Transcript Document

Optimizing GI Function and
Heavy Metal Burden in Lyme
Disease
Raj Patel, MD
Medical Options for Wellness
Los Altos, CA
650-964-6700
www.DrRajPatel.net
Raj Patel, M.D.
Overview
A. Optimize GI Function
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Antibiotic induced diarrhea
Intestinal dysbiosis (definition, causes, treatment)
Liver/GB Support
B. Heavy Metals
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Prevalence
Signs & symptoms
Testing
Treatment options
Methylation in non-responders
C. Conclusion
Raj Patel, M.D.
A. Optimize GI Function
1. Antibiotic Induced Diarrhea (AID)
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Common complication from extended antibiotic use
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Probability increases with use of >2 antibiotics
Doxy + Flagyl for 10 d caused a significant increase
in GI and vaginal candida counts than either alone.
Maraki S. J Chemother. 2003 Aug;15(4):369-73.
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Certain antibiotics more commonly associated with
AID (Cephalosporins and Penicillins)
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Clostridium difficile induced enterocolitis
Symptoms: diarrhea, abdominal pain, fevers
Incidence: only accounts for 10-20% of all AID cases
E. Bergogne-Bérézin Int J Antimicrob Agents. 2000 Dec;16(4):521-6
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Non-Clostridium AID
Common pathogens include Clostridium perfringens,
Staphylococcus aureus, Klebsiella oxytoca, Candida species,
and Salmonella species.
Accounts for 80-90% of all AID cases
Clin Infect Dis. 1998 Oct;27(4):702-10
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AID Treatment Options
Mild Symptoms: Saccharomyces boulardii
Probiotics
Bland diet
Drug holiday/Change antibiotics
Elmer GW. et al JAMA. 1996 Jul 3 ;276(1):29-30 Biotherapeutic agents. A neglected
modality for the treatment and prevention of selected intestinal and vaginal infections.
Severe Symptoms: Metronidazole
Vancomycin
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2. Intestinal Dysbiosis
a. Definition:
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Term originally coined by Metchnikoff to describe altered pathogenic
bacteria in gut. Today, abnormal milieu due to bacterial and fugal
imbalance.
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These abnormal bacteria have been shown to produce:
toxic products- endotoxins, phenols, ammonia, & indoles
Macfarlane C et al. Proteolysis and amino acid fermentation. In: Gibson GR, Macfarlane GT, eds.
Human Colonic Bacteria: Role in Nutrition, Physiology, and Pathology. Boca Raton, FL:
CRC Press; 1995:75-100.
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Chronic degenerative diseases - inflammatory bowel disease,
ankylosing spondylitis, & RA
Peltonen R, Nenonen M, Helve T, et al. Br J Rheumatol 1997;36:64-68.
Brandtzaeg P. Review article: Aliment Pharmacol Ther 1997;11:24-37.
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Intestinal Dysbiosis (con’t)
b. Functions of the microflora
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Immune stimulation
Vitamin synthesis (B group & K)
Enhancement of gut motility, digestion & nutrient absorption
Improve epithelial function via increased SCFA production,
decreased apoptosis, increased barrier integrity
Inhibit pathogenic bacteria via decreasing luminal pH, decreasing
epithelial binding, and decreasing epithelial invasion
Metabolism of certain drugs
Holzapfel WH, et al. Int J Food Microbiol 1998;41:85-101.
Noack J, et al. J Nutr 1998;128:1385-1391.
Gibson GR, Roberfroid MB. J Nutr 1995;125:1401-1412.
Sartor, RB. J. Clin. Gastro 2007;41:537-543
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Intestinal Dysbiosis (con’t)
c. Causes of Intestinal Dysbiosis
I. Antibiotics-based on spectrum
of activity, route of excretion, dosage, &
length of use.
Hawrelak, JA Alternative Medicine Review Vol 9, No 2 2004
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Effects of Antibiotics on Intestinal Flora
Antibiotics
Enterobacteria
Enterococci
Anaerobic
Resistant
Strains
Lactobacilli
/Bifidus
Candida
Ampicillin
Amoxicillin
Cefaclor
Ceftriaxone
Ciprofloxacin
Clindamycin
Doxycycline
Metronidazole
Moxalactam
Ofloxacin
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Hawrelak, JA Alternative Medicine Review Vol 9, No 2 2004
c. Causes of Intestinal Dysbiosis (con’t)
II. Stress:
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Altered gut motility and increased bicarbonate production
potentially leading to decreased survival/adherence/replication of
healthy flora
Lenz HJ. Et al. Gastroenterology 1988;94:598-602.
Lenz HJ. Proc Natl Acad Sci U S A 1989;86:1417-1420.
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Decreased mucin and mucopolysaccharide production leading to
increased adherence and replication of dysbiotic flora
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c. Causes of Intestinal Dysbiosis (con’t)
III. Lyme and Coinfections
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Lyme is well documented to invade and multiply in the GI tract
Fried MD, et al Gastrointestinal pathology in children with Lyme disease. Jour. of Spirochetal
& Tick-Borne Diseases 1996; 3:101-04
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Lyme and more commonly ehrlichiosis, tick borne relapsing fever,
& Rocky Mountain Spotted Fever are commonly associated with
diarrhea and intestinal dysbiosis.
Reisinger EC. et al. Nat. Clin. Pract. Gastrenterol. Hepatol. 2005 May; 2(5):216-22.
Zaidi SA. et al. Clin. Infect. Dis. 2002 May 1;34(9):1206-12
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c. Causes of Intestinal Dysbiosis (con’t)
IV. Maldigestion
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Pancreatic exocrine deficiency
Fecal elastase marker for pancreatic enzyme production
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Gallbladder dysfunction with decreased bile production -> fat
maldigestion
Consider fecal fat testing
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Increased intestinal permeability/inflammation
Microscopically characterized by blunting/loss of micro-villi and
compromised tight junctions between cells
Corresponding loss of disaccharidases resulting in carbohydrate
maldigestion, increased disaccharide load to colon, and resulting
dysbiosis.
Diagnosed by Lactulose/Mannitol test (increased ratio indicates
increased permeability)
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c. Causes of Intestinal Dysbiosis (con’t)
V. Diet - Composition of diet affects type and metabolic activity of
gut flora
Gibson GR. Dietary modulation of the human gut microflora using prebiotics. Br J Nutr
1998;80:S209-S212.
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High Protein Diet: Typical American diet contains 100g of protein per
day. Up to 12g can escape digestion & become
available for fermentation by colonic bacteria.
The resulting harmful byproducts include ammonia,
sulfides, indoles, phenols & amines-> migraines,
carcinogens, damage lining, contribute to portal
encephalopathy.
Significant issue in Lyme patients with
compromised GI function
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c. Causes of Intestinal Dysbiosis (con’t)
V. Diet (con’t)
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High Carbohydrate Diet:
High refined carbohydrate diet
-> slows bowel transit time
-> increases bacterial fermentation
-> increases exposure to potentially toxic bowel contents (96)
-> promotion of fungal overgrowth (esp. in presence of multiple
antibiotics)
Lewis SJ, Heaton KW. Am J Gastroenterol 1999;94:2010-2016.
High carbohydrate diet (esp gluten and casein)
-> increases disaccharide load to colon (due to intestinal
inflammation and disaccharidase deficiency)
-> abnormal bacterial overgrowth and fermentation
Raj Patel, M.D.
Intestinal Dysbiosis (con’t)
d. Treatment Options for Intestinal Dysbiosis
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Antibiotics: All things being equal choose antibiotics with less effect on
gut flora.
Support intestinal flora-probiotics (research carefully)
prebiotics (FOS, etc.)
fermented foods
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Stress: Help patients manage stress effectively
Support endocrine systems esp. adrenals and thyroid as covered
earlier
Treat insommnia aggressively (melatonin, 5HTP, Ramelteon,
Trazodone, etc.)
Treat depression/anxiety if needed
Raj Patel, M.D.
Intestinal Dysbiosis (con’t)
d. Treatment Options for Intestinal Dysbiosis
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Lyme: Expect improvement in gut issues as load of Lyme and
coinfections reduced
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Maldigestion: Digestive enzmes-Use broad spectrum digestive aids
that include protease, lipase, & amylase as well as
disaccharidases (lactase, maltase, and sucrase)
Gallbladder support-Taurine, ox bile, and bile salts can
aid in bile production and fat digestion
Intestinal inflammation/permeability-Glutamine,
slippery elm, and DGL aid in reducing gut
inflammation. Eliminate allergenic/intolerant foods
& consider desensitization
Raj Patel, M.D.
Intestinal Dysbiosis (con’t)
d. Treatment Options for Intestinal Dysbiosis (con’t)
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Diet: Consider decreasing protein intake if excessive
Eliminate gluten, casein, and refined carbohydrates
Consider Specific Carbohydrate Diet (SCD) in those severely
carbohydrate intolerant
Gottschall, E (1994). Breaking the Vicious Cycle: Intestinal Health Through Diet,
Revised edition, Kirkton Press..
Raj Patel, M.D.
Intestinal Dysbiosis (con’t)
3. Liver/Gallbladder Function
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Dysfunction/Inflammation of liver and gallbladder
I. Lyme and coinfections
II. Antibiotics: Elevate liver function tests
Those with biliary excretion can result in GB dysfunction
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Testing
I. Comprehensive liver detoxification screen to evaluate phase I & II
function
II. Genomic testing
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Hepatic nutritional support
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Hepatic Nutritional Support
Bio-Chem Site
Cause
Intervention
Phase I
Upregulated
Dysgiosis/gut derived toxins
increased intes. Permeab.
environ. Toxic exposure
Address source
Antioxidants
Support phase II
Phase I
Downregulated
P450 inhibitors (HM, drugs,
EFA deficiency, hypothyroid,
& increased sat. fat intake
Correct source, liver support
with PC, taurine, silymarin,
EFAs, & antioxidants
Phase IIGlucoronidation
Mitochondrial damage, Fe
deficiency, drugs, genetic
uniqueness (Gilbert’s)
Address underlying cond’t.
Cruciferous veg. to induce
conjugation enzymes, B6, Mg,
L-glutamine, asp acid, niacin
Glycination
Hepatic disease, nutritional
deficiency, genetics
Glycine, alkaline foods to
enhance glycination, B5, Mg,
cysteine
Glutathione
conjugation
Glutathione depletion due to
increased toxic load, nutritional
deficiency, genetics
Reduced glutathione, N-acetyl
cysteine, glycine,
L-methionine, L-glutamine
Sulfate depletion, toxic load,
hepatic disease, genetics
High sulfur foods, red.
Glutathione, L-methionine,
L-cysteine, Zn, Cu, Se, Mg,
B6, B12, Mg, FA
Sulfation
Raj Patel, M.D.
Patrick Hanaway, MD Genova Diagnostic Laboratories
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.
Raj Patel, M.D.
B. Heavy Metals (con’t)
3. Treatment - best done once Lyme/coinfection load reduced
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Pharmacological Chelators: DMPS
DMSA
EDTA
Penicillamine
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Non-pharmacological chelators: Sauna
Alginate/Chlorella
Zeolite
Raj Patel, M.D.
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-as outlined earlier
Raj Patel, M.D.
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
Raj Patel, M.D.
Methylation Cycle
5,10 MTHF
Methionine
Mg
Zn
SAM
MSR
Methionine
Synthase
MTHR
B12
SAH
5 MTHF
Homocysteine
Homocysteine
P5P
CBS
Cystathione
P5P
Cysteine
Raj Patel, M.D.
Taurine
Glutathione
B. Heavy Metals
4. Assess methylation in non-responders (con’t)
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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
Raj Patel, M.D.
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:
Methyl B12 / Cyano B12
TMG (or DMG)
Folic/Folinic acid
P5P/B6
Reduced Glutathione
Raj Patel, M.D.
C. Conclusion
1. Aggressive GI support before, during and after antibiotic treatment can
greatly assist in reducing complications and improve outcome
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, with appropriate methylation support as needed,
may improve outcome and potentially reduce the likelihood of relapse
Raj Patel, M.D.