Functional Vitamin, Mineral and Antioxidant Assessment. J.F. Crawford, PhD. SpectraCell Laboratories, Inc. Houston, TX

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1 Functional Vitamin, Mineral and Antioxidant Assessment J.F. Crawford, PhD. SpectraCell Laboratories, Inc. Houston, TX 1

2 Recent Publications Antioxidant supplementation increases morbidity and mortality. JAMA,

3 Micronutrient testing offers a unique, scientifically based evaluation of functional deficiencies that allows targeted treatment with nutritional supplements improving patient compliance with tailored therapy and success in the treatment of a variety of diseases. Mark Houston, M.D. Hypertension Institute St Thomas Medical Center &Vanderbilt University 3

4 4

5 IMMUNOCOMPETENCE CELL-MEDIATED IMMUNITY T-LYMPHOCYTES (Th1) HUMORAL IMMUNITY B-LYMPHOCYTES (Th2) 5

6 T-LYMPHOCYTES Th1 (Cell Mediated Immunity) Attack Intracellular Pathogens - DTH skin responses to viral + bacteria Ag - CANCER cells Organ Specific Autoimmune Disease (Arthritis, MS, Type I Diabetes) 6

7 B-LYMPHOCYTES Th2 (Humoral( Immunity) Protection Against Extra Cellular Pathogens Antibody Production Allergy + Related I g E based disease (Systemic Autoimmune Disease) 7

8 8

9 Improved Cellular Performance Your cellular performance may also be improved after information obtained from micronutrient testing. 9

10 T-Lymphocytes are used for MNT 10

11 Technology Summary Day 1 Isolation of Lymphocytes Incubation & Growth in defined culture media Long term nutritional marker Patented technology 15 yrs development at U.T. Austin Days 2-3 Mitogen stimulation & growth Vary components growth dependent on intracellular levels Day 4 3 H Thymidine incorporation 200 growth measurements Day 5 Growth response measurement Deficiency, transport & metabolic requirements 11

12 Intracellular Micronutrient Testing Nutrients Analyzed Thiamin (B1) Riboflavin (B2) Niacin (B3) Pantothenate (B5) Pyridoxine (B6) Cobalamins (B12) Folate Biotin Inositol Choline Chromium Calcium Magnesium Zinc Serine Glutamine Asparagine Oleic Acid Insulin Sensitivity CoenzymeQ10 Lipoic Acid Fructose utilization Spectrox antioxidant function Glutathione Cysteine Selenium Vitamin C Vitamin E Vitamin D (2) Vitamin K Carnitine Copper 12

13 Nutrient Deficiencies and Previous Supplementation Multiple deficiencies with no previous supplementation Multiple deficiencies with previous supplementation 38% 43% 19% Subjects showing no deficiency 13

14 Intracellular Micronutrient Deficiencies 35.0% 30.0% ZINC 25.0% 20.0% B12 CALCIUM GLUTATHIONE SELENIUM 15.0% B1 E 10.0% FOLATE LIPOIC D 5.0% B2 MAG 0.0% 14

15 Factors Affecting Nutrient Status Dietary Intake Absorption Transport Storage Receptors Activation Inhibition Metabolism Excretion Hormonal Status Genetic Influences Disease Lifestyle Factors Pharmaceuticals Age Gender Socioeconomic Cultural/Ethnic Pregnancy Exercise Smoking Alcohol 15

16 High-dose Vitamin Therapy Stimulates Variant Enzymes with Decreased Coenzyme Binding Affinity: Relevance to Genetic Diseases and Polymorphisms Bruce N. Ames, M.D., et al., The American Journal of Clinical Nutrition, Vol 75, No 4, April

17 Medications & Nutrient Deficiency Anti-Depressants Elavil, Tofranil, Sinequan, Aventyl Anti-Inflammatory Aspirin, Advil, Motrin Prednisone, Cortisone Statins B12, CoQ10 Vit C, Folate D, Folic, Cal, Mag, Selenium, Zinc CoQ10, B12, D, E, Folic, A Hormone Replacement Therapy Evista, Premarin, Estratab B2, B6, B12, C, Folate, Mag, Zinc 17

18 Proliferation Index I N D E X YEARS Average < 25% > 75%

19 Biochemical Pathways Methionine S-Adenosyl Methionine Homocysteine B 6 B 12 Cystathionine B 6 THF Methyl-THF Cysteine Folate 19

20 Homocysteine & Vascular Disease Genetic and Dietary Determinants of Serum Homocysteine Concentrations Genetic Cystathionine-beta-synthase deficiency Methionine synthase deficiency MTHFR deficiency Nutritional * Vitamin B 6 Vitamin B 12 Folate Defective absorption of B 12 or Folate Prevalence: 30% Female 25% Male * 75% of cases of Hyperhomocysteinemia are nutritional in origin 20

21 Homocysteine & Vascular Disease Effects of Treatment With N-Acetyl Cysteine (NAC) 20 O.Wiklund et al. / Atherosclerosis 119(1996) Homocysteine (um) Before During After Before During After PLACEBO NAC 21

22 Model of Inflammation and Inflammatory Disease Classical Inflammatory Mediators Cellular attack ( free O 2 ) Macrophage releases lymphokines producing IL-1 T-lymphocytes produce IL-2 I-1 and I-2 proliferation of T-lymphocytes produce interferon Cell-killing activity of T-cells and NKC enhanced and free radical production 22

23 The Magic Bullet

24 Major Cellular Antioxidants Antioxidant Nutrients Vitamin C (Ascorbate( Ascorbate) Vitamin E (Tocopherols) Selenium Glutathione Antioxidant Enzymes Superoxide Dismutase (Zn Cu, Mn) Catalase (Fe) Glutathione Peroxidase (Se) 24

25 Markers of Oxidative Stress Thiobarbituric Acid Reactive Substances (Tbars( Tbars) Lipid Peroxides Isoprostanes Guanosine Derivitives Selenium Protein Carbonyls Orac & Trap Lymphocyte Culture (Spectrox)

26 Antioxidant Balance Arachadonic acid peroxyl radical Prostaglandins (E series) thromboxanes, leukotrines 12-HETE (alcohol) 12-HPETE (hydroperoxide endoperoxide) tocopherol tocopherol radical ox Dehydroascorbate Ascorbate Glutathione (GSH) Glutathione disulfide (G-S-S-G) NADP NADPH 26

27 Spectrox - Total Antioxidant Function Status Result: 51.2 Percentile Reference Range: Desired > 65th percentile Average 40th to 65th percentile Deficient < 40th percentile Desired Average/Deficient P E R C E N T I L E SPECTROX 65th 50th 40th Desired Results Average Deficient Total Antioxidant Function 27

28 Antioxidant Testing 100% Complete + Cells + Free Radicals = Spectrox 1 100% Complete + Cells + Selenium = Saturated Cells Saturated Cells + Free Radicals = Spectrox 2 Measurement: % improvement in Spectrox 1 28

29 Figure 1 % Change After Treatment Pre-Treatment Spectrox Value Range: 1<25, 2= 25-40, 3=40-55, 4=55-70, 5>75 (p<0.05) 29

30 TSH Iodine Ferritin Vit D 3 T 4 to T 3 decreased by rt 3, deficiencies of selenium, zinc, chromium, etc. T 4 Zinc T 4 to T 3 increased by abnormal cortisol, TPO antibodies, T 4 medication (Synthroid), estrogen (Good) T3 rt3 (Bad) (Excess) 30

31 T 4 & rt 3 T 3 Ferritin Cell membrane Cell nucleus T 3 Blocked by rt 3, TPO antibodies low or high cortisol T 3 has 3 molecules of iodine that are stripped off if iodine levels are low RE Vitamin D & zinc Retinoic Acid Retinol HCY T 3 receptor density is influenced by cortisol, inadequate if too high or too low 31

32 Nutrition and Estrogen Metabolism Cholesterol Testosterone Insulin Mediated (Mg ++, Chromium, B-complex ) Estrogen B6, B12, THF, Mg++ 2-Methoxyestrogen Good estrogen Oxidation Can be prevented with anti-oxidants 3,4 Quinones Potential Carcinogens Selenium, Glutathione Mediated Conversion GSH Mercapturates 32

33 Essential Hypertension Diagnosis + treatment of intracellular nutrient deficiencies, oxidative stress, + insulin resistance will: Reduce Blood Pressure Improve Vascular Health Improve Endothelial Function Mark Houston, MD, In Press, Therapeutic Advances in Cardiovascular Disease (2010) 33

34 Percentage Deficiency in Hypertensive & Control Hypertension Populations Control Serine 10.9% 6.3% Insulin 18.9% 14.1% Calcium 21.6% 14.8% Vitamin D 32.2% 21.6% CoQ % 9.1% P Mark Houston, MD, In Press, Therapeutic Advances in Cardiovascular Disease (2010) 34

35 Essential Hypertension Replacement of the micronutrient deficiencies, as well as high dose therapy of selected nutraceuticals in combination with optimal diet, exercise and weight management resulted in control of blood pressure to goal levels in 62% of the hypertensive population over a period of 6 months with complete tapering and discontinuation of anti-hypertensive drugs. Mark Houston, MD, In Press, Therapeutic Advances in Cardiovascular Disease (2010) 35

36 Coenzyme Q10 Deficiency in Patients on Statin Therapy Without Q10 Supplementation Serum FIA 4/15 47/ % 51.1% With Q10 Supplementation Serum FIA 2/15 28/ % 31.1% 36

37 37

38 38

39 Immune Response Score (Th 1 ) IRS 39

40 >90 Years IRS vs Age Years Years Years Years Years Age Group Years Years <20 Years Average LPI

41 Borderline Deficiencies 41

42 42

43 The Modifiable Risk Factors for Optimal Aging Strengthen Immune Function Optimize Methylation Metabolism Limit Inflammatory Processes Improve Mitochondrial Function Reduce Chronic Stress Regulation of Glycemic / Insulin Function 43

44 T H E B A L A N C E 44

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