The Shoemaker Protocol: The Research Behind Each Step

80 papers · Curated by Lauren Lowenstein, The Biotoxin Lady

When I first saw the words "Shoemaker" and "HLA" in a stranger's post, I had no idea they'd change my family's life.

The Shoemaker Protocol is the step-by-step framework Dr. Ritchie Shoemaker developed to diagnose and treat Chronic Inflammatory Response Syndrome (CIRS). What makes it different is that it's sequential and measurable. Each step targets a specific problem, and objective biomarkers are retested to see whether that step worked before moving on.

The order matters:

  1. Remove from exposure. Nothing else holds if you're still being exposed.
  2. Binders (cholestyramine or Welchol) to help clear biotoxins.
  3. Eradicate MARCoNS.
  4. Then correct, one at a time: antigliadin antibodies, androgens, ADH/osmolality, MMP-9, VEGF, C3a, C4a and TGF-β1
  5. Finish with VIP for people who meet the criteria.

This hub collects about 80 research papers behind the protocol, many authored or co-authored by Dr. Shoemaker, along with work from colleagues and independent groups on the CIRS diagnosis, biomarkers, VCS testing, NeuroQuant brain imaging and transcriptomics.

If you're a practitioner, this is your evidence base. If you're a patient, it's proof that what you're going through has been studied, published and taken seriously, even if your last doctor didn't.

See the protocol step by step (click each tile) in my Shoemaker Protocol guide.

Educational only, not medical advice. The protocol should be overseen by a Shoemaker-trained provider.

— Lauren Lowenstein, The Biotoxin Lady · Last reviewed October 19, 2026

Key facts

  • The Shoemaker Protocol is a sequential, biomarker-guided treatment framework for CIRS.
  • Removing exposure is Step 1. Binders and MARCoNS treatment come early, and VIP comes last.
  • Progress is tracked with objective labs and VCS testing, not symptoms alone.

Key research papers

  1. The Shoemaker Protocol

    A Heyman et al. · 2023

  2. Assessment of visual contrast sensitivity in biotoxin-exposed individuals using four testing methods

    Ingrid Astrid Jimenez-Barbosa et al. · Annals of Medicine · 2026

  3. Herbal Therapeutics for CIRS Biomarkers in Autism Spectrum Disorders: A Mechanistic and Molecular Approach for Neuroimmune Pathology in Pediatrics

    Jodie A Dashore et al. · Medical Research Archives · 2026

  4. Chronic Inflammatory Response Syndrome (CIRS): A Review of Diagnosis, Immunological Mechanisms and Treatment Challenges

    T. Rama Rao et al. · International Journal of Current Science Research and Review · 2025

  5. Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment

    Ming Dooley et al. · Annals of Medicine and Surgery · 2024

  6. Chronic Inflammatory Response Syndrome (CIRS) and Metabolism

    Ritchie C. Shoemaker et al. · 2023

  7. Integrating Field, Laboratory and Clinical data for the IAQ investigation. Comparison of indices of human health and building healthy: SAIIE meets ERMI. Round Table, Minneapolis. R Shoemaker, S Vesper, G Boothe, G Cormier, K Lin

  8. Effectiveness of Shoemaker cholestyramine in the detoxification of zearalenone as determined in mice. Bull Environ Contam Toxicol 54:128-134 (1995)

    Underhill KL et al. · 1995

  9. Shoemaker M.D. Second Edition Arcadia Press: 1998

    Does Yours? Ritchie C · 1998

  10. Learning and memory difficulties after environmental exposure to waterways containing toxin-producing Pfiesteria or Pfiesteria-like dinoflagellates

    Grattan L et al. · The Lancet · 1998

  11. Sick building syndrome (SBS) and exposure to water-damaged buildings: Time series study, clinical trial and mechanisms

    Ritchie C. Shoemaker et al. · Neurotoxicology and Teratology · 2006

  12. A time-series study of sick building syndrome: chronic, biotoxin-associated illness from exposure to water-damaged buildings

    Ritchie C. Shoemaker et al. · Neurotoxicology and Teratology · 2005

  13. TUBB1, TUBA4A and MAPK as Indicators of Die-Back Degenerative Central Nervous System Disease in Patients Sickened by Specific Exposure to the Interior Environment of Water- Damaged Buildings

    Ritchie C. Shoemaker et al. · Medical Research Archives · 2023

  14. Possible estuary-associated syndrome: symptoms, vision, and treatment.

    Shoemaker RC et al. · Environmental Health Perspectives · 2001

  15. Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: A case/control study

    Ritchie C. Shoemaker et al. · Neurotoxicology and Teratology · 2010

  16. Treatable metabolic and inflammatory abnormalities in Post COVID Syndrome (PCS) define the transcriptomic basis for persistent symptoms: Lessons from CIRS

    Ritchie C. Shoemaker et al. · Medical Research Archives · 2021

  17. A Novel Therapeutic Approach to Parkinson's Disease: Using Transcriptomics to Identify Unique Patterns of Gene Expression including 'Triple Positives,' Toll receptors, and Endotoxin Exposure

    R Shoemaker et al. · Medical Research Archives · 2025

  18. Newer Molecular Methods Bring New Insights into Human- And Building-Health Risk Assessments from Water-Damaged Buildings: Defining Exposure and Reactivity, the Two Sides of Causation of CIRS-WDB Illness

    R. L. Shoemaker et al. · Medical Research Archives · 2021

  19. Transcriptomics and Brain Volumetrics Define the Causes of Cognitive Impairment in Patients with CIRS and Support the use of VIP in Treatment

    Ritchie C. Shoemaker et al. · Medical Research Archives · 2023

  20. Exposure to Actinobacteria resident in water-damaged buildings and resultant immune injury in Chronic Inflammatory Response Syndrome

    Ritchie C. Shoemaker et al. · Medical Research Archives · 2021

  21. Complement split products C3a and C4a are early markers of acute lyme disease in tick bite patients in the United States

    Ritchie C. Shoemaker et al. · International Archives of Allergy and Immunology · 2008

  22. The Evolution of Chronic Inflammatory Response Syndrome (CIRS) and the Biotoxin Pathway

    Ritchie C. Shoemaker et al. · 2023

  23. Autism Spectrum Disorders and Lyme Disease: Exploring Shared Neuro-Inflammatory and Immune Pathways

    Jodie Dashore et al. · Medical Research Archives · 2025

  24. Screening for Biomarkers of Actinobacteria Associated with Water-Damaged Buildings – Part 1

    Ritchie C. Shoemaker et al. · Medical Research Archives · 2022

  25. Urinary Mycotoxin Testing

    Ritchie C. Shoemaker et al. · 2023

  26. PITFALLS OF MYCOTOXIN TESTING: EVIDENCE-BASED FINDINGS CONFIRM MYCOTOXIN ASSAYS USING ANTIBODY TESTING AND URINARY ELISA ARE BASED ON FLAWED SCIENCE

    Ritchie C. Shoemaker et al. · Medical Research Archives · 2026

  27. THIRTY YEARS OF PUBLISHED RESEARCH ON HUMAN HEALTH EFFECTS OF EXPOSURE TO THE INTERIOR ENVIRONMENT OF WATER-DAMAGED BUILT ENVIRONMENTS

    Ritchie C. Shoemaker et al. · Medical Research Archives · 2025

  28. A Transcriptomic Fingerprint for Parkinson's Disease Found in Patients with Chronic Inflammatory Response Syndrome: Implications for Diagnosis, Treatment and Prevention

    Ritchie C. Shoemaker et al. · Medical Research Archives · 2024

  29. Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant

    Ritchie C. Shoemaker et al. · Neurotoxicology and Teratology · 2014

  30. EXPOSURE TO THE INTERIOR ENVIRONMENT OF WATER-DAMAGED BUILDINGS CAN ACTIVATE HIF 1A, INDUCE PROLIFERATIVE PHYSIOLOGY AND IMPAIR MITOCHONDRIAL METABOLISM: IMPLICATIONS FOR HYPOXIC PULMONARY HYPERTENSION IN CHRONIC INFLAMMATORY RESPONSE SYNDROME

    Ritchie C. Shoemaker et al. · Medical Research Archives · 2024

  31. Sick building syndrome in water-damaged buildings: generalization of the chronic, biotoxin-associated illness paradigm to indoor toxigenic fungi

    Ritchie C. Shoemaker et al. · Bioaerosols, Fungi, Bacteria, Mycotoxins and Human Health · 2005

  32. Transcriptomic signatures in whole blood of patients who acquire a chronic inflammatory response syndrome (CIRS) following an exposure to the marine toxin ciguatoxin

    James C. Ryan et al. · BMC Medical Genomics · 2015

  33. Treatment of persistent Pfiesteria-human illness syndrome

    Ritchie C. Shoemaker · Maryland medical journal · 1998

  34. Diagnosis of Pfiesteria-human illness syndrome

    Ritchie C. Shoemaker · Maryland medical journal · 1997

  35. Pediatric Neuroimmune and Inflammatory Overlap: Immunopathology of PANS/PANDAS in Autism Spectrum Disorder

    Jodie A Dashore et al. · Medical Research Archives · 2026

  36. Residential and Recreational Acquisition of Possible Estuary-Associated Syndrome: A New Approach to Successful Diagnosis and Treatment

    Shoemaker RC · Environmental Health Perspectives · 2001

  37. Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings

    Ritchie C. Shoemaker et al. · Health · 2013

  38. Innate immunity, MR spectroscopy, HLA DR, TGF beta-1, VIP and capillary hypoperfusion define acute and chronic human illness acquired following exposure to water-damaged buildings. 2008. International Healthy Buildings (conference peer review)

    Ritchie C. Shoemaker et al. · 2008

  39. Biology of Fungi, International Mycology Congress 2009 (conference peer review)

    Shoemaker R · 2009

  40. Atovaquone plus cholestyramine in patients coinfected withBabesia microti andBorrelia burgdorferi refractory to other treatment

    Shoemaker R et al. · Advances in Therapy · 2006

  41. Chronic Inflammatory Response Syndrome: Exploring Neuroimmune Pathology and Multisystem Framework for Differential Diagnosis in Pediatrics- Part 1

    Jodie A Dashore et al. · Medical Research Archives · 2025

  42. Exposure to interior environments of water-damaged buildings causes a CFS-like illness in pediatric patients: a case/control study. 2009 bulletin of the IACFS

    Ritchie C. Shoemaker et al. · 2009

  43. Cytokine, complement, and endotoxin profiles associated with the development of the adult respiratory distress syndrome after severe injury

    Thomas J. Donnelly et al. · Critical Care Medicine · 1994

  44. ACOEM position statements on mold: ploys and lies. Published on line 2011

    Shoemaker R · 2011

  45. Use of visual contrast sensitivity and cholestyramine in diagnosis and treatment of indoor air acquired, chronic, neurotoxin-mediated illness. 9/2003 (conference peer review)

    Ritchie C. Shoemaker · 2003

  46. Linkage disequilibrium in alleles of HLA DR: differential association with susceptibility to chronic illness following exposure to biologically produced neurotoxins. American Society of Microbiology 2003. (conference peer review)

    Shoemaker R · 2003

  47. Results of health screening and visual contrast testing. St. Bernard’s Parish, Louisiana. 2006. published on-line

    Ritchie C. Shoemaker et al. · 2006

  48. Inside Indoor Air Quality: Environmental Relative Moldiness Index (ERMI)

    Shoemaker R et al. · Filtration News · 2007

  49. Characterization of chronic human illness associated with exposure to cyanobacterial harmful algal blooms predominated by Microcystis. 2009 Cyanobacterial harmful algal blooms pg 653

    Shoemaker R et al. · 2009

  50. Rigor, transparency, and disclosure needed in mold position paper

    Ritchie C. Shoemaker et al. · The Journal of Allergy and Clinical Immunology · 2006

  51. Pfiesteria in Estuarine Waters: The question of health risks

    Ritchie C. Shoemaker et al. · Environmental Health Perspectives · 2007

  52. A letter of comment on "Human health effects of exposure to Pfiesteria piscicida: a review" by Swinker and colleagues

    H. Kenneth Hudnell et al. · Microbes and Infection · 2003

  53. Poster H05, Treatment of Possible Estuarine Associated syndrome: Neurotoxins, contrast sensitivity and cholestyramine. CDC National Conference on Pfiesteria: From Biology to Public Health 10/18-10/20/2000 , Stone Mountain, Georgia

    Ritchie C. Shoemaker · 2000

  54. Sick building Syndrome: possible association with exposure to mycotoxins from indoor air fungi. 8th International symposium of Neurotoxicology, Neurobehavioral methods and effects in occupational and environmental health, Brescia, Italy, 6/26/02

    Hudnell HK et al.

  55. Poster 539-P. ADA funded research; Use of pioglitazone to prevent intensification of persistent symptoms following cholestyramine treatment of patients with the Post-Lyme Syndrome. (Abst

    Ritchie C. Shoemaker · ) Diabetes · 2002

  56. Atovaquone (Mepron) plus cholestyramine (Questran) in patients who are co-infected with Babesia Microti and Borrelia burgdorferi and refractory to antibiotics and cholestyramine alone. American Society of Tropical Medicine 51st annual meeting, 11/11/02, Denver, Colo, (abst ) AJTMH

    Shoemaker RC et al. · 2002

  57. Treatment of persistent Pfiesteria – human illness syndrome, Maryland Med J 47(2): 64-66 (1998)

    Ritchie C. Shoemaker · 1998

  58. http://cfpub2.epa.gov/ordpubs/nerlpubs/nerlpubs_mcear_2004.cfm?ActType=Pu CDC/New Orleans

    Frederick R et al. · Exposure of children to indoor molds. EPA Science Forum · 2004

  59. Use of pioglitazone to prevent intensification of persistent symptoms following cholestyramine treatment of patients with Post- Lyme syndrome

    Ritchie C. Shoemaker et al. · 2000

  60. Diagnosis of Pfiesteria human illness syndrome, Maryland Med J 46(10): 521-23 (1997)

    Ritchie C. Shoemaker · 1997

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