Optimizing GI Function and Heavy Metal Burden in Lyme Disease

1
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
2
Overview

• Optimize GI Function
• Antibiotic induced diarrhea
• Intestinal dysbiosis (definition, causes,
  treatment)
• Liver/GB Support
• B. Heavy Metals
• Prevalence
• Signs symptoms
• Testing
• Treatment options
• Methylation in non-responders
• C. Conclusion

3
A. Optimize GI Function

• 1. Antibiotic Induced Diarrhea (AID)
• Common complication from extended antibiotic
  use
• Probability increases with use of gt2
  antibiotics
• Doxy Flagyl for 10 d
  caused a significant increase
• in GI and vaginal candida
  counts than either alone.
• Maraki S. J
  Chemother. 2003 Aug15(4)369-73.
• Certain antibiotics more commonly associated
  with
• AID (Cephalosporins and
  Penicillins)
• 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 Dec16(4)521-6

4

• 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
  Oct27(4)702-10
• 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

5

• 2. Intestinal Dysbiosis
• a. Definition
• Term originally coined by Metchnikoff to
  describe altered pathogenic
• bacteria in gut. Today, abnormal
  milieu due to bacterial and fugal
• imbalance.
• 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 199575-100.
• Chronic degenerative diseases - inflammatory
  bowel disease,
• 
  ankylosing spondylitis, RA
• Peltonen R, Nenonen M, Helve T,
  et al. Br J Rheumatol 19973664-68.
• Brandtzaeg P. Review
  article Aliment Pharmacol Ther 19971124-37.

6

• Intestinal Dysbiosis (cont)
• b. Functions of the microflora
• 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 19984185-101.
• Noack J, et al. J Nutr
  19981281385-1391.
• Gibson GR, Roberfroid MB. J Nutr
  19951251401-1412.
• Sartor, RB. J. Clin. Gastro
  200741537-543

7

Intestinal Dysbiosis (cont) 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

8
Effects of Antibiotics on Intestinal Flora
Antibiotics Entero-bacteria Entero-cocci Anaerobic ResistantStrains Lactobacilli/Bifidus Candida
Ampicillin
Amoxicillin
Cefaclor
Ceftriaxone
Ciprofloxacin
Clindamycin
Doxycycline
Metronidazole
Moxalactam
Ofloxacin
Hawrelak, JA Alternative Medicine Review Vol 9,
No 2 2004
9

• c. Causes of Intestinal Dysbiosis (cont)
• II. Stress
• Altered gut motility and increased bicarbonate
  production
• potentially leading to decreased
  survival/adherence/replication of
• healthy flora
• Lenz HJ. Et al.
  Gastroenterology 198894598-602.
• Lenz HJ. Proc Natl Acad Sci
  U S A 1989861417-1420.
• Decreased mucin and mucopolysaccharide production
  leading to
• increased adherence and
  replication of dysbiotic flora

10

• c. Causes of Intestinal Dysbiosis (cont)
• III. Lyme and Coinfections
• 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 3101-04
• 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 134(9)1206-12

11

• c. Causes of Intestinal Dysbiosis (cont)
• IV. Maldigestion
• Pancreatic exocrine deficiency
• Fecal elastase marker for pancreatic
  enzyme production
• Gallbladder dysfunction with decreased
  bile production -gt fat
• maldigestion
• Consider fecal fat
  testing
• Increased intestinal permeability/inflamma
  tion
• 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.

12

• c. Causes of Intestinal Dysbiosis (cont)
• 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
• 199880S209-S212.
• 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-gt migraines,
  
• 
  carcinogens, damage lining, contribute to portal
  
• 
  encephalopathy.
• 
  Significant issue in Lyme patients with
  
• 
  compromised GI function

13

• c. Causes of Intestinal Dysbiosis (cont)
• V. Diet (cont)
• High Carbohydrate Diet
• High refined carbohydrate
  diet
• -gt slows bowel
  transit time
• -gt increases
  bacterial fermentation
• -gt increases exposure
  to potentially toxic bowel contents (96)
• -gt promotion of
  fungal overgrowth (esp. in presence of multiple
• antibiotics)
• Lewis SJ, Heaton
  KW. Am J Gastroenterol 1999942010-2016.
• High carbohydrate diet (esp
  gluten and casein)
• -gt increases
  disaccharide load to colon (due to intestinal
• inflammation and
  disaccharidase deficiency)
• -gt abnormal bacterial
  overgrowth and fermentation

14

• Intestinal Dysbiosis (cont)
• d. Treatment Options for Intestinal Dysbiosis
• Antibiotics All things being equal choose
  antibiotics with less effect on
• gut flora.
• Support
  intestinal flora-probiotics (research carefully)
• 
  prebiotics (FOS, etc.)
• 
  fermented foods
• 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

15

• Intestinal Dysbiosis (cont)
• d. Treatment Options for Intestinal Dysbiosis
• Lyme Expect improvement in gut issues as load
  of Lyme and
• coinfections reduced
• 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

16

• Intestinal Dysbiosis (cont)
• d. Treatment Options for Intestinal Dysbiosis
  (cont)
• 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..

17

• Intestinal Dysbiosis (cont)
• 3. Liver/Gallbladder Function
• 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
• Testing
• I. Comprehensive liver
  detoxification screen to evaluate phase I II
  
• function
• II. Genomic testing
• Hepatic nutritional support

18
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 II- Glucoronidation Mitochondrial damage, Fe deficiency, drugs, genetic uniqueness (Gilberts) Address underlying condt. 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
Sulfation Sulfate depletion, toxic load, hepatic disease, genetics High sulfur foods, red. Glutathione, L-methionine, L-cysteine, Zn, Cu, Se, Mg, B6, B12, Mg, FA
Patrick Hanaway, MD Genova Diagnostic
Laboratories
19

• 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)

20

• 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

21

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)

22

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

23

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

24

• 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

25

• B. Heavy Metals (cont)
• 3. Treatment - best done once
  Lyme/coinfection load reduced
• Pharmacological Chelators DMPS
• 
  DMSA
• 
  EDTA
• 
  Penicillamine
• Non-pharmacological chelators Sauna
• 
  Alginate/Chlorella
• 
  Zeolite

26

• 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-as outlined
  earlier

27

• 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

28
Methylation Cycle
5,10 MTHF
Methionine
SAM
MSR
Methionine Synthase
MTHR
SAH
5 MTHF
Homocysteine
Homocysteine
CBS
Cystathione
Cysteine
Glutathione
Taurine
29

• B. Heavy Metals
• 4. Assess methylation in non-responders (cont)
• 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

30

• 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
• 
  Methyl B12 / Cyano B12
• 
  TMG (or DMG)
• 
  Folic/Folinic acid
• 
  P5P/B6
• 
  Reduced Glutathione

31

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