Using Customized Nutrition to Treat

1. Using Customized Nutrition to Treat Mitochondrial Insufficiency, Type II Diabetes, and Male and Female Infertility

2. 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.

3. 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)

4. 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.

5. Mitochondrial Insufficiency

6. 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.

7. 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 are staggering as I mentioned yesterday.

8. How Toxins Affect Health This stage requires the most energy

9. 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.

10. 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.

11. 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.

12. 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???

13. 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.

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

15. Quick Tip • 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.

16. 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 test should always include Uric Acid which isn’t typically included. • The pattern in the differential of White Blood Cells is helpful in determining the type of infection.

17. 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.

18. 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.

19. Quick Tip • 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.

20. Type II Diabetes Testing Strategies

21. Type II Diabetes • With any diabetic, running a comprehensive blood chemistry should be a given. • Monitoring blood sugar, triglycerides, cholesterol with LDL and HDL are critical to any dietary intervention. • Electrolyte depletion, particularly sodium, potassium, magnesium, calcium, bicarbonates and chlorides are often seen and need to be addressed if deficient. • Some of the markers for oxidation like uric acid are also seen along with elevated fibrinogen.

22. Type II Diabetes • Here is the pattern often seen with people with Type II diabetes: • Elevated: Alkaline Phosphatase, Basophils, Cholesterol, Creatinine, Fibrinogen, Glucose, GGT, Hemoglobin A1c, LDL, Triglycerides, BUN, and Uric Acid • Decreased: Albumin, CO2, Calcium, Chloride, HDL, Iron, Phosphorus, Potassium, and Sodium.

23. Type II Diabetes • Plasma amino acids can also help with a support protocol for people with diabetes. • Cysteine and Taurine are beneficial in preventing kidney failure. • Taurine is helpful in counteracting oxidative stress commonly found in diabetics. • It should be used with caution as it can lower blood sugar due to its action of potentiating insulin. • GABA is thought to increase insulin’s effect and the use of 2-4 grams can significantly decrease blood sugar.

24. Type II Diabetes • Alanine is well known to help reduce triglycerides, reduce ketosis (common with diabetics). • It may parallel blood sugar levels in both diabetics and hypoglycemics. • Before using amino acid therapy you should check their plasma levels to make sure you are using a biochemically individualized protocol. • While amino acid therapy is a powerful tool to use with diabetics, it can become a double edged sword if used incorrectly.

25. Type II Diabetes • An Environmental Pollutants Biomarker test is also very helpful if the person has been exposed to high levels of a number of toxins. • Phthalates have been shown to affect insulin resistance. • Stahlhut, R., E. Wijngaarden, et al. (2007). "Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males." Environmental Health Perspectives115(6): 876-82. • Chemicals like toluene, xylene, benzene and styrene have been implicated in a wide array of endocrine disruption and blood sugar regulation.

26. Type II Diabetes • When it comes to these chemicals, they are well known to bind to the PPAR gamma receptor which when turned on, stabilizes blood sugar levels. • According to Dr. Lindsay Berkson in her great book, Hormone Deception she says the following: “Well, if science has termed the estrogen receptor as promiscuous – meaning it will mate with a wide variety of chemical partners – the PPAR receptor is even more indiscrete about its bedfellows…. It may be that endocrine-disrupting compounds are contributing to insulin resistance by inhibiting this receptor.”

27. Type II Diabetes • Many of the chemicals and heavy metals that may affect the receptors also affect the thyroid. • People with diabetes who develop hypo- or hyperthyroidism have a much harder time controlling their blood sugar. • Making sure the diabetic patient is controlling their toxic loads and are becoming good toxin excretors will go a long way in helping them control their blood sugar and insulin levels. • This is why a urine test is so important. It no longer is a question of whether we have the toxins in our blood but do we excrete them efficiently.

28. Quick Tip • Fibrinogen is a noted risk factor for coronary and vascular disease. • But is this a causative factor? • Fibrinogen it turns out, is actually an antioxidant. • According to Olinescu and Kummerow, Journal of Nutritional Biochemistry, Vol 12, Num 3, March 2001, “Fibrinogen, albumin, ceruloplasmin, and transferrin act as a supplementary antioxidant defense mechanism against oxidative stress arising from inflammatory conditions.” • Fibrinogen is a marker for oxidative and inflammatory stress not as a causative factor in CVD.

29. Type II Diabetes • Urinary Organic Acids are a tertiary test to use because it can help identify the following problems known to occur in diabetics: • Excessive Fatty Acid Oxidation • Carnitine Deficiencies • Keto-acidosis • Disordered Gluconeogenesis • Excessive Oxidative Stress • Intestinal Dysbiosis • B-Complex Competency • Liver Detox Dysfunction • Poor Energy Production

30. Type II Diabetes • As with most disorders, inflammation is a key component in the progression and/or control of diabetes. • Diet is critical. • Assessing the foods that can trigger inflammatory reactions is important in helping your patient achieve optimal help. • This is another good reason to utilize the LEAP MRT blood test.

31. Type II Diabetes • The LEAP MRT test is beneficial in order to isolate those foods, regardless of their affect on blood sugar, that might induce an inflammatory response. • Reducing this response will improve the quality of life of the diabetic since many of them have numerous other symptoms like arthritis. • Drugs used to treat arthritis like anikinra (Kinemet) have been shown to help regulate blood sugar because of their effect on the cytokine IL-1 (interleukin-1).

32. Type II Diabetes • The immune system produces cytokines in response to inflammation in the body. The cytokine, Interleuken-1 (IL-1) shows up in areas of inflammation, like in the joints or other places in the body. Anakinra blocks the production of interleukin-1. That's why it's used to treat arthritis. • In diabetes, interleukin-1-beta is produced in the pancreas. High glucose levels appear to trigger the release of interleukin-1-beta. This not only reduces the function of beta cells in the pancreas, but can cause beta cells to self-destruct. • This is why using LEAP MRT with diabetics may be highly beneficial.

33. Infertility/Pregnancy Testing Strategies

34. 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

35. 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.

36. Infertility/Pregnancy • This 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.

37. 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.

38. Child Development • 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.

39. Child Development • 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.

40. Child Development • 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 critical.

41. Infertility/Pregnancy • When it comes to testing strategies, with 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 Perspectives116(3): 334-9.

42. 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.

43. 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.

44. 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.

45. Quick Tip • 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.

46. Infertility/Pregnancy • In the book “The Carnitine Miracle” author unknown, it 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

47. Infertility/Pregnancy • 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 for the risk of developing pre-eclampsia. • 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.

48. Infertility/Pregnancy • In our CardioHormone saliva/blood spot test, the pattern looks like this – • Elevated: Triglycerides • Decreased: Estradiol, Insulin, Progesterone, and Free-T4 • 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.

49. 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.

50. 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.