Medical Evaluation of Multiple Chemical Sensitivity Patients; Overview

http://www.mcsbeaconofhope.com/ziem.html

 

Introduction

II Toxic Encephalopathy

III Reactive Airways

IV Evaluation of Chemical Exposure

V Exposure Control

VI Accommodation

VII Home Controls

VIII Medical Measures

IX Glutathione

X Sauna

XI Symptom Log

XII Neurologic Evaluation

XIII Hyperbaric Oxygen Therapy (HBOT)

XIV Hyperbaric-Like Oxygen Therapy (HBLOT)

XV Patient Characteristics for Subsequent Data Discussion

XVI Adrenal Function & Testing

XVII Amino Acid Balance Evaluation and Treatment

XVIII Mitochondrial Function Evaluation & Energy Metabolism

XIX Detoxification

XX Evaluation and Management of Essential Fatty Acid Disorders in Cell Membranes

XXI Evaluation of the Gastro-Intestinal System

XXII Evaluation of Intracellular Trace Minerals in Toxic Injury Patients

XXIII Evaluation of Other Trace Nutrients

XXIV Other Endocrine Changes

XXV Other Changes

XVI Summary

XVII Bibliography

 

I       Introduction

1      Patient’s often present with toxic encephalopathy and reactive airways

2      Other abnormalities include;

A)   Adrenal/cortisol changes-usually deficiency

B)   Protein deficiency, especially detoxification related amino acids

C)   Changes in Phase II Detoxification following challenge

D)   Deficiency of Glutathione and Superoxide Dismutase

E)    Increased Lipid peroxides and other free radicals

F)    Altered cell membrane lipid composition due to pro-inflammatory status

G)   Secretory IgA deficiency

(1)  Frequent Parasites

(2)  Candida

H)   Pancreatic deficiency demonstrated by low stool Chymotrypsin

(1)  http://www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=11235X&labCode=SJC

(2)  http://www.gdx.net/product/10140 (includes yeast culture)

I)     Food intolerances

(1)  http://www.gdx.net/product/10145

(2)  http://www.immunolabs.com/physicians/products/blood-print/#154

J)     Intracellular essential mineral deficiency

K)   Reduced antioxidant function

L)    Altered energy Metabolism

M) Micronutrient deficiencies

(1)  Esp. Vitamin B12-essential for myelin synthesis

3      Toxic exposures were typically symptomatic and repeated

4      Causal agents include;

A)   Petrochemicals

B)   Solvents

C)   Pesticides (Organophosphates, Pyrethroid, Chlordane, Benzyl Benzoate

D)   Vehicle exhaust in building

E)    “Sick building”

(1)  Mycometrics testing 732-355-9018

F)    Volatiles, VOC’s

G)   Adhesives

H)   Inorganic chlorines

I)     Formaldehyde

J)     Glutaraldehyde

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II     Toxic Encephalopathy

1      ICD-9; 349.82, ICD-10; G92

2      Causes (either repeated, often low-level or even brief single-exposures)

A)   Petrochemicals

B)   Sick buildings

C)   Combustion products, pesticides, VOC’s, solvents, inorganic and organic chlorines, hydrogen sulfide

D)   Repeated exposure causes further damage; early Dx/avoidance is essential

E)    Lipid-soluble agents are often involved, concentrating in myelin and support elements.

3      Symptoms

A)   Short attention span

B)   Reduced memory

C)   Concentration difficulty

D)   Headache

E)    Balance disturbance

F)    Ataxia

4      High metabolic rate of neural tissue increases susceptibility

5      Small numbers of neurons utilizing acetylcholine and dopamine increase the vulnerability to profound reductions in coordination and memory

6      Impaired energy metabolism greatly increases the risk of CNS damage

7      Petrochemicals directly attack membranes of neurons causing injury.

8      SPECT scans after toxic exposure to petrochemicals show reduced blood flow and reduced uptake of radiotracers in the early phase of injection more than in the late phase

A)   SPECT changes are most pronounced in the

(1)  Frontal

(a)   Impaired short-term memory, reduced concentration

(2)  Temporal

(3)  Limbic

(a)   Can cause mood/psychological/neuropsychiatric conditions, Irritability

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III   Reactive Airways

1      ICD9; 493.90, 493.92;  ICD-10; J68.3

2      Repeated low level exposure, higher single dose exposure can cause permanent reactive airway disease

A)   Upper and lower airways may be involved (Rhinitis, Asthma).

(1)  May be induced by Volatile Organic Compounds (VOC’s)

(a)   New carpets

(b)  New paint

(c)   Plastic

(d)  Scented products

(e)   Cleaning products

(2)  Petrochemicals

(3)  Ammonia

(4)  Chlorine

(5)  Solvents

(6)  Pesticides

B)   Considered long-standing or permanent after initial exposure has ceased.

C)   Effects are more than additive

(1)  Increases with number of substances present

(2)  Increases with more fat-soluble substances

(3)  Worse if prior exposures have happened, causing prior irritation

(4)  “sicker quicker” after low-level exposures

D)   Non-respiratory symptoms are common

(1)  Aching

(2)  Fatigue

(3)  Reduced nasal mucus increases ability of toxins to enter the brain.

E)    Generally do react to methacholine challenge

F)    CXR/PFT’s are unreliable predictors of reactivity

G)   Often fail to respond to beta-2 Agonist therapy or steroids

H)   Commonly accompanied by headache (HA), fatigue, musculoskeletal aching

I)     With challenge testing, airways and even eyes are involved

J)     Perfume testing below perceptible smell level can trigger patients with HA/Fatigue/eye irritation

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IV   Evaluation of Chemical Exposure

1      Lowering exposure reduces the risk of adverse health effects.

2      Need to evaluate for toxic related organ changes as noted below.

3      John’s Hopkins School of Hygiene and Public Health/Dr. Davidoff et all have a validated peer-reviewed questionnaire56.

A)   Describes duration of exposure

B)   Characterizes exposure in easily understood language

C)   Assesses intensity, characterizes the response

4      Another good question; “How long does it usually take to feel as good as you did before?” to assess recovery time.

5      Careful evaluation of the environment is important

A)   Home

(1)  Largest amount of time spent here, most important to evaluate.

(2)  Relocation may be necessary

B)   Work

C)   School

6      Evaluate timing of symptoms relative to location of possible exposures.

A)   More symptomatic at home/work/school?

B)   Most notable early in the course of the illness/syndrome

C)   After prolonged illness, significant improvement may not occur quickly enough to be noticeable, may require months away

D)   What tasks are being performed?

E)    Evaluate HVAC, air quality/monitoring

F)    Common-use areas such as hallways, restrooms etc.

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V     Exposure Control

1      The most significant factor for future health is the extent to which exposures can be controlled below symptomatic levels.

2      Once chemical sensitivity is induced, it can be re-triggered by exposure elsewhere

3      Reducing exposure to chemicals was very helpful for 71% of patients in one study, but only 17% of patients who used psychological or psychiatric services/treatment found these to be very helpful.

4      It’s important to focus on exposure control where the person spends the most time; work/school/home.

5      Current occupational exposure limits (TLVs) have shown no statistical correlation with health effects.

6      Adverse health effects are often reported in the literature below these exposure limits.

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VI   Accommodation

1      If symptoms significantly interfere with major life activities, patient is considered to have a qualifying condition under various disability legislation/regulations.

2      Nontoxic and least toxic pest control methods have been developed for virtually all weeds and pests; these should be requested as indicated.

3      Illness reactions to scented products in the general population affect 20% or more of the population.

A)   Can cause migraine

B)   Sinus HA

C)   Sinus congestion

D)   Hoarseness

E)    Asthma reactions

4      Areas with moisture problems should use HEPA filter to capture mold particles/spores

A)   HEPA may not be needed if no mold is present

(1)  ERMI Testing; Mycometrics testing 732-355-9018

(2)  The Shoemaker Protocol provides details on proper care for mycotoxic patients.

5      Consider noise level with filtration systems to avoid future hearing loss.

A)   Whole-house filtration can reduce noise if properly located.

B)   Leave the system running at all times to avoid contaminant build-up.

6      Water with chlorine may cause problems with cooking/drinking/shower

A)   Chlorine reacts with organic debris to form chloroform

B)   Wells near areas of pesticide application need charcoal filtration.

C)   Consider bottled water for drinking/cooking

D)   Consider whole-house activated charcoal filtration system.

E)    Investment in filtration systems can be offset by less medical expenses and disability

F)    Monitor filter status/periodic scheduled changes are necessary.

7      Workplace accommodations;

A)   Change in schedule to reduce exposure to rush-hour traffic

(1)  Charcoal filters can be helpful

(2)  Ion generators don’t help much/can cause exacerbations.

B)   Be near a window that can be opened if outdoor air is cleaner than indoor air.

C)   Advance notification for planned painting, pest control procedures

D)   Use of less-toxic products for above.

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VII Home Controls

1      Location;

A)   Try for a relatively nontoxic house with electric heat and appliances

B)   Tile/hardwood floor is preferable

C)   Buffer of land, ideally water, at least a mile from areas of agricultural pesticide use

D)   >0.25 miles from major highway

E)    No odor from nearby industrial facilities

2      Freestanding home under control of patient-not a condo or apt

A)   Impermeable barrier between attached garage and house

B)   Windows that open easily in bedroom, kitchen and major living areas

C)   Ceiling fans can help reduce the need to close the house during the summer

3      Major improvements in health occur with such housing.

4      Extra caution in the bedroom; often 60 hours/week spent there.

A)   Can reduce episodes of respiratory irritation

B)   Less fatigue

C)   Fewer neurologic symptoms

5      Bedding without

A)   Petrochemical flame retardants

B)   Pesticides

C)   Mold control agents

(1)  Cotton grown without pesticides for bedding is ideal

(2)  Mold control with a tightly-woven mattress and pillow enclosure called barrier cloth

(3)  Small amounts of off-gassing form a pillow can exacerbate respiratory symptoms

(a)   Avoid synthetic pillows

D)   Wool containing pillows may be preferred

E)    Utilize barrier cloth is down is used.

(1)  Down can initiate allergy to dander, especially if used without a barrier cloth.

6      Respiratory congestion with newsprint can be reduced with a reading box

A)   Nontoxic airtight containers to store printed matter indoors

7      Synthetic clothing may cause skin irritation
Store food in containers of glass, metal or wood-derived cellophane to reduce phthalates

8      Organic food is preferred to avoid pesticide ingestion

9      Try to avoid being house-bound, we’re social creatures!

A)   If severely intoxicated, remain house-bound until improvement occurs then try to get out and about

B)   Social interaction can be improved with a car filter

C)   Educate friends about your condition

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VIII        Medical Measures

1      Due to memory impairment, instructions must be written down

2      Micellized agents are useful due to impaired pancreatic enzyme production

3      Exacerbations produce relative acidosis

A)   pH strip monitoring of urine can be helpful

(1)  Try to keep urine pH >6-7

(2)  Bisalt mixture such as 2 parts NaHCO3 in water to one part KHCO3 orally as needed

(a)   Hypokalemia despite acidosis is also common

(b)  Check potassium levels during exacerbations

B)   Improved pH with an alkalinizing diet can be helpful.

4      If patient experiences neurologic, respiratory or cardiovascular symptoms

5      during exacerbations then

A)   Oxygen 3-4 LPM via ceramic mask and Tygon 2075 tubing to reduce exposure to plasticizing chemicals until significant symptom improvement occurs.

6      Relative hypothermia is treated with a metal “hot water bottle” in a quilted sack filled with hot tap water, not heated on the stove to avoid burns.

7      Baseline daily broad range of antioxidant protection is important

A)   Buffered Ascorbate (Vitamin C) 1-11 gram daily in divided doses

B)   Vitamin E 300-400 IU/d

C)   Micellized Vitamin A 5,000 IU/d

D)   Broad spectrum bioflavonoids

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IX   Glutathione

1      The most important intracellular antioxidant in the body, it can significantly reduce the severity of exacerbations.

2      It is not effective orally

3      Micellized sublingual sprays can be helpful as can enemas

4      Injectable glutathione is the best delivery system

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X     Sauna

1      Beware of glues, certain woods, insulation materials and construction substances can release VOC’s causing exacerbations.

2      Avoid use of a sauna which allows laying down; sleep in the heat can e lethal due to hyperthermia!

3      Petrochemicals are stored in fatty tissues in equilibrium with blood levels

A)   Increased fat levels cause increased levels in blood and other tissues

B)   Reducing body-burden helps improve detoxification with reduced risk of adverse effects

4      Organochlorines, PCB’s are removed with sauna as well.

A)   Serum and fat decrease in PCB’s of 42% & 30% respectively

B)   A black substance was found in the sweat during sauna

5      Symptom improvements;

A)   Neurocognitive; IQ increase of 6.7 points in one study with improvements in;

(1)  Memory

(2)  visual images

(3)  block design

(4)  trails

(5)  reaction time

(6)  motor speed

(7)  digits backward

B)   Less myalgias/arthralgias

C)   8 of 9 had improved IBS symptoms

D)   Dermatitis improved in 7 of 8 patients

E)    Migraine & thyromegally improved in ¾ of patients

F)    Less acne & adenopathy

G)   Fatigue, respiratory symptoms and sleep improved

H)   There is some legal precedent that patients cannot be denied reimbursement for sauna when no traditional therapy has been shown to be effective in reducing body burden of petrochemical compounds 75.

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XI   Symptom Log

1      Waxing/waning is common

2      Tracking symptom severity after exposure

3      Focus on exposures/places/situations in the 6-8 hours before onset of symptoms or before symptom exacerbation.

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XII Neurologic Evaluation

1      Recommended for patients with complaints of;

A)   Confusion

B)   Disorientation

C)   Reduced memory and/or concentration

D)   Difficulty thinking quickly or clearly

E)    Balance disturbance

F)    Paresthesias

2      Dr. Kilburn 14 has described evaluation of neurologic function after toxic exposure.

3      Toxins include;

A)   Hydrogen sulfide

B)   Chlorine

C)   Hydrogen chloride

D)   Arsenic

E)    Chlordane

F)    PCB’s

G)   Trichloroethylene

H)   Diesel exhaust

I)     Combustion products with toluene-rich vapor

J)     Vinyl chloride

4      Culture Fair testing of intelligence (2A) and Trail Making B are the most sensitive of the neurocognitive tests

5      Neurocognitive testing is more sensitive than reflex latency, visual fields and simple and choice reaction time.

6      Neurocognitive testing can be used as a basis for focusing cognitive rehabilitation

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XIII        Hyperbaric Oxygen Treatment (HBOT)

1      Toxic injury is associated with reduced brain perfusion/ischemia on SPECT scan

2      HBOT reduces ischemia & lipid peroxides (rancid membrane fats), facilitating healing in the brain and peripheral nervous system

3      Increased lipid peroxides are present in most toxic injury patients from ischemia & direct toxic changes with;

A)   Increased free radical formation

B)   Via inflammation

4      Cytochromes are essential for detoxification

A)   Can be disturbed by toxin exposure

B)   Can improve with HBOT

5      Superoxide dismutase is important for clearing toxins from the body

A)   Decreased levels in toxic injuries

B)   Increases with HBOT

6      HBOT helps improve many symptoms

7      Procedure;

A)   Chamber should be metal to avoid phthalates

B)   Pressure of 1.3-1.5 atmospheres except with Hx of seizures

(1)  For seizure patients, 1.25 atmospheres is preferred

C)   Avoid disinfectants in the chamber (VOC problems).

(1)  May cause exacerbations, not improvements

D)   1 hour/d treatment sessions are recommended as tolerated

(1)  Follow up evaluation after a few treatments then periodically

(2)  Severely affected patients may require 2 months Tx

(3)  May stop once maximum improvement is reached.

(4)  Benefits are long-lasting in absence of repeated exposures

8      Patient must avoid future exposures; return to toxic environment will cause relapse and require re-treatment.

9      Timing to give HBOT after reduction in environmental and body-burden of toxin is recommended

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XIV        Hyperbaric-like Oxygen Therapy (HBLOT)

1      Technique includes a metal mask and Tygon tubing for the face seal and Tygon 2075 tubing, glass jar as a water reservoir and wood-derived cellophane humidity mixing chamber 86.

2      On the first day of treatment, an ABG is drawn after 1 hour of Oxygen therapy

A)   Pa)2 of 250 Torr is optimal

B)   Pulse oximetry testing is inadequate as it cannot measure this level of supra-oxygenation.

3      Procedure;

A)   Special mask/delivery/humidification systems as noted

B)   Oxygen 6L/minute.

4      Virtually all patients with toxic brain effects treated daily for 6-8 weeks experience sustained improvement in cognitive function but not as much as with HBOT

5      HBOT is preferred over HBLOT.

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XV  Patient characteristics for subsequent data discussion

1      Criteria for toxic cause of exposure;

A)   Patient was relatively healthy, able to work/conduct daily activities prior to exposure

B)   Symptomatic exposure with symptoms occurring during exposure and improving away from exposure on multiple occasions.

C)   Symptoms consistent with type of exposure

D)   Onset of chronic illness within hours or days of a symptomatic exposure to toxin(s).

2      Mold/sick building syndrome is the most common cause of exposure with it’s associated Volatile Organic Compounds (VOC’s).

3      The most common chemical class is pesticides including

A)   Organophosphates

B)   Chlorpyrifos

C)   Diazinon

D)   Synthetic Pyrethroid resmethrin

E)    Chlordane

F)    Benzyl benzoate containing dust mite spray in home carpet

G)   Glutaraldehyde disinfectant

H)   Occupational handling of plants, which had been treated with above.

4      Solvent exposures including

A)   Sterilizing agents

B)   Formaldehyde

C)   Inorganic chlorine compounds including Sodium Hypochlorite

D)   Carpet adhesive

E)    Drywall adhesive containing n-hexane

F)    Vehicle exhaust, (diesel and gasoline)

G)   Ultraviolet inks containing acrylates and epoxies

(1)  Included severe photosensitivity

(2)  Difficulties with balance testing in front of un-blinded windows despite wearing sunglasses indoors

H)   Medical cleaning towelettes

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XVI        Adrenal Function Testing and Treatment

1      Reactive airway disease & Chemical sensitivity are both associated with increased inflammation.

2      Petrochemical metabolism generates free radicals which perpetuate inflammation

3      Inflammation causes pain

A)   Induces cortisol release from the adrenals

B)   Long-term continuation can deplete adrenal reserve causing

C)   Adrenal insufficiency

4      Most cortisol is protein-bound

A)   Less active

B)   Affected by protein status

5      Venipuncture for collection can cause pain/stress and increase levels

6      Salivary collection reduces this problem

A)   0700-0800

B)   1100-1200

C)   1600-1700

D)   2300-2400

E)    http://www.metametrix.com/test-menu/profiles/hormones/adrenal-stress

F)    http://www.gdx.net/product/10199 (includes Secretory IgA & Antigliaden antibodies)

7      Most common reduction will initially be AM, later reduced function will be more global, and sometimes the initial reduction will be at a non-early morning time.

A)   Isolated elevations are also possible early in the course of the syndrome.

B)   This is further evidence of Hypothalamic-pituitary-adrenal axis problem

C)   HPA impairment leaves the patient more susceptible to physical and psychological stressors

8      The mean DiHydroEpiAndosterone (DHEA) levels of patients with cortisol elevations was 3.0, the mean DHEA for suppressed values was 2.1 (normal 3-10 ng/ml); DHEA is the precursor to estrogen and testosterone.

9      Patients with reduced AM Cortisol levels and fatigue improve with cortisol/hydrocortisone supplementation until the adrenals can adequately recover and heal.

10   Keep Cortisol levels in the normal range to avoid impeding ACTH activity and adrenal suppression

11   Nighttime elevations of cortisol can aggravate sleep disturbances.

A)   Phosphatidylserine can reduce the cerebral response to cortisol elevation when taken 0 minutes prior to the evening meal.

12   To help heal adrenal function, several measures are helpful;

A)   Reducing exposure is essential to reduce inflammation and promote healing

B)   Pain control requires identifying and correcting other causes of pain.

(1)  Pharmaceutical intolerance with impaired metabolism may allow lower doses of analgesics

(2)  Intestinal inflammation is common, caused by

(a)   Parasites

(b)  Candida

(c)   Food intolerance

(i)    May need probiotics

(ii)  May benefit from digestive enzymes

(iii) Consider IgG food sensitivity profile

(3)  Pro-inflammatory state can be aggravated by imbalanced fatty acids

(a)   Low levels of Omega-3 (DHA/EFA

(b)  High levels of Omega-6

(c)   High Arachnidonic acid levels

(d)  Butyric acid supplementation can restore lipid balance

(4)  Daily walking/gentle activity up to 40 minutes/d important!

(a)   Don’t push to the point of increased pain/fatigue

(b)  Fatigue or excess pain will aggravate cortisol deficiency.

(5)  Low glycemic carbohydrates are critical

(6)        Insulin release drops glucose

(a)   Releases more cortisol

(b)  Stresses the adrenals further

(7)  Carbohydrate:Protein balance

(a)   1:1 ratio in protein deficient patients

(b)  2:1 if no protein deficiency

(8)  Decrease stress on adrenals by

(a)   Relaxation

(b)  Comedy

(c)   Biofeedback

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XVII      Amino Acid Profile

1      Protein deficiency is common

2      Specific amino acids will be especially depleted

A)   The most depleted are those involved in Phase II Detoxification

(1)  Sulfur containing for Detox via sulfination using inorganic sulfates and glutathione conjugation

(a)   Taurine

(b)  Glutamine (used to make Glutathione)

(c)   Glycine used to create

(i)    Glutathione

(ii)  Purines

(d)  Cysteine

(i)    Derived from Methionine as is Taurine

(ii)  Methionine is also a methyl donor

(iii) All involved in Phase II Detoxification

B)   Branched-Chain amino acids

(1)  Specific branched chain amino acids include

(a)   Tryptophan

(b)  Phenylalanine

(c)   Tyrosine

(2)  Reduced in chronic liver disease

(3)  Can function as neurotransmitters

(a)   Tryptophan

(i)    Forms Serotonin

(ii)  Serotonin converts to Melatonin

(b)  Phenylalanine

(i)    Converts to Dopamine via several steps then to norepinephrine then epinephrine

(c)   Tyrosine

(i)    From Phenylalanine

(ii)  Converts to Thyroxine

(4)  Branched chain are the only amino acids which can enter the inner mitochondrial membrane

3      Supplementation is done via a mixture that addresses the specific tested deficiency profile

4      Extra amounts to support detoxification are often useful

(a)   Taurine

(b)  Glutamine

(c)   Glycine

(d)  Cysteine

5      Strive to correct deficiencies while minimizing supra-therapeutic levels

6      Dietary correction is ideal but may not be possible without specific supplements

7      Correcting amino acid & mineral deficiencies without controlling for adrenal insufficiency is difficult to do; correct the adrenal issues!

8      Testing Resources;

A)   https://www.questdiagnostics.com/testcenter/testguide.action?dc=TS_AminAcidAnal

B)   http://www.gdx.net/product/10050

C)   http://www.metametrix.com/patients/faqs/amino-acid-profiles

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XVIII    Metabolic/Energy Metabolism

1      Organic Acid evaluation measures various acids in the tricarboxylic (Krebb’s/TCA) Cycle

2      Low alpha ketoglutarate

A)   Feeds directly into the electron transport chain

B)   Required for formation of Coenzyme Q10/inner mitochondrial membrane antioxidant

3      Isocitrate requires Vitamin B3 (as NADH), Mg, MN.

A)   Mineral testing is necessary;

4      Branched chain amino acid deficiencies are also problematic as they are the only amino acids that can cross the mitochondrial membrane

5      Carnitine is essential to shuttle fatty acids into the mitochondria

A)   Deficiency can be associated with fatigue

B)   Increased adipate or suberate (medium-chain fatty acids) often occurs with carnitine deficiency

6      Toxins that impair energy metabolism include

A)   Phthalate plasticizer exposure may exacerbate fatigue

(1)  IV bags, tubing, oxygen masks

(2)  Food/beverage containers

B)   Styrene

C)   PCB’s

D)   Toluene

E)    Trichloroethane

F)    2,4,6 trichlorophenol

G)   Pentachlorophenol

H)   Other pesticides

7      Testing;

A)   https://www.questdiagnostics.com/testcenter/testguide.action?dc=TS_OrgAcFull

B)   http://www.gdx.net/product/10083

C)   http://www.metametrix.com/test-menu/profiles/organic-acids/organix-comprehensive

D)   http://www.greatplainslaboratory.com/home/eng/full_oat.asp

8      Treatment of Mitochondrial Disorders

A)   Avoid toxic agents

Drugs with Mitochondrial Toxicity

Medication

Symptoms

Mechanism

Valproic acid

Hepatomegally; infrequently, direct encephalopathy

Inhibition of fatty acid oxidation, citric acid cycle, oxidative phosphorylation, carnitine depletion, Complex IV inhibition (contraindicated in mitochondrial depletion syndromes

Anti-retrovirals

Peripheral neuropathy, liver dysfunction, myopathy

Impairment of mitochondrial DNA (mDNA) replication causing mDNA depletion, carnitine deficiency, lactic acidosis, lipodystrophy

Statins

Myopathy

Multiple postulated effects including CoQ10 depletion

Aspirin

Reye Syndrome

Inhibition and uncoupling of oxidative phosphorylation

Aminoglycosides

Hearing loss, cardiac & renal toxicity

Impaired mDNA translation

Aminoglycoside & platinum chemotherapy

Hearing loss, cardiac & renal toxicity

Impaired mDNA translation

Acetaminophen

Hepatopathy

Oxidative stress

Metformin

Lactic acidosis

Inhibition of oxidative phosphorylation, enhanced glycolysis

Beta-Blockers

Reduced exercise tolerance

Oxidative stress

Steroids

Reports of deterioration in Kearns-Sayre syndrome

 

B)   Myer’s Cocktails to drive vitamins across mitochondrial diffusion barrier

C)   Maintain proper levels of trace minerals & co-factors

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XIX        Detoxification

1      Detoxification of petrochemicals involves 2 phases

A)   Phase I; cleaving the molecule creating a free radical

(1)  Occurs in Cytochrome p450

(a)   Challenge testing done by ingesting 200 mg of caffeine

(b)  Assesses common p450 isomers

B)   Phase II; linking the radical to another substance

(1)  4 pathways are assessed

(2)  Using Acetaminophen 650 mg to assess

(a)   Glutathione conjugation

(b)  Sulfation

(c)   Glucuronidation

(3)  Using 650 mg Aspirin

(a)   Glycine conjugation

(4)  Urine is collected for metabolites for 10 hours after acetaminophen and aspirin challenge

(5)  Excess activity of Phase II predominates with excessive activity in all 4 Phase II pathways

(6)  Excessive activity probably precedes diminished activity when depletion of metabolites occurs

C)   Other pathways exist involving conjugation with

(1)  Glutamine

(2)  Taurine

(3)  Methyl groups from

(a)   Methionine

(b)  Folate etc.

(4)  Acetyl groups

2      Increased lipid peroxides are found in over 1/3 of patients, a grave concern;

A)   Lipids comprise ~2/3 of brain content

B)   Form membranes for all cells in the body

C)   Form functional membranes within mitochondria for energy formation

D)   Abound in cell nuclei for proper DNA function

E)    Glutathione deficiency exacerbates lipid peroxidation

(1)  Nebulized and injected glutathione can help

(a)   Alpha lipoic acid can help conserve glutathione, is able to access water and fat-soluble tissues

(b)  Selenium is necessary for Glutathione

(c)   Excessive selenium is harmful, testing is necessary

(2)  Adequate levels of Vitamin C intake are needed (up to 10 grams/d)

3      Superoxide Dismutase (SOD)

A)   Intracellular antioxidant which reduces tissue damage from free radicals

B)   Reduced 33% in toxic/inflammatory states

C)   Requires cofactors

(1)  Copper

(2)  Manganese

(3)  MUST evaluate mineral/trace element status!

(4)  http://www.gdx.net/product/10157

(5)  http://www.spectracell.com/clinicians/products/mnt/

D)   Despite excessive Phase II activity, most patients have elevated levels of free radicals, emphasizing the need for antioxidant protection

E)    Elevated free radicals are associated with

(1)  Chronic and degenerative disease states

(2)  Stroke

(3)  Heart disease

(4)  Cancer

(5)  Cognitive decline

(6)  Increased rate of aging

(7)  Damage to

(a)   Enzymes

(b)  Other proteins

(c)   Cell membranes

(d)  Nerve cells

(e)   Virtually all body tissues

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XX  Essential Fatty Acids in Cell Membranes

1      Impaired tissue perfusion due to non-deformable RBC’s has been documented after toxic injury

2      Omega-3 Fatty Acids have an anti-inflammatory role

A)   Alpha Linoleic Acid (ALA)

(1)  ALA can be converted to EPA by enzymatic process’

(2)  The process is damaged by free radicals

(3)  Involved in oxygen transfer

(a)   From air to lungs

(b)  From lungs to hemoglobin

(c)   Holds oxygen in the cell membrane where it acts as a barrier to

(i)    Viruses

(ii)  Bacteria

(iii) & Other pathogens

B)   Eicosapentanoic acid (EPA)

(1)  EPA can be converted to DHA

C)   Docosahexanoic acid (DHA)

(1)  Highly concentrated in the cerebral cortex

(2)  Comprises 30% of the essential fatty acid in

(a)   Phosphatidyl serine

(b)  Phosphatidyl ethanolamine

D)   Fatty acid testing should be done for each acid as the conversion processes can be damaged by free radicals as noted above.

E)    Cell membrane rigidity/fluidity is affected by the essential fatty acid composition of cell membranes

(1)  Omega-3’s affect membrane rigidity

(2)  Omega-3 deficiency after toxic injury can impair passage through capillaries impairing vital exchanges.

F)    Gamma Linoleic Acid (GLA) is the precursor to

G)   DiHomo-Gamma-Linoleic acid (DGLA)

(1)  Anti-inflammatory

(2)  Precursor for the series-one anti-inflammatory prostaglandins

H)   Arachnidonic acid (AA)

(1)  Essential Fatty Acid

(2)  Pro-inflammatory in excessive amounts

(a)   Forms pro-inflammatory leukotrienes

(i)    Attract WBC’s, PMN’s, Macrophages in inflammation

3      High levels of pro-inflammatory factors increases

A)   Aching

B)   Respiratory congestion etc.

4      Essential Fatty Acid Testing

A)   https://www.questdiagnostics.com/testcenter/testguide.action?dc=TS_Omega_3_6

B)   http://www.metametrix.com/test-menu/profiles/fatty-acids/fatty-acids-plasma

C)   Can be damaged by contact with

(1)  Light

(2)  Heat

(3)  Air

(4)  Sealed, dark containers and refrigeration are needed

5      Supplementation

A)   Based on results of testing

B)   Micellized form absorbed without digestive enzyme degradation (which can be deficient in chronic toxic injury patients)

C)   Richest sources are cold-water fish

(1)  Mackerel

(2)  Salmon

(3)  Sardine

(4)  Bluefish
herring

(5)  Trout

(6)  Whitefish

D)   Up to 4 grams/d to suppress excess inflammation

E)    Farm-raised fish is inadequate due to their diet

F)    Arachnidonic acid is rich in red meat and shellfish

G)   Butyrate also helps to correct membrane imbalances of Omega-3 and Omega-6 essential fatty acids

(1)  Available as a daily dose taken daily

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XXI        Gastrointestinal Testing

1      Diagnostic testing

A)   Stool secretory IgA deficiencies are common in toxic injury patients.

B)   H. Pylori IgG antibody testing

(1)  http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=29407

(2)  https://www.labcorp.com/wps/portal/!ut/p/c1/04_SB8K8xLLM9MSSzPy8xBz9CP0os_hACzO_QCM_IwMLXyM3AyNjMycDU2dXQwN3M6B8JG55AwMCuv088nNT9SP1o8zjQ11Ngg09LY0N_N2DjQw8g439TfyM_MzMLAz0Q_QjnYCKIvEqKsiNKDfUDVQEAOrk-dE!/dl2/d1/L0lJWmltbUEhL3dQRUJGUUFoTlFBaERhQUVBWEtHL1lJNXlsdyEhLzdfVUU0UzFJOTMwT0dTMjBJUzNPNE4yTjY2ODAvdmlld1Rlc3Q!/?testId=408339

C)   Entamoeba histolytica evaluation by salivary secretory IgA specific antibodies if available

(1)  http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=34278

D)   Toxoplasma assessed by secretory IgA antibodies

(1)  http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=8636

(2)  https://www.labcorp.com/wps/portal/!ut/p/c1/04_SB8K8xLLM9MSSzPy8xBz9CP0os_hACzO_QCM_IwMLXyM3AyNjMycDU2dXQwN3M6B8JG55AwMCuv088nNT9SP1o8zjQ11Ngg09LY0N_N2DjQw8g439TfyM_MzMLAz0Q_QjPYCKIvEqKsiNKDfUDVQEAMDfYEE!/dl2/d1/L0lJWmltbUEhL3dQRUJGUUFoTlFBaERhQUVBWEtHL1lJNXlsdyEhLzdfVUU0UzFJOTMwT0dTMjBJUzNPNE4yTjY2ODAvdmlld1Rlc3Q!/?testId=408304

E)    Giardia assessed by organism-specific antibodies

(1)  http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=39480 (includes cryptosporidium)

(2)  https://www.labcorp.com/wps/portal/!ut/p/c1/04_SB8K8xLLM9MSSzPy8xBz9CP0os_hACzO_QCM_IwMLXyM3AyNjMycDU2dXQwN3M6B8JG55AwMCuv088nNT9SP1o8zjQ11Ngg09LY0N_N2DjQw8g439TfyM_MzMLAz0Q_QjvYCKIvEqKsiNKDfUDVQEAF3QYtg!/dl2/d1/L0lJWmltbUEhL3dQRUJGUUFoTlFBaERhQUVBWEtHL1lJNXlsdyEhLzdfVUU0UzFJOTMwT0dTMjBJUzNPNE4yTjY2ODAvdmlld1Rlc3Q!/?testId=4179382 (includes cryptosporidium)

F)    Cryptosporidium assessed by organism specific antibodies

G)   Clostridium dificile Toxins A & B (more specific than either type alone)

(1)  http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=16947

(2)  https://www.labcorp.com/wps/portal/!ut/p/c1/04_SB8K8xLLM9MSSzPy8xBz9CP0os_hACzO_QCM_IwMLXyM3AyNjMycDU2dXQwN3M6B8JG55AwMCuv088nNT9SP1o8zjQ11Ngg09LY0N_N2DjQw8g439TfyM_MzMLAz0Q_QjfYCKIvEqKsiNKDfUDVQEALvGFag!/dl2/d1/L0lJWm1LYVlvS1VRIS9JSGhBQ0VvQUJBaktBQVFJS2dBRUNLYWdBRUFLNkdEaGtaVWdBRUFRL1lJNXlsMHN0eW9RIS83X1VFNFMxSTkzME9HUzIwSVMzTzROMk42NjgwL3ZpZXdUZXN0L3Nob3dBbGxSZXN1bHRz/?testId=407832&criterion=%3Ci%3EClostridium+difficile%3C%2Fi%3E+Toxins+A+and+B%2C+EIA

H)   Candida

(1)  http://www.gdx.net/product/10140

(2)  https://www.labcorp.com/wps/portal/!ut/p/c1/04_SB8K8xLLM9MSSzPy8xBz9CP0os_hACzO_QCM_IwMLXyM3AyNjMycDU2dXQwN3M6B8JG55AwMCuv088nNT9SP1o8zjQ11Ngg09LY0N_N2DjQw8g439TfyM_MzMLAz0Q_Qj_YCKIvEqKsiNKDfUDVQEACbJFzE!/dl2/d1/L0lJWmltbUEhL3dQRUJGUUFoTlFBaERhQUVBWEtHL1lJNXlsdyEhLzdfVUU0UzFJOTMwT0dTMjBJUzNPNE4yTjY2ODAvdmlld1Rlc3Q!/?testId=1770939

2      Although parasite serology is the most sensitive, 3 stool O&P tests were also done

A)   https://www.labcorp.com/wps/portal/!ut/p/c1/04_SB8K8xLLM9MSSzPy8xBz9CP0os_hACzO_QCM_IwMLXyM3AyNjMycDU2dXQwN3M6B8JG55AwMCuv088nNT9SP1o8zjQ11Ngg09LY0N_N2DjQw8g439TfyM_MzMLAz0Q_QjXYGKIvEqKsiNKDfUDVQEAOJ2twA!/dl2/d1/L0lJWmltbUEhL3dQRUJGUUFoTlFBaERhQUVBWEtHL1lJNXlsdyEhLzdfVUU0UzFJOTMwT0dTMjBJUzNPNE4yTjY2ODAvdmlld1Rlc3Q!/?testId=407746

B)   http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=6652

3      Treatment

A)   Parasites are treated then testing is repeated to verify cure

(1)  Regimen’s may need to be varied slightly depending on patient tolerance of the therapy

B)   Toxoplasma

(1)  Mepron 750 mg (5cc) bid with food for 21 days

(a)   Need to monitor LFT’s baseline and after 7-10 days

C)   Entamoeba histolytica

(1)  Triple therapy is necessary to clear intestine and spread to other areas of the body

(2)  Yodoxin 650 mg tid for 10 days

(3)  Tetracycline 500 mg tid for 10 days then

(4)  Tinidazole 500 mg tid for 10 days

(a)   Tinidazole is structurally related to Metronidazole but better tolerated and effective.

D)   H. Pylori (10 day treatment course)

(1)  Tinidazole 500 mg tid with

(2)  Bismagel 5 cc 30 minutes before meals and

(3)  Amoxicillin 500 mg tid

E)    Cryptosporidium

(1)  Tinidazole 500 mg tid for 10 days

F)    Candida

(1)  Opportunistic, ubiquitous, reinfection is likely unless gut conditions and inflammation are changed, requiring

(a)   Digestive enzymes

(b)  Human probiotics

(c)   Adequate gastric acid production

(d)  Steroid avoidance

(2)  Usually clear without specific anti-fungal therapy

(3)  Nystatin 1 tsp qid

(4)  Diflucan 200 mg/d

G)   Following antibiotics, start human strain probiotics (unlike the non-human strains which compromise most of the available brands)

(1)  Acidophilus

(2)  Bifidus

(3)  Etc.

4      Chymotrypsin

A)   Stool marker for pancreatic/digestive insufficiency

(1)  http://www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=11235X&labCode=SJC

(2)  http://www.gdx.net/product/10140 (includes yeast culture)

B)   May lead to food intolerances requiring further testing

(1)  http://www.gdx.net/product/10145

(2)  http://www.immunolabs.com/physicians/products/blood-print/#154

(3)  Secretory IgA stool testing may also be required

(a)   http://www.gdx.net/product/10199

C)   Avoiding intolerant foods may improve symptoms, especially

(1)  Fatigue

(2)  Aching

(3)  After an interval of  3-6 months without the foods, reintroduction can be gradually attempted.

D)   Gliadin-sensitive patients need to avoid

(1)  Wheat

(2)  Rye

(3)  Barley

(4)  Oats

(5)  Kamut

(6)  May be able to tolerate small amounts of

(a)   Corn

(b)  Quinoa

(c)   Amaranth

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XXII      Red Blood Cell/Intracellular Minerals in Toxic Injury Patients

1      Testing will be necessary

(1)  http://www.gdx.net/product/10157

(2)  http://www.spectracell.com/clinicians/products/mnt/

2      Less influenced by recent dietary intake, less likely to change levels short-term compared to serum/plasma testing

3      Calcium deficiency is uncommon

4      Chromium is often deficient or low

A)   Higher levels are needed to repair toxin-damaged tissues

B)   Trauma increases losses

C)   Carried by transferrin

(1)  Due to toxin induced hypoproteinemia, levels may be lower than reported

D)   Chromium picolinate is the preferred therapy, inorganic salts are poorly absorbed

E)    Deficiency is associated with glucose intolerance, elevated cholesterol and triglycerides, low density of insulin receptors

5      Copper deficiency

A)   Essential for

(1)  superoxide dismutase

(2)  Cytochrome oxidase hemoproteins

(3)  Mitochondrial energy generation

(a)   Deficiency is linked with impaired energy generation

(4)  Liver enzymes

B)   Competes with Zinc for absorption

C)   Requires carrier proteins

(1)  Initially albumin

(2)  Later, ceruloplasmin

(3)  May have low levels due to hypoproteinemia which can make levels appear higher than they are/worse deficiency than appreciated

D)   Involved in healing of inflammation/tissue repair

(1)  May be used up quickly, requiring more repletion/supplements

E)    Deficiency is linked with LDL elevations and cholesterol elevations

F)    Best absorbed as a chelate

G)   Food sources include

(1)  Whole grains

(2)  Nuts

(3)  Legumes

(4)  Avocado

6      Magnesium deficiency

A)   The most common deficiency in toxic injury patients

B)   Mg absorption is reduced with intestinal malabsorption

C)   Loss is increased by acidosis which is common in toxic injury

(1)  Try to maintain urinary pH >6-7 to promote absorption.

D)   Deficiency symptoms include

(1)  Muscle twitching/cramping/spasm/jerking

(2)  Symptoms often improve within 30-40 minutes of rapidly absorbed oral supplement such as

(a)   MgCl

(b)  Mg Acetate

(3)  Hypertension

(4)  Angina

(a)   Once Mg deficiency is corrected NTG use may decrease

E)    Required for many ATP-dependent enzyme reactions

(1)  Cofactor for conversion of CHO & fat into energy

F)    Needed for adequate bone-mineral metabolism

(1)  The majority of the body’s Mg stores are osseous

G)   Well-absorbed forms cause less diarrhea

(1)  Mg Glycinate (can improve glycine stores for detox)

H)   Mg-rich foods

(1)  Whole grains

(2)  Nuts

(3)  Seeds

(4)  Leafy plants/chlorophyll rich

7      Manganese deficiency

A)   Essential for energy metabolism

B)   Superoxide dismutase

C)   Cartilage formation

(1)  Hyaluronic acid

(2)  Chondroitin sulfate

D)   Bone mineralization

E)    Formation of membrane phosphatidylinositol

F)    Blood distribution probably involves transferrin/implications for protein deficiency

G)   Absorption

(1)  increased by

(a)   Citrate

(2)  Reduced by

(a)   Calcium

(b)  Iron

(c)   Phytates

H)   Dietary sources;

(1)  Whole grains (richest source is the germ)

(2)  Nuts

(3)  Leafy vegetables

8      Molybdenum deficiency

A)   Detoxifies aldehydes

B)   Necessary for conversion of cysteine to sulfate for detox

(1)  Cysteine to sulfate ratios are often decreased

C)   Required for inactivation of otherwise destructive sulfite compounds

D)   Required for oxidase systems requiring Flavin

E)    Found naturally in

(1)  Germ of grains

(2)  Legumes   

F)    Best absorbed as an amino acid chelate or picolinate

G)   Absorption impaired in the presence of sulfate or enhanced sulfur containing proteins (which may be necessary for toxic injury patients/timing of intake should be adjusted accordingly)

9      Potassium deficiency

A)   Most Potassium is intracellular, not within plasma

(1)  Plasma levels underestimate deficiency

(2)  Plasma levels are essential to control for medical reasons

B)   Essential for membrane function

C)   Potassium may drop following exposure

D)   Supplements can irritate the GI tract

(1)  KCl or KNaHCO3 helpful during acid exacerbations

10   Selenium deficiency

A)   Interferes with glutathione peroxidase

B)   Deficiency reduces Glutathione levels

C)   Glutathione peroxidase is an anti-inflammatory, it detoxifies

(1)  Peroxides

(2)  Free radicals

D)   Necessary for the deiodinase system that concerts T4 to T3 in peripheral tissues

E)    Glutathione peroxidase activity improves with Selenium supplementation as selenomethionine

(1)  Selenium can also be given as an

(a)   Amino acid chelate

(b)  Picolinate

F)    Food content depends on soil concentration

G)   Dietary sources

(1)  Garlic

(2)  Onion

(3)  Asparagus

(4)  Grains from selenium-adequate soils

(5)  Meats

(6)  Seafood

H)   Vanadium deficiency

(1)  May bind to Glutathione

(2)  Important for Glucose metabolism

(a)   Able to mimic effect of insulin on fat cells

(b)  Subsequent metabolism may prefer the Pentose pathway more than insulin

(3)  May stimulate bone mineralization by promoting osteoblasts

(4)  Carried by transferrin

(5)  Poorly absorbed

(6)  Food quantity reflects soil content

(7)  Potentially more toxic than chromium

(a)   Chromium adequacy should be addressed prior to concerns for Vanadium levels

I)     Zinc deficiency

(1)  Essential for normal detoxification via superoxide dismutase

(a)   SOD requires both copper and zinc

(b)  Is present in all body cells

(c)   Red cell levels play an important role in controlling superoxide free radicals, protecting other cells from this free radical

(2)  Necessary for the activity of digestive enzymes

(3)  Essential for normal function of Vitamin A as an antioxidant

(4)  Critical to normal immune function

(5)  May be required for normal ACTH activity

(a)   Related to cortisol deficiency in toxic injury…

(6)  Increased rates of loss are common after injury

(7)  Pancreatic insufficiency can cause deficiency

(8)  Increased body loss occurs with

(a)   Pancreatic insufficiency

(b)  Liver disease

(c)   Porphyrin metabolism disturbance

(i)    Common in toxic injury

(d)  Parasitic disturbances

(i)    Common in toxic injury

J)     Essential mineral deficiency

(1)  Common in toxic injury patients

(2)  Chronic adrenal activity leads to adrenal insufficiency

(a)   Due to adrenal “burnout”

(b)  Can depletion of many minerals/trace elements

(3)  Reduced carrier proteins for some minerals also reduce effective transport to body cells that require them

(4)  Impaired digestive enzymes impair food breakdown

(a)   Less bioavailable minerals

(5)  Chronic GI inflammation

(a)   Reduces inflammation

(b)  Increases rate of loss

(c)   Can be 2’ to parasites

(d)  Increased due to pro-inflammatory state

(6)  Neurogenic inflammation involves

(a)   GI tract

(b)  GU tract

(c)   Respiratory tract

(7)  Impaired levels of Zn/Cu/Mb in inflammation

(a)   Impairs SOD/antioxidant activity

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XXIII    Other Nutrients

1      Testing for these involves lymphocyte activity

A)   http://www.spectracell.com/clinicians/products/mnt/

B)   Lymphocytes are present in lipid-rich lymphatic fluid

(1)  Increases potential for exposure and side-effects of lipid-soluble chemicals

(2)  Can effect other lipid-dense tissues

(a)   Brain

(b)  Cell membranes

(c)   Mitochondrial membranes

2      Thiamine (Vitamin B1)

A)   Important in 2 steps of energy metabolism

B)   Reduced levels impair

(1)  Attention span

(2)  Memory

(3)  Can cause peripheral neuropathy

(4)  Brain cell viability (brain has a high metabolic rate)

3      Riboflavin (Vitamin B2)

A)   Critical to energy metabolism

B)   Functions as part of 2 co-enzymes

(1)  FAD

(2)  FMN

C)   Essential for production of ATP

D)   In severe deficiency glossitis and cheilitis may be seen

(1)  This physical sign occurs to late in the deficiency spectrum to be much help clinically

(2)  Labs provide earlier recognition

E)    Niacin (Vitamin B3)

(1)  Nicotinic acid

(2)  Converted to Nicotiniamide Adenonine Dinucleotide (NAD)

(a)   Essential to the mitochondrial Electron Transport System

(b)  Also essential for utilization & synthesis of essential fatty acids

F)    B1, B2, & B3

(1)  Are ALL involved in energy metabolism

(2)  Essential to the function of every cell, enzyme and other body function

(3)  43% of Toxic Injury patients are deficient in one or more of these

(a)   Deficiency defined as lab value >2 standard deviations below the mean

G)   Pantothenate (Vitamin B5)

(1)  Essential for Coenzyme A

(2)  CoA is necessary for

(a)   Energy metabolism

(b)  Mitochondrial oxidation of fats for energy

(3)  Essential for phospholipid synthesis

(a)   Brain

(b)  Other cell membranes

(4)  Increases GI motility

H)   Pyridoxine (Vitamin B6)

(1)  Necessary for the formation of other amino acids with the function of liver transaminases and their action on essential amino acids

(2)  Needed for formation of neurotransmitters

(a)   Serotonin

(b)  Gama Amino Butyric Acid (GABA)

(3)  Needed for

(a)   Porphyrin metabolism

(b)  Synthesis of brain lipids

(c)   Synthesis of the critical detoxification amino acids…

(i)    Taurine

(ii)  Glycine

I)     Cobalamine (Vitamin B12)

(1)  Deficient in most toxic injury patients at a higher rate of deficiency than any other B-vitamin

(2)  Needed for

(a)   Maintenance and repair of Myelin

(b)  Melatonin secretion

(3)  Key nutrient in the S-AdenosylMethiomine (SAM) cycles which provides methyl groups for Phase II Detoxification/Methylation

(4)  Complex absorption, requires Intrinsic Factor from stomach to help in it’s ileal absorption.

(a)   Other carrier proteins are required in the blood

(5)  Deficiency exacerbates neurologic dysfunction

J)     Total antioxidant function is an evaluation of combined antioxidant capability of various individual antioxidants

K)   Nearly ¾ of tested patients were deficient in numerous factors, given the significant incidence of free radicals

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XXIV    Other Endocrine Changes

1      Melatonin

A)   Levels at night are often low

B)   Antioxidant activity for hydroxyl free radicals

C)   Need to ensure adequate Tryptophan (precursor) intake

(1)  Eggs

(2)  Low-fat milk

(3)  Beef

(4)  Chicken

(5)  Turkey

(6)  Soy

(7)  Nuts

(8)  Tuna

(9)  Legumes

(10)        Banana

(11)        Oatmeal

D)   Indirect full-spectrum light or sunlight improves daily melatonin rhythm

(1)  15 minutes Spring & Summer

(2)  45 minutes Fall & Winter

E)    Reducing bright evening lights and electromagnetic fields near bedtime  is helpful

(1)  Problems occur with

(a)   Electric blankets

(b)  LED clocks at the bedside

F)    Is excreted from the body after Phase II sulfation >glucuronidation

G)   Caution with supplementation

(1)  1 mg SR in the evening

(2)  Excess can have adverse effects on other endocrine functions

(3)  Levels decline with aging

(a)   Free radicals (common in toxic injury) accelerate aging

2      Reproductive hormones

A)   Lack of ovulation often present in pre-menopausal women

(1)  Estrogen dominance very prevalent

(a)   Increased risk of cancer

(i)    Breast

(ii)  Other reproductive organs

(b)  Exacerbation of migraine

(c)   Avoid HRT in toxic injury patients

(d)  Consider aromatase inhibition therapy

(2)  Progesterone deficiency is often but not always present

(a)   Levels should be kept within physiologic range

(b)  Avoid synthetic hormone supplements

(i)    They cannot be tested for levels

(c)   Natural BID HRT preferred

(i)    Better tolerated by these patients

B)   Reduced testosterone is common

(1)  Reduced muscle mass & strength

(2)  Reduced libido in men & woman

C)   Thyroid autoimmune disease is the most common autoimmune disease in toxic injury patients

(1)  Contributes to fatigue

(2)  Lower body temperature/hypothermia can have other causes

(a)   Limited energy metabolism

(b)  High energy needs especially

(i)    Brain

(ii)  Heart

(c)   Limited energy reserves

(d)  Average body temperature is 9.4’F

(e)   Illustrates the need of monitoring body temperature

(i)    Daily AM temperature is a good idea

(ii)  Rise >1-2’F is thus “febrile”

(iii) WBC elevations often won’t happen with Toxic Injury patients

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XXV      Other Changes

1      Medication intolerance

A)   Impaired ability to metabolize/excrete

B)   Often require lower doses of many meds

2      Decision to initiate antibiotics is more complex

A)   Body temperature monitoring

(1)  If >1’ F above normal, consider patient “febrile”

(2)  Need daily AM temperatures for a baseline

B)   Leukopenia is common

(1)  Periodic monitoring can help uncover real leukocytosis

(2)  Absolute PMN/neutrophil count is more useful

C)   C&S is very important for antibiotic selection

(1)  Low Secretory IgA

(2)  Side effect profile of medications in the face of

(3)  Impaired medication metabolism

3      Exercise-induced dysrrhythmias are common during exercise

A)   Holter or event monitor can be helpful

4      Consider Peak-Flow Meter before/during/after exercise in the face of dyspnea complaints

5      Hypertension rarely develops in toxic injury patients

A)   Elevations typically occur with exposure to toxin

B)   Home/outpatient BP monitoring is recommended

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XXVI    Summary

1      Exposure control is the single most important intervention

A)   Focus where most time is spent

(1)  Home

(2)  Work

(3)  School

B)   Assist patients in obtaining reasonable accommodation

2      Toxic brain injury improves with

A)   Hyperbaric oxygen therapy (HBOT)

(1)  1.3-1.5A

(2)  <1.25A if seizure-prone

B)   Cognitive rehabilitations helps with residual side effects

(1)  Some residual may persist

C)   Autonomic neuropathy can cause dysrrhythmias/increased heart rates

(1)  Usually improves with

(a)   Oxygen

(b)  HBOT preferred

D)   Mitral Valve Prolapse is common

(1)  Improves with HBOT

3      Exposure to Petrochemicals, combustion products/other irritants affect

A)   Adrenal function/cortisol/ACTH circadian rhythms

B)   Energy metabolism

C)   Amino acid profile

D)   Detoxification

(1)  Lower Glutathione levels

(2)  Increased free radicals

E)    Altered membrane lipids

F)    Reduced secretory IgA

(1)  Increased prevalence of

(a)   Candida

(b)  Parasites

G)   Reduced pancreatic enzymes

(1)  Stool chymotrypsin as a marker for this

(2)  May improve with digestive enzyme supplementation

H)   Increased food intolerances

I)     Reduced intracellular minerals

J)     Reduced B-vitamins

K)   Reduced total antioxidant function

(1)  Especially after lipophilic toxin exposure

L)    Reproductive changes

(1)  Anovulation

(2)  Estrogen dominance in pre- and post-menopausal women

(3)  Testosterone deficiency

(4)  Probable aromatase deficiency

M) Melatonin deficiency

N)   For nutritional supplementation

(1)  Try to only introduce 1 supplement at a time, beginning with very small doses, increasing as tolerated.

(2)  Goal is to develop a diet that helps to

(a)   Replace deficient nutrients

(b)  Avoid food intolerances

(c)   Supply adequate

(i)    Protein

(ii)  Antioxidants

(d)  Low glycemic index

(i)    Causes less adrenal stress

(ii)  Improves control of Candida

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Bibliography

[1]   GE. Ziem,  J McTamney, “Profile of patients with chemical injury and sensitivity”,  Environ Health Perspect: 417-436, 1997. 

[2]   TJ. Callender, et al., “Olfactory intolerance and dynamic neurophysiological abnormalities in patients with toxic encephalopathy”, Advances in the BioSciences 93: 611 - 619, 1994.   

[3]    M.J. Hodgson, et al., “Encephalopathy and vestibulopathy following short-term hydrocarbon exposure”, J Occup Med 31: 51-54, 1989. 

[4]   S. M. Antelman, “Time dependent sensitization in animals”, Toxicol. Ind. Health,

      10:335-342, 1994.

[5]   I. R. Bell, “Neuropsychiatric aspects of sensitivity to low-level Chemicals: A neural sensitization model”, Toxicol. Ind. Health, 10:277-312, 1994.

[6]   L.A. Morrow, et al., “Alternations in cognitive and psychological functioning after organic solvent exposure”, J. Occup Med, 32:444-450, 1990.

[7]   S.C. Foo, et al., “Chronic neurobehavioral effects of toluene”, J. Ind. Med, 47:480-44, 1990.

[8]   P. Orbaek , M. Lindgren, “Prospective clinical and psychometric investigation of patients with  chronic toxic encephalopathy induced by solvents”, Scand J Work Environ Health, 14:37-44, 1988.

[9]   B.P. Stollery , M.L.H. Flindt, “Memory sequelae of solvent intoxication”,Scand J Work Environ Health, 14:45-48, 1988.

[10]  C. Edling, et al., “Long-term follow-up of workers exposed to solvents”, British J Indust Med 47:75-82, 1990.

[11]  H. Rasmussen, et al., “Risk of encephalopathia amongst retired solvent-exposed workers”, J. Occup Med,27:581-565, 1985.

[12]  P. Bruhn, et al.,  “Prognosis in chronic toxic encephalopathy: A two year follow-up study in 26 house painters with occupational encephalopathy”,  Acta Neurol. Scand, 64: 259-272, 1981.

[13]  P. Gregersen, et al.,  “Chronic toxic encephalopathy in solvent-exposed painters in Denmark 1976-1980: Clinical cases and social consequences after a 5-year follow-up”, Am J Ind Med 11: 399-417, 1987.

[14]  K.H. Kilburn, Editor,  Chemical Brain Injury,  Van Nostrand Reinhold 1998.

[15]  CE Fincher, et al., “Comparison of single photon emission computed tomography findings in cases of healthy adults and solvent-exposed adults”, Am J. Ind Med 31: 4-14, 1997.

[16]  J.L. O’Donoghue, Editor, Neurotoxicity of Industrial and Commercial Chemicals, Vol.I and II, CRC Press, 1985.

[17]  P. Arlien-Soborg, Editor, Solvent Neurotoxicity, CRC Press, 1992.

[18]  A. Englund, K. Ringen, M. Mehlman, Editors, Advances in Modern Environmental Toxicology, Vol. II,   Occupational Health Hazards of  Solvents, Princeton Scientific Publishers, 1982.

[19]   L Molhave, et al. "Human reactions to low concentrations of volatile organic compounds", Env Int 12:167-175, 1986.

[20]  S. Elofsson, etal., “Exposure to organic solvents”, Scand J Work Envorn Health,

6:239-273, 1980.

[21]  A.M. Seppalainen, et al.,  “Neurophysiological effects of long-term exposure to a mixture of organic solvents”, Scand. J. Work Environ Health, 4: 304-314, 1978.

[22]  E.J. Jonkman, et al.,  “Electroencephalographic studies in workers exposed to solvents or pesticides”, Electroencephalogr Clin Neurophysiol, 82: 439-444, 1992.

[23]  A.I. Bokina, et al.,  “Investigation of the mechanism of action of atmospheric pollutants on the central nervous system and compararative evaluation of methods of study”, Environ. Health Perspect, 13: 37-42, 1976.

[24]  P. Gregersen, “Neurotoxic Effects of Organic Solvents in Exposed Workers: Two Controlled Follow-up Studies After 5.5 and 10.6 Years”, Am J. Ind Med, 14: 681-701, 1988.

[25]  L.M. Odkvist, et al., “Otoneurologic disturbances caused by solvent pollution”, Otolaryngolgy-Head and Neck Surg., 106: 687-692, 1992.

[26]  L. Morrow, et al.,  “A distinct pattern of personality disturbance following exposure to mixtures of organic solvents”,  J Occup Med, 31: 743-746,  1989.

[27]  S.M. Gospe and M.J. Calaban, “Central nervous system distribution of inhaled toluene”, Fundam Appl Toxicol, 11:540-545, 1988.

[28]  Principals of neurotoxicity risk assessment, US EPA, Federal Register August 17, 1994.

[29]  L. Hastings and J.E. Evans, “Olfactory primary neurons as a route of entry for toxic agents into the central nervous system”, J. of Neurotoxicology 12:707-714, 1991.

[30]  GE Ziem, “Profile of patients with chemical injury and sensitivity”,  Int J Toxicol 18:401-409, 1999. 

[31]  H. Savolainan, “Some aspects of the mechanisms by which industrial solvents produce neurotoxic effects”, Chem. Biol. Interactions, 18:1-10, 1977.

[32]  T. J. Callender, et al.,  “Three-dimensional brain and metabolic imaging in patients with toxic encephalopathy”, Environ. Res 60: 295-319, 1993.

[33]  T.J. Callender, et al.,  “Evaluation of chronic neurological sequelae after acute pesticide exposure  using SPECT brain scans”.  J. Toxicol. Envirion. Health 41:275-284, 1995.

[34]  G. Heuser, et al.,  “Neurospect findings in patients exposed to neurotoxic chemicals”,  Toxicol Ind Health, 10: 561-571, 1994.  

[35]  H.M. Kipen, et al., “Asthma experience in an occupational medicine clinic.  Low dose reactive airway dysfunction syndrome”, J. Occup. Med. 36:1133-1137, 1994.

[36]  S.M. Brooks, et al., “Reactive airway dysfunction syndrome”, J. Occup. Med. 27, 473-476, 1985.

[37]   S.M. Tarbo and I. Broder, “Irritant-induced occupational asthma”, Chest 96:297-300, 1989.

[38]   WJ  Meggs, “RADS and RUDS-The toxic induction of asthma and rhinitis”, Clinic Toxic 32(5): 487-501, 1994.

[39]  WJ Meggs et al., “Nasal pathology and ultrastructure in patients with chronic airway inflammation (RADS and RUDS) following an irritant exposure”, Clinic Toxic 34(4): 383-396, 1996.

[40]   W.J. Meggs, “Neurogenic inflammation and sensitivity to environmental chemicals”, Enviorn. Health Perspect, 101:234-237, 1993.

[41]  A Hempel-Jorgensen et al., “Sensory eye irritation in humans exposed to mixtures of volatile organic compounds”, Archiv Environ Health 54: 416-424, 1999.

[42]  N.H. Proctor and J.P. Hughes, Editors, Chemical Hazards of the Workplace, J.B. Lippincott, Philadelphia, PA.

[43]  R.E. Lenga, Editor, The Sigma-Aldrich Library of Chemical Safety Data, pp. 1-3636, Sigma Aldrich Corporation, Milwaukee, WI.

[44]  HK Hudnell etal,. “Exposure of humans to volatile organic mixture. II. sensory”, Archiv Environ Health 47:31-38, 1992.

[45]  JE Cometto-Muniz et al., “Agonist sensory effects of airborne chemicals in mixtures: odor, nasal prengency and eye irritation”, Percept Psychophysiol 59: 665-674, 1997.

[46]  WJ Meggs, “Health effects of indoor air pollution”, NC. Med J 53(7): 354-358, 1992.

[47]  L. Perfetti et al.,  “Changes in IgE-mediated allergy to ubiquitous inhalants after removal from or diminution of  exposure to the agent causing occupational asthma”, Clin and Exp Allergy 28: 66-73, 1998.

[48]  S.M. Brooks, et al., “Reactive airway dysfunction syndrome”, J. Occup. Med. 27, 473-476, 1985.

[49]  S.M. Tarbo and I. Broder, “Irritant-induced occupational asthma”, Chest 96:297-300, 1989.

[50]  HK Hudnell et al., “Time course of odor and irritation effects in humans exposed to a mixture of 22 volatile organic compounds”, Proc Indoor Air ‘93 1: 567-572,1993.

[51]  C Shim, MH Williams Jr., “Effect of odors in asthma”, Am J Med 80: 18-22, 1986.

[52]  C. Baldwin et al., “Odor sensitivity and respiratory complaint profiles in a community-based sample with asthma, hay fever, and chemical odor intolerance”, Toxicol Ind Health  15: 403-409, 1999.

[53]  E Millqvist et al., “Sensory hyperreactivity-a possible mechanism underlying cough and esthma-like symptoms”, Allergy 53: 1208-1212, 1998.

[54]   E Millqvist et al., “Provocations with perfume in the eyes induce airway symptoms in patients with sensory hyperreactivity”, Allergy 54: 495-499, 1999.

[55]  CD. Clayson, MO. Amdur, J. Doull, Editors, Casarett and Doull's Toxicology: The Basic Science of Poisons, MacMillan Publishing Co., New York, NY. 

[56]  AL. Davidoff, PM. Keyl, “Symptoms and health status in individuals with multiple chemical sensitivity  syndrome from four reported sensitizing exposures and a general population comparison group”, Archiv Environ Health 51:201-213, 1996. 

[57]   HM. Kipen, et al. “Measuring chemical sensitivity prevalence: A questionnaire for population studies”, Am J Public Health 85: 574-577, 1995. 

[58]   MB Lax, PK Henneberger, “Patients with Multiple Chemical Sensitivities in an Occupational Health Clinic: Presentation and Followup”, Archiv. Env. Health 50:425-431, 1995.

[59]   “Treatment efficacy, a survey of 305 MCS patients,”  The CFIDS Chronicle, Winter 1996, pp. 52-53.

[60]   T.H. Davis, L.A. Jason, and M.A. Banghart, “The Effect of Housing on Individuals With Multiple Chemical Sensitivities”, Arch. Env. Health, 50:425-431, 1995.

[61]   C S. Miller, “Multiple Chemical Sensitivity Syndrome”, J.  Occup. Env. Med., 37:13-23, 1995.

[62]  SA Roach and  SM Rappaport, “But they are not thresholds: A critical analysis of the documentation of threshold limit values”, Am J Indust Med 17:727-753, 1990.

[63]  G Ziem and B Castleman, “Threshold limit values:Historical perspectives and current practice”, J Occup Med 31:910-918, 1989.

[64]  Beyond Pesticides, 701 E St. SE, Washington, DC.

[65]  JL McCarman, Weeds and Why They Grow, Sand Lake, MI, 1994.

[66]  N Gorman, Editor,  Less-Toxic Alternatives , Optimun Publishing Company, DeKalb, TX. 1997.

[67]  IR Bell, et al., “Self-reported illness from chemical odors in young adults without clinical syndromes or occupational exposures”, Archiv Environ Health 48: 6-13, 1993.

[68]   IR Bell, et al.,  “Possible time-dependendent sensitization to xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an older adult poulation”, Archiv Environ Health 48 315-327, 1993.

[69]   Residential Air Cleaning Devices: A Summary of Available Information.  United States Environmental Protection  Agency 400-1-90-002.

[69]  Matrix International, 24663 Clover Rd. Willits, CA. 95490, (707-459-3832).

[70]   Z. Tretjak etal, “PCB reduction and clinical improvement by detoxification”, Human Experiment Tox, 9:235-44, 1990. 

[71]   D. Schnare and M. Shields, “Body burden reduction of PBS’s, PBB’s and chlorinated pesticides in human subjects”, Ambio 13:378-80, 1954. 

[72]   D. Root and G. Lionelli, “Excretion of a lipophilic toxicant through the sebaceous glands”, International Agency for Research on Cancer Symposium, June 24-28, 1985. 

[73]   D.W. Schnare, etal, “Evaluation of a detoxification regiment for fat stored xenobiotics”, Medical Hypotheses 9:265-82, 1982. 

[74]   Z. Tretjak, etal, “Xenobiotic reduction and clinical improvements in capacitor workers”, J. Environ. Sci Health

[75]   Hanlon vs. Arizona Chemical Corp., State of Florida Department of Labor and Employment Security.  

[76]   BS Levy and D. H. Wegman, Occupational health: recognizing and preventing work-related disease, Little, Brown and Company, Boston, Massachusetts, 1988. 

[77]   S. Hagstadius, et al., “Regional cerebral blood flow at the time of diagnosis of chronic toxic encephalopathy induced by organic-solvent exposure and after the cessation of exposure”, ­Scan J Work Environ Health15:130-135, 1989.

[78]   T. J. Callender, et al.,  “Three-dimensional brain and metabolic imaging in patients with toxic encephalopathy”, Environ. Res 60: 295-319, 1993.

[79]   T.J. Callender, et al.,  “Evaluation of chronic neurological sequelae after acute pesticide exposure using SPECT brain scans”.  J. Toxicol. Envirion. Health 41:275-284, 1995.

[80]   G. Heuser, et al.,  “Neurospect findings in patients exposed to neurotoxic chemicals”,  Toxicology Industrial Health, 10: 561-571, 1994.  

[81]   CE Fincher, et al., “Comparison of single photon emission computed tomography findings in cases of healthy adults and solvent-exposed adults”, Amer J. Ind Med 31: 4-14, 1997.   

[82]    K.K. Jain, Textbook of Hyperbaric Medicine, Hogrefe and Huber Pub Co., Seattle, WA, 1999.

[83]    G.E. Ziem, clinical test results on dozens of chronically ill toxic injury patients in Dr. Ziem’s medical practice.

[84]    E.P. Kindwell and H.T. Whelan, editors, Hyperbaric Medicine Practice, Best Publishing Co., 1999.

[85]   G.E. Ziem, “Profile of patients with Chemical injury and sensitivity, Part II”, Int. J. Toxicol., 18:401-409, 1999.

[86]   Mixing chamber obtainable through the Environmental Health Foundation, Dallas, TX. 

[87]   I. Ezeonu, et al., “Fungal production of volatiles during growth on fiberglass”, Appl. Environ. Microb., 60:4172-4173, 1994.

[88]    C. Bayer, “Volatile emissions from fungi”, Engineering Solutions to Indoor Air Quality Problems, Environmental Protection Agency Symposium, July 22-24, 1995, published by the Air and Waste Management Association, Pittsburgh, PA.

[89]   C. Bayer, et al., “Production of volatile emissions by fungi”, Practical Engineering  for Indoor Air Quality,  IAQ 95, Symposium of October 22-24, 1995, Denver, CO, sponsored by U.S. Environmental Protection Agency,  US Department of Energy and American Society of Heating, Refrigerating, and Air Conditioning Engineers, Inc.

[90]   D Ahearn, “Fungal colonization of air filters and insulation in a multi-story office building: Production of volatile organics”, Curr Microbiol 35: 305-308, 1997.

[91]   TW Robinson, et al., “Generation of glycoladehyde from guinea pig air way epithelial monolayers exposed to nitrogen dioxide and its effects on sodium pump activity”, Environ Health Perspect 104:852-856, 1996.

[92]   Kahn, JP, etal, “Salivary cortisol:  a practical method for evaluation of adrenal function”, Biol Psychiatry 23: 35-349, 1988.

[93]   Bolufer, P. etal, “Salivary corticosteroids in the study of adrenal function”, Clinica Chemica Acta 183: 217-226, 1989.

[94]   MH Laudat, etal, “Salivary cortisol measurement:  a practical approach to assess pituitary-adrenal function”, J Clin Endocrinol Metab 66: 343, 1988.

[95]   E Bernton, etal., “Adaptation to chronic stress in miliary trainees”, Ann NY Acad Sci 774:217-231, 1995.

[96]   The author’s patients have achieved significant adrenal function improvement with these measures.

[97]   RK. Murray, D J. Granner, PA. Mayes, VW. Rodwell, editors, Harper's Biochemistry, Appleton and Lange, Norwalk CT. 

[98]   B Levine, Editor,  Environmental Nutrition Hingepin, Vason Island, WA., 1999.

[99]   A Spector, “ Review: oxidative stress and disease”, J Ocul Pharmocol Thera 16:193-201, 2000.

[100]  M Avirum, “Review of human studies of oxidative damage and antioxidant protection related to cardiovascular diseases”, Free Radic Res 33: Supp S85-97, 2000.

[101]  RW Alexander, “Hypertension and the pathogenesis of arteriosclerosis. Oxidative stress and the mediation of  arterial inflammatory response”, Hypertension 25:155-161, 1995.

[102]  CB Ambrosone, “Oxidants and antioxidants in breast cancer”, Antioxid Redox Signal 2:903-917, 2000.

[103]  CF Babbs, “Free radicals and the etiology of colon cancer”, Free Radic Biol Med  8:191-200, 1990.

[104]  IL Chapple, “Reactive oxygen speciec in inflammatory disease”, J Clin Periodontol 24:287-296, 1997.

[105]  S Toyokuni, “Reactive oxygen species-induced molecular damaged and its application in pathology”, Pathol Int  49:91-102, 1999.

[106]  JA Knight, “The biochemistry of aging”, Adv Clin Chem 35:1-62, 2000.

[107]  L. O. Simpson, New Zealand Medical Journal 106: 104-107, 1993

[108]  Great Smokies Diagnostic Laboratory, Asheville, N.C.

[109]  MetaMetrix Laboratory, Norcross, G.A. 

[110]   M. C. Linder, Nutritional Biochemistry and Metabolism Appleton and Lange, Norwalk CT, 1991.

[111]   U. Erasmus, Fats That Heal, Fats That Kill Alive Books, Burnaby, British Columbia, Canada, 1993. 

[112]  M Boosalis, et al., “Impaired handling of orally administered zinc in pancreatic insufficieny”, Am J Clin Nutr 37: 268-271, 1983.

[113]   P. Borner, “Functional intracellular analysis of nutritional and antioxidant status”, Journal of the American Neutraceutical Association 4: 27-41, 2001.

[114]   JE Pizzorno and MT Murray, editors, Textbook of Natural Medicine, Churchill Livingstone on, New York, NY. 

[115]  K. L. Becker, editor, Principals and Practice of Endocrinology and Metabolism, J. B. Lippincott Company, Philadelphia, PA, 1995. 

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