Biofilms, Methylation

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Biofilms, Methylation Heavy Metal
Detoxification in Lyme Disease

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Overview

• Biofilms
• Gastrointestinal physiology
• Definition of Biofilms
• Examples
• Prevalence
• Treatment
• B. Heavy Metals
• Prevalence
• Signs symptoms
• Testing
• Treatment options
• Methylation in non-responders
• C. Conclusion

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Raj Patel, MD

• Education
• MS-Rutgers University
• MD Robert Wood Johnson Medical School
• Residency-Family Medicine
• Post Graduate studies in Autism Spectrum
  Disorders
• Research
• Ampligen-CFIDS (Hemispherx Pharmaceutical)
• Clinical
• 16 years clinical experience
• Active member of Defeat Autism Now (DAN)
• Active member of International Lyme and
  Associated Diseases Society (ILADS)

Raj Patel, MD Medical Options for Wellness 5050
El Camino Real, 110 Los Altos, CA
94022 650-964-6700 http//www.DrRajPatel.net
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B. Biofilms in Lyme Disease 1. GI
Physiology Structure of normal intestinal
lining

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B. Biofilms in Lyme Disease 1. GI
Physiology Structure of intestinal lining in
Gluten intolerance

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B. Biofilms in Lyme Disease 1. GI
Physiology Microbial Flora
I. One hundred trillion bacteria in
gut comprises 500 different species
II. Disruption early leads to immune problems,
allergies, and autoimmunity later
III. Functions modulates immune system
destroys toxins introduced with food
suppress growth of pathogenic bacteria
production of key vitamins digestion
and absorption of carbohydrates
prevention of allergies prevention of
inflammatory bowel disease

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B. Biofilms in Lyme Disease 2. Definition
a. Community of bacteria and
other organisms surrounded by a extracellular
polymeric substance (EPS) b. EPS is composed
of DNA, protein, and polysaccharides. Its
negative charge attracts Ca/Mg/Fe to strengthen
it c. Organisms within a biofilm can
communicate and exchange genetic material.
d. EPS provides resistance to antibiotics
requiring 100-1000X higher levels for
eradication. Testing the
susceptibility of bacteria in biofilms to
antimicrobial agents . Antimicrobial Agents and
Chemo. Nov 1990 e. EPS provides this
organisms protection from UV exposure, pH
changes, heavy metal toxicity, and phagocytosis.



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B. Biofilms in Lyme Disease 3. Examples of
Biofilms a. Teeth b.
Catheters and IV Lines c. Stagnant pools of
water, rivers and streams d. Contact lens e.
Polluted areas f. Blood (Fry et al)

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B. Biofilms in Lyme Disease 4. Prevalence
of Biofilms a. Autism Spectrum
Disorders b. Chronic Lyme Disease c. Chronic
Fatigue Immune Dysfunction Syndrome d.
Fibromyalgia e. Autoimmune Illness

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B. Biofilms in Lyme Disease 3. Examples of
Biofilms

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• B. Biofilms in Lyme Disease
• 5. Role of EDTA in Dissolving Biofilm
• a. EDTA serves to bind and remove the Ca/Mg/Fe
  holding biofilms together
• b. Staph biofilms could not be eradicated by
  Vancomycin or EDTA alone. Together the two
  agents successfully removed the biofilm (Kim
  2005)
• c. EDTA and Gentamycin are 1000X more effective
  at killing Pseudomonas than either agent alone.
  This effect is completely blocked when Ca or Fe
  are added (Banin 2005)

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• B. Biofilms in Lyme Disease
• 6. Treatment of Biofilms
• a. Enzymes
• b. EDTA
• c. Antimicrobials
• Antifungals
• d. Fiber
• Brown Algae
• Modified Citrus Pectin
• Activated Charcoal
• Zeolite
• e. Probiotics
• Prebiotics (fresh fruit, legumes, chicory,
  FOS, inulin)

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• B. Heavy Metals
• 1. Heavy Metals - Hg, Cd, Pb, Ar are the
  best studied
• a. Hg
• I. Sources
• Thimersol (50 Hg by volume) was the preservative
  in most
• vaccines until approx 2001.
• Cumulative dose in vaccines from birth to age 5
  years exceeded the EPA guidelines for safety.
• Large population of older children and young
  adults have had significant exposure.
• Study on NYC adult population revealed 24.8 had
  bloodlevels at or exceeding 5ug/l, the NY State
  reportable level.
• McKelvey W. Environ Health Perspect. 2007
  Oct115(10)1435-41
• Seafood, dental amalgams, and industrial output
  account for the major sources of exposure today.
  (26,27)

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• 1. Heavy Metals (cont)
• a. Hg
• II. Toxicity
• Low level chronic exposure can lead to nervous
  system
• damage resulting
  in depression, anxiety cognitive loss
• Weiss B, Clarkson
  TW, Simon W. Environ Health Perspect 2002 110
  (Suppl 5) 8514
  
• Autoimmunity
• 
  Hultman, P. et al. The FASEB Journal Nov 1994
  1183-90
• Paresthesias, insommnia, cognitive
  difficulties,
• neuromuscular
  changes, headaches and anxiety.
• 
  http//www.epa.gov/iris/subst/0692.htm

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1. Heavy Metals (cont)
b. Cd I. Sources Color pigment
(dyes paints)
Cigarette smoke
Ni-Cd batteries
Phosphate fertilizers
Jarup L et al. Health effects of
cadmium exposurea review of the literature and
a risk
estimate. Scand J Work Environ
Health 1998 24 (Suppl 1) 151
WHO. Cadmium.
Environmental Health Criteria, vol. 134. Geneva
World Health
Organization, 1992
II. Toxicity Kidney damage
Osteoporosis
Cancer


Jarup, L. Br. Med. Bull. 68167-182 (2003)

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1. Heavy Metals (cont)
c. Pb I. Sources Gasoline
(Worldwide major source but not in US)
Lead in drinking water
primarily due to the presence of lead
in certain
pipes, solder, and fixtures.
In kids toys
and lead based paints in old homes
II. Toxicity Decreased IQ
Memory deterioration
Cancer
Anemia
Peripheral nerve symptoms


WHO. Lead.
Environmental Health Criteria, vol. 165. Geneva
World Health
Organization, 1995
Steenland K,
Boffetta P. Am J Ind Med 2000 38 2959

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1. Heavy Metals (cont)
d. Ar I. Sources Wood
preservative
Fish
Pesticides/food
Industrial exposure II.
Toxicity Cancer-lung, bladder, kidney
Peripheral neuropathy
Anemia
GI Effects
WHO. Arsenic and Arsenic Compounds.
Environmental Health Criteria, vol. 224. Geneva
World Health
Organization, 2001
Chilvers DC, Peterson PJ. Global cycling of
arsenic. In Hutchinson TC, Meema KM (eds) Lead,
Mercury, Cadmium and
Arsenic in the Environment. Chichester John
Wiley Sons, 1987 279303
www.epa.gov/ttn/atw/hlthef/arsenic.html

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• B. Heavy Metals (cont)
• 2. Testing for Heavy Metals
• Blood levels useful for acute exposure, but
  unreliable tool for chronic
• low level exposures.
• Mercury has affinity for fatty
  tissue. Rarely seen in blood.
• The half-life of Pb in blood is
  about one month whereas the
• half-life in bone is 20-30
  years. (35)
• WHO. Lead. Environmental
  Health Criteria, vol. 165. Geneva World Health
  Organization, 1995
• Difficult to accurately assess total body
  burden. Urinary porphyrins
• have some utility currently probably
  the best clinical test available.
• Hair Mineral Analysis may be helpful, but show
  false negative in
• individuals with compromised
  detoxification pathways
• Provocative challenge-involves administering a
  test dose of a chelator
• (DMPS, DMSA, or EDTA) and
  measuring pre- and post- fecal /or

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• B. Heavy Metals (cont)
• 3. Treatment (cont)
• Nutritional support during chelation essential
• I. Gut binding
  agents-Bentonite
• 
  Charcoal
• 
  Cholestyramine
• II. Mineral replacement-dependi
  ng on the chelator used, replace
• minerals aggressively with
  special attention to Ca Mg
• with EDTA and Cu Zn with
  DMPS/DMSA
• III. Antioxidant
  support-necessary to quench free radicals
  generated
• during heavy metal
  removal. Supplement with A, C, E, Zn,
  
• selenium, and reduced
  glutathione.
• IV. Hepatic support

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Options for Detoxification

• Testing
• Urinary porphyrin testing
• Hair Mineral Analysis (useful if detoxification
  intact)
• RBC Analysis (for recent exposure)
• Fecal/Urinary testing in conjunction with a
  provoking agent
• Treatment
• DMSA or DMPS
• EDTA

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• B. Heavy Metals
• 4. Assess methylation function in
  non-responders
• Definition
• Methylation involves transfer of methyl
  group
• Methylation plays a role in
• Neurotransmitter
  synthesis and breakdown
  
• Renal disease
• Cardiovascular
  disease
• Cancer
• Heavy metal
  detoxification
• Anti-viral immune
  modulation

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Methylation Cycle
5,10 MTHF
Methionine
SAM
MSR
Methionine Synthase
MTHR
SAH
5 MTHF
Homocysteine
Homocysteine
CBS
Cystathione
Cysteine
Glutathione
Taurine
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• B. Heavy Metals
• 4. Assess methylation in non-responders (cont)
• Impairments in Methylation can be the result of
  the following
• Single Nucleotide Polymorphisms (SNPs)
• Can impair methylation
• Commonly found in the general
  population
• SNPs involving MTHFR C677T have a
  47 incidence among
• Caucasians
• Ulrich CM. et al.
  Cancer Epidemiol Biomarkers Prev. 1999
  Aug8(8)659-68
• Heavy metals at low levels can suppress key
  enzymes involved in methylation
• Viruses can impair methylation
• Munzel and Koschel, Proc. Natl. Acad. Sci.
  (USA) 79(1982) 3692-6

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• B. Heavy Metals
• 4. Assess methylation in non-responders (cont)
• Testing to assess methylation genomic testing
• 
  urine/serum amino acid analysis
• Nutritional Support to open/bypass areas of
  impairment
• MS/MSR
  Methyl B12 / Cyano B12
• BHMT
  TMG (or DMG)
• MTHFR
  Folic/Folinic acid
• CBS
  P5P/B6
• CBS
  Reduced Glutathione

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Glutathione Deficiency

• Rationale
• Studies show low glutathione (critical
  antioxidant) in Lyme Disease due to heavy metals
  and presence of multiple infections.
• Defects in methylation can result in low
  glutathione.
• These two factors independently and together
  result in impaired excretion of mercury and other
  toxic metals/chemicals. Resulting in a higher
  body burden

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Glutathione Deficiency

• Recommendations
• Testing Measure level of glutathione (fasting
  plasma or RBC).
• Treatment Oral tabs/caps of glutathione are
  poorly absorbed (perhaps 15). Alternatives
  include liposomal, transdermal or IV glutathione,
  with or without N-acetyl cysteine.

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C. Conclusion 1. Treatment of gut and
systemic biofilms in LD can greatly reduce the
reservoir of borrelia and its associated
coinfections resulting in a greatly diminished
risk of relapse 2. Heavy metals are
ubiquitous. They can compromise immune
functioning, promote overgrowth of
candida as well as dysbiotic flora.
Judicial heavy metal detoxification, once the
lyme/coinfection load has been reduced
or concurrently, with appropriate methylation
support as needed, may improve outcome
and potentially reduce the likelihood of relapse

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Raj Patel, MD
Medical Options for Wellness 5050 El Camino Real,
110 Los Altos, CA 94022 650-964-6700 http//www.
DrRajPatel.net