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Food Sensitivity Testing: Does IgG Predict Intolerance?

Written by | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by | Last updated:
food sensitivity tests

Food sensitivity tests are a popular new way to look for the root cause of symptoms like bloating, rash, and migraine. But do they work? What does the science say? Let’s take a deep dive into how they might work and what immunoglobulin G can really tell us.

What are Food Sensitivity Tests?

You may have seen them in ads online or on TV: companies promising that in just a few short weeks and with a few drops of blood, you can be free of all the foods that cause gut problems, rashes, and migraines. It sounds great, but it has a hefty price tag, and the science is shaky at best.

Food sensitivity or intolerance is a complicated topic with a lot of room for confusion.

We go back to the beginning and explore what food sensitivity is and how to find it in our previous two posts:

In this post, we’ll cover:

  • How “food sensitivity tests” are supposed to work,
  • Why they don’t work, and
  • How to actually find and address food sensitivity.

IgG Food Sensitivity Testing

How is it Supposed to Work?

IgG food sensitivity tests assume that all IgG is pro-inflammatory. According to the companies that offer IgG food sensitivity tests, removing foods with “high IgG reactivity” is associated with reduced gastrointestinal, skin, and migraine symptoms. These are some big claims—what are they based on?

Immunoglobulin G

So, foods cause inflammation and inflammatory symptoms. On that much, we agree with the companies that offer food sensitivity testing. Thus far, however, we haven’t touched on the biological marker than such companies use to find food sensitivities: IgG.

Immunoglobulin G, or IgG, is the most common antibody in your blood. Curiously, IgG can either promote or prevent inflammation depending on whether and which sugars are bound to it [1, 2, 3].

Pro-Inflammatory IgG

IgG attaches to pathogens and other foreign materials and helps your white blood cells pick their targets. Your body produces highly specific IgG and immune responses against pathogens that it has encountered before. That’s why you’re so unlikely to get diseases like chickenpox more than once, for example [4, 5].

When IgG binds to a pathogen that it “recognizes,” white blood cells attack it, engulfing or killing it. As white blood cells arrive on the scene, they tend to produce inflammatory signals [4].

These steps are all part of a healthy immune response to a direct threat [4].

Anti-Inflammatory IgG

Researchers are still fleshing out their understanding of how binding to sugars changes IgG’s function. What we know is this: certain sugars act like a switch that flips IgG from a pro-inflammatory to an anti-inflammatory molecule [6, 7].

Let’s back up: what role do sugars have? Which ones are anti-inflammatory?

The Role of Sugars

Multiple sugars can be bound to IgG, including fucose, galactose, and sialic acid. These change the function of the IgG molecule and send specific signals to immune cells [8, 9, 10, 11, 6].

When IgG is bound with fucose, it is said to be fucosylated. Likewise, IgG bound to galactose is galactosylated and IgG bound to sialic acid is sialylated.

Generally speaking, high fucosylation and low galactosylation and sialylation are associated with higher inflammation. That is, fucose bound to IgG tends to increase inflammation, while galactose and sialic acid tend to decrease it. The higher the ratio of fucose to the other two, the greater the inflammatory association, and vice versa [12].

Sialic acid can’t attach to IgG without a galactose molecule. When these two sugars are bound, the immune system tends to relax and stop responding to the IgG’s target antigen. Thus, galactose and sialic acid protect against allergies and autoimmune disorders. Human breast milk is extremely high in sialic acid, while red meat and dairy are the main dietary sources [12, 13, 14, 8, 15, 16].

Metabolism, Lifestyle & Sugar Binding

Various metabolic factors known to either increase or decrease inflammation also interact with the sugars bound to IgG.

CRP and interleukin-6 (IL-6) are signals that promote inflammation; they are associated with low sialic acid and galactose binding to IgG. High blood triglycerides and insulin have the same effect. HDL cholesterol, the “good” cholesterol that decreases inflammation, is associated with high sialic acid and galactose binding to IgG [12].

The direct relationship between lifestyle choices and sugar-bound IgG has not been well studied. However, the links between CRP, IL-6, cholesterol, triglycerides, insulin, and IgG status suggest that optimizing these metabolic markers could improve galactosylation and sialylation. Further research will paint a clearer picture [12].

Autoimmunity & Remission

In autoimmune disease, the immune system attacks an antigen in one of the body’s own tissues. For example, in rheumatoid arthritis, the immune system attacks the joint tissues and causes painful inflammation [13, 17].

Adults and children with rheumatoid and juvenile arthritis have significantly less galactose and sialic acid bound to their IgG. The same happens in people with Wegener’s granulomatosis, an autoimmune disease that causes inflammation and death of blood vessels [6, 18].

On top of that, more galactose and sialic acid bind to IgG during pregnancy. According to some researchers, this may be why some women with rheumatoid arthritis experience less pain or even disease remission while they are pregnant. Sialic acid then concentrates in breast milk, which protects breastfed babies from infections and helps them build a healthy gut flora [6, 19, 20].

Anti-inflammatory IgG increases tolerance; that is, it tells the body not to attack an antigen. Unsurprisingly, then, galactosylation and sialylation of IgG prevent tissue death and may cause some autoimmune diseases to go into remission [4, 13].

Predicting Tolerance in Allergies

People with allergies have IgE reactions to certain allergens, and they also tend to have high IgG against those same allergens. This is one of the reasons some people give for using IgG testing to find food sensitivities [21].

However, high IgG may actually predict the development of tolerance; that is, if you have high IgG against an allergen that triggers an IgE response, you’re more likely to outgrow that allergy later in life [22, 21, 14].

Anti-inflammatory IgG may block allergic reactions. The higher the ratio of IgG to IgE, the more likely we are to tolerate trigger foods over time [23].

IgG Takeaway

All this is to say that IgG is a complex molecule and that simply having high levels of IgG in your blood doesn’t mean you’ll have inflammation. Some IgG is anti-inflammatory; it tells your body not to attack.

Remember that antibodies, on the whole, tell your immune system that something is foreign, or not “self.” Galactosylated and sialylated IgG probably change that message a little bit, saying, “This is foreign, but it’s safe.”

Arguments in Favor of IgG-Based Elimination Diets

Some companies that offer IgG tests provide lists of studies that they say support the use of their product.

Such studies claim that eliminating IgG-reactive foods reduces symptoms of irritable bowel syndrome and improves stool quality. At least one study also found that people with Crohn’s disease have significantly higher levels of IgG [24, 25, 26].

Another study found that eliminating IgG-reactive foods reduced symptoms in two people with severe asthma [27].

Some studies have found a connection between IgG-reactive foods and the frequency and severity of migraines. The connection is not especially clear, however, and may be dependent on whether a person also has irritable bowel syndrome [28, 29].

One study found a correlation between IgG and depression. However, the subjects of this study also had increased zonulin expression; IgG was in no way confirmed as depression’s cause [30].

Many of the studies listed on the testing websites either suffer from design flaws or actually conclude that there is no significant link between IgG and intolerance. Many also assume that IgG is pro-inflammatory, with no mention of the anti-inflammatory function of IgG [31, 32, 33, 34].

Why Doesn’t Food Sensitivity Testing Work?

Several leading medical organizations (the European Academy of Allergy and Clinical Immunology, the Canadian Society of Allergy and Clinical Immunology, and the American Academy of Allergy, Asthma & Immunology) advise strongly against using IgG-based food sensitivity tests [35, 36, 37].

So, why do so many experts advise against IgG-based food sensitivity testing?

Everyone Has IgG Against Common Foods

Remember that the immune system produces antibodies when it encounters foreign materials. Food, as it happens, is a foreign material. Multiple studies have shown that people have IgG in their blood against foods that they commonly eat, and that IgG does not correlate to symptoms of intolerance [38, 35, 39, 40, 41].

In one study, more than 21,000 Chinese adults were tested for food-specific IgG. All of them had IgG against foods that they ate regularly. Quantities of IgG against specific foods did not correlate with symptoms from eating those foods, either [39].

As discussed above, IgG tends to indicate tolerance – not intolerance – to specific foods [23].

Learn more about food sensitivity tests with the CEO of SelfDecode Joe Cohen and Dr. Tommy Wood: 

Commercial Tests Can’t Detect Anti-Inflammatory IgG

Commercial tests don’t (and probably can’t) distinguish between the pro-inflammatory and anti-inflammatory versions of these antibodies. As was the case with the Chinese study, your test results might come back with IgG against most or all of your staple foods, with no information about what kind of IgG it is [39].

Commercial Tests are Unreliable

Another huge problem with commercial tests is that they’re unreliable.

In science, one of the most important things about a given study is whether it can be reproduced: given the right materials, could I conduct the same experiment and get the same result? If yes, then the experiment has produced good, solid evidence. If not, then something is wrong [42].

Commercial IgG tests don’t even seem to be doing the same experiment, so to speak. In one case report, a researcher ordered multiple commercial tests for herself: each one told her to avoid different foods. Not a single food gave a positive result across all tests [41, 43].

This same researcher conducted her own tests later. She removed various foods from her diet and reintroduced them later, one by one, to see if they produced symptoms. Only four of the ten foods identified by the commercial tests produced measurable symptoms; she also experienced symptoms from foods not identified by any of the tests [43].

Is IgG Testing Ever Appropriate?

Some studies suggest that IgG testing may help people with migraines, inflammatory bowel disease, or celiac disease avoid inflammatory triggers. However, most professionals warn that IgG testing should only be used as a last resort, after other types of tests have failed. These tests should never be the only diagnostic tool employed, and the results of an IgG test should not take precedence over other tests [44, 45, 35].

Furthermore, avoiding foods based on IgG testing only appears to reduce the incidence of migraines in the short term. In one study, such an avoidance diet reduced the incidence of migraines after four weeks, but not after twelve weeks [45].

Elimination Diets vs. IgG Testing

We’ve established now that IgG testing is inconsistent and ineffective, but also that food sensitivities exist and should be addressed to increase the quality of life. How do we address them? Is there no lab test to help us?

Unfortunately, unless you have a true food allergy, it would seem that lab tests are expensive shortcuts that don’t provide much useful information. Elimination diets and “oral challenges” may be the best way to find out what’s really making us sick [46, 47].

In an elimination diet, we remove the suspected trigger food or substance from our diet for some time. We determine if our symptoms are gone, and then reintroduce the food to see if symptoms reappear or worsen [46, 47].

Elimination and oral challenge tests are time-consuming and often difficult to interpret; health professionals will sometimes guide the process. For example, they may instruct a patient to avoid wheat and conduct the oral challenge in a controlled clinical or hospital setting. The patient might receive wheat flour or a placebo, thereby reducing the risk of bias in the diagnosis [46].

The most reliable and effective way to conduct an elimination diet is with the guidance of a doctor or dietitian. You may wish to conduct your own elimination and oral challenge tests with some of the common dietary triggers, but be careful of your own biases. Try to keep an open mind throughout the process, and don’t draw conclusions until after the tests are complete.

Takeaway

IgG-based food sensitivity tests don’t work as advertised. They assume that all IgG is pro-inflammatory, when a lot of it is anti-inflammatory. The technology is based on shaky science, and it comes with a three-figure price tag.

The best way to find out if your health problems are caused by food sensitivity is to conduct elimination diets. Cutting a type of food out of your diet and reintroducing it (an oral challenge) later can help determine if that food is causing symptoms of intolerance. Your doctor or dietitian is best equipped to help guide you through this process.

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