Detoxifying Your Body - Water Filtration 101

Jessica Bonovich, RN, BSN

Hello, and welcome back to the GPL Blog.  Today we are talking about water filtration, which is a subject a lot of clients have asked about since we introduced our GPL-TOX test.  What we have seen through our studies, and those of other labs is that many of the toxins assessed by GPL-TOX have been found in many water supplies.  Any treatment plan needs to encompass a plan to prevent re-exposure. 

I recently reached out to over 12 water filter distributors and manufacturers to learn about the best filtration system for removing volatile organic compounds (VOC’s) from water and why. I was very transparent about the needs of our patients and the company I work for. I also reviewed information provided by The Environmental Working Group, who offers this Water Filter Buying Guide.  In addition, I contacted the Industrial Wastewater Management Center, the Department of Natural Resources, NSF Public Health and Safety Organization, and the Environmental Protection Agency.  Here is what I learned:

Carbon Block Filters

Carbon block is the commercially available standard for removing VOC’s. These very small compounds adhere to a surface of carbon (a process called adsorption) but will not be removed through reverse osmosis, ceramic, deionization, ozone, or ultraviolet light filtration. Factors that affect adsorption include the concentration of the compound, surface area, and the contact time between the water and the carbon. Of these factors, filters control the latter two.

The surface area of the carbon refers to the size of the pores in the carbon filter. This is where the “block” comes in. The filtration companies pack the carbons in very tightly which creates a very small pore size. The smaller the pore size the greater the chance of catching very small molecules like the VOC’s. The pore size of carbon block filters is generally measured in microns and ranges from 0.5 up to 1 micron.  This is sometimes also called submicron filtration. These tiny pores also remove lots of other small molecules like bacteria and particulate matter. Our main concern here is the removal of VOC’s because the carbon is the only filtration that will eliminate these compounds. Many other kinds of filters are available to remove the other materials. It’s a bonus but not a big selling point.

The contact time equates to how much water can contact the filter over a given period and directly affects the gallons per minute (gpm) of filtration. Companies intentionally build in methods to restrict the water flow to increase the amount of contact time the water has with the filter. The water restriction lowers the gpm which can slow the water flow. Consumers tend to want higher gpm for greater water pressure but this can affect the removal of contaminants.  The size of the filter also influences the removal. So, if you want high water flow (gpm) you need a larger filter that will handle the larger volume. This will cost you a bit more. If budget is your main concern, low gpm is the priority. Whole house filtration systems are not as effective at removing VOC’s because they are geared toward optimizing the water flow, in other words, fast filtration. The size of the filter needed to overcome the pressure drop on whole house filters is cost prohibitive for most people. Several companies do make carbon block filters for your shower head which is a nice option for reducing the VOC contaminants in your shower water. The under-the-sink and counter top units are often called point of use (POU) filters. The industry standard for good carbon block filters is between 0.5 and 1 gpm. The filter size that is needed to accommodate the larger gpm and still remove VOC’s can be deduced by looking at the performance data sheets that companies provide. This is what people should focus on to determine how robust the filter really is.

Filter Specifications

Understanding filter specifications can be a learning curve in itself. Companies will have third parties test the amount of contaminant coming in (called influent) and the amount going out (called effluent) through a company called NSF. The data sheets do not report the actual effluent, but instead report the “maximum permissible product water concentration” established by the EPA. This number will be the same on all data sheets. This testing is an important factor because we know that the concentration of the compound influences the ability of the filter to adsorb. NSF spikes water samples with a known amount of a compound and then measures the amount that is still in the specimen after filtration. These reports vary considerably and range from very well-organized to quite confusing. Some performance data sheets list these figures as a chart, while others use graphs. The only real difference is the percent reduction. This is the amount that was eliminated during the testing. I have asked multiple companies why they do not provide the actual effluent data and even contacted NSF about this. No one has been able to tell me why they don’t provide the raw data.

Filter Housing Options

Choosing the housing for your filter is the final step. Most of the companies use stainless steel, aluminum, or polypropylene plastic housing. Polypropylene is considered nontoxic by the Environmental Working Group. However, it can be oxidized when exposed to stress like heat and UV.  On top of this, many of our patients have developed severe chemical sensitivity. Once this acute phase has established itself, it can be difficult to predict what the patient will react to. I recommend the stainless steel option to remove any concern about plastic toxicity. Once your water has been filtered, do not store water in a container for more than 24 hours. Without chlorine, the water becomes a target for microbes to take up residency. 

Testing Your Water

Most filtration companies recommend that you have your water tested prior to getting a filtration system so you know exactly what you need. I have focused on single stage filtration designed to remove VOC contaminants. If you have heavy metals or bacterial contamination, you will need a multistage filter that will remove all the other contaminants. To find a laboratory in your area that can test your water, the EPA suggests that you start with your local municipality. I contacted the local water department here in Johnson County, KS to test this theory and they provided me the names of three local laboratories that can test water for contaminants.  Only one of these companies responded to my request and they offered to test for 29 VOC’s for $140.

An acceptable level of contamination has not been established for every chemical compound. The VOC’s that do have a limit are listed on pages 257-533 of this document.  According to the most current information available on the EPA website, municipal water suppliers must test the water for these VOC’s four times per year. If there are no contaminants reported for three years, the municipality can test just once per year. Municipalities can go a step further and apply for a waiver that exempts them from testing any VOC’s for up to six years. If a contamination is found, quarterly monitoring is required. If the municipality does not comply with this, there are no stated penalties or further requirements, which is a bit disconcerting. If you find that your water exceeds any of these standards, you should report this contamination to your state EPA office.  

Final Thoughts

The company (and person) that was the most helpful to me by far on this journey was Ron at Water2drink.com. All of their filter performance sheets are disclosed here. Individual requirements will vary based on price and available space. If you want my personal opinion for a good filter to remove VOC contaminants, this is a great place to start.

Oxalates

Hello. Welcome back to the GPL-Blog.  My name is Jessica Bonovich, RN, BSN.  I’m the nurse consultant here at The Great Plains Laboratory.  Today I’m going to be discussing oxalates, which are one of the many things that are tested for in the Organic Acids Test (OAT). Oxalates are of particular interest to patients who have pain and in non-verbal children with behavioral issues. Frequently, these individuals are experiencing pain as the result of oxalate crystals precipitating with minerals in tissue, including the formation of kidney stones. The Organic Acid Test is well suited to determine if this is likely occurring. When determining the best course of action we look at the proportion of the oxalate, the metabolite of oxalate, and the patient’s symptoms.

As the nurse consultant at the lab, it is my primary job to review test results with people. and as a result, I see a lot of Organic Acids Tests. Doctors and patients are often surprised to learn that Candida and Aspergillus species can produce oxalates. These species have certain enzymes that allow them to use glyoxalate as a means of making energy (it is an intermediate in their TCA cycle).  Individuals with elevations in Candida or Aspergillus frequently have a subsequent elevation in oxalate metabolites. The degree of elevation may or may not be proportional to the yeast/mold overgrowth and this is an important distinction when evaluating the significance of the markers.  If the elevation is proportional, I can easily point toward yeast as the culprit. If the oxalates are disproportional, it can be related to several other factors.

To some extent, all individuals will obtain oxalates from three sources: liver cells (endogenously), yeast species (exogenously), and food (also exogenous). The reference ranges on our test show the typical accumulation of oxalate metabolites from all three sources.

In humans and in yeast, glyoxalate is the parent compound that can be converted into the three metabolites measured on the Organic Acids Test (OAT): glyceric, glycolic, and oxalic acid (Figure 1).

Figure 1

Figure 1

It can also be converted into glycine which is not measured on the OAT. Individuals with primary, secondary, or tertiary hyperoxaluria have genetic deficiencies in the enzymes that drive these pathways and cause the distinguishing features of the disease. People who are predisposed to stone formation may or may not have deficiencies in these enzymes. The degree to which a person will favor each pathway depends on a number of metabolic factors (including available precursor and pH of the cell). Elevations in all three metabolites can occur because of yeast and endogenous production. Food and Aspergillus on the other hand, produce oxalate in the body directly. So, when these are the source of excess, only oxalate will be elevated on the test.

Patient symptoms are a key component to all of this. It almost goes without saying that we treat the patient and not the number. Low oxalate values do not rule out an oxalate issue and extremely elevated values are not always equated with pain (though the potential certainly exists).  

Let’s get back to the disproportional oxalate scenario. If a patient has mildly elevated yeast and moderately to highly elevated oxalate, what do you think would be the most likely cause?

a.      Endogenous production

b.      Yeast

c.       Food

d.      A combination of b. and c.

The correct answer is d. Food is a direct source of oxalate and the most common cause of disproportionately elevated oxalates. Yeast is contributing to the oxalates in this scenario but is not likely to be the only cause of the elevation. Patients like these should introduce calcium and magnesium supplementation with meals to help bind up excessive oxalates in the food (so they can be eliminated in stool). Many conventional doctors falsely believe that calcium supplementation should be avoided when oxalate stones are a problem. They forget that calcium levels are maintained at precise levels in the blood no matter what the intake is. This is because without calcium, the heart will not pump. So, several mechanisms are in place to ensure adequate levels are maintained at all times. Avoiding calcium is only likely to increase osteopenia and not at all likely to reduce stone formation.

Let’s walk through another scenario. An individual presents with extreme pain in the muscles and history of stone formation. The patient has very elevated Candida and eats a high oxalate diet. All of the oxalate metabolites on the OAT are normal. What is the most likely scenario?

a.      Oxalates are not a problem

b.      Endogenous production

c.       Food and yeast are not a problem

d.      None of the above

The correct answer is d. This is a scenario that I refer to as hidden oxalate toxicity. This patient should have elevated oxalate metabolites.  Based on their history and lab results, oxalates would be expected. It is likely that oxalates are present in the body. However, they are precipitating in tissues before they ever make it into the urine. These patients are usually the most extreme cases of pain. They are also the people who do very well once all of the sources of oxalate have been eliminated. It is important to remember that when patients are in pain, removing oxalates should be done SLOWLY. Otherwise the patients are likely to experience an increase in pain as a result of “oxalate dumping”. When oxalate crystals are already in the tissues, mobilizing them can cause irritation. I recommend that patient introduce therapies one at a time, thoughtfully, over several weeks to months.

Okay, last one. This is a patient with moderately high yeast metabolites, a diet rich in fruits and veggies, and severely elevated oxalate metabolites.  To give this some perspective, the reference range for oxalates is 100 mmol/mol. This patient has close to 1000. The patient has symptoms of yeast overgrowth and fatigue as the chief complaints. What is the most likely cause of the extremely elevated oxalates?

a.      Yeast

b.      Diet

c.       Endogenous production

d.      All of the above

If your answer was d, you are correct. This patient has disproportional oxalates beyond what would be expected in diet. The patient certainly has the potential to accumulate oxalates in the tissues. However, since she is eliminating it effectively, it is not causing her pain at this time. Measures should still be taken to decrease the oxalate burden. We have much more to learn about the tendency for a person to form oxalate crystals.  Several genes (AGXT, GRPHR, and HOGA1) have been implicated (all of which are identified on the GPL SNP1000 test). Even if these genes are not mutated, some individuals still have a tendency toward oxalate stone formation. The high glyoxalate production is only one factor. 

Remediation of high oxalates is a multi-step process. Elimination of yeast is always important and not only because of excessive production. Pathogenic yeast can also cause an imbalance in beneficial bacteria that help to degrade oxalates.  Many studies have demonstrated that oxalobacter can reduce oxalate stone formation (hence the name). As of right now, testing for oxalobacter is available primarily in research settings and supplements are not widely available to the public (though I expect that they will be soon). Fortunately, there are other beneficial bacteria species shown to reduce oxalic acid. Many of these are already available probiotic form. These include Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium breve, and Bifidobacterium lactis all of which are available in Lactoprime and Ther-biotic Complete probiotic formulas.

Awareness of oxalates in food and elimination of those foods highest in oxalate (like spinach, soy, almonds, sweet potatoes, and raspberries) is important. Keep in mind that a low oxalate diet should only be done with the help of a practitioner and only when there is a clear need. The foods that contain oxalate are healthy and provide many nutrients that our bodies need to maintain healthy homeostasis. People forget that the oxalate content alone is not the only factor in oxalate absorption. The oxalate to calcium/magnesium ratio should be taken into account when we consider the potential for oxalate accumulation. If a food has equal amounts of both calcium and oxalate, it is likely that neither one will be absorbed very well. Plenty of bile acid needs to be available to prevent fats from binding with calcium. Both taurine and glycine strengthen bile acid but glycine increases oxalate. Glycine is where our endogenous production of glyoxalate starts. Keep this in mind when you are choosing supplements.

Lastly, sufficient B6 is required to help with the conversion of glyoxalate to glycine in the body. Maintaining sufficient levels of vitamin B6 will help with the endogenous production. However, the active form (P5P) is poorly absorbed.  I recommend that patients in pain start with low doses of pyridoxine hydrochloride (10 mg) and work up to higher doses as tolerated. The upper limit is 100 mg per day. Patients without pain can usually safely start at 50 mg per day.   

Wow, so that was a lot. Oxalates are a topic of much interest in our patient population so I want to be as thorough as possible. If in doubt, call the lab and speak with a consultant. We have lots of experience looking at tests results and can provide insight into the patterns that are occurring on the results.


References:

Finkielstein, V., Goldfarb, D., (2006). Strategies for preventing calcium oxalate stones. Canadian Medical Association Journal , 174 (100). Published online doi: 10.1503/cmaj.051517

Herb, Nutrient, and Drug Interactions. (1st edition). (2008). St. Louis, MO, Mosby, Elsevier

Liebman, M., Costa, G. (2000). Effects of calcium and magnesium on urinary oxalate excretion after oxalate loads. Journal of Urology, 163(5): 1565-1659.

Matkovic, V., Heaney, R.P., (1992). Calcium balance during human growth: evidence for threshold behavior. The American Society for Clinical Nutrition, 55(5): 992-996.

Pennistion, K., Nakada, S. (2009). Effect of Dietary Changes on Urinary Oxalate Excretion and Calcium Oxalate Supersaturation in Patients With Hyperoxaluric Stone Formation. Urology, 73(3):484-489.

Physicians Desk Reference for Nutritional Supplements. (2nd edition). (2008). Montvale, NJ: Thomson PDR

Rushton, HG., Spector, M. (1982). Effects of magnesium deficiency on intratublar calcium formation and crystalluria in hyperoxaluric rats. Journal of Urology, 127(3): 598-604.

Poore, R.E., Hurst, C.H., Assimos, D.G., Holmes, R.P. (1997). Pathways of hepatic oxalate synthesis and their regulation. Cell Physiology. 272(1), C289-C294

Shaw, W. (2009). Autism: Beyond the Basics. Self Published, USA.

Weaver, C. (1994). Age related calcium requirements due to changes in absorption and utilization. Journal of Nutrition, 124(8): 1418S-1425S.

Detoxification of Environmental Pollutants

Welcome back to the GPL-Blog.  This month we’ve been discussing how we are exposed to thousands of environmental chemicals on a daily basis, and how GPL can help you determine your toxic load.  We have now expanded our GPL-TOX Profile to measure a patient’s exposure to over 300 chemicals.  We are also the only CLIA-certified lab that performs a test for glyphosate.  Today I’m going to discuss how to prevent exposure to some of these compounds, what treatments have been effective for detoxification, and I’ll give an example of how these treatments can reduce the toxic stress on the body.

The first step to reducing the amount of toxins in your body is to reduce the amount entering your body in the first place.  One of the most important changes people can make is to switch to eating only organic foods.  Most conventional crops are exposed to larger and larger doses of pesticides and herbicides, and by switching to organic you will prevent exposure to hundreds of different organophosphates, 2-,4Dichlorophenoxyacetic acid (2-,4,D), and pyrethroid insecticides. 

The second step is to install some type of high-quality water filtration system in your home.  A lot of the chemicals that we test for have contaminated many public water supplies.   Your options are pitcher filters, faucet filters, reverse osmosis filters, and under-the-counter filters.  The most commonly used and the least expensive are the pitcher filters.  These are easy to use and do remove some chemicals.  Many of these pitcher filters do not remove pesticides, pharmaceutical residues, herbicides, and industrial toxicants.  They do remove mercury, copper, and cadmium.  However, in today’s environment we really need more than that.  Reverse osmosis filters are more expensive, but they do remove a large number of contaminants.  However, they produce a lot of wastewater (50% of all water that goes through the system) and they do not remove organic chemicals, herbicides, or pesticides.  There are several higher quality faucet filters available that do remove pesticides and drug residues.  Finally we have the under-the-counter filters.  These unfortunately are the most expensive, but they are also the best at removing the chemicals that are polluting our water supply.

The third step is to change the products you use on yourself.  Instead of using a plastic cup or water bottle, switch to glass or metal.  Make sure your shampoo, soaps, lotions, and other beauty products are free of phthalates and parabens.  Restrict the use of harsh chemicals for cleaning. Favor gentle cleaning agents such as vinegar, baking soda, citric acid, and antimicrobial oils (tee tree oil). Limit your exposure to cigarette smoke which contains xylene, benzene, and hundreds of other chemicals.  Avoid the use of pesticides and herbicides on the lawn. Make sure you wear shoes when playing in a park because many parks are sprayed with pesticides and herbicides.  Limit the amount of time you or your children spend on playing surfaces produced from ground up tires.  These are just several of the recommendation that could help limit your exposure.  Just be mindful when you are doing anything about what chemicals you could be exposing yourself to. 

Our fourth recommendation is infrared sauna therapy and exercise.  Studies have shown that many of these toxicants are best eliminated through sweat.  Now I suggest that anyone who starts a sauna regimen or exercise regimen do so under a medical practitioner’s care.  I also recommend infrared sauna over conventional sauna because it reaches deeper into the body.  Infrared sauna is useful because it increases the circulation in all of your blood vessels and causes your body to start to release many of the chemicals stored in body fat.  Some of the many chemicals released would be MTBE/ETBE, xylene, vinyl chloride, organophosphates and 2-,4-D.    

There are two particular supplements that people are using to improve detoxification.  The first is glutathione, or its precursor N-acetyl cysteine.  Glutathione is one of the main phase two conjugates that the body covalently bonds to toxicants in order to eliminate them. Certain factors could deplete your glutathione.  These include illness, stress, mutations, diet, or exposure to toxicants.  If you are constantly exposed to toxicants your stores of glutathione could be depleted.  You can check your glutathione levels with the Organic Acids Test that we provide here at GPL.  The second supplement is vitamin B3 (Niacin).  Now I know a lot of people don’t like the flushing experience after taking Niacin.  However, this flushing is from the blood vessels expanding, which is useful in the detoxification process.  At least 50 mg of nicotinic acid is required to induce flushing. Nicotinamide, while identical to nicotinic acid in vitamin activity varies in its pharmacological activity and is not associated with vasodilation. Vasodilatation greatly increases the chances of hypotension which is also be accelerated by the sauna. This type of therapy should only be done under close supervision by a physician. Certain medications are contraindicated while on this therapy (statins in particular can cause serious reactions). Niacin is excreted as methylated pyridones which requires adequate S-adenosylmethionine (SAM). Caution should be used in patients with impaired methylation. The depletion of SAM is thought to be responsible for most of niacin’s adverse affects. Niacin and nicotinamide may also make allergies worse by increasing histamine.

In our work with doctors who have ordered GPL-TOX and our Glyphosate Test, we have started to gather some results for patients that had high environmental toxicant levels.  Here is a result from one patient’s Glyphosate Test (see figure 1):

Figure 1

This patient reported eating an organic diet, but has a high amount of glyphosate.  This patient lives in the Midwest, where it seems glyphosate has contaminated some water supplies.  This patient installed a water filtration system, did several months of infrared sauna treatment, and was then re-tested (see figure 2):

Figure 2

As you can see from these results, this patient was able to decrease the amount of glyphosate in her body by more than half. 

Here are some results from a second patient’s GPL-TOX test.  This patient had high amounts of vinyl chloride and benzene (see figure 3):

Figure 3

This patient started an exercise and infrared sauna regimen.   One important note to remember is to wipe off the sweat regularly, because you don’t want the toxins to reabsorb back into the body.  This patient also started to take regular doses of glutathione.  After three months, we saw drastic results (see figure 4): 

Figure 4

Figure 4

As you can see, this patient went from very high amounts of vinyl chloride and benzene to non-detectable amounts.

The take away from this month’s blog articles is that testing for environmental toxicants is very important because these chemicals can lead to the formation of many chronic diseases. We are exposed to thousands of toxins every day.  The scientists here at GPL have developed tests to measure the most commonly occurring exposures.  With this information and the information obtained through the Organic Acids Test, we can better determine what the underlying cause of many chronic problems is and form plans to solve them.  I hope this was helpful.  Please share your questions, trials, and triumphs with us at GPLblog@gpl4u.com.

Integrative Medicine for Mental Health (IMMH)

Welcome back to the GPL Blog.  One of my roles at the Great Plains Laboratory is to inform the public that our tests exist, what they do, and what people can do with the information.  One part of this entails going to lots of conferences in our field, which allows me to experience what each has to offer.  I really enjoy the conference experience.  I always come away having met a lot of new and interesting people with lots of great questions and insight, and I always get new bits of information or ideas to implement here at GPL.     

This week I have decided to talk about my favorite conference that I go to every year which is run by Integrative Medicine for Mental Health (IMMH).  In the interest of full disclosure, GPL is affiliated with IMMH and we are very proud to be, as IMMH has built an ever growing and improving annual conference that focuses on multiple aspects of integrative medicine and how they apply to mental health and various neuropsychiatric disorders.   At last year’s conference there were talks on the roles of nutritional deficiencies, food allergies, toxic chemicals, infections, and inflammation in disorders like depression, multiple sclerosis, autism,  Lyme disease,  anxiety, eating disorders, and many more.  In my opinion, anyone that wants to practice integrative medicine would benefit from this conference.  The conference does a solid job of providing offerings that benefit those that are still learning the basics of integrative medicine and to those that have been using it for years, and based on what I’ve seen about this year’s conference so far, I think it will do that better than ever before.  Don’t just take my word for it though.  Here is a review of IMMH 2015 written by Dr. Ira Goodman, Examiner for the American Academy of Anti-Aging Medicine and practitioner of functional medicine: (Click here to read the article)

From my experience and the feedback I get from the attendees at IMMH, the best part of the conference is how all of the speakers use their personal experiences to illustrate how they use different types of testing and how they treat different types of cases.  I personally think that IMMH has some of the best speakers of any conference I attend the whole year.  I know that the IMMH staff goes out of their way to get feedback from the community about what speakers they find the most useful and interesting, and then recruit them to speak.  Having looked through the speaker list for the conference in Washington, DC this coming fall, I can attest that this might be the best group I’ve ever seen.  Since I’ve heard most of these speakers at multiple conferences, having them together in one conference is quite a treat.  For all IMMH 2016 conference details, go to www.IMMH2016.com.

So, who are some of the speakers that I think you should be excited about?  Well, the first is James Greenblatt, MD.  Dr. Greenblatt is a prominent integrative psychiatrist who will be giving multiple lectures on tools of integrative medicine for mental health disorders.   I’ve seen Dr. Greenblatt speak several times and I’ve heard his webinars.  He is very insightful.  He has published several books about using integrative practices in psychiatry.  His talks at IMMH 2016 will focus on mood and anxiety disorders.  However, his lectures touch upon many tools that practitioners can use to help their patients.  


IMMH 2016 will also feature Kelly Brogan, MD. Dr. Brogan is a holistic women’s health psychiatrist.  She focuses on the root causes of many chronic psychiatric conditions.  She is a great person to follow on Twitter.  She has recently published a book titled A Mind of Your Own: The Truth About Depression and How Women Can Heal Their Bodies and Reclaim Their Lives.  She does an excellent job of explaining the biochemistry issues that can cause anxiety and depression. 


Another highlighted speaker for IMMH 2016 is Daniel Amen, MD - ten-time NY Times best-selling author and popular psychiatrist.  His SPECT brain imaging techniques have helped over 100,000 people.  This technology has allowed many patients to determine the underlying causes of their conditions.  I know of patients whose lives have literally been saved by his work.  The scan technology is useful for ADHD, behavior disorders, depression, anxiety, PTSD, traumatic brain injury, as well has many other diseases.  He is a great speaker who often leaves his audience in tears. 


Finally, IMMH 2016 will be having one of my favorite speakers I’ve ever heard, Terry Wahls, MD.  Dr. Wahls suffers from multiple sclerosis, but through her specific diet and treatment protocol that she created through her research, she has recovered from being wheelchair bound.  Her message is quite powerful.  Dr. Wahls is a professor at the University of Iowa and works in the VA Health System.  Her studies have implications for a number of chronic issues from MS and Parkinson’s to multiple other autoimmune diseases.  She uses many case studies in her talks.  One thing I really like about her presentations is that she has a great protocol, she tells compelling stories, and she has done thorough research that shows why her protocol works. 


Besides these four excellent speakers there are another fourteen expert speakers who will provide you with a variety of new tools to put into your integrative medicine tool box.  There are so many great conversations that occur during the breaks when you can network with fellow attendees, speakers, and exhibitors.  New for this year’s conference, Dr. Kurt Woeller, one of our GPL consultants who is a fixture at IMMH, will be giving a full-day seminar (optional track on day one) on how to integrate the Organic Acids Test into your practice.  Some of the best providers of testing, equipment, and nutraceuticals in the industry are also exhibiting at IMMH.  If you are available from September 29-October 2 and would like to visit the Washington, DC area, I think this is the conference for you.  I hope to see you there! 

Your Body’s Detoxification Pathways

Welcome back to the GPL-BLOG.  Over the past several weeks we’ve been discussing a lot of the environmental toxins that everyone is exposed to on a daily basis.  These toxins must be processed and detoxified.  Most of this is done in the liver through several different processes that include Cytochrome P450 (P450) biotransformation, glutathione conjugation, enzyme hydrolyzing, sulfation, and glucuronidation.

Detoxification is often referred to as a two stage process (phase 1 and phase 2) of metabolism (Figure 1).  Phase 1 metabolism involves the reduction or hydrolysis of the compound (usually caused by the addition of an oxygen molecule).  The addition of oxygen to a compound is referred to as oxidation.  This process is usually performed by the P450 enzymes.

Figure 1

The P450s are a family of enzymes that are found in numerous tissues throughout the body. However, a majority of these are found in the liver.  The P450s are important for the detoxification of many foreign substances, including environmental toxicants and medications.  The P450s are also important in controlling the levels of different molecules produced in the body such as the synthesis and breakdown of hormones, steroids, and multiple other molecules. 

In humans, 58 different P450s have been discovered.  However, only a subset of these is involved in the degradation of xenobiotics (chemicals that come from outside the body).  These enzymes have different substrates, which are determined by the activity pocket of each enzyme.   In regards to detoxification the most important P450s are Cyp1A2, Cyp2A6, Cyp2C9, Cyp2C19, Cyp2D6, Cyp2E1, and Cyp3A4.  Besides detoxification, these enzymes metabolize a majority of medications (figure 2).

Here are some important detoxification enzymes:

Figure 2

Cyp1A2 is important for the metabolism of polycyclic aromatic hydrocarbons (PAHs), which are found in cigarette smoke.  Other substrates include medications, aflatoxin B1, caffeine, and acetaminophen.  The major polymorphism is Cyp1A2*1K, which results in a decrease of activity.

Cyp2A6 is involved in the metabolism of nicotine.  Cyp2A6 is also involved in the metabolism of medications.  The major polymorphic alleles are Cyp2A6*4 and Cyp2A6*9 (which can have between 35% -70% activity depending on if you have one or two polymorphic copies). 

Cyp2C9 is involved with the metabolism of a large number of medications including NSAIDs, warfarin, and tamoxifen.  There are multiple polymorphisms that affect activity of the enzyme. 

Cyp2C19 is involved with the metabolism of multiple medications.  The most common are diazepam, omeprazole, and sertraline.  Cyp2c19 also metabolizes progesterone.   There are two major variants that result in loss of activity.  These are Cyp2C19*2 and Cyp2C19*3.

Cyp2D6 is involved with the metabolism of about 20% of drugs on the market.  It also metabolizes serotonin and neurosteroids.  There are five different polymorphisms that can lead to decreased activity.  Some of the classes of drugs that are metabolized by Cyp2D6 are antidepressants, SSRIs, opioids, and antipsychotics. 

Cyp2E1 is involved with the detoxification of many industrial pollutants, as well as carcinogens.  Cyp2e1 also metabolizes ethanol to acetaldehyde and acetate.  Cyp2e1 is also responsible for bioactivating a number of carcinogens, including cigarette smoke. 

Cyp3A4 is responsible for metabolizing more compounds than most other P450s.  It is responsible for metabolizing sex hormones, caffeine, statins, SSRIs, antifungals, antidepressants, and many other medications.  Some antibiotics can negatively affect its activity. Also, grapefruit and pomegranate juice have been shown to be potent inhibitors. 

Sulfur transferase is a phase 2 enzyme that adds sulfur groups to compounds in order to make them more water soluble and less reactive.  This process is used on a wide variety of toxic molecules including phenols, amines, acetaminophen, and food dyes.  Many chemicals that are able to become airborne are sulfated.  Patients with autism have been found to have impaired sulfation ability, which will make these individuals more sensitive to toxins.

Glutathione transferase is a phase 2 enzyme that catalyzes the conjugation of glutathione to substrates.  The addition of glutathione to toxins prevents these compounds from interacting with proteins in the body and allows them to be excreted via urine or bile.  There are a wide variety of compounds that are conjugated with glutathione.  A partial list includes pesticides, herbicides, carcinogens, acetaminophen, and mycotoxins.   

Glucuronosyltransferase (UGT) is another phase 2 enzyme that is responsible for the glucuronidation of many different toxic chemicals.  This process involves the addition of a glucuronosyl group to substrate molecules making them more polar and more easily excreted by the kidneys. 

Paraoxonase 1 (PON1) is an enzyme that is able to perform paraoxonase activity on substrates.  This enzyme is able to hydroylse and detoxify many different types of organophophate molecules.  PON1 is one of the major pathways that protects people from these types of compounds.  Mutations to PON1 could lead someone to be more sensitive to pesticides.  Infants do not have a lot of PON1 activity.  PON1 becomes active between birth and seven years of age. 

These are the major pathways that you should be aware of when you are thinking about detoxification.  Please see Table 1 to help you understand which pathway is mostly responsible for detoxifying these common toxicants.  Also see Figure 1 to help you understand what you can do to help support type 1 and type 2 detoxification pathways.  Detoxification of compounds by glutathione can be assisted by the supplementation of additional glutathione.  Next week I will discuss some additional methods to help with detoxification.  

Email gplblog@gpl4u.com if you have any questions about this blog post.

Toxic Crumb Rubber: The Dangers Below our Children’s Feet

Welcome back to the GPL Blog.  This month we’ve been talking about toxicity and how the Great Plains Laboratory can help you assess toxic burden.   This week I thought I would talk about a topic that has been getting quite a bit of publicity lately and that is the use of ground up rubber tires for playgrounds and sports fields.

In the last two decades, many playgrounds, soccer fields, and football fields have been replacing their natural surfaces with a synthetic surface of rubber granules made up of ground tires.  Despite the popularity of these types of surfaces many different activist groups have expressed concern that these synthetic materials may be a toxic burden on our children.

In 2006 a commentary was written in Environmental Health Perspectives detailing how little we knew about the material we are having our children play on (Anderson et al, 2006).  In the years since, there have been some insightful studies performed that give clues into how harmful prolonged exposure to these rubber play areas may be.  In 2007, a study from the nonprofit organization Environment and Human Health, Inc. and the Department of Analytical Chemistry at the Connecticut Agricultural Experimental Station produced one of the first reports about chemicals found leaching from artificial surfaces made from rubber tires.  This report indicated that benzothiazole, butylated hydroxyanisole, n-hexadecane, 4-(t-oxtyl) phenol, and zinc was found leaching from the tires.  These chemicals are known carcinogens and neurotoxicants (Brown et al., 2007).

A second report in 2008 in the Journal of Exposure Science and Environmental Epidemiology provided some additional data on the chemicals that could affect children.  The report indicated that the rubber granules have a much higher amount of polycyclic aromatic hydrocarbons (PAHs) than soil.  Zinc and chromium were also found to be much higher in the artificial surfaces than in soil.  The report also stated that although lead was not found to be much higher than in soil the bioaccessibility was much higher (Zhang et al, 2008).  PAHs are known neurotoxic chemicals which have been found in air pollution from fossil fuel combustion.  A recent study published in PLOS One from the University of Columbia discovered a link between PAH exposure and the development of attention deficit and hyperactivity problems (Perera et al., 2014).

So how can we determine if our children are being exposed to these chemicals?  The GPL-TOX profile has two markers that can be used to measure chemicals commonly leached from tires.  These two markers are N-acetyl (3,4-dihydroxybutyl) cysteine (whose parent is 1,3 butadiene) and Phenylglyoxylic acid (whose parent is styrene).   The presence of 1,3 butadieneand styrene in urine have been linked to rubber exposure.  I also recommend doing a hair metals test.  USA Today reported in 2015 that “lead levels high enough to potentially harm children have been found in artificial turf used in thousands of schools, playgrounds and day-care centers.”  By utilizing the GPL-TOX profile and the hair metals test you should be able to determine the amount of tire chemicals your child has absorbed.

In two weeks I will be talking about the detoxification pathways that the body uses to get rid of toxins, and the following week I will discuss which detoxification methods seem to be delivering the best results.  I have been working with several doctors to help develop methods.  I will provide some GPL-TOX results from patients’ pre and post detoxification. 

 

Email gplblog@gpl4u.com if you have any questions about this blog post.

New Analytes for GPL-TOX

Today is a very exciting day for me.  I really love when we unveil new tests or improved tests.  Today is the latter.  Our scientists have worked very hard to make our tests the best in the industry.  We want to make sure that they can be as useful to the community as possible.  We also strive to make them as affordable as possible.  That is why I’m excited to announce the addition of eight new analytes to the GPL-TOX test at no addition cost.  Just by ordering our GPL-TOX you will get these eight new analytes in addition to the previous analytes and it is still just the one first morning urine sample that is needed.


Here are our new analytes, listed with the parent first and the metabolite we are measuring in parentheses.

Acrylamide N-acetyl-S-(2-carbamoylethyl)-cysteine

Acrylamide can polymerize to form polyacrylamide.  These chemicals are used in many industrial processes such as plastics, food packaging, nail polish, cosmetics, dyes, and treatment of drinking water.    Food and cigarette smoke are also two major sources of exposure.  Acrylamide has been found in foods like potato chips and French fries.  This is because asparagine, an important amino acid for central nervous system function, can produce acrylamide when cooked at high temperature in the presence of sugars.  Foods rich in asparagine include asparagus, potatoes, legumes, nuts, seeds, beef, eggs, and fish, so use caution when cooking these foods at high temperatures.   High levels of acrylamide can elevate a patient’s risk of cancer.  In addition, acrylamide is known to cause neurological damage. 

Acrylonitrile (N-acetyl(2-cyanoethyl)cysteine)

Acrylonitrile is a colorless liquid with a pungent odor.  It is used in the production of acrylic fibers, resins, and rubber.  Use of any of these products could lead to exposure to acrylonitrile.  Smoking tobacco and cigarettes is another potential exposure.  Exposure to acrylonitrile can lead to headaches, nausea, dizziness, fatigue, and chest pains.  The European Union has classified acrylonitrile as a carcinogen.

Diphenyl phosphate

This is a metabolite of the organophosphate flame retardant triphenyl phosphate (TPHP), which is used in plastics, electronic equipment, nail polish, and resins.  TPHP can cause endocrine disruption.  Studies have also linked TPHP to reproductive and developmental problems. 

Perchlorate

This chemical is used in the production of rocket fuel, missiles, fireworks, flares, explosives, fertilizers, and bleach.  Studies show that perchlorate is often found in water supplies.  Many food sources are also contaminated with perchlorate.  Perchlorate can disrupt the thyroid’s ability to produce hormones.  The EPA has also labeled perchlorate a likely human carcinogen.  Patients that are high in perchlorate can use a reverse osmosis water treatment system to eliminate the chemical from their water supply.

1,3 butadiene (N-acetyl (3,4-dihydroxybutyl) cysteine)

This is a chemical made from the processing of petroleum.  It is often a colorless gas with a mild gasoline-like odor.  Most of this chemical is used in the production of synthetic rubber.  1,3 butadiene is a known carcinogen and has been linked to increased risk of cardiovascular disease.  Individuals that come into contact with rubber, such as car tires, could absorb 1,3 butadiene through the skin.  The increased use of old tires in the production of crumb rubber playgrounds and athletic fields is quite troubling.  

Propylene oxide (N-acetyl(2,hydroxypropl) cysteine)

This chemical is used in the production of plastics and is used as a fumigant.   Propylene oxide is used to make polyester resins for textile and construction industries.  It is also used in the preparation of lubricants, surfactants, and oil demulsifiers,  as well as a food additive, an herbicide, a microbicide, an insecticide, a fungicide, and a miticide.  Propylene oxide is a probable human carcinogen. 

1-Bromopropane (N-acetyl (propyl) cysteine)

1-BP is an organic solvent used for metal cleaning, foam gluing, and dry cleaning.  Studies have shown that 1-BP is a neurotoxin as well as a reproductive toxin.  Research indicates that exposure to 1-BP can cause sensory and motor deficits.  Chronic exposure can lead to decreased cognitive function and impairment of the central nervous system.  Acute exposure can lead to headaches.

Ethylene oxide ( N-acetyl(2-hydroxyethl)cysteine)

Ethylene oxide is used in many different industries including agrochemicals, detergents, pharmaceuticals, and personal care products.  Ethylene oxide is also used as a sterilizing agent on rubber, plastics, and electronics. 

Chronic exposure to ethylene oxide has been determined to be mutagenic to humans.  Multiple agencies have reported it as a carcinogen.  Studies of people exposed to ethylene oxide show an increased incidence of breast cancer and leukemia.  Caution is needed with ethylene oxide because it is odorless at toxic levels. 

I think these new compounds are going to make the GPL-TOX profile that much more useful.  If you are concerned about your toxic burden, we believe that this test will give you the most comprehensive assessment of your exposure.  I really hope we’ve created a test that can be a useful tool in achieving better health for you and your patients.

More Sources of Information About the Dangers of Glyphosate

More Sources of Information About the Dangers of Glyphosate

GPL was at the Environmental Health Symposium, March 4-6 in San Diego, where we were able to showcase our GPL-TOX Profile and Glyphosate Test with everyone who attended.  The response was rather amazing.  Glyphosate is the primary chemical in RoundupTM and is the world's most widely used herbicide.  Prominent glyphosate researcher, Gilles-Eric Séralini spoke ath the conference on Sunday and did a segment with the local FOX affiliate in San Diego as well.  Click the video to watch

Glyphosate: Trying to Roundup where Your Toxicity is Coming From

Welcome back to the GPL Blog.  This month we’ve discussed the analytes that have been added to GPL-TOX since it launched last year, and we’ve discussed the nine new analytes that we’ve added just this month.   This week I want to discuss another test you can add onto GPL-TOX and that is our Glyphosate Test.  Glyphosate is the active ingredient in Roundup© (there is some controversy on this, but glyphosate tracks with all of the other ingredients).   Roundup© is the most widely used herbicide on the planet (1).   The most recent numbers indicate that over 180 million pounds of it were used in the US in 2007 (followed by Atrazine, one of our new analytes).   

The Great Plains Laboratory Glyphosate Test can be performed on the same urine sample from an Organic Acid Test (OAT) or GPL-TOX. To simplify this process and because we think these tests work well together, we have packaged them into our Enviro-TOX panel, which provides all three tests at a discount. 

So why is measuring glyphosate important?  First of all, there are data indicating that glyphosate is tied to a number of chronic medical conditions (I will expand of this point later).  Second, not everyone has high glyphosate.  Now, I’m not saying that not everyone is contaminated with glyphosate, because I have not seen one patient with an immeasurable amount, but this is t just evidence of how sensitive our test is.  The lower limit of quantification (LLOQ) for our test is 0.38 μg/g of creatinine, so we have a very sensitive test.  Here is an example of our report (Figure 1).

Figure 1

What you will notice from this report is the amount of glyphosate found normalized to creatinine, and then three values.  We have the LLOQ, the 75th percentile, and the 95th percentile.  These percentiles were produced from our own studies, but I have received confirmation from several other scientists that these values seem correct.  If your value is in the 75th percentile this means that 75 out of 100 people would have a value lower than yours.  I generally tell patients that they may want to start a detoxification regimen if their value is higher than 1.8 μg/g creatinine (the 75th percentile). 

Why is testing for glyphosate important?  A recent scientific paper listed Roundup© as one of the most toxic herbicides or insecticides tested (2).  Exposure to glyphosate has been linked to autism, Alzheimer’s, anxiety, cancer, depression, fatigue, gluten sensitivity, inflammation and Parkinson’s (3,4).  The causes for these disorders have been linked to glyphosate’s impact on gut bacteria, metal chelation, and P450 inactivation (5, 6).   

Glyphosate works by inhibiting the synthesis of tryptophan, phenylalanine, and tyrosine in plants. This pathway (called the shikimate pathway) is also how bacteria, algae, and fungi produce the same amino acids. This pathway is not present in humans. So, manufactures of glypohsate claim this compound is “non-toxic” to humans. Evidence is showing that there are human consequences to the wide spread use of this product. The first should be obvious. Humans need to obtain these amino acids from food sources. When food sources have scarce amounts of these amino acids, due to glyphosate use , humans are at risk for deficiency too. Humans also require bacteria to maintain a healthy immune system. Research indicates that glyphosate decreases the amount of good bacteria in the gut such as bifidobacteria and lactobacilli and allows for the overgrowth of harmful bacteria such as campylobacter and C. difficile (7).  Our lab actually has observed this in patients.  We had a female patient who was suffering from depression who did a Glyphosate Test and an OAT.  Here glyphosate results where 2.99 (figure 2), which was over the 95th percentile.

Figure 2

Upon analyzing her OAT we noticed two things.  The first was that her 4-cresol was extremely high (Figure 3).  As I mentioned above, glyphosate exposure decreases the good bacteria and allows C. difficile to invade.

Figure 3

C. difficile produces a toxin called 4-cresol, which we measure in the OAT.  Research has shown that 4-cresol inhibits dopamine beta-hydroxylase (8).  Dopamine beta-hydroxylase converts dopamine to norepinephrine.  In the OAT we measure both homovanillic acid (dopamine metabolite) and vanilymandelic acid (norepinephrine metabolite).  We have observed patients with a high 4-cresol value have elevated homovanillic acid, which indicates an inability to convert dopamine to norepinephrine. The results from our patient mentioned above were consistent with these results (Figure 4). The recommendations for this patient were to treat her glyphosate exposure and to treat her C. difficile infection.   

Figure 4

These results are indicative of why using the OAT and Glyphosate Test together is so valuable.  I hope this information was helpful and that our testing helps you find the best treatment for you or your patients.

Email gplblog@gpl4u.com if you have any questions about this blog post.

REFERENCES

1. https://www.epa.gov/sites/production/files/2015-10/documents/market_estimates2007.pdf
2. Mesnage R et al. (2014) Biomed Res Int.  2014:  179691
3. Samsel A and Seneff S. (2013).  Interdiscip Toxicol.  6:  159-184.
4. Samel A and Seneff S. (2015).  Surg Neurol Int.  6:  45. 
5. ShehataAA et al. (2013) Curr. Microbiol.  66:  350-358. 
6. Larsen K. et al. (2014) Int J Toxicol.  33:  307-318. 
7. Clair E. et al. (2012) Curr Microbiol.  64:  486-491. 
8. DeWolf WE jr. (1988)  Biochemistry.  27:  9093-9101.  

Toxic Chemicals and the Increasing Rates of Chronic Illnesses

Toxic Chemicals and the Increasing Rates of Chronic Illnesses

Every day, we are exposed to hundreds of toxic chemicals through products like pharmaceuticals, pesticides, packaged foods, household products, and environmental pollution. As we have become more accustomed to chemical-laden products, and as our environment has become more contaminated, we have been confronted with an accelerating rate of chronic illnesses like cancer, heart disease, chronic fatigue syndrome, chemical sensitivity, autism spectrum disorders, ADD/AD(H)D, autoimmune disorders, Parkinson's disease, and Alzheimer's disease. In this webinar, our lab director, Dr. William Shaw reviewed the common toxic chemicals tested by the GPL-TOX profile, how to prevent exposure to these toxins, and possible treatments.

GPL-TOX: Managing our Toxic Environment

Welcome back to the GPL blog.  I am really excited to be entering our second month of providing what we hope is useful information to the community.  Last month I discussed some of the uses of the GPL-SNP1000 test.  This month we will be discussing environmental toxicants.  Some of the topics covered will be the most prevalent toxicants in our environment, the best way to test for them, and relevant case studies. In the last blog this month I’ll cover some ways to detoxify the body and what tests can determine how well a patient is able to detoxify.

The Great Plains Laboratory introduced GPL-TOX (our toxic organic chemical profile) last July that measures 168 different toxic chemicals.  Our goal was to provide a test that measured as many chemicals as possible for a reasonable price.   These compounds fall into the categories of phthalates, benzene, pyrethrin insecticides, xylenes, styrene, fuel additives, 2,4-Dicholrophenoxyacetic (2,4-D), and organophosphate pesticides. Once a person has been exposed, the chemicals undergo several metabolic changes in the process of elimination and detoxification.  We measure the end products in the urine to determine how much chemical exposure has taken place.  Last October we introduced a test for the toxic compound glyphosate which is the world’s most widely produced herbicide. You have probably heard of it already, as it is the active ingredient in the broad-spectrum herbicide Roundup TM.  

Here at GPL, our scientists are continually working to improve our tests.  Later this month we are introducing eight new analytes to our GPL-TOX test for no additional cost. The new analytes are acrylamide, acrylonitrile, diphenyl phosphate (fire retardant metabolite), perchlorate, butadiene metabolite (carcinogenic component of rubber), dimethyl thiophosphate (pesticide metabolite),  propylene oxideacid and bromopropane.  Even before our recent update, GPL-TOX was one of the most comprehensive toxic chemical tests available.  Next week, I will discuss how all of these new analytes can affect a patient’s health.   This week I am going to provide more details about the analysis and review  a few of our current toxic analytes. I am also going to provide a few examples of case studies.   

To better understand the relevance of GPL-TOX, I’d like to explain the percentiles on our report.  The CDC issues a report of the exposure of many different chemicals to the US population.  Our percentiles are pulled from these reports.  If you are in the 95th percentile, then that means that only 5 percent of the population would have a higher value than yourself.  Since we do not know what the safe amounts are for many of these compounds we recommend reducing levels as much as possible. 

Every year over 1,000 million tons of organophosphates are used in the agricultural industry and in our home gardens.  This is a problem that is affecting us all, because even if we eat exclusively organic food, there is evidence that many of these organophosphates have contaminated the water supply.  The evidence of this has been centered on the increasing prevalence of depression, ADHD, pervasive developmental disorder, and birth defects, linking these toxins to these disorders. GPL-TOX looks at two metabolites related to organophosphates, Dimethylphosphate (DMP) and diethylphoshate (DEP).  Together these two metabolites allow us to track over 151 different organophosphates through urine, including nine of the ten most commonly used organophosphates. 

Another marker that makes GPL-TOX useful is monoethylphlate (MEP), which is a metabolite of phthalate exposure.  Many of us know about the pervasiveness of these compounds, which seem to be found in so many common products.  These products include lubricants, paints, perfumes, children’s toys, gels, and pesticides.  We are seeing many of our sickest patients possessing high values of phthalates.  Some of the symptoms we are seeing are fatigue, depression, ADHD, and arthritis.   

I want to share a couple of case studies to help illustrate what we are seeing.  The first is a painter with arthritis, fatigue, and depression.  The MEP on this patient’s GPL-TOX report came back at 19,110 (see Figure 1), which was ten-fold higher than our 95th percentile.  We recommended a detoxification program to this patient, which many of our patients are using with great success.  I will discuss different means of detoxification in my blog on May 30th, so check back for that.

Figure 1

Figure 1

Here is one more interesting case study.  We have all heard about fracking (the process of injecting liquid chemicals at high pressure far underground, in order extract natural gas or oil) and some of the resulting damage it does to the environment and our water supplies. The results below are from an extremely autistic patient with PANDAS who lives near fracking wells in the summer (see figures 2-4).  This sample was taken months after he was exposed.

Figure 2

Figure 2

Figure 3

Figure 3

Figure 4

Figure 4

These results are pretty alarming.  Obviously not everyone has high values like this, but even if we don’t live near fracking sites, we are exposed to toxic chemicals in our environment more and more every day.  If you do come up high for one or more of these chemicals, there is hope.  On May 30th I will discuss potential treatment options to detoxify the body and recommendations to avoid future exposures.  After treatment and avoidance, I recommend running the test again to make sure that you have sufficiently decreased the toxicants. 

Next week I will talk about the new analytes for the GPL-TOX test and why measuring these particular analytes is important.  In the meantime, stay vigilant about the many chemicals you and your family may be exposed to on a regular basis in every area of your home, from the food you eat and the water you drink, to all your household products.

Email gplblog@gpl4u.com if you have any questions about this blog post.

The Importance of Genetic Testing for Mental Health

Two weeks ago I talked about how we are starting to move into the age of personalized medicine.  Our goal at The Great Plains Laboratory is to determine what factors lead to chronic illnesses and what treatments may help.  Previously I discussed how the Organic Acids Test (OAT) and the GPL-SNP1000 DNA Sequencing Profile work well together to determine both the risk for and causes of many chronic illnesses and how useful these two tests are in helping practitioners develop individualized treatments.  Last week I specifically discussed the DNA methylation pathway, of the GPL-SNP1000.  This week I am going to go over the mental health pathway of the this same test.  I will talk about what genes are most important, some specific polymorphisms to be aware of, how the OAT can help diagnosis these disorders, and what treatments seem to work best. 

The two most important genes in this pathway are MAO-A (monoamine oxidase A) and COMT (catechol-o-methyltransferase) (Please see Figure 1). Both enzymes are required for metabolizing neurotransmitters critical to mental health. Mutations to either one can have serious consequences relating to how we think, feel, and interpret the world around us.

Figure 1

MAO-A
Monoamine oxidase A is important for the metabolism (breakdown) of biogenic amines such as the neurotransmitters dopamine, norepinephrine, and serotonin (figure 2).  Mutations to this gene have also been linked to depression, borderline personality disorder, and bipolar disorder. 

 

Figure 2

 

There are two different types of polymorphisms involved with MAO-A.  The first type, which is characterized by rs6323 , causes an increase in activity of the enzyme. Rapid metabolism resulting from this mutation causes depletion in the neurotransmitter. This depletion is directly related to the extent of the enzyme activity which can be determined on the Organic Acid test (OAT) by measuring the production of Homovanillic acid (HVA) and Vanillylmandelic acid (VMA) which are the end products of dopamine and epinephrine metabolism (see figure 1).  Patients who are rapid metabolizers will show an increase of HVA of VMA (Figure 3).  Such patients will have a depletion of these neurotransmitters which leads to multiple neurological diseases including depression. Treatment for these polymorphisms includes supporting the methylation pathway which helps to promote the cofactor required for neurotransmitter synthesis and providing neurotransmitter precursors such as tyrosine, B6 and 5-HTP.

Figure 3

A second type of polymorphism to MAO-A is one that decreases activity (rs72554632,  Gln296X), whichcauses a premature stop codon in the gene..  This polymorphismwill lead to a buildup of neurotransmitters, which can lead to the development of Brunner syndrome.  Brunner syndrome is characterized by a decrease of mental capabilities, increased impulsivity, mood swings, and sleep disorders. These individuals will have a decrease of HVA and VMA metabolites on the OAT. Without the benefit of genetic testing, these results could lead a practitioner to treat with neurotransmitter precursors. Increasing neurotransmitters for individuals with this type of mutation would actually exacerbate the condition. Treatments include decreasing the amine containing foods such as fish, cheese, and fruit, taking progesterone to increase MAO; taking inositol(which reduces 5HT2A serotonin receptor), taking riboflavin (increases MAO activity), or taking ginkgo, which has been shown to decrease aggressiveness in MAO-A deficient patients.

COMT
Catechol-O-methltransferase (COMT) is present in the body in two different forms.  The short form is called soluble catechol-O-methyltransferase (S-COMT).  The longer form is called membrane-bound catechol-O-methyltransferase (MB-COMT).   MB-COMT is mainly present in the nerves of the brain, while S-COMT is located in the liver, kidney, and blood.  In the brain, MB-COMT is responsible for degrading neurotransmitters called catecholamines, which include dopamine, epinephrine, and norepinephrine. Therefore the membrane bound form is believed to have a greater affect on mental health, though both forms may be implicated in disease since both are capable of metabolizing catecholamines.

GPL-SNP1000 analyzes six different SNPs for COMT.   Of these, the most extensively studied is a mutation to rs4680 (Val158Met). Despite the many studies available about this mutation, the scientific community is still at odds about the degree to which this mutation causes disease. What is known is that individuals with this mutation have lower activity of the enzyme.  Mutations to COMT will lead to dopamine and epinephrine not being broken down properly, which can be detected by a decrease in the HVA metabolite in the Organic Acids Test.

Figure 4

Interestingly, some individuals may benefit from increased dopamine while others may benefit from less. Dopamine functions differently depending on the area of the brain it is produced in and there are likely other mutation to this gene may also influence its function and expression. These interactions are still being investigated and are why GPL is looking beyond the most common mutation to help inform results.  Conditions associated with these mutations include OCD, depression, and schizophrenia.  Symptomatic patients may benefit from treatment aimed at promoting the enzyme function so that dopamine and epinephrine can be metabolized. This is a SAM dependant enzyme and methylation support can be helpful in patients with this mutation.

APOE
Apolipoprotein E (APOE) combines with lipids in the body to form lipoproteins.  Lipoproteins are responsible for packaging cholesterol and other lipids and carrying them through the bloodstream.  Like so many genes in the human body, this is not its only function. The ApoE protein is involved with more than was originally thought. In this case, it has a role in immune expression, cognitive function, and telomere regulation.  There are four different gene versions of APOE called e1 (the double mutant), e2 (rs7412), e3, and e4 (rs429358).  The most common version is e3, the most detrimental is e4

 Mutations to APOE can lead to an increased risk of developing Alzheimer’s disease. People who inherit even one copy of the APOE e4 allele have an increased risk of developing the disease. Certain mutations to this protein impair the ability of the body to phosphorylate NMDA (glutamate) receptors causing a reduction in activity (Glutamate receptors have been implicated in a number of neuropsychiatric disorders including depression, biopolar disorder, schizophrenia, and Autism (PMID: 12404584, 21315104). While this gene is being extensively studied for its role in Alzheimer’s disease, vulnerable patients may also be predisposed to other psychiatric disorders. (PMID: 25751510, 15557508). Patients with certain ApoE mutations may develop cognitive symptoms well before onset of Alzheimer’s disease (http://psycnet.apa.org/journals/neu/16/2/254/).  Patients with these polymorphisms should look for early signs of the development of Alzheimer’s disease.  Treatment with estrogen has demonstrated some encouraging results.

DAOA
The D-amino acid oxidase activator (DAOA) protein (also known as G72) is a 153 amino acid protein that localizes in the brain, spinal cord, and testis.  This protein is located in the endoplasmic reticulum and the mitochondria cellular compartments.   DAOA is a modulator of D-amino acid oxidase (DAO) activity.  If DAO is hyper activated it can result in a decrease in the D-serine level and hypo function of the NMDA receptor.  Overexpression of DAOA has been found in schizophrenics and those suffering from bipolar disorder.  Mutations to DAOA have been linked to a higher incidence of schizophrenia and bipolar disorder. 

It is important to remember that our genes influence our mental health and well being but do not necessarily determine the eventual outcome. There are countless factors that play an equal role in how we perceive the world including diet and lifestyle.   I believe that understanding the most common mutations and their function is very helpful in diagnosing, treating, and preventing different neurological disorders.  Using the GPL-SNP1000 test in combination with the OAT can further help determine the extent to which our genes are being expressed metabolically. The combination of these two tests can help bring about the best chance to achieve emotional health and physical well being.

Email gplblog@gpl4u.com if you have any questions about this blog post.

 

DNA Methylation Pathway

In my post last week I briefly talked about the methylation pathway, also called the MTHFR cycle and how disruptions in this pathway may appear on an Organic Acid Test (OAT).  Today, I will go more in-depth into this pathway. Since most practitioners have at least some knowledge of this its function, I’ve decided to focus on the more important polymorphisms (SNPs) common to these genes and on the treatments that work the best for these mutations.  Patients should talk to their healthcare practitioner before starting any treatment. 

The important role of methylation is gaining in popularity among functional medicine groups these days because mutations are quite common and lead to many different chronic conditions. Practitioners interested in treating the root cause of illness are especially interested in learning about this pathway because nucleotide synthesis, neurotransmitter function, detoxification, and numerous other processes are greatly improved once these mutations have been compensated for, leading to much better patient outcomes.

If you’re not already familiar, the methylation pathway is a process by which carbons are added onto folic acid from amino acids and redistributed onto other compounds throughout the body.  This process is responsible for the formation of methionine, S-Adenosyl methionine (SAM), and thymidylate monophosphate (dTMP).  Mutations in this pathway usually lead to the reduction of methionine which leads to the absence of S-adenosyl methionine (SAM). This compound facilitates virtually every methylation reaction in the body. These reactions include the promotion of several neurologically important agents, histamine breakdown, CoQ10 synthesis, and tissue-specific gene expression. The accumulation of homocysteine, which is caused by mutations in this pathway, has been directly linked to oxidative stress which influences multiple factors of disease.      

When we designed the GPL-SNP1000 test, we knew that most other genetic tests were only reporting about 35 SNPs of the common methylation pathway enzymes. When we did our literature research, we found 105 different methylation SNPs that could potentially cause health conditions and included all of these to provide a more useful tool for practitioners.

MTHFR

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that converts 5,10-methylenetetrahydrofolate to 5,methyltetrahydrofolate, which is the active form of folate.  Mutations in this gene cause the accumulation of homocysteine and a lack of available folate for cellular functions. Both of these factors have been linked to oxidative stress, vascular disease (including cardiovascular), neural tube defects, neurological disorders (including schizophrenia and bipolar disorder), cancer, preeclampsia, hypotonia, and seizures.  Common mutations are rs1801133 (C677T), rs1801131 (A1298C), and rs2274976 (G1793A).  The C677T polymorphism is present in about 39% of caucasians as heterozygotes and 17% as homozygotes.  Table 1 provides data on how much activity your MTHFR enzyme would possess with different combinations of the C677T and the A1298C.

TABLE 1

TABLE 1

Patients with polymorphisms in MTHFR may consider supplementing with methyl-B12 (also called methylcobalamin) and methyl-folate.  We recommended starting at a very low doses and building up.

MTR

Methionine synthase (MTR) is also known as 5-methyltetrahydrofolate-homocysteine methyltransferase.  This enzyme facilitates the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine using cobalamin (B12) and MTRR enzyme as a catalyst. The end products of this reaction are the amino acid methionine and the vitamin tetrahydrofolate.  Mutations in this gene lead to a lack of methionine and the accumulation of homocysteine in the body (hyperhomocysteinemia).  The pathological consequence of the gene mutation depends on how profoundly these methylation pathways are affected and the degree of homocysteine accumulation in the body.  The most common polymorphism is rs1805087 (A2756G), which most genetic tests do analyze.  However, we decided to look at seven different SNPs including the rs121913581 (R52Q) polymorphism.  This is a rare polymorphism; however it could dramatically affect the activity of patients with MTR polymorphisms, who should also consider methyl-B12, as well as S-adenosyl methionine (SAM) supplementation.  ).

MTRR

Methionine synthase reductase (MTRR) is also known as 5-methyltetrahydrofolate-homocysteine methyltransferase reductase.   MTRR is important for the methylation of cobalamin and subsequent activation of methionine synthase (MTR).  Mutations in this gene lead to a lack of methionine and the accumulation of homocysteine in the body (hyperhomocysteinemia). Some common mutations in this pathway are RS1801394 and RS10380.  Patients who are heterozygous for MTHFR mutations and concomitant mutations to MTRR have a greater loss of function and increased levels of homocysteine. Patients with MTRR polymorphisms should consider methyl-B12 and SAMe supplementation. 

AHCY

Adenosylhomocysteinase (AHCY) is also known as S-adenosylhomocysteine hydrolase.  AHCY is an enzyme involved in the degradation of the amino acid methionine.  AHCY converts the methionine substrate S-adenosylhomocysteine (SAH) to adenosine and homocysteine. This reaction is an important part of the regulation of methyl groups which are added to DNA, RNA, proteins, and lipids (fats).  Methyl groups help regulate what parts of the genome are active and control protein activity.  Mutations to the AHCY gene can cause methionine to accumulate in the blood, which is called hypermethioninemia (MET).  Two common mutations are Trp112X which causes tryptophan to be replaced with a premature stop signal and Tyr143Cys.  MET  can manifest in neurological problems, delays in motor skills, muscle weakness, and liver problems.  Patients with MET should consult with a dietician to avoid the amino acid methionine.

BHMT

Betaine-homocysteine methyltransferase (BHMT) and BHMT2 are the only enzymes that can metabolize betaine.  This reaction is considered the alternate or short route for methylation.  BHMT uses zinc as a co-factor to catalyze the transfer of a methyl group from betaine to homocysteine.  There are several mutations in the human population that decrease the activity of this enzyme.  BHMT mutations can result in fatty liver and hepatocellular (liver) carcinomas.  BHMT mutations in mothers increase the risk of Down syndrome for their children.  Patients with BHMT polymorphisms are recommended to take betaine and zinc.

CBS

Cystathione beta-synthase (CBS) is a pyridoxal-5’-phosphate (vitamin B6) dependent enzyme that converts L-serine and L-homocysteine into L-cystathionine.   L-cystathionine is later converted into the amino acid cysteine.  Mutations to the CBS gene are the most common cause of hereditary hyperhomocysteinemia.   The adverse effects of homocysteine accumulation in the body are related to the substitution of homocysteine for methionine in protein synthesis. The resulting complications include an increase in immune response, increase in cell death, and protein damage. The degree of homocysteinemia is relative to the mutation.  Hyperhomocysteinemia has been linked to multiple mutations to the CBS gene.  The most common of these are the Ile278Thr and the Gly307Ser, which cause homocysteine to build up in the blood.  Complications of hyperhomocysteinemia include mental retardation, seizures, and vascular disease. One of the most common causes of death for patients with homocystinuria (CBS deficiency) is heart attack.   Patients with CBS polymorphisms are recommended to take glutathione and B6.  There are reports that the CBS polymorphisms A360A (rs1801181) and N212N (rs2298758) can lead to an increase in CBS activity.  Some claim that these mutations lead to a buildup of ammonia and decrease in glutathione. Since ammonia is a very unstable compound that must be measured STAT for accurate results, the better marker for increased ammonia is orotic acid which is very stable and accumulates when excessive amines are filtered through the urea cycle. I recommend that patients with this mutation do an Organic Acid test (OAT) and look at marker 60 (orotic acid) for ammonia and markers 58-59 (Pyroglutamic and 2-hydroxybutyric acid) for glutathione synthesis and cysteine accumulation respectively.

SHMT1

Serine hydroxymethyltransferase (SHMT1) is important for linked reactions.  The first is the conversion of tetrahydrofolate to 5,10-methylenetetrahydrofolate.  The second is the conversion of L-serine to glycine.  It also has a role in mediating the synthesis of dTMP and SAM. It preferentially selects for dTMP biosynthesis which is the precursor to the nucleic acid thiamine. Mutations in this enzyme may cause elevations in uracil which can build up when dTMP synthesis in impaired.  Uracil is marker 40 in the OAT.  

SUOX

Sulfite oxidase (SUOX) is an enzyme that is located in the mitochondria of cells.  The enzyme oxidizes sulfite to sulfate.  The physiological damage that occurs as a result of enzyme deficiency may be due to the accumulation of toxic levels of sulfite, from the absence of sulfate, or both. Sulfite is a reactive product of cysteine metabolism found in high concentrations in the brain. Its toxicity is exacerbated by glutathione depletion. Sulfate plays an important role in detoxification and deactivation of toxic compounds. Sulfate deficiency has been linked to autism, Parkinson’s disease, and Alzheimer’s disease.  Individuals with SUOX genetic mutations may benefit from a reduction in dietary methionine and cysteine.

VDR

Vitamin D receptor (VDR) is a nuclear hormone receptor for vitamin D3.  Vitamin D3 interacts with this receptor to influence multiple biological activities by regulating gene transcription.  Vitamin D3 is associated with maintenance of calcium distribution. More recently, it has been implicated in inflammatory processes, vascular integrity, and collagen formation. Mutations in VDR have been linked to metabolic syndrome.  Individuals with VDR mutations have greater propensity for insulin insensitivity, higher triglycerides, and lower HDL levels.  Vitamin D receptor mutations can also lead to vitamin-D-dependent rickets type 2.  Patients with VDR polymorphisms are recommended to take 1000 units/day for children or 5000 units/day for adults. 

I hope this information is helpful.  I know many of these pathways can be very intimidating, but hopefully we can work together to produce useful treatment plans for everyone.  Next week I plan on talking about the mental health genes MAO and COMT.

Email gplblog@gpl4u.com if you have any questions about this blog post.

Genetic Testing and Organic Acids Testing: A Dynamic Duo of Diagnostics

Today I have two words for you:  Personalized medicine.  What does this phrase mean to you?  When I think of personalized medicine I think of treatments that are custom designed for each individual patient, and I believe this is the ultimate goal for all of us in the field of functional medicine.  To make this happen, we will have to work together as a team - the healthcare practitioner, the lab, and the patient.  If we do so effectively, the result should be better health and improved lives of our patients.  The only way to get there is to design a treatment plan that addresses the underlying cause(s) of our patient’s ailments and not try to just suppress the symptoms. 

When I talk to both practitioners and patients, they often ask “Where do we start?” or “What is your most important test?”, and until recently I would have always said that the Organic Acids Test (OAT) is the obvious place to start.  The reason for this is that the OAT provides more information than any other test.  The OAT gives us a metabolic snapshot of multiple pathways in the body, offering insight into possible underlying causes of symptoms, as well as what kind of nutritional support is needed.  However, now the OAT by itself is no longer the obvious choice.  I am now recommending the OAT + GPL-SNP1000 combo because these two tests, one metabolic and one genetic, work so well together.   Today I would like to share some of the markers in each of these tests that work really well in tandem.    The primary pathways where we see overlap between the two tests are methylation, mental health, detoxification, and oxalate metabolism. 

The first pathway that GPL-SNP1000 covers is the DNA methylation pathway, also called the MTHFR pathway.  This pathway is a process by which carbons are added onto folic acid from amino acid and redistributed onto other compounds throughout the body.  This process is responsible for the formation of methionine, S-Adenosyl methionine (SAMe), and thymidylate monophosphate (dTMP).  These compounds are then used in neurotransmitter metabolism, detoxification, nucleotide synthesis, and multiple other processes.  I can’t say enough about how important neurotransmitter metabolism and detoxification of chemicals are to everyone’s health.  We have so many patients for whom the majority of their symptoms result from the upset of these two processes.  Since the methylation pathway is so important we decided to make it a high priority in our new genetic test.   GPL-SNP1000 looks at 105 different methylation SNPs (single-nucleotide polymorphisms).   Next week I plan on going more in-depth on the methylation pathway and how GPL-SNP1000 can be useful.

So what markers in the OAT are important for patients with MTHFR mutations?  The first one we have is vitamin B12.  We evaluate B12 levels by measuring the amount of methylmalonic acid (see Figure 1).  B12 is an important cofactor for many of these methylation enzymes.  The second important marker is pyridoxic acid, which is a form of vitamin B6. I have counted over 50 enzymes that require B6 in the body.  It is an important cofactor in the methylation pathway.  It is directly involved with the function of CBS enzyme and indirectly involved with MTHFR, BHMT, and SHMT.  Another marker involved with the MTHFR pathway is uracil.  Having an elevated uracil level can be indicative of folate pathway malfunction.

The next pathway that is helpful to analyze in both the OAT and GPL-SNP1000 is the mental health pathway, which involves the synthesis and breakdown of neurotransmitters in the brain.  The combination of measuring the neurotransmitter metabolites and knowing if the enzymes involved are functional will help guide us to the best treatment options.  GPL-SNP 1000 covers 14 different mental health genes, which I will cover next week (I’m trying not to make these blog posts too long).  Three of the best markers in the OAT for measuring neurotransmitter metabolism are homovanillic acid (a dopamine metabolite), vanilymandelic acid (epinephrine/norepinephrine), and 5-HIAA (serotonin, marker).  These markers are the metabolites of the neurotransmitters by the enzymes MAOA and COMT (see Figure 2), the genes for which are analyzed in GPL-SNP1000.  Deficiencies in these enzymes due to faulty SNPs  may cause low neurotransmitter levels, which may also be caused by low amounts of precursors, cofactors, or increased inhibitors which is why information from both the OAT and GPL-SNP1000 is so incredibly useful.   

The third pathway that I will briefly touch on today is the detoxification pathway, and specifically for glutathione (GSH).  Detoxification is so important in today’s industrial, polluted, and toxic world.  Every day we are inundated by hundreds of chemicals.  We are exposed to many through the environment and some by choice (like medications).  Our bodies have to process these chemicals in some way.  GPL-SNP1000 looks at dozens of genes that are important for detoxification.  A good marker in the OAT for how well the body is detoxifying is pyroglutamic acid.  Elevated values of pyroglutamic acid are indicative of glutathione deficiency due to excessive toxic exposure or a genetic issue. 

The final pathway I’m going to discuss today is oxalate metabolism.  Oxalates are crystalline molecules that we absorb from our diet (high oxalate foods) or are produced by an infection, like yeast/fungal overgrowth.  These oxalates can accumulate in the body and cause inflammation.  The symptoms of oxalate accumulation include pain, nephrolithiasis, and neurological symptoms. Oxalates are known to cause/create kidney stones.  Children with autism who exhibit eye-poking behavior have been shown to have a build-up of oxalates behind their eyes, causing tremendous pain, and thus the eye-poking.  GPL-SNP1000 covers five different genes involved with the production and elimination of oxalates.  The OAT has three oxalate markers:  glyceric, glycolic, and oxalic acids. (Figure 3)  In addition, low B6 and increased yeast or fungal markers are associated with increased oxalates. 

I think that is all I’ll cover today.  In the future I will cover the methylation pathway and the neurotransmitter pathway a little more in-depth.  If there is another pathway you want me to cover in greater detail, please let me know.  I want to be a part of your healthcare team as we all work together for the better well-being of our patients.

Email gplblog@gpl4u.com if you have any questions about this blog post.

Introduction to GPL Blog


Welcome to the Great Plains Laboratory’s new blog!  First, I would like to introduce myself.  I am Matt Pratt-Hyatt, Associate Laboratory Director at The Great Plains Laboratory.  I am excited to announce this new venue for sharing some of the information that GPL staff have gathered over the years during research and development.  Right here, every Monday, I will be writing and posting a weekly blog, however, we also plan to have guest bloggers contribute.  To supplement our weekly blogs, we will also provide additional content about twice a week, which may include relevant articles and multimedia.   

The Great Plains Laboratory, Inc. was founded by William Shaw, PhD back in 1996, building on the skills and knowledge that he acquired during his time at the Centers for Disease Control and Prevention and at Children’s Mercy Hospital of Kansas City.  In the subsequent years, we have helped over 400,000 patients address root causes of a variety of chronic health disorders, from autism and depression, to fibromyalgia and irritable bowel disease.    

I am looking forward to this opportunity to interact with you – our community of integrative health practitioners.  After working in academic research for 17 years, it has been a great experience joining the GPL team, which I have been a part of for about two years now.  As director of Research & Development, I am thrilled that our team has brought you new, cutting-edge tests like our Phospholipase A2 (PLA2) Test, GPL-TOX (our Toxic Organic Chemical Profile), Glyphosate, and GPL-SNP1000, our Next-Generation DNA Sequencing Profile.  I also enjoy talking with our clients by phone and at conferences, learning more about how you practice and how we can continue giving you even better diagnostic tools to improve the health of your patients. 

Through our interactions with both practitioners and patients, we have been able to further refine our test interpretations to explain how various biological markers reveal many different disease conditions.  We also share what we have learned about the best courses of treatment to recommend.  Through our one-on-one consultations, we have helped thousands achieve better health, but we have been seeking a better way to disseminate this information to an even larger audience ─hence our new blog.  

In addition, I will use this space to discuss the new tests that we will be launching in the future (and trust me, we have some important new tests coming out this year).  I look forward to your feedback on what you’d like to see from this blog.  What are your interests when it comes to integrative medicine? What kind of information would you find most valuable?  How have we helped to improve your life or a patient’s life?  Let us know.  I am happy to be working with you as we embark on this next part of our journey.  Our primary goal in all we do is to find more ways to help you and your patients achieve enhanced wellness.