Amsterdam 16Point

Why Detoxify?

◼ Autoimmune Disease Risk ↑

◼ Parks CG, et al. Expert panel workshop consensus statement on the role of the environment in the
development of autoimmune disease. Int J Mol Sci. 2014; 15: 14269-14297.

◼ Cancer risk ↑

◼ Guyton, K., et al. Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate.
Lancet Oncology, Vol 16, No. 5, p490–491, May 2015

◼ ↑ Risk of COPD, Obesity, Diabetes

◼ Hancock et al., 2008; Chakraborty et al., 2009; Hayden et al., 2010; Slotkin 2011

◼ Toxins Increase Neuroinflammation through
Microglial Activation in Children and Adults

◼ Jones KL et al. Autism with intellectual disability is associated with increased levels of maternal
cytokines and chemokines during gestation. Mol Psych. 2017 Feb;22(2):273-279

◼ Traffic-related air pollution increased the risk of Parkinson's disease in Taiwan: A nationwide study.
Environ Int. 2016;96:75-81.

Endogenous & Exogenous Toxins:

Quinolinic Acid and Mold Toxins

◼ Quinolinic Acid is a neurotoxic metabolite of the L-
tryptophan pathway (used to make brain
neurotransmitters) that can damage nerves

◼ Lyme patients have been shown to have ↑ levels
of Quinolinic acid. ? Role in CNS dx ?Role for IV GSH
& antioxidant therapies ? Role for Probenecid

1) -Oxidative stress as a mechanism for quinolinic acid-induced
hippocampal damage: protection by melatonin and deprenyl
W.M.H. Behan, et al. British Jnl Pharm (1999) 128, 1754-1760

2) -Enhanced neuronal damage by co-administration of quinolinic acid
and free radicals, and protection by adenosine A2A receptor
antagonists W.M.H Behan et al. British Jnl Pharm (2002) 35, 1435-1442

3) -Quinolinic Acid Is Extruded from the Brain by a Probenecid-Sensitive Carrier System: A Quantitative
Analysis. Morrison et al, Jnl of Neurochemistry 1999, 72, 2135-2144

Toxins & Detoxification: The Role of

Glutathione/Liver Support

◼ IV GSH has been shown to be effective in a subset of
resistant Lyme patients

◼ IV GSH also addresses heavy metal burden, and mold, but
it is unclear which chemicals/toxins are being removed w/
treatment. Since GSH may have an effect within min’s in
select patients to improve CNS (f), is there an effect on
removing inflammatory cytokines & Quinolinic acid?

◼ Detoxification support is essential in Lyme-MSIDS

◼ Detox protocols would include Mag++, NAC, GLY, α lipoic
acid, DIM, sulforaphane, diet w ↑ protein, cruciferous
vegetables, oral/IV glutathione, PC, Butyrate, binders, MCP

◼ Brewer, J., Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome Toxins 2013, 5, 605-617

Optimize bowel health Insure hydration
(Probiotics, fiber, colon cleanses)

Minimize toxic Detoxification ↑Antioxidant
Exposure Principles Reserve

(air & H2O purifiers, clean diet) (alpha lipoic acid, diet)

Optimize Assist &
mitochondrial function
(NT factor, CoQ 10, NADH) Balance biotransformation
(NAC, Gly, B vit’s)

Detoxification & Nutritional Support:
Mold/Metal/Toxins

◼ Detoxification: Skin (FIR saunas), Colon (probiotics, fiber,
?Questran, cleanses/enemas), Kidneys (↑fluids), liver

(vit’s, min’s, herbs to ↑ phase I & II detox pathways)

◼ Mold detox: oral (? IV) PC Xchange, with GSH, NAC, ALA, N-
butyrate, binding agents (charcoal, clay, cholestyramine..)

◼ Nutritional Supplementation: NAC [1800-2400 mg], Gly, MCP
broccoli compounds (DIM, sulforaphane), αLA [300-600 BID],
MTV w/ min’s (Mag++[malate, up to 1000/d], Zn+ citrate [15-60
QD], iodine, copper, Se [200mcg]), K+ citrate [10meq BID], B
complex [↑B 1], methionine [600 mg], Mb [1-2 mg], silymarin

◼ Tokar V., et al. Chronic effects of fluorides on the pit-thyroid system in industrial workers" Gig Tr Prof
Zabol (9):19-22 (1989)Sulforaphane Treatment of Autism Spectrum Disorder (ASD). Singh, K. et al.,
Autism Ms PNAS Submission Final 08312014, Sept 14, 2014



Data Mining of MSIDS Variables:
V. Allergies

◼ Allergies: 163 (81.5%) of participants had allergies

◼ 90 (45%) had food allergies

◼ 43 (21.5%) had environmental allergies (e.g. seasonal
allergies, allergy to animals, etc.)

◼ 7 (3.5%) had high IgE levels

◼ 3 (1.5%) had high histamine levels (not all patients were
tested for histamine sensitivity or MCAD)

◼ 112 (56%) had drug allergies

◼ 12 (6%) had allergies categorized as “other”

◼ Manzel, A.; Muller, D. N.; Hafler, D. A.; Erdman, S. E.; Linker, R. A.; Kleinewietfeld, M. Role of
“Western diet” in inflammatory autoimmune diseases. Curr. Allergy Asthma Rep. 2014, 14, 404

Allergic/Sensitive Foods Can Increase
Inflammation

V: Allergies and Lyme-MSIDS

◼ Food allergies/sensitivities to wheat, dairy, corn, nuts,
shellfish, & food additives are common→ fatigue, HA’s,
allergic rhinitis, eczema, asthma, irritability, conc prob’s

◼ Check IgE & IgG levels [immediate hypersensitivity reaction
(IgE), or delayed hypersensitivity reaction (IgG)]. Check
zonulin levels (leaky gut), CDSA (Candida overgrowth,
calprotectin..) +/- breath test for leaky gut. Avoidance,
rotation diets, IgG26 (Xymogen) 2x/day, DAO may help

◼ Check histamine, tryptase, chromogranin A, urine PGD2
for pathogen induced mast cell activation disorder (MCAD)

◼ Red meat allergies likely result of lone star tick→ alpha-gal
sugar in beef, pork, venison: Hives, swelling, SOB, V+,
diarrhea, delayed anaphylaxis 4-6 hours after eating red
meat (chicken & turkey OK).

http://www.sciencedaily.com/releases/2014/02/140220102727.htm

Data Mining of MSIDS Variables:
6. Nutritional/Enzyme Deficiencies

◼ 76% had one or more nutritional deficiencies

◼ 5 (2.5%) had AA and 2 (1%) had fatty acid deficiencies

◼ 36 (18%) had iodine deficiencies

◼ 14 (7%) had copper deficiencies: 3 (1.5%) had deficiencies in

serum copper; 6 (3%) had deficiencies in red blood cell [RBC]
copper; 5 (2.5%) had deficiencies in plasma copper

◼ 31 (16%) had magnesium deficiencies: 3% had deficiencies

in serum magnesium; 13% had deficiencies in RBC magnesium

◼ 36 (18%) had zinc deficiencies: 22 (11%) had deficiencies in

serum zinc; 7 (3.5%) had deficiencies in RBC zinc; 7 (3.5%) had
deficiencies in plasma zinc; 105 (52.5%) had MTHFR mutations

◼ Prasad, A. S.; et al. Zinc supplementation decreases incidence of infections in the elderly: effect of
zinc on generation of cytokines and oxidative stress. Am. J. Clin. Nutr. 2007, 85, 837–844.

VI. Nutritional/Fnl Med Deficiencies

◼ Mag++ → Necessary in approximately 300 detox enzymes
in the body. Deficiency results in muscle spasm, tremors,
anxiety, Raynauds phenomenon, arrhythmias.. (also ?
Asthma., LBP, IBS…)

◼ Cu+→ SOD, superoxide dismutase (free radicals)

◼ Zn++ → Necessary in > 90 enzymes (alcohol
dehydrogenase, Phase I reaction, converts alcohols→
aldehydes. If low, biochemical bottlenecks may result, with
a shift to chloral hydrate and toxic brain symptoms)

◼ Testing: serum & RBC minerals (Mag++, Cu), AA & FA

◼ For deficiencies: minimum of 500 mg Mag++, 30-50 mg Zn,
3.125 mg iodine, 1 mg of copper. Check levels post chelation

◼ Metal-dependent gene regulation in the causative agent of Lyme disease, Troxell, B. et al. Front. Cell.
Infect. Microbiol., 15 November 2013

VII: Mitochondrial Dysfunction in Lyme-

MSIDS

◼ Mitochondrial membrane components are
especially susceptible to free radical damage
(exposed to O2 in ATP production)

◼ Certain nutrients are essential for proper mitochondrial (f)
and energy production, i.e., CoQ10, NADH, acetyl-L-
carnitine, essential phospholipids (NT factors), α-keto
glutarate, B vitamins

◼ Testing: lipid peroxides, 8 OH-dG, Organix test
(Metametrix) may provide indirect evidence through free
radical exposure; check mtDNA mutations ? DNA adducts

◼ Treatment: NT factors (glycosylated phospholipids, ATP
Fuel 5/d), CoQ10, NADH, L-carnitine, occasionally D-ribose,
alpha keto glutarate

◼ Seidman, M. Polyunsaturated PC in NT factor improves mitochondrial function. Anti Aging Med Nov
2001

Mitochondrial Damage 2° Medication

◼ Many different medications can adversely affect
mitochondrial function: analgesics,
antidepressants/antianxiety meds, cancer drugs,
cholesterol, DM & epilepsy meds, & tetracyclines

◼ Mitochondrial Diseases: linked to fibromyalgia, aging,
metabolic syndrome, atherogenesis, visual & hearing
problems, dementia and chronic Lyme disease!

◼ Consider mitochondrial regeneration post AB’s: NT

Factors (5/day), CoQ10 (100 mg 2-3x/day), acetyl-l-carnitine (1
gm BID), NADH (5 mg), D-ribose (5 gm BID), B vit’s, Mag..

◼ Nicholson et al. Lipid Replacement Therapy with a Glycophospholipid Formulation with NADH and
CoQ10 Significantly Reduces Fatigue in Intractable Chronic Fatiguing Illnesses and Chronic Lyme Disease
Patients. International Journal of Clinical Medicine, 2012, 3, 163-170.

◼ http://www.digitaljournal.com/life/health/tetracycline-antibiotics-disrupt-cellular-
mitochondria/article/428869#ixzz3VIZYQXzK

Data Mining of MSIDS Variables:
VII. Mitochondrial Dysfunction

◼ Defined by those who had positive responses to the
following mitochondrial support supplements: ATP fuel
(NT Factors, i.e., glycosylated phospholipids), Coenzyme
Q10 (CoQ10), acetyl-l-carnitine, d-ribose)

◼ 15 (7.5%) had mitochondrial dysfunction

◼ Published literature: up to 1/3 of patients with chronic
Lyme symptoms respond to lipid replacement therapy

◼ Dapsone combination therapy was highly effective in this
group of patients, making it difficult to see changes

◼ Horowitz, R.I.; Freeman, P.R. Precision Medicine: The Role of the MSIDS Model in Defining,
Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other
Chronic Illness: Part 2. Healthcare 2018, 6, 129.

Data Mining of MSIDS Variables:
VIII. Psychological Disorders

◼ Psychological issues: 177 (88.5%) participants self-
reported at least one psychological problem:

◼ 154 (77%) had depression

◼ 134 (67%) had anxiety

◼ 4 (2%) had Obsessive Compulsive Disorder (OCD)

◼ 11 (5.5%) had Post Traumatic Stress Disorder

◼ 9 (4.5%) had other psychological issues

◼ Bransfield, R. C. The Psychoimmunology of Lyme/Tick-Borne Diseases and its Association with
Neuropsychiatric Symptoms. Open Neurol. J. 2012, 6, 88–93

◼ Bransfield, R. C. Suicide and Lyme and associated diseases. Neuropsychiatr. Dis. Treat. 2017, 13,
1575–1587, doi:10.2147/NDT.S136137.

VIII: Psychological Dysfunction In
Lyme- MSIDS

◼ Psychological dysfunction is common & suicide is
possible

◼ Lyme and associated co-infections will cause
previous psychological patterns to intensify, or new
patterns to emerge (i.e., depression, anxiety, PTSD,
psychosis, OCD, manic-depressive disorder)

◼ Ask about previous psych hx, and refer for help!
◼ Treatment: Medications (SSRI’s, buproprion, folate,

Remeron, anxiolytics,), CBT (PTSD), Journey work
(Brandon Bays), EMDR, EFT (Neurofeedback), DNRS
Integrative: Herbs (SJW, Valerian, L-theanine),
homeopathy, meditation, yoga, Tai Chi..

Meditation/Yoga Improves Mental
Health

◼ Authors from JAMA reviewed 18,753 citations, & included
47 trials with 3515 participants

◼ Mindfulness meditation had moderate evidence of
improved anxiety, depression and pain

◼ Meditation also had an effect on increasing telomere
length (Blackburn, National Academy of Sciences in
December 2004) by ↑ telomerase activity

◼ Yoga also can have a positive effect on depression

◼ Meditation Programs for Psychological Stress and Well-being: A Systematic Review and Meta-analysis.
JAMA Intern Med. Published online January 06, 2014

◼ Kuyken W, et al. Efficacy of Mindfulness-Based Cognitive Therapy in Prevention of Depressive Relapse
An Individual Patient Data Meta-analysis From Randomized Trials. JAMA Psychiatry. 2016 Apr 27.

◼ Uebelacker LA, et al. Adjunctive yoga v. health education for persistent major depression: a randomized
controlled trial. Psychol Med. 2017 Apr 6:1-13.





IX: Neurologic Disorders in Lyme MSIDS

◼ Neurological manifestations with Lyme-MSIDS:

◼ Subjective: Headaches, visual disturbances,
hearing/balance issues, tinnitus, memory and
concentration problems, neuropathies

◼ Objective: cranial nerve palsies (optic neuritis, Bell’s palsy,
trigeminal neuralgia), MS presentations, ALS
presentations..

◼ Veterans are 2 X more likely to develop ALS: ? Tick bites, ?
Environmental toxins

◼ ? Role of HBOT: PLOS One 2013: Israeli research has shown
benefits in brain injury ? Treat early Alzheimer’s

◼ Lyme Disease –Induced Polyradiculopathy Mimicking Amyotrophic Lateral Sclerosis. Posted online on
January 7, 2014. (doi:10.3109/00207454.2013.879582)

Data Mining of MSIDS Variables:
IX. Neurological Dysfunction

◼ Neurological Dysfunction: 190 (95%) had at least
one or more neurological symptom/disorders:

◼ 188 (94%) had neuropathy
◼ 5 (2.5%) had Chronic Inflammatory Demyelinating

Polyneuropathy (CIDP)
◼ 3 (1.5%) had Multiple Sclerosis
◼ 2 (1%) had seizures
◼ 2 (1%) had other neurological issues (e.g. Parkinson’s

symptoms)

◼ Fallon, B. A.; Levin, E. S.; Schweitzer, P. J.; Hardesty, D. Inflammation and central nervous system
Lyme disease. Neurobiol. Dis. 2010, 37, 534–541, doi:10.1016/j.nbd.2009.11.016.

IX: Lyme, AD & The Brain: Symptoms Due

to ↑ Inflammation & Cytokine Production

◼ Fallon et al. Inflammation and central nervous system Lyme disease. Neurobiology of
Disease, 37, 2010, 534-541

◼ Pachner AR, Steiner I. , Lyme Neuroborreliosis: infection, immunity and inflammation Lancet
Neurology 2007 6:544-52

◼ Miklossy J. Historic evidence to support a causal relationship between spirochetal infections
and Alzheimer’s disease. Front. Aging Neurosci. 7:46. 16 April 2015.

◼ Tobranik previously showed inflammation ↑ AD sx

◼ Inflammatory markers and the risk of Alzheimer disease: the Framingham Study Edward
Tobinick MD. Neurology. 2008 Apr 1;70(14):1222-3

◼ Targeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative
Diseases. Frankola KA, Greig NH, Luo W, Tweedie D. CNS Neurol Disord Drug Targets. 2011
Feb 2

◼ Tumour necrosis factor modulation for treatment of Alzheimer’s disease: rationale and
current evidence. Edward Tobinick MD. CNS Drugs. 2009 Sep 1;23(9):713-25

◼ Anti-TNF-alpha reduces amyloid plaques and tau phosphorylation and induces CD11c-
positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Shi JQ, et al. J. Brain Res.
2011 Jan 12;1368:239-47

Data Mining of MSIDS Variables:
X. Endocrine Abnormalities

◼ Endocrine Abnormalities: 195 (97.5%)

◼ 121 (60.5%) had thyroid abnormalities

◼ 144 (72%) had adrenal abnormalities

◼ 82 (41%) had sex hormone abnormalities

◼ 136 (68%) had vitamin D deficiencies

◼ 3 (1.5%) had pregnenolone deficiencies

◼ 74 (37%) had DHEA abnormalities

◼ Berczi, I. The pituitary gland, psychoneuroimmunology and infectious disease.” In Friedman, H.,
Klein, T. W., Friedman, A. L., eds., Boca Raton, FL: CRC Press, 1996. pp. 79–109. In
Psychoneuroimmunology, Stress and Infection.; Friedman, H., Klein, T., Friedman, A., Eds.; CRC
Press: Boca Raton, FL, 1996; pp. 79–109.



X: Endocrine Abnormalities in MSIDS

◼ Cytokines may directly affect the HPA axis, and affect
hormone levels. Common abnormalities: abnormal adrenal
function and low sex hormone levels (low T), with low
T3/free T3 (decreased T4 conversion), increased rT3

◼ Common cause of resistant fatigue
◼ MSH, VIP, ADH: with mold & Lyme, the posterior pituitary

may also be affected. Check levels, consider
replacement/? MARCONS spray/? BEG/? Silver-mucopiricin
◼ Treatment: ? Cortef (hydrocortisone), Adrenal support (Vit
B6, pantothenic acid, Cordyceps, Ginsenosides,& Rhodiola),
Adrenal complex (adrenal glandular, PHP), ? B-HCG, DHEA
(Biosom, Metagenics) + pregnenolone 10-20 mg (hormone
precursors) Clomid (clomiphene), Testosterone/hormone
replacement, Arimidex (aromatase inhibitors),
selenium/iodine (thyroid support)

Endocrine Medications/Supplements

◼ Precursors: DHEA (2-3 pumps Biosom, held under the

tongue X 30 sec’s), pregnenolone (10-30 mg), iodine (225
mcg +), selenium (200 mcg). Check levels hormones!

◼ Adrenal: Cortef (5 mg/day to 25-30 mg/day, divided

doses. Rapid metabolizers, ? QID), Adrenal essence
(Xymogen, one BID), Adaptanall (2 am); Glandular: Adrenal
complex (PHP, 1-8 day), AdrenaLiv (Xymogen, aver 1-2/d)

◼ Sex Hormones: BHRT (Bi-Est), Progesterone (PO, cream)

100-200 mg (HS, ? Helps with sleep), Test troches (2.5-5 mg)
Clomid (1/2 50 mg 2-3x/week), Arimidex (1 mg/week),
Testoplex (Xymogen, mung bean extract 4 am)

◼ Thyroid: T3, T4 compounded, Synthroid, Armour..

XI: Lyme and Sleep Disorders

◼ Impaired sleep correlates directly with impaired
immune functioning

◼ Sleep and the immune system. Int J Immunopharmacol 1995;17:649-54
◼ Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome.

Adv Neuroimmunol 1995;5:39-56
◼ Adv Management of sleep disorders in fibromyalgia. Rheum Dis Clin North Am. 2002;28:53-65

◼ Sleep disorders are commonly associated with
chronic inflammatory diseases and chronic
age/stress disorders, such as RA, FM, and CFS.

◼ Lorton D et al. Neuroimmunomodulation. 2006;13(5-6):357-74. Epub 2007 Aug 6

◼ Chronic sleep restriction leads to elevations in IL-6
and pain symptoms in healthy volunteers

◼ M. Haack, et al. J Pain; April 2004, Supplement 1, Vol 5, 3

Data Mining of MSIDS Variables:
11. Sleep Disorders

◼ 98% had one or more sleep disorders:

◼ 23 (11.5%) had Obstructive Sleep Apnea (OSA)
◼ 1 (.5%) had Restless Leg Syndrome (RLS)
◼ 7 (3.5%) had Benign Prostatic Hyperplasia (BPH)
◼ 4 (2%) were in menopause/ 2 (1%) had high adrenals
◼ 1 (.5%) had medication induced sleep problems (? Caff)
◼ 189 (94.5%) had other sleep problems, i.e., difficulties

with insomnias, hypersomnias, circadian rhythm
disorders (secondary to Lyme and tick-borne diseases)

◼ Greenberg, H. E.; Ney, G.; Scharf, S. M.; Ravdin, L.; Hilton, E. Sleep quality in Lyme disease. Sleep
1995, 18, 912–916.

XI: Sleep Disorders in Lyme-MSIDS

◼ Causes: Lyme & co-infs, OSA, Stimulants, Caffeine,
Nocturia (BPH), Depression, Anxiety, Restless Leg
Syndrome, Shift worker Sx, menopause, ↑ cortisol

◼ Evaluation: Sleep Study ? MLST, DHEA/cortisol test

◼ Treatment : Activating Agents in the AM (Modafinil,
Buproprion (Wellbutrin), Sleep promoting agents in the PM
(Non-Benzo’s, ie Ambien, Lunesta, Sonata), that encourage stage
3/stage 4 REM sleep (pregabalin [Lyrica], doxepin, mirtazapine
[Remeron], Trazadone, Gabitril, Seroquel, 1/3 Amrix, anti-H, Xyrem..)

◼ CAM: 5-HTP/GABA-L theanine, Valerian, melatonin, PS

◼ Ford ES, et al. Trends in outpatient visits for insomnia, sleep apnea, and prescriptions for sleep
medications among U.S. adults: findings from the National Ambulatory Medical Care Survey 1999‐2010.
Sleep. 2014;37(8):1283–1293.

Doses of Medication/Supplements

◼ Trazadone: 50 mg to 200 mg average (QT): Helps anxiety
◼ Gabitril: 4 mg to 20 mg HS: hits GABA R’s. ? Mix w/GABA
◼ Lyrica: 50 mg to 200 mg HS: FM, neuropathy…
◼ Mirtazipine: 15 mg, lowest dose, ? 7.5 mg: depression
◼ Doxepin: 10 mg HS: anti-H1 effect
◼ Flexeril (Amrix, LA): 5 mg (1/3 capsule Amrix): spasm
◼ Atarax: 10-25 mg HS: anti-H1
◼ Xyrem: 3-4.5 ml four hrs apart (only for OSA, narcolepsy)
◼ Suppl’s: melatonin 1-10 mg HS, GABA-L theanine (oral, cream),

Kavinase, Cerenity PM, Herbsom, PS (Adrenavive), Mag (Optimag
Neuro, Mag malate), Honokiol (2 HS), SynovX calm (valerian root)

Other Sleep Tips

◼ Don’t nap: Daytime napping was significantly associated

with increased pain, depression, anxiety, fatigue, memory
difficulties and sleep problems:

◼ Daytime napping associated with increased symptom severity in fibromyalgia syndrome. Theadom et al.
BMC Musculoskeletal Disorders (2015) 16:13

◼ Treat Overlapping Medical Conditions: Chronic pain,

GERD, Urinary incontinence, Obesity w/OSA, Hot flashes..

Joffe H et al. A gonadotropin-releasing hormone agonist model demonstrates that nocturnal hot flashes
interrupt objective sleep. Sleep 2013 Dec; 36:1977

◼ Consider Cognitive Behavioral Therapy: helps 70-

80% of individuals with insomnia

◼ Morin CM,Contributions of cognitive-behavioral approaches to the clinical management of insomnia.
Prim Care Companion J Clin Psychiatry 2002; 4:Suppl 1:21

◼ Consider Dynamic Neural Retraining: (Annie Hopper)

◼ www.RetrainingTheBrain.com

XII: Autonomic Nervous System
Dysfunction/POTS

◼ The ANS involves elements of the CNS (brain & spinal cord),
and PNS (hypothalamus). Regulates breathing, BP/heart
rate, and digestion/elimination.

◼ The Parasympathetic nervous system: ↓ heart rate, and
BP, but ↑ gastric secretion & intestinal/bladder activity

◼ The Orthosympathetic nervous system ↑ heart rate and
BP, regulating the contraction of blood vessels

◼ There are 4 mechanisms responsible for low BP, fatigue,
dizziness & palpit’s: ↓ blood volume, ↓ venous tone
w/pooling, AI neuropathy, auto AB’s to nerve receptors:

◼ Jacob G., et al. Am J Med 1997;103:1008-1014; Verino,N Engl J Med 2000;343:847-855
◼ Vernino S. et al. Autoantibodies to ganglionic AchR’s in autoimmune autonomic neuropathies. N Engl J

Med 2000;343:847-855

XII: ANS Dysfunction/POTS & MSIDS

◼ Symptoms: Patients often complain of resistant
fatigue, dizziness (standing/changing position),
palpitations, concentration problems, anxiety,
pre/syncopal events

◼ BP is often low on exam (< 100/60), with associated
tachycardia (?> 100 BPM at rest) and anxiety

◼ Testing: Tilt table test, BP log with home readings,
sitting and standing BP & pulse (0, 3, 6, 9 min’s)
during a P.E. to evaluate ↓ BP, ↑ heart rates

◼ ? Antiganglioside AB’s ? Overlapping MCAD

◼ Gibbons C., et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of
neurogenic orthostatic hypotension and associated supine hypertension. J Neurol (2017) 264:1567–1582

Data Mining of MSIDS Variables:
12. ANS Dysfunction/POTS

◼ ANS Dysfunction/POTS: 83 (41.5%) of participants

◼ 23 (11.5%) had mild POTS (1-10 mm Hg drop in BP,
and/or 1-10-point increase in heart rate after standing)

◼ 41 (20.5%) had moderate POTS (11-29 mm drop in BP,
and/or 11-29-point increase in heart rate after standing)

◼ 9 (4.5%) had severe POTS (30+ ↑ in heart rate standing)

◼ 19 (9.5%) had dysautonomia (e.g. gastroparesis, chronic
constipation, bladder dysfunction, or dysfunction in
temperature regulation) & 2 (1%) had ‘other’ (tremors
and/or discoloration hands/feet)

◼ Kanjwal, K.; Karabin, B.; Kanjwal, Y.; Grubb, B. P. Postural orthostatic tachycardia syndrome
following Lyme disease. Cardiol. J. 2011, 18, 63–66.

XII: Treatment ANS Dysfunction/POTS

◼ Salt (3-4 grams/day, ? 1 gram tablets), ↑ fluids (2-3 liters)

◼ Licorice: (Metagenics, Licorice +, 2 am), Adrenal support

◼ Florinef: 0.1 mg PO starting dose, ↑ if inadequate
response. Long term effects: ? immunity, bone density

◼ Midodrine: ? 2.5 TID, gradually ↑ 5 mg TID, then 10 mg
TID. ½ life is 3-4 hours. Dose accordingly

◼ ? Northera (droxidopa) = Start 100 mg TID, gradually
increase Q 1-2 days to max 600 mg TID (100, 300 mg cap’s)

◼ Cortef (? Adrenal insufficiency), and/or B blockers (Toprol
XL 25 mg/day [if ↑ palpitations], increase as needed)

◼ Rarely clonidine (hyperadrenergic POTS), SSRI’s (Zoloft)

◼ Treat MCAD, Mold if present (? underlying etiol’s), + DNRS

Data Mining of MSIDS Variables:
13. Gastrointestinal Dysfunction

◼ G.I. Dysfunction: 159 (79.5%) had 1 or more GI abn’s:

◼ 10 (5%) had gluten Sensitivity/10 (5%) had celiac disease
◼ 2 (1%) had colitis
◼ 43 (21.5%) had Candida
◼ 15 (7.5%) had leaky gut/ 90 (45%) had food allergies
◼ 35 (17.5%) had parasites
◼ 17 (8.5%) had H. Pylori exposure
◼ 37 (18.5%) had gastroesophageal reflux disease (GERD)
◼ 0 % had a history of C. Difficile during treatment with dapsone
◼ 83 (41.5%) had ‘other’ gastrointestinal dysfunction (IBS)

◼ Rooney, P. J.; Jenkins, R. T.; Buchanan, W. W. A short review of the relationship between intestinal
permeability and inflammatory joint disease. Clin. Exp. Rheumatol. 1990, 8, 75–83.

Data Mining of MSIDS Variables:
14. Liver Dysfunction

◼ Elevated Liver Function Tests (LFTs): 148 (74%) had

one or more of the following transient elevation in LFTs
at some point during treatment:

◼ 90 (45%) had elevated AST

◼ 104 (52%) had elevated ALT

◼ 36 (18%) had alkaline phosphatase

◼ 47 (23.5%) had elevated T. Bilirubin

◼ 5 (2.5%) had ‘other’ (low albumin)

◼ Zaidi, S. A.; Singer, C. Gastrointestinal and hepatic manifestations of tickborne diseases in the United
States. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2002, 34, 1206–1212, doi:10.1086/339871.

◼ Shimizu, Y. Liver in systemic disease. World J. Gastroenterol. WJG 2008, 14, 4111–4119,
doi:10.3748/wjg.14.4111

Gastrointestinal Dys(f) & MSIDS

◼ Symptoms: unexplained gastroparesis, N+, V+, chronic

constipation (vagal nerve dysfunction), diarrhea, bloating

◼ Laboratory: unexplained↑ LFT’s after ruling out other

sources: hepatitis A,B,C, hemochromatosis, Wilson’s dx, α-
1-antitrypsin def, toxin exposure (VOC’s, carbon tet..),
drugs, fatty liver (NASH), ETOH, AI hepatitis, PBC, hyperlip

◼ Check above etiologies with ANS testing (BP/pulse
sitting/standing, ? HUT, small fiber bx..) & check viral AB’s,
PCR/RNA, Fe, TIBC, ferritin, Cu, ceruloplasmin, toxin panel,
US liver, gluten (S), ANA, AMA, SIBO, Candida, & TBD’s
(Lyme, RF, Ehr, Anapl, Bab, RMSF, Q-fever, Tularemia)

◼ Shimizu, Y. Liver in systemic disease. World J Gastroenterol 2008; 14 (26): 4111-4119

Treatment of Elevated LFT’s

◼ Treat source(s) of the problem (TBD, NASH….)
◼ Treat symptomatically, addressing etiologies:
◼ Milk thistle (ex: Xymogen Liver protect, one BID)
◼ Hepa #2 (TCM, Zhang) 2 PO BID
◼ MedCaps DPO (Xymogen) 1-2 PO BID
◼ NAC 600 mg BID, diet high in protein/cysteine
◼ Alpha lipoic acid (ALAMAX, 600 mg BID)/? GSH 1 g
◼ Selenium up to 200 mcg/day (needed for GST)

◼ Shedlofsky et al, In: Kimball ES, ed. Cytokines and inflammation. Boca Raton: CRC Press, 1991: 235-
261.

Data Mining of MSIDS Variables:
15. Pain Syndromes

◼ Pain Syndromes: 185 (92.5%) had migratory pain,
which other research has demonstrated is one of
the hallmark symptoms of active Lyme disease

◼ Lyme disease can ↑ pro-inflammatory cytokines
IL-1, IL-6, and TNF-α→↑ fatigue & pain as well as
PNS and CNS neurological symptoms

◼ Inflammatory cytokines can be produced by not
only infections but environmental toxins

◼ Sommer, C., et al. Recent findings on how proinflammatory cytokines cause pain: peripheral
mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci. Lett. 2004, 361, 184–187

◼ Loggia, M. L. et al. Evidence for brain glial activation in chronic pain patients. Brain J. Neurol. 2015,
138, 604–615, doi:10.1093/brain/awu377.

XV: Pain Syndromes & Lyme-MSIDS

◼ Some LD patients present with severe pain, and may be on
high dose narcotics. Narcotics may interfere with deep,
regenerative sleep, + → rebound pain and headaches

◼ Consider a pain management specialist for resistant pain
and detox program if appropriate. ? Tried COX-2 inhibitor

◼ LDN has been shown to be beneficial in decreasing pain,
esp. when used with Nrf2 antagonists, Celebrex..

◼ Consider a trial of LDN (4.5 mg HS), NAC + GSH (1-2 gm/d) +
PC, + ALA & detox strategies to ↓ inflammatory cytokines:
MCP, drainage remedies (PEKANA, 15 drops TID of each),
Nrf2 activators (curcurmin, green tea, resveratrol, sulforaphane),
omega 3 FA’s, min’s (MinRx, Xymogen), chlorella, binders
(charcoal, clay, CSM..), trisalts/Na bicarb, detox baths..

XVI: Deconditioning & Lyme-MSIDS

◼ Depression has been associated with higher levels
of proinflammatory cytokines, i.e. IL-6 and tumor
necrosis factor α. Exercise → antidepressant effect
& high levels of exercise ↓ inflammatory cytokines

◼ SSRIs also ↓ cytokines, & ↑ TNF levels seem to
predict resistance to SSRI treatment (?Zoloft, Paxil)

◼ Patients need to be placed on a regular exercise
program once their physical condition permits.
Start slow and refer to PT/OT if necessary

◼ Rethorst CD et al. Pro-inflammatory cytokines as predictors of antidepressant effects of exercise in
major depressive disorder. Mol Psychiatry 2013 Oct; 18:1119;

◼ NEJM JW Psychiatry Mar 29 2010

Data Mining of MSIDS Variables:
16. Deconditioning

◼ Deconditioning: 64 (32%) were disabled and/or in
physical therapy

◼ Patients who benefitted the most from PT
suffered from significant musculoskeletal pain
and/or POTS/dysautonomia

◼ Crane, J. D., et al. Massage Therapy Attenuates Inflammatory Signaling After Exercise-Induced
Muscle Damage. Sci. Transl. Med. 2012, 4, 119ra13-119ra13, doi:10.1126/scitranslmed.3002882.

◼ Moser, M. M. C. Treatment for a 14-Year-Old Girl With Lyme Disease Using Therapeutic Exercise and
Gait Training | Physical Therapy | Oxford Academic Available online:
https://academic.oup.com/ptj/article/91/9/1412/2735165 (accessed on May 27, 2018).

◼ Nazıroğlu, M., et al. Vitamins C and E treatment combined with exercise modulates oxidative stress
markers in blood of patients with fibromyalgia: A controlled clinical pilot study. Stress 2010, 13, 498–
505, doi:10.3109/10253890.2010.486064.

16 Point MSIDS Map: Evaluate all of
the Sources of Inflammation

◼ Primary Sources: ◼ Downstream effects:

◼ 1) Chronic infections ◼ 7) Endocrine disorders:
low T, low adrenal (f)
◼ 2) G.I.: Dysbiosis of
intestinal bacteria ◼ 8, 9) Neurological,
Psychological dysfunction
◼ 3) G.I. : Leaky gut w/ Food
allergies and sensitivities ◼ 10) POTS/dysautonomia

◼ 4) Sleep disorders:↑ IL-6 ◼ 11) Mitochondrial Dys(f)

◼ 5) Environmental toxins ◼ 11) Pain Syndromes
(heavy metals, mold…) ◼ 12) Liver Dysfunction

◼ 6) Nutritional Deficiencies ◼ 13) Autoimmune phen.

What is the Common Denominator?

Multiple (Intracellular) Infections + toxins +
nutritional deficiencies, leaky gut, food all’s +↓
sleep→ Inflammation & Immune Dysfunction

◼ Borrelia, Bartonella spp., Mycoplasma spp., Chlamydia,
tularemia, Brucella, Ehrlichia, Anaplasma & Rickettsial
infections (RMSF, Q-fever) are all intracellular infections

◼ Intracellular infections may be resistant to therapy &
located in biofilms, persisting despite standard therapies

◼ Girschick, H. J., Huppertz, H. I., Russmann, H., et al. “Intracellular persistence of Borrelia burgdorferi in
human synovial cells.” Rheumatol Int 16 no. 3 (1996): 125–32.

◼ Ma, Y., Sturrock, A., and Weis J. J. “Intracellular localization of Borrelia burgdorferi within human
endothelial cells.” Infect Immun 59 no. 2 (February 1991): 671–78.

◼ Montgomery, R. R., Nathanson, M. H., and Malawista, S. E. “The fate of Borrelia burgdorferi, the agent
for Lyme disease, in mouse macrophages. Destruction, survival, recovery.” J Immunol 150 no. 3
(February 1993): 909–15.

Mycobacterium Drugs + Essential Oils
Affect Lyme, Co-infections & Biofilms

◼ Recent scientific research has identified Lyme as a
“persister” bacteria, similar to TB and leprosy

◼ Persisters are a small fraction of quiescent bacterial cells
(stationary phase) that survive lethal antibiotics but can
regrow leading to post-treatment relapse. Ex’s: TB, leprosy,
syphilis, endocarditis, biofilm infections

◼ Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells. Sharma
B, et al. Antimicrobial Agents And Chemotherapy, pii: AAC.00864-15. Online first, 2015 May 26

◼ Persisters, persistent infections and the Yin–Yang model, Ying Zhang; Emerging Microbes and
Infections (2014) 3, e3; doi:10.1038/emi.2014.3;

◼ Zhang, Y (2015) Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication
Achieved by Using Daptomycin, Cefoperazone and Doxycycline. PLoS ONE 10(3): e0117207

◼ Identification of new compounds with high activity against stationary phase Borrelia burgdorferi from
the NCI compound collection. Zhang, Y. Emerging Microbes and Infections (2015) 4, e31

www.cangetbetter.com

PZA in Lyme, Bartonella, Behcet’s Dx:

Horowitz & Freeman JSM Arthritis, July 2016

◼ Evidence of persistent Bartonella, Tularemia, HHV6

Persistence: The Biofilm Barrier to

Treatment

• Microbial biofilms are largely responsible for the
recalcitrance of many infections to conventional anti-
microbial therapy (C. diff, Candida, SBE…)

• Up to 1000-fold decreases in antimicrobial
susceptibility have been observed for biofilms

• Stewart PS. Mechanisms of antibiotic resistance in bacterial biofilms. Int J Med Microbiol.
2012:107–113.

• Sapi E, et al.(2012) Characterization of biofilm formation by Borrelia burgdorferi In vitro. PLoS
ONE 7(10)

• Sapi E, Balasubramanian K, Poruri A, Maghsoudlou JS, Socarras KM, Timmaraju KR., et al.
Evidence of in vivo existence of borrelia biofilm in borrelial lymphocytomas. Eur J Microbiol
Immunol. 2016;0:1–16.

Treat the Infections: Biofilm Busters

• Dr Ying Zhang et al: “oregano, cinnamon bark, and
clove bud completely eradicated all viable cells
without any regrowth in subculture”

• Biofilms: Stevia, herbal extracts (Biocidin, oregano
oil): liposomal formulations help ↑ penetration of
herbal compounds into biofilms. Use all three!

• Feng J, et al. Front. Med, 11 October 2017

Front. Med., 11 October 2017 | https://doi.org/10.3389/fmed.2017.00169

Selective Essential Oils from Spice or
Culinary Herbs Have High Activity
against Stationary Phase and
Biofilm Borrelia burgdorferi

Jie Feng1, Shuo Zhang1, Wanliang Shi1, Nevena Zubcevik2,

Judith Miklossy3and Ying Zhang1*