Toxicity, Neurotoxins, Cognitive Dysfunction: Laboratory Testing and Practical Treatment Options

Mark Schauss, DB Lab Interpretation, LLC Copyright 2008 Lab Interpretation LLC

Toxicity, Is it in you?

• When the topic of toxicity is discussed, we should no longer wonder whether our patient is toxic or not, but whether they are good excretors of toxins.

• This is especially true when dealing with petrochemical solvents as well as heavy metals.

• Other toxins like the byproducts of bacterial, parasitic and viral metabolism should also be monitored.

• The toxicity of stress is another issue that should be monitored.

Toxicity, Is it in you?

• Tonight’s discussion will center on the appropriate laboratory tests that will help you assess whether your patient is properly excreting the toxins that they are exposed to and the biochemically individualized ways that you can help them become efficient detoxifiers.

Detoxification

• Detoxification should be thought of as a three step process.

• First step is to identify the toxins (never assume there is only one) and begin a specific detoxification protocol.

• This is where you determine the patient’s ability to naturally detoxify, support whatever phase of detoxification is efficient (if any) and bolster the phase that is inefficient in an individualized manner.

Detoxification

• The second step, the part I feel is most important is to identify the source of the toxicity.

• If phthalates are the problem, look into the sources like cosmetics, air fresheners, perfumes and colognes, microwaving of plastics, etc… • If it is stress, look into their lifestyles, behaviors, home life, and their past to name a few.

• Have them do an inventory of their environment to see where the toxins are and have them work on eliminating them.

Detoxification

• The third step may be the hardest to convey.

• We no longer live in a world where “living clean” makes you free of toxic exposure.

• Eating organic, making sure you avoid toxicity in your home and work area is important but it does not keep you safe.

• We live in a toxic world.

• Because of this concept, we need to become efficient excretors of toxins for life.

Detoxification

• People need to have tools to become efficient excretors and they need to do this on a daily basis.

• All of us, need to practice this on ourselves before we practice it on our patients.

• Educating the patient that this is a life long change that they need to commit to is critical to their ability to achieve victory over this toxic world.

• Turning ones face to the onslaught of toxins and denying it is an invitation to disease, morbidity and eventually mortality.

Mitochondrial Insufficiency

• Mitochondrial diseases typically present as neurological disorders but can manifest as other disorders such as diabetes, myopathies, cardiovascular disease, stroke, epilepsy and retinitis pigmentosa.

• These diseases are linked because of cellular damage causing oxidative stress and the accumulation of Reactive Oxygen Species (ROS).

• These oxidants then damage the mitochondrial DNA resulting in mitochondrial dysfunction and cell death.

Mitochondrial Insufficiency

• In our discussions today, we are not going to delve into the world of mitochondrial myopathies (MM) which include:

– Kearns-Sayre syndrome (KSS) – Leigh's syndrome – mitochondrial DNA depletion syndrome (MDS) – mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) – myoclonus epilepsy with ragged red fibers (MERRF) – mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) – neuropathy, ataxia and retinitis pigmentosa (NARP) – Pearson syndrome – progressive external ophthalmoplegia (PEO)

Mitochondrial Insufficiency

• • We will be delving into the impairment of the proper and optimal functioning of the cells powerhouse.

• First we need to talk about the major causes of mitochondrial insufficiency.

– Nutrient Deficiencies – carnitine, Coenzyme Q10, taurine, trace minerals, B vitamins, alpha lipoic acid, and NADH.

– Toxicity – heavy metals, organochloric and organophosphic compounds, petrochemical solvents and others.

– Infections – bacterial and viral – Stress Kidd, PM, Neurodegeneration from Mitochondrial Insufficiency: Nutrients Stem Cells, Growth Factors, and Prospects for Brain Rebuilding Using Integrative Management, Alternative Medicine Review, Vol 10, Num 4, December 2005.

Mitochondrial Insufficiency

• The current thinking is that most mitochondrial diseases are the result of one or more complex inheritance patterns. Most mitochondrial diseases are the result of mutations (changes) in DNA located in the nucleus of the cell. Only mitochondrial disorders caused by mutations in the mitochondrial DNA (a specific structure in living cells, located outside the nucleus) are inherited exclusively from mothers.

• What we will be discussing is where the mitochondria become inefficient, unable to fully carry out their jobs and how that affects optimal health.

Mitochondrial Insufficiency

• The Krebs Cycle aka Citric Acid Cycle is part of the process that leads to the production of energy (ATP for one example).

• In my research and review of thousands of lab tests, toxins have a dramatic effect on the ability to create energy within the Citric Acid Cycle.

• The implications on diseases like obesity and neurological disorders are staggering.

Mitochondrial Insufficiency

#1 Homeostatic State Good Health #2 Toxic Exposure #5 Return to Good Health #4 Detoxification Intervention #3 New Homeostatic Acute Survival

Mitochondrial Insufficiency

• To test for disruptions to the Citric Acid Cycle and to find out what detoxification interventions are needed, I recommend two tests.

• The first is a urinary organic acid test from either MetaMetrix or US Biotek.

• The second is an Environmental Pollutants Biomarker urine test from US Biotek for the presence of metabolites of petrochemical solvents.

• The use of the LabAssist™ interpretive report is the only way to determine the level and area of disruption along with the proper protocols of detoxification.

Mitochondrial Insufficiency

• Most solvents have similarities in detoxification protocols with some minor and/or major differences.

• One that needs a different approach for safety reasons is in the detoxification of benzene.

• In a dysbiotic gut, taking either tyrosine or phenylalanine could cause the production of phenol compounds.

• These phenol compounds could cause an increase in the carcinogenicity of benzene.

Mitochondrial Insufficiency

• One of the most important issues in today’s society is aging.

• With our aging population, a lot of people want to know how to slow down the process.

• Here is what we do know: – Aging is about oxidation • The use of anti-oxidants do not seem to slow down the aging process all that much.

Mitochondrial Insufficiency

• You can cut back the speed at which you age by cutting back on the amount of food you eat drastically.

– Numerous studies suggest that it is the quantity of food that is the key. When you eat very little the cells last longer. Or is that the real mechanism???

Mitochondrial Insufficiency

• The real key to living longer is reigning in inflammation.

• In an excellent, but hard read, Professor Caleb E. Finch wrote the book –

The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans

, 2007 Academic Press discusses the issue.

• Does the longevity research into low-calorie diets only mean that the low intake is the sole anti-aging driver?

• Another possibility is that when you restrict you diet, you avoid inflammatory foods.

Mitochondrial Insufficiency

• The LEAP MRT Food Sensitivity test is a good way to find out what foods increase the inflammatory response.

• By avoiding these foods, you can drastically reduce inflammation which is beneficial not just in slowing down the aging process but in a myriad of inflammatory diseases ranging from coronary heart disease, migraines, arthritis, irritable bowel syndrome, and any neurodegenerative disease.

• We know that inflammation can also affect the mitochondria so any time we can reduce inflammation we protect the mitochondria.

Mitochondrial Insufficiency

• We know that chronic infections cause oxidative stress (Wen et al, 2006).

• Monitoring the patient using a Comprehensive Blood Chemistry is highly beneficial.

• The pattern in the differential of White Blood Cells is helpful in determining the type of infection.

• The test should always include Uric Acid which isn’t typically included.

Mitochondrial Insufficiency

• Uric Acid is one of the bodies natural antioxidants.

• Increased levels are typically caused by the bodies need for antioxidant help. • It is known to scavenge peroxynitrate.

• Multiple sclerosis patients have low Uric Acid and high peroxynitrate.

• Lower serum Uric Acid levels in MS patients may represent a primary, constitutive loss of protection against Nitric Oxide.

• Stimulating xanathine oxidase through the use of molybdenum may be beneficial.

Mitochondrial Insufficiency

• Neutrophils are typically indicative of a bacterial infection but an increase of the absolute numbers can occur with inflammation.

• Eosinophils are typically seen in allergic responses but also in infestations of parasites.

• Basophils are rarely seen but when they are elevated it is indicative of an allergic response and correlates to elevated histamine in the blood.

• Monocytes, the largest of the white blood cells are phagocytic as they are viewed as scavengers but they also produce the antiviral agent interferon.

Mitochondrial Insufficiency

• Lymphocytes are a primary defense against viruses but they are also seen in the early and late stages of inflammation.

• Looking at the pattern of these cells both in percentages of the total and in absolute numbers can give you a very accurate picture of what is going on immunologically.

• With LabAssist™ we have already pre programmed many of these patterns.

• Through that we have even been able to reveal a case of Psittacosis.

Mitochondrial Insufficiency

• If you have a person that has done a saliva hormone test and noticed that their cortisol levels do not go down through the day as expected the mechanism may be toxic in nature.

• In a study published in EHP this February, Gump et al showed that lead levels, even low ones below 10 μg/dL can alter corticosteroid levels and interfere with heightened reactivity to acute stress.

• This is also found quite often in large cities with high powered executives. • The higher lead levels in big cities like New York may explain the higher stress readings of inhabitants.

Infertility/Pregnancy

• At no time in human history has infertility reached such epidemic proportions.

• The blame clearly has to lie at the feet of our toxic environment.

• According to the Center for Disease Control’s National Survey of Family Growth the fastest growing segment of the population with “impaired fecundity (infertility) is women under the age of 25.” • In 2005 the CDC did a survey across America where the average citizen had the presence of 148 chemicals in their blood. The report is 475 pages long.

– Third National Report of Human Exposure to Environmental Chemicals, Centers for Disease Control and Prevention 2005. www.cdc.gov/exposurereport/pdf/thirdreport.pdf

Infertility/Pregnancy

• One line in the report struck me for different reasons than it might strike others.

• Under Public Health Uses of the

Report

it states “To establish reference ranges that can be used by physicians and scientists to determine whether a person or group has an unusually high exposure.” • As we know with laboratory testing, often times reference ranges are skewed due to an abnormal population. Case in point TSH levels. Most labs use .5 to 5 as a range. LabAssist ™ uses 1.1 to 2.5 because so many in our population are hypothyroid they skew the range.

Infertility/Pregnancy

• This report makes it so that it will somehow be used to allow for an “acceptable level” of toxicity for each of you and your patients.

• Some chemicals have an effect at low levels only.

• Polymorphisms in genes coding for metabolizing enzymes contribute to interindividual variability and may vary by more than 50-fold in humans (Guengerich et al. 1991). • What is a poison for you may not be for me.

Infertility/Pregnancy

• According to research done by the EPA on Bisphenol A (BPA), they only looked at the changes to the weight of rat brains to determine toxicity levels.

• Some studies found changes in rodents' reproductive organs and brains at doses as low as 0.002 mg per kilogram of body weight per day. • is just one-25,000th the dose that the EPA said was the lowest exposure having an observable adverse effect. • Newer research into the subtle effects of BPA on hormone levels indicates that far lower doses can have profound effects on the development of human fetuses and on adult health, especially women.

Infertility/Pregnancy

• In the 1970’s, Danish researcher Niels Skakkebaek of the Copehagen University Hospital showed links between testicular cancer in adults and abnormalities in genital development.

• At 3 months, baby boys experience a surge of testosterone.

• In a study of 65 infants published in 2006, they discovered that the higher the level of phthalates, the greater the evidence of anti-androgenic hormonal activity.

Infertility/Pregnancy

• Ana Soto of Tufts University School of Medicine was studying the effect of estrogen on a breast cancer cell line. • Much to her chagrin, the cancer cells were proliferating like crazy as if a bottle of estradiol had been dumped in them.

• Turns out, the tubes storing a component of the medium growing the cells had nonylphenol to improve impact resistance.

• The chemical, injected into rats, made the epithelial lining of the uterus proliferate – a sign of its being an estrogen.

Infertility/Pregnancy

• If the findings that chemicals like Bisphenol A (BPA) are found in the drinking water, house dust, and ambient air are true and at tiny levels they can affect estrogen receptors think of the types of cancers our children will have.

• In the 1950’s a woman’s lifetime risk of breast cancer was 1 in 22. • Today it is 1 in 7.

• It is not a genetic epidemic, it is environmental, it is due to endocrine disruption.

• BPA is worth $100 million an hour.

• Banning it will take enormous guts.

• Becoming good detoxifiers forever is therefore critical.

Infertility/Pregnancy

• I believe that for all people, male or female, it is imperative to do an Environmental Pollutants Biomarker test.

• Phthalates, xylene, toluene, benzene, styrene, and dimethylbenzene are all developmentally toxic.

• Phthalates can damage male DNA in sperm.

• It can also cause shortening of pregnancies by up to two weeks and according to research full-term babies have markedly higher cognitive scores later in life (Larroque, et al, The Lancet, Vol 371, pg 823).

• Urinary markers of phthalates are vastly superior to serum.

– Hogberg, J., A. Hanberg, et al. (2008). "Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vunerable populations." Environmental Health Perspectives

116

(3): 334-9.

Infertility/Pregnancy

• Becoming an effective excretor of petrochemicals is an important factor in developing a healthy fetus.

• In a study published by Hansen, Barnett, and Pritchard, in EHP, March 2008, it was found that air pollution can actually affect ultrasound measures during mid pregnancy.

• Fetuses were physically affected in body measurement by air pollution.

• While the study focused of measurements of ozone, nitrogen dioxide, sulfur dioxide and particulate matter, being a good excretor of any chemical would be beneficial.

Infertility/Pregnancy

• For women, I would highly suggest doing two additional tests.

• A Whole Blood Elements test from DDI would be #1 as quite often women trying unsuccessfully to have a child are very mineral deficient.

• Also, any toxic heavy metal load could decrease the chances for a healthy pregnancy.

• In the March 2008 EHP journal, researchers led by Leasure, et al, showed that gestational lead exposure produced permanent male-specific effects including an increase in obesity as well as motor deficit, and altered dopamine.

• The responses were dose-dependent.

Infertility/Pregnancy

• Secondarily, a Plasma Amino Acid test often times show broad deficiencies in both essential and conditionally essential amino acids.

• With women, there have been some issues with increased tryptophan and elevated serotonin (especially with 5-HTP) and an increase in miscarriages, dysmenorrhea and tubal spasms.

• With males, it may improve sperm viability.

• In a study by Schacter in 1973, 4 grams of arginine was used on 178 men and 111 had significant improvement, 21 moderate and only 25 showed no improvement in sperm motility and sperm counts.

Quick Insight

• Total Cholesterol levels are different depending on the time of the year.

• In Spring and Summer, Cholesterol is lower than in the Fall and Winter.

• When comparing Cholesterol levels be aware of this difference which can be as high as 20%.

• If you were to design a study to prove your drug was good at lowering Cholesterol you would take the first measurement in the Winter and the second in Late Spring, Early Summer.

Infertility/Pregnancy

• In the book “The Carnitine Miracle” by Robert Crayhon, the role of carnitine was discussed in relation to its ability to “defend the body from stress.” • Also there is a higher quantity of carnitine in male sperm.

• A comprehensive blood chemistry is also a very important tool to use, especially in women.

• Pre-eclampsia is an important issue to address for women seeking to get pregnant or are pregnant.

• The LabAssist™ has a pattern developed to evaluate the results of a CBC

Infertility/Pregnancy

• The pattern is as follows: – Elevated: sGOT, sGPT, Alkaline Phosphatase, Hematocrit, Potassium, Triglycerides, and Uric Acid.

– Normal: Hemoglobin – Decreased: Albumin, CO2, Calcium, Glucose, Protein, Sodium, Thyroxine, and BUN.

• In a healthy pregnancy, there are a number of test results that are normal and expected that would be considered abnormal otherwise.

• LDL, Total Cholesterol and Uric Acid should actually be elevated.

Infertility/Pregnancy

• A urine iodine challenge is another critical test to do for pregnant women. • In the autism pesticide study (Roberts, et al, 2007 EHP), iodine deficiency may be the mechanism by which the incidence of autism rose to exposed mothers.

• Since many environmental toxins affect the thyroid and the lack of iodine can adversely affect the fetus, this is another very important test to run.

Infertility/Pregnancy

• If there is a hesitation to do all of the testing here are a few tried and true general recommendations.

• Since we all have petrochemically based toxins in our system, both the mother and the father should begin using a broad spectrum amino acid complex with at least one gram of glycine per serving.

• Women should be put on a broad spectrum trace mineral supplement.

• They should also be put on a balanced electrolyte. • Add DHA/EPA combination.

Autism

• In my many years of work, it is striking that in the field of autism more unnecessary tests are run on autistic children than any other disease or syndrome which testifies to the desperation of parents of autistic children.

• My goal is to provide the least number of tests necessary to make the greatest impact on children with autism.

• Another important issue is not putting the children through traumatic testing more often than is necessary.

• Conservation of resources while improving outcome is essential and should be the overriding principle.

Autism

• Here are a few tests I would avoid for the treatment of most autistic children.

• RBC fatty acids – Fatty acids are typically abnormal in most autistic children but there is no evidence that targeting fatty acids through a test is beneficial.

– Co-factors such as magnesium and vitamin B6 can lower arachidonic acid which is not uncommonly high in autistics.

– There are better tests not requiring a blood draw that can give you the same information.

– One researcher has astonishingly claimed that autistic children have higher Omega 3 to 6 levels!

Autism

• Fatty acid metabolism can be negatively affected by environmental toxins. • Affecting the fatty acids does not address the toxicity issue.

• It is minimally beneficial in removing heavy metals or pollutants. • When dealing with autistic children, if we can avoid a blood draw, you reduce the stress on these children.

• A traumatic draw can change the results on a test.

– Levels of liver enzymes, hormones, electrolytes, blood cell counts can all be negatively affected by the way the draw is done.

Autism

• Urinary porphyrin testing is the latest rage.

• It is theoretically useful if the specimen is handled correctly.

• There in lies the rub.

– Porphyrin’s are highly light and air sensitive.

– Pee into a bucket with a fluorescent light and half the analyte is gone.

– Shaking instead of gently rocking the specimen can cause depletion of the porphyrin analyte.

• There is a very high incidence of false negatives with this test.

• Even with proper handling, the false negative rate reduces clinical utility.

Autism

• Urine heavy metal challenge tests are also commonly used with children with autism.

• It’s clinical utility is questionable.

• The risk of developing side-effects due to the use of a chelating substance is substantial.

• It does not indicate the burden and/or the disruption of biochemical pathways due to mercury or other heavy metals.

• A hair elements test, using the counting method developed by Dr. Andrew Cutler and spelled out in his books Hair Test Interpretation and Amalgam Illness (available at www.noamalgam.com) is safer and superior.

Autism

• According to the data from the DAN website, chelation therapy has a very high positive outcome with a low negative and relatively low no effect rate.

• http://www.autism.com/treatable/form34qr.htm

• Out of 803 cases reported the positive response rate was 74% with negative results being at 3% and no response being the lowest of all treatments at 23%.

Autism

• Urine Organic Acids (OAT) along with an environmental pollutants biomarker test is a non invasive, helpful test to assess abnormal biochemical pathways in autistic children.

• Yeast markers among these children using an OAT test has been vastly over blown.

• The markers Tartarate and Citramalic acid are not markers for yeast.

• Tartaric Acid actually kills yeast and is not a byproduct of yeast.

Autism

• So why do children with autism improve using anti-fungals if yeast is not so prevalent?

• Many children with autism have upregulated Phase I detoxification pathways and down regulated Phase II.

• The intermediary chemicals created in Phase I are more neurologically toxic than the original chemical, especially with petrochemical solvents.

• Anti-fungal drugs down regulate Phase I which allows Phase II to catch up.

• This is also why they do so poorly after removing the drugs.

• Improving Phase II through the use of amino acids such as Glycine will help upregulate Phase II.

Autism

• I see a high percentage of autistic children, especially boys with high urinary phthalate levels.

• They also often times have other solvents such as xylene, toluene, styrene, and benzene.

• Detoxifying these ubiquitous chemicals seems to lower many of the common traits such as stimming, head banging and hand flapping.

• This may be due to the upregulation of Phase II detoxification from the detoxification protocols reported in the LabAssist Interpretive Reports.

Autism

• A Plasma, Blood Spot or Urine Amino Acid test would be beneficial in assessing these important builders of neurotransmitters.

• LabAssist TM has developed a method to customize the My Aminoplex based on a Plasma or Blood Spot Amino Acid test.

• We see a number of children with autism with dramatically abnormal amino acid profiles.

• Taurine is typically low and autistic children benefit greatly from its supplementation.

Detoxification Tips

• Most people with petrochemical exposure (almost everyone) would do well to take 1-2 grams of glycine daily.

• Taurine at 1 gram a day is another highly beneficial amino acid in a detoxification protocol.

• Probiotics are another almost universally necessary supplement for toxic people.

• Electrolytes are critical in helping pump toxins and nutrients in and out of cells.

Detoxification Tips

• One concept though is absolutely critical in giving your patients the utmost ability to detoxify for the short- and long-term.

• Treat them as biochemically individualized people.

• There is no “one shoe size fits all” protocol.

• Lab testing is the only way to go and will increase the effectiveness of any program you put together for your patient.

Heavy Metal Neurotoxicity Effects

• Promote lipid peroxidation • Inhibit antioxidative enzymes/processes • Affinity for sulfhydryl groups • Disrupt ion homeostasis (Ca, Na, K) • Disrupt neurotransmitter metabolism

Heavy Metal Neurotoxicity Effects

• Primary mechanisms of Pb neurotoxicity are due to disruption of Ca metabolism • Lead enters cells through Ca channels, keeps Ca channels open about 5X longer than Ca

Heavy Metal Neurotoxicity Effects

• Pb +2 and /or  Ca +2   spontaneous NT release: responsiveness: distractibility, impulsivity and motor restlessness • Pb +2  dopamine uptake and serotonin levels • Inhibits NMDA receptor • Alters metabolism of

dopaminergic, cholinergic, and glutamanergic neurotransmitters J Neurochem(1996)67:1540-50 Excellent Review: Ann Rev Pharmacol Toxicol(1995)35:391

Heavy Metal Neurotoxicity Effects

• Manganese Neurotoxicity • Phase I Psychiatric Abnormalities: Hyperirritability, violence, compulsiveness, forced laughter, apathy, sleep disturbance, paranoiac behavior • Phase II Neurological Disorder of Extrapyramidal Motor System: Tremor, loss of speech/motion coherence, high-stepping gait (“velcro feet”), mask-like face • Phase III Bradykinesia, rigidity

Heavy Metal Neurotoxicity Effects

 Mechanisms of Manganese toxicity  Oxidative stress/damage  Abberant neurotransmitter metabolism  levels of dopamine and norepinephrine in brain  binding of serotonin to membranes

Heavy Metal Neurotoxicity Effects

• Accumulation of toxic metals can adversely affect virtually every major organ system and instigate chronic diseases.

• Lead is

still

an important health issue for all ages.

• Middle-aged women are very vulnerable to “old” Pb.

• Selenium, zinc and iodide are important anti-cancer elements.

• Early assessment and elimination of toxic metals should be an integral component of all comprehensive medical practices.

Contact Information

Dr. Mark Schauss, DB Lab Interpretation LLC 18124 Wedge Parkway, Ste 432 Reno, NV 89511 775-851-3337 [email protected]

www.labinterpretation.com

www.CrayhonResearch.com

www.MarkSchauss.com

www.ToxicWorldBook.com