/patient is not compliant with the protocols. By month 4-6, if they are compliant with reducing their exposure and taking their recommended supplements and food protocols, you will see one of the following two scenarios: 

1. Their toxins will show higher indicating they are releasing toxins from their body 

2. Their toxins will show lower because they have already released a good portion of their toxic load quickly. 

If they are still showing the same levels after 3 months on deep detox, they are either still exposing themselves, not taking their protocols as recommended, or both. Keep in mind this is reflective for the protocols in our practice and may vary based on the protocols you establish. 

Q: For a colonized fungal infection in the gut do you cycle, rotate, or use one over-the-counter anti-fungal at a time? 

A: It depends. If the client/patient is not showing symptoms directly related to the fungal infection I focus instead on the broader picture with my deep detox protocols which also address fungal infections. If they are having considerable symptoms from the fungal infection, then yes, I put them on a fungal protocol first to mitigate their symptoms. Then I resume with my 12-month protocol system. 

Q: I have a 34-year-old female with extreme CFS, ADHD and depression for 12 years. Organic Acids Test results are within normal limits except for borderline high arabinose and low Vitamin C. MycoTOX Profile results are positive for ochratoxin A, citrinin, and chaet (from previous home). Dealing with severe debilitating brain fog, memory issues, poor executive function. She wants to go back on Adderall but worried that it will affect mitochondria/adrenals. Any insight on the negative effects of psychostimulants on CFS? 

A: We prefer to avoid those at all costs because of the negative side effects and potential damage they can have. If you are using effective protocols your client should be able to detox her mold toxins in an average of 9 months and you can include added brain and energy support during this time to help her… that could look like added high dose DHA, phospholipids, AA therapy, adrenal support, or even addressing vitamin and /or mineral deficiencies (according to labs) because those are common and can exacerbate brain fog, memory, etc. 

Q: Can you comment on use of Vitamin D with Vitamin K? Why do you use Vitamin K? 

A: High level overview on this: there are a percentage of people who have the VDR taq genetic variant and need Vitamin K to process their Vitamin D. Also, it simply ensures that the Vitamin D has the best chance at being utilized by the body. So, we are covering the bases without having to add more costly testing like genetic testing to their overall costs.  

Q: Just wondering the rationale for doing just the methyl B12/folate vs. a good B complex with activated forms? How do they replete the other B vitamins if given just the folate and B12? 

A: We do like using a good B complex with the methylated B12 and folate. However, at this time we have not found, nor have we been able to formulate a B complex that has the high therapeutic grade doses of methyl B12 methyl folate we prefer to use… therefore we use just the Methyl B12 and Methyl folate that we created in our brand at BioOne Sciences. There are some clients that we will put on additional B Complex. And all our clients that go into a year 2 program with us (which is most of them), get switched over to a B Complex (with the methylated B12 and Folate). We haven’t had an issue with repletion of the other B’s. 

Q: Could we get your pdf form for patients to record their lab results and significance? 

A: Please reach out to us at info@modernholistichealth.com We will be emailing our practitioners who are interested in learning our systems with information on our first live, in person training that we want to do and from that training we will share all our forms and protocols with you. 

Q: What is in your tox bundle? OAT, MycoTOX Profile, Heavy Metals and what else?  

A: Yes, those plus the environmental toxins and Glyphosate. 

Q: What was the biofilm agent you said you used?  

A: It’s our TCG Activation product that is humic/fulvic based.  

Q: Is it normal for a patient to get full body edema during a detox? 

A: No, it is not normal. It sounds like their detox pathways are not open and you should have your patient stop immediately. Be sure you check their blood labs for kidney and liver function, make sure they are having full evacuation bowel movements, and check for methylation challenges with some genetic testing. You might also get a history on any issues with their lymphatic system as well and determine if they have any allergies or sensitivities to any of the ingredients in the supplements you have them on. 

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LEARN NEW WAYS TO HELP PATIENTS WITH DIFFICULT-TO-DIAGNOSE AND CHRONIC HEALTH ISSUES.

The tests discussed throughout each workshop are all used to help identify exposure sources and biochemical imbalances in individuals with chronic health conditions. The Organic Acids Test (OAT) contains multiple markers which may be influenced by environmental and mold toxins. Often, the combination of the OAT, MycoTOX Profile, and GPL-TOX Profile can be used to help identify how a patient might be getting exposed, as well as assist with correlating their symptoms back to these sources. Determining the underlying causes of chronic illnesses for patients is the key to integrative medicine, not just treating the symptoms. The Great Plains Laboratory continues to find new ways to detect these causes of many illnesses and study the correlations between the results and conditions.

Registration includes:

1. Ability to purchase GPL tests discussed throughout the program at special workshop-only discounted rates.

2. 60-day access to the full conference recordings.

3. Permanent PDF access to each speaker’s slides.

4. The option to purchase continuing education credits (5 credits per day), whether you attend in-person, watch Live Online, or watch the conference recordings at a later date! See detailed information about credits.

5. An interactive Workshop Hub website where you can live chat and network with attendees and ask questions to the speakers.

6. And last, but most certainly not least, qualified practitioners will receive a free OAT.

Kidney: The Often-Forgotten Part of Detoxification

Quick glance

• Toxicants can be absorbed via three main pathways: respiratory tract via inhalation, integumentary system via direct skin contact, or gastrointestinal tract (GI) via consumption (2).

• Chemical toxicants passing through the kidneys can be measured in urine.

• Included are recommendations that can be put in place to ensure your patients’ kidneys function well and are prepared to do the work of detoxification of any type of toxic intruder.

By: Lindsay Goddard, M.S., R.D.N., L.D.

Too often the liver and the GI tract are the first two organs that spring to mind when the word detoxification is mentioned.  Granted, these two systems do a lot of important work in removing toxins from the body, but another vital organ that detoxifies the body are the kidneys.

The kidneys are instrumental in detoxifying a wide range of end products of metabolism. Toxins which have gone through phase II liver detoxification or direct excretion, and excess water-soluble nutrients such as B vitamins and Vitamin C are also filtered out by the kidneys (1). The kidneys allow these compounds to be removed from the body via urine, which along with stool, is the major pathway of elimination. Sweat, tears, saliva, hair, nails, and milk, all are a part of elimination as well, but to a lesser degree (2). In this blog we will discuss the kidneys and the roles they play in elimination of toxins, especially ones found on the MycoTOX Profile and the GPL-TOX Profile.

How the Kidney Works

Let’s first review the kidney and its function. It is a complex, and sophisticated organ that is so important, nature felt two were necessary. These bean shaped organs have many functions, but one of the major roles is filtering out excess water and cleaning the blood from toxins. They are so efficient, they can clean all the blood in the body in just under an hour on average (3).

The three layers of the kidney are the cortex (outer layer), medulla (inner part), and the central pelvis. Unfiltered blood travels through the cortex via the renal artery into the nephron. The nephrons are basically the blood filtering units composed of bundles of blood vessels called glomerulus, within the Bowman capsules.

When the blood passes through the glomeruli, within the medulla, waste and excess water diffuse into the capsule. The excess is then carried away by tubules to form urine, while useful substances that can be recycled are absorbed by the capillaries. The filtered blood is sent back to the heart via the renal vein. The urine is then carried through the tubules to the central pelvis, which is then emptied into two tubes called ureters, ultimately going to the bladder (2).

To be fair, the kidneys have other notable functions as well, such as release of certain hormones, stimulation of red blood cell production, and supporting fluid homeostasis within the body, but those details are outside the scope of this blog.

Figure 1: Basic Structure of the Kidney. Adapted from the University of Michigan. http://websites.umich.edu/~elements/web_mod/viper/kidney_function.htm (4).

Eliminating Toxicants

How do toxicants enter our systems? Toxicants can be absorbed via three main pathways: respiratory tract via inhalation, integumentary system via direct skin contact, or gastrointestinal tract (GI) via consumption (2).

The pulmonary route of absorption can be quite significant as the lung tissue is highly vascularized and has a larger surface area. The GI tract also has a larger surface area, but pH has a greater influence on this systems ability to absorb.

The skin isn’t as permeable (unless there is an opening), and it’s mainly the lipid-soluble compounds that are the most worrisome, as they can be absorbed more efficiently via passive diffusion. In a very, very simplistic view, once the toxicant is absorbed via the skin or respiratory tract, it ultimately ends up in the blood where it can travel throughout the system.

The GI tract absorption is different in that if it passes through the membranes, it will likely pass through the liver before it enters general circulation. Ultimately, the body’s goal is to eliminate toxicants. As noted previously, urinary excretion via the kidney is an extremely important mechanism for this to occur.

When toxicants enter the kidney, a large amount are filtered across the glomerulus with relative ease if they are not protein bound in the plasma and/or are relatively small. Ionized toxicants tend to remain in the urine, while toxicants that are more lipophilic can re-enter renal circulation through reabsorption (2). This is the case with Ochratoxin A (OTA) from Great Plains Laboratory’s MycoTOX Profile.

OTA is quite nephrotoxic, and this is likely because as it is going through organic anion transport in the tubules of the kidney, it is actively being reabsorbed. It is also transported with smaller carrier proteins, allowing the compound to pass through the glomerular membrane at an increased rate (5-7). Other than OTA, there are other mycotoxins that can impact the kidneys while they pass through it.

Other Ochratoxins, particularly C, can be damaging to the kidney, though the direct mechanism of action is still being investigated (8). Mycotoxins from Fusarium and Aspergillus, particularly some of the aflatoxins (B2, G1, M1 and M2), and the T2 toxin have all been documented in literature to influence the kidneys during excretion (9-12).

Evidence also indicates that Gliotoxin has cytotoxicity to renal epithelial cells, even at lower concentrations (13). Verrucarin A and Roridin E have both been found to be highly absorbed into the kidneys, even more so than the liver or lungs (14, 15).

Mycophenolic Acid (MPA) goes through glucuronidation in the kidneys, and is mainly eliminated via urine by active tubular secretion and glomerular filtration (16-18). These mycotoxins are all measured on the GPL’s MycoTOX Profile, and can be a helpful clue into what assaults are occurring on the kidneys, along with the other added benefits of running a MycoTOX Profile.

Eliminating Chemical Toxicants

Chemical toxicants passing through the kidneys can be measured in urine. The structure of the chemical compound has a large influence on its excretion through the kidneys. The more lipophilic the compound, the more likely it will be reabsorbed, or in other words, have a difficult time eliminating. The more hydrophilic compounds are, the easier they are to eliminate (1,2).

Please do not think of chemicals that are easy to eliminate as not as toxic as others. Though they may not bioaccumulate as well, the damaging effects they can have while in the system prior to elimination are still of concern, especially with chronic exposure.

Saturation plays a factor in the kidney’s ability to eliminate, meaning it only has a certain capacity it can filter. Mitochondrial function can also be a factor since the ATP generated from the citric acid cycle can help actively move the toxicants out (1).

When you look at toxicants on the GPL-TOX Profile, one can get an idea of the more water-soluble compounds by the metabolite name. If the metabolite is the same name as the parent compound, then it did not have to go through much metabolism to be eliminated. Toxicants such as Diphenyl Phosphate, Perchlorate, and 2,4-Dichlorophenoxyacetic Acid (2,4-D) all fit that description. The others are more complex, and it gets even more complex with heavy metals, but we can save that for another blog.

How to Support the Kidneys

So, we now know what the kidneys do, and what assaults can negatively impact them, the next question  is how can I support it? How do we take care of the kidneys so they can do their job(s) well?

If you have been looking into the world of environmental toxins, it is abundantly clear that the most important thing to do is remove/reduce the toxicant loads. That is a whole other topic, and some really great blogs/webinars have been produced that already delve into mold testing for your body and your home as well as identifying toxins in your environment. If you don’t remove the source, no matter what you do, the problem will persist.

Additional Recommendations

Below are some additional recommendations that can be put in place to ensure our kidneys function well and are prepared to do the work of detoxification of any type of toxic intruder.

1. Drinking enough clean water. Keeping fluid moving through the body and the kidneys will help them run efficiently and get the toxicants out quicker. There is no specific amount, as everyone is different, but a good general guideline is half the body weight in ounces (e.g. a 120lb person should consume around 60oz of water, minimum). Also, check the urine color to help. Too yellow means more water, clear urine means too much water, as it should have a tinge of yellow to it.

2. Decrease Sodium and Phosphorus Intake. Sodium and Phosphorus in excessive amounts (not the kind in natural foods, rather the kind in processed foods) can cause imbalances in the kidneys and put additional strain on them, causing them to work harder.

3. Movement. Improving blood and lymph flow through movement can help the kidneys function optimally. Walking, Yoga (added bonus with the breathing - that’s a part of detoxing too believe it or not!), bicycling, etc. Whatever movement brings joy, it will help.

4. N-acetyl Cysteine (NAC). NAC has been known to protect kidneys from various assaults. A meta-analysis found that supplementation with NAC improved glomerular filtration rate and serum creatinine, indicating supportive effects (19).

5. Functional Foods. Various foods can have direct effects on kidney improvement. Beets can support better blood flow throughout the system, in particular the kidneys (20). Blueberries and cabbage have been shown to help with reducing inflammation in the kidneys (21, 22). Curcumin has evidence suggesting it can be helpful in protecting the renal mitochondria (23). Cinnamon, although the effects are not directly towards the kidneys, can help control blood sugar which in turn helps support the kidneys (24).

6. Be aware that some herbals can be toxic for the kidneys, while other herbs may have influences on kidney function, if the kidney is already in distress. Be mindful with herbal tinctures depending on the current state of the kidney (25).

There are other supports for the kidneys out there, but these should at least be a good start.

The kidneys are incredibly important in helping with the elimination of toxicants, and it is important to support them with lifestyle and diet. We need to support our bodies for the environment in which we live and take care of our systems to ensure they can work properly to withstand the challenges.

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Lindsay Goddard, M.S., R.D.N., L.D.

Lindsay Goddard is a Registered Dietitian, with a Master’s Degree in nutrition. She has been involved in integrative and functional nutrition for over 10 years. She has worked in a variety of specialty areas such as genetic and metabolic disorders along with NICU and pediatrics. She also had a private practice where she specialized in gastrointestinal disorders. Lindsay now works as a GPL consultant and is currently earning her graduate certificate in Toxicology through The University of South Florida.

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References: 

1. Pizzorno J. The Kidney Dysfunction Epidemic, Part 1: Causes. Integr Med (Encinitas). 2015 Dec;14(6):8-13. PMID: 26807064; PMCID: PMC4718206.

2. Richards I and Bourgeois M. Principles and Practice of Toxicology in Public Health. 2014. ISBN: 9781449645267

3. A, Fardon J, Friend J, Temple N, Routh, K. et al. The Amazing Body. Smithsonian. 2017. First American Edition. Pg. 154-155. ISBN: 978-1-4654-6239-8

4. University of Michigan. Kidney Function. http://websites.umich.edu/~elements/web_mod/viper/kidney_function.htm

5. Khoury A and Atoui A. Ochratoxin A: General Overview and Actual Molecular Status. Toxins. 2010. 2(4): 461-493. PMID: 22069596

6. Gupta, Ramesh C. Veterinary Toxicology. Basic and Clinical Principles 3rd edition. 2018. 

7. Plumlee KH. Mycotoxins Toxicokinetics. Clinical Veterinary Toxicology. 1st Edition. 2004

8. Abramson D. MYCOTOXINS Toxicology. Encyclopedia of Food Microbiology. 1999. Pages 1539-1547. ISBN 9780122270703. https://doi.org/10.1006/rwfm.1999.1150.

9. Mohan J, Sheik Abdul N, Nagiah S, Ghazi T, Chuturgoon AA. Fumonisin B2 Induces Mitochondrial Stress and Mitophagy in Human Embryonic Kidney (Hek293) Cells-A Preliminary Study. Toxins (Basel). 2022 Feb 25;14(3):171. doi: 10.3390/toxins14030171. PMID: 35324667; PMCID: PMC8954924.

10. Coppock RW, Dziwenka MM. Mycotoxins. Biomarkers in Toxicology. 2014. Pages 549-562.ISBN 9780124046306. https://doi.org/10.1016/B978-0-12-404630-6.00032-4. https://www.sciencedirect.com/science/article/pii/B9780124046306000324. 

11. Nassar AY, Megalla SE, El-Fattah HM, Hafez AH, El-Deap TS. Binding of aflatoxin B1, G1 and M to plasma albumin. Mycopathologia. 1982 Jul 23;79(1):35-8. doi: 10.1007/BF00636179. PMID: 6811900.

12. Adhikari M, Negi B, Kaushik N, Adhikari A, Al-Khedhairy AA, Kaushik NK, Choi EH. T-2 mycotoxin: toxicological effects and decontamination strategies. Oncotarget. 2017 May 16;8(20):33933-33952. doi: 10.18632/oncotarget.15422. PMID: 28430618; PMCID: PMC5464924.

13. Gayathri, L., Akbarsha, M. & Ruckmani, K. In vitro study on aspects of molecular mechanisms underlying invasive aspergillosis caused by gliotoxin and fumagillin, alone and in combination. Sci Rep 10, 14473 (2020). https://doi.org/10.1038/s41598-020-71367-2

14. Amuzie CJ, Islam Z, Kim JK, Seo JH, Pestka JJ. Kinetics of satratoxin g tissue distribution and excretion following intranasal exposure in the mouse. Toxicol Sci. 2010;116(2):433-440. doi:10.1093/toxsci/kfq142

15. Amuzie CJ, Islam Z, Kim JK, Seo JH, Pestka JJ. Kinetics of satratoxin g tissue distribution and excretion following intranasal exposure in the mouse. Toxicol Sci. 2010;116(2):433-440. doi:10.1093/toxsci/kfq142

16. Food and Drug Association. Mycophenolic acid (Myfortic). https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050791s002lbl.pdf

17. Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, and KE.PharmGKB. Mycophenolic Acid Pathway. Pharmacogenetics and genomics.2014. PMID:24220207. https://www.pharmgkb.org/pathway/PA165964832

18. Hooijmaaijer E, Brandl M, Nelson J, Lustig D. Degradation products of mycophenolate mofetil in aqueous solution. Drug Dev Ind Pharm. 1999 Mar;25(3):361-5. doi: 10.1081/ddc-100102183. PMID: 10071831.

19. Ye M, Lin W, Zheng J, Lin S. N-acetylcysteine for chronic kidney disease: a systematic review and meta-analysis. Am J Transl Res. 2021 Apr 15;13(4):2472-2485. PMID: 34017406; PMCID: PMC8129408.

20. Kolluru GK, Kevil CG. Beets, bacteria, and blood flow: a lesson of three Bs. Circulation. 2012 Oct 16;126(16):1939-40. doi: 10.1161/CIRCULATIONAHA.112.136515. Epub 2012 Sep 19. PMID: 22992323; PMCID: PMC4078643.

21. Nair AR, Masson GS, Ebenezer PJ, Del Piero F, Francis J. Role of TLR4 in lipopolysaccharide-induced acute kidney injury: protection by blueberry. Free Radic Biol Med. 2014 Jun;71:16-25. doi: 10.1016/j.freeradbiomed.2014.03.012. Epub 2014 Mar 19. PMID: 24657730.

22. Asiwe JN, Kolawole TA, Anachuna KK, Ebuwa EI, Nwogueze BC, Eruotor H, Igbokwe V. Cabbage juice protect against lead-induced liver and kidney damage in male Wistar rat. Biomarkers. 2022 Mar;27(2):151-158. doi: 10.1080/1354750X.2021.2022210. Epub 2022 Jan 3. PMID: 34974788.

23. Trujillo J, Chirino YI, Molina-Jijón E, Andérica-Romero AC, Tapia E, Pedraza-Chaverrí J. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol. 2013 Sep 17;1(1):448-56. doi: 10.1016/j.redox.2013.09.003. PMID: 24191240; PMCID: PMC3814973.

24. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003 Dec;26(12):3215-8. doi: 10.2337/diacare.26.12.3215. PMID: 14633804.

25. National Kidney Foundation. Use of Herbal Supplements in Chronic Kidney Disease. 2009. https://kidneyhi.org/use-of-herbal-supplements-in-chronic-kidney-disease/

Webinar Q+A: Autoimmune Disease and Fungal Infections

On May 19, 2022, The Great Plains Laboratory hosted Autoimmune Disease and Fungal Infections webinar with Kurt Woeller, DO. Fungal infections of various types can initiate immune dysfunction leading to systemic infection and serious disease. The overuse of antibiotics and subsequent microbiome disruption, along with other factors, e.g., nutrient imbalances, mucosal surface damage, can increase the potential for autoimmunity and related diseases. Various immune cells and their cytokines are intimately involved in regulating mucosal reactivity to opportunistic fungus. It is the dysregulation of these factors which create the potential for fungal related autoimmunity. This webinar will explore these details and more.

The following Q+A is a grouping of responses from Dr. Woeller’s presentation.

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Webinar Attendee Q+A

Q: Should I be concerned about fungal resistance to fluconazole?

A: There is the potential for resistance to any antifungal or antibiotic. However, for the most part it still works well against many yeast species, including Candida.

Q: What factors make a fungal infection chronic and persistent, prone to relapse?

A: There are many including poor overall health, lack of microbiome diversity, ongoing inflammation, particularly in the digestive system, chemicals like glyphosate, mold and mycotoxin exposure, poor diet, etc.

Q: What are the implications of a leaking breast implant and how that affects thyroid autoimmune and inflammatory autoimmune, and would this eventually help to cause fungal infection/candida?

A: Fungus could certainly take advantage of a situation like this. You will need to research the specific mechanisms involved regarding breast implants, but I am sure it involves immune dysregulation involving Th1, Th2, and Treg cells.

Q: Can systemic candida infections be the root cause of seborrheic eczema, dermatitis, and dandruff?

A: I am sure they could be or at least play a role. Do some research into this area as this would be worth knowing more about.

Q: I have sometimes seen slightly high chloride in serum of my patients.  Does the hypochlorous acid release during the Neutrophil activity ever account for the finding of slightly high Chloride in serum of patients with CFS and Candidiasis?

A: Good question, but I do not know. Most likely is it not a major factor as the hypochlorite ion is acting at a local area.

Q: How can the Innate immune system have a memory component?

A: I am not aware of innate immunity with regards to memory cells, but certain B-cells, specifically B-1 B cells (from the spleen, bone marrow, and peritoneum) and MZ B cells (spleen), produce natural antibodies like polyreactive IgM or Natural IgM (nIgM). Perhaps there is a recall mechanism in place for these nIgM? The role of nIgM is significant, including in the assistance of phagocytic cell activity in engulfing an apoptotic cell. Other mechanisms include complement cascade activation against pathogens, e.g., bacteria and direct pathogen neutralization, e.g., virus. Check out the article by Panda and Ding titled Natural Antibodies Bridge Innate and Adaptive Immunity in the Journal of Immunology, September 2021.

Q: What is an example of a genetically susceptible individual?

A: Certain types of human leukocyte antigen (HLA) patterns are genetic linked. For example, HLA-B27 is associated with increased risk for reactive arthritis secondary to certain gut bacteria. Ankylosing Spondylitis is another disease where the immune system attacks the spine and is linked to cross-reactivity to various PAMPs in B27 individuals.

Q: Does the website https://candidamasterycourse.com/ go over protocols for overcoming candidiasis?

A: Yes. We go into intervention, testing, pathogenicity mechanisms and much more in the Candida Mastery Course.

Q: Can you link here the website to get the bonus sheet?

A: https://integrativemedicineacademy.com/webinar-bonus/

The material contained within this article and webinar is not intended to replace the services and/or medical advice of a licensed healthcare practitioner, nor is it meant to encourage diagnosis and treatment of disease. It is for educational purposes only. Any application of suggestions set forth in the portions of this article is at the reader's discretion and sole risk. Implementation or experimentation with any supplements, herbs, dietary changes, medications, and/or lifestyle changes, etc., is done so at your sole risk and responsibility.

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Kurt Woeller, DO

FOUNDER OF INTEGRATIVE MEDICINE ACADEMY
Kurt N. Woeller, DO, has been an integrative medicine physician and biomedical Autism specialist for over 20+ years. He is an author of several health books including Autism – The Road To Recovery, Methyl-B12 Therapy For Autism, Methyl-B12 for Alzheimer’s Disease and Dementia, and 5 Things You MUST Do Right Now To Help With Your Rheumatoid Arthritis. He is an international speaker, educator, and practicing clinician offering specialized interventions for individuals with complex medical conditions. His health consulting practice for Autism alone is multinational with families from various countries. Dr. Woeller serves as a clinical and lab consult for Functional Medicine Clinical Rounds, as well as provides educational seminars for Great Plains Laboratory. He is co-founder of Integrative Medicine Academy (www.IntegrativeMedicineAcademy.com), which is an online training academy for health practitioners learning integrative medicine.

Organic Acids, Mycotoxins & Heavy Metals - Common Questions

The Great Plains Laboratory has been educating practitioners for over 15 years on how to help patients heal through cutting-edge testing, research and protocols. In our recent 3-Day Master Practitioner Workshop, speakers shared detailed information on how the MycoTOX Profile, IgG Food MAP and Glyphosate Test can work for you. As well as gave additional information about markers in the OAT and GPL-TOX.

The following Q+A is a response to remaining questions Dr. Woeller was unable to answer during his presentations.

The material contained within this article is not intended to replace the services and/or medical advice of a licensed healthcare practitioner, nor is it meant to encourage diagnosis and treatment of disease. It is for educational purposes only. Any application of suggestions set forth in the following portions of this article is at the reader's discretion and sole risk. Implementation or experimentation with any supplements, herbs, dietary changes, medications, and/or lifestyle changes, etc., is done so at your sole risk and responsibility.

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Kurt Woeller, DO

Functional Medicine
and the Organic Acids Test

Kurt N. Woeller, D.O. has been an integrative and functional medicine physician and a biomedical autism specialist for over two decades. He is an author, lecturer and clinical practitioner offering specialized diagnostic testing and health interventions for individuals with complex medical conditions such as autism, autoimmune conditions, gastrointestinal and neurological disorders.

Q: How does viral genome interfere with this intracellular mechanisms - EBV for example?

A: Viral infections would likely trigger oxidative stress in the cell leading to mitochondrial damage. One of the reasons for high quinolinic acid is interferon production secondary to viral infection.

Q: What’s the difference between blood spot and blood serum vitamin d test?

A: Best to ask Great Plains directly From my understanding there is no difference when looking at 25(OH)D.

Q: Which stool test do you recommend?

A: The CDSA that Great Plains Laboratory has is very good. I also do the Doctors Data GI 360 Profile too.

Q: What markers could correlate with ALS and what other tests would be recommended?

A: No specific pattern for ALS. In anyone with a chronic degenerative condition like ALS I would personally be running the OAT, GPL-TOX, Glyphosate, MycoTOX and Hair Metals Test.

Q: If a patient comes to you with medications, antibiotics, etc. And you recommend doing the OATs. Do you suspend the medications to take the sample?

A: No. I do not have them stop their medications.

Q: Do you use botanicals for yeast overgrow instead of nystatin for some individuals who cannot tolerate Nystatin?

A: Yes, all the time.

Q: This is off the yeast/mold topic but now that Dr. Shoemaker believes that most of CIRS is due to Actinomycetes, is there a test you use that is specific to this bacteria?

A: Not that I know of.

Q: Do you compound this, or do you feel that pharmaceutically available is fine?

A: Usually, the regular pharmacy is okay, but I will compound for sensitive patients.

Q: What is wrong with higher doses, e.g. 100,000 BID?

A: Only the potential for die-off.

Q: Will these also bind helpful nutrients?

A: Yes. They can and should be taken away from supplements and medications by at least a few hours.

Q: To clarify will the zeolite etc.. also bind nutrients, how to avoid this?

A: Likely, it will. Separate by at least a few hours from other medications and supplements.

Q: Is isocitrate lyase a Candida enzyme that disrupts the Krebs Cycle?

A: It’s a enzyme within its own kreb cycle that produces oxalate. So, if you have candida in the gut it has the ability to produce oxalate in the digestive system.

Q: Can you give core biotics to young children? Age 2

A: I have, but conservatively like one capsule.

Q: I'm sure you have heard speculation that there may be correlation between glyphosate use in agriculture in our country starting in the 1950's (I believe) and increasing since that time. I understand that glyphosate is very inflammatory and is a microbiome disruptor.

A: It is a major toxin to the gut microbiome from my research.

Q: Can saccharomyces boulardi impact the arabinose marker?

A: It won’t cause the Arabinose or produce it. But, instead go after Candida that produces it.

Q: Do you test the glyphosate level in your patients with a lot of abnormalities on the OAT?

A: I combine that with the GPL-TOX Profile. I am always concerned about Glyphosate with recurrent clostridia.

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Q: What’s the significance of 5 hydroxybenzoic?

A: Could come from Paraben exposure.

Q: What was the name of the site for practitioners ?

A: Functional Medicine Clinical Rounds – https://functionalmedicineclinicalrounds.com.

Q: Can you speak about SIFO in relation to OATS test?

A: Could cause a lot of markers seen on page #1. But, in my experience the OAT only suggests SIBO/SIFO and is not absolutely diagnostic for it.

Q: I have used Geova neutraval for several years. Can you please comment on why OAT is "better" test?

A: The GPL OAT has the HPHPA and 4-cresol which are really important to obtain because of their significant toxicity. Also, it has the oxalate information which is also important to obtain.

Q: Can supporting these deficiencies (B-6 etc) cause dumping of oxalates into tissues, how to avoid?

A: It is not going to drive dumping, but instead help to divert substrate away from being converted into oxalic acid.

Q: Are there specific metals that may have a higher affinity to oxalates than others? Nickel for example?

A: I do not know of all metal specificities, but Lead and Mercury are certainly high.

Q: Can collagen 20 gram increase oxalates? What about High dose vitamin c at 25 GMs? All of this is possible.

A: The prevalence with regards to this happening I do not know specifically.

Q: So is this SNPs testing to know? Or is this on the OATS Test?

A: The OAT does not have the SNPS. The genetics for oxalates would have to tested through genetic testing.

Q: Any headaches associated with oxalate?

A: Yes. They could be.

Q: Does someone need to stay on a lifelong low oxalate diet or temporarily?

A: It depends on what is causing the oxalates to be high. If it is primarily genetic based then a low oxalate diet is going to be necessary. If the oxalates are from poor nutrients, e.g. B1, B6 and/or mold or yeast produced, then the diet is likely just temporary.

Q: Can you explain your take on fat malabsorption and oxalates? I believe it is important to aid fat digestion when dealing with high oxalates.

A: Fat maldigestion will cause increase oxalate absorption.

Q: What if a patient has high arabinose and oxalic acid, but is unable to tolerate B6 and B1 supplementation?

A: Then you have to work on reducing high oxalate foods in their diet and treat the yeast as best as possible. Hopefully, in time they become more tolerant of these B-vitamins.

Q: When you do the Epsom salts baths how long do you sit in it to be effective?

A: Could be done nightly or at least 3 to 4 times per week. 15 to 20 minutes is a bath is often sufficient.

Q: What kind of diet is suggested before taking OATS test? How many days previous?

A: There are no specific diets needed prior to testing.

Q: Also, I believe there is a Epsom salt cream. Is that effective?

A: It can be, but I think the baths work better.

Q: Do you recommend avoiding high oxalate foods in the days before collecting the oat?

A: No.

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Q: Do you know how phosphatidylcholine compares to CDP-choline? Is there a reason you prefer one over the other for PLA2 inhibition? Any thoughts on Choline Bitartrate?

A: The CDP-Choline combination is what lowers PLA2. Just choline with bitrate will not do it.

Q: If you have nigh arabinose, would you avoid taking extra Vitamin C?

A: No.

Q: What does HVA/VMA ratio means?

A: it is related to the ratio between HVA (dopamine) and VMA (norepinephrine). If the ratio is high than not enough dopamine is getting converted to norepinephrine.

Q: And HVA/DOPAC indicate?

A: Ratio between HVA and DOPAC.

Q: What do it mean when all markers of Beta-Oxidation are high?

A: Problem in fatty acid metabolism with the cell.

Q: Where is lithium listed on OATS, under which heading?

A: It is not in the OAT. It is measured in a Hair Analysis.

Q: What if you’ve been taking NAC (600 mg 2 times a day) and it is not showing up on the OAT test. Why would that be? Will taking glutathione be the next step?

A: That it likely is getting converted over to Cysteine. If the glutathione is still deficient than giving glutathione directly is the next best option.

Q: Oxo-4-methiolbutyric what would cause this to be high?

A: That is a rare genetic disorder linked to Maple Syrup Kidney Disease. Low levels could occur from consuming beets, blueberries and cashews.

Q: Any thoughts come to mind with consistent eye pupil dilation in a 23-year old with AU?

A: I would first start looking at heavy metal toxicity.

Q: Is serotonin syndrome clinically significant in patient on SSRI who wants and try L-tryptophan or 5-http?

A: I personally have never seen serotonin syndrome. It is always possible if too much tryptophan or 5-HTP were taken, but not common in my experience. There may be other doctors who have more experience with this.

Q: Can you say how long you need to treat candida with botanicals, Treatment duration?

A: At least two months. It may require longer.

Q: Do you find twice daily dosing work with Biocidin?

A: Not as great compared to three times daily, but for a low level infection that is not overly bothersome for someone twice a day can work. I have some people where twice daily did the trick.

Q: Do you have to get rid of mold in the environment before you do the antimicrobial treatment for clostridia?

A: No. It is always best to work on the mold, but I have people where I am treating them while they are doing remediation.

Q: What are you favorite soil-based probiotics brands?

A: I use a lot of CoreBiotic from Researched Nutritionals and Proflora 4R from BioBotanical Research.

Q: NADB since the west coast fires have been burning so much? Or is it elevated from rubber mostly? What happened to the RA when clostridia treated?

A: Improved.

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Q: What was the dose of Biocidin you used in the RA patient for 3 months?

A: From what I recall it was two capsules three times daily.

Q: Why test when additional testing with expected positive results will not change your treatment? Or how would you change the treatment if mycotoxins, chemicals were elevated.

A: Because if the person has high Mycotoxins they are going to need to figure out where the mold is coming from. Also, I have seen patients where all the mold markers are normal on the OAT, but they have very high levels of mycotoxins.

Q: What else to look at when #56 NAC is elevated, and Indicators of Detoxification are in the normal range?

A: It could be a deficiency of the enzyme that deacetylates the NAC. I do not know of a specific test for this though.

Q: How do you dose GI Detox, when and how many?

A: For adults I have them start at one capsule twice daily between meals with a range of 1 to 3 capsules as tolerated. If a person can handle three times daily that may be preferred in real bad mycotoxin scenarios. It is all based on tolerance and person must watch out for constipation. I would suggest contacting BioBotanical Research directly for more insight and their recommendations on dosing of their products.

Q: Regarding Small Intestinal Fungal Overgrowth, is there any OAT Info that would equate to diagnosing SIFO? Perhaps Arabinose marker, plus other marker?

A: In my experience, most people with SIBO and SIFO have underlying yeast and fungal problems. Sometimes, they have clostridia too. I always run the OAT on anyone with SIFO or SIBO or who is suspected of having these issues.

Q: If a patient cannot tolerate even one drop of Biocidin do to die off, who has problems with clostridium, candida, and mold, what do you do?

A: This would require a much larger discussion about the various things going on with the patient, their environment, history, etc. In some of these cases there are not easy answers. We developed a website called Functional Medicine Clinical Rounds – https://functionalmedicineclinicalrounds.com to help practitioners work through some of these details. Research the Cell Danger Response. This is likely what is happening with your patient.

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Glyphosate, Parkinson’s Disease & Mycotoxins Questions Answered

The Great Plains Laboratory has been educating practitioners for over 15 years on how to help patients heal through cutting-edge testing, research and protocols. In our recent 2-Day OAT + TOX Workshop, speakers extolled the virtues of comprehensive metabolic tests like the Organic Acids Test (OAT) and the MycoTOX Profile to help with difficult-to-diagnose patients.

The participants heard ways of how to implement these tests along with other diagnostic assessments, as well as effective treatment methods.

The following Q+A is a response to remaining questionsour participating speakers were unable to answer during their presentations.

The material contained within this article is not intended to replace the services and/or medical advice of a licensed healthcare practitioner, nor is it meant to encourage diagnosis and treatment of disease. It is for educational purposes only. Any application of suggestions set forth in the following portions of this article is at the reader's discretion and sole risk. Implementation or experimentation with any supplements, herbs, dietary changes, medications, and/or lifestyle changes, etc., is done so at your sole risk and responsibility.

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Evan Brand

Mold, Mycotoxins, Case Studies & Protocols

Evan Brand, CFMP, FNTP is a Podcast Host, Certified Functional Medicine Practitioner and Nutritional Therapist. He is passionate about healing the chronic fatigue, obesity, and depression epidemics after solving his own IBS and depression issues. His Evan Brand Podcast has over 7 million downloads and counting.

Q: please repeat info on companies that have lymphatic support supplements.

A: Beyond balance and wish garden have lymph supports

Q: With the legalization of marijuana, I have not heard anyone discuss the mold in marijuana.

A: I have heard of moldy cannabis; you could grind it up and put it on a mold petri dish to test it

Q: How can you detect mold in coffee which is drank daily for thousands?

A: It’s a very common issue.

Q: Can you talk about how to detox children under five from mycotoxins?

A: Would prefer to discuss this on a consult, but in general, gentle binders like liquid chlorella, small doses of charcoal mixed with applesauce. Email me at office@evanbrand.com if you need more help.

Q: Do the mycotoxins cross into the eggs produced by exposed poultry?

A: Sounds reasonable to me.

Q: Which markers on the OAT are indicative of mold toxicity? And what levels are considered high?

A: Page one shows mold colonization but the MycoTOX Profile is what looks at actual toxin levels.

Q: Where would we find a source for nebulizable glutathione and a protocol?

A: Thernaturals carries the one for the nebulizer, we mix it with 2-3ml of saline and 1 cap glutathione and put into nebulizer to breathe it in

Q: Are you not concerned with using medicinal mushrooms with mold and fungal overgrowth?

A: No, I’ve never found it to be an issue, even with those that have histamine issues.

Q: What do you think about treating heavy metals with mold? Do you have an order of operations with that? And what about with EBV as well?

A: The binders are broad spectrum and we likely fix both at the same time.

Q: Is it harder to treat mold when eating high histamine foods?

A: Histamine issues due to mast cell activation and mold issues are common, lower histamine diets can be helpful to lower the work.

Q: Are you familiar with Beth O’Hara’s work with Mast Cell Activation Syndrome?

A: Yes, Beth is a very nice woman and has done a great job of educating the public about mast cell and histamine issues

Q: What sauna do you recommend? If you can’t afford a big one, what about the portable one.  Is it effective?

A: I have the ClearLight, tell them Evan sent you for a discount. I don’t know much about portable ones but heard Therasage 360 is decent.

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Q: For high dose choline, have you seen blood sugar problems increase?

A: Never

Q: Do you use either phosphatidylserine or phosphatidylcholine or use both at same time?

A: I use both at the same time for different purposes.

Q: What herbs did you use to treat H. Pylori?

A: My microbiome support 1 formula on auraroots.com

Q: Have you had much success in treating mycoplasma infection and what did you use?

A: I have success with mycoplasma using astragalus and cats claw.

Q: How did you do the test for babies from a distance? What company are you using for lyme and co-infection testing?

A: DNA connexions urine test

Q: I have a patient on binders and he can’t live without them. Given binders inhibit absorption of everything, how long can I keep him on them?

A: Forever. Ask Dr. Neil Nathan

Q: Can you state again the company you use for the petri-dishes?

A: Immunolytics

Q: Thoughts on ERMI home testing?

A: It is ok. I like petri dishes better.

Q: Herbs can be very powerful, are you concerned about doing damage to the microbiome?

A: No

Q: What have you researched to be the best HVAC filtering?  Do you recommend UV light in the HVAC system?

A: I recommend point of contact filters like Austin Air. UV is ok.

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Shanhong Lu

Glyphosate, Neuroinflammation Nation, & Parkinson’s Disease

Dr. Shanhong Lu, MD, PhD is a Internal Medicine Specialist in Mount Shasta, CA and has over 34 years of experience in the medical field. She graduated from Beijing Med University medical school in 1987.

Q: What are your best tools for detox of glyphosate?

A: Decrease exposure, Ultimate immune 8 a day, ultimate eaze 1-3 a day and OPC, with OR WITHOUT GLYCINE 4-5 GRAM TWICE A DAY- most of my 90 day data are based on 8 ultimate immune a day, please email drlu@drlumd.com for complimentary case discussions

Q: Does her approach / treatment help with epilepsy/seizure disorders patients?

A: Yes, please email drlu@drlumd.com for complimentary case discussions

Q: Cytokine storm Ebola virus works by this as probably SIDS from vaccine administration. No one has looked at routine vaccination but since vaccines with adjuvants produce a nonspecific immune provocation, wouldn’t that also be factor in Parkinson’s disease?

A: Vaccine injuries are not the cause of adult PDs because most of them have not received vaccines

Q: Even though organic foods are contaminated, do you recommend them as a better choice?

A: Absolutely

Q: Do you think an organic, plant based diet is safer overall than let’s say carnivore, with regard to levels of glyphosate?

A: I wish I could say that because I am a vegan and have been finding vegans are tested high in glyphosate (more often than meat eaters) but we have had less consequences … please email me drlu@drlumd.com since the keto people are more toxic with fat soluble toxins EDCs.

Q: Because glyphosate is a glycine mimic, would glycine supplementation help to detoxify by binding to its receptor and preventing glyphosate from binding? Do you prescribe supplemental Glycine to mitigate the effects of glyphosate exposure-injury?

A: In theory, but glycine alone will not be adequate

Q: What are your favorite tests to assess Toxic Burden?

A: The GPL-TOX Profile (Toxic Non-Metal Chemicals) and the Great Plains Laboratory Glyphosate Test.

Q: Would you name a few immune modulators please?

A: Muramyl peptide, beta glucans

Q: What lab/ tests do you use for total body burden & antioxidant SnPs? I use GPL and detox project and HRIlabs.org

A: GXsciences.com for SNPs and GPL-tox and GPL-glyphosate and oligoscan for tissue levels of minerals heavy metals and vitamins

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Q: Is L-glutamine a concern for Parkinson. I heard it may pass the blood brain barrier.

A: Do you mean glyphosate? Yes glyphosate accesses the brain via BBB also the vagal nerve from the gut enteric plexus.

Q: You said heavy metals take forever to detox. What about kiddos with mouths full of mercury amalgam fillings? Thoughts about considering that fact?

A: ClearDetox pro for life and remove amalgam fillings

Q: More specifically, how do you activate PON1 for detox of glyphosate?

A: Email me drlu@drlumd.com

Q: What are your favorite detox methods?

A: WFPB organic diet+ A systemic core detox system please email or text me at 530-925-0565 drlu@drlumd.com and we can email you a recorded webinar

Q: How do we join the group?

A: Email me drlu@drlumd.com

Q: Since glyphosate is pretty much everywhere, even if we eat organic and minimize environmental toxins… how else can we counteract the effects of it?

A: Email me drlu@drlumd.com

Q: I don’t see glycine for detoxing from glyphosate. Where is it?

A: Glycine can replace glyphosate in theory but most of our data comes from glucarate 3000 mg a day and leaky gut and stress prevention

Q: I was wondering if glyphosate is also found in organic pea protein isolate? You mentioned it is present in the organic pea protein.

A: YES and that is why I take a regimen daily to prevent accumulation- I call a cellular shower) please email me drlu@drlumd.com

Q: Is it best Ca-d-glucarate on an empty stomach. Any suggestion dose wise. Once daily BID etc mg. please and thank you

A: 3000 mg a day with or without food in my experience and make sure Glutathione deficiency is corrected and Th1 and Th2 immune system is balanced (often time during detox Th1 switches to Th2 – cytokine storm)

Dr. Shanhong Lu is looking for participants to join a national and international detox project by first making toxins visible and gather data in relationship to clinical illnesses. If interested, please contact her at drlu@drlumd.com

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Suzanne Gazda

The Neurological Effects of Mold and a Look into Integrative Neurology

Dr. Suzanne Gazda, MD has uniquely combined a dedication to outstanding care with an authentic commitment to patients as people first. From this desire to find more ways to achieve wellness as a means of treating illness came Integrative Neurology, providing you with individualized solutions specific to your health.

Q: Do you incorporate Botanical anti-fungals in your protocols?

A: Yes, I love to use botanicals . But , like Dr Shaw, I believe in most patients, antifungal RX like Itraconazole is needed to fully remove fungal colonization but I can imagine that if we use antifungal botanicals (which can also boost immune health) .. long enough, patients can improve as well.

Q: What would be your sequence of evaluations for a child with ADHD and dysgraphia, tremors after testing w/ OAT, and MOAT?

A: The same as an AE patient : MRI, NQ , Lab, Cunningham panel and in some w/u for mold and lyme and heavy metals etc.

Q: Any good practical resources how to fight the mold? EMF exposure?

A: I will defer to Dr. Shaw on this one.

Q: I am a mother with five sons 2 of which have been diagnosed with Pans/pandas. One of those two have Lyme. According to labs, we have high levels of strep in the gut, how would you suggest to break the cycle?

A: This is such a complicated question. You are welcomed to email me so we can set up a time to speak about your sons.

Q: Small amount of Chitinase is endogenous to humans no ? Chitinase in CSF would mean the body is trying to break down fungi no?

A:I believe so in a certain subset of patients , especially those that we worry have mold exposure.

Q: Which lake in Shasta is high in aluminum?

A: HERE

Q: I see a lot of recommendation for chlorophyll and spirulina but I think there would be a potential risk of BMAA exposure by ingesting these?

A: Yes, I agree depending on the source.

Q: I am a physician in OK. How do i order the Cunningham and neuroquant tests?

A: You can ask Moleculera labs to send you some kits and for the NQ…go to the Core Techs website and send info and ask for a center near you that does NQ HERE.

Q: Do you get concerned with use of D-ribose and increased acetylated glycolic endpoints?

A: This is a question I will defer to Dr Shaw . Take good care!!

Q: More on the NeuroQuant please?

A: I am soon going to have a blog on my website about the NQ …. Check back within a couple of weeks. But, I already have quite a bit of info HERE.

Q: Is the neuroquant and MRI that needs to be ordered by a physician?

A: Since in most cases they are private pay (about 300 dollars ) I suspect anyone could order / not sure.

Q: are you working with MS patients doing plasmalogen replacement?

A: I am excited to explore more and am doing that now. In my experience, so much of what we would like to do in FM…well, the patients just can’t afford to do it all. I hope that changes one day.

Q: which is Dr. Dan Goodenowe's plasmalogen replacement work?

A: The data is strong. Check back with me in a few months after I have had a few patients try this.

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Indicators of Detoxification: The Assessment of Pyroglutamic Acid

By JASMYNE BROWN, ND, MS

In assessment of the Organic Acid Test (OAT), a beneficial section is the “Indicators of Detoxification,” The first marker found in this section, marker 58, gives insight into detoxification and glutathione synthesis. As this marker increases, it can guide practitioners to the possibility of toxic exposure being a piece to the client’s clinical picture. In understanding the biochemistry of this marker, further dysfunction may potentially be prevented.

Marker 58 In this section is a urinary metabolite known as pyroglutamic acid. This is a functional marker of glutathione status.  Though it does not directly look at glutathione status, it measures the activity of the rate limiting enzymatic process in the production of glutathione. Thus, it is assessing the process of antioxidant production, and when upregulated informs us of increased stress on the system. Glutathione, itself, is the major antioxidant produced in abundance in the liver. It is composed of three amino acids: cysteine, glycine, and glutamate. In periods of nutritional deficiency, stress, increased reactive oxygen species (ROS), toxicity, mitochondrial dysfunction, cellular proliferation, Phase 2 detoxification, etc. glutathione stores are depleted, and the production status is upregulated. Prolonged glutathione depletion leads to mitochondrial dysfunction, that can be assessed on the OAT, and is directly supported with glutathione administration.

In general, the production of glutathione involves a series of enzymatic reactions that combine the three necessary amino acids for its production. On a regular basis the following process is completed to produce daily needed amounts of glutathione:

The process of glutathione production is known as the gamma-glutamyl cycle. In this cycle pyroglutamate, also known as 5-oxoproline, is degraded by the ATP dependent enzyme 5-oxoprolinase into glutamate. Glutamate is then combined with cysteine via the enzyme gamma-glutamyl cysteine synthetase. The next step is the incorporation of glycine via GSH synthetase to make glutathione itself. Glutathione is then transported out of the cytosol for use throughout the body. For the cycle to continue, reduced glutathione is transported back into the cytosol. In order to be transported back into the cell, it must be enzymatically cleaved by gamma glutamyl transpeptidase (GGT- another significant blood biomarker for glutathione status) to break it down into a cysteine-glycine complex and free glutamate. The cysteine-glycine complex is then cleaved further into the respective amino acids then transported into the cell. The glutamate is then transported into the cell as gamma-glu-aa and is transformed into 5-oxoproline via gamma glutamyl cyclotransferase. From here it can then be cleaved into glutamate via 5-oxoprolinase, continuing the cycle. This process is always happening at some extent regularly in the human body.

During this process, as glutathione is produced, there is a negative feedback loop. When in abundant supply, glutathione inhibits the gamma-glutamyl cysteine synthetase enzyme. This blocks the combining of cysteine and glutamate before being joined with glycine to form more glutathione. This is the body's way of regulating the amount of glutathione in the system. In times of oxidative stress, toxic exposure, inflammation, etc the glutathione production cycle is upregulated due to an increased need for glutathione to protect the body. When glutathione is deficient, the negative feedback loop is dysregulated allowing for more cysteine to be joined in the production of more glutathione. Since the regulation is no longer happening the entire cycle of production is upregulated. Thus, there is also an upregulation of 5-oxoproline being converted into glutamate. Because the enzyme, 5-oxoprolinase, is ATP dependent and the rate limiting enzyme of the whole cycle there becomes a buildup in pyroglutamic acid. This is because the need for glutathione production, in times of stress and toxicity, outweighs the rate in which 5-oxoprolinase can transform 5-oxoproline into glutamate. So, 5-oxoproline builds up leading to elevated urinary values of pyroglutamic acid.  Also, due to the ATP dependent nature of the enzyme, energy depletion is seen and stimulates the expression of energy depletion symptoms.

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When evaluating marker 58 on the OAT, elevations give insight to how upregulated the glutathione cycle is at the moment of testing. In instances of true elevations, out of the reference range, there is clear glutathione deficiency. It can be said that the person’s body is struggling to make adequate glutathione. In situations like this all aspects of the client’s health presentation and medications/supplements should be evaluated. Certain pharmaceuticals, like large amounts or regular small doses of acetaminophen, which is known for its hepatotoxicity, stimulate the need for more glutathione. This is especially significant when people are taking multiple pharmaceuticals that may be liver toxic and have a cumulative effect. Other things that deplete glutathione include alcohol, recreational drug use, a fructose rich diet, the natural aging process, prolonged fasting (24 hours or longer), and anything that causes increases in oxidative stress. If this has been ruled out as the cause of elevations in pyroglutamic acid, then toxic exposures can be assessed. As stated, glutathione production is upregulated during a toxic exposure. Since the body upregulates glutathione for various reasons, it's hard to pinpoint which toxin test to perform. It could be heavy metals, non-metal toxins, mold toxins, or a combination. Consider running GPL offered profiles: MycoTOX, GPL-TOX, Heavy Metal Testing.

Assessing for depleting causes is helpful in the healing process as it can open up people to environmental testing and detoxification. Pyroglutamic acid is a useful marker and upregulation can give insight to glutathione needs. 

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References

1.    CG. Alfafara, A., CG. Alfafara, K., Anderson, M., A. Anschau, L., M. Ask, V., A. Ayer, C., . . . X. Zhang, H. (1992, January 01). Microbial production of glutathione. Retrieved December 11, 2020, from HERE

2.    Francini F;Castro MC;Schinella G;García ME;Maiztegui B;Raschia MA;Gagliardino JJ;Massa ML;. (n.d.). Changes induced by a fructose-rich diet on hepatic metabolism and the antioxidant system. Retrieved December 11, 2020, from HERE

3.    M;, E. (n.d.). Acetaminophen toxicity and 5-oxoproline (pyroglutamic acid): A tale of two cycles, one an ATP-depleting futile cycle and the other a useful cycle. Retrieved December 11, 2020, from HERE

4.    M;, E. (n.d.). Acetaminophen toxicity and 5-oxoproline (pyroglutamic acid): A tale of two cycles, one an ATP-depleting futile cycle and the other a useful cycle. Retrieved December 11, 2020, from HERE

5.    Martensson, J., & Meister, A. (1989). Mitochondrial damage in muscle occurs after marked depletion of glutathione and is prevented by giving glutathione monoester. Proceedings of the National Academy of Sciences, 86(2), 471-475. doi:10.1073/pnas.86.2.471

6.    Pizzorno, J. (2014, February). Glutathione! Retrieved December 11, 2020, from HERE

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8.    An Under Recognised Cause of Metabolic Acidosis. (2018, September 13). Retrieved December 11, 2020, from HERE

Vogt, B., & Richie, J. (2002, November 05). Fasting-induced depletion of glutathione in the aging mouse. Retrieved December 11, 2020, from HERE

Dopamine Beta Hydroxylase Enzyme: Its Function and Dysfunction

By Jasmyne Brown, ND, MS

Dopamine beta hydroxylase (DBH) is an enzyme crucial to the balance of dopamine and norepinephrine in the body.  It is required for the conversion of dopamine into norepinephrine.  DBH is like a lock associated with tyrosine and tyrosine derivatives fit like keys in the lock.  Dopamine, a derivative of tyrosine, fits on the DBH enzyme just as a key fits into a lock.  DBH then transforms it into norepinephrine when it is functioning adequately, leaving us with proper levels of both dopamine and norepinephrine in the system.  When DBH is functioning properly, we experience balanced moods and adequate energy levels.  When DBH dysfunction occurs, a wide range of abnormalities can develop.

The Effects of DBH Dysfunction

During times of DBH dysfunction, no matter the cause, there will be a decreased conversion of dopamine to norepinephrine.  This causes a subsequent rise in dopamine levels and decrease in norepinephrine.  Symptoms associated with elevated dopamine include anxiety, depression, fatigue, low blood pressure, sluggish deep tendon reflexes, ptosis, hypotonic muscles, hyperflexible reflexes, weakened facial muscles, and increased stress. Conditions associated with DBH dysfunction are wide ranging.  Mental health disorders such as depression, anxiety, bipolar disorder, and schizophrenia have been documented to be associated with dysfunction in the DBH enzyme.  Other conditions include postural orthostatic hypotension (POTS), exercise intolerance, fainting, autism spectrum disorder, ADHD, seizures, neurologic conditions, and alcoholism.

Causes of DBH Dysfunction

There are various reasons why DBH function can be altered.  These include elevations in clostridia toxins, cofactor deficiency, and genetic single nucleotide polymorphisms (SNPS).  When clostridia toxins are elevated, dysfunction of DBH ensues.  The toxins produced by this species of bacteria are tyrosine derivatives.  Clostridia, when given the opportunity to overgrow, takes tyrosine to produce its toxic metabolites.  The most common of these toxins are 4-cresol and HPHPA.  These toxins are the tightest binding toxins clostridia produces, although the other tyrosine metabolites of clostridia cause dysfunction too.  Since these toxins are produced using tyrosine, they look very similar to dopamine and take its place on the DBH enzyme.  This is an irreversible binding that occurs and inhibits DBH function.  An Organic Acids Test (OAT) will assess whether a patient has elevated clostridia metabolites and will also assess neurotransmitter status.

When DBH cofactors are deficient, the enzyme does not have the necessary nutrients to efficiently do its job.  Cofactors for the DBH enzyme are vitamin C and copper. It has been shown that vitamin C and copper levels can be decreased in patients with neurological disorders.  In some populations, individuals may be at a high risk of not getting an adequate amount of these nutrients, like in those with eating disorders or patients that do not have adequate micronutrient nutrition.  Also, there are those that have arsenic toxicity.  This has been correlated with decreased vitamin C and copper.  A heavy metals test should be conducted to rule out this possibility.  Supplementation with vitamin C should commence but keep in mind if the person also has elevated oxalates, high doses of vitamin C can potentiate their production.  For copper, check their levels using the Copper + Zinc Profile. This information will guide you on dosing copper in respect to zinc.

If clostridia toxins are not elevated, and cofactors are at normal levels, there is always the possibility of someone having a genetic predisposition to decreased enzyme function. There are various SNPs that can impact the function of this enzyme.  In these individuals, the symptoms of fatigue, low blood pressure, exercise intolerance, bed wetting, etc. would be expected to be present most of their life or a family history of these symptoms.  Genetic testing would give you clues into which SNPs may be playing a role here.  Unfortunately, this does not give insight to the functionality of the enzyme.  GPL’s Dopamine Beta Hydroxylase Test assesses the functionality of the DBH enzyme via a serum sample.  It allows the practitioner to understand how the patient’s genetics is phenotypically affecting them biochemically.  The beauty of this test is that even if a person has an inhibition via clostridia toxin, there is no interference and it can be done with accuracy.  Practitioners can get a clear understanding of the enzyme’s function and the patient’s ability to adequately convert dopamine to norepinephrine.

Treatment for DBH Dysfunction

Finding out whether the patient has elevated clostridia metabolites should be done first via Organic Acids Test (OAT) or Microbial Organic Acids Test (MOAT).  If they do have elevated clostridia toxins (4-cresol or HPHPA), those should be treated, then re-evaluated for treatment efficacy.  This may improve or resolve DBH function and thus any symptoms they have been experiencing due to the clostridia toxins’ inhibition of DBH. 

In individuals with decreased DBH functionality found with the Dopamine Beta Hydroxylase Test, there is treatment available.  Currently on the market there is a prescription medication, called Droxidopa.  Droxidopa is a synthetic amino acid that is converted to norepinephrine by dopamine decarboxylase.  This takes the place of the norepinephrine that would have been made via DBH.

In summary, if a patient is having the aforementioned symptoms of DBH dysfunction, various GPL tests are warranted:  The first test to screen for DBH dysfunction is the Organic Acids Test (OAT).  The markers in the neurotransmitter section will give insight. The HVA, VMA, and HVA/VMA ratios are important.  In DBH dysfunction, HVA will be elevated, VMA will be proportionally decreased, and the HVA/VMA ratio will be elevated.  This is showing that dopamine is not adequately being converted and there is something blocking the DBH enzyme.  Also on the OAT, the clostridia markers (4-cresol and HPHPA) should be assessed to rule in or out its involvement.  From here, consider running the Dopamine Beta Hydroxylase Test, a heavy metals test,  and the Copper + Zinc Profile for further understanding of a patient’s DBH functionality.

References

1. Beuger, M., van Kammen, D. P., Kelley, M. E., & Yao, J. (1996, July). Dopamine turnover in schizophrenia before and after haloperidol withdrawal. CSF, plasma, and urine studies. Retrieved 4AD, from https://www.ncbi.nlm.nih.gov/pubmed/8797194

2. Cross, A. J., Crow, T. J., Perry, E. K., Perry, R. H., Blessed, G., & Tomlinson, B. E. (1981). Reduced dopamine-beta-hydroxylase activity in Alzheimers disease. Bmj, 282(6258), 93–94. doi: 10.1136/bmj.282.6258.93

3. Garland, E. M. (2019, April 25). Dopamine Beta-Hydroxylase Deficiency. Retrieved April 30, 2020, from https://www.ncbi.nlm.nih.gov/books/NBK1474/

4. Kaufmann, H., Norcliffe-Kaufmann, L., & Palma, J.-A. (2015). Droxidopa in neurogenic orthostatic hypotension. Retrieved April 30, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509799/

5. Rahman, M. K., Rahman, F., Rahman, T., & Kato, T. (2009, December). Dopamine-β-Hydroxylase (DBH), Its Cofactors and Other Biochemical Parameters in the Serum of Neurological Patients in Bangladesh. Retrieved 28, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614808/

6. Shaw, W. (2010, June). Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Retrieved April 28, 2020, from https://www.ncbi.nlm.nih.gov/pubmed/20423563