Technical Overview of Micronutrient Testing J.F. Crawford, Ph. D. SpectraCell Laboratories, Inc. Houston, TX
Recent Publications Antioxidant supplementation increases morbidity and mortality. JAMA, 2007 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 4
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Improved Cellular Performance Your cellular performance may also be improved after information obtained from micronutrient testing. 6
Lymphocytes are used for MNT 7
Technology Summary Isolation of Lymphocytes Long term nutritional marker Day 1 Incubation & Growth in defined culture media 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 8
Intracellular Micronutrient Testing Nutrients Analyzed: Thiamin (B1) Calcium Riboflavin (B2) Magnesium Niacin (B3) Zinc Pantothenate (B5) Serine Pyridoxine (B6) Glutamine Cobalamins (B12) Asparagine Folate Oleic Acid Biotin Insulin Sensitivity Inositol CoenzymeQ10 Choline Lipoic Acid Chromium Fructose utilization Spectrox antioxidant function Glutathione Cysteine Selenium Vitamin A Vitamin C Vitamin E Vitamin D (3) Vitamin K Carnitine Copper 9
Nutrient Deficiencies and Previous Supplementation Multiple deficiencies with no previous supplementation Multiple deficiencies with previous supplementation 38% 43% 19% Subjects showing no deficiency 10
Intracellular Micronutrient Deficiencies 35.0% 30.0% 25.0% ZINC 20.0% 15.0% B1 B12 CALCIUM GLUTATHIONE E SELENIUM 10.0% FOLATE LIPOIC D 5.0% B2 MAG 0.0% 11
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 12
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 2002. 13
Medications & Nutrient Deficiency Anti-Depressants Elavil, Tofranil, Sinequan, Aventyl Anti-Inflammatory Aspirin, Advil, Motrin Prednisone, Cortisone Statins Hormone Replacement Therapy Evista, Premarin, Estratab B12, CoQ10 Vit C, Folate D, Folic, Cal, Mag, Selenium, Zinc CoQ10, B12, D, E, Folic, A B2, B6, B12, C, Folate, Mag, Zinc 14
Proliferation Index I N D E X 2 1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 20 25 30 35 40 45 50 55 60 65 70 75 80 YEARS Average < 25% > 75% 15
Biochemical Pathways Methionine S-Adenosyl Methionine Homocysteine B 6 B 12 Cystathionine B 6 THF Methyl-THF Cysteine Folate 16
Homocysteine & Vascular Disease Genetic and Dietary Determinants of Serum Homocysteine Concentrations Genetic Cystathionine-beta-synthase deficiency Methionine synthase deficiency MTHFR deficiency Defective absorption of B 12 or Folate Prevalence: 30% Female 25% Male Nutritional Vitamin B 6 Vitamin B 12 Folate 17
Homocysteine & Vascular Disease Pathophysiology of Homocysteine Interference with normal thrombolysis Decreased antithrombin III activity; Activation of factor V or XII Inactivation of protein C Promote binding of Lp(a) to fibrin Platelet inhibition (interaction with nitric oxide) Promote SMC proliferation Promote LDL oxidation Direct toxicity to endothelium 18
Homocysteine & Vascular Disease Effects of Treatment With N-Acetyl Cysteine (NAC) 20 O.Wiklund et al. / Atherosclerosis 119(1996) Homocysteine (um) 15 10 5 0 Before During After Before During After PLACEBO NAC 19
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 20
The Magic Bullet 21
Major Cellular Antioxidants Antioxidant Nutrients Vitamin C (Ascorbate) Vitamin E (Tocopherols) Selenium Glutathione Antioxidant Enzymes Superoxide Dismutase (Zn Cu, Mn) Catalase (Fe) Glutathione Peroxidase (Se) 22
Markers of Oxidative Stress Thiobarbituric Acid Reactive Substances (Tbars) Lipid Peroxides Isoprostanes Guanosine Derivitives Selenium Protein Carbonyls Orac & Trap Lymphocyte Culture (Spectrox) 23
Antioxidant Balance Prostaglandins (E series) thromboxanes, leukotrines Arachadonic acid peroxyl radical 12-HETE (alcohol) 12-HPETE (hydroperoxide endoperoxide) tocopherol tocopherol radical ox Dehydroascorbate Ascorbate Glutathione (GSH) Glutathione disulfide (G-S-S-G) NADP NADPH 24
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 Total Antioxidant Function Desired Results Average Deficient 25
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) 26
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 T 3 receptor density is influenced by cortisol, inadequate if too high or too low Retinol HCY
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 28
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) 29
Percentage Deficiency in Hypertensive & Control Populations Hypertension Control P Serine 10.9% 6.3% 0.0001 Insulin 18.9% 14.1% 0.0136 Calcium 21.6% 14.8% 0.0007 Vitamin D 32.2% 21.6% 0.0294 CoQ10 16.9% 9.1% 0.0294 Mark Houston, MD, In Press, Therapeutic Advances in Cardiovascular Disease (2010) 30
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) 31
Coenzyme Q10 Deficiency in Patients on Statin Therapy Without Q10 Supplementation Serum MNT 4/15 47/92 26.6% 51.1% With Q10 Supplementation Serum MNT 2/15 28/90 13.3% 31.1% 32
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Clinical Evidence of Wellness Working Peer Financial: Merritt Patients Prescription Costs $7.92 $39.59 Bed Days per 1,000 537 1389 (Medicare) Bed Days per 1,000 247 387 (private pay) 34
Reporting Results 35
Repletion Suggestions 36
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 37
T H E B A L A N C E 38
Commonly asked questions 1. Will I receive a copy of the presentation slides? YES 2. Is the presentation being recorded? YES **You will receive an email linking to both within the next 24 hours. It will also be available on our website at www.spectracell.com in our webinar library. 39