Lyme Disease An Integrative Approach

1
Lyme DiseaseAn Integrative Approach

• Robert LaCava, MD
• Constantine A. Kotsanis, MD

2
References

• www.cdc.gov
• The Great Imposter
• ILADS
• Emedicine.com
• Uptodate.com

3
The Discovery of Insulin (1920)A Canadian
Medical Miracleof 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)

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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)

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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.

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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

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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

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Some New Terminology
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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 (Contd)

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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 24121-130, 1986.
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How could this be?
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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
2731452-1457, 1987
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Supraphysiologic concentrations of insulin can
replace the IGF-I requirement in defined media
through cross-reaction with the IGF-I
receptor.Goustin et al. Growth factors and
cancer. Cancer Res 461015-1029, 1986.
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• Increased
• Sensitivity to
• Antimicrobials
• Increased
• drug potency

Ligand effect is a function of receptor
concentration
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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

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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.

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Antimicrobial Therapy

• I - Membrane Effect

II - Metabolic Effect
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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
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Mechanisms of Membrane Effects 1) Insulin
activation of delta-9 desaturase
Stearic acid Oleic acid
- saturated - -
monounsaturated - Tristearin
Triolein m.p. 68 deg. C
m.p. 5 deg. C
At 37 deg. C Membrane
fluidity/permeability
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Mechanisms of Membrane Effects (contd)
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
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IPT Antimicrobial Therapy

• II - Metabolic Effect

• Increased sensitivity to antimicrobial drugs
• Drugs become more potent
• Microbial drug resistance is eliminated or
• greatly reduced

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• Increased
• Sensitivity to
• Antimicrobials
• Reduction or .
• elimination of
• microbial drug
• resistance

Ligand effect is a function of receptor
concentration
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IPT Drug Therapy

• Smart Bomb effect Excess of insulin-sensitive
  receptors on human diseased cells causes
  predominance of insulin effect in diseased cells,
  sparing normal host tissues INCREASED SAFETY
• Synergy of insulins membrane and metabolic
  effects enhances antimicrobial drug action in
  diseased cells INCREASED EFFICACY

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Insulin Potentiation Therapy
A Renaissance in Chronic Disease States
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Lyme Disease An Integrative Approach

• Robert LaCava, MD

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Lecture Goals

• Present a broader concept of IPT for
• Lyme Disease and Mold Illness
• Present integrative approaches to treat
• Lyme Disease

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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

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Basic Facts
Natures Dirty Needle Ixodes pacificus (Western
Black Legged Tick) So tiny it can be
missed. Only 16 recall a tick bite. Painless.
Spirochetes are long and slender gram negative
bacteria that are tightly coiled looking like
telephone cords

• 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.

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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

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Three Phases of Lyme Disease

• Early localized
• Early disseminated disease
• Chronic Lyme disease late
• ill with Lyme for one or more years

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Why The Concern?Illness Can Vary From Mild To
Severe

• 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, Parkinsons disease,
  Depression, Adrenal fatigue, Thyroid disorders,
  Personality disorders

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Why The Concern? - continuedIllness Can Vary
From Mild To Severe

• More medical errors from incorrect diagnosis and
  unnecessary or dangerous treatments
• Fibromyalgia, MS/CFS, depression, ALS (Lou
  Gehrigs disease), malingering, Munchausens
  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.

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Diagnosing Lyme the SymptomsA difficult task

• 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

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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

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Blood Testing

• LYME (Borrelia burgdorferi)
• Serologic tests (ELISA, Western Blot)
• PCR also poorly sensitive - lt30
• CD57 (Natural Killer Cells)
• Low counts seen in Chronic Lyme when the
  infection has been active gt 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

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Serologic Testing

• A two-tiered strategy recommends
• ELISA IFA may substitute
• Western Blot
• ELISA testing usually derives from the whole
  organism. B. burgdorferi antigen are similar to
  others. Therefore cross-reaction is not uncommon.
  
• 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

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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

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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.

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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.

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Treatment For Chronic Lyme

• Antibiotics used in cycles
• Oxidative therapy
• Silver hydrosol treatment
• Detoxification
• Immune modulation
• Anti Inflammatory Regimens

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TreatmentMore 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!

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Integrative Approaches

• Detox very important!
• 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

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Integrative Approaches

• Bowel irrigation/colonics with ozone
• IV chelation
• Glutathione IV
• Metabolic and Immune Support
• 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.

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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

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Homeopathic Approaches To Lyme

• Syphilinum 9c/30c
• Lachesis matus
• Ledum palustre
• Rhus Tox/Apis Mellificia
• Check modalities for joint pain first
• Anti-metal helps
• Plumbum metallicum, mercurius solubilis
• Belladona

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Herbal Approach To Lyme

• Byron White Formulation
• Aa Baab A-Bart A Lyme
• Samento

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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 5-10ccs of DMSO in patients with
  CNS and joint symptoms
• IPT is the only therapy that crosses the blood
  brain barrier

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Schema of IPT Mechanisms
Exogenus Insulin
x4
Low Dose Antibiotic
Insulin Receptors
MEMBRANE EFFECTS
Ligand effect is a function of receptor
concentration

• Altered cell membrane permeability
• Increased intracellular dose intensity

Infected Cell
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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
  receptor-mediated endocytosis

50
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

51
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

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Lyme Disease Left Untreated
TEST 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
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Protocols To Integrative Treatment For Lyme Mold

• CASE STUDY 1
• C.E. a 35 year old female.
• 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)

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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
•  

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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 

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Protocols To Integrative Treatment For Lyme
Mold

• CASE STUDY 2
• J.S. 30 year old female.
• History 2-3 years of severe pain
• Chief complains constant muscle/joint pain,
  exhaustion, inability to concentrate
• Diagnosis
• Original diagnosis before coming to us
  Fibromyalgia/CFIDS
• Diagnosis/treatment with us Mold
• Tests taken
• ELISA, CBC with differential platelet (high RDW),
  Tricothecene (),

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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

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Protocols To Integrative Treatment For Lyme
Mold

• CASE STUDY 3
• S.S. 37 year old female.
• History illness since 1995 (17yrs), diagnosed
  mold exposure 10/2012, Lyme disease 10/2012,
  orthoscopic surgery (both knees),
• Reason she came treatment for mycotoxins
• 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
• ELISA Ochrathoxin (), Allergies, Western Blot
  (),

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Protocols To Integrative Treatment For Lyme
Mold

• Original Mission
• Treatment of Lyme mycotoxicosis
• Methods
• IPT for Lyme and mycotoxins
•  
• Results
• Complete resolution of fatigue, joint pain and
  brain fog
• Ochratoxin levels went down 50
• CD8 CD57 levels went up 49L/uL (36 to 85)

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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

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Bibliography/References

• Cullen J.K., Yee D., Sly W.S. et al
• Insulin-like growth factor receptor expression
  and function in human breast cancer. Cancer res
  5048-53, 1990
• Papa V., Pezzino V., Constantino A., et al
• Elevated insulin receptor control in human breast
  cancer. J Clin Invest 861503-1510, 1990
• Rosen O.M.
• After insulin binds. Science 273 1452-1457, 1987
• Alabaster O., Vonderhaar B.K., Shafie S.M
• Metabloic modification by insulin enhanced
  cytotoxicity in MCF-7 human breast cancer cells.
  Eun J Cancer Clin Oncology 171097-1103, 1981
• Burrascano Joseph J
• Adrenal topic in Lyme disease. Managing Lyme
  disease, 18th edition, October 2008
• www.cdc.gov
• The Great Imposter
• ILADS
• Emedicine.com
• Uptodate.com