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Section 3 (PDF)

By Alex Vasquez, DC, ND, DO, FACN

Small intestinal bacterial overgrowth leads to systemic absorption of toxins that impair brain/nerve and muscle/mitochondrial function.


SIBO is associated with overproduction and absorption of bacterial cellular debris (eg, LPS, bacterial DNA, peptidoglycans, teichoic acid, exotoxins) and anti-metabolites – substances which are directly toxic to cellular energy/ATP production and muscle and nerve function – such as D-lactic acid, tyramine, tartaric acid, and hydrogen sulfide (H2S).
Intestinal gram-negative bacteria produce endotoxin (LPS), which impairs skeletal muscle energy/ATP production.


Endotoxin also raises blood lactate under aerobic conditions in humans.18 Thus, via direct and indirect effects on cellular metabolism, chronic, low-dose, bacterial LPS exposure can result in impaired muscle metabolism and reduced ATP synthesis via impairment of mitochondrial function.19 Intestinal bacteria also produce D-lactate, a metabolic toxin in humans; SIBO often results in variable levels of D-lactate acidosis, severe cases of which can progress from fatigue and malaise to encephalopathy (ie, confusion, ataxia, slurred speech, altered mental status) and death.20

Supporting the proposal that bacterial overgrowth with D-lactate-producing bacteria is a contributor to the chronic fatigue syndromes including fibromyalgia is an excellent study published in 2009,21 showing that patients with chronic fatigue syndrome (CFS) have intestinal overgrowth of bacteria that produce the toxin D-lactate; specifically the research showed that these chronic fatigue patients have a 7-fold increase in D-lactate-producing Enterococcus and an 1100-fold increase in D-lactate-producing Streptococcus. Energy/ATP underproduction and lactate overproduction cause muscle fatigue and muscle pain.

An additional cellular toxin produced by intestinal bacteria is hydrogen sulfide, which causes DNA damage22 (noted previously to be increased in fibromyalgia patients) and impairs cellular energy production, a finding relevant to, but not limited to, the pathogenesis of ulcerative colitis.23,24 Bacteria and yeast in the intestines produce H2S, which can bind to the mitochondrial enzyme cytochrome c oxidase (part of Complex IV of the electron transport chain), thereby impairing oxidative phosphorylation and ATP production.


This may partly explain the association of GI dysbiosis and SIBO with conditions such as CFS and fibromyalgia.25
Mitochondrial dysfunction in muscle leads to the cellular/cytologic and histologic/tissue changes that are typical and well documented in cell and muscle samples of patients with FM.26,27 These peripheral (eg, non-brain) changes in muscle also prove beyond any doubt that fibromyalgia is not a “brain disease” or solely a “disorder of pain processing.”


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The migraine-fibromyalgia protocol excerpted from Inflammation Mastery (PDF cover, PDF contents) has been developed and published since Dr Vasquez was professor of Orthopedics and Rheumatology at Bastyr University nearly 20 years ago. Since then, the protocol has been repeatedly verified and updated, including a commissioned continuing medical education (CME) monograph published by Institute for Functional Medicine in 2008. Dr Vasquez has presented this information to international audiences of healthcare providers and has published related information in journals such as Nature Reviews Rheumatology and Journal of the American Osteopathic Association.

The exact same migraine protocol is available in different formats, contexts, and under different titles, depending on whether you want 1) the entire protocol or just a smaller section, 2) migraine with fibromyalgia or just migraine alone, and 3) paper book or digital ebook:

  1. Inflammation Mastery 4th Edition: This is the complete protocol and context at 1,200 pages; also published separately as two volumes titled Textbook of Clinical Nutrition and Functional Medicine with Chapter 5 published as volume 2

  2. Pain Revolution in full-color, includes the protocols for migraine and fibromyalgia, since these conditions commonly occur together; available as paper book and digital ebook

  3. Brain Inflammation printed in discounted grayscale, ie, black and white; available as paper book and digital ebook

  4. Migraine and Headache Revolution: Digital ebook exclusively focused on migraine

pain revolution photo iphone.jpg

Inflammation Mastery 4th Edition (PDF cover, PDF contents) is the "master textbook" that details the functional inflammology protocol, described below. The full-color paper book is available for international shipping from ICHNFM.ORG while paper and digital versions are available from major bookstores such as (also in the UK and in Germany...) and Because the information in this book has already been time-proven via previous publications and extensive peer-review and thousands of citations to authoritative sources, it will not change nor be replaced in the foreseeable future. Any necessary updates will be provided by articles, videos, live webinars, and an extending separate "volume 3" described below.

Sample PDF downloads: ​


Contents: Preamble/Contextualization, Chapters/subsections

  1. Patient Assessments, Laboratory Interpretation, Clinical Concepts, Patient Management, Practice Management and Risk Reduction: This chapter introduces/reviews/updates patient assessments, laboratory interpretation, musculoskeletal emergencies, healthcare paradigms; the common and important conditions hemochromatosis and hypothyroidism are also included in this chapter since these need to be considered on a frequent basis in clinical practice 

  2. Wellness Promotion & Re-Establishing the Foundation for Health: Reviewed here are diet, lifestyle, psychosocial health, and—given the pervasiveness of persistent organic pollutants and their increasingly recognized clinical importance—an introduction to environmental medicine

  3. Basic Concepts and Therapeutics in (Nondrug) Musculoskeletal Care and Integrative Pain Management: Nonpharmacologic management of musculoskeletal problems is preferred over pharmacologic (e.g., NSAID, Coxib, steroid, opioid) management because of the collateral benefits, safety, and cost-effectiveness associated with manual, dietary, botanical, and nutritional treatments. A brief discussion of the current crisis in musculoskeletal medicine is provided for contextualization and emphasis of the importance of expanding clinicians' knowledge of effective nondrug treatments

  4. The Major Modifiable Factors in Sustained Inflammation: Major components of the “Functional Inflammology Protocol” are reviewed here, from concepts and molecular biology to an emphasis on practical clinical applications: A few sections have been printed separately and are thus linked

    1. Food & Basic Nutrition  307

    2. Infections: Dysbiosis / Viral Infections  396 / 540

    3. Nutritional Immunomodulation  609

    4. Dysmetabolism, Mitochondrial Dysfunction/ERS/UPR, and mTOR  622

    5. Special Considerations: Sleep, Sociopsychology, Stress, Surgery  674

    6. Endocrine Imbalances  688

    7. Xenobiotic Immunotoxicity  699

  5. Clinical Applications 

    1. Hypertension  727

    2. Diabetes Mellitus  819

    3. Migraine & Headaches  863 (also published separately)

    4. Fibromyalgia  901 (also published separately)

    5. Allergic Inflammation  984

    6. Rheumatoid Arthritis  1019

    7. Psoriasis and Psoriatic Arthritis  1038

    8. Systemic Lupus Erythematosus  1053

    9. Scleroderma & Systemic Sclerosis  1074

    10. Vasculitic Diseases  1094

    11. Spondyloarthropathies & Reactive Arthritis  1108

    12. Sjögren Syndrome/Disease  1119

    13. Raynaud's Syndrome/Phenomenon/Disorder  1127

    14. Clinical Notes on Additional Conditions: Behçet's Disease, Sarcoidosis, Dermatomyositis and Polymyositis  1131

  6. Index & Appendix (PDF)

Available in one large volume or 2 smaller volumes, in paper or digital ebook for phones, iPads, computers: ​

  • Same content either all together or in 2 volumes: Because Inflammation Mastery 4th Edition is large at nearly 1,200 pages and because the previous version of chapters 1-4 had been published as "volume 1" in 2004, the book was also published separately as two volumes titled Textbook of Clinical Nutrition and Functional Medicine; this was done at the request of the students who use the book in their classes and clinical work and also to respect those who had purchased the previous version of chapters 1-4 and who simply needed to add chapter 5, which is published as volume 2

  • Paper book version: The general consensus is that people learn information at a deeper level when they read paper books because they interact with the material physically, can take notes directly on the page, and can easily flip pages to see other related information.

  • Digital ebook version: The digital ebook version for example via Amazon's Kindle platform allows the owner to read the book on phone, iPad and computer and to make highlights and notes that are synchronized across all devices. The Kindle app is free; download a *free* sample of Inflammation Mastery 4th Edition here via the *free* Kindle software from Amazon.


News and updates: ​

  • Volume 3 which will focus exclusively on dysbiosis and the microbiome and its clinical implications and treatments will be published in 2018 or more likely 2019. The information in this new 3rd volume will be completely new, derived from Dr Vasquez's 30-hour video course Human Microbiome and Dysbiosis in Clinical Disease.

  • See smaller updates and news at Dr Alex Vasquez 's Inflammation Mastery on

Bulk discounts (orders of 5 or more books shipped to the same address) are available for students, book clubs, and study groups by emailing

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