An increasingly common alternative medicine intervention is to diagnose patients with a food sensitivity and then prescribe eliminating that food from the diet. This all sounds very “integrative” and scientific. After all, food allergies are a real thing. The diagnosis often comes from taking a thorough history, and is then “confirmed” with a blood test, showing antibodies to the offending food. Eliminating the food will then often seem to help whatever subjective symptoms are of concern through nothing more than placebo effects. In this way an entire modality of medical intervention can seem quite legitimate, even if it is based on nothing. That is the essence of integrative or alternative medicine – they never bother to do (or they simply ignore) the kinds of research that would determine whether or not a reasonable sounding idea is actually true. If an intervention is proven in this way then it’s just medicine, and does not have to be “integrated”.

While food allergies are real and demonstrable, food “sensitivities” are controversial and not supported by sufficient scientific evidence. An allergic reaction is a specific immune hypersensitivity that involves a specific type of antibody known as IgE, and activates cells that release chemicals that cause the allergic reaction. Reactions are often unequivocal, causing a visible rash, runny eyes, swelling, and even difficulty breathing. Severe allergic reactions can be life threatening.

There is also a category of reactions to food known as food intolerance, but these have nothing to do with the immune system. A food intolerance typically results from digestive problems. The most common type is lactose intolerance, which results from a paucity of the enzyme lactase, which is necessary to digest the lactose sugar in dairy products.

A food sensitivity is neither an allergy nor an intolerance, but is alleged to be a more subtle immune response that causes – well, whatever ails you. That leaves a lot of wiggle room to impose the diagnosis on patients, because it does not require objective clinical findings and can be matched to a host of possible symptoms. One CAM site gives a typical description:

But what many people don’t know is that food sensitivities can affect our health and our moods. What’s more, food sensitivities are largely undiagnosed. While they may be less scary than a food allergy, these mysterious and highly individualistic food sensitivities can still make us experience unpleasant and unwanted symptoms.

Mysterious and individualistic – very CAM. A positive review of the concept of food sensitivity in migraine headaches noted:

“While food sensitivities and intolerances are recognized within the clinical medicine community, diagnosing these sensitivities and intolerances can be challenging because symptoms are usually delayed hours to days and may not occur after every exposure to the allergen.”

This is a pattern we are very familiar with at SBM – a variable delay between exposure and symptoms, and an inconsistent relationship. This does not prove by itself that the correlation is spurious, but it is highly suspicious. Such an inconsistent pattern is ripe for confirmation bias. It’s also hard to disprove – you can’t just do a challenge test, because the reaction does not always occur.

This is also where the IgG testing comes in, because it gives the appearance of legitimacy and objectivity to an otherwise nebulous syndrome. What is more scientific in medicine than a blood test? However, as the Academy of Nutrition and Dietetics summarizes:

IgG antibodies have not been shown to reliably identify either food allergies or sensitivities. Most people produce IgG antibodies after eating food. They are not specific to a person’s sensitivity, although past or frequent exposure to a food may cause these levels to be higher.

Studies have not validated IgG antibody testing as a clinical test. But the full story is a bit more complex, so let’s look at what’s published. It does seem that IgG antibody titers can increase after ingestion of certain foods. The question is – are these antibodies causing any symptoms or clinical syndrome. There is also evidence that some of these IgG antibodies may increase gut permeability. However, critically:

Notably, neither IgG titers to wheat, eggs, and dairy, nor permeability biomarkers, were increased in symptomatic participants compared to those without symptoms.

So the research has not closed the loop – whatever is happening does not appear to correlate with actual symptoms. This is also a pattern we commonly see – biology is complex, and often if you look at a basic science level you will see that stuff is happening. But we cannot simply extrapolate from the fact that biomarkers are changing to any specific clinical outcome. Biomarkers are a notoriously poor predictor of net clinical outcomes, unless clinical research specifically shows a connection. Here we are explicitly seeing no connection between IgG food titers and symptoms.

In fact the research shows that increases in IgG titers after ingesting food is a normal immune response, without any clinical implications. If anything, a specific subtype – IgG4 – may be associated with tolerance of food, because these antibodies block the allergy causing IgE antibodies.

Several companies provide panels of IgG testing for food sensitivity. But they have never validated their tests. They have not demonstrate that repeated testing, for example, gives the same results. Perhaps whatever antibodies are detected are determined entirely by what the subject recently ate, and would be different every time. They have not demonstrated that IgG titers predict a positive response to removing the target foods from the diet. This is why, as the AAAAI states:

Due to the lack of evidence to support its use, many organizations, including the American Academy of Allergy, Asthma & Immunology and the Canadian Society of Allergy and Clinical Immunology have recommended against using IgG testing to diagnose food allergies or food intolerances / sensitivities.

IgG antibody testing for food sensitivity is a classic example of the difference between CAM and science-based medicine. The only real functional difference is that the latter relies upon scientific evidence and the former does not.



Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.