Raj Patel, M.D.

Biofilms, Methylation & Biofilms, Methylation & Heavy Metal Detoxification Heavy Metal Detoxification

in Lyme Disease in Lyme Disease

Raj Patel, M.D.

OverviewOverview

A. 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, MDRaj Patel, MD Education:

MS-Rutgers UniversityMD – Robert Wood Johnson Medical SchoolResidency-Family MedicinePost Graduate studies in Autism Spectrum Disorders

Research:Ampligen-CFIDS (Hemispherx Pharmaceutical)

Clinical:16+ years clinical experienceActive member of Defeat Autism Now (DAN)Active member of International Lyme and Associated Diseases Society (ILADS)

Raj Patel, MDMedical Options for Wellness5050 El Camino Real, #110Los Altos, CA 94022

650-964-6700http://www.DrRajPatel.net

Raj Patel, M.D.

B. Biofilms in Lyme Disease

1. GI Physiology: Structure of normal intestinal lining

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Raj Patel, M.D.

B. Biofilms in Lyme Disease

1. GI Physiology: Structure of intestinal lining in Gluten intolerance

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Raj Patel, M.D.

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 Linesc. Stagnant pools of water, rivers and streamsd. Contact lense. Polluted areasf. Blood (Fry et al)

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B. Biofilms in Lyme Disease

4. Prevalence of Biofilms

a. Autism Spectrum Disorders b. Chronic Lyme Diseasec. Chronic Fatigue Immune Dysfunction Syndromed. Fibromyalgiae. Autoimmune Illness

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Raj Patel, M.D.

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:

Thimersol (50% Hg by volume) was the preservative in mostvaccines 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 Oct;115(10):1435-41

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:

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

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 (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

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 urine for heavy metals.

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B. Heavy Metals (con’t)

3. Treatment (con’t)

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 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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Methionine

MethionineSynthase

Homocysteine

SAH

SAM

5 MTHF

5,10 MTHF

MSR

B12

Zn

Mg

Cystathione

Cysteine

Glutathione

Homocysteine

Taurine

CBS P5P

P5P

Methylation Cycle

MTHR

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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

Heavy metals at low levels can suppress key enzymes involved in methylation

Viruses can impair methylationMunzel 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)

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 DeficiencyGlutathione DeficiencyRationale: 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 DeficiencyGlutathione 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, MDRaj Patel, MD

Medical Options for Wellness5050 El Camino Real, #110Los Altos, CA 94022650-964-6700http://www.DrRajPatel.net