Transcript Biofilms, Methylation & Heavy Metal Detoxification in Lyme

Biofilms, Methylation &
Heavy Metal Detoxification
in Lyme Disease
Raj Patel, M.D.
Overview
A. Biofilms
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Gastrointestinal physiology
Definition of Biofilms
Examples
Prevalence
Treatment
B. Heavy Metals
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Prevalence
Signs & symptoms
Testing
Treatment options
Methylation in non-responders
C. Conclusion
Raj Patel, M.D.
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
Raj Patel, MD
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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)
Supportive nutrients (slippery elm, okra, NAG, ecklona cava,
colostrum)
f. Drainage
g. GO SLOW
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B. Heavy Metals
1. Heavy Metals - Hg, Cd, Pb, & Ar are the best studied
a. Hg
I. Sources:
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Thimersol (50% Hg by volume) was the preservative in most
vaccines until approx 2001.
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Cumulative dose in vaccines from birth to age 5 years exceeded
the EPA guidelines for safety.
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Large population of older children and young adults have
had significant exposure.
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Study on NYC adult population revealed 24.8% had blood
levels at or exceeding 5ug/l, the NY State reportable level.
McKelvey W. Environ Health Perspect. 2007 Oct;115(10):1435-41
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Seafood, dental amalgams, and industrial output account for
the major sources of exposure today. (26,27)
WHO. Methyl Mercury. Environmental Health Criteria, vol. 101. Geneva:
World Health Organization, 1990
Sallsten G, et.al., J Dent Res 1996; 75: 594–8
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1. Heavy Metals (con’t)
a. Hg
II. Toxicity:
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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): 851–4
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Autoimmunity
Hultman, P. et al. The FASEB Journal Nov 1994; 1183-90
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Paresthesias, insommnia, cognitive difficulties,
neuromuscular changes, headaches and anxiety.
http://www.epa.gov/iris/subst/0692.htm
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1. Heavy Metals (con’t)
b. Cd
I. Sources: Color pigment (dyes & paints)
Cigarette smoke
Ni-Cd batteries
Phosphate fertilizers
Jarup L et al. Health effects of cadmium exposure—a review of the literature and a risk
estimate. Scand J Work Environ Health 1998; 24 (Suppl 1): 1–51
WHO. Cadmium. Environmental Health Criteria, vol. 134. Geneva: World Health
Organization, 1992
II. Toxicity: Kidney damage
Osteoporosis
Cancer
Jarup, L. Br. Med. Bull. 68:167-182 (2003)
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1. Heavy Metals (con’t)
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: 295–9
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1. Heavy Metals (con’t)
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; 279–303
www.epa.gov/ttn/atw/hlthef/arsenic.html
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B. Heavy Metals (con’t)
2. Testing for Heavy Metals
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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
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Difficult to accurately assess total body burden. Urinary porphyrins
have some utility – currently probably the best clinical test available.
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Hair Mineral Analysis may be helpful, but show false negative in
individuals with compromised detoxification pathways
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Provocative challenge-involves administering a test dose of a chelator
(DMPS, DMSA, or EDTA) and measuring pre- and post- fecal &/or
urine for heavy metals.
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B. Heavy Metals (con’t)
3. Treatment (con’t)
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Nutritional support during chelation essential
I. Gut binding agents-Bentonite
Charcoal
Cholestyramine
II. Mineral replacement-depending 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
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Definition:
Methylation involves transfer of methyl group
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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
Mg
Zn
SAM
MSR
Methionine
Synthase
MTHR
B12
SAH
5 MTHF
Homocysteine
Homocysteine
P5P
CBS
Cystathione
P5P
Cysteine
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Taurine
Glutathione
B. Heavy Metals
4. Assess methylation in non-responders (con’t)
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 Aug;8(8):659-68
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Heavy metals at low levels can suppress key enzymes involved in
methylation
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Viruses can impair methylation
Munzel and Koschel, Proc. Nat’l. Acad. Sci. (USA) 79(1982) 3692-6
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B. Heavy Metals
4. Assess methylation in non-responders (con’t)
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Testing to assess methylation: genomic testing
urine/serum amino acid analysis
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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
Raj Patel, M.D.
Raj Patel, MD
Medical Options for Wellness
5050 El Camino Real, #110
Los Altos, CA 94022
650-964-6700
http://www.DrRajPatel.net
Raj Patel, MD
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