Can Blood Tests Detect Food Sensitivity?

The use of IgG “food sensitivity” testing is widespread within functional and integrative medicine. Numerous companies currently sell consumer based tests as part of a multi-million dollar industry with lucrative financial incentives and many practitioners use these tests as the backbone of their clinical approach.

But does research actually support the use of food sensitivity testing? Can IgG blood tests actually detect a “food sensitivity”?

The short answer to both of these questions is no and no. Now that the pot is a little stirred, let’s jump in to see why!

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 individuals 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 “not-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.
  • Individuals addressing concerns with food reactivity should first consider an empirically designed elimination diet that prioritizes the elimination of commonly immunogenic foods. Examples of dietary interventions that may improve food reactivity include but are not limited to: Paleo diet, Low FODMAP diet, Low Histamine diet, AIP diet, Specific Carbohydrate diet and a partial or full elemental diet. Individuals should weigh the potential risks and benefits of an elimination diet based on their primary symptoms and current diet, work with a qualified healthcare provider when necessary, and aim to use the least restrictive, most accessible diet possible to achieve the desired therapeutic outcome.
  • Outside of dietary and lifestyle based treatments, individuals should strongly consider implementing gut directed interventions to address food reactions given the correlations of food allergy with a disturbed gut microbiome and an altered gut barrier – immune system interface.
  • Alongside gut directed and nutritional therapy, individuals should consider addressing underlying nervous system dysregulation or high perceived stress that could be contributing to the symptoms of food reactivity.

What is a food reaction?

Food reactions are incredibly real phenomena. A food reaction can be best described as any symptom or constellation of symptoms that one reasonably correlates to the consumption of a given food (or processed “not-food”).

To help us understand our terms and the topic at hand, I want to clarify my use of the term food reaction as compared to other commonly used terms such as food allergy, food sensitivity and food intolerance.

Food Allergy, Food Intolerance, Food Sensitivity

As commonly used, the terms food allergy, food sensitivity and food intolerance all describe some type of food reaction, often delineating from each other based on the theoretical mechanism behind the reaction.

Food allergies are understood to result from an antibody known as IgE and involve a distinct immunologic response.

Food intolerances typically describe foods that are maldigested or malabsorbed in the GI tract such as the sugar lactose.

The term “food sensitivity”, however, has emerged as an attempt to describe the remainder of food reactions that do not fit nicely into the categories of food allergy or food intolerance. For other reasons that are not entirely clear to me, the term “food sensitivity” has been causally connected with an immune response involving the antibody IgG. Unfortunately, the totality of the evidence I have reviewed to date does not support the concept of a pathologic IgG mediated “food sensitivity”.

The Issue of “Food Sensitivity”

Sadly, the term “food sensitivity” has come to engulf the incredibly broad spectrum of food reactions that have not been considered food allergies or food intolerance. Despite the fact that the food reactions experienced in this diverse space involve a number of different immune mechanisms, the concept of a pathological IgG mediated immune response to food has emerged to seemingly describe all of the reactions in the waste basket of “food sensitivities”. And this is simply not true.

The Immuno“logical” Fallacy

Who wouldn’t be enticed, clinician and patient both, with the idea that one can, with just a simple blood sample, find ALL the foods that are creating food reactions? The question of whether a food is “good or bad” will likely never fizzle out and so we will continue to observe the elusive search for a way to answer the unanswerable.

As the IgE mediated food allergy is well described and understood immunologically, it would, on the surface, seem rational to think that other types of food reactions could be related to a similar, but distinct immune mechanism involving perhaps another immunoglobulin such as IgG or IgA.

To the best I can discern, I believe that the improper grouping of all food reactions that cannot be described as food allergies or food intolerances as “food sensitivities” and the incorrect application of the IgE concept of food allergy to describe “food sensitivities” has lead us into unfortunate confusion and prevented individuals from actually addressing the underlying reasons for experiencing real food reactions.

What does an IgG antibody to a food actually represent?

While a pathological IgG “food sensitivity” does not appear to exist, this does not mean that an IgG antibody to a food or food complements isn’t a detectable immunological phenomena.

Here are some summary statements from a selection of medical organizations and research studies describing the IgG food antibody.

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 reactions and the testing available to determine such reactions 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”

IgG antibodies to food, you see, are real and detectable immunologic phenomena, but IgG food antibodies do not appear to be clinically reliable markers to indicate or describe a food reaction as commonly experienced by most individuals.

In the timeless words of Inigo Montoya from The Princess Bride,

“You keep using that word (test). I do not think it (that test) means what you think it (that test) means.”

Is IgG “food sensitivity” testing flawed from the start anyway?

While the majority of evidence I have reviewed suggests that IgG based “food sensitivity” testing is not clinically viable, let me also highlight other inherent issues with IgG “food sensitivity” testing that would make it clinically challenging to use EVEN IF the results of such testing represented something of clinical utility.

Even if we were to give IgG “food sensitivity” 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, there 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 (unlike food allergy). Thus no company can readily provide a reliable and clinically relevant measure of its test’s sensitivity or specificity.

Extending this further, we see that even if an IgG “food sensitivity” test actually could detect a clinically meaningful food reaction or allergy, when foods are tested via a panel of 100, 150 and 200 foods, the chances/number of false positives or negatives increases dramatically through a concept known as multiple hypothesis testing. 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 false 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 and why IgG “food sensitivity” tests are, in my opinion, flawed from the start.

But there is research saying IgG food sensitivity tests work and I have seen people get better using these tests. What gives?

In one of the most commonly cited studies in support of IgG based “food sensitivity” 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 such as AIP.

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 versus a standard 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, and 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 really behind food reactions then?

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 disturbances to one’s gut health.

The most likely mechanisms behind common 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 (food allergy)
  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 “noti-food” and other compounds that disrupt the epithelial and mucus barrier

While I cannot go into exquisite detail about each of these mechanisms, I have shared a number of helpful papers in the references section of this article to further explain the likely mechanisms behind most food reactions. Focusing on a few of the more pertinent mechanisms, I want to highlight the previously cited 2015 review by Lomer, suggesting that many individuals experience symptoms of food reaction related to the consumption of dietary FODMAPs, a specific type of carbohydrate that can be metabolized by certain gut microbiota. Lomer’s paper also highlights the 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 these food chemicals, while individually unique, all center around neurohormonal responses within the GI tract (not IgG responses). Moving further into the world of the gut microbiome, 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 and food reactions despite the removal of gluten and GI symptoms improved after the pharmacologic treatment of their SIBO.

As part of a continuing education newsletter for functional medicine practitioners, colleagues in my collaborative clinic documented the improvement of a patient with GI symptoms, food reactions 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 food allergies and food reactions.

Final Thoughts: What You Can Do!

Food reactions are a very real and sometimes challenging phenomenon to treat. While it seems clear IgG testing is not a reliable and helpful modality for identifying reactive foods, there is some emerging research examining the effectiveness of testing for food antigen and complement – IgG immune complexes as a method for identifying foods causing food reactions. While the concept is intriguing, there is insufficient peer reviewed research to suggest the use of such testing at this time and these tests are unlikely in the future to be of much clinical utility.

As testing is unlikely to be helpful in one’s efforts to identify reactive foods, most individuals who wish to address concerns of food reactivity should first consider an empirically designed elimination diet that prioritizes the elimination of commonly immunogenic foods. Examples of dietary interventions that may improve food reactivity include but are not limited to: Paleo diet, Low FODMAP diet, Low Histamine diet, AIP diet, Specific Carbohydrate diet and a partial or full elemental diet. Individuals should weigh the potential risks and benefits of an elimination diet based on their primary symptoms and current diet, work with a qualified healthcare provider when necessary, and aim to use the least restrictive, most accessible diet possible to achieve the desired therapeutic outcome.

Outside of the implementation of empirically formulated nutrient dense elimination diets, individuals should strongly consider implementing additional gut directed interventions to address food reactions. You can read more about my thoughts for improving gut health to treat autoimmune disease in a previous blog: How Healing Your Gut Can Help Treat Autoimmune Disease.

Lastly, I have seen individuals achieve great benefit in reducing their symptoms of food reactivity by addressing underlying nervous system dysregulation or high perceived stress. There are numerous approaches in this domain that can include meditation, prayer, gratitude journaling, the use of adaptogenic herbs or amino acids, as well neural retraining programs such The Gupta Program or DNRS.

Let us know in the comments your thoughts and what has worked for you!

References

  1. Lomer MC. Review article: the aetiology, 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.
    https://pubmed.ncbi.nlm.nih.gov/25471897/
  2. 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.
    https://pubmed.ncbi.nlm.nih.gov/18489614/
  3. 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.
    https://pubmed.ncbi.nlm.nih.gov/31785367/
  4. 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.
    https://pubmed.ncbi.nlm.nih.gov/15361495/
  5. 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.
    https://pubmed.ncbi.nlm.nih.gov/33288166/
  6. 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.
    https://pubmed.ncbi.nlm.nih.gov/32824107/
  7. 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.
    https://pubmed.ncbi.nlm.nih.gov/32098318/
  8. 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
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337109/
  9. 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.
    https://pubmed.ncbi.nlm.nih.gov/2331107/
  10. 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.
    https://pubmed.ncbi.nlm.nih.gov/20130407/
  11. 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.
    https://pubmed.ncbi.nlm.nih.gov/20647174/
  12. 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.
    https://pubmed.ncbi.nlm.nih.gov/24524388/
  13. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. The relevance of using the C3d/immunoglobulin G test in clinical intervention. Altern Ther Health Med. 2015 Jan-Feb;21(1):16-27. PMID: 25599429.
    https://pubmed.ncbi.nlm.nih.gov/25599429/

 

About Rob Abbott, M.D.

Rob Abbott, M.D. is Autoimmune Wellness's resident Medical Advisor. He is medical director and the functional physician for Resilient Roots: Functional and Evolutionary Medicine in Charlottesville, Virginia. He completed his family medicine internship with VCU-Shenandoah Valley in Winchester Virginia and is a graduate of the University of Virginia (U.Va.) School of Medicine where he served as a student ambassador for the U.Va. School of Nursing’s Compassionate Care Initiative, promoting resilience, compassion and self-care. He has completed additional training with the Institute for Functional Medicine, is a Kresser Institute ADAPT Level 1 trained clinician, and is an AIP Certified Coach. Rob approaches medicine from an evolutionary and functional perspective and practices what he calls “spiritually focused and evolutionarily informed functional medicine.” In his free time, Rob enjoys creative expression through writing, sharing blogs, poetry and podcasts through his website amedicinalmind.com.

2 comments

  • srd says

    Genuine question: Isn’t IgG testing used to screen for Celiac, with a positive result then confirmed by a biopsy to make a final diagnosis? Is that testing technology different than what is “debunked” in your article? Wouldn’t a more comprehensive gluten panel (looking at IgG numbers for the other proteins in gluten) be as reliable as the two proteins screened for Celiac?

  • Afm says

    Hi, I also have a genuine question. It was my understanding that Eosinophilic Esophagitis, with which I have been recently diagnosed, is an IgG4 mediated immune response? It is considered food-allergy driven.

    I’m not making the argument for IgG blood testing, but wondering more how EoE fits in with the definitions of allergy/intolerance/sensitivity above. Thanks for your time!

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