1

© P

urp

ose Inc.

Welcome!

This presentation is copyrighted by Purpose Inc. with all rights reserved, available for student reuse strictly subject to the terms outlined in the student program agreement.

2

© P

urp

ose Inc.

Tracy’s health counseling

certification is from Columbia

University for the Institute of

Integrative Nutrition in New

York.

She has completed ongoing

training and is working on a

certification in understanding

the root causes of chronic

illness with the Institute of

Functional Medicine and on an

additional Masters degree in

Human Nutrition at Bridgeport

University.

She holds a Masters degree in

Engineering from MIT and a

Masters degree in Management

from The Sloan School at MIT.

SAFM™ Deep Dive Clinical Courses

Take lots of notes! The more often you see these connections, the more readily you will be able to recall them in your practice.

An online Q&A bulletin board for this course is available to you for follow-up at any time (on the SAFM course page). Make use of this option to expand your and others’ learning. Please note this tool is for expanding and clarifying questions on the course material itself and not detailed case study review.

Plan to review this course material again, at least once more in the short-term (and ideally a third time later in the future to help you retain this knowledge).Remember: Repetition breeds Retention.

If you ever have any technical trouble with your SAFM membership or site access, please don't hesitate to contact our team at Admin@SchoolAFM.com

3

© P

urp

ose Inc.

Fibromyalgia Demystified

Part 2

This presentation is copyrighted by Purpose Inc. with all rights reserved, available for student reuse strictly subject to the terms outlined in the SAFM student program agreement.

4

mm

Agenda

Root Cause Reminders

Disease Begins in the Gut: SIBO, Intestinal Permeability, & LPS

Pain Sensitization and Serotonin

Mitochondrial Dysfunction

Case Study

Recommendations Summary

5

Getting to the Roots

6

Defining Fibromyalgia: The Bottom Line?

“A disorder characterized primarily by immense confusion and disagreement on the part of both patients and healthcare providers as to(1) what a person actually has (tyranny of the diagnosis) (2) what is actually causing the dynamic (primary vs. secondary causes)

and(3) what treatment is merited & effective (standard of care vs. research findings)all while the patient is still experiencing very real suffering.

- Tracy

7

Fibromyalgia Defined

True Fibromyalgia is body-wide, “global” perceived pain. Not localized to specific body parts or segments of the body (e.g. right vs left).

Fibro patients tend to be generally sensitive to a wide range of things, “irritable everything”. It’s not just about body pain.

Fibro is typically accompanied by many other chronic symptoms such as strong fatigue, sleep, memory and mood issues. Also commonly…

Insomnia/sleep disruption

Irritable bowel syndrome

“Fibro Fog” issues with cognitive processing, recall, or reasoning ability

Extreme fatigue (including ‘waking up exhausted’)

Mood disorders e.g. depression, anxiety, mood swings

8

mm

“The presence of numerous abnormalities in FM muscle structure and biochemistry has been well established by the work of many investigators.

This information – this reality – has never ceased to exist; rather, it has simply been buried by an avalanche of drug-sponsored articles promoting the primary central sensitization model and the corresponding “need” and “rightness” of endless drug treatment.”

- Dr. Alex Vasquez, ND, DO, DC, FACN

International College of Human Nutrition and Functional Medicine

Peeling the Onion

9

Root Causes of Fibromyalgia

Genetic and familial factors

Early-life emotional trauma or crisis

Gut dysbiosis, often SIBO

Intestinal permeability and endotoxicity from LPS (lipopolysaccharides)

Insufficient level or insufficient action of serotonin

Increased level or increased action of glutamate

Impaired ATP production from mitochondria

Increased oxidative stress

And all of the items we covered in Part 1 can be exacerbating factors!

10

Fibromyalgia Interconnectedness

Early-lifehypervigilance programming

Dysbiosis / SIBO

Intestinal Permeability and GI Dysfunction

Possible Genetic bias

Possible Genetic bias

Endotoxicity(e.g. LPS)

Compromised Immunity

Sympathetic/Stimulatory dominance in nervous system

Hypersensitivity/Pain

Lower serotonin state

Other inflammation (e.g. food sensitivities)

Poor sleep

Mitochondrial Dysfunction

Low Vitamin D(and A, Mg, Zn, etc.)

Stress

Poor Eating Hygiene, Poor Digestion

Toxicity (e.g. heavy metals)

Medications

11

Dis-ease Begins in the Gut.

Again.

12

mm

“Dysbiosis is not so much about the microbe as it is about the effect of that microbe on a susceptible host; in other words, it is about the relationship between host and microbe.”

- Dr. Gerry Mullin

Professor of Gastroenterology

Johns Hopkins University

It’s All About Relationships

13

mm

Who's the Host?

● We have hundreds of trillions of microbes within us! Together they are the largest “organ” in the GI tract (~ 4 lbs).

● Approximately 500 different species – bacteria, yeast, fungus, parasites - all competing for space and food and nutrients.

● These microbes eat residue from our diet (e.g. fiber, sugars, maldigested protein or starches) and secrete vitamins, beneficial fats (SCFAs), and (sometimes) toxins.

● Balanced bacteria in our gut helps to keep our immune system calm and not over-reactive (e.g. allergy, asthma, inflammation such as arthritis, or auto-immune illness).

● It is normal (and well-tolerated in most people) to have small amounts of potentially pathogenic microbes (e.g. H. Pylori, C. Albicans)

● Disease can begin with microbes in the gut in many ways: Toxic microbes (e.g. clostridia difficile, H Pylori, C Albicans), Lack of endemic beneficial microbes, or Overgrowth of endemic (normally commensal) microbes.

Our health depends on the health of our microbial partners: beneficial bacteria

14

14 DistributionBillions

Millions*

Billions

Trillions and Trillions and Trillions...

Mouth/

http://www.livescience.com/515-bacteria-thrive-hostile-human-bellies.htmlOr a more technical review of the same: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334644/

Helicobacter Pylori

15

15

SIBO (Small Intestinal Bacterial Overgrowth)

Normally there are 100,000 times more microbes in the colon (large intestines) than in the small intestines.

Location, location! Simple carbohydrate digestion takes place higher up in the small intestines than starches.

SIBO results when that higher density of bacteria in the colon creeps back up into the small intestines – and gets access to a much larger food source (more starches and some sugars). An overabundance of these bacteria’s metabolic processes is what wreaks havoc on the gastrointestinal system in SIBO.

More than 75% of those with IBS symptoms test positive for SIBO. IBS typically includes bloating, flatulence, GI cramping, and irregular bowel movements. **

Typically diagnosed with a lactulose breath test (measuring the timing of hydrogen and methane expelled after ingestion of the sugar).

Typically bacteria expelling more methane cause constipation; the presence of more hydrogen counteracts the methane and may lead more often to looser stools .*

Comprehensive stool testing may not show major abnormalities (may show elevated SCFAs but not necessarily). BUT can be helpful for identifying contributing issues (e.g. poor digestion, low SCFAs, secondary pathogens. Organic acids testing may show elevated levels of Indican.

Remember: the culprits in SIBO are not “bad” bacteria.*** They are typical, commensal bacteria in the wrong place in the gut, wreaking havoc!

SIBO is defined as a high density of microbes in the small intestines. The offenders vary and typically might include Escherichia coli, Streptococcus, Bacteroides, Enterococcus, Klebsiella, and Clostridium species. Archaea e.g. methanobrevibacter smithii.

* http://jama.jamanetwork.com/article.aspx?articleid=199251#REF-JCR40043-38** Pimentel, Mark, “A New IBS Solution”, p. 62-65.*** http://www.medicine.virginia.edu/clinical/departments/medicine/divisions/digestive-health/nutrition-support-team/nutrition-articles/zaidelarticle.pdf

16

Date of download: 1/17/2013Copyright © 2012 American Medical

Association. All rights reserved.

From: Small Intestinal Bacterial Overgrowth: A Framework for Understanding Irritable Bowel Syndrome

JAMA. 2004;292(7):852-858. doi:10.1001/jama .292.7.852

A, In the normal gut, easily digestible starch undergoes complete digestion and absorption within the proximal small intestine and is not available for fermentation in the distal ileum and colon where bacterial colonization is the greatest. In contrast, gas production results from bacterial fermentation of poorly digestible starch that is not assimilated by the proximal gut. B, In small intestinal bacterial overgrowth, the concentration of bacterial flora increases proximally allowing fermentation of both easily digestib le and poorly digestible starches.

17

17

SIBO Testing

Validity of breath testing has been strongly challenged. Clinical study results are highly variable and have struggled to demonstrate high results in IBS patients vs. in controls. * Test preparation is critical

Lactulose or glucose challenge; both have limitations. Neither is optimally selective.** Risk of under-diagnosing!

Choose wisely. Should measure both methane and hydrogen. Should test for at least a full two hours.

At-home test kits for SIBO e.g. Commonwealth Labs and Gut-Chek are becoming increasingly available Test preparation per instructions is key!

Address dysmotility first to maximize likelihood of viable results.

Normalization of breath levels correlates well with symptom improvement. ***

** https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155069/

*** https://www.ncbi.nlm.nih.gov/pubmed/12591062

* https://www.ncbi.nlm.nih.gov/pubmed/18371134 and http://pdf.medrang.co.kr/Kjg/056/Kjg056-04-06.pdf and https://www.ncbi.nlm.nih.gov/pubmed/22472730 and https://www.ncbi.nlm.nih.gov/pubmed/20467896

18

18

SIBO & Intestinal Permeability Risk Factors

Drugs Especially NSAIDs (damage mucosal layer), hormones (e.g. OCP, steroids) and those affecting serotonin

(e.g. SSRIs), PPIs and others which suppress stomach acid, antibiotics by decimating endemic bacteria and lowering SCFAs and also increasing toxic bacterial release.

Microbial overgrowth via byproducts which erode the mucosal lining

Low levels of endemic, beneficial bacteria

Low Vitamin D as well as other key nutrients such as zinc and Vitamin A

Moderate alcohol intake

Poor immune function. Nutrients above but also low WBCs, secretory IgA, etc..

Intake of pesticides/herbicides and other chemicals, artificial ingredients

Persistent stress. High cortisol increases permeability, impairs immune system

Gluten consumption (may promote greater zonulin secretion)

Poor Migrating Motor Complex function

Poor digestion e.g. low stomach acid, pancreatic output or bile

Poor eating hygiene Can cause many other above e.g. poor digestive secretions due to

sympathetic nervous system mode, poor motility, grazing or frequent meals limits MMC waves, overconsumption of water can dilute stomach acid.

* See the posted course document “Intestinal Permeability and Disease” for more details.

19

19

SIBO Rebalancing and Healing

Typically non-absorbed antibiotics(e.g. rifaximin) are used to counterSIBO. For archaea, this is often paired with neomycin. Antibiotictherapy may increase the risk of yeast or fungal overgrowths(or antibiotic resistant bacteria).

SIBO recurrence rate is high: 9 mos after antibiotic treatment was 44%. ** As we know, if you don’t eliminate the root cause, dis-ease returns! Sometimes, with a vengeance.

Herbal antimicrobials are as effective or better than rifaximin. *** This study’s herbal regime included 2 capsules twice daily of Biotics’ Dysbiocide and FC Cidal –or- Metagenics’ Candibactin-AR and Candibactin-BR.

Remember: cellular metabolism affects all body tissues. In stubborn cases, it may be necessary to support adrenal and/or thyroid function prior to antimicrobial therapy (or coincident) to ensure immune system strength.

Often critical to boost digestion to minimize microbial food fodder (the “buffet”) with digestive enzyme support (stomach acid and/or bile support as appropriate).

* Excellent slideshow on SIBO is here: http://www.slideshare.net/AdamRindeND/small-intestinal-bacterial-overgrowth-update-2015** https://www.ncbi.nlm.nih.gov/pubmed/18802998*** https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030608/

20

20

IBS Relief During SIBO Healing

Spasms (magnesium glycinate (~400mg, 1-2x/day), peppermint/fennel/ginger oils (as directed, 2-4x/day but do not use if there is acid reflux))

Constipation (magnesium citrate (as above, at night), stimulating herbs temporarily if needed, especially while using antimicrobials (e.g. senna, Dr. Schulze Formula #1), as directed))

Diarrhea (activated charcoal, Bentonite clay, L. Plantarium, L. Rhamnosus, S. Boulardi, add soluble fiber to diet e.g. chia seeds, banana). Note: I don’t typically recommend psyllium husks with SIBO right away as too much risk of worsening in the short-term.

Bloating (activated charcoal, low residue diet, digestive enzymes )

B12 deficiency (common in SIBO as microbes disconnect B12 and intrinsic factor, methylcobalamin and stomach acid support – see Gut 101 course)

Mucosal damage may impair absorption of other nutrients as well, especially minerals and fats and fat-soluble vitamins. Wise labwork includes RBC Zinc, RBC magnesium, Vitamin A, Vitamin D. Fecal fats from a comprehensive stool test may also be helpful.

Stress management (e.g. the right amount of exercise, acupuncture, meditation, gratitude journaling, healing visualization). Restorative sleep is also key! Sleep remains a key Rapid Relief focus, especially in Fibromyalgia.

21

21

SIBO Healing Diet

A low “FODMAP” diet is often recommended for IBS and SIBO (see course handout for specific guidelines). My experience is that this is hard to navigate.

I have had good success recommending a “Starve 'Em Out” Diet (this is similar to the “Specific Carbohydrate Diet” but has some differences). Specifically include

Vegetables, clean protein, ample healthy fats, nuts and seeds, fresh fruits (If necessary, consume only cooked vegetables & fruits to minimize bloating and cramping during initial healing stages.)

Legumes as tolerated (and perhaps necessary for dietary variety and protein)

Teach your clients how to prepare legumes to increase ease of digestion e.g. soaking at least 24 hours with water and vinegar, cooking thoroughly. If using from a can, choose BPA-free brands and rinse very thoroughly before use.

100% gluten and dairy free

No added sugars or artificial sweeteners (xylitol or stevia are usually fine, if a must-have)

No grains. Use veggie starches (e.g. sweet potato).

Ideally no alcohol, but definitely no beer, wine, cider, and no sweetened mixers.

No sugar alcohols (beware chewing gum and mints).

Most importantly, avoid in-between-meal snacking (to maximize cleansing waves).

Each person is different and may have unique intolerances give the SIBO (plus remember that personal food sensitivities would be on top of any general plan such as this).

22

22

Gut Healing 5Rs

Order of operations is important, BUT each patient or client is unique. Especially for fibromyalgia relief, these steps will overlap and will likely come in close succession to balance relief and healing as priorities.

Remove (e.g. harmful microbes, allergen/sensitivity foods, foods that feed undesired microbes, make sure no constipation)

Replace (e.g. digestive enzymes, stomach acid support, bile acids, herbal remedies to boost immune system insufficiency, adrenal and/or thyroid support)

Re-innoculate (probiotics, prebiotics)

Repair (villi regeneration, nurturing mucosal layer, increasing SCFA (e.g. butyrate) with larch gum or other fiber additions)

Rebalance (stress relief, long-term diet changes, attitude)

23

23

SIBO: Rebalancing the Microbes

Antimicrobial herbs

There are MANY options – and formulas available to accommodate various allergies or sensitivities. For example, berberine, uva ursi, sage, oregano, thyme, ginger, licorice, garlic. I often recommend Metagenics CandiBactin-AR and -BR at max dosage 3x/day for two to three months. Use these agents in daily food as well, especially garlic, ideally raw if tolerated.

Non-absorbed antibiotics (e.g. Rifaximin, xifaxin) might be necessary (especially if stooltest confirms high levels of specific pathogenic microbes with acute symptoms),

but many of my clients have gotten relief without them.

If significant relief is not achieved after ~3 weeks, I recommend stopping antimicrobials,adding prebiotics (yes!), and starting 2 weeks of a biofilm-disrupting formula

e.g. Klaire Labs Interfase and resuming antimicrobials after first ~3 days.

Probiotics

For SIBO, my top recommendation now is a mixed HSO-soil-based organism formula e.g. PreScript Assist. Start slowly (1/2 cap/day until well tolerated) and build to taking 1 cap twice daily for 30 days; then reduce back to 1/day. If this is too strong, consider Garden of Life Primal Defense Ultra.

For clients with compromised immune systems or taking immunosuppressive drugs, I recommend sticking with endemic human probiotic clients. Choose ones that includes L. plantarum and/or L. rhamnosus (and S. Boulardi if yeast is tolerated)e.g. Metagenics’ Acute Care or Klaire Lab’s TherBiotic Complete.

24

24

SIBO: Healing the Gut

These systemic effects (fibromyalgia) of SIBO are evidence of damage to the intestinal mucosal layer and intestinal permeability.

For ongoing healing (and relief!), healing the gut lining and sustaining strong barrier function is key.

L-glutamine is helpful to heal villi for poor nutrient absorption and leaky. However, use caution in those with Fibromyalgia and anyone with strong anxiety to avoid exacerbating glutamate surplus/sensitivity.

Ensure Vitamin D sufficiency to prevent future permeability.

Mucilaginous herbs are key to support mucosal layer regeneration such as slippery elm, marshmallow, DGL, and zinc carnosine.

My top recommendation is Designs for Health G.I. Revive, which combines these in a base of L-glutamine for ease but relatively low-dose glutamine.

Thorne’s G.I. Encap is a good option which avoids glutamine entirely.

Foods which naturally help to soothe the gut lining include okra, chia seed, ground flaxseed, artichoke, legumes, gelatin (e.g. bone broth). Collagen powder can be added to a daily smoothie as well.

25

Fibromyalgia & SIBO

Remember: IBS is very common in Fibro. Diagnosed in up to 81% of those with a Fibromyalgia diagnosis (significant variability depending on the study). #

Abnormal hydrogen breath tests (for SIBO) were found in 100% of Fibro patients and 84% of those diagnosed with IBS (compared to ~15% for controls). Hydrogen breath abnormality was higher in Fibro patients than in those with just IBS. The degree of somatic pain correlated significantly with the severity of the hydrogen breath elevation.**

In another study, of 123 Fibro patients, 78% were found to have SIBO which was treated with antibiotics. Dramatic improvements in their IBS and Pain symptoms were achieved after antibiotic therapy and validation of SIBO elimination or improvement. *

72% of Fibro patients have enhanced intestinal permeability (compared to ~2% of controls). ***

42% of these did not have any GI symptoms. A key concept to remember!

# https://www.ncbi.nlm.nih.gov/pubmed/16614951 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921083/ and https://www.ncbi.nlm.nih.gov/pubmed/15361320 and https://www.ncbi.nlm.nih.gov/pubmed/12879267* http://www.tandfonline.com/doi/abs/10.1300/J094v09n03_10** https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1754959/pdf/v063p00450.pdf*** https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1754959/pdf/v063p00450.pdf

26

Intestinal Permeability, LPS & Fibro

“The truth about a Leaky gut is like Las Vegas… What happens in the gut does not stay in the gut.” Dr. Alessio Fasano

The systemic body becomes exposed to what was supposed to be isolated within the intestines (that is “outside” the body): partially digested food, microbes and their byproducts (many of which are toxic), and chemicals. This can trigger a heightened immune response and downstream dysfunction from the toxicants.*

Intestinal permeability (IP) increases the likelihood of food sensitivities and immune reactions to microbial debris (e.g. LPS, bacterial DNA) and also byproducts (e.g. d-lactate, hydrogen sulfide).

SIBO increases the risk of IP. Hydrogen sulfide gas in the intestines breaks downthe protective mucosal layer and

encourages permeability. **

* See the posted course document on Intestinal Permeability and Disease. Also, an excellent educational slideshow on SIBO and intestinal permeability is here: http://www.slideshare.net/AdamRindeND/small-intestinal-bacterial-overgrowth-update-2015** https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2890937/ and http://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(16)00013-7 and http://www.medscape.com/viewarticle/732378_10?

27

Fibromyalgia & SIBO & LPS

Lipopolysaccharides (LPS, or Endotoxins) are part of the outer membrane of the cell wall of certain Gram-negative bacteria. *

LPS build-up increases intestinal permeability. LPS will provoke a strong immune reaction when it enters the blood after the intestinal barrier is breached. *

SIBO can create elevated levels of d-lactate from certain bacteria which impairs mitochondrial function (measurable in urine in organic acids test). The presence of these microbes and the higher levels of d-lactate have been confirmed in Chronic Fatigue Syndrome. There is a theory that excess hydrogen sulfide is a key player in CFS too. # (D-lactate is also a marker on most organic acid tests.)

Resulting inflammation from LPS can penetrate the blood-brain barrier and affect other systemic tissues. Fibro patients do not necessarily have elevated, systemic inflammation markers (e.g. CRP, ESR). However, they do have increased secretion of specific cytokines (e.g. IL-8) in cerebrospinal fluid (and not necessarily in the blood) .**

* http://textbookofbacteriology.net/endotoxin.html and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871685/ and http://www.nature.com/emm/journal/v42/n12/full/emm201084a.html and https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-5-37** http://rheumatology.oxfordjournals.org/content/40/7/743.full and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666439/ and # http://iv.iiarjournals.org/content/23/4/621.long and https://sqmymas.files.wordpress.com/2013/12/nueva-hipc3b3tesis-sobre-la-causa-del-sfc-desregulacic3b3n-del-sulfuro-de-hidrc3b3geno-2008-inglc3a9s.pdf

28

Fibromyalgia & SIBO & LPS - 2

Pain induction in Fibromyalgia is not a typical prostaglandin-induced mechanism (this is why NSAIDs are often not helpful and wreak havoc on the GI tract at the same

time.) Rather, both IL-8 and IL-6 are found to be elevated in these patients (and not those with other pain syndromes). IL-8 specifically induces sympathetic dominance in the nervous system and causes pain amplification. ***

“The immune response to bacterial antigen in SIBO provides a framework for understanding the hypersensitivity in both fibromyalgia and IBS.”*

“…altered gut microbiota in SIBO may play a role in the induction of somatic or visceral hypersensitivity, with affected patients meeting the diagnostic criteria for IBS, Fibromyalgia, or both disorders.”**

SIBO commonly impairs nutrient absorption which might involve key nutrients involved in Fibro exacerbation (e.g. Vitamin D, magnesium). Some microbes can cause bile acid deconjugation, leading to fat malabsorption.

Exposure to LPS causes increased sensitivity to painful stimuli. #

* https://www.ncbi.nlm.nih.gov/pubmed/15316000** http://www.medscape.com/viewarticle/568375_1# https://www.ncbi.nlm.nih.gov/pubmed/15474652*** https://www.ncbi.nlm.nih.gov/pubmed/16855138 and https://www.ncbi.nlm.nih.gov/pubmed/23124693 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372266/ and https://www.researchgate.net/publication/284722475_IL-8_and_IL-6_primarily_mediate_the_inflammatory_response_in_fibromyalgia_patients

29

Fibromyalgia & SIBO Resolutions

Moderate exercise has been shown to decrease both IL-8 and IL-6 in fibromyalgia patients and (perhaps unexpectedly) reduce pain symptoms. ##

Complementary therapies that involve calming the mind and both exercising and focusing on the body have been shown to be effective in reducing symptoms (e.g. tai chi, yoga, Mind/Body interventions in general, meditation-based interventions, mindfulness-based stress reduction, hypnosis or guided imagery). #

Individuals with Fibromyalgia with confirmed SIBO who took antibiotic therapy (and had confirmed SIBO resolution) experienced dramatic improvement in both gastrointestinal and body pain symptoms. *

Customized treatment that includes both gut microbial balance as well as hormone insufficiencies (e.g. thyroid) resulted in dramatic symptoms relief in one clinic’s patient group. **

Remember our discussion in Part 1 of this course about the possibility (likelihood?) of thyroid and/or adrenal hormone imbalances.

## http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074524 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584481/# https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515506/• http://www.tandfonline.com/doi/abs/10.1300/J094v09n03_10** https://secure.endfatigue.com/resources/Effective-Treatment-Of-Severe-Chronic-Fatigue-States.html

30

Nervous System Sensitization

31

Neurotransmitters

Chemical messengers

Over 100 distinct neurotransmitters (N/T)

Serotonin, Dopamine, GABA, Glutamate, Glycine, Epinephrine, Acetylcholine, …

Glutamate is our primary stimulatory N/T. GABA is our primary inhibitory one. Serotonin also plays key inhibitory roles.

Released from one neuron in order to cause another neuron to fire. Then “re-uptaken” by the original neuron or destroyed.

Specific neurons (and tissues) have varying levels of receptors for various neurotransmitters, depending on their role and adaptation in each genetically unique individual.

We cannot directly measure neurotransmitters in the human brain in any routine manner#. We can measure their metabolites in the urine; the accuracy/usefulness of this testing is hotly debated.*

# Other than in a brain or spinal cord biopsy of cerebrospinal fluid* http://www.ncbi.nlm.nih.gov/pubmed/20696183* http://www.moodcure.com/pdfs/urinetesting.pdf

32

Foxes in the Hen House?!

The blood-brain barrier (BBB) is intended to protect the brain from a wide range of chemicals or microbes circulating in the rest of the body while still providing nutrition to the brain.

But there are exceptions!

Cytokines (from all sources of inflammation)

Some microbes (e.g. Borrelia which causes Lyme Disease)

Peptides such as gluteomorphins and caseomorphins from gluten and dairy foods (often created by insufficient digestive enzymes).

Amino acids which, though natural, can still overwhelm brain balance (e.g. glutamate from MSG or aspartame)

Nanoparticles, as found in many sunscreens

Leaky brain. Semi-permiable membrane, just like in the gut.

Mercury increases BBB permeability.*

Oxidative stress and just plain ol' stress increase BBB leakiness too.**

* http://link.springer.com/article/10.1007%2FBF00688496** http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949263/ and http://www.ncbi.nlm.nih.gov/pubmed/9443836

33

The Role of Serotonin & Tryptophan

The neurotransmitter serotonin plays a key role in sleep, pain thresholds, vascular constriction and dilation, and dynamics of hunger/satiety and libido. Women make less than men. #

Made from tryptophan with Vitamin B6 being a particularly important cofactor, over 95% of the body’s serotonin is made in the gut (in the enteric nervous system).

Fibro patients have lower levels of tryptophan in their blood. Bacteria such as E. Coli and Bacteroidessecrete tryptophanase with destroys tryptophan in the gut. IBS increases endogenous enzymes which break down tryptophan as well. ###

Serotonin mediates production of Substance P, a neuromodulator that increases pain perception. Fibro patients with low serotonin metabolites and low tryptophan had higher levels of Substance P and lower quality of sleep and more pain. *

Four independent studies show that patients with fibromyalgia have approximately threefold higher concentrations of substance P in the central nervous system compared with normal controls.*

Treatment with 100mg 5-HTP (3x/day) improved pain, fatigue, and anxiety symptoms in at least 50% of participating patients.##

Serotonin depletion results from ongoing use of serotonin reuptake inhibiting drugs (e.g. SSRI, SNRI – yes, the drugs most commonly prescribed to Fibro patients!). Natural synthesis in neurons begins to shut down. Destruction of serotonin receptors results in up to 40-60% fewer receptors. The transporter system in the synapse that rids the brain of excess neurotransmitters is upregulated. **

# http://www.altmedrev.com/publications/3/5/367.pdf## http://imr.sagepub.com/content/20/2/182.full.pdf and https://www.ncbi.nlm.nih.gov/pubmed/2193835### http://journals.lww.com/pain/Abstract/1978/06000/Plasma_tryptophan_and_musculoskeletal_pain_in.7.aspx and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648992/* https://www.ncbi.nlm.nih.gov/pubmed/10025591 and Russell et al., 1996; Russell, 1998; Schwarz et al., 1999.** Wamsley, et al, “Receptor Alterations Associated with Serotonergic Agents”, J. Clinical Psychiatry, 48:3, 1987 and http://static1.1.sqspcdn.com/static/f/1072889/14961082/1320352016393/Antidep+SSRIs+increase+in+serotonin+transporters+Wegerer+1999.pdf?token=g4f4nf1cSrsH0dhrQSvP2tivNec%3D

34

Serotonin and Glutamate

In urinary organic acids testing, 5-HIAA (5-hydroxyindoleacetate) is the primary serotonin metabolite measurable. Kynurenate and quinolinate are made by tryptophan & are involved in host defenses against pathogens.

Kynurenate is a conclusive marker of insufficient B6 to promote conversion. Fibromyalgia patients have elevated levels of kynurenate relative to 5-HIAA. ***

Quinolinate (QUIN) is an inflammatory marker, evidence of the immune system using tryptophan to stimulate macrophages. Quinolinate strongly increases glutamate action (via NMDA receptors) and can be neurotoxic when it accumulates.

LPS promotes central sensitization via increased glutamate activity (activation of NMDA receptors) and increasing pain perception. *

Increased glutamate transmission is a hallmark of fibromyalgia. These patients have increased levels of glutamate in cerebrospinal fluid. **

Both serum and RBC magnesium levels are significantly lower in Fibromyalgia. Via its NMDA receptor blocking, insufficient magnesium plays a key role in pain hypersensitivity. Transdermal magnesium significantly reduced Fibro patients’ symptoms. ****

Prior exposure to high glucocorticoids increases CNS inflammation and increases LPS-stimulated allodynia.# Presumably endogenous or from drugs (e.g. prednisone)?

* https://www.ncbi.nlm.nih.gov/pubmed/15474652** https://www.ncbi.nlm.nih.gov/pubmed/17894924 and https://www.ncbi.nlm.nih.gov/pubmed/15315529*** https://acr.confex.com/acr/2009/webprogram/Paper16277.html and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729338/**** https://www.ncbi.nlm.nih.gov/pubmed/22271372 and http://www.ahjonline.com/article/0002-8703(84)90572-6/abstract and https://www.ncbi.nlm.nih.gov/pubmed/26343101 # https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166396/

35

Fibro and Melatonin

Melatonin is made from serotonin. Insufficient serotonin by definition will impair melatonin synthesis.

In addition to being required for sleep, melatonin is a potent antioxidant. Melatonin also increases ATP production by boosting enzyme activity in the electron transport chain.*

Fibromyalgia patients produce 31% less melatonin than healthy controls. Less sleep definitively increases pain perception and fatigue.**

Both sleep quality and perceived pain assessment improved significantly in Fibro patients with melatonin supplementation at night (3mg).“After 15 days, all patients (100%) developed a normal sleep/wake cycle.” ***

* https://www.ncbi.nlm.nih.gov/pubmed/15617531 ** https://www.ncbi.nlm.nih.gov/pubmed/21682138 and https://www.ncbi.nlm.nih.gov/pubmed/9828904*** https://www.ncbi.nlm.nih.gov/pubmed/10752492

36

Mitochondrial Dysfunction

37

37

Welcome to the Average Human Cell

Tens of trillions of cells in the human body.

The cell membrane as the cellular “brain”

Nucleus as the cellular “control center”

Endoplasmic reticulum as the cellular “kitchen”

Golgi complex as the cellular “shipping depot”

Lysosomes as the cell's “garbage disposal”

Mitochondria are cellular “energy factories”

Cytosol is the cellular liquid “space to move around in”

An interesting exception, red blood cells have neither a nucleus nor mitochondria.

* http://people.eku.edu/ritchisong/301notes1.htm

38

38

Mighty Mitochondria

Mitochondria arose from the capture of a bacterium by an ancestral eukaryotic host cell. * Mitochondria have their other DNA (only maternal inheritance) which is more vulnerable to oxidative damage than our primary DNA.

Number of mitochondria in a cell varies widely given its function.** We have the most mitochondrial density in our muscle cells (including the heart).

The inner membrane is tightly packed in folds called cristae (like small intestines) which houses the mitochondrial matrix.

The Electron Transport Chain takes place by passing electrons between special proteins in the Inner membrane which pumps protons into the Intermembrane space. The return of these protons (through a channel) into the matrix generates energy like turbines on a dam.

Transporter proteins allow ATP out of the mitochondria***

* http://www.ncbi.nlm.nih.gov/pubmed/10690412/** http://www.nature.com/scitable/topicpage/mitochondria-14053590*** http://www.ncbi.nlm.nih.gov/books/NBK22470/

39

39

Cellular Respiration

* "Cell Respiration" by RegisFrey. Licensed under CC BY-SA 3.0 via Wikimedia Commons

40

40

Oxidative Stress

Infections, Toxins, Radiation, Stress… Most of the bad guys have similar bullets in their guns: free radicals.• “Very reactive particles that can burn most things they touch through a process called

oxidation.” - Dr. Russell Blaylock, MD

Biggest source of oxidative stress in the body? Normal cellular metabolism!

Antioxidants “quench” (i.e. disarm) free radicals – either directly or via a triggered process. There are thousands of different kinds – some we consume, some we make. They work in “teams” or cascades.

• E.G. Vitamin C, Vitamin E, phenols, flavonoids, phenolic acids, curcumin, Glutathione, N-Acetyl-Cysteine, Uric Acid

An imbalance in the free radicals generated and the antioxidants available to disarm them causes oxidative damage.

Free radicals can damage any tissue via oxidation e.g. fatty acids (cell membranes), proteins, and DNA (including mitochondrial DNA).

• Unabated DNA damage is a precursor to most types of cancer.

• DNA damage turns on genes that were otherwise turned off

• Our internal DNA repair processes become less and less efficient as we age.

• Poor nutrient intake or absorption reduces our ability to repair oxidative damage.

41

Fibromyalgia & Mitochondrial Dysfunction*

There is strong evidence of cellular metabolic dysfunction in Fibromyalgia patients.

Reduced blood flow to muscles upon exertion, increased cellular lactate (reduced oxygenation) to tissue, fewer mitochondria, less ATP synthesis, microcirculation impairment, damage to mitochondrial DNA, higher interstitial lactate and pyruvate, increased oxidative stress in the mitochondria, impaired mitochondrial membranes, less CoQ10 within mitochondria, increased autophagy of damaged mitochondria).

Fibromyalgia patients have higher markers of oxidative stress within cells (vs. in blood plasma) from the mitochondria. There are also increased markers of lipid peroxidation.

The extent of oxidative stress/damage correlates with symptom severity in fibromyalgia and chronic fatigue syndrome.

Oxidative damage within the cell increases inner membrane permeability (“leaky mitochondria”) and is a major inducer of mitochondrial autophagy.

* http://link.springer.com/article/10.1007/s11926-000-0053-3 andhttp://www.tandfonline.com/doi/abs/10.1300/J094v03n03_02 andhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1754917/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1065312/ and

https://www.medicaljournals.se/jrm/content/?doi=10.2340/16501977-0581 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586064 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875645/ and https://www.ncbi.nlm.nih.gov/pubmed/19133251/ , https://www.ncbi.nlm.nih.gov/pubmed/20424583 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203929/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875645/ and https://www.ncbi.nlm.nih.gov/pubmed/12531455/ and https://www.ncbi.nlm.nih.gov/pubmed/11388705/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654204/ and http://www.reumatologiaclinica.org/en/oxidative-stress-in-fibromyalgia-pathophysiology/articulo/S2173574311000086/

42 Fibro patients have fewer

mitochondria and more mitochondrial autophagy. In this photo, you can clearly see mitochondrial autophagy in the patient cells (vs. the normal control). Mitochondria with lower CoQ10 are more prone to autophagy. *

CoQ10 in Fibro patients is nearly 2X higher in blood and 40% less within cells than in normal controls.**

Higher CoQ10 levels are correlatedwith lower levels of reactiveoxygen species (ROS). **

Oxidative stress can cause central sensitization and alter nociception resulting in hyperalgesia.***

Antioxidant status is lower in Fibro patients than controls. Lower glutathione levels correlated with higher morning stiffness. ****

To summarize, mitochondrial dysfunction increases oxidative stress which promotes pain hypersensitivity.

* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875645/and https://www.ncbi.nlm.nih.gov/pubmed/19115482/** https://www.ncbi.nlm.nih.gov/pubmed/19133251/*** http://jpet.aspetjournals.org/content/309/3/869.long **** https://www.ncbi.nlm.nih.gov/pubmed/16805968

Fibromyalgia & Mitochondrial Dysfunction

43

In addition to directly driving ATP production, CoQ10 is also a strong antioxidant.

200mg daily of both CoQ10 and Gingko biloba for ~3 months was shown to significantly improve symptoms in two-third of Fibromyalgia patients.*

Gingko biloba improves vasodilation and circulation, increases ATP production, and is an antioxidant.

In multiple other studies, 300mg daily CoQ10 led to significant reduction in symptoms over nine months. **

All steps of ATP production require B-vitamins. Malabsorption from SIBO, inadequate diet, toxicity, or genetic needs (e.g. MTHFR) may exacerbate a lack.

Oxygen is critical for ATP production. Be alert to allergy, asthma, food sensitivities, or sleep apnea which might impair oxygen availability.

* https://www.ncbi.nlm.nih.gov/pubmed/12025528and https://www.ncbi.nlm.nih.gov/pubmed/22898267** https://www.ncbi.nlm.nih.gov/pubmed/21496502 and http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035677

Mitochondrial Dysfunction Remedies

44

Case Study

45

Meet Jennifer

54 y/o female, 5’3”, 168 lbs

Primary complaints: Fibromyalgia (Dx 4 yrs prior), including body-wide pain and “heaviness” in all limbs. Strong fatigue, sleeps 6 fitful hrs/night but never feel rested. Severe stiffness when she wakes up. No GI symptoms except persistent mild bloating.Bowel movement 2-3 times daily.

Key history: Thyroid removed in 8th grade (tumor was causing rapid weight loss). Born with a goiter. Takes Synthroid. “Used to have cluster headaches and migraines, but finding God saved me from that ever again.”

Lifestyle elements: Homemade but SAD diet, “hot bread feels like a lover”. Working out hurts; only go to the gym to walk on the treadmill 1-2 days/month.“I am the original, top-shelf enabler. And then of course, people walk all over me.”

Key Initial Labs: Vitamin D 24, TSH 1.3, Free T4 0.9, RBC Mg 4.2, ESR 56.

46

Blessed Data!

47

48

49

Helping Jennifer

Clear validation of SIBO, dysbiosis, intestinal permeability, and food sensitivities. BUT remember she only reported mild bloating for GI symptoms.

Ran out of funds to do organic acids testing. Unwilling to go back to doctor for more basic Labwork, including thyroid panel (“I just can’t handle him telling me one more time that these drugs are my only option and that I’m ‘silly’ for not taking them.”)

Healing Plan

Counter SIBO and Candida with antimicrobials (CandiBactin-AR and –BR together at full dose for 3 months. SF722 and daily fresh garlic)

Support rest and rejuvenation (sleep hygiene focus, stopped all caffeine except green tea, built up to 150mg 5-HTP, SleepyTime tea, 200mg magnesium malate 3x/day, daily walking even if slowly)

Probiotics (Metagenics Acute Care, twice daily)

Food eliminations (All grains (“dear precious bread”), chocolate (ouch), specific vegetables and fruits, all sweeteners and dairy (because of yeast – especially painful for her re: cheese)

Heal gut lining (2 months of GI Revive and ongoing slippery elm lozenges)

Reduce inflammation and support mitochondria (daily B-complex, 100mg CoQ10 twice daily, 1500mg omega-3stwice daily (Metagenics EPA-DHA 720). Metagenics UltraInflamX 360

as daily breakfast shake. Tried Meriva but it bothered her stomach.)

(eventually) Support detoxification and toxin clearance

50

The Road to Recovery

And it was indeed a long, hard, challenging road for this lovely woman.

Many fits-and-starts with food eliminations, especially bread.

A great example of the need to meet clients where they are and be lovingly firm all at once.“Isn’t there a way I can get better without dumping the bread?” No. Probably not.

Wow – I had not idea how bloated I must’ve been. “I thought I was just that fat.”

Focused on sleep and food eliminations first. Teaching her simple, healthy cooking.

2nd priority was mitochondrial support and anti-inflammatory agents (and she felt better)

3rd priority was antimicrobials (and for a few weeks, she felt much worse!)

4th priority was probiotics; then (after one month of antimicrobials) on to gut healing

She had a huge learning curve about healthy eating overall (e.g. organic, whole foods, healthy cooking oils, not burning food, drinking water)

In the end, after 6 months….

No body pain at all. Lost 11 lbs. Reintroduced all foods except grains and gluten. Learned to see sugar and bread as addictive drugs. Continued supplements: B-complex, Co-Q10, 5-HTP, Ultimate Flora Vaginal Support. Got up the courage to go see another (functional medicine) doctor and get a full thyroid panel and switch to Armour thyroid. Taking vigorous yoga class 3x/week. Did a ten-day cleanse with my group program and has continued 2x/year. Jennifer has referred 6 clients to me.

51

Fibromyalgia Recommendations

52

Fibromyalgia Remedies - 1

Increase serotonin (reduce pain, increase melatonin to improve sleep)

100mg 5-HTP with B6 at bedtime; increase as needed. Experiment with day-time 5-HTP to reduce pain perception and enhance mood.

3-5mg melatonin may also be added short-term as needed. Watch for excess w/5-HTP.

Practice good Sleep Hygiene to stimulate natural conversion (especially avoidance of full-spectrum light and stimulatory activities/conversations).

Eradicate SIBO, heal intestinal permeability and gut lining, restore microbiome

Antimicrobials, probiotics, digestive enzymes, mucilaginous herbs.

Optimize immune function

Vitamin D (at least 50 ng/ml), Vitamin A and Zinc (both upper half of RR)

Change the diet to organic, whole-foods, high-vegetable* (high potassium) diet. Only wild or grass-fed, organic animal products.

Also assess food sensitivities. Long-term gluten-free and dairy-free. Caution with grains. No artificial sweeteners. No MSG. No refined carbohydrates.

Exercise to reduce inflammation and mental-emotional stress

Yoga and/or tai-chi to begin. Increase walking and stretching as priorities.

* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC57816/

53

Fibromyalgia Remedies - 2

Reduce nervous system stimulation Boost magnesium significantly (to upper third of RR), ideally magnesium malate alone or in

combination with other forms (e.g. 400mg twice daily).

L-theanine: 100mg/dose once or twice daily; 300-400mg as needed an hour before bed to calm the brain.

Calming herbs may be helpful, especially in tea forms as calming ritual e.g. valerian, passionflower, lemon balm, chamomile.

If needed, promote more GABA (vs. glutamate) conversion with taurine and n-acetyl-cysteine (500-1000mg each). Avoid free glutamate food sources (e.g. whey powder).

Increase cellular metabolism D-ribose, 5 grams 3x/day (I recommend the loose powder for ease)

CoQ10, 100mg 2-3x/day (ubiquinol form for those 40 y/o and older)

Acetyl-l-carnitine, 500mg 2-3x/day

Daily B-complex supplement (adjust as needed given MTHFR or other uniqueness)

Increase antioxidant capacity and reduce inflammation Ginkgo biloba, 100-200mg 2x/day

Omega-3 blend, 1000-1500mg 2x/day, heavy EPA emphasis

DGLA (e.g. borage, evening primrose) 500mg, twice daily

Proteolytic enzymes (in between meals), 2x/day

Greens food or other superfood blend – in daily shake or green smoothie e.g. Pure Synergy Superfood

54

Fibromyalgia Remedies - 3

Mindfulness and positivity practices to enhance mindset long-term (e.g. gratitude journaling, vision board, regular love letters to oneself).

A comfortable and compatible spiritual practice (e.g. meditation, prayer, temple, inspirational reading)

Trusting, healthy, meaningful relationships.

Daily purpose and value contribution in life.

Chiropractic care (at least a consultation to identify ongoing issues)

Light touch bodywork therapy (to begin to develop trusting relationship with touch) e.g. light touch or lymphatics massage, cranial-sacral therapy.

55

Helping the Whole Person

You now know much more about Fibromyalgia than the typical MD.

Be empowered. Don't try to take on too much. Address key, basic needs for systemic benefit.

Each client is one, whole, single, unique person!

Not a list of separate, unconnected symptoms or diagnoses.

Everything is interconnected. Everything.

Acute care may be critical and quite valuable, but ultimately, the root cause needs to be assessed and fully addressed for long-term healing.

Your clients need you.And you can do it!

4

© P

urp

ose Inc.

Fibromyalgia Demystified

Part 2

This presentation is copyrighted by Purpose Inc. with all rights reserved, available for student reuse strictly subject to the terms outlined in the student program agreement.

Thank You for Joining Us!