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Textbook Table of Contents

Laboratory Evaluations For Integrative and Functional Medicine

Laboratory Evaluations For Integrative and Functional Medicine

Chapter 1 – Basic Concepts

A New Role for Clinical Laboratories

 

Issues in Assessment

Static Measurements

Methods of Assessment

Enzyme Stimulation Assays

Nutrient Concentrations and Biochemical Markers

Loading Tests or Saturation Measures

Challenge Tests

Other Procedures

Instrumentation

GC/MS

ICP/MS

DRC ICP/MS

LC/MS/MS

HPLC:FLD, DAD

Reliability of Tests Results

Analytical Factors: Accuracy, Precision, Se4nsitivity, and Specificity

Non-Analytical Factors

Reference Intervals

95% Reference Interval

Quintile Ranking

Quality Assurance

Quality Assurance Program

Standard Operating Procedure Manual (SOPM)

Personnel Records

Quality Control  Data

Proficiency Testing

Workflow Assessment

Licensing and Certification

Monitoring by External Agencies

Conclusions

References

 


 Chapter 2 – Vitamins

Introduction

Methods of Vitamin Assessments

Assessing Vitamin Status

Vitamin A (Retinol) and beta-carotene

Vitamin B (Thiamin)

Vitamin B (Riboflavin)

Vitamin B (Niacin, Niacinaide, Nicotinamide)

Vitamin B (Panthothenic Acid)

Vitamin B (Pyridoxine)

Vitamin B (Cobalamin)

Tetrahydrobiopterin (BH)

Folic Acid

Biotin

Vitamin C (Ascorbic Acid) and dehydroascorbic acid (DHA)

Vitamin D (D, Cholecalciferol and D, Ergocalciferol)

Vitamin E (Tocopherol)

Vitamin K (Phylloquinone)

Carnitine

Coenzyme Q

Lipoic Acid (Thioctic Acid)

Choline

Summary

Case Illustrations

2.1 – Fat Soluble Vitamin Supplementation Patern

2.2 – Functional Markers of B-complex Deficiency

2.3 – Multiple Methylation Cofactor Deficiency

2.4 – High Homocysteine Associated with Folate but Not Vitamin B Deficiency

2.5 – Vitamin D Measurement to Avoid Insidious Bone Loss

References


 Chapter 3 – Nutrient and Toxic Elements

General Concepts

Biochemistry and Toxicology of Elements

Nutrient and Toxicant Interactions

Intervention Options

Element Status Assessment

Choosing the Best Speciment for Element Testing

Blood

Hair

Urine

Chelation Challenge (“Provocation”) Tests

Urinary Pophyrin rofiling

The Major Elements

Calcium (Ca)

Magnesium (Mg)

Potassium (K)

Sodium (Na)

Phosphorous (P)

Trace Elements

Iron (Fe)

Zin (Zn)

Copper (Cu)

Manganse (Mn)

Iodine (I)

Selenium (Se)

Molybdenum (Mo)

Chromium (Cr)

Cobalt (Co)

Elements of Uncertain Human Requirement

Boron (B)

Nickel (Ni)

Lithium (Li0

Vanadium (V)

Strontium (Sr)

Toxic Elements

General Mechanisms of Metal Toxicity

Toxic Metal Assessment

Aluminum (Al)

Arsenic (As)

Cadmium (Cd)

Lead (Pb)

Mercury (Hg)

Elements of Potential Toxicity

Thallium (Th)

Uranium (U)

Tin (Sn)

Antimony (Sb)

Titanium (Ti)

Conclusions

Case Illustrations

General Pattern of Element Deficiencies

A 49-Year Old Female Undergoing Chelation with Multiple Lab Assessments

Osteoporosis and Hair Analysis

Ventricular Tachycardia

Hemochromatosis and Toxic Elements

Fatigue and Copper Deficiency

Iodine Deficiency and Thyroid Goiter

Toxic Elements in Urine of Patients Living in Western Massachuetts

Neurologic Effects of Lead Poisoning

Toxic Metals and Dementia


Chapter 4 – Amino Acids

Amino Acids in Human Health

Amino Acids Classifications

Amino Acid Requirements for Protein and Polypeptide Synthesis

Fasting Plasma Amino Acids

Differences in Amino Acid Status Between Individuals

Inherited Metabolic Diseases Effects

Life-Cycle Effects

Dietary Protein Intake

Protein Digestion and Amino Acid Absorption

Diseases

Exercise and Injury

Amino Acid Transport

Amino Acid Profiling in Clinical Practice

Identifying Candidates for Amino Acid Profiling

Selecting a Test: Fasting Plasma, Whole Blood or Urine

Anabolic/Catabolic Responses and Tissue pH Regulation

A Class of Their Own for the Most Versatile Amino Acids

Glutamate (Glu) and Glutamine (Gln)

Ureagenesis and pH Modulation

Brain Regulation

Gluconcogensis

Dietary Protein Influences

Clinical Revelance and Treatment

The Urea Cycle and Nitrogen Management

Arginine (Arg)

Asymmetric dimethylarginine (ADMA)

Citrulline (Cit)

Ornithine (Orn)

Aspartic Acid (Asp)

Asparagine (Asn)

Essential Amino Acids for Prote4ins and Energy

The Branched-Chain  Amino Acids (BCAA)

Valine (Val), Leucine (Leu) and Isoleucine (Ile)

Threonine (Thr)

Histidine (His)

Lysine (Lys), alpha-Aminoadipic Acid (α-AAA) and Pipecolic Acid

Neutrotransmitter Precursors

Phenylalanine (Phe) and Tyrosine (Tyr)

Tryptophan (Trp)

α-Amino-N-butyric Acid (AANB)

γ-Aminobutyric Acid (GABA)

Sulfur-Containing Amino Acids for Methylation and Glutathione Synthesis

Methionine (Met)

Cysteine (Cys) and Cystine (Cyss); (tCys)

Homocysteine, Homocystine (HCys) and Cystathionine

Taurine (Tau)

Precursors of Heme, Nucleotides and Cell Membranes

Glycine (Gly) and Serine (Ser)

Sarcosine (N-Methylglycine)

Alanine (Ala)

Ethanolamine (EtN), Phosphoethanolamine (PE) and Phosphoserine (PS)

Bone Collagen-Specific Amino Acids

Proine (Pro)

Hydroxyproline (HPro)

Hydroxylysine (HLys)

B-Amino Acids

B-Alanine

B-Aminoisobutyric Acid

Carnosine and Anserine

The Methylhistidines

1-Methylhistidine (1-MHis)

3-Methylhistiidine (3MHis)

The Polyamines

Putrescene

Spermine

Cadaverine

Free-Form Amino Acid Supplement Formulas

Correction of Abnormal Amino Acid Levels

Free-Form Amino Acid Supplementation

Cofactors

Case Illustrations

4.1 – Metabolic Fragility from Insufficient Glu & Gln

4.2 – High Glu/Gln Ratio in a Patient with Autism

4.3 – Apparent Ornithine Transcarbamylase Deficiency

4.4 – Plasma Histidine in Major Cognitive Failure

4.5 – Indication of Impaired SN1-SN2 Transporter

4.6 – Essential Amino Acid Support in Schizophrenia

4.7 – Anxiety Correction by Lysine

4.8 – Tyrosine Utilization Cofactors in Bronchospasms

4.9 – Apparent Diet-Induced Taurine Deficiency with Cardiovascular Consequences

References


Chapter 5 – Fatty Acids

Introduction

Fatty Acid Status and Disease

Membrane Fluidity Changes

Fatty Acid Structure and Metabolism

Naming Fatty Acids

Grouping Based on Double Bonds

Control of Fatty Acid Supply and Distribution

Fatty Acid Metabolism

Transport and Oxidation

Elongation and Desatration

Organelle-Specific Steps

Phosphatides,Pospholipases, and Membrane Turnover

PUFA-Derived Cell Regulation Products

Eicosanoids

Endocannabinoids

The Fat-Sensing System: Peroxisome Plasticity

Blood Plasma and Erythrocyte Specimens

Interpretation of Fatty Acid Profiles

The Clinically Relevant Patterns

General Fatty Acid Deficiency or Excess

Omega-3 Deficiency or Excess

Omega-3 Class Deficiencies

Specific ALA Deficiency

Specific EPA and DHA Deficiency

ALA or EPA Excess

Omega-6 (n-6) Class Deficiency or Excess

Omega-6 Class Deficiency

Omega-6 Class Excesses

Hydrogenated Oil Toxicity

Micronutrient Deficiencies

Zinc Deiciency

Copper Deficiency

Vitamin B-12 or Biotin Deficiency

Metabolic and Genetic Disorders

Hypertriglyceridemia

The Metaboli Syndrome

Multiple Acyl-Coenzyme A Dehydrogenation Disorders

Adrenoleukodystrophy (ALD)

Fatty Acid Ratios and Indices

Red-Cell Stearic/Oleic Index

The Polyunsaturated to Saturated Fatty Acid Ratio (P/S)

Total Fatty Acid Concentration (Calculated)

Case Illustrations

5.1 – A Pro-inflammatory Pattern

5.2 – Omega-3 Dominant Pattern 1

5.3 – Omega-3 Dominant Pattern 2

5.4 – Omega -3 Dominant Pattern 3

5.5  -Zinc Insufficiency Sign

5.6 – Metabolic Syndrome

5.7 – Very Long Chain Fatty Acyl CoA Dehydrogenase Deficiency

References


Chapter 6 – Organic Acids

Introduction

Detecting and Monitoring Inborn Errors of Metabolism

Mitochondrial Function Assessment

Fatty Acid Metabolism Markers

Adipate and Suberate

Ethylmalonate

Carbohydrate Metabolism Markers

Lactate and Pyruvate

β-Hydroxybutyrate

Oxalate

Central Energy Pathway Markers

Citrate, Isocitrate, and cis-Aconitate

α-Ketoglutarate

Succinate

Fumarate and Malate

Hyroxymethylglutarate

B-Complex Vitamin Markers

Vitamins B-1,2,3 and 5

α-Ketoisovalerate, α-Ketoisocaroate, and α-Keto-β-Methylvalerate

Vitamin B-6

Xanthuerenate

Biotin

β-Hydroxyisovalerrate

Methylation Pathway Markers

Vitamin B-12

Methylmalonate

Folic Acid

Formiminoglutamate

Neurotransmitter Metabolism Markers

Catecholamines

Vanilmandelate and Homovanillate

Serotonin

5-Hydroxyindolaeacetate (5-HIAA)

NMDA Modulators

Kynurenate and Quinolinate

Picolinate

Oxidative Damage and Antioxidant Markers

Cell Proliferation

ρ-Hydroxyphenyllactate (HPLA)

DNA Oxidative Damage

8-Hydroxy-2-deoxyguanosine (8-OHdG)

Homogentisate (HGA)

Detoxification Markers

Xylene exposure

2-Methylhippurate

Ammonemia

Orotate

Hepatic Phase I and II Activity

Glucarate

Glutathione Status

α-Hydroxybutyrate (2-Hydroxybutyrate)

Pyroglutamate (5-Oxoproline)

Sulfate

Intestinal Dysbiosis Markers

Bacterial and Protozoal Phenolic Products

Benzoate and Hippurate

Phenylacetate and Phenylpropionate

Cresol and Hydroxybenzoate

Hydroxyphenylpropionate

3,4-Dihyroxyphenylpropionate

Bacterial Products from Tryptophan

Indican

Products of Dietary Carbohydrate

D-Lacate

Tricarballylate

Products of Fungi (Yeast)

D-Arabinitol

Putative Yeast Makers and Promising Bacterial Markers

Actions to Consider for Elevated Dysbiosis Markers

Case Illustrations

6.1 – Carnitine Insufficiency in Schizophrenia

6.2 – α-Ketoglutarate Dehydrogenase Deficiency

6.3 – Apparent Succinate Dehydrogenase Deficiency

6.4 – Signs of HMG-CoA Lyase Deficiency in Autism

6.5 – Specific Ketoisovaleric Aciduria as a Sign of Genetic Abnormality

6.6 – Undetectable Quinolinate

6.7 – Redox Stress in COPD

6.8 – Three Glutathione Demand Scenarios

6.9 – Scenarios for Abnormal Benzoate and Hippurate

6.10 – An Unusual Microbial Phenyl Compound Pattern

References


Chapter 7 – Gastrointestinal Function

Gastrointestinal Impact on Nutrient and Toxicant Status

The Stomach

Determination of Stomach Acid

The Pancreas and Gallbladder

Fecal Chymotrypsin

Fecal Pancreatic Elastase

Fecal Fat

Fecal Steroids

Fecal Fibers

The Small Intestine: Digestion and Absorption

Schilling Test

The Physical Barrier

Intestinal Hyperpermeability (Leaky Gut Syndrome)

Lactulose-Mannitol Intestinal Permeability Challenge Test

Markers of Mucosal Inflammation

Enteropathies Induced by Gliadin

Neutrophil-Derived Inflammatory Proteins

Fecal Histamine

Mucosal Defensins

The Immune Barrier

Secretory IgA

Food-Directed Antibody Testing

Food-Specific IgG Antibody Testing

Types of Adverse Food Reactions

Test Report Interpretation

IgE Food Antibodies

The Microbial Mass

Microbial Population Assessment

Intestinal Pathogens, Symbioses and Parasites

Opportunistic Overgrowth and Disease

Dysbiosis and Inflammatory and Autoimmune Disease

Dysbiosis and SIDS

Dysbiosis and Colon Cancer

Colon Cancer Marker (Fecal M2-PK)

The Transitional Gut

Breath Hydrogen and Methane

[14C] Xylose Breath Test

Breath Ethanol

Urinary Markers of Bacterial Overgrowth

Urinary Markers of Yeast Overgrowth

The Colon: Assessing Microbes in Stool

Difficulties in Assessing Intestinal Microbiota

Conventional Techniques versus New Technologies

Microbial Detection with DNA Probes and PCR

Parasitology

Antibiotic-Resistant Genes

Intestinal Microbiota Associated with Obesity

Microbial Metabolic Markers from Stool Testing

Fecal β-Glucuronidase

Fecal pH

Fecal Short-Chain Fatty Acids (SCFAs)

Fecal Phenolics

Fecapentaenes

Ammonia

Intestinal Wellness Options

Summary

Case Illustrations

7.1 – Poor Predominant Flora and Urinary Dysbiosis Products

References


Chapter 8 – Toxicants and Detoxification

Introduction

Terminology and Scope

Sources and Effects of Toxins

Physical, Chemical and Immunologic Barriers

Mechanisms of Cell Injury Induced by Toxins

Oxygen Radicals and Ammonia

Testing Toxin Load

Toxic Heavy Metals

Organotoxins

Products of Glycation or Lipoxidation

Testing Toxin Effects

Urinary Porphyrin Profiling

Inherited Enzyme Defects

Environmental Toxicant Effects

Clinical Applications

Detoxification Mechanisms

Clinical Laboratory Assessments of Detoxification

Toxicant Indications from Standard Serum Chemistry Profiles

Urinary Markers of Detoxification

Testing for Hepatic Detoxification Capacity

Phase I Testing by Caffeine Clearance

If Caffeine Clearance is HIGH

If Clearance Rate is LOW

Phase II Testing

Benzoic Acid Clearance

Acetaminophen Conversation

Phase II Testing by Salicylic Acid Challenge

The Phase I/Phase II Ratios

The Cysteine/Sulfate Ratio

Methylation Status Assessment

Ethanol Intoxication

Intervention Options

Toxin-Related Nutrient Status

Clinical Management of Detoxification

Conclusion

Case Illustrations

8.1 – Diet-Induced Transient Toxic Symptoms

References


Chapter 9 – Oxidant Stress

Origins and Effects of Oxidative Stress

Free Radical Damage and Protection

Antioxidants

Antioxidant Activities of Metabolic Products

Uric Acid

Serum Albumin

Glutathione

Antioxidant Nutrients

Vitamins A,C and E and β-Carotene

Isoflavones

Copper, Manganese, Selenium, Zinc and Riboflavin

Can Antioxidant Supplements Be Dangerous to Health?

Markers of Oxidant Damage

Total Antioxidant Capacity

Lipid Oxidation

Malondialdehyde (Lipid Peroxides)

Isoprostanes

4-Hydroxy-2-Nonenal

Oxidized Low-Density Lipoprotein

Protein Oxidation

3-Nitrotyrosine (3NT)

Methionine Sulfoxide

Nucleotide Oxidation

8-Hydroxy-2′-Deoxyguanosine

DNA Strand Breakage (Comet assay)

Oxygen Radical Absorption Capacity

Endogenous Oxidative Stress Modulators

pHydroxyphenyllactate

Homogentisate

Pathogen Invasion

Treatment Options

Reduce Pro-Oxidants

Increase Antioxidants

Other Lifestyle Factors

Case Illustrations

9.1 – 8-Year Multiple Sensitivity, Oxidative Stress

References


 Chapter 10 – Hormones

Introduction

Nutrient and Hormone Interactions

Growth and Homeostasis

Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I)

Thyroxine

Insulin

The Stress Response

Corticotropin-Releasing Hormone (CRH) and Adrenocorticotrophic Hormone (ACTH)

Dehydroepiandrosterone (DHEA)

Cortisol

Epinephrine and Norepinephrine

Patterns of Adaptive Responses

Assessment of Adrenal Hormones

Salivary Cortisol

ACTH Challenge Test

Markers of Stress

Secretory IgA

Antigliadin Antibodies (AGA)

The Sex Hormones

Gonadotropin-Release Hormone (GnRH)

Estrogens

Estrogen Clearance and the 2:16 Ratio

Progesterone

Testosterone

Other Levels of Cell Controls

Cytokine Signaling Pathways

The AKT Signaling Pathway for Apoptosis

Specimen Choices

Hormone Replacement Therapy

Bioidentical Hormones

Hormone Biotransformation (Detoxification)

References


Chapter 11 –  Genomics

Molecular Biology 101

Genetic Variability

The Era of Personalized Medicine

Pharmacogenomics

Nutrigenomics

Further Considerations

Conclusions

Case Illustrations

11.1 – Combined COMT and MTHFR Homozygous Effects

11.2 – COMT Homozygous Effects

11.3 – Evidence for Glycine Conjugase Polymorphism from Metabolic Data

References


Chapter 12 – Pattern Analysis

Comprehensive Nutritional Evaluation

Multiple Markers

A Case Study – Multiple Markers Within a Single Profile

Case History

Energy Pathway Intermediates

B-Vitamin Markers

Detoxification Markers

Intestinal Dysbiosis Markers

Advanced Study of the Case – The Power of Simultaneous Multiple Profiles

Serum Vitamins and Antioxidant Status

Elemental Status

Fatty Acid Status

Amino Acid Status

Fatty Acids and Organic Acids in a Case of Chronic Fatigue

Integrating Clinical Impressions with Multiple Laboratory Profiles

Mr. L’s Amino Acids

History and Observations

Impressions

Interventions

Four Week Follow-up

Long-term Follow-up

Discussion

Mr. F’s Stages of Health

Stage I

Stage II

Mrs. O’s Fibromyalgia

Chief Complaints – Medical History

Test Results

Treatment Protocol

Follow-up: 2 Weeks

Follow-up: 6 Weeks

Follow-up: 12 Weeks

Discussion

More on Pattern Recognition and Illustrative Scenarios

A Common Phenotype of Autism

Heal the Gut

Improve Digestion

Oxidative Challenge With Trace Element Involvement

Detoxification and Mitochondrial Inefficiency

Toxic Elements and Glutathione Depletion

Algorithms for Supplementation from Metabolic Profiles

Conclusion

 

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