Protocole Horowitz PDF

Classical and Integrative Medical
Classical and Integrative Medical

Approaches in Chronic Lyme
Approaches in Chronic Lyme
Disease: New Paradigms in
Disease: New Paradigms in
Diagnosis & 1reatment
Diagnosis & 1reatment
Dr Richard lorowitz Dr Richard lorowitz
ludson Valley lealing Arts Center ludson Valley lealing Arts Center
4232 Albany Post Road 4232 Albany Post Road
lyde Park, N.\. 12538 lyde Park, N.\. 12538
845 845- -229 229- -89 89
Septra/Bactrim Septra/Bactrim
Quinolones Quinolones
Rifampin Rifampin
Macrolides Macrolides / / Ketolides Ketolides
Inestigatie 1reatment Protocols or Inestigatie 1reatment Protocols or
Lyme Disease and Multiple Co Lyme Disease and Multiple Co- -inections inections
Candida: Candida: Nystatin, Nystatin,
Diflucan, Acidophilus Diflucan, Acidophilus
?Leaky Gut ?Leaky Gut
?Food Allergies ?Food Allergies
?El syndrome, Heavy ?El syndrome, Heavy
metal toxicities metal toxicities
?Multiple chemical ?Multiple chemical
sensitivities sensitivities
Hormonal d/f Hormonal d/f
Therefore, drug regimens which are effective against multiple
organisms simultaneously and penetrate intracellularly and into
the CNS may be necessary to achieve significant clinical
improvement.
Immune Immune
dysregulation dysregulation: :
ANA+, HLA DR4 + ANA+, HLA DR4 +
Plaquenil Plaquenil
?Herbs / CAM ?Herbs / CAM tx tx
Tetracyclines Tetracyclines
Cleocin & Quinine Cleocin & Quinine
Mepron&Zithromax Mepron&Zithromax
Lariam Lariam
Artemesia Artemesia
Malarone Malarone
? Mycoplasma
? Chlamydia
Ehrlichia/Anapl.
Babesia
Viruses
Bartonella
Cell Wall: Cell Wall:
Penicillin / Penicillin /
Cephalosporins Cephalosporins
Cyst: Flagyl/Plaquenil Cyst: Flagyl/Plaquenil
?Neurotoxins ?Neurotoxins
?HBOT ?HBOT
?Heat Therapy ?Heat Therapy
?IV Glutathione ?IV Glutathione
Anti Anti- -Virals Virals
Borrelia burgdorferi
Virtually all human diseases result

Virtually all human diseases result
from the interaction of genetic
from the interaction of genetic
susceptibility factors and modifiable
susceptibility factors and modifiable
environmental factors, broadly
environmental factors, broadly
defined to include infections,
defined to include infections,
chemical, physical, nutritional, and
chemical, physical, nutritional, and
behavioral factors
behavioral factors
Office of Genetics and Disease Prevention, CDC Office of Genetics and Disease Prevention, CDC
Chronic Lyme Disease: Differential
Diagnosis
Diagnosis
1. 1.
Inections
Inections
:
:
a,
a,
Bacterial
Bacterial
: Lyme disease,
: Lyme disease,
Lhrlichiosis
Lhrlichiosis
,
,
Bartonella
Bartonella
,
,
Mycoplasma
Mycoplasma
, Chlamydia, RMSl,
, Chlamydia, RMSl,
1yphus, 1ularemia, Q
1yphus, 1ularemia, Q
-
-
leer, 1ick paralysis
leer, 1ick paralysis
.
.
b,
b,
Parasites
Parasites
:
:
Babesiosis
Babesiosis
and other
and other
piroplasms
piroplasms
,
,
iliariasis
iliariasis
,
,
amebiasis
amebiasis
,
,
giardiasis
giardiasis
.
.
c,
c,
Viruses
Viruses
: LBV, llV
: LBV, llV
-
-
6, llV
6, llV
-
-
8, CMV, St
8, CMV, St
Louis Lncephalitis, \ Nile,
Louis Lncephalitis, \ Nile,
Powassan
Powassan
encephalitis and other iral
encephalitis and other iral
encephalopathies
encephalopathies
d,
d,
Candida
Candida
and other ungi
and other ungi
Diagnosis
Diagnosis

2,
2,
Immune dysunction
Immune dysunction

3,
3,
Inlammation
Inlammation

4,
4,
1oxicity
1oxicity
: Multiple Chemical Sensitiity,
: Multiple Chemical Sensitiity,
Lnironmental Illness, leay Metals, Mold and
Lnironmental Illness, leay Metals, Mold and
Neurotoxins ,external and internal
Neurotoxins ,external and internal
biotoxins
biotoxins
,
,

5,
5,
Allergies
Allergies
: oods, drugs, enironmental
: oods, drugs, enironmental
.
.

6,
6,
Nutritional
Nutritional
& Lnzyme
& Lnzyme
Deiciencies
Deiciencies
,
,
unctional medicine abnormalities in
unctional medicine abnormalities in
biochemical pathways
biochemical pathways

,
,
Mitochondrial
Mitochondrial
dysunction
dysunction
Diagnosis
Diagnosis

8,
8,
Psychological
Psychological
: stress, P1SD, abuse,
: stress, P1SD, abuse,
depression, anxiety, OCD
depression, anxiety, OCD
.
.

9,
9,
Lndocrine
Lndocrine
abnormalities
abnormalities
: thyroid, Gl,
: thyroid, Gl,
adrenal, sex hormones, pituitary,
adrenal, sex hormones, pituitary,
Vit
Vit
D de
D de

10,
10,
Sleep
Sleep
disorders
disorders
: Acute and Chronic ,OSA,
: Acute and Chronic ,OSA,
Medications, Pain,
Medications, Pain,
Nocturia
Nocturia
,
,
Depression,Anxiety, RLS
Depression,Anxiety, RLS
.
.

11,
11,
Autonomic
Autonomic
Nerous System ,ANS,
Nerous System ,ANS,
Dys,
Dys,
,
,
Diagnosis
Diagnosis

12,
12,
Gastrointestinal
Gastrointestinal
: Leaky Gut, Candida,
: Leaky Gut, Candida,
Dysbiosis
Dysbiosis
, Celiac Disease, Colitis, Cancer
, Celiac Disease, Colitis, Cancer
.
.

13,
13,
Lleated
Lleated
Ll1
Ll1
`
`
s
s
: AB
: AB
`
`
s, L1Ol, lepatitis,
s, L1Ol, lepatitis,
lemochromatosis
lemochromatosis
, \ilsons disease,
, \ilsons disease,
-
-
-
-
1A1
1A1
deiciency, chemicals ,carbon
deiciency, chemicals ,carbon
tet,drugs
tet,drugs
,
,
.
.

14,
14,
Drug use,Addiction
Drug use,Addiction

15,
15,
Deconditioning
Deconditioning
: Need or P1,Lxercise
: Need or P1,Lxercise
program..
program..
I: Infections In Chronic Lyme
I: Infections In Chronic Lyme
Disease
Disease

1,Bacterial :
1,Bacterial :
a, a,Borrelia Borrelia burgdoreri burgdoreri: Combine drugs to address all 3 : Combine drugs to address all 3
orms o Bb simultaneously 2 orms o Bb simultaneously 2 to the ability o the to the ability o the
organism to shit between dierent orms, go dormant, organism to shit between dierent orms, go dormant,
and eade immune sureillance. Continue treatment and eade immune sureillance. Continue treatment
until the patient is 2 months symptom ree until the patient is 2 months symptom ree
-
-Cell \all orms Cell \all orms Amoxicillin, Amoxicillin, Augmentin Augmentin, , Cetin Cetin , ,Cedax Cedax, ,
Omnice Omnice, IM , IM Bicillin Bicillin, IV , IV Rocephin Rocephin, IV , IV Claoran Claoran, IV , IV
Vancomycin Vancomycin, IV , IV Primaxin Primaxin. .
- -Cystic orms Cystic orms , L , L- -orms, orms, spheroplasts spheroplasts, C\D orms.., , C\D orms..,
Plaquenil Plaquenil , ,hydroxychloroquine hydroxychloroquine,, GSL, ,, GSL, llagyl llagyl , ,metronidazole metronidazole,, ,,
1indamax 1indamax , ,tinidazole tinidazole, ,
- -Intracellular orms Intracellular orms tetracyclines tetracyclines , ,doxycycline doxycycline, , minocycline minocycline, ,
tetracycline lCL,, tetracycline lCL,, macrolides macrolides , ,azithromycin azithromycin, , clarithromycin clarithromycin,, ,,
quinolones quinolones , ,Cipro Cipro, , Leaquin Leaquin, , Aelox Aelox,, ,, Riampin Riampin. .
Persistence of Lyme
Persistence of Lyme
Borreliosis
Borreliosis
:
:
Atypical Iorms/Cystic Iorms
Atypical Iorms/Cystic Iorms
Preac Preac- -Mursic Mursic, V et al, lormation and Cultiation o , V et al, lormation and Cultiation o
Borrelia burgdoreri Borrelia burgdoreri Spheroplast Spheroplast- -L L- -orm Variants, orm Variants,
Inection 24 ,1996,,No 3:218 Inection 24 ,1996,,No 3:218- -26 26
Brorson,O Brorson,O et al, 1ransormation o cystic orms o et al, 1ransormation o cystic orms o
Borrelia burgdoreri to normal, mobile spirochetes, Borrelia burgdoreri to normal, mobile spirochetes,
Inection 25 ,199,, No 4:240 Inection 25 ,199,, No 4:240- -45. 45.
Alban PS et al, Serum Alban PS et al, Serum- -staration induced changes in staration induced changes in
protein synthesis and morphology o Borrelia protein synthesis and morphology o Borrelia
burgdoreri, Microbiology ,2000,, 146:119 burgdoreri, Microbiology ,2000,, 146:119- -2 2
Brorson Brorson, O et al, A rapid method or generating , O et al, A rapid method or generating
cystic orms o Borrelia burgdoreri, and their cystic orms o Borrelia burgdoreri, and their
reersal to mobile spirochetes, APMIS, 106 reersal to mobile spirochetes, APMIS, 106
,1998,:1131 ,1998,:1131- -41 41
1reatment Relapses and Iailures
1reatment Relapses and Iailures
with Short
with Short
-
-
term 1herapy
term 1herapy
Logigian Logigian ,1990, : Ater 6 mo ,1990, : Ater 6 mo` `s o therapy, 10,2 patients s o therapy, 10,2 patients
treated with IV AB treated with IV AB` `s relapsed or had treatment ailure. s relapsed or had treatment ailure.
Pister Pister ,1991, : 33 patients with ,1991, : 33 patients with neuroborreliosis neuroborreliosis were treated were treated
with IV AB with IV AB` `s. Ater a mean o 8.1 months 10,2 were s. Ater a mean o 8.1 months 10,2 were
symptomatic and symptomatic and borrelia borrelia persisted in the CSl in 1 pt persisted in the CSl in 1 pt
Shadick Shadick ,1994, : 10,38 pts relapsed ,5 with IV, within 1 year ,1994, : 10,38 pts relapsed ,5 with IV, within 1 year
o treatment, and had repeated AB treatment o treatment, and had repeated AB treatment
Asch ,1994, : 28 relapsed w, major organ inolement 3.2 Asch ,1994, : 28 relapsed w, major organ inolement 3.2
years ater initial treatment years ater initial treatment
Valesoa Valesoa ,1996, :10,26 relapsed or progressed at 36 mo ,1996, :10,26 relapsed or progressed at 36 mo
1rieb 1rieb ,1998, : 50 pts symptomatic ater 4.2,-, ,1998, : 50 pts symptomatic ater 4.2,-,- - 1.2 yrs 1.2 yrs
Shadick Shadick ,1999, : 69,184 ,3, report a preious relapse ,1999, : 69,184 ,3, report a preious relapse
Benefit of Longer treatment Regimes
for Disseminated Lyme Disease
1. 1. \ahlberg,P \ahlberg,P. et al, 1reatment o late Lyme . et al, 1reatment o late Lyme
borreliosis borreliosis. J Inect, 1994. 29,3,: p255 . J Inect, 1994. 29,3,: p255- -61 61 31 31
improed w, 14 d improed w, 14 d Rocephin Rocephin, 89 improed w, , 89 improed w,
Rocephin Rocephin - 100d o - 100d o Amox Amox and and Probenecid Probenecid, 83 , 83
improed w, improed w, Rocephin Rocephin, then 100 days o , then 100 days o
cephadroxil cephadroxil
2. 2. Donta Donta, S1., 1etracycline therapy or chronic Lyme , S1., 1etracycline therapy or chronic Lyme
disease. disease. Clin Clin Inect Inect Dis Dis, 199. 25 , 199. 25 Suppl Suppl 1: p.S52 1: p.S52- -6. 6.
2 pts with 2 pts with chr chr LD treated between 1 LD treated between 1- -11 mo: 11 mo:
20 cured, 0 improed, 10 treatment ailure 20 cured, 0 improed, 10 treatment ailure
3. 3. Oksi Oksi, J et al., Comparison o oral , J et al., Comparison o oral ceixime ceixime and intraenous and intraenous
cetriaxone cetriaxone ollowed by oral amoxicillin in disseminated ollowed by oral amoxicillin in disseminated
Lyme Lyme borreliosis borreliosis. . Lur Lur J J Clin Clin Microbiol Microbiol Inect Inect Dis Dis, 1998. , 1998.
1,10, :p 15 1,10, :p 15- -9 9
30 pts w, 30 pts w, chr chr Lyme treated or 100 d, 90 w, good or Lyme treated or 100 d, 90 w, good or
excellent responses excellent responses
4. 4. Oksi Oksi, J., et al. Borrelia burgdoreri detected by culture and , J., et al. Borrelia burgdoreri detected by culture and
PCR in clinical relapse o disseminated Lyme PCR in clinical relapse o disseminated Lyme borreliosis borreliosis. .
Ann Med, 1999. 31,3,:p.225 Ann Med, 1999. 31,3,:p.225- -32 32
32,165 pts w, disseminated Lyme treated or 1 or more 32,165 pts w, disseminated Lyme treated or 1 or more
months o AB months o AB` `s showed that een 3 mo o treatment s showed that een 3 mo o treatment
may not eradicate the spirochete, longer term therapy may may not eradicate the spirochete, longer term therapy may
be necessary be necessary
Infections in Chronic Lyme Disease

1,Bacterial:
1,Bacterial:
b, b,Lhrlichiosis Lhrlichiosis: : tetracyclines tetracyclines ,doxy, ,doxy, minocycline minocycline, ,
or or riampin riampin or allergic,intolerant patients or allergic,intolerant patients
c, c,Bartonella Bartonella, , Mycoplasma Mycoplasma, Chlamydia, RMSl, , Chlamydia, RMSl,
1yphus, 1ularemia, Q 1yphus, 1ularemia, Q- -eer , eer ,Coxiella Coxiella, ,. .
these are all intracellular co these are all intracellular co- -inections, and are diicult to inections, and are diicult to
completely eradicate rom the intracellular compartment. completely eradicate rom the intracellular compartment.
Consider 2 intracellular drugs simultaneously to improe clinic Consider 2 intracellular drugs simultaneously to improe clinical al
outcomes , outcomes ,doxycyline doxycyline w, w, macrolide macrolide, , macrolide macrolide - - riampin riampin, ,
tetracycline - tetracycline - quinolone quinolone. ., and use , and use Plaquenil Plaquenil to alkalize the to alkalize the
intracellular compartment to achiee better intracellular killin intracellular compartment to achiee better intracellular killing g
, ,Maurin Maurin et al. et al. Phagolyosomal Phagolyosomal Alkalinization Alkalinization and the Bactericidal and the Bactericidal
Lect o Antibiotics. J. Inect Dis1992, 166:109 Lect o Antibiotics. J. Inect Dis1992, 166:109- -1102, 1102,
I one regimen o an intracellular combo ails, rotate the r I one regimen o an intracellular combo ails, rotate the regimen egimen
to another double intracellular regimen, and consider treating to another double intracellular regimen, and consider treating
other co other co- -inections not addressed , inections not addressed ,Babesiosis Babesiosis, iruses.., , iruses..,
Infections In Chronic Lyme Disease
Infections In Chronic Lyme Disease
2, Parasites: 2, Parasites: Babesiosis,Piroplasmosis Babesiosis,Piroplasmosis
- - Classical 1reatment options Classical 1reatment options: : Mepron Mepron , ,atoaquone atoaquone, and a , and a
macrolide macrolide , ,Zithromax Zithromax, , Biaxin Biaxin, -, , -,- - Septra Septra, , Malarone Malarone, , Larium Larium
, ,meloquine meloquine,, ,, Cleocin Cleocin and Quinine or and Quinine or Biaxin Biaxin , , Riamet Riamet.. ..
- -CAM CAM: : Artemisinin Artemisinin ,wormwood,: anti ,wormwood,: anti- -malarial, malarial, antiparasitic antiparasitic, ,
antiiral, anti antiiral, anti- -tumor. Modiied orm o tumor. Modiied orm o Artemesinin Artemesinin, , artesunate artesunate, ,
has been ound eectie or has been ound eectie or Babesia Babesia in itro. Complete in itro. Complete
inhibition o B. inhibition o B. equi equi and and caballi caballi occurred at 0,2 and 1.0 mcg,ml occurred at 0,2 and 1.0 mcg,ml
respectiely. respectiely.
- -Dosage Dosage: 500mg,d x30 : 500mg,d x30- -40 days or malaria, Best dosage or 40 days or malaria, Best dosage or Bab Bab
- -In malaria, eectie dose is 500 In malaria, eectie dose is 500- -1000mg 1 1000mg 1
st st
day, then 500 day, then 500
mg,day x4 days ,but relapse rate ~ 39, mg,day x4 days ,but relapse rate ~ 39,
I the dosage is increased to 800 mg,day, relapse rate I the dosage is increased to 800 mg,day, relapse rate to 3 to 3
In China they use 800 In China they use 800- -1600mg,d x 3 days, repeated in 2 wks 1600mg,d x 3 days, repeated in 2 wks
- -Side eects Side eects: GI at high dose: : GI at high dose: apetite apetite, N-, V-, diarrhea , N-, V-, diarrhea
- -Contraindications Contraindications: Pregnancy : Pregnancy
Artemesia
Artemesia
: Scientific References
: Scientific References
Lckstein Lckstein- -Ludwig, U. et al. Ludwig, U. et al. Artemesinins Artemesinins target the SLRCA o target the SLRCA o
Plasmodium Plasmodium alciparum alciparum, Nature 2003,424,6951,:95 , Nature 2003,424,6951,:95- -61 61
Gordi Gordi et al. et al. Artemesinin Artemesinin pharmacokinetics and eicacy in pharmacokinetics and eicacy in
uncomplicated malarial patients treated with two dierent uncomplicated malarial patients treated with two dierent
dosage regimens, Antimicrobial Agents dosage regimens, Antimicrobial Agents Chemother Chemother
2002,46,4,:1026 2002,46,4,:1026- -31 31
\ong, J. et al. 1herapeutic equialence o a low dose \ong, J. et al. 1herapeutic equialence o a low dose artemesinin artemesinin
ormulation in ormulation in alciparum alciparum malaria patients, Journal o Pharmacy malaria patients, Journal o Pharmacy
and Pharmacology 2003,55,2,:193 and Pharmacology 2003,55,2,:193
Jung, M. et al. Recent adances in Jung, M. et al. Recent adances in artemesinin artemesinin and its deriaties and its deriaties
as as antimalarial antimalarial and antitumor agents, and antitumor agents, Curr Curr Med Med Chem Chem
2004,11,10,:1265 2004,11,10,:1265- -84 84
latimi latimi, S. et al. In itro ealuation o , S. et al. In itro ealuation o antileishmania antileishmania actiity o actiity o
Artemesia Artemesia herba herba Asso Asso, Bull Soc , Bull Soc Pathol Pathol Lxot Lxot 2001, 94,1,:29 2001, 94,1,:29- -31 31
Kim, J. et al. In itro Kim, J. et al. In itro antiprotozoal antiprotozoal eects o eects o artemesinin artemesinin on on
Neospora Neospora caninum caninum, Vet , Vet Parasitol Parasitol 202,103,1 202,103,1- -2,:53 2,:53- -63 63
CHRONIC PERSISTENT BABESIOSIS AFTER ACUTE TREATMENT
WITH CLEOCIN AND QUININE, AND ATOVAQUONE AND
AZITHROMYCIN
Persistent parasitemia after acute babesiosis was described by
Krause (NEJM 7/98, Vol 339, 160-165) when patients were
given Cleocin and Quinine (C+Q), and an experimental
regimen with Atovaquone and Azithromycin (M+Z) was noted
to possibly cure human babesiosis. Horowitz described
significant clinical improvement in a cohort of chronic Lyme
patients co-infected with babesia when given Atovaquone +
Azithromycin, but relapses were seen at the completion of
therapy, and PCR studies were needed to elucidate the
eradication rate of the organism (Horowitz, R.I.: Atovaquone
and Azithromycin therapy: A new treatment protocol for
Babesiosis in co-infected Lyme patients, in Abstracts of the
11
th
International Scientific Conference on Lyme disease,
NYC, NY April 1998). This report describes PCR + RNA
evidence of persistent parasitemia with both antibiotic
regimens.
12th International Scientific Conference on Lyme Disease, April 1999, New
York City
Dr Richard Horowitz 4232 Albany Post Road Hyde Park, N.Y. 12538
CHRONIC PERSISTENT BABESIOSIS AFTER ACUTE TREATMENT WITH
CLEOCIN AND QUININE, AND ATOVAQUONE AND AZITHROMYCIN
Results:
72 of 189 serum specimens were PCR positive, and 38 of 58
specimens were RNA positive. 33 charts were analyzed
among patients who received one or more courses of M+Z or
C+Q and remained PCR and/or RNA positive post treatment.
PCR testing and RNA testing remained positive up to 9
months and 5 months respectively, with several patients who
were both IFA and PCR negative turning PCR positive after
treatment. The majority of patients clinically improved while
on the regimens but relapsed shortly after the antibiotics were
stopped, with flares occurring often during treatment. Only 4
out of 27 patients became PCR/RNA negative post treatment.
Crossing over from one regimen to the other was generally
ineffective as PCR/RNA values remained positive, except in 2
cases. M+Z was better tolerated than C+Q, and lab values
generally remained within normal limits with both regimens,
with an occasional mild elevation of liver functions.

3,
3,
Viruses
Viruses
:
: LBV, CMV, llV6 & 8, \. Nile, LBV, CMV, llV6 & 8, \. Nile,
Powassan Powassan encephalitis and other iral encephalitis encephalitis and other iral encephalitis
- -ex llV6 ex llV6 there is a link to ClS,lM. Causes there is a link to ClS,lM. Causes roseola roseola
in childhood & nearly 100 o adults are exposed. Can in childhood & nearly 100 o adults are exposed. Can
reactiate later in lie 2 reactiate later in lie 2 to to immunol,enir immunol,enir actors actors
can lead to hepatitis, can lead to hepatitis, meningoencephalitis meningoencephalitis.. coactor in .. coactor in
Autism, ADD, MS, lM, ClS Autism, ADD, MS, lM, ClS
- -Classical treatment Classical treatment: : antiirals antiirals , ,Valtrex Valtrex, , lamir lamir, acycloir, , acycloir,
gancycloir gancycloir.., .., Valcyte Valcyte ,ongoing trial at Stamord Uniersity by ,ongoing trial at Stamord Uniersity by
Dr Montoya, Dr Montoya,
- -CAM CAM: 1ranser actors , : 1ranser actors ,colostrum colostrum,, mushroom deriaties that ,, mushroom deriaties that
increase NK cells and 1 cells ,1 increase NK cells and 1 cells ,1- -3 and 3 3 and 3- -6 B 6 B glucan glucan..,. Another ..,. Another
scientiically proen compound is Olie lea extract and its act scientiically proen compound is Olie lea extract and its actie ie
component component oleuropein oleuropein. 1his was ound by researchers at Upjohn . 1his was ound by researchers at Upjohn
labs to be labs to be irucidal irucidal against many iruses including herpes, against many iruses including herpes,
inluenza A, inluenza A, coxsackie coxsackie and others. and others.
Juen Juen B. et al. B. et al. Sudies Sudies on the Mechanism o Antimicrobial Action on the Mechanism o Antimicrobial Action
o o Oleuropein Oleuropein. . Jnl Jnl o Applied Bacteriology 35 ,190,, 559 o Applied Bacteriology 35 ,190,, 559- -56 56
I: Infections in Chronic Lyme
I: Infections in Chronic Lyme
Disease
Disease

4,Candida and other ungi
4,Candida and other ungi: \east syndrome : \east syndrome
yeast oergrowth in the intestinal tract leads to yeast oergrowth in the intestinal tract leads to
ermentation o dietary sugars and starches. Can be 2 ermentation o dietary sugars and starches. Can be 2
to antibiotic use or Lyme disease to antibiotic use or Lyme disease
Symptoms Symptoms include: atigue, include: atigue, lA lA` `s s, dizziness, brain og, , dizziness, brain og,
abdominal pain with bloating, muscle and joint pain..& abdominal pain with bloating, muscle and joint pain..&
may oerlap with classic Lyme symptoms may oerlap with classic Lyme symptoms
1esting 1esting: Stool CDSA, : Stool CDSA, Genoa Genoa Diagnostics w, Diagnostics w,
sensitiity to ungal agents. sensitiity to ungal agents. Metametrix Metametrix Organix Organix test test
Classical treatment Classical treatment: : Dilucan Dilucan , ,luconazole luconazole,, ,, Sporanox Sporanox, ,
Oral Oral Nystatin Nystatin
CAM CAM: ligh dose : ligh dose probiotics probiotics ,acidophilus,, ,acidophilus,,
Saccharomyces Saccharomyces boulardii boulardii, , Candibactin Candibactin, , Caprylic Caprylic Acid, Acid,
Berberain Berberain, Oregano oil, Garlic, Pau , Oregano oil, Garlic, Pau D D` `Arco Arco
II: Immune
II: Immune
Dysregulation
Dysregulation
and Lyme
and Lyme
Blebs are shed particles containing partial DNA, Blebs are shed particles containing partial DNA,
requently plasmids. requently plasmids.
- -Radol Radol JD et al. Analysis o JD et al. Analysis o Borrelia Borrelia burgdoreri burgdoreri membrane architecture by membrane architecture by
reeze reeze- -racture electron microscopy. Journal o Bacteriology. Jan racture electron microscopy. Journal o Bacteriology. Jan
1994,16,1,:21 1994,16,1,:21- -31 31
- -Garon Garon Cl, Cl, Dorward Dorward D\, Corwin MD. Structural eatures o D\, Corwin MD. Structural eatures o Borrelia Borrelia
burgdoreri burgdoreri- -the Lyme disease spirochete: siler staining or nucleic acids. the Lyme disease spirochete: siler staining or nucleic acids.
Scanning Llectron Microscopy. 1989 3:109 Scanning Llectron Microscopy. 1989 3:109- -115 115
lighly stimulatory to the immune system lighly stimulatory to the immune system
- -\hitmire \hitmire \M, \M, Garon Garon Cl. Speciic and nonspeciic responses o Cl. Speciic and nonspeciic responses o murine murine B cells to B cells to
membrane blebs o membrane blebs o Borrelia Borrelia burgdoreri burgdoreri. Inection & Immunity, 1993 61:1460 . Inection & Immunity, 1993 61:1460- -146 146
Intra Intra- -cellular blebs conert host cells into targets or the cellular blebs conert host cells into targets or the
immune system immune system
- -Beerman Beerman C, C, \underli \underli- -Allenspach Allenspach l et al. Lipoproteins rom l et al. Lipoproteins rom Borrelia Borrelia burgdoreri burgdoreri applied applied
in in liposomes liposomes and presented by and presented by dendritic dendritic cells induce CD8,-, 1 cells induce CD8,-, 1- -lymphocytes in itro. lymphocytes in itro.
Cell Immunology May 2000,201 ,2,:124 Cell Immunology May 2000,201 ,2,:124- -131 131
II: Immune
II: Immune
Dysregulation
Dysregulation
and Lyme
and Lyme
Positie ANA, Rl and other autoimmune markers , Positie ANA, Rl and other autoimmune markers ,Plaquenil Plaquenil, ,
Increased seerity with genetic lLA markers ,lLA DR2, 4, Increased seerity with genetic lLA markers ,lLA DR2, 4,
Lleated pro Lleated pro- -inlammatory cells: inlammatory cells:
- -IL IL- -6, 1Nl 6, 1Nl- - , IlN gamma , IlN gamma
Propensity to excessie Propensity to excessie proinlammatory proinlammatory response in Lyme response in Lyme
borreliosis borreliosis. . Kisand Kisand et al, APMIS. 200 leb, 115,2,:134 et al, APMIS. 200 leb, 115,2,:134- -41 41
Interleukin Interleukin- -6 is expressed at high leels in the CNS in Lyme 6 is expressed at high leels in the CNS in Lyme
neuroborreliosis neuroborreliosis. . Pachner Pachner et al. Neurology 199 Jul,49,1,c14 et al. Neurology 199 Jul,49,1,c14- -52 52
INl INl- -gamma alters the response o Bb actiated endothelium to gamma alters the response o Bb actiated endothelium to
aor chronic inlammation. J. aor chronic inlammation. J. Immunol Immunol. 200 Jan 15,18,2,:112 . 200 Jan 15,18,2,:112- -9 9
Decreased anti Decreased anti- -inlammatory cells: IL inlammatory cells: IL- -10 10
Abnormal helper,suppressor cell ratio Abnormal helper,suppressor cell ratio ,CD4,CD8,. ,CD4,CD8,.
Both Lyme and ASD hae immune Both Lyme and ASD hae immune dysregulation dysregulation, and it is , and it is
known that systemic inections ,Bb, iruses.., with associated known that systemic inections ,Bb, iruses.., with associated
inlammation can aect chronic inlammation can aect chronic neurodegeneration neurodegeneration
Perry et al. Nature Reiews Immunology , 161 Perry et al. Nature Reiews Immunology , 161- -16 ,leb 200, 16 ,leb 200,
Mycoplasma Inections May Contribute to Immune
Mycoplasma Inections May Contribute to Immune
Dysregulation
Dysregulation
in Chronic Lyme Disease
in Chronic Lyme Disease
Discussion Discussion: ( : (con con` `t t, , Mycoplasmas Mycoplasmas hae been shown to hae been shown to
interact non interact non- -speciically with B speciically with B- -lymphocytes resulting in the lymphocytes resulting in the
modulation o immunity promoting autoimmune reactions modulation o immunity promoting autoimmune reactions
and rheumatoid diseases , and rheumatoid diseases ,Simecka Simecka et.al. et.al. Clin Clin. Inect. Dis. . Inect. Dis.
1993,1,Suppl 1,:516 1993,1,Suppl 1,:516- -5182,. Mycoplasmal inections also 5182,. Mycoplasmal inections also
increase increase proinlammatory proinlammatory cytokines including IL cytokines including IL- -1,2, and 6 1,2, and 6
, ,M M hlradt hlradt et.al. Inect. et.al. Inect. Immunol Immunol. 1991,58:123 . 1991,58:123- -1280,, and 1280,, and
hae been ound in the joint tissues o patients with hae been ound in the joint tissues o patients with
rheumatological rheumatological diseases suggesting their pathogenic diseases suggesting their pathogenic
inolement , inolement ,lurr lurr et.al. Ann. et.al. Ann. Rheumatol Rheumatol. Dis. 1994,53,183 . Dis. 1994,53,183- -
184,. lurther studies thereore need to be done to elucidate 184,. lurther studies thereore need to be done to elucidate
the role o mycoplasmal inections in Lyme Disease patients the role o mycoplasmal inections in Lyme Disease patients
with chronic persistent symptomatology. with chronic persistent symptomatology.
III: Role of Inflammatory Mediators
III: Role of Inflammatory Mediators
in Neurotoxicity
in Neurotoxicity
Inlamm Inlamm processes are inoled in the neurotoxicity o processes are inoled in the neurotoxicity o
AD and other CNS diseases. Microglia are actiated by AD and other CNS diseases. Microglia are actiated by
B B amyloid amyloid & & proinlamm proinlamm cytokines. Actiated microglia cytokines. Actiated microglia
in turn release in turn release proinlamm proinlamm cytokines ,IL cytokines ,IL- -1 1- - , IL , IL- -6, 6,
1Nl 1Nl- - , that may lead to neuronal death and , that may lead to neuronal death and dys, dys,, by a , by a
ariety o mechanisms, including: ariety o mechanisms, including:
1, Lnhancement o glutamate 1, Lnhancement o glutamate- -induced induced excitotoxicity excitotoxicity
2, Inhibition o long term 2, Inhibition o long term potentiation potentiation, which limits ,, plasticity , which limits ,, plasticity
ater neuronal injury ater neuronal injury
3, Inhibition o 3, Inhibition o hippocampal hippocampal neurogenesis neurogenesis
Recent studies hae reported Recent studies hae reported 1Nl 1Nl- - leels in the CSl o AD leels in the CSl o AD
pts, and a single nucleotide polymorphism in the 1Nl pts, and a single nucleotide polymorphism in the 1Nl- - gene is gene is
associated w, earlier onset AD associated w, earlier onset AD
Lyme Lyme dx dx pts are known to hae pts are known to hae leels o IL leels o IL- -1, 6, & 1Nl 1, 6, & 1Nl- - . .
Role o these Role o these proinlamm proinlamm cytokines w, CNS LD cytokines w, CNS LD
& Role o & Role o Actos Actos,LDN to modulate leels o 1Nl ,LDN to modulate leels o 1Nl- - ,cytokines ,cytokines
Role of Inflammatory Mediators and
NO/ONOO Cycle in Illness
A Common Ltiologic Mechanism or ClS, MCS, lM, A Common Ltiologic Mechanism or ClS, MCS, lM,
P1SD and CLD : Dr Martin Pall, Proessor o P1SD and CLD : Dr Martin Pall, Proessor o
Biochemistry and Basic Medical Sciences, \ash State Biochemistry and Basic Medical Sciences, \ash State
Uni. Uni.
Aboe illnesses share many Aboe illnesses share many sx sx in common in common
Illnesses can be initiated by a ariety o actors ,iral, Illnesses can be initiated by a ariety o actors ,iral,
bacterial, physical or bacterial, physical or emot emot trauma, exposure to trauma, exposure to VOS VOS` `s s , ,
pesticides pesticides. ., ,
1hese dierse stressors can all 1hese dierse stressors can all NO, and several NO, and several
can can NMDA receptor activity & NMDA receptor activity & NO & its NO & its
oxidant product oxidant product peroxynitrite peroxynitrite
NO NO peroxynitrite peroxynitrite oxidatie stress oxidatie stress stimulates Nl stimulates Nl- -
B B production o production o iNOS iNOS ,nitric oxide ,nitric oxide synthetase synthetase, , NO in NO in
a icious cycle a icious cycle
Nl Nl- - B B IL IL- -1, IL 1, IL- -6, IL 6, IL- -8, 1Nl 8, 1Nl- - , IlN , IlN which may which may
contribute to symptoms and signs o these aried illnesses contribute to symptoms and signs o these aried illnesses
1esting or immune 1esting or immune dys, dys,,: Autoimmune panel ,ANA, Rl, LSR, ,: Autoimmune panel ,ANA, Rl, LSR,
ss ss - -ds ds DNA, DNA, Sjogrens Sjogrens AB AB` `s,, Immunoglobulin leels and s,, Immunoglobulin leels and
subclasses, lLA classes.. subclasses, lLA classes..
Classical therapy Classical therapy: immune modulators , : immune modulators ,Plaquenil Plaquenil, , DMARD DMARD` `s s,, ,,
drugs drugs w,antiinlamm w,antiinlamm eect , eect ,macrolides macrolides, , tetracyclines tetracyclines,, IVIG or ,, IVIG or
decreased decreased immunoglob immunoglob` `s s
CAM 1herapy: CAM 1herapy: ocus on down ocus on down- -regulation o NO,ONOO cycle regulation o NO,ONOO cycle
biochemistry with subsequent biochemistry with subsequent o inlammatory markers: o inlammatory markers:
Antioxidants, CoQ10, B Antioxidants, CoQ10, B it it` `s s, , - -lipoic lipoic acid, acid, Mag Mag--, Zn--, --, Zn--,
omega 3 lA omega 3 lA` `s, glutathione precursors, s, glutathione precursors,. .
Cytokines in JH
Cytokines in JH
rxns
rxns

Jarish
Jarish
-
-
lerxheimer,llare
lerxheimer,llare
protocols:
protocols:
-
-
Alkalize: lemons,limes, Alka
Alkalize: lemons,limes, Alka
-
-
Seltzer gold 4x per
Seltzer gold 4x per
day ,or Na
day ,or Na
bicarb
bicarb
, x 1
, x 1
-
-
2 days and increase luids
2 days and increase luids
-
-
Burbur
Burbur
or Parsley 10 drops q 10 min x 1
or Parsley 10 drops q 10 min x 1
-
-
2 hours
2 hours
-
-
LDN: start 2mg lS, work up to 4.5 mg lS
LDN: start 2mg lS, work up to 4.5 mg lS
w,Pekana
w,Pekana
drainage remedies 15 drops each
drainage remedies 15 drops each
3x,day
3x,day
-
-
Glutathione: IV 2g, oral, PR, dermal
Glutathione: IV 2g, oral, PR, dermal
IV: 1oxicity and Chronic Lyme
IV: 1oxicity and Chronic Lyme
Disease
Disease

Lnironmental toxins: Multiple Chemical
Lnironmental toxins: Multiple Chemical
Sensitiity ,MCS,, Lnironmental Illness ,L.I.,
Sensitiity ,MCS,, Lnironmental Illness ,L.I.,
due to exposure to a multitude o
due to exposure to a multitude o
chem
chem
`
`
s
s
in the
in the
enironment ,PCB
enironment ,PCB
`
`
s, dioxins, plastics, heay
s, dioxins, plastics, heay
metals, 1CL,
metals, 1CL,
VOS
VOS
`
`
s
s
.., \e will ocus on 3 major
.., \e will ocus on 3 major
categories:
categories:

1,leay Metals
1,leay Metals

2,Mold
2,Mold

3,Biotoxins 2
3,Biotoxins 2
to Lyme and associated co

to Lyme and associated co
-
-
inections, Lxternal toxin exposure
inections, Lxternal toxin exposure
Magnitude of Lxposure to 1oxins
Magnitude of Lxposure to 1oxins
1. 1. Pesticides Pesticides: LPA oice o Preention, Pesticides, & : LPA oice o Preention, Pesticides, &
1oxic substances 1oxic substances
1999 4 billion lbs. o pesticides produced 1999 4 billion lbs. o pesticides produced
2. 2. LPA LPA: 1982 National Adipose 1issue Surey : 1982 National Adipose 1issue Surey
100 o Americans: benzene, 100 o Americans: benzene, xylene xylene, toluene, , toluene,
styrene, dioxin, PCBs styrene, dioxin, PCBs
- - 1hese are some o the most potent cancer causing chemicals 1hese are some o the most potent cancer causing chemicals
known to mankind known to mankind
3. 3. CDC CDC: 2005, 6.5 million dollar study. Discoered 116 : 2005, 6.5 million dollar study. Discoered 116
dierent toxins in oer 50 patients studied ,13 dierent toxins in oer 50 patients studied ,13
heay metals, 14 combustion byproducts, 10 heay metals, 14 combustion byproducts, 10
pesticides pesticides
1oxicity Associated Symptoms & Conditions
1oxicity Associated Symptoms & Conditions
leadaches leadaches
Mineral imbalances , Mineral imbalances ,zn zn & ca, & ca,
Kidney dysunction Kidney dysunction
lertility problems lertility problems
Abnormal pregnancy Abnormal pregnancy
outcome outcome
Immune system depression Immune system depression
Multiple chemical sensitiities Multiple chemical sensitiities
libromyalgia libromyalgia
Recurrent yeast inections Recurrent yeast inections
1innitus 1innitus
Contact dermatitis Contact dermatitis
Learning disorders Learning disorders
Cancer Cancer
Panic attacks Panic attacks
Memory loss Memory loss
Parkinson Parkinson` `s disease s disease
Broad mood swings Broad mood swings
latigue latigue
Chronic atigue syndrome Chronic atigue syndrome
Muscle weakness Muscle weakness
Unusual response to meds or Unusual response to meds or
supplements supplements
Increasing sensitiity to Increasing sensitiity to
exogenous exposures: odors, exogenous exposures: odors,
medications, etc. medications, etc.
\orsening o symptoms ater \orsening o symptoms ater
anesthesia or pregnancy anesthesia or pregnancy
OVLRLAPPING SX OI HLAVY ML1ALS AND 1BD OVLRLAPPING SX OI HLAVY ML1ALS AND 1BD' 'S S
Suscept Suscept to infection to infection
Wt loss Wt loss
Psych sx Psych sx
Auditory sx Auditory sx
Visual sx Visual sx
Urinary sx Urinary sx
Abd sx Abd sx

Ataxia / Ataxia /
Incoordination Incoordination
Cognitive d/f Cognitive d/f
Paresthesias Paresthesias
Joint pain Joint pain
IMS sx IMS sx
Iatigue Iatigue
LD/CO LD/CO- -INIX INIX HLAVY ML1AL HLAVY ML1AL SYMP1OMS SYMP1OMS
MLRCURY MLRCURY
- -CIS, IMS, joint pain CIS, IMS, joint pain
- -metallic taste, changes metallic taste, changes
in vision & hearing in vision & hearing
- -tremors, ataxia tremors, ataxia
- -cognitive dysfunction, cognitive dysfunction,
depression, irritability depression, irritability
- -renal and GI renal and GI
disturbances disturbances
- -weight loss weight loss
- -increased increased
susceptibility to susceptibility to
infections infections
- -peripheral neuropathy peripheral neuropathy
- -autoimmunity autoimmunity
Clinical Symptoms Clinical Symptoms
- -SH binding SH binding
- -Oxidative stress Oxidative stress
- -Penetrates nerves and binds Penetrates nerves and binds
to to cysteines cysteines on Ach on Ach
receptors resulting in receptors resulting in
neurologic dysfunction. neurologic dysfunction.
- -retrograde axonal transport retrograde axonal transport
- -Denervation Denervation of nerve fibers of nerve fibers
similar to the pathology of similar to the pathology of
MS, and Hg can leak into MS, and Hg can leak into
the BBB and reduce nerve the BBB and reduce nerve
conduction velocity and conduction velocity and
VLP VLP
- - Mining and Mining and
Chemical Chemical
Industries Industries
- - Iish/Shellfish Iish/Shellfish
- - Dental work and Dental work and
medical treatment medical treatment
( (thimerasol thimerasol) )
Biochemistry Biochemistry Sources Sources
LLAD LLAD
- -Iatigue Iatigue
- -Lncephalopathy with Lncephalopathy with
impaired impaired
concentration, short concentration, short- -
term memory deficits, term memory deficits,
insomnia, anxiety, insomnia, anxiety,
depression, irritability, depression, irritability,
decreased IQ decreased IQ
- -Llevated BP, chronic Llevated BP, chronic
renal failure, anemia renal failure, anemia
- - Abd colic, peripheral Abd colic, peripheral
nerve dysfunction, nerve dysfunction,
reproductive reproductive
dysfunction dysfunction
Clinical Symptoms Clinical Symptoms
- -SH binding SH binding
- -Alters calcium Alters calcium- -mediated mediated
cellular processes cellular processes
- -Reduces nerve conduction Reduces nerve conduction
velocity in peripheral nerves velocity in peripheral nerves
- -Interferes in the Interferes in the heme heme
biosynthetic pathway biosynthetic pathway
leading to anemia leading to anemia
- -Drinking water Drinking water
- -Dinnerware with Dinnerware with
lead glazing lead glazing
- -Paint products Paint products
- -Soil around older Soil around older
homes painted homes painted
with lead based with lead based
paints are still paints are still
contaminated contaminated
with lead with lead
Biochemistry Biochemistry Sources Sources
DMSA
DMSA
leay metals accumulate x years leay metals accumulate x years leaes the leaes the
blood blood no longer measurable there no longer measurable there start start
compartmentalizing. compartmentalizing.
DMSA diuses into and eectiely competes with DMSA diuses into and eectiely competes with
tissue binding sites tissue binding sites releases metals rom releases metals rom
sequestered sites in tissues. sequestered sites in tissues.
Rationale or proocation test w, chelating agent Rationale or proocation test w, chelating agent
1oxic metals accumulate in non 1oxic metals accumulate in non- -exchange pools in exchange pools in
speciic tissues. speciic tissues.
DMSA disturbs the body stores o toxic metals & binds DMSA disturbs the body stores o toxic metals & binds
to them, so a certain quantity will redistribute into the to them, so a certain quantity will redistribute into the
blood as a stable complex blood as a stable complex eliminated in the urine eliminated in the urine
Do a 6 hour urine DMSA challenge ,30 mg,kg 1x dose, Do a 6 hour urine DMSA challenge ,30 mg,kg 1x dose,
Levels of heavy metals post provocation w/ 6 hour Levels of heavy metals post provocation w/ 6 hour
urine DMSA challenge: urine DMSA challenge: Hg, Hg, Pb Pb, , As, As, Cd Cd
Importance of Detoxifying Heavy
Importance of Detoxifying Heavy
Metals
Metals
15 15- -20 o CLD pts improe 20 o CLD pts improe sx sx o atigue, o atigue, myalgias myalgias, ,
arthralgias arthralgias, and , and neuro neuro- -cognitie cognitie sx sx with detoxiication with detoxiication
o heay metals o heay metals
Responsible or AI oerlap in certain CLD pts ,lg, Responsible or AI oerlap in certain CLD pts ,lg,
leay metal burden may lead to mineral deiciencies leay metal burden may lead to mineral deiciencies
, ,Mag Mag--, Zn, and has an eect on immune ,,, --, Zn, and has an eect on immune ,,,
oxidatie stress, and inlammatory cytokines oxidatie stress, and inlammatory cytokines
1esting 1esting: : 6 hr urine DMSA challenge to Doctors Data. 6 hr urine DMSA challenge to Doctors Data.
Use 30mg,kg 1x as a loading dose Use 30mg,kg 1x as a loading dose
1reatment 1reatment: : Chelation Chelation using DMSA 100 using DMSA 100- -200 mg Q3rd 200 mg Q3rd
night with night with Algas Algas ,10 drops, and Chlorella ,split cell, ,10 drops, and Chlorella ,split cell,
tab tab` `s, w, 600 mg NAC, Med Caps DPO ,B itamins, s, w, 600 mg NAC, Med Caps DPO ,B itamins,
NAC, NAC, - -- -lipoic lipoic acid..,, DMPS, LD1A acid..,, DMPS, LD1A
Replace minerals the next day ,M1V w, Ca, Replace minerals the next day ,M1V w, Ca, Mag Mag, Zn, , Zn,
IV: 1oxicity and Lyme Disease
IV: 1oxicity and Lyme Disease
Apart rom heay metal toxicities, the most common Apart rom heay metal toxicities, the most common
toxic exposures include external toxins ,PCB toxic exposures include external toxins ,PCB` `s, s,
Dioxins, Plastics and plasticizers, Pesticides, Dioxins, Plastics and plasticizers, Pesticides, VOS VOS` `s s.., ..,
and mold exposure and mold exposure
- -CDC 2003: 6.5 million > study w, 2500 patients: ound 116 CDC 2003: 6.5 million > study w, 2500 patients: ound 116
dierent pollutants ,13 heay metals, 14 combustion dierent pollutants ,13 heay metals, 14 combustion
byproducts, 10 pesticides, One o those toxins 1CL, was byproducts, 10 pesticides, One o those toxins 1CL, was
responsible or a leukemia outbreak in \oburn, MA, and responsible or a leukemia outbreak in \oburn, MA, and
requently causes learning disabilities, requently causes learning disabilities, paresthesias paresthesias... ...
1esting 1esting: : Accuchem Accuchem labs, 1exas, labs, 1exas, Stachybotris Stachybotris titers titers
Other toxins may result rom exposure to bacteria Other toxins may result rom exposure to bacteria
and iruses, and iruses, ie ie biological eects o these agents in our biological eects o these agents in our
bodies , Bb bodies , Bb tox tox 1, 1, Quinolinic Quinolinic Acid Acid. ., ,
Role of Lndogenous
Role of Lndogenous
Lxotoxins
Lxotoxins
Quinolinic Quinolinic Acid , Acid ,Quin Quin, is a , is a neurotoxic neurotoxic metabolite o metabolite o
the L the L- -tryptophan tryptophan- -kynurenine kynurenine pathway that actiates the pathway that actiates the
NMDA receptor class o excitatory AA receptors to NMDA receptor class o excitatory AA receptors to
produce produce excitotoxic excitotoxic lesions. Lyme lesions. Lyme dx dx pts hae been pts hae been
shown to hae shown to hae leels o leels o Quinolinic Quinolinic acid. Role in acid. Role in
CNS CNS dx dx Role or IV GSl & antioxidant therapies Role or IV GSl & antioxidant therapies
1, 1, - -Oxidatie stress as a mechanism or Oxidatie stress as a mechanism or quinolinic quinolinic acid acid- -induced induced
hippocampal hippocampal damage: protection by melatonin and damage: protection by melatonin and deprenyl deprenyl
\.M.l. Behan, et al. British \.M.l. Behan, et al. British Jnl Jnl Pharm Pharm ,1999, 128, 154 ,1999, 128, 154- -160 160
2, 2, - -Lnhanced neuronal damage by co Lnhanced neuronal damage by co- -administration o administration o quinolinic quinolinic acid acid
and ree radicals, and protection by adenosine A2A recepto and ree radicals, and protection by adenosine A2A receptor r
antagonists \.M.l Behan et al. British antagonists \.M.l Behan et al. British Jnl Jnl Pharm Pharm ,2002, 35, 1435 ,2002, 35, 1435- -1442 1442
3) 3) - -Neuroprotective Neuroprotective effects of the mGlu5R antagonist MPEP towards effects of the mGlu5R antagonist MPEP towards
quinolinic quinolinic acid acid- -induced induced striatal striatal toxicity: involvement of pre toxicity: involvement of pre- - and and
post post- -synaptic mechanisms and lack of direct NMDA blocking synaptic mechanisms and lack of direct NMDA blocking
activity. activity. Popoli Popoli et al. et al. Jnl Jnl of Neurochemistry 2004, 89, 1479 of Neurochemistry 2004, 89, 1479- -1489 1489
4) 4) - -Quinolinic Quinolinic Acid Is Extruded from the Brain by a Acid Is Extruded from the Brain by a Probenecid Probenecid- -
Sensitive Carrier System: A Quantitative Analysis. Morris Sensitive Carrier System: A Quantitative Analysis. Morrison et al, on et al, Jnl Jnl of of
Neurochemistry 1999, 72, 2135 Neurochemistry 1999, 72, 2135- -2144 2144
Glutathione
Glutathione
IV GSl has been shown to be eectie in a subset o IV GSl has been shown to be eectie in a subset o
resistant Lyme patients, implying a need to include a resistant Lyme patients, implying a need to include a
detoxiication regime in the treatment plan. detoxiication regime in the treatment plan.
Detox Detox protocols would include protocols would include Mag Mag--, NAC, GL\, --, NAC, GL\,
lipoic lipoic acid, DIM, acid, DIM, suloraphane suloraphane glucosinalate glucosinalate, diet w , diet w
prot prot, , cruci cruci eg eg` `s s
IV GSl also addresses heay metal burden, but it is IV GSl also addresses heay metal burden, but it is
unclear which unclear which chem chem` `s s,toxins are being remoed w, ,toxins are being remoed w,
treatment. Since GSl may hae an eect within min treatment. Since GSl may hae an eect within min` `s s
in select pts to improe CNS ,,, is there an eect on in select pts to improe CNS ,,, is there an eect on
remoing remoing inlamm inlamm cytokines & cytokines & Quinolinic Quinolinic acid acid
Intravenous Glutathione: A Novel Approach for Treating Resistant Symptoms in
Chronic Lyme Disease
Background:
Chronic Lyme Disease must be seen in the light of multiple tick borne diseases,
including HME, HGE, Babesiosis, Mycoplasma infections, and Bartonella henselae.
The mechanisms responsible for ongoing symptoms have been hypothesized to be
secondary to persistent Borrelial infection, occult and/or resistant co-infections,
autoimmune mechanisms, and/or other neurotoxins.
Among known toxins, heavy metals such as mercury and lead have been found in Lyme
disease patients with a small percentage of patients (10-15%) reporting improvement in
resistant symptoms (fatigue, joint aches, cognitive dysfunction) with removal of the
corresponding heavy metals (Horowitz, Abstract 16th International Lyme Conference,
June 2003).
A novel approach to remove toxins from the body involves Glutathione (GSH)
(Perlmutter, 2000). GSH is an endogenous peptide made in the liver, which plays an
important role in various metabolic functions including its role as an antioxidant and in
Phase II liver detoxification of various chemicals. A trial of GSH was therefore
undertaken to determine its role in patients with Lyme Disease with chronic resistant
symptoms.
Method:
118 patients with Lyme Disease were given IV GSH over a 5-10 minute period. 80
patients were given 1000mg of GSH and 38 patients were given 2000mg of GSH. The
GSH was stored in a refrigerator and protected from direct light until patient
administration. Patients symptoms scores before and after treatment with GSH (0-
100% self reported scale) were recorded after a 30-minute interval.
Results:
Among 80 patients given 1000mg GSH, 36% (29/80) had no clinical improvement (0%
improvement on self-reported scale), 40% (32/80) had a mild clinical improvement (1 to
10% improvement), 6% (5/80) had moderate clinical improvement (11 to 20%
improvement), and 18% (14/80) had marked clinical improvement (21 to 60%
improvement in clinical symptom scores). Mean improvement in symptoms after 30
minutes of 1000mg of GSH administration was 9%.
Among 37 patients given 2000mg of GSH, 27% (10/37) had no clinical improvement,
46% (17/37) had mild clinical improvement, 16% (6/37) had moderate clinical
improvement, and 11% (4/37) had marked clinical improvement. Mean improvement in
symptoms after 30 minutes of 2000mg of IV GSH was 9.5%.
Improvements from a single dose of IV GSH lasted from several hours to 2-3 days
before patients experienced a relapse in symptoms. There were no significant adverse
effects from GSH except for transient nausea & rare pressure like feelings and
paresthesias. One patient had a vagal event with needle insertion (before GSH
administration) and 2 patients experienced a flare up of Lyme symptoms after injection,
which subsequently resolved.
Intravenous Glutathione: A Novel Approach for Treating
Resistant Symptoms in Chronic Lyme Disease
Results: (contd)
There were also 8 chronic Lyme Disease patients who underwent
a 1-2 month GSH trial, with doses ranging from 400mg IV 3x/wk to
2000mg per day. These patients generally comprised a group of
difficult to treat non-responders. There were no adverse side
effects from longer-term use of GSH. Among that group, 1 patient
out of 8 had no clinical response, and the other 7 patients had
sustained positive clinical improvements ranging from 10% to
35%, with a mean improvement of 20%. These patients reported
consistent improvements in cognitive functioning, energy,
headaches, muscle strength, muscle pain, and joint pain.
Discussion:
Patients who experienced the most significant benefit from Glutathione
were often patients who had failed multiple antibiotic regimens in the past and
were considered treatment resistant. Several patients who had significant
neurologic dysfunction with dysarthria, incoordination, and muscle weakness
experienced a rapid and dramatic improvement in symptoms with a single dose
of IV GSH.
Metabolic functions of GSH include DNA synthesis and repair, protein
synthesis, prostaglandin synthesis, amino acid transport, enzyme activation,
prevention of oxidative cell damage, enhancement of immune system function,
and metabolism of toxins and carcinogens (Annals of Pharmacotherapy:
Glutathione in Health & Disease: pharmacotherapeutic issues:1995 Dec., Vol.
29, 1263-1273). Since patients reported improvement in fatigue, joint pain,
muscle pain, mood swings, headaches, balance, dizziness, speech problems,
and cognitive difficulties within 30 minutes of administration, GSH may be
acting to metabolize toxins in the short term, and may have an effect on
prostaglandins, interleukins, oxidative stress & immune modulation in the long
term. Alternatively, the rapid initial improvement in symptoms may be a
placebo response due to the novelty of trying a new treatment approach;
however, the sustained response among patients given longer term treatments
suggests that something other or in addition to a placebo response is in effect.
Upregulation of Phase II Metabolic Pathways of the Liver
Glutathione
Conjugation
Glutathione
NAC
Ellagic Acid
Watercress
Silymarin
Sulfation
Sodium Sulfate
MSM
Cysteine
Alpha Lipoic Acid
Glucuronidation
Preventium
Artichoke Leaf
Acetylation
Pantothenic Acid
Magnesium
Vitamin B6
Methylation
Folate
Vitamin B12
Vitamin B6
Amino Acid
Conjugation
Glycine
Prostaglandins
Leukotrienes
PetroleumDistilates
Estrogen
Testosterone
Thyroxine
Cortisol
Adrenaline
Melatonin
DHEA
Bile Acids PABA
Estrogen
Fat Soluble Vitamins
Steroid Hormones
Pesticides (DDT)
Histamine
Estrogen
Mercury
Lead
Cadmium
Dopamine
Epinephrine
Modulators of Phase I Metabolic Pathways of the Liver
Cytochrome P450
Ellagic Acid Green Tea Catechins Watercress glucosinolates Silymarin
Insure hydration
Optimize bowel health
(Probiotics, fiber, colon cleanses)
Detoxification
Principles
Antioxidant
Reserve
(alpha lipoic acid, diet)
Optimize
mitochondrial function
(NT factor, CoQ 10, NADH)
Minimize toxic
Exposure
(air & H2O purifiers, clean diet)
Assist &
Balance biotransformation
(NAC, Gly, B vits)
Detoxification/
Detoxification/
Chelation
Chelation
/Nutritional
/Nutritional
Supplementation
Supplementation
Detoxiication Detoxiication: Skin ,saunas,, Colon , : Skin ,saunas,, Colon ,probiotics probiotics, iber, , iber,
Questran Questran, cleanses,, Kidneys , , cleanses,, Kidneys , luids,, lier , luids,, lier , it it` `s s, min , min` `s, s,
herbs to herbs to phase I & II phase I & II detox detox pathways, pathways,
Chelation Chelation : 6 hr urine DMSA challenge, then using oral : 6 hr urine DMSA challenge, then using oral
,DMSA, DLPLN..,, rectal ,LD1A,, ,DMSA, DLPLN..,, rectal ,LD1A,, transdermal transdermal ,DMPS, ,DMPS,
GSl,, or IV ,DMPS, LD1A, to remoe heay metals, GSl,, or IV ,DMPS, LD1A, to remoe heay metals,
replacing minerals. A recent study at the lVlAC ound replacing minerals. A recent study at the lVlAC ound
that 100mg DMSA Q 3 that 100mg DMSA Q 3
rd rd
night x mo night x mo` `s to be sae & s to be sae &
eectie, w, ALA, chlorella, NAC, replacing eectie, w, ALA, chlorella, NAC, replacing it it,min ,min` `s s
Nutritional Supplementation Nutritional Supplementation : locus on using NAC, : locus on using NAC,
Glycine Glycine, DIM, , DIM, Suloraphane Suloraphane glucosinalate glucosinalate, Med Caps , Med Caps
DPO, DPO, - - lipoic lipoic acid, M1V w, min acid, M1V w, min` `s , s ,Mag Mag--, Zn-.., --, Zn-..,
Lect o 1oxins on an Indiidual: Notion o 1oxic load Lect o 1oxins on an Indiidual: Notion o 1oxic load, ,
indiidual susceptibility,genetics indiidual susceptibility,genetics
V: Allergies and CLD
V: Allergies and CLD
lood allergies are requently seen in the general population, lood allergies are requently seen in the general population,
especially to common allergens such as wheat, dairy, corn, nuts, especially to common allergens such as wheat, dairy, corn, nuts,
shellish, ood dyes and addities, etc. It may present as an shellish, ood dyes and addities, etc. It may present as an
immediate hypersensitiity reaction , immediate hypersensitiity reaction ,IgL IgL,, or delayed ,, or delayed
hypersensitiity reaction , hypersensitiity reaction ,IgG IgG, ,
Allergies are a common complaint o Allergies are a common complaint o indi indi` `s s with ClS & lM, and with ClS & lM, and
are requently seen in L.I. Syndrome are requently seen in L.I. Syndrome
1hey may be related to 1hey may be related to Candidiasis Candidiasis and a leaky gut, and should and a leaky gut, and should
prompt inestigation into these 2 diagnoses prompt inestigation into these 2 diagnoses
Common maniestations Common maniestations: : atigue, headaches, allergic rhinitis, atigue, headaches, allergic rhinitis,
eczema, asthma, irritability, concentration eczema, asthma, irritability, concentration prob prob` `s s
1esting: 1esting: local IGL ,Quest, expanded ood allergy proile,, or local IGL ,Quest, expanded ood allergy proile,, or IgG IgG
, ,Metametrix Metametrix 90 ood allergy panel, 90 ood allergy panel,
1reatment: 1reatment: Classical: Aoidance, rotation diets, Classical: Aoidance, rotation diets, Immuniz Immuniz` `s s
1reatment: 1reatment: CAM: plus treat underlying Candida or leaky gut i CAM: plus treat underlying Candida or leaky gut i
present, use enzyme therapy, NAL1, NM1 present, use enzyme therapy, NAL1, NM1. .. .
VI: Nutritional & Lnzyme
deficiencies
deficiencies
Digestie disorders which are common in ClS may Digestie disorders which are common in ClS may
stem rom an enzyme deiciency stem rom an enzyme deiciency
Lnzyme deiciencies Lnzyme deiciencies poor digestion o proteins, poor digestion o proteins,
carbohydrates, and ats carbohydrates, and ats deiciency o ital nutrients deiciency o ital nutrients
necessary or proper cellular unction necessary or proper cellular unction
Detoxiication reactions o enironmental chemicals Detoxiication reactions o enironmental chemicals
require an ongoing supply o essential itamins, require an ongoing supply o essential itamins,
minerals, AA minerals, AA` `s, atty acids and s, atty acids and phytonutrients phytonutrients to be to be
eectie. 1he higher the toxic load, the more likely eectie. 1he higher the toxic load, the more likely
nutritional deiciencies will be present in an indiidual nutritional deiciencies will be present in an indiidual
Lffect of Mineral Deficiencies on
Lffect of Mineral Deficiencies on
Biochemical (f)
Biochemical (f)
Mag Mag-- -- Nec Nec in in appx appx 300 300 detox detox enzymes in the body. enzymes in the body.
Deiciency results in muscle spasm, tremors, anxiety, Deiciency results in muscle spasm, tremors, anxiety, Raynauds Raynauds
phen phen, arrhythmias, , arrhythmias,
Cu- Cu- SOD ,ree radicals,, SOD ,ree radicals,, polyphenol polyphenol oxidase oxidase , ,detox detox chem chem` `s s,, ,,
tyrosinase tyrosinase & & dopa dopa oxidase oxidase ,neurotransmitters,, ,neurotransmitters,, Cytochrome Cytochrome C C
oxidase oxidase ,energy, ,energy,
Zn-- Zn-- Nec Nec in 90 enzymes ,alcohol in 90 enzymes ,alcohol dehydrogenase dehydrogenase, Phase I , Phase I
rxn rxn, conerts alcohols , conerts alcohols aldehydes aldehydes. I low, . I low, biochem biochem bottleneck, bottleneck,
with shit to chloral hydrate and toxic brain symptoms, with shit to chloral hydrate and toxic brain symptoms,
- -Older pts gen hae Older pts gen hae signi signi lower leel o plasma Zn, lower leel o plasma Zn, leels o leels o
inlammatory cytokines and IL 10, and inlammatory cytokines and IL 10, and plasma oxidatie stress. plasma oxidatie stress.
Compared to the placebo Compared to the placebo gp gp, Zn supplemented , Zn supplemented gp gp had had
incidence o inections, incidence o inections, 1Nl 1Nl- - , & , & plasma oxidatie stress plasma oxidatie stress
markers ,NIl unded study, markers ,NIl unded study,
Am J Am J Clin Clin Nutr Nutr 200, 85: 83 200, 85: 83- -844 844
deficiencies
deficiencies
1esting 1esting: serum minerals , : serum minerals ,Mag Mag--, Zn..,, RBC minerals --, Zn..,, RBC minerals
, ,Mag Mag--,, AA & lA analysis, ION test, --,, AA & lA analysis, ION test, Organix Organix test test
, ,Metametrix Metametrix labs, to test unctional biochemical labs, to test unctional biochemical
pathways pathways
Lipid peroxides, sulates, nitrates , Lipid peroxides, sulates, nitrates ,Metametrix Metametrix, to check , to check
ree radical exposure ,important in CNS disease, ree radical exposure ,important in CNS disease,
ALS ALS. .,, ,, detox detox pathways, NO pathway ,indirect, pathways, NO pathway ,indirect,
1reatment 1reatment: Replace : Replace it it` `s s, minerals, AA , minerals, AA` `s, s, LlA LlA` `s s, ,
enzymes ,plant or pancreatic w,amylase, lipase, enzymes ,plant or pancreatic w,amylase, lipase,
proteases, proteases,
CAM CAM: Role o enzymes between meals or iral : Role o enzymes between meals or iral in in` `s s, ,
inlammation inlammation
- -Morley, J.L. et al. Nutritional Modulation o Neural lunction. U Morley, J.L. et al. Nutritional Modulation o Neural lunction. UCLA lorum CLA lorum
in Medical Sciences 28 ,San Diego, CA: in Medical Sciences 28 ,San Diego, CA: Academica Academica Press, 1988, Press, 1988,
- -Jaeger, C.B, et al. Jaeger, C.B, et al. Polymer Lncapsulated Polymer Lncapsulated Dopaminergic Dopaminergic Cell Lines as Cell Lines as
Alternatie Neural Grats Alternatie Neural Grats` ` Progress in Brain Res 82 ,1990,, 41 Progress in Brain Res 82 ,1990,, 41- -6 6
VII: Mitochondrial Dysfunction
VII: Mitochondrial Dysfunction
Mitochondrial membrane components are especially Mitochondrial membrane components are especially
susceptible to ree radical damage, as they are exposed susceptible to ree radical damage, as they are exposed
to molecular 02 which is constantly utilized or A1P to molecular 02 which is constantly utilized or A1P
production, and hae high concentrations o molecules production, and hae high concentrations o molecules
that are easily oxidized ,unsaturated atty acids,. that are easily oxidized ,unsaturated atty acids,.
Certain nutrients are essential or proper Certain nutrients are essential or proper mitoch mitoch ,, and ,, and
energy production, energy production, ie ie CoQ10, NADl, L CoQ10, NADl, L- -carnitine carnitine, ,
essential phospholipids, essential phospholipids, - -keto keto glutarate glutarate
1esting 1esting: lipid peroxides, : lipid peroxides, Organix Organix test , test ,Metametrix Metametrix, may , may
proide indirect eidence through nutritional proide indirect eidence through nutritional
deiciencies, ree radical exposure deiciencies, ree radical exposure
1reatment 1reatment: N1 actors , : N1 actors ,gycosylated gycosylated phospholipids,, phospholipids,,
CoQ10, NADl, L CoQ10, NADl, L- -carnitine carnitine
- -Laboratory Laluations in Molecular Medicine: Nutrients, 1oxican Laboratory Laluations in Molecular Medicine: Nutrients, 1oxicants, and Cell ts, and Cell
Regulators. J. Alexander Regulators. J. Alexander Bralley Bralley, PlD. IAMM, Norcross, GA , PlD. IAMM, Norcross, GA
- -Seidman Seidman, M. Polyunsaturated PC in N1 actor improes mitochondrial , M. Polyunsaturated PC in N1 actor improes mitochondrial
unction. Anti Aging Med No 2001 unction. Anti Aging Med No 2001
VIII: Psychological Iactors In CLD
VIII: Psychological Iactors In CLD
Many patients with CLD hae oerlapping Many patients with CLD hae oerlapping
psychological psychological dys, dys,,, ,, ie ie history o depression, anxiety, history o depression, anxiety,
OCD, P1SD with abuse ,physical, emotional, sexual, OCD, P1SD with abuse ,physical, emotional, sexual,
Lyme and associated co Lyme and associated co- -inections will cause preious inections will cause preious
psychological patterns to intensiy, or cause new psychological patterns to intensiy, or cause new
patterns to emerge , patterns to emerge ,ie ie psychosis, manic psychosis, manic- -depressie depressie
disorder.., disorder..,
lealth care proiders should ask about preious psych lealth care proiders should ask about preious psych
hx hx, and reer or counseling,psychiatric help. , and reer or counseling,psychiatric help.
1reatment 1reatment: Medications , : Medications ,SSRI SSRI` `s s, , buproprion buproprion, , Remeron Remeron, ,
anxiolytics anxiolytics,,, Stress reduction ,yoga, meditation, ,,, Stress reduction ,yoga, meditation, 1aiChi 1aiChi, ,
CAM CAM: lerbs ,SJ\, Valerian, Kaa : lerbs ,SJ\, Valerian, Kaa Kaa Kaa L L- -theanine theanine,, ,,
Cognitie processing therapy ,P1SD,, Journey work Cognitie processing therapy ,P1SD,, Journey work
,Brandon Bays,, Ll1 ,Brandon Bays,, Ll1. .
IX: Lndocrine Abnormalities
IX: Lndocrine Abnormalities
lypothalamic lypothalamic- -pituitary axis may be aected pituitary axis may be aected check check
lSl, Ll, Gl and IGl1, 1Sl & AC1l leels, lSl, Ll, Gl and IGl1, 1Sl & AC1l leels,
DlLA, DlLA,Cortisol Cortisol, sex hormones , sex hormones
Impt Impt to test ull to test ull 1l1 1l1` `s s ,new range 1Sl 0.5 ,new range 1Sl 0.5- -2.5, 1 or 2.5, 1 or
less may be necessary or signiicant clinical less may be necessary or signiicant clinical
improement, with thyroid AB improement, with thyroid AB` `s,13, 14, r13, 13,r13 s,13, 14, r13, 13,r13
ratio. Consider 1Rl stimulation test~ Gold standard. ratio. Consider 1Rl stimulation test~ Gold standard.
A poorly unctioning thyroid conerts 14 to r13 ,can A poorly unctioning thyroid conerts 14 to r13 ,can
be w, stress, asting, illness, increased be w, stress, asting, illness, increased cortisol cortisol, & leads , & leads
to low 13 syndrome to low 13 syndrome
Normal Normal` ` ranges may not be applicable ranges may not be applicable
Xenoestrogens Xenoestrogens,toxins blocking receptor sites ,toxins blocking receptor sites
certain pts need to hae hormone leels at the higher certain pts need to hae hormone leels at the higher
range o range o normal normal` ` to hae clinical improement to hae clinical improement
Lndocrine Problems Among Lyme
Lndocrine Problems Among Lyme
Patients : Adrenal Iatigue
Patients : Adrenal Iatigue
Adrenal atigue Adrenal atigue: A spectrum disorder in between : A spectrum disorder in between
Addison Addison` `s and Cushing s and Cushing` `s disease s disease
Ltiology Ltiology: Any orm o chronic stress ,physical, : Any orm o chronic stress ,physical,
emotional, psychological, enironmental, inectious, in emotional, psychological, enironmental, inectious, in
combination, combination,
Symptoms Symptoms: atigue, non : atigue, non- -regeneratie sleep, salt craing, regeneratie sleep, salt craing,
hypoglycemia, hypoglycemia, libido, libido,
low BP, postural hypotension, depression,irritability, low BP, postural hypotension, depression,irritability,
memory,ocus, memory,ocus, time to recoer rom illness, injury, time to recoer rom illness, injury,
or trauma or trauma
Associated Diseases Associated Diseases: ClS, libromyalgia, alcoholism, : ClS, libromyalgia, alcoholism,
RA, Chronic allergies,asthma RA, Chronic allergies,asthma
Laboratory 1esting for Adrenal
Laboratory 1esting for Adrenal
Iatigue
Iatigue
Problems w, blood testing Problems w, blood testing: population used to : population used to
standardize the tests may hae included many people w, standardize the tests may hae included many people w,
some leel o adrenal atigue, & lab tests are deined & some leel o adrenal atigue, & lab tests are deined &
standardized based on statistical norms, not standardized based on statistical norms, not
physiologically optimal norms physiologically optimal norms
24 hr urinary 24 hr urinary cortisol cortisol test test i leels are in the bottom i leels are in the bottom
1,3 o 1,3 o Normal Normal` ` range, suspect range, suspect adrenal ,, adrenal ,,
Blood tests Blood tests: do not measure tissue leels : do not measure tissue leels
AC1l Challenge AC1l Challenge: - i : - i cortisol cortisol leels 2x leels 2x
DlLA, DlLA,Cortisol Cortisol saliary testing saliary testing: measures tissue leels, : measures tissue leels,
reliable marker. Labs: Aeron, reliable marker. Labs: Aeron, Metametrix Metametrix, , Genoa Genoa, ,
Diagnostek Diagnostek. .
Consider adrenal Consider adrenal suppl suppl` `s s ,B ,B it it` `s s, , Vit Vit C, C, rhodiola rhodiola, ,
licorice.., and low dose licorice.., and low dose Corte Corte or replacement i or replacement i leels leels
X: Sleep Disorders
X: Sleep Disorders
Impaired sleep correlates directly with impaired immune Impaired sleep correlates directly with impaired immune
unctioning unctioning
- -Sleep and the immune system. Sleep and the immune system. Int Int J J Immunopharmacol Immunopharmacol 1995,1:649 1995,1:649- -54 54
- -Sleep, Sleep, neuroimmune neuroimmune and and neuroendocrine neuroendocrine unctions in ibromyalgia and chronic atigue syndrome. Ad unctions in ibromyalgia and chronic atigue syndrome. Ad
Neuroimmunol Neuroimmunol 1995,5:39 1995,5:39- -56 56
- -Ad Management o sleep disorders in ibromyalgia. Rheum Ad Management o sleep disorders in ibromyalgia. Rheum Dis Dis Clin Clin North Am. 2002,28:53 North Am. 2002,28:53- -65 65
Sleep disorders are commonly associated with chronic inlammator Sleep disorders are commonly associated with chronic inlammatory y
diseases and chronic age,stress disorders, such as RA, lM, and diseases and chronic age,stress disorders, such as RA, lM, and
ClS. ClS.
- -Lorton D et al. Lorton D et al. Neuroimmunomodulation Neuroimmunomodulation. 2006,13,5 . 2006,13,5- -6,:35 6,:35- -4. 4. Lpub Lpub 200 Aug 6 200 Aug 6
- -M. M. laack laack, et al. J Pain, April 2004, Supplement 1, , et al. J Pain, April 2004, Supplement 1, Vol Vol 5, no 3 5, no 3
Chronic sleep restriction leads to eleations in IL Chronic sleep restriction leads to eleations in IL- -6 and pain 6 and pain
symptoms in healthy olunteers. symptoms in healthy olunteers.
- -M. M. laack laack, et al. J Pain, April 2004, Supplement 1, , et al. J Pain, April 2004, Supplement 1, Vol Vol 5, no 3 5, no 3
X: Sleep Disorders
X: Sleep Disorders
Causes: Obstructie Sleep apnea, Medications, Caeine, Causes: Obstructie Sleep apnea, Medications, Caeine,
Nocturia Nocturia, Depression,Anxiety, RLS.. , Depression,Anxiety, RLS..
Laluation: Sleep Study i unresponsie to standard Laluation: Sleep Study i unresponsie to standard
treatment regimens treatment regimens
1reatment : Actiating Agents in the AM, Sleep 1reatment : Actiating Agents in the AM, Sleep
promoting agents in the PM, especially those that promoting agents in the PM, especially those that
encourage stage 3,stage 4 RLM sleep , encourage stage 3,stage 4 RLM sleep ,Lyrica Lyrica, ,
1razadone 1razadone, , Gabitril Gabitril, , Seroquel Seroquel, , Xyrem Xyrem, ,
CAM: check neurotransmitter leels. Balance CAM: check neurotransmitter leels. Balance
neurotransmitters with 5 neurotransmitters with 5- -l1P, to increase GABA. l1P, to increase GABA.
Valerian root, L Valerian root, L- -theonine theonine also useul also useul
X: Sleep Disorders, Normalizing the
X: Sleep Disorders, Normalizing the
Amplitude of Circadian Rhythm
Amplitude of Circadian Rhythm
Actiating Agents ,AM, Actiating Agents ,AM,
Modaniil Modaniil , ,Proigil Proigil, ,
Stimulants Stimulants
Bupropion Bupropion , ,\ellbutrin \ellbutrin, ,
Noradrenergic Agents Noradrenergic Agents
SSRI SSRI` `s s
Actiating Actiating Atypicals Atypicals
1hyroid 1hyroid
Sleep Promoting ,PM, Sleep Promoting ,PM,
Pregabilin Pregabilin , ,Lyrica Lyrica, ,
1razadone 1razadone
Gabitril Gabitril
Seroquel Seroquel
Xyrem Xyrem
Non Non- -Benzos Benzos: : Ambien Ambien, ,
Lunesta Lunesta, Sonata , Sonata
Benzodiazepines Benzodiazepines
Mirtazipine Mirtazipine , ,Remeron Remeron, ,
Doxepin Doxepin, , Llail Llail
Melatonin, Melatonin, Ramelton Ramelton
XI: Autonomic Nervous System
Dysfunction
Dysfunction
1he ANS inoles elements o the CNS ,brain & spinal 1he ANS inoles elements o the CNS ,brain & spinal
cord,, and PNS, sensory motor branches, which is cord,, and PNS, sensory motor branches, which is
controlled by the hypothalamus. It regulates automatic controlled by the hypothalamus. It regulates automatic
body unctions such as breathing, heart rate, and body unctions such as breathing, heart rate, and
digestion. digestion.
1he Parasympathetic nerous system 1he Parasympathetic nerous system: : heart rate, and heart rate, and
BP, but increases gastric secretion and intestinal actiity BP, but increases gastric secretion and intestinal actiity
1he 1he Orthosympathetic Orthosympathetic nerous system nerous system is associated is associated
with arousal and stress, increases heart rate, BP and with arousal and stress, increases heart rate, BP and
muscle tension and regulates the contraction and muscle tension and regulates the contraction and
expansion o blood essels. expansion o blood essels.
Dysfunction
Dysfunction
Certain Chronic Lyme disease patients will complain o Certain Chronic Lyme disease patients will complain o
atigue, dizziness, & concentration problems despite atigue, dizziness, & concentration problems despite
classical therapies. BP will be low on exam , 90,60,, classical therapies. BP will be low on exam , 90,60,,
with associated tachycardia , 100 BPM, at rest. with associated tachycardia , 100 BPM, at rest.
1esting 1esting: 1ilt table test, blood pressure log with home : 1ilt table test, blood pressure log with home
readings readings
1reatment 1reatment: salt ,minimum 3 : salt ,minimum 3- -4 grams,day,, increase 4 grams,day,, increase
luids ,3 liters -,, consider luids ,3 liters -,, consider llorine llorine, , Corte Corte, and,or B , and,or B
blockers i inadequate response blockers i inadequate response
XII:
XII:
Gastointestinal
Gastointestinal
Disorders
Disorders

Celiac disease
Celiac disease: one o seeral : one o seeral malabsorption malabsorption
syndromes, due to gluten sensitiity. Clinical eatures syndromes, due to gluten sensitiity. Clinical eatures
include muscle wasting, small stature, weight loss, include muscle wasting, small stature, weight loss,
paresthesias paresthesias, muscle cramps, diarrhea. Look or , muscle cramps, diarrhea. Look or
laboratory eidence o laboratory eidence o malabsorption malabsorption: : albumin, albumin, chol chol, ,
Ca--, Ca--, Mag Mag--, B12, w, --, B12, w, macrocytic macrocytic anemia, anemia, le, K- le, K-

1esting
1esting: : Antigliadin Antigliadin AB, 11G, aoid gluten as AB, 11G, aoid gluten as
therapeutic trial therapeutic trial

Other GI
Other GI: : Crohns Crohns, UC, parasites, Candida,Leaky , UC, parasites, Candida,Leaky
gut, gut,dysbiosis dysbiosis, other , other malabsorption malabsorption syndromes syndromes
XIII: Llevated
XIII: Llevated
LI1
LI1
'
'
s
s
Patients requently present with Patients requently present with Ll1 Ll1` `s s at some at some point point
during treatment. during treatment.
Ltiologies: 1ick Ltiologies: 1ick- -borne disorders borne disorders - -
, ,Lhrlichiosis,Anaplasmosis Lhrlichiosis,Anaplasmosis, Q , Q- -leer, leer, Babesia Babesia..,, ..,,
antibiotics, L1Ol use, lepatitis, antibiotics, L1Ol use, lepatitis, lemochromatosis lemochromatosis, ,
\ilson \ilson` `s disease, Autoimmune, s disease, Autoimmune, hyperlipidemia hyperlipidemia, ,
chemical or drug exposure chemical or drug exposure
1esting: ANA, 1esting: ANA, lep lep B, C screen, le B, C screen, le- -1IBC, 1IBC,lerritin lerritin, ,
Ceruloplasmin Ceruloplasmin leels, leels, - -antitrypsin leels, tick antitrypsin leels, tick- -borne borne
panel, lipid leels.. panel, lipid leels..
1reatment: 1reat symptomatically i aboe etiologies 1reatment: 1reat symptomatically i aboe etiologies
ruled out. CAM: Milk thistle , ruled out. CAM: Milk thistle ,silymarin silymarin,, ,, lepa lepa 42 42
,1CM,, NAC, alpha ,1CM,, NAC, alpha lipoic lipoic acid.. acid..
XIV: Drug Use/ Addiction
XIV: Drug Use/ Addiction
XV:
XV:
Deconditioning
Deconditioning
Some CLD patients present with seere pain, and may Some CLD patients present with seere pain, and may
be on chronic be on chronic NSAID NSAID` `s s & high dose narcotics to & high dose narcotics to
control pain. control pain.
Narcotics may interere with deep, regeneratie sleep, Narcotics may interere with deep, regeneratie sleep,
and rebound pain and headaches may result which and rebound pain and headaches may result which
becomes part o a chronic symptom complex which is becomes part o a chronic symptom complex which is
diicult to treat. Consider a pain management specialist diicult to treat. Consider a pain management specialist
or resistant pain and or resistant pain and detox detox program i appropriate. program i appropriate.
Patients need to be placed on a regular exercise Patients need to be placed on a regular exercise
program once their physical condition permits. Start program once their physical condition permits. Start
slow and reer to P1,O1 i oerlapping muscle slow and reer to P1,O1 i oerlapping muscle
weakness and ine motor coordination are aected. weakness and ine motor coordination are aected.
Role of Integrative 1herapies in CLD
Role of Integrative 1herapies in CLD
lVlAC has seen oer 11,000 CLD pts oer the last 20 lVlAC has seen oer 11,000 CLD pts oer the last 20
years. Antibiotics are useul in treating the underlying years. Antibiotics are useul in treating the underlying
inections, but do not clinically appear to completely inections, but do not clinically appear to completely
eradicate the inections as the ast majority o patients eradicate the inections as the ast majority o patients
relapse upon discontinuation o antibiotics. 1hereore relapse upon discontinuation o antibiotics. 1hereore
CAM therapies hae been inestigated as an alternatie CAM therapies hae been inestigated as an alternatie
to antibiotics. to antibiotics.
Success in treating patients requires addressing the 3 Success in treating patients requires addressing the 3 I I` `s s: :
Inection, Immunity, and Inlammation while Inection, Immunity, and Inlammation while
inestigating other oerlapping etiologies responsible inestigating other oerlapping etiologies responsible
or ongoing or ongoing sx sx ,hormones, heay metals, neurotoxins, ,hormones, heay metals, neurotoxins,
iruses, parasitic inections, leaky gut, ood allergies, iruses, parasitic inections, leaky gut, ood allergies,
autoimmunity autoimmunity. .., .,
Herbal/CAM therapies used for
Herbal/CAM therapies used for

Buhner protocol ,
Buhner protocol ,
Samento
Samento
,
,
Andrographis
Andrographis
,
,
Japanese
Japanese
knotwood
knotwood
..,
..,

Schart
Schart
protocol ,
protocol ,
Dilucan
Dilucan
, Pen,
, Pen,

Zhang protocol ,
Zhang protocol ,
1CM
1CM
Coptis
Coptis
, ll, Circ P,
, ll, Circ P,

lomeopathic protocols ,
lomeopathic protocols ,
Ledum
Ledum
, syphilitic and
, syphilitic and
malarial
malarial
nosodes
nosodes
,
,

Salt &
Salt &
Vit
Vit
C protocol
C protocol

Rie machines
Rie machines
-
-
None o these hae been scientiically alidated
None o these hae been scientiically alidated
by large controlled studies
by large controlled studies
Cowden Protocol Results
Cowden Protocol Results
lull Cowden protocol, no AB lull Cowden protocol, no AB` `s : N~50 s : N~50
0 0 had had improement improement in in sx sx ,scale ,scale - -3 to -3,, median at 2 ,moderate 3 to -3,, median at 2 ,moderate
improement, w, 6,50 ,12, w, mild improement, 14,50 ,28, w, improement, w, 6,50 ,12, w, mild improement, 14,50 ,28, w,
moderate improement, and 15,50 ,30, w, signiicant improement moderate improement, and 15,50 ,30, w, signiicant improement. 1here . 1here
was also a was also a 35 35 oerall improement ,scale 0 oerall improement ,scale 0- -100, 100,
Limited Cowden protocol, no AB Limited Cowden protocol, no AB` `s : N~ 32 s : N~ 32
2 2 had had improement improement in in sx sx ,scale ,scale - -3 to -3,, median at 2 ,moderate 3 to -3,, median at 2 ,moderate
improement, w 6,32 ,19, w, mild improement, 11,32 ,34, w, improement, w 6,32 ,19, w, mild improement, 11,32 ,34, w,
moderate improement, and ,32 ,22, w, signiicant improement. moderate improement, and ,32 ,22, w, signiicant improement. 1here 1here
was also a was also a 13. 13. oerall improement ,scale 0 oerall improement ,scale 0- -100, 100,
lull Cowden protocol, w, AB lull Cowden protocol, w, AB` `s : N~13 s : N~13
had had improement improement in in sx sx ,scale ,scale - -3 to -3,, median at 1 ,mild 3 to -3,, median at 1 ,mild
improement, w, 8,13 ,62, w, mild improement,1,13 ,8, w, mode improement, w, 8,13 ,62, w, mild improement,1,13 ,8, w, moderate rate
improement, and 2,13 ,15, w, improement, and 2,13 ,15, w, signi signi improement. 1here was also a improement. 1here was also a
12. 12. oerall improement in oerall improement in sx sx ,scale 0 ,scale 0- -100, 100,
Limited Cowden protocol, w, AB Limited Cowden protocol, w, AB` `s : N~3 s : N~3
66 66 had had improement improement in in sx sx ,38 mild improement, 28 moderate to ,38 mild improement, 28 moderate to
signi signi improement,, median at 1 ,mild improement, w, improement,, median at 1 ,mild improement, w, 1.5 1.5 oerall oerall
improement ,scale 0 improement ,scale 0- -100, 100,
Putting It 1ogether: Integrating
Putting It 1ogether: Integrating
Classical and CAM therapies
Classical and CAM therapies
lerbs can be added at any time during an antibiotic lerbs can be added at any time during an antibiotic
protocol to address inlammation and eleated protocol to address inlammation and eleated
cytokines , cytokines ,andrographis andrographis, , polygonum,reseratrol polygonum,reseratrol, ,
smilax, smilax, stephania stephania, , samento samento. ., and to , and to the number o the number o
antibiotics used, especially i there is GI intolerance antibiotics used, especially i there is GI intolerance
Once a patient has achieed a signiicant leel o Once a patient has achieed a signiicant leel o
improement, consider rotation onto an herbal improement, consider rotation onto an herbal
protocol, and maintain or at least 1 year ,relapses were protocol, and maintain or at least 1 year ,relapses were
seen with the Cowden protocol 6 months,. seen with the Cowden protocol 6 months,.
Controlled clinical trials need to be done to ealuate the Controlled clinical trials need to be done to ealuate the
role o dierent herbal medicines in Chronic Lyme role o dierent herbal medicines in Chronic Lyme
Disease. It is not known at this time which combination Disease. It is not known at this time which combination
o herbs in dierent clinical circumstances may yield o herbs in dierent clinical circumstances may yield
the saest and most eicacious results. the saest and most eicacious results.
Putting It 1ogether: Integrating the JS
Putting It 1ogether: Integrating the JS
Differential Diagnoses into a Comprehensive
Differential Diagnoses into a Comprehensive
1reatment Plan
1reatment Plan
Chronic Lyme Disease is a symptom complex o Chronic Lyme Disease is a symptom complex o
borreliosis borreliosis and multiple co and multiple co- -inections with associated inections with associated
inlammation and immune dysunction. 1reat the 3 inlammation and immune dysunction. 1reat the 3
I I` `s s` ` simultaneously simultaneously
1reating all 3 orms o Bb, co 1reating all 3 orms o Bb, co- -inections, hormonal inections, hormonal
abN abN` `s s, heay metals and neurotoxins, sleep , heay metals and neurotoxins, sleep d,o d,o, ,
psychiatric issues, and nutritional deiciencies are the psychiatric issues, and nutritional deiciencies are the
most commonly ound most commonly ound abN abN` `s s at the lVlAC that hae at the lVlAC that hae
the greatest impact on regaining health the greatest impact on regaining health
Laluate all 15 dierential diagnostic categories and Laluate all 15 dierential diagnostic categories and
prioritize those that most need to be addressed early on prioritize those that most need to be addressed early on
in the illness in the illness
Putting It 1ogether: Chronic Infections and
Putting It 1ogether: Chronic Infections and
Neurobiological Lffects
Neurobiological Lffects
1hese agents create inlammation through arious 1hese agents create inlammation through arious
pathways ,IL pathways ,IL- -1, IL 1, IL- -6, 1Nl 6, 1Nl- - , NO and its metabolites, , NO and its metabolites,
which creates ree radicals and oxidatie stress which which creates ree radicals and oxidatie stress which
damages cell membranes, mitochondria, and nere cells damages cell membranes, mitochondria, and nere cells
Some inectious agents produce neurotoxins Some inectious agents produce neurotoxins
, ,Quinolinic Quinolinic Acid.., which aect nere cells Acid.., which aect nere cells
Autoimmunity may also result rom antibodies cross Autoimmunity may also result rom antibodies cross
reacting with our own tissue antigens reacting with our own tissue antigens
Mitigating these eects requires treating the 3 Mitigating these eects requires treating the 3 I I` `s s
,inection, immune issues, inlammation, while ,inection, immune issues, inlammation, while
supporting supporting detox detox pathways and eliminating pathways and eliminating
enironmental triggers ,heay metals, which enironmental triggers ,heay metals, which
inlammation as well as addressing inlammation as well as addressing ALL ALL issues ound issues ound
during the ealuation o 15 dierential diagnoses during the ealuation o 15 dierential diagnoses
Wisdom is the marriage of knowledge
and experience bound by compassion.

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Classical and Integrative Medical

Classical and Integrative Medical

Virtually all human diseases result

to Lyme and associated co

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