Lyme Disease
An Integrative Approach
Robert LaCava, MD
Constantine A. Kotsanis, MD
1
References
 www.cdc.gov
 The
Great Imposter
 ILADS
 Emedicine.com
 Uptodate.com
The Discovery of Insulin
(1920)
A Canadian Medical Miracle
of the 20th Century
 Frederick Grant Banting, MD (1891 – 1941)
 Charles Herbert Best, MD (1899-1978)
 John James Richards Macleod, MD (1876-
1935)
 James Bertram Collip, MD (1892-1965)
3
History of Insulin
Potentiation Therapy (IPT)
 Donato Perez Garcia, Sr., M.D. (1896 – 1971) a.k.a.
“Donato 1” (the inventor)
Surgeon Lieutenant in the Mexican Army
 Donato Perez Garcia Bellon, M.D. (1930 – 2000) a.k.a.
“Donato 2”
 Donato Perez Garcia, Jr., M.D. a.k.a. “Donato 3”
 Steven G. Ayre, M.D. (Introduced IPT to USA in 1970s)
4
Insulin Potentiation
Therapy (IPT)
 IPT is a pharmaceutical-based protocol using
insulin as a biologic response modifier of the
endogenous mechanisms of any disease.
 In IPT, insulin is used to selectively target
diseased cells with lowered doses of
pharmaceuticals, enhancing drug effects
on diseased cells and, at the same time,
effectively reducing dose-related
pharmaceutical side effects on host normal
tissues.
5
Insulin
A peptide hormone, produced by beta cells of
the pancreas and regulates carbohydrate and
fat metabolism
 Human insulin is composed of 51 aa
 Stored in the body as a hexamer
 The active form is a monomer
6
Insulin-Like Growth Factor 1
(IGF-1)








Also known as somatomedin C
A hormone similar in molecular structure as insulin
Important in childhood growth
Has anabolic effect in adults
Consists of 70 aa
Primarily produced by the liver
Production is stimulated by GH
One of the most potent activators of AKT signaling
pathway
 Potent inhibitor of programmed cell death
7
Some “New” Terminology…
Modes of Cellular Secretion
Endocrine
Paracrine
Exocrine
Autocrine
8
The Mechanisms of Disease
The combination of insulin and
IGF-I operates autonomously at
the cellular level within diseased
cells, and this operation is free
from any higher level of
integrated control…
(Cont’d)…
9
The Mechanisms of Disease
The two work together in an
autocrine and/or paracrine
manner and in a complementary
fashion, with IGF-I being the major
anabolic hormone responsible for
mediating messages about
growth of the disease, while
insulin regulates and provides the
fuel for these processes.
Zapf J., Froesch E.R. Insulin-like growth factors/somatomedins: structure, secretion,
biological actions and physiological role. Hormone Res 24:121-130, 1986.
10
How could this be?
How does
it work?
11
Insulin receptors are widely
distributed in mammalian
organisms with their being
from 100 to 100,000 receptors
per cell in different tissues.
Rarely are there any cells
having no receptors at all.
Rosen OM. After insulin binds. Science 273:1452-1457, 1987
12
Supraphysiologic
concentrations of insulin
can replace the IGF-I
requirement in defined
media through crossreaction with the IGF-I
receptor.
Goustin et al. Growth factors and cancer. Cancer Res 46:1015-1029,
1986.
13
Schema of IPT Mechanisms
Exogenous Insulin
X6
Insulin
Receptors
Low-Dose
Antimicrobials
IGF
Receptors
X
10
METABOLIC
EFFECTS
MEMBRANE
EFFECTS
- Altered Cell
−Increased
Membrane
Sensitivity to
Permeability
- Increased
Intracellular
Dose Intensity
Synergy
Antimicrobials
−Increased
drug potency
Ligand effect is a function of receptor concentration
14
Problem Areas in Full Dose
Antimicrobial Therapy
1) An adequate intracellular dose intensity
requirs the systemic administratoin of high
doses of drugs
2) Lack of antimicrobial specificity for drugs
3) Drug resistance
4) 1) + 2) + 3) = Widespread dose-related drug
side effects
15
What would be the Elements of an
Ideal Solution to this Antimicrobial
Dilemma?
1) To develop a mechanism that bypasses
microbe drug resistance.
2) To deliver lowered doses of drug more
specifically into this diseased cell population.
3) To maintain and /or enhance pharmaceutical
cell-killing effectiveness in any disease.
4) To reduce or avoid drug side effects in
normal cells.
16
Antimicrobial Therapy
I - Membrane Effect
II - Metabolic Effect
17
IPT & Antimicrobial Therapy
I - Membrane Effect
- Increased cell membrane permeability
- Increased intracellular dose intensity
- Lowered total dose of drugs
- Reduced dose-related side effects
- Shorten treatment cycle intervals
18
Mechanisms of Membrane Effects
1) Insulin activation of delta-9 desaturase
Stearic acid
- saturated -
Tristearin
m.p. 68 deg. C
At 37 deg. C
Oleic acid
- monounsaturated -
Triolein
m.p. 5 deg. C
Membrane fluidity/permeability
19
Mechanisms of Membrane Effects
(cont’d)
2) Drug adsorption onto glucose
molecules with transmembrane
transport then occurring via the
insulin-activated glucose transport
protein
3) Adsorption of drug molecules onto
insulin with the resulting chimeric
drug-insulin complex being
internalized into the cell by a
process of receptor-mediated
endocytosis
20
IPT & Antimicrobial Therapy
II - Metabolic Effect
- Increased sensitivity to antimicrobial drugs
- Drugs become more potent
- Microbial drug resistance is eliminated or
greatly reduced
21
Schema of IPT Mechanisms
Exogenous Insulin
X6
Insulin
Receptors
Low-Dose
Antimicrobials
IGF
Receptors
X
10
METABOLIC
EFFECTS
MEMBRANE
EFFECTS
- Altered Cell
−Increased
Membrane
Sensitivity to
Permeability
Antimicrobials
- Increased
Intracellular
Dose Intensity
Synergy
−Reduction or .
elimination of
microbial drug
resistance
Ligand effect is a function of receptor concentration
22
IPT & Drug Therapy
 “Smart Bomb” effect: Excess of insulinsensitive receptors on human diseased
cells causes predominance of insulin effect
in diseased cells, sparing normal host
tissues = INCREASED SAFETY
 Synergy of insulin’s membrane and
metabolic effects enhances antimicrobial
drug action in diseased cells = INCREASED
EFFICACY
23
Insulin Potentiation
Therapy
A Renaissance in
Chronic Disease States
24
Lyme Disease
An Integrative Approach
Robert LaCava, MD
Lecture Goals
•
•
Present a broader concept of IPT for
Lyme Disease and Mold Illness
Present integrative approaches to treat
Lyme Disease
Thanks to
 Donato
Perez Garcia, M.D.
 Steven G. Ayre, M.D.
 Joe Burrascano, M.D.
 Sean Devlin, D.O.
 Constantine A. Kotsanis, M.D.
 ILADS General Information
Basic Facts
“Nature’s Dirty Needle”
Ixodes pacificus
(Western Black Legged
Tick)
So tiny it can be
missed.
Spirochetes are long
and slender gram
negative bacteria that
are tightly coiled
looking like telephone
cords
Only 16% recall a tick
bite. Painless.
• A spirochete that causes Lyme disease. Inappropriate name for this
disorder – which is more exactly a type of multiple microbial
inflammatory disorder (MMID) involving several different infection
agents including Borrelia burgdorferi, babesios, bordetellosis, HHV-6,
parasites, ehrlichiosis, etc.
• Lyme disease was first recognized in U.S. and published in the
N.E.J.M. in 1975 by Dr. Allan Steere following a mysterious outbreak
of possible juvenile rheumatoid arthritis, near the community of Lyme,
Connecticut.
Facts & Statistics
•
Fastest growing vector-borne infectious disease in the USA
•
•
CDC estimates are over 200,000 new cases per year!
In the USA, rate of new cases exceeds that of HIV/AIDS
Anyone can get it – affects all ages, both genders, and even
our pets
• Present worldwide.
•
•
•
Lyme has been reported in all 50 states
Ticks can survive down to 17 degrees below zero! (may still
get tick bites in wintertime)
• There are more new strains of Borrelia identified
• In many areas, lawns have higher tick concentrations than the
surrounding woods
Three Phases of Lyme Disease
•
•
•
Early localized
Early disseminated disease
Chronic Lyme disease – late
•
ill with Lyme for one or more years
Why The Concern?
Illness Can Vary From Mild To Severe
•
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Early Lyme, if promptly recognized and appropriately treated,
can be cured
Untreated Lyme may progress, causing a very severe illness
and disability
Can be latent for months to years, and later result in
catastrophic, permanent damage
Deaths have been reported
Most symptoms are non-specific
Mild symptoms often are dismissed
The Great Imitator
•
Osteoarthritis, Rheumatoid arthritis, 1 degree & 2 degree A-V block,
Epilepsy, MS, ACS, Atrial fibrillation, Atrial flutter, Dementia, Meningitis,
Wasting Syndrome, Cancers, Auto-immune syndrome, Parkinson’s
disease, Depression, Adrenal fatigue, Thyroid disorders, Personality
disorders
Why The Concern? -
continued
Illness Can Vary From Mild To Severe
•
More medical errors from incorrect diagnosis and unnecessary or
dangerous treatments
•
•
Fibromyalgia, MS/CFS, depression, ALS (Lou Gehrig’s disease),
malingering, Munchausen’s syndrome
•
Often, patients see literally dozens of doctors and undergo an
encyclopedia of tests, Lyme is missed, and they still have no
diagnosis; interpretation of possible negative testing is of great
concern
Even negative testing needs to be interpreted.
When medical doctors cannot find a cause for the complaints, they
refer patients to a psychiatrist (blame the patient for his/her illness!)
Can be transmitted from mother to child; trans-placentally
Transmitted as a blood borne pathogen
•
Probably sexually transmitted according to UK doctors.
•
•
•
Diagnosing Lyme – the
Symptoms
A difficult task
•
•
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•
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Headaches, photophobia, stiff neck
Fatigue, intolerance of exercise
Aches in and around joints
Numbness, tingles, sense of vibration
Poor coordination, imbalance, light-headed, need to sit or lie
down, especially in afternoon
Forgetful, confused, speech errors, ADD-like
Sleep disturbance
Intolerance of stress, alcohol, sleep deprivation (any of these
will make all symptoms worse)
Subtle onset of nonspecific “viral-like” symptoms often obscure
the diagnosis
The Rash
• Erythema migrans with central clearing and
necrotic center
• Typical “Bullseye” rash occurs in only 1/3 to
1/2 cases
• Expands over time, painless, raised, may
be warm RINGWORM
• Scaly center
• Reference. Looks like a SPIDER BITE
Blood Testing
•
LYME (Borrelia burgdorferi)
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•
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CD57 (Natural Killer Cells)
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Serologic tests (ELISA, Western Blot)
PCR – also poorly sensitive - <30%
Low counts seen in Chronic Lyme when the infection has been
active > 1 year
Can be a screening test
Predicts a relapse if low when antibiotics end
Even a spinal tap serology will miss over 90% of cases!
Blood test may miss up to 1/2 of cases!!!
CO-INFECTIONS
Situation is worse – pick up 30% at best!!!
Conclusion: LYME IS A CLINICAL DIAGNOSIS
Serologic Testing
•
A two-tiered strategy recommends
•
•
•
ELISA testing usually derives from the whole organism. B.
burgdorferi antigen are similar to others. Therefore crossreaction is not uncommon.
•
•
ELISA – IFA may substitute
Western Blot
I find ELISA test of very little value and tend to go immediately to
Western Blot testing or immunblot.
Western Blot are antigen specific and can detect either lgM or
lgG antibodies
• PCR (polymerase chain reaction) tests for the DNA of the
Lyme disease spirochete
• Western Blot, ELISA, PCR can all be profound on either
blood test or lumbar puncture
Selective Approaches to
Lyme Disease Testing
•
•
•
•
•
DOT – Blot studies
Epitope studies
Selective studies of 31 band, lgC and lgM equivocal
colorimentiuric variants
New lab – selective culture – of Joe Barrascano –
Philadelphia, Advanced Laboratories IGC (10 day turn
around)
VISEC6, ELISA CCG
•
•
Comparable sensitivity to the lg ELISA with improved specificity
Point System for making a clinical diagnosis by Joe
Barrascano
Problem of Antibiotic Therapy
in MMID (“Lyme”)
•
•
•
•
•
An adequate intracellular dose internally requires the
systemic administration of very high doses of drugs
Lack of absolute specificity of drugs administered in
MMID.
Need of drugs to cross the blood brain barrier to deal
with certain neurologic effects.
Systemic toxicity (i.e. hepatic) to large doses of
immunologic agents
Combination of the above leads to widespread potential
drug side effects.
What would be the elements of
an ideal solution to this
antibiotic dosing dilemma?
•
•
•
Develop a method to differentiate the infected cell
population for the normal cell population
To deliver lowered dosage of drugs more specifically to
the infected cells
To reduce or avoid antibiotic therapy side effects to
normal cells.
Treatment For Chronic Lyme
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•
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Antibiotics used in cycles
Oxidative therapy
Silver hydrosol treatment
Detoxification
Immune modulation
Anti Inflammatory Regimens
Treatment
More Than Antibiotics!
•
Enforced rest
• NO caffeine
• NO alcohol
• NO smoking at all
• Low-carb
• High quality protein diet
• Daily vitamins and other nutritional support
• Maintain hydration
• Exercise program
• Never any steroids!
Integrative Approaches
•
Detox: very important!
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Must keep these patients well hydrated
Encourage active detox with FIR (saunas and mats)
Oral treatment with zeolite, chlorella, fulvic acid and bentonite
clay
Patients encouraged to exercise 30-60 minutes at least 5 days
a week
Intermittent fasting with juicing
Ionic foot baths
Deep tissue therapy/lymphatic massage
Meditation (TM, Audio assisted)
Biofeedback
Skin brushing
Homeopathic detox
Integrative Approaches
•
Bowel irrigation/colonics with ozone
• IV chelation
• Glutathione IV
• Metabolic and Immune Support:
•
•
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IV Myers Cocktail
IV Vit C and Freamine
Vit D3, zinc, selenium po
Mushroom extract: turkey tail, chaga, Maitake, Reishi and
Cordyceps
Low dose Cortef and adrenal cortical extract
These treatment regimens represent a group of options that
are ‘outside of the box’ and have been show to help our
patients who have been failed by traditional therapy.
Integrative Approaches
•
Oxidative therapy:
•
•
There are many styles and approaches. Ones we use include
Major Autohemotherapy (IM), Prolozone (Joint and soft tissue)
utilizing ozone, IV H202 is also used in tandem with the ozone
treatments
Silver hydrosol:
•
•
Given IV and orally.
Patient have been treated for as long as 9 months
Homeopathic Approaches
To Lyme
•
•
•
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Syphilinum 9c/30c
Lachesis matus
Ledum palustre
Rhus Tox/Apis Mellificia
•
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Anti-metal helps
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Check modalities for joint pain first
Plumbum metallicum, mercurius solubilis
Belladona
Herbal Approach To Lyme
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Byron White Formulation
Aa Baab; A-Bart; A Lyme
Samento
Insulin Potentiation Therapy
•
IPT:
•
•
•
•
•
Using the insulin receptors as gateways to target
intracellular organism with antibiotics and nutraceuticals
IV Abx used include ceftriaxone (500-1000mgs) and
Doxycycline (Vibramycin, 100-200mgs)
IM/IV Abx used is Penicillin G (8-12 million units)
Flush meds with 5-10cc’s of DMSO in patients with CNS
and joint symptoms
IPT is the only therapy that crosses the blood brain
barrier
Schema of IPT Mechanisms
Exogenus Insulin
x4
Insulin
Receptors
Low Dose
Antibiotic
MEMBRANE
EFFECTS
-
-
Altered cell
membrane
permeability
Increased
intracellular
dose intensity
Infected Cell
Ligand effect
is a function
of receptor
concentration
Mechanism of Membrane
Effects of Insulin
•
•
•
Insulin activation of dela-9 desacturase at 37 degrees
Celsius – membrane fluidity and permeability
increased
Drug absorption into glucose molecules with
transmembrane transport then occurring via the
insulin activated glucose transport protein
Absorption of drug molecules onto insulin with the
resulting chimeric drug insulin complex being
internalized into the cell by a process of receptormediated endocytosis
IPT and MMID (“Lyme”)
Membrane Effect
•
•
•
•
•
Increased cell membrane permeability
Increased intercellular dose intensity
Lowered total dose of drugs concentrate
Reduced dose related side effects
Shortened time course of cycle intervals
IPT and MMID (“Lyme”)
•
•
•
IPT targets the affected, inflammatory area for
therapy – kind of a “smart bomb” effect
IPT allows specificity of therapy with different agents
IPT allows the introduction of multiple antibiotics in
very low dosages to the area for specific killing effect
to microbes
TEST
Lyme Disease
Left Untreated
RESULTS MARCH
2011
RESULTS JUNE 2013
Lyme IgM Western Blot
18 kDa.
**23-25 kDa.
28 kDa.
30 kDa.
**31 kDa.
**34 kDa.
**39 kDa.
**41 kDa.
45 kDa.
58 kDa.
66 kDa.
**83-93 kDa.
NEGATIVE
+
+
-
NEGATIVE
IND
IND
IND
++
++
IND
Lyme IgG Western Blot
18 kDa.
**23-25 kDa.
28 kDa.
30 kDa.
**31 kDa.
**34 kDa.
**39 kDa.
**41 kDa.
45 kDa.
58 kDa.
66 kDa.
**83-93 kDa.
NEGATIVE
IND
IND
+
IND
POSITIVE
++
+
IND
++
+
-
Abs. CD8-CD57+ Lymphs 24
8
Protocols To Integrative Treatment For
Lyme & Mold
•
•
CASE STUDY # 1
C.E. a 35 year old female.
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History of seizures and severe pain (Sept 2011).
Came to us for possible Lyme disease.
Chief complaints: seizures & severe pain (due to Lyme disease)
Diagnosis
•
Original diagnosis before IMO: seizure disorder
•
Diagnosis/treatment for at IMO: probable Lyme disease,
severe arthritis
Tests Taken
Tests taken: Western Blot, Salivary cortisol,
High levels of Trichothecene Mycotoxins (systemic yeast
infestation)
Protocols To Integrative Treatment
For Lyme & Mold
•
Original Mission
•
Relieve pain
•
Methods
•
IPT
•
Treated with mixed antibiotics; rocephin, doxycycline,
tygacil, clindamycin
•
Supplements: daily vitamins – thyroid & adrenal
support
•
Medications: thyroid, adrenals, roxithromycin
•
Protocols To Integrative Treatment
For Lyme & Mold
•
Results
•
Complete resolution in 6 weeks
• No further ambulation
• No further joint or lumbar pain
• No further seizures
•
Excellent improvement in sleep (5 = GREAT)*
•
Excellent improvement in appetite (5 = GREAT)*
•
Overall feeling on a scale of 1 (Poor) – 5 (Great) = 5
GREAT*
Protocols To Integrative Treatment
For Lyme & Mold
•
•
CASE STUDY # 2
J.S. 30 year old female.
•
History: 2-3 years of severe pain
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Chief complains: constant muscle/joint pain, exhaustion,
inability to concentrate
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Diagnosis
•
Original diagnosis before coming to us: Fibromyalgia/CFIDS
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Diagnosis/treatment with us: Mold
•
Tests taken
•
ELISA, CBC with differential platelet (high RDW), Tricothecene
(+),
Protocols To Integrative Treatment
For Lyme & Mold
•
•
Original Mission
•
Relieve pain
Methods
•
IPT for anti fungals
•
•
Results
•
Complete relief of pain and brain fog
•
Mycotoxin count down to 0
•
Note. Patient went back to work environment and mycotoxins
rose again
Protocols To Integrative Treatment
For Lyme & Mold
•
•
CASE STUDY # 3
S.S. 37 year old female.
•
History: illness since 1995 (17+yrs), diagnosed mold exposure
10/2012, Lyme disease 10/2012, orthoscopic surgery (both knees),
•
Reason she came: treatment for mycotoxins
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Chief complaint(s): digestive, joint pain/stiffness/swelling, mental
cognition
•
Diagnosis
•
Original diagnosis before coming to us: mycotoxins, Lyme disease,
food sensitivities
•
Diagnosis/treatment with us: As well as above; Mold, thyroid
•
Tests taken
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ELISA – Ochrathoxin (+), Allergies, Western Blot (+),
Protocols To Integrative Treatment
For Lyme & Mold
•
Original Mission
•
Treatment of Lyme & mycotoxicosis
•
Methods
•
IPT for Lyme and mycotoxins
•
•
Results
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Complete resolution of fatigue, joint pain and brain fog
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Ochratoxin levels went down 50%
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CD8 –CD57+ levels went up 49L/uL (36 to 85)
Conclusion
•
IPT is a unique therapy for targeting inflamed and
infected areas
• IPT is a unique drug delivery system to get to specific
places
• IPT is the only therapy that crosses the blood brain
barrier
Bibliography/References
•
Cullen J.K., Yee D., Sly W.S. et al
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•
Papa V., Pezzino V., Constantino A., et al
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•
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Metabloic modification by insulin enhanced cytotoxicity in MCF-7 human breast cancer
cells. Eun J Cancer Clin Oncology 17:1097-1103, 1981
Burrascano Joseph J
•
•
After insulin binds. Science 273: 1452-1457, 1987
Alabaster O., Vonderhaar B.K., Shafie S.M
•
•
Elevated insulin receptor control in human breast cancer. J Clin Invest 86:1503-1510,
1990
Rosen O.M.
•
•
Insulin-like growth factor receptor expression and function in human breast cancer.
Cancer res 50:48-53, 1990
Adrenal topic in Lyme disease. Managing Lyme disease, 18th edition, October 2008
www.cdc.gov
The Great Imposter
ILADS
Emedicine.com
Uptodate.com