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Future of Functional Health Review Clinical Newsletter

Practical Solutions for Practitioners – August 2021

by Robert Abbott, MD and the Ruscio Institute for Functional Medicine Clinical Team

Medically reviewed & fact checked by a
board-certified doctor
Medically reviewed & fact checked by a
board-certified doctor
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Using GI Treatments to Significantly Improve Menstrual Symptoms

Patient Info: 

  • Jill, 31 years old, female
  • Previous Dx
    • PCOS
    • Fibroids
    • IBS
  • Rx 
    • Spironolactone,
    • OCP, continuous (no inert/placebo use)
    • Diclofenac, for back pain secondary to menstrual cramps
    • Zofran, for nausea and vomiting
  • Chief Complaints 
    • “Gastric episodes”: bloating, diarrhea, flushing, vomiting 2 weeks before menstruation – severe
    • Body/joint pain, only around period – severe
    • “Hormone imbalance,” breakthrough bleeding – severe

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Visit 1 (Day 1) – History and Exam

Initial impression: Jill is a pleasant 31 y/o female with a good diet, lifestyle, and perspective suffering from severe menstrual-related GI symptoms.

  • Dx: 
    • PCOS
    • Uterine Fibroids
    • IBS
  • Previous Testing:
    • Laparoscopic exploration: no endometriosis, one fibroid
  • Onset:
    • Reports a lot of food intolerances as a kid
    • Became overweight in highschool 
    • Developed irregular periods in college, endocrinologist started her on Metformin
    • A lot of family stressors during college and early-adulthood
  • Family History: 
    • Cardiometabolic disease on both sides of family
    • Mom and maternal grandmother suffered with some infertility
  • Prior Treatments:
    • Metformin, discontinued
  • Previous Diets:
    • Elimination diet, some help
  • DDX:
    • IBS, dysbiosis, digestive insufficiency
    • Histamine intolerance, MCAS
    • Limbic system activation
    • Endometriosis, fibroids, infertility, elevated androgens
    • Insulin resistance
  • Notes: 
    • As I evaluate her cyclic and episodic symptoms including symptoms of GI and hormone imbalances, I am suspecting elements of primary gut dysfunction with secondary immune hyperreactivity and hormone dysregulation. I am also mindful of psychological inputs as well as metabolic dysregulation that could be present.
  • Prognosis:
    • Fair to good given her persistence and good outlook on her condition. Will need to work slowly with her given history of reactivity.

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Visit 2 (A Few Days Later) – Testing and Initial Recommendations

  • Testing:
    • CBC w/ differential, CMP, GGT
    • ANA
    • Iron Profile, homocysteine, magnesium, vit D
    • hsCRP, ESR
    • Lipid panel, apoB, A1C, fasting insulin
    • TSH, fT4, fT3, TPO Ab
    • Testosterone, DHT, progesterone
  • Rationale:
    • I am starting with a more comprehensive panel of bloodwork to help identify non-specific, but concerning underlying inflammatory or immune processes, nutritional imbalances, blood sugar or lipoprotein dysregulation, or hormonal imbalances with specific concerns for abnormal thyroid states or androgen excess. As I will begin my treatment utilizing empiric and iterative gut-focused therapy, I will not start with any GI-specific testing as this will not impact my initial series of treatment recommendations.
  • Treatment Recommendations:
    • Diet and Lifestyle
      • 2-4 day elemental reset then use as morning meal
      • Use low FODMAP template for other meals
      • Spearmint tea with meals
    • Supplementation
      • Multivitamin

      • Omega 3
  • Rationale:
    • Given that she was already following a reasonable diet, we decided to pursue an elemental diet reset followed by a partial elemental diet combined with a low FODMAP way of eating. Spearmint tea may be helpful to reduce androgens if elevated. I recommended some baseline nutritional replacement therapy as a foundational, low-risk support, however, if I were treating her today, I would likely save this therapy for a future visit (post-testing for example).

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Visit 3 (6 Weeks Later) – Lab Interpretation and Treatment Evaluation

  • Subjective Assessment:
    • Nausea, improved
    • Diarrhea, improved
    • Bloating, improved
  • Lab Results:
    • Ferritin: 159 (H), iron saturation %: 31
    • hs-CRP: 1.5 (H), ESR: 8
    • Folate: 12, Vitamin D: 50, B12: 500, homocysteine: 9
    • ANA: negative
    • LDL-C: 140, triglycerides: 182 (H), ApoB: 124
    • Insulin: 7.5, A1C 5.2
    • TSH, fT4: normal without antibodies
    • DHT: 54 (H)
  • Lab Interpretation:
    • Reasonable B vitamin and Vitamin D status
    • Early, mild insulin resistance and mixed hyperlipidemia
    • No signs of autoimmunity
    • Mild iron overload? (could be secondary to inflammatory state)
    • Nonspecific mild inflammation
    • Androgenic environment
  • Impression:
    • Jill has made some significant improvement with my initial recommendations of an elemental diet reset followed by a partial elemental diet with a core low FODMAP template. The lab results indicating mild insulin resistance, non-specific inflammation, and elevated DHT suggest a PCOS phenotype with female hormone imbalance. I continue to suspect that these imbalances are secondary to disturbances/imbalances in the GI tract. Given these clinical suspicions, we will continue to focus on correcting dysbiosis, maldigestion, and possible issues with histamine intolerance/immune reactivity.
  • Updated Treatment Recommendations:
    • Starting
      • Triple probiotic therapy

      • Digestive Enzymes with HCl
      • Quercetin Ascorbate

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Visit 4 - 4 Weeks Later

  • Subjective Assessment:
    • Diarrhea, improved – probiotics helping but only taking 1x/day
    • Gastric “burning,” worse – suspects HCl in digestive replacement 
    • Hair growth/nail health, improved – suspected elemental diet is helping
    • Female hormone balance, improved – less breakthrough bleeding and cramping
    • Energy, worse – feels limited with low FODMAP options
  • Impression:
    • Jill is making global improvements in her symptoms with the use of triple probiotic therapy and a continued partial elemental diet with a low FODMAP way of eating. This further points to dysbiosis and increased pathologic intestinal permeability as a source of symptoms. We will continue our GI-focused therapy and then move into remediating hormonal imbalances if necessary. Today’s nutritional assessment revealed low carbohydrate intake and good consistency with low FODMAP choices. Given her reported decrease in energy, she can work to increase carbohydrates throughout the day. As she also inquired about ways to exercise without causing intense fatigue, I encouraged her to explore light aerobic training starting at 2x per week.
  • Recommendations:
    • Diet and Lifestyle
      • Increase carbohydrate/starch intake (potatoes, rice, squash)
      • Introduce aerobic training days 2x/week. Aim for 20-50 minutes on a bike, treadmill, run, or rower where you only breathe through your nose or 120-140 beats per minute. This is to aid with recovery and is less stress on your body. 
    • Supplementation
      • Discontinue enzymes
        • *Note*: Looking back I would have waited to introduce enzymes in order to minimize variables and more rigorously apply our clinical rule – treat dysbiosis and gut inflammation before gastric secretions
      • Increase probiotic dose to 2x/day
      • Add gut healing nutrients

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Visit 5

  • Subjective Assessment:
    • Nocturnal diarrhea, worse – experiencing diarrhea in middle of night that wakes her up from sleep
    • Bloating, improved – still present during period of breakthrough bleeding
    • Menstrual cramping, resolved
    • Nausea, resolved
    • No “gastric episodes” since last visit
  • Impression:
    • Jill has made drastic improvements with iterative GI-specific therapy. Her nocturnal diarrhea is perhaps a negative response to something in her current treatment regimen. I am encouraged that she has not had any “gastric episodes” of nausea/vomiting and has improvements with abdominal discomfort. Her residual symptoms of bloating/gas seem to be worse around breakthrough bleeding but much less severe than when she first saw me.
    • In the visit, she inquired about gut-related testing and wanted to pursue further assessment. While we have been making progress in treatment, I will oblige her request and order a GI Map. She is almost at her goal but feels like she still has some work to do.
    • *Note*: I considered layering in female hormone support after this visit but since she responded so well to the elemental diet with supportive GI treatments, I suggested we simply push further into this approach.
  • Updated Treatment Recommendations:
    • Diet and Lifestyle
      • Perform 1-2 week trial of low histamine diet, go back to previous diet if no improvement
      • Consider performing another 2-4 day elemental reset around the worst part of her menstrual cycle – breakthrough bleeding
    • Supplementation
      • Stop gut healing nutrients and quercetin temporarily, add back in after a few days to see if they are contributing to nocturnal diarrhea
    • Further Testing
      • GI Map

Clinical Rules Applied

  1. Functional Medicine is foundationally a diet and lifestyle-based approach and should leverage and prioritize such low risk interventions initially and throughout treatment.
  2. Give time for healing before adding new treatments. Avoid “novelty bias” by continuing beneficial treatments in an iterative fashion for clinically appropriate periods of time BEFORE adding new treatments or significant treatment modifications.
  3. Exhaust low risk, empirically informed treatments PRIOR TO the consideration of testing to guide/modify treatment recommendations.
  4. Address underlying gut imbalances in cycling women PRIOR TO additional supplementation directed at female hormone support.

Clinician’s Comments 

This case study highlights the very important but often overlooked gut-female hormone connection. Many functional medicine clinicians would have pursued female hormone testing given this patient’s timing of symptoms, but given her initial responses with empiric trials of gut-directed therapies, it was clear that her gut was the primary source of symptoms. It also highlights a number of clinical rules. When given the option to add something new to a protocol (e.g. female hormone support) or do more of what is already working (e.g. elemental diet), we should, in most cases, continue providing time for the treatments to provide more benefit before jumping into newer treatments. The case is also a great demonstration of how we should seek to exhaust empiric treatments including lower risk dietary and lifestyle intervention before more complicated treatments or testing.

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Clinical Review: The Validity and Role of IgG “Food Sensitivity” Testing In Clinical Practice

  • Clinical Question
    • Should clinicians utilize IgG based “food sensitivity” testing for patients with GI and/or certain extraintestinal symptoms including neurologic, skin and immunologic symptoms?
  • Summary of Key Points
    • IgG food sensitivity testing IS NOT robustly supported by clinically directed research
    • Consumer based and practitioner directed IgG testing suffers from a lack of clinical validity and testing reliability
    • Individuals implementing restrictive diets based on IgG food sensitivity testing may achieve benefit as a result of an enhanced placebo effect, the indirect/incidental removal of nutrient-poor foods, and the inclusion of more nutrient-dense and compatible foods for their gut microbiome amidst other theoretical mechanisms
    • The majority of food reactions experienced by patients can likely be explained by gut dysbiosis, maldigestion, limbic system reactivity, IgE based allergic reactions, neurohormonal responses secondary to the consumption of certain food chemicals, histamine intolerance or mast cell activation, increased perceived stress/allostatic load and the excessive consumption of detergents, processed “anti-food” and other compounds that disrupt the epithelial and mucus barrier and NOT IgG mediated immune responses
    • Newer food sensitivity assays examining complement and IgG immune complexes have been proposed as more sensitive and specific tests to determine clinically relevant food antigen-antibody immune complexes, but there is insufficient peer-reviewed research to suggest their regular adoption in clinical practice at this time
  • Clinical Recommendations
    • We do not recommend the use of IgG based food sensitivity testing in clinical practice.
    • Patients presenting with food intolerances and food reactions should be evaluated for underlying reasons for their symptoms. Clinicians should consider gut dysbiosis, SIBO, non-celiac gluten sensitivity, maldigestion/digestive insufficiency, limbic system reactivity, increased perceived stress/allostatic load, the consumption of microbially incompatible fibers or food chemicals, and the over-consumption of processed and high pesticide residue foods as the most common reasons for food reactions. Clinicians should also be mindful of rarer causes of food intolerances and food reactions that include, but are not limited to celiac disease, eosinophilic esophagitis, oral allergy syndrome, and tick mediated allergy / alpha-Gal syndrome.
    • Clinicians treating food reactivity should first consider an empirically designed elimination diet that prioritizes the elimination of commonly immunogenic foods. Examples of dietary intervention that may improve food reactivity include but not limited to: Paleo diet, low FODMAP diet, Low Histamine diet, AIP diet, Specific Carbohydrate diet, and a partial or full elemental diet. The clinician should weigh the risks and benefits of an elimination diet based on the patient’s presenting symptoms and current diet, aiming to use the least restrictive, most accessible diet possible to achieve the desired therapeutic outcome.
    • Alongside nutritional therapy, the clinician should consider addressing underlying nervous system dysregulation or high perceived stress that could be contributing to the patient’s symptoms of food reactivity.
    • Outside of dietary and lifestyle-based treatments, clinicians should strongly consider gut-directed interventions for those with food reactions given the correlations of food allergy with a disturbed gut microbiome and an altered gut barrier – immune interface.
  • What We Are Doing At Our Center
    • At the time of publication, we currently are not utilizing any form of IgG food sensitivity testing and do not have plans in the near future to explore this time of testing even for research directed purposes.
    • We also see food reactivity as one of the main complaints at our center and see a number of patients labeled as ‘chronic’, ‘complex’ or ‘sensitive’.

Primary References

Lomer MC. Review article: the etiology, diagnosis, mechanisms, and clinical evidence for food intolerance. Aliment Pharmacol Ther. 2015 Feb;41(3):262-75. doi: 10.1111/apt.13041. Epub 2014 Dec 3. PMID: 25471897.

Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S, Vieths S, Kleine-Tebbe J; EAACI Task Force. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Allergy. 2008 Jul;63(7):793-6. doi: 10.1111/j.1398-9995.2008.01705.x. Epub 2008 May 16. PMID: 18489614.

Bentz S, Hausmann M, Piberger H, Kellermeier S, Paul S, Held L, Falk W, Obermeier F, Fried M, Schölmerich J, Rogler G. Clinical relevance of IgG antibodies against food antigens in Crohn’s disease: a double-blind cross-over diet intervention study. Digestion. 2010;81(4):252-64. doi: 10.1159/000264649. Epub 2010 Jan 30. PMID: 20130407.

Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia. 2010 Jul;30(7):829-37. doi: 10.1177/0333102410361404. Epub 2010 Mar 10. PMID: 20647174; PMCID: PMC2899772.

Caio G, Volta U, Tovoli F, De Giorgio R. Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity. BMC Gastroenterol. 2014 Feb 13;14:26. doi: 10.1186/1471-230X-14-26. PMID: 24524388; PMCID: PMC3926852.

Wilson JM, Platts-Mills TAE. α-Gal and other recent findings that have informed our understanding of anaphylaxis. Ann Allergy Asthma Immunol. 2020 Feb;124(2):135-142. doi: 10.1016/j.anai.2019.11.024. Epub 2019 Nov 28. PMID: 31785367; PMCID: PMC7318893.

Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004 Oct;53(10):1459-64. doi: 10.1136/gut.2003.037697. PMID: 15361495; PMCID: PMC1774223.

Muthukumar J, Selvasekaran P, Lokanadham M, Chidambaram R. Food and food products associated with food allergy and food intolerance – An overview. Food Res Int. 2020 Dec;138(Pt B):109780. doi: 10.1016/j.foodres.2020.109780. Epub 2020 Oct 15. PMID: 33288166.

Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Histamine Intolerance: The Current State of the Art. Biomolecules. 2020 Aug 14;10(8):1181. doi: 10.3390/biom10081181. PMID: 32824107; PMCID: PMC7463562.

Lyons DO, Pullen NA. Beyond IgE: Alternative Mast Cell Activation Across Different Disease States. Int J Mol Sci. 2020 Feb 22;21(4):1498. doi: 10.3390/ijms21041498. PMID: 32098318; PMCID: PMC7073060.

Lu X, Hisada A, Anai A, et al. Study of the Correlation Between Multiple Chemical Sensitivity and Personality Using the Quick Environmental Exposure Sensitivity Inventory Questionnaire and the Temperament and Character Inventory. J Occup Environ Med. 2020;62(7):e348-e354. doi:10.1097/JOM.0000000000001899

Gaddis GM, Gaddis ML. Introduction to biostatistics: Part 3, Sensitivity, specificity, predictive value, and hypothesis testing. Ann Emerg Med. 1990 May;19(5):591-7. doi: 10.1016/s0196-0644(05)82198-5. PMID: 2331107.

Is food antigen IgG testing supported by clinical research?

The use of IgG food sensitivity testing is widespread within functional medicine. Numerous companies currently sell consumer based tests as part of a multi-million dollar industry with lucrative financial incentives. Proponents of the IgG test often point to the mechanism of a disrupted intestinal barrier function that can lead to the unregulated trafficking of incompletely digested food fragments into the bloodstream followed by a concomitant inflammatory response that may involve the creation of IgG based antibody as the rationale for the test’s implementation, but do clinical outcomes support this mechanism?

What do medical organizations and the latest clinical review have to say?

As part of a 2008 Practice Parameter evaluating allergenic specific diagnostic testing, The American Academy of Allergy, Asthma and Immunology placed IgG and IgG4 food testing in a category of tests as unproven.

  • “IgG antibodies to common foods can be detected in health and disease. This reflects the likelihood that circulating immune complexes to foods occur in most normal individuals, particularly after a meal that would be considered a normal physiologic finding. It was therefore concluded that food specific IgG or IgG subclasses should not be used in the diagnostic evaluation of food allergy.”

A 2008 paper from the European Academy of Allergy and Clinical Immunology also robustly recommended against the use of IgG/IgG4 based food sensitivity testing profiles.

  • “In contrast to the disputed beliefs, IgG4 against foods indicates that the organism has been repeatedly exposed to food components, recognized as foreign proteins by the immune system. Its presence should not be considered as a factor which induces hypersensitivity, but rather as an indicator for immunological tolerance, linked to the activity of regulatory T cells. In conclusion, food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints.”

A 2015 review article by Lomer that examined the potential mechanisms behind food intolerances and the testing available to determine such intolerances reiterated again the recommendations from the previously cited medical organizations that IgG or IgG4 food allergy testing should be AVOIDED.

  • “The presence of IgG or IgG4 against foods represents exposure to that particular food and indicates immunological tolerance. Therefore, increases in IgG or IgG4 concentration against food or food components are common and clinically irrelevant”

While simply accepting the recommendations and proclamations from medical organizations would be falling into a logical fallacy of appealing to authority, we should likely take pause to better examine any clinical evidence that is present to support the use of such testing and recognize that the use of IgG based testing would indeed go against medical recommendations.

Is the IgG based test flawed from the start as a clinical tool?

In order for a test to warrant use, it must detect something of clinical utility, usually discerning between a sick and healthy population, AND come with a degree of certainty or accuracy about the test result. Essentially, the test must have BOTH clinical validity as well as reliability or accuracy as a test.

In the case of IgG food sensitivity tests, it is more likely, based on currently accepted theories of immunological function, that IgG antibodies to a food antigen do not represent a pathological immune phenomenon with a definitive clinical correlation. Even if IgG tests are 100% accurate, which they most assuredly are not, the results of such testing provide, at best, unclear value, and at worse, distracting non-value.

How do we know if an IgG test is even accurate?

Even if we were to give IgG testing the clinical benefit of the doubt, how can we confirm the accuracy of specific IgG tests? Are there published data about the specificity and sensitivity of such tests? For tests to have a determined sensitivity or specificity, that has to be a gold standard method for determining who actually has the “disease” or condition for which a test is claiming to detect. For IgG food sensitivity testing, there is essentially no gold standard determinant or agreed upon disease state. Thus no company can readily provide a reliable and clinically relevant measure of its tests sensitivity or specificity.

Extending this further, we see that even if an IgG food sensitivity test actually could detect a clinically meaningful food allergy (most data says it does not), when foods are tested via a panel of 100, 150 and 200 foods, the chances/number of false positives or negatives increases dramatically. So EVEN IF a test had a 90% sensitivity and specificity, by testing an array of 50, 100 or 200 foods you will obtain a non-trivial number of false positives and negatives AND not know which ones are false versus true. This is a massive issue when considering the use of any test to guide clinical treatment.

See these helpful reviews for basic introductions to clinically relevant biostatistics

Gaddis GM, Gaddis ML. Introduction to biostatistics: Part 3, Sensitivity, specificity, predictive value, and hypothesis testing. Ann Emerg Med. 1990 May;19(5):591-7. doi: 10.1016/s0196-0644(05)82198-5. PMID: 2331107.

Ranganathan P, Pramesh CS, Buyse M. Common pitfalls in statistical analysis: The perils of multiple testing. Perspect Clin Res. 2016;7(2):106-107. doi:10.4103/2229-3485.179436

Why did I share this background?

As a clinician, it is imperative that we understand at least the basics of biostatistics including the concepts of sensitivity and specificity as well as pre-test probability or the likelihood that a positive result on a test actually represents something clinically meaningful for a patient. Where most clinicians get into trouble is selecting tests for patients with a LOW pretest probability or a LOW likelihood of a positive result having any clinical relevance. MORE positives does not mean better. Additionally, clinicians can get into trouble when they perform SINGLE tests with poor reliability, unclear clinical significance or significant biological/circadian variability.

IgG food sensitivity testing falls into all of these categories.

Why is then IgG testing so widespread?

You may be asking, “Why is IgG food sensitivity testing so widespread if it suffers from a lack of clinical validity and testing reliability?” Good question. The short answer, in my opinion, is that there is some research that is commonly shared (by practitioners and lab testing companies alike) as support for its clinical utility specifically with GI conditions and migraines. But are these reasonable and accurate conclusions? Let’s explore:

In one of the most commonly cited studies in support of IgG based testing Atkinson et. al. randomized patients with IBS to receive a specialized diet based on IgG antibodies or a sham diet. While it’s not entirely clear from the paper if the patients understood during the consenting process that they could receive a sham diet, I applaud the researchers for trying to have some control against the placebo effect. In order to truly control for placebo in a dietary intervention such as this, the individual receiving a personalized diet must truly believe that the diet one is given is based on one’s IgG testing and will make one better. Commentary aside, what the researchers found was that on the whole, there was a minimal clinical difference between the group receiving the IgG based diet versus the sham diet. When the researchers looked at the reported adherence to the diet, however, they noted a signal that suggested that those with a stronger adherence to the IgG based diet WERE clinically better off after 3 months than those receiving the sham diets. Based on this subpopulation, the researchers concluded that “Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.” A not unreasonable conclusion. But what foods did the IgG group most commonly eliminate?

Selections from Table 2 from the study

  1. Yeast: 86.7% (of individuals eliminated this food based on IgG testing)
  2. Milk: 84.3%
  3. Whole Egg: 57.3%
  4. Wheat: 49.3%
  5. Cashew: 49.4%
  6. Pea: 38.6%
  7. Almond: 28%
  8. Barley: 26.7%
  9. Beef: 24%
  10.  Corn: 22.7%
  11.  Brazil Nut: 22.7%
  12.  Shellfish: 21.3%

I have bolded the foods widely accepted as the most commonly immunogenic with regards to IgE mediated allergies. You see almost all of the foods eliminated by the IgG group came from foods that would be commonly eliminated on an empiric elimination diet, as was stated in Healthy Gut, Healthy You years ago. More to come here.

What is perhaps even more important to note from Table 2 of the study is the percentage of participants in the sham group who eliminated the foods most commonly eliminated by the IgG testing group.

Selections from Table 2 from the study

  1. Yeast: 0% (of individuals in sham group eliminated this food)
  2. Milk: 1.3%
  3. Whole Egg: 26.7%
  4. Wheat: 8%
  5. Cashew: 8%
  6. Pea: 1.3%

In looking at this data, it appears then what the researchers ULTIMATELY studied was the effect of a reasonably formulated elimination diet. They did not really study the effectiveness of a personalized diet based on IgG testing.

There is another wrinkle to this study worth exploring further.

You may be asking, if the sham group didn’t eliminate the foods that the IgG testing group most commonly eliminated, what did they actually eliminate?

Selections from Table 2 from the study

  1. Potato: 61.3% (of individuals in the sham group eliminated this food) compared to 9.3% in the IgG group
  2. Rice: 54.7% compared to 8% IgG group
  3. Tomato: 44% compared to 4% IgG group
  4. Apple: 33% compared to 1.3% IgG group
  5. Walnut: 29.7% compared to 2.7% IgG group

What we see now, is not only did the sham group NOT eliminate the foods the IgG group most commonly tested positive for, they most commonly ELIMINATED the foods that the IgG group DID NOT test positive for and, outside of walnuts, DO NOT come from any of the commonly accepted immunogenic foods.

To summarize my distillation of what was actually studied.

  • A group of individuals who eliminated some of the most commonly immunogenic and problematic foods


  • A group of individuals who eliminated foods that are both NOT commonly accepted as immunogenic and did not show up frequently on IgG testing for the group as a whole.

And what happened?

The group following the sham diet actually got a little better. Yes, the sham group that still included all the commonly problematic foods, who eliminated foods that were very unlikely to be an issue, got better. When the researchers looked at all individuals (both low and strong adherence) the sham and IgG groups were clinically no different. The only sub-analysis that demonstrated clinically and statistically significant differences was between the strongly adherent groups (both sham and IgG testing group). The strongly adherent IgG testing group (commonly eliminating wheat, eggs, and dairy) got better by a larger margin than the most strongly adherent to the sham diet. BUT, those strongly adherent sham dieters following the significantly bogus diet that still contained wheat, eggs, dairy amidst other potentially problematic foods improved their IBS symptom scores by over 50 points (the clinically significant threshold) by the end of the 3-month study.

They STILL got better.

Placebo is powerful, folks.

What is then really behind food intolerance and reactions?

The reason I suspect that many functional medicine practitioners (and patients) have gone down the route of IgG food sensitivity testing is that food reactions or symptoms attributed to the consumption of food ARE VERY REAL and patients (and practitioners) have an idealized goal that one can identity via a test the precise foods one should and should not consume in order to heal and have robust health.

When we look at the literature and evidence from clinical practice to determine what could mechanistically be behind an individual’s food reactions, there are a number of possibilities, with most stemming from disturbance to one’s gut health.

Most Likely Common Mechanisms Behind Food Reactions

  1. Gut dysbiosis
  2. Microbially incompatible diets and FODMAP sensitivity
  3. Maldigestion
  4. Non-celiac gluten sensitivity
  5. Limbic system reactivity
  6. IgE based reactions
  7. Neurohormonal responses secondary to the consumption of certain food chemicals including
  8. Histamine intolerance and/or mast cell activation
  9. Increased perceived stress/allostatic load
  10. Excessive consumption of detergents, processed “anti-food” and other compounds that disrupt the epithelial and mucus barrier

Returning to the previously cited 2015 review by Lomer, we see that many individuals can experience symptoms of food intolerance related to the consumption of dietary FODMAPs. A 2003 study of celiac disease patients found that SIBO or small intestinal dysbiosis was found in a majority of patients with persisting GI symptoms despite the removal of gluten and GI symptoms improved after the pharmacologic treatment of their SIBO.

Lactose intolerance related to enzymatic deficits and an inability to digest the sugar lactose is commonly accepted in clinical practice as a mechanism for intolerance to certain dairy products. Lomer’s paper also highlighted potential mechanisms (all non IgG) for food reactions related to caffeine, salicylates, and high glutamate and histamine (or other amine) containing foods. The proposed mechanisms for each food group, while individually unique, all centered around neurohormonal responses within the GI tract.

Returning to FODMAPs, a 2017 randomized controlled trial demonstrated an eight-fold decrease in histamine levels in those adopting a low FODMAP diet, suggesting both a therapeutic intervention and mechanism for food reactions. In the January 2021 FFMR case study we documented the improvement of a patient with GI symptoms with food intolerances and “food fear” through the implementation of a nervous system/limbic retraining program, highlighting the critical influence of our neurohormonal systems and food reactions. In one of the most important review papers of anaphylaxis and allergy published in 2019, authors Wilson and Platts-Mills discuss our evolving understanding of how the gut microbiome and our recent influx of novel environmental exposures coupled with modern hygiene practices are likely causal in the development of allergy.

Final Thoughts

While this review has focused primarily on the role of IgG food sensitivity testing in clinical practice, a few lab companies have recently launched a new form of food sensitivity test that seeks to identify immune complexes of IgG alongside a complement cascade fragment known as C3d. Developers of the test suggest that the presence of the C3d complement fragment in connection with IgG food antibody provides greater evidence for a pathologic immune-activating response to a specific food. While mechanically this test may lead to greater specificity and potential clinical relevance, there is insufficient evidence from clinical outcome studies at this time for us to suggest the routine adoption of this test in clinical practice.

Additional References

Bentz S, Hausmann M, Piberger H, Kellermeier S, Paul S, Held L, Falk W, Obermeier F, Fried M, Schölmerich J, Rogler G. Clinical relevance of IgG antibodies against food antigens in Crohn’s disease: a double-blind cross-over diet intervention study. Digestion. 2010;81(4):252-64. doi: 10.1159/000264649. Epub 2010 Jan 30. PMID: 20130407.

Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia. 2010 Jul;30(7):829-37. doi: 10.1177/0333102410361404. Epub 2010 Mar 10. PMID: 20647174; PMCID: PMC2899772.

Caio G, Volta U, Tovoli F, De Giorgio R. Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity. BMC Gastroenterol. 2014 Feb 13;14:26. doi: 10.1186/1471-230X-14-26. PMID: 24524388; PMCID: PMC3926852.

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Practitioner Question

Listener asks:

“How do you attract new clients? How do you expand a Functional Medicine practice?”

This is a common question we see and while all practitioners will face their own individual challenges based on the nature of their personal circumstances, the best way to think about growing a practice starts by identifying the “barriers to entry” for new patients. The three largest barriers to entry are:

  1. Awareness, Visibility, and Understanding (of your practice and Functional Medicine in general)
  2. Cost – Payment Structure
  3. Service Delivery Method 
Awareness, Visibility, and Understanding (of your practice and functional medicine in general)

The biggest initial hurdle with starting a practice is generating authentic awareness about your clinical endeavors. There are obviously a number of ways to go about this, but the most important are to have an easily navigable website with a corresponding detailed Google My Business page. New patients need to be able to find you via an internet search and these are basic places to start.

For your website, you need to be as specific as possible about precisely what you do. The more specific the better. You need the patient to have a clear understanding of what you can offer them and how you will do that. One great way of doing this and building further rapport with patients is by creating a short video about you and your specific clinical techniques. This video should be very visible on your website. You should also have an easy one-click capacity to book any introductory sessions or consultations with your practice.

If you provide services with a local community, you should make a list of like-minded professionals with whom you can receive referrals and reach out to them to make them aware of your practice. Even having only 1-2 professionals who understand your practice can turn into consistent practice referrals.

It is also important to collect patient experiences in your practice (we prefer this term over testimonials). Video patient experiences are quite powerful, but written/text is also helpful for potential patients to see how you could help them.

If you have completed any training with a professional organization that has a directory listing, you should keep this updated for greater visibility.

Cost – Payment Structure

Most new patients are used to the broken health insurance system. They may ask questions regarding health insurance and if you accept insurance. Overall cost (or perceived value and investment) from the patient is perhaps the biggest barrier for patients to begin work with you if you are using a cash-based practice. You should clearly state the financial structures of your practice on your website as this will cut down on dead-end inquiries. If you are starting out a practice, you should consider making prices more affordable than they may be after 2 years of practice when volumes and demand have increased. Keep billing as simple as possible, but consider the use of payment plans if care is provided over a series of visits – weeks or months.

Service Delivery Method 

You must decide how you will primarily work with your patients. Will the relationship be via telemedicine or in-person? Will you be acting as a health consultant or medical provider? If you are providing in-person services, your local visibility is MUCH more critical for patient acquisition and you should direct your efforts here accordingly. If you are seeking to draw from a much larger pool via telemedicine, you will technically have a much larger audience to draw from, but you will also be fishing with many more fishermen. This brings me back to an earlier point about needing to be very specific about your clinical practice, having as many questions answered on your website as possible and including a thorough, but not overly verbose video that allows potential patients to know you.

Final Thoughts

It is important to remember that it takes tremendous dedication and TIME to grow a practice. It will take multiple years to grow the volume, awareness, and sustainability of your practice – this has been the experience with each of the founding doctors of the Ruscio Institute for Functional Medicine and should not be overlooked or forgotten.


I care about answering your questions and sharing my knowledge with you. Leave a comment or connect with me on social media asking any health question you may have and I just might incorporate it into our next listener questions podcast episode just for you!