After breaking down hormone testing earlier in the week (article linked here), someone asked me what my opinion was on food intolerance testing… Instead of lecturing her for half an hour, I said I’d tackle that topic here instead…
The problem with that is that food intolerance testing is a much more complex topic than hormone testing, because it involves understanding the immune system and how it functions, along with comprehending how gastrointestinal status, nervous system function and a whole of host of other factors which are nothing to do with the immune system influence the immune reactivity to foods and therefore impact the utility of intolerance testing itself.
So I began, as always, with trying to answer whether these tests were at all useful? Obviously, I came up with the answer of ‘it sort of depends…’ but I also realised that there was a lot of nonsense out there about food intolerances and the testing that can be useful, so I wanted to put an explanation of my thoughts, and the science behind them, here.
I do want to preface this article by saying that if you’ve paid roughly £25 for a fingerprick test, got your test through a Groupon offer or used any one of those ‘upgraded’ packages which cost roughly £250 and have promised you a call with a BANT registered nutritionist after you’ve got a little packet at home which you’ve used to self-test… I’m not going to even comment on these tests here. They’re regularly discredited, for good reason, and are practically nonsense. If I was talking about those tests, this article would be very short. The answer to the title’s question would be, “no, they’re rubbish, move on”.
However, there are quality intolerance tests out there, and this article is an analysis of the accuracy, utility and potential role for using these, more well-researched tests in clinical practice.
Food Allergy, Intolerance, Sensitivity… What’s the Difference?
The terminology used to explain food reactivities can become very confusing. I actually don’t think this is entirely the fault of unqualified people conversing using terminology they barely understand. Instead, I think it is a reflection of the nature of food reactivity – it is a complex situation where the lines between sensitivity reactions, intolerance reactions and allergies can often blur when several of these are occurring at once.
So what’s the difference?
Well, broadly speaking, you can react to food through an immune pathway, i.e. the food is flagged by markers in your immune system and when ingested stimulates an immune response wherein a host of killer cells and inflammatory markers are released to attack that food as it enters your GI tract. This is what is known as an allergy or a sensitivity.
Alternatively, you can react to food in a way that doesn’t involve the immune system. This would result from a challenge in digestion – either you lack the enzymes to break down certain foods or you may have a bacterial imbalance which creates symptoms on ingestion of certain foods. This is what we refer to as an ‘intolerance’, i.e. foods’ indigestibility causes symptoms.
An classic example of this would be lactose intolerance wherein you lack the lactase enzyme to digest lactose sugars from dairy. This can be tested, yes – typically using a breath test. This is food intolerance testing.
But this is not typically what people are asking me about when they want to know the validity of food testing. What they want to know revolves around the accuracy and utility of food sensitivity testing – they want to know if their immune system is reacting to a specific food.
The differentiation between allergy, or between different types of sensitivity, is determined by what level and type of reaction the immune system mounts in response to the invading substance (antigen).
The immune system makes immunoglobulins, which are essentially proteins which act as markers of external ‘invaders’ (antigens). What type of immunoglobulin is attached to which substance is dependent on the threat level presented by it (and also the shape of the antigen, but that’s a bit too much chemistry for the purposes of this article).
In humans there are five different immunoglobulin types (antibodies) and the letters which distinguish them stand for the type of bond chain found in the middle of the molecule (again, way too involved chemistry, but this bond formation basically shapes how each antibody binds to each antigen).
You will have heard of IgA, IgG, IgM, IgE, though possibly not the fifth – IgD (which may be relevant for a discussion of food sensitivities but is still a little bit of a puzzle to the scientific community so i won’t go into it here).
I could geek right out and explain that there are also subfractions to all of these antibodies, but to simplify this right down, just know that the immune system is multifaceted and complex because it is the failsafe for multiple potential enemies and, as such, needs many, many different methods of recognising, tagging, attacking and eliminating all threats. The different immunoglobulin responses is how it is able to tackle these differing threats.
Allergy – IgE
IgE reactivities usually present with the classic allergy response – also known as Hypersensitivity Type I. The release of IgE antibodies heralds an immediate and rapid release of cytokines which lead to what you will recognise as an allergic reaction – hives, throat swelling, anaphylaxis, redness, heat etc. This Type I Hypersensitivity usually requires immediate attention, for example using an epi-pen, which is an epinephrine injection designed to counteract the immune response.
The IgE subfraction of immunoglobulins is a remarkably low percentage of total immune activity in any human being, but it is capable of the most extreme responses.
If you have ever had a skin prick test with an allergist, they’re checking for IgE-mediated allergy responses. If you have a classic IgE-mediated allergy to something you will get bumps and redness on your skin fairly swiftly if it is pricked whilst a solution containing that substance is sitting on it. This is what your typical conventional allergy specialist does as a first-stage analysis.
IgE reactivity is rare and also, particularly if severe, spotted early because you have reactions immediately on interaction with an antigen and often require immediate medical assistance.
As an aside, you can grow out of these IgE allergies, and it is hypothesised that this is because of a beautiful function of one of our other immunoglobulins: IgG. IgG can learn to identify a protein and actually block the IgE release whilst mounting its own, milder response – once the immune system has witnessed the allergy enough times. This could potentially be why children ‘grow out’ of their allergies.
For the most part, the reactivity that I deal with in clinic is mediated by IgA, IgG and IgM responses to food (or pollens, toxins, chemicals etc.)
You may have heard of IgA in association with Secretory IgA, because this is the immunoglobulin which hangs around in mucosa, though it also exists in serum and can be tested via blood. Contrary to IgE, this is the most prolific immunoglobulin and basically should be in all of your secretory fluids, because it is protecting you from microbial proliferation activity which can occur in such secretions (i.e. in the GI tract, tear ducts, sweat etc.)
We test SIgA in every stool test and we are not looking for zero levels. We need to see at least some activity because microbes are everywhere and this secretory immunoglobulin level is our first line of defence.
Sensitivity – IgG, IgM and IgA (Serum/Blood)
And yet, after all of this preamble, what people really care about when asking me about food intolerance testing isn’t anything that I’ve mentioned thus far.
They are really asking me whether there are any reliable food sensitivity tests which can assess their immunoglobulin release (IgG, IgA… sometimes IgM) to certain foods.
The IgG and IgM antibodies are produced as part of the secondary immune response, wherein the immune system recognises things that are potentially threatening and produces specific, highly nuanced and targeted attack markers to them over time.
Of all the immunoglobulins, IgG is by far the most prolific and specific. It also remains in the body for a long time after exposure to an antigen. It can be thought of a sign that the body has been exposed to a certain substance and the immune system has flagged it for further attention. The presence of an IgG marker in your blood towards a specific antigen (for our purposes here, a food) is proof that your immune system has seen that food before and tagged it as worth paying attention to as a foreign invader.
IgM is slightly different. It is typically produced right at the start of an infection or virus, drops off considerably, and levels can raise higher after recent exposure to that antigen. It is a more rough-and-ready antibody, but serves a vital purpose. Presence of IgM antibodies to an antigen in the blood is an indication that the body has recently been exposed to that antigen.
And serum IgA, much like secretory IgA measured in mucosal fluid, is an indicator that immune reactions have occurred in areas where bodily fluids are present, such as gastrointestinal mucosa.
Can We Reliably Test for IgG, IgM, IgA Levels? ELISA, ALCAT & Cyrex
So you may be thinking that the best way to test for food sensitivities is therefore to take a sample of blood and test it for whether our immune system has ever created IgG, IgM or IgA antibodies in response to the presence of a whole litany of foods.
That is a great idea – and it has been done. But are these tests reliable? (Again, read the first paragraph – not the nonsense mail-order ‘kits’ which are little better than a sham, but instead the higher quality tests which require centrifuged blood and have led the field in sensitivity analysis).
The first thing to consider is that we eat some foods only when they are prepared a specific way. For example, it is very, very unusual to consume proteins raw. Chicken, meat, fish, eggs, beans etc. are all cooked well prior to consumption. To be accurate, therefore, it is essential that we test blood antibodies to foodstuffs only when they are prepared in the manner that they would be consumed.
It has definitely been suggested that certain laboratories do not factor this into their testing and are returning false positive results to patients simply because the raw food would have been allergenic, though it is never consumed as such.
It is also widely postulated that most ELISA tests (enzyme-linked immunosorbant assays) and the ALCATs (antigen leukocyte cellular antibody tests) are created ‘in-house’, i.e each company has their own, patented version of the testing. One question that is rarely answered, therefore, is how foods are prepared for testing.
Chopping a herb up incredibly small, for example, will expose far more of the plant phytochemicals to the blood sample than would be bioavailable were you simply chewing the herb itself. Pulverising grains, seeds and hard, indigestible fibres renders them in a state that is completely foreign to the human digestive tract. Can evidence of IgG antibodies to such foodstuffs even vaguely resemble the way our immune system ‘sees’ these foods in nature?
Additionally, the quality of the food prior to processing is not established. Is the gluten, for example, a non-GMO, non-pesticide-sprayed, organic sample? Are the vegetables organic or from nutrient depleted or pesticide-laden soil? If not, are the antibodies to the foodstuff or the ‘stuff’ that comes along with it?
And how is the food applied to the slide itself? Sometimes solvents and alcohols used to bind, dilute and/or adhere the sample to ‘trays’. How can we be sure that the IgG antibody is to the food alone, and not how it has reacted to the preparation?
And more than this, if your digestive system receives a meal containing a plethora of ingredients, it is not guaranteed that the response in this setting (i.e. real life) can be matched by laboratory, isolationist tests.
These testing vagaries are supposedly eliminated with larger, more reputable labs – such as Cyrex, about which I will detail more later – but testing methodologies are basically trademarked for the large majority, so it’s hard to fully validate each individual process to see whether this method of testing makes sense.
The bigger concern for me isn’t about questioning whether the lab results are accurate, however. I do believe that if you spend the money on the industry gold standard labs then you are gaining accurate results.
What worries me is that we really have to grasp that the immune system is not just immunoglobulins. Knowing IgG and IgA status doesn’t show us what our immune system really, fully does in response to a food.
Something which illuminates this point exceptionally is the reality of testing for coeliac disease.
I will personally never be able to perform this test on myself because to do so accurately I would need to be eating gluten for at least a month at the rate of at least one slice of bread per day. I’m not going to do this, because I value being joint-pain free too much. But it does illustrate an interesting point.
The reason that I would have to consume bread at this level for so long is because I haven’t consumed gluten for over 6 months (it’s actually years, but just 6 months would have been enough). Even the high quality laboratory, Cyrex, will not show antibodies in my system now to gluten. I simply haven’t been exposing my immune system to this protein.
And this highlights the fact that our immune system is as liable as our psyche to act from a sort of ‘recency bias’. That means that it tends to flag that which it has seen recently. It doesn’t always flag stuff which it hasn’t seen for a while, because IgG markers in particular are a slower, secondary immune learning process which takes time to marshal and deploy.
The fact that accurate IgG coeliac testing requires recent, repetitive exposure demonstrates precisely one reason why these food sensitivity tests may be unhelpful: false negatives. If it’s been a long time since consumption, you may not show immunoglobulin activity to something that is, in fact, a real problem.
Is Everything Marked, Definitely A Problem?
Adding insult to injury, the immune system is hyper-protective. It will flag/mark/produce antibodies to far more than it actually needs to mount an immune response to. Basically, IgG presence is not always proof positive that the body will release a host of inflammatory cytokines in response to the presence of that antigen. This is the second reason why food sensitivity testing may be unhelpful: false positives.
I can speak to this personally: my immune system is sparky and reactive. It is hyper-vigilant because of several quirks of my genetics and my tendency towards intestinal permeability. I know that testing myself for food sensitivities simply shows up what I’ve been recently consuming, completely misses things like oats, rye and gluten (because I haven’t eaten them in a long while) and basically just shows me that I shouldn’t be eating anything I’m eating. Sound familiar? Yes, this is such a common report from my clients that I am heartbroken every time I tell them their expensive tests weren’t reflective of real issues.
Again, I repeat, none of this is to doubt the accuracy of the high quality blood tests. Cyrex testing is the aforementioned industry “Gold Standard” for things like gluten and chemical sensitivity, simply because of the quality of their methodology and breadth of the markers they test.
And yet clinical relevance and laboratory accuracy does not always translate to clinical utility. It is not useful to me to know that I have antibodies in my blood to a host of things. Antibodies do not always a problem make. And also… this snapshot and moment in time is reflective of one thing and one thing only: things which the immune system has recently seen.
This has a potential utility in diagnosing intestinal permeability, because if you’re lighting up a Cyrex array in countless places the chances are that you have a weakened gut lining which is basically exposing your blood to countless antigens from food which should not be there. Exposure = antibody production = positives on food sensitivity tests.
But the problem in this situation isn’t the foods, necessarily. Instead, it’s the health of the gut. In true Functional Medicine style, therefore, we perhaps shouldn’t worry about what foods crop up on these tests, we should be repairing the gut lining, boosting digestive potential and assisting the immunomodulatory effects by ensuring our nervous system is in check and not over-reactive to ‘invaders’, right?
As always, it’s not that straightforward. There is often merit to excluding foods that you are showing IgG/IgA markers for – however temporarily – because an immune system in ‘high-reactivity’ mode will simply perpetuate inflammation and prevent the very healing that you’re attempting to perform in the gut. The foods may not be the problem, but they may be exacerbating it – and therefore may hold ONE of the keys to the solution. TEMPORARY exclusion of the highest ‘sensitivity’ foods may be indicated.
Mediator Release Testing & LEAP
But if this is the case, and there are ‘sensitivity’ foods all over the place – often any ‘elimination’ diet would exclude almost every food. So we need to assess which are the worst offenders.
Cyrex can help only marginally here. Though Cyrex testing marks antibodies as Positive, Equivocal and Negative, this is not a linear, ranked score for reactivity. Again, it is telling us what our immune system has noticed and marked – not what the immune system will actually do when it sees that antigen.
Whilst it can be hypothesised that the immune system will release cytokines upon seeing an antigen that it has produced IgG antibodies to, it is not absolutely certain what the precise immune response will be. It could be minor or major, involve just a few inflammatory cytokines or many.
Here is where a relatively new, potentially interesting, method of testing has stepped in to fulfill the need of mapping the total immune response to a protein or food substance, rather than just checking for antibodies. This test is the Mediator Release Test.
Apparently this test measures “subtle volumetric changes in leukocytes, neutrophils, monocytes and eosinophils”. How it does this is yet more maths and science, and they have a cool animation on their website linked here, but basically it’s all about adding up the portion of blood vs. plasma in samples after having been exposed to hundreds of foods. As immune responses involve white blood (i.e. plasma) it is hypothesised that an increase in volume of plasma after exposure to a ‘reactive’ food determines the level of immune sensitivity to it.
I’m sceptical of the methodology, I have to say. I don’t 100% trust the volumetric changes they’re extolling as evidence of immune response and cytokine release.
However, to be fair to them, I have heard positive things from practitioners about LEAP, the methodology which incorporates MRT into a full dietetics guideline for patients. I have colleagues who have qualified in this method and who believe it gives them more power to assist their clients in navigating onto a symptom-free diet in order for supportive, holistic healing to take place…
This technology is supposedly able to give dose-dependent precision because it quantifies the level of reactivity which takes place within the white blood cells. However, I have looked at the scientific papers listed on the nowleap.com website. Mostly, they’re descriptions of allergic processes and case study reports of anecdotal, one-off stories where the LEAP diet method improved symptom outcomes.
The reality is that assessing the validity of the assay (i.e. the test) is very, very different from validating the LEAP dietary intervention approach. Instigating a dietary change based on best-practice principles of anti-inflammatory diets is Functional Medicine 101… no sensitivity testing required.
Conclusion – Part 1
Those who have tried sensitivity testing, avoiding the foods that it flagged and felt subsequent symptom relief will swear that the sensitivity testing both worked and was 100% worth it. If that was the majority of my patient sample, I’d absolutely endorse the use of sensitivity testing for every client.
The reality is that, whilst I don’t have accurate data from a whole host of practitioners, it is my perspective that for as many who found positivity through this testing, an equal number have found the tests less than useless.
By “less than useless” I mean that they have attempted to stick to the diet left when they eliminate all their ‘sensitive foods’ and are still suffering, sometimes they are even worse than before.
From a purely amateurish, non-scientific assessment, I notice this more with those who have ELISA and ALCAT testing from any number of laboratories and online testing facilities. I have noticed less of this problem with Cyrex testing, but it still exists. And there are still practitioners and online web ordering portal which flog Cyrex testing as important and a vital first step. This irks me, because it is an investment of finance and trust which does not always reap rewards.
This article has a whole secondary part to it, which I will save for next time – this is already long enough! And yet I hope that what I have covered here gives you some clarity into what can and cannot be ascertained using laboratory diagnostics for food sensitivities.
There really are labs that are more trustworthy than others, and there really are shams and questionable diagnostics out there.
What I cannot say is whether you’ll be one of the patients for whom sensitivity testing will succeed or fail. The reason for that is because sensitivity testing is not so useful in patients who have a lot else going on. You really have to work with a practitioner to decide on whether sensitivity testing is appropriate in your case.
My next article will cover precisely this topic – which patients may benefit from testing, the dangers of trusting the sensitivity test and constructing protocols upon it, the (much cheaper) alternatives to these tests and my biggest bugbear – practitioners’ use of these tests which aren’t exactly ethical or accurate.
I will also touch on why, in a world where sensitivities and intolerances seem to be burgeoning, these sensitivity tests might actually be inflating the problem…
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