Detoxification Companion Doc

8/12/2019 Detoxification Companion Doc

http://slidepdf.com/reader/full/detoxification-companion-doc 1/38

Laboratory Markers

of Toxins and

Detoxification

Dr. Eve Bralley and

Dr. Elizabeth Redmond



Introduction

• Humans are constantly exposed to

exogenous and endogenous toxins.

• Detoxification is the process of

transforming and removing xenobiotics.

• Biotransformation occurs in steps I and II

•

Detoxification and biotransformation havetheir own energy, nutrient and regulatory

requirements



Classes of Toxins and

Methods of DetoxificationFigure 1



http://www.alternative-therapies.com/at/web_pdfs/ifm_proceedings_low.pdf

The Proceedings From the 13thInternational Symposium of

The Institute for Functional Medicine

Managing Biotransformation:The Metabolic, Genomic, and

Detoxification Balance Points



Detection of Toxic Burden

• Ammonia burden

– Citrate, isocitrate, cis-aconitate

– Orotate

• 8-OH-dG

• p-hydroxyphenyllactate

•

2-Methylhippurate• Dysbiosis markers



Additional Markers of

Toxicant Exposure

• Urinary glucarate

– Phase I and II upregulation

– herbicide, fungicide, petrochemical, alcoholand drug exposure

• Urinary benzoate – Glycine conjugation



Detection of Toxic Burden

• Porphyrins

• Heavy Metals

–

Whole blood, RBC, serum – Urine

– Hair



Phases of Detoxification

• Phase I: – primarily cytochromes

– addition of functional groups

• Phase II: – conjugation reactions

– attaches a water-soluble moiety

• Phase III: – antiporter system



Intermediate

MetaboliteToxins

Phase I

(Cytochrome P450)

Reactions: Oxidation

Phase II

(Conjugation Pathways)

Sulfation

Amino Acid conjugationGlucronidation

Glutathione

Metnhylation

ROS

Cell damage

Free

Radicals

Antioxidants:

Phytonutrients

Vitamin C, E

Minerals

Excretion:

BloodUrine

Feces

Phase II Nutrients:

Glycine

NAC

B vitamins

Phase I Nutrients:

B vitamins

Glutathione

Flavanoids



Phase I

• Operates via Cytochrome P450 enzymes (Cyp)

• Bioactivation – adds an attachment site to the

toxin - Requires NADH (from niacin)

• Can result in a more toxic toxin

• Generates reactive oxygen species – thus

ensuring antioxidant status is important





Phase II• Products of phase I detoxification are further

metabolized

• Water soluble molecules are added creating

inactive products called conjugates that are

excreted in bile and urine• Conjugases

– Sulfation

– Glucuronidation

– Amino acid conjugation• glycination

– Glutathione conjugation

– Methylation

– Acetylation



Glutathione and Sulfate Conjugate Formation





Use of Challenge Compounds to

Evaluate Phases of Detoxification



Caffeine Clearance

• 200 mg dose

• 2 and 8 hour saliva collection

•

Phase I microsomal P450 mixed functionoxidase activity



Caffeine Clearance

If High: – Liver is actively removing caffeine

– Enzyme induction

– Minimize exposure to environmental toxins

If Low: – Genetic polymorphisms or loss of liver function

– Processing and degradation of foreign compounds is

slower than normal – Xenobiotics could accumulate in adipose tissue

– Drugs: cimetidine, amphetamines, grapefruit

(narengenin)

– Low exposure to toxins



Acetominophen Biotransformation

• 650 mg dose

• Urinary acetaminophen sulfate and

acetaminophen glucuronide

• Sulfate and B-vitamin status



Aspirin Biotransformation

• 650 mg dose

• O-hydroxyhippurate

•

Glycine, pantothenic acid status



Conjugation Pathways Used for

Specific Compounds



Phase I/II Ratios

• Bioactivation

• Impairment in phase II conjugation could

lead to accumulation of toxic intermediates

• Supplement with antioxidant nutrients

– Free radicals

– Cell injury

– DNA modification

– Haptens



Factors that influence detoxification:

• Age

• Gender

• Diet and Lifestyle

• Environment

• Disease State

• Genetic polymorphisms

• Supplement use

• Intestinal Health



Supporting Detoxification

• Co-factors and Nutrients

– Nicain, B6, glycine, NAC

• Antioxidants/protective nutrients

– vitamin C and E, zinc, lipoic acid

• Phytonutrients can trigger the activity ofgene response elements

– Sulforaphane from broccolli



Polymorphysims

• There are many knownpolymorphysims that can affectdetoxification.

• Example of effects;

Felton, J.S. What do diet-induced changes in phase

I and phase II enzymes tell us about prevetnionfrom exposure to heterocyclic amines? Journal ofNutrition, Oct 2006. 136(10); 2683-4S

http://jn.nutrition.org/cgi/content/full/136/10/2683S





Case 1

• Case 1

•

52 year old man

• Suffers from

occasional abdominal

cramps, fatigue, and

malaise.



Case 1



Case 2

• 50 year old female

• Fatigue, depression,

joint pain, IBS

symptoms

D ifi i C i P fil



Case 2

Detoxification Capacity Profile



Case 2

Amino Acid Profile – 20 - Plasma



Case 2

OrganixSM Profile

GIfx



Case 3

• 49 year old male

• Depression, fatigue,

headaches, overweight

• Moderate alcohol

intake



Case 3




Amino Acid Profile – 20 - Plasma

Elements Erythrocytes/Whole Blood



e e ts yt ocytes/ o e ood

OrganixSM Profile



Case 4

• 41 year old, painter

• Environmentally

sensitive



Case 4




Case 4

OrganixSM Profile

GIfx



Documents

Detoxification Companion Doc