Toxic Chemicals

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.

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

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.