The Controversy of IgG Food Sensitivity Testing

Episode Intro:

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DrMichaelRuscio:

Hey, everyone. Welcome back to Dr. Ruscio Radio. This is Dr. Ruscio. Today, let’s jump in and try to give a somewhat definitive answer on the question – “Is there any validity to food allergy testing?” This is an excerpt from our August, 2021 Future of Functional Medicine Review. Again, just trying to continually point you this month to this resource. We went through a review of the evidence to publish in our FFMR so that whoever is a member – whether they be a clinician, provider or a lay person – can access this overview of IgG food allergy testing/sensitivity testing. Is this something that’s clinically validated? The short answer on this is no, but let’s dig into some of the detail. Again, great write-up here in the newsletter. I’m just going to hit some of the high points. The summary of the key points — IgG food sensitivity testing is not robustly supported by research and consumer and practitioner directed IgG testing suffers from a lack of clinical validity and testing reliability.

The Validity of IgG Food Allergy Testing

DrMR:

People who claim they benefited from following the results of the testing may have achieved benefit as a result of an enhanced placebo effect – or indirectly because they essentially improved their diet quality and reduce the amount of foods that are commonly problematic for people. The majority of food reactions experienced by patients can likely be explained by gut dysbiosis, maldigestion, limbic system reactivity, IgE-based reactions or neurohormonal responses. These are reactions to things like histamine or perceived stress that really may underlie where the food recommendations are coming from. The newer assays examining the complement and IgG immune system complexes have been proposed as more sensitive and more specific, but they suffer from insufficient peer review and research to suggest their regular adoption into clinical practice is something that makes sense.

DrMR:

The few evidence points that I find to be most compelling here – There was a 2008 practice guideline review by the American Academy of Allergy, Asthma and Immunology. They placed IgG and IgG4 food testing in the category of tests marked as unproven. Here’s a quote, in particular, I found quite compelling: “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 and that they are found or considered a normal physiological finding.” I think that’s really important to keep in mind. Some immune system prevalence and reactivity is considered normal. I think where the mistake has been is in thinking that any detectable immune response is pathological.

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DrMR:

Then, another paper from the European Academy of Allergy and Clinical Immunology had a similar finding – “In contrast to the disputed beliefs, IgG4 against foods indicates that the organism has been repeatedly exposed to food components and recognized foreign proteins by the immune system. Its presence [the IgG4 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. So in conclusion, food specific IgG4 does not indicate food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components, therefore tasking for IgG to foods is considered as irrelevant for the laboratory workup of food allergy or intolerance as should not be performed.” Sorry, some of these quotes are quite wordy. So, essentially what they’re saying is this is a normal physiological response, part of tolerance and IgG4 testing is irrelevant for the laboratory workup of food allergy or intolerances, and should not be performed. A 2015 review paper stated – “Therefore, increased IgG or IgG4 concentrations against food or food components are common and clinically irrelevant.”

DrMR:

Now, we also wanted to include evidence points that were not from major bodies in allergy or immunology because perhaps there is some bias there. So we want to look at this from multiple vantage points. I think probiotics are a good example of this. I just saw a Medscape article on probiotics and IBS. They hit SIBO, low FODMAP and peppermint oil – and then there’s a one-liner stating there’s not good evidence showing that probiotics help IBS. It’s just amazing to me how discordant with the data these findings are. I mean, you’re mentioning peppermint oil – which has four, maybe five clinical trials – and probiotics and IBS have dozens and dozens of clinical trials. It’s just hard to wrap your mind around that, so we are going to be careful not to just look to major bodies’ recommendations. We will look at those – and those are important to look at, of course. However, we’ll also toggle over to more of the raw data/clinical trial data and look at what this says in case there are any gaps or bias in what some of the larger reviews and bodies in allergy and immunology are concluding.

Food Allergy Testing Study

DrMR:

This leads us to an often cited study supporting the utility of food allergy testing by Atkinson, et al. and a few key takeaways. You can see the more detailed write-up in the FFMR. There was a minimal clinical difference between the group receiving the IgG-based diet vs. the sham diet. What that means is half the participants received the diet tailored to the testing results and the other half got this arbitrary sham diet. The participants didn’t know, but this was like a placebo in control. There was minimal difference between the two. Now, there is one sliver of benefit here. At the three month mark, those who were the most adherent to the IgG-based diet were better off than those receiving the sham diet. However – and this is something I wrote about in Healthy Gut, Healthy You – what you see in terms of what the IgG-based diet participants were following is pretty much what you get when you go on the paleo diet or perhaps paleo-autoimmune diet. The most common allergens were yeast, milk, eggs, wheat, nuts (including cashews and almonds), peas, corn and shellfish. So, there is some sliver there.

DrMR:

This is one study and one component of one study. To be the most generous, what you see in a subset of one study is that the most adherent participants were better off at the three month mark than those who were following the sham diet. It leads you right back to common allergens that a clinician will have a patient addressing early on via elimination and re-introduction. Clinically, the more challenging part about this is that some of the food allergy tests now are north of $1,000. So, to spend $1,000+ to get what one could figure out in one or two months – and almost for certain more accurately – makes it very hard to support these tests. Why I say “almost for certain more accurately” is because you also have FODMAP, which is massive for patients with gut issues and histamine, which is important for a subset. You won’t get any of that when pursuing these tests.

DrMR:

Another component here that I think is worth mentioning is that the individuals that went on the sham diet did not end up removing commonly problematic and inflammatory foods (hence the sham diet). They weren’t really given a treatment. Yet, they still reported improvement, which tells you that there’s something to placebo here that’s very important to be factoring in. I’ve said this many times before on the podcast – We have to be careful when a clinician says, “Well, I see it work clinically.” That’s not worth that much if the clinician is either ‘placeboing’ their patients or even worse yet, if the clinician is a bit placebo themself or operating underneath confirmation bias. ‘Placeboing’ a patient is where the clinician will say, “Well, I’m having people follow the tests and they get better.” This is a true observation. However, what’s not being seen here is that you could have them go on a standard diet template – paleo, low FODMAP or whatever elimination diet fits your philosophy – because most of the benefit probably comes from a handful of foods and diet quality and see the same improvement in patients. So, this is why I think it’s important to not let clinicians just play that card of “Well, I see it work clinically” because that doesn’t always carry weight if the clinician isn’t being scrupulous about weeding out placebo.

DrMR:

The other aspect that is crucially important to understand is that there are many facets of diet you will not get on a food allergy test. Meal timing, meal frequency or intermittent fasting would be the other side of that coin; FODMAPs, fiber and histamine would also be a few very important ones. As I also learned, if your gut is a mess, you’re going to react to a whole boatload of foods. Trying to eliminate foods to heal a parasite or SIBO or inflammatory bowel disease… it’s really not going to get you there unless you’re doing interventions to repair the cause of the damage and the cause of the reactivity.

FFMR Plus Study Summaries

DrMR:

I’d also like to shift gears to an assortment of studies that were flagged and summarized in our FFMR Plus. That is the weekly digest that we publish that has a short 3 to 5 bullet point summary of the latest impactful research. This, to me, has been a godsend. As you know, it used to take an hour per night of reading, but now I can read this digest in 15 to 20 minutes once per week and get the same as 7 hours. It’s been very helpful.

DrMR:

There was a study looking at the histology – the tissue – of IBS patients. They found that when compared to healthy controls, the IBS subjects had increased intraepithelial lymphocytes. Essentially, they had more white blood cells or immune cells, which would suggest that there’s a component to IBS that is immune in nature. How I’ve described the way immunoglobulin therapy works- and this is just a rough heuristic – you have the microbiota and you have the immune system and these are two components that are essential for a healthy gut. We can get pretty far with modulation of the microbiota. Low FODMAP diet can be helpful, probiotics can be helpful and antimicrobials can be helpful. However, there’s this other type of support, which is more targeted at the immune system. This is where immunoglobulins can be quite helpful, as well as limbic retraining. So, just one study where they are finding there’s more immune system activity – or white blood cells – in IBS patients.

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DrMR:

Another study looked at serum gastrin. Gastrin is a marker that tracks with stomach acid. Richard McCallum had come on the podcast a few years ago. He was arguing that SIBO more often tends to be this top down phenomenon where oral cavity bacteria are seeding the overgrowth – rather than this Pimentel motility hypothesis, where you’re seeing colonic bacteria reflux upward and cause the seeding for the SIBO. He was postulating that gastrin could be a marker to look at that would predict if someone had sub-optimal stomach acid. Therefore, it would open the door for this oral bacteria down seeding. This study was entitled ‘Serum gastrin predicts hydrogen producing small intestinal bacterial overgrowth in patients with abdominal surgery.’ They found that both surgery itself – and separately gastrin – were independent predictors of SIBO.

DrMR:

Now, this is my intuition so take it with a grain of salt, but I’ve been tracking gastrin since that conversation. Now it’s been well over a year, I believe. My sense was that the gastrin being above 70 or 75 – which is what McCallum considered a cutoff for indicating that stomach acid may be inadequate – didn’t seem to correlate with those who had SIBO. Again, the grain of salt is important because it can be very challenging to recall who had what lab finding and what SIBO finding. Arbitrarily, let’s say the yield is only 5%. Now, that 5% is more than nothing. It’s not a mathematical chance. It could be statistically significant, but it may not be enough to register in the mind of a clinician.

DrMR:

This is why something like a retrospective chart review that we’ll do can also be helpful. I’m hoping to publish on that at some point in the next year or so. In 30 healthy controls and 146 patients that had either a hysterectomy, gastrectomy or cholecystectomy did find there was an increased risk. The risk was about 23% elevation as compared to controls, but this was lumping together the gastrin and the surgery. So, we’re doing a follow-up probe on this to see if we can get a better sense for what degree of increased risk the gastrin imposed, but nonetheless, there you have it.

DrMR:

Another study looked at Bifidobacterium and cognitive function. It found that after 16 weeks, 80 older adult patients who had mild cognitive impairment had better cognitive performance after probiotics. There was another study looking at Lactobacillus plantarum and it found that pregnant women had better retention of normal iron levels when taking a probiotic. This is, ostensibly, because of improved absorption. Another study found a 4 week, low starch and low sucrose diet led to improvements in IBS symptoms – probably no shocker there – but, I always think it’s helpful to see these studies coming in. One study looked at the effect of a single dose fecal microbiota transplant for ulcerative colitis found no benefit over placebo. Another study found that FMT – Fecal Microbiota Transplantation – did not show significant improvements for regular C. diff, but it did for recurrent C. diff. So, this is probably even more reason not to jump the gun too much on C. diff positionally, but also to build a case for FMT.

DrMR:

Another quite interesting study was about subjects consuming fermented milk. It found that probiotics in the milk, even under the highly acidic environment of the stomach, could make it through into the colon. Now, this may not actually be super relevant, but I wanted to use this study as a springboard into an aside. Getting probiotics into the colon, in my opinion, may not be as important because where we’re trying to cause an immunological and micro-biological impact is the small intestine. I wrote about this in Healthy Gut, Healthy You and some of the researchers were making this same speculation. The small intestine is more prone to overgrowth, dysbiosis, leaky gut and malabsorption. Presumably, with the probiotics, we want to have activity in the small intestine because this is where your leaky gut, inflammation and SIBO are all occurring. It’s also likely where the probiotics can have the most clinical effect – as evidenced by the fact that IBS seems to be more of a small intestinal phenomena. SIBO obviously is a small intestinal phenomena.

DrMR:

So, what we’re likely trying to influence is in the small intestine. So, these things that are enteric-coated to make sure they get all the way through the small intestine and then popped out and activated in the colon — I think we should re-examine that position. Another study found – this was a meta-analysis of 40 studies, almost 20,000 patients – that H. pylori increased the risk of adverse cardiovascular events by about 50% and was even higher when someone had the CagA virulence factor. That is reported on the GI map, by the way. That’s a nice benefit of the GI map.

DrMR:

One other study that I think is quite important for us to cover is the association of overt and subclinical hyperthyroidism with the risk of cardiovascular events. Yes – I said hyperthyroidism. What they found was that even for subclinical hyperthyroidism, there was an association with an increased risk of ischemic heart disease. Why does this matter? It matters because providers who are aggressively treating their patients with thyroid hormone will be causing subclinical hyperthyroidism. This is when you see people with TSH’s that are dwindling very low – either right at the cutoff of being frankly low or into the low levels. So, it’s important to keep in mind the evidence that substantiates too much thyroid hormone is a problem. We’ve talked about the meta-analysis that found that 34% of patients were able to come off their thyroid hormone and be just fine. In some of those patients, the medications were actually causing adverse events. This is another data point potentially showcasing that this is not subclinical hypothyroidism that is a derivative of iatrogenesis (meaning it’s not from medication). I want to be careful in disclosing that, but it does show you that having subclinically elevated levels of thyroid hormone can harm an individual.

DrMR:

I showcase and highlight this because there’s so much talk about, “Well, you’re not feeling good because you don’t have enough thyroid. We know that your endocrinologist said that your thyroid is fine, but the functional lab ranges are more narrow. Your TSH is 2.2 and your free T4 is 0.9 so you need to get on medication, we need to get your thyroid hormone levels up and that’s why you’re fatigued, constipated and depressed.” It’s important to countervail that messaging with the fact that if you push too hard there, you could exacerbate fatigue, insomnia, cause palpitations and damage the heart. That’s why I think this study is important to point to. Again, this is not a study that showed patients who are taking too much medication had these problems. This was naturally occurring hyperthyroidism, meaning they ostensibly had subclinical Graves’ disease. It still showcases the observation that there is damage associated with having thyroid hormone levels that are too high. Thyroid is not this “Push it, push it, push it… the more, the better… we want you at the upper end of the range for your T4 and we want you at the low end of the range for your TSH… your metabolism is revving… you’re super healthy.” It’s well-intentioned and it’s trying to get people to do things to improve their health, which I appreciate. However, when there’s ample evidence showing that this can harm people, that’s when we want to re-evaluate and re-appraise a system of beliefs.

Dr Ruscio Resources:

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DrMR:

These studies were all taken from the September 13th issue of the FFMR Plus. This is why I find these write-ups so helpful. You get these short snippets of information that give you this continual stream of data to either help you re-examine a belief or give you a better evidentiary basis for whatever belief or position you have. In any case, those are some updates all from the FFMR and FFMR Plus.

DrMR:

Remember, for the month of October, if you sign up at any point, it’s just $1 and you get your full 30 days of all access to see if it’s something that would benefit you or your patients – or if you’re a layperson, would help you navigate the maze of functional medicine care. You can access that at DrRuscio.com/review. I hope you will check it out and join us there. That’s really the clinical focus we’re trying to put out to give providers something to get behind, to help them do better and to improve and reform the field. I also hope you found these insights informative. We’ll talk to you next time. All right. Bye-bye.

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