The Allergy Unit at the Royal Prince Alfred Hospital in Australia has been a pioneer in food intolerance research. The unit is directed by Dr. Robert Loblay, a clinical immunologist who has spent the better part of his career helping patients suffering from food allergy, food intolerance, and celiac disease. Working with Head Dietitian Anne Swain (whose doctoral thesis documents the research behind the well-known RPAH Elimination Diet) and a team of doctors and dietitians, Dr. Loblay has laid out the basic ideas of food intolerance, namely that reactions are dose dependent, not limited to one type of food, and most easily diagnosed after a suitably restrictive elimination diet.
Today we’ll ask Dr. Loblay some questions that address common misconceptions about food intolerance.
Q: Thank you, Dr. Loblay, for spending time with us. Let’s start with a few quick questions. First off, does food intolerance cause weight gain?
A: No.
Q: Can you become intolerant to a food if you eat it too often?
A: No. But reactions are dose-dependent, so if you have a tendency to intolerances, eating them more often might provoke symptoms and bring them to attention.
For foods eaten at subthreshold levels, we generally advise: “Not too much…Not too often…”
Q: Is there a cure for food intolerance? Are there any supplements or enzymes that people can take to prevent food intolerance reactions?
A: No, and No.
Q: As both an immunologist and a food intolerance expert, what is your opinion on the ‘delayed allergies’ (sometimes referred to as food intolerance) that are supposed to be picked up by IgG blood tests? Do these tests provide any meaningful results?
A: We have not found any correlation between challenge results and IgG blood tests, so we don’t think they’re helpful. IgG antibodies to food are simply a marker of exposure, and IgG4 subclass levels correlate with the development of clinical tolerance in people who have outgrown their IgE mediated food allergies. This has nothing to do with intolerances, in my opinion.
Q: In the time since the RPAH Allergy Clinic began looking at food intolerance, histamine intolerance has become a hot topic. Do you test for histamine intolerance specifically? In real-life meal planning, does the distinction between histamine and other biogenic amines make a difference?
A: ‘Histamine intolerance’ is a misnomer, popularized in Europe, used to describe people who get certain symptoms in response to foods containing biogenic amines. They fail to recognize that (1) such people are usually also sensitive to one of more other substances, and (2) that their skin responses to a standard prick test with histamine (the positive control used in allergy skin tests) are perfectly normal.
We find that our standard challenge tests with tyramine and phenyl ethylamine (done with purified chemicals and/or selected foods) are sufficient for identifying people with intolerance to biogenic amines and to guide real-life meal planning.
Q: In your experience, do people with food intolerance usually have some inkling that their symptoms are related to food? How many are truly surprised to find that they have food intolerance?
A: About half the people we see have an ‘inkling’ that food is involved. The rest are unaware and many are ‘truly surprised’. There are 2 likely reasons: (1) natural chemical intake accumulates from many different food sources which vary from day-to-day, so individual foods do not stand out; (2) reactions can be delayed by many hours or a day or more, so the cause-effect relationship is often not obvious. When people on the elimination diet are tested with carefully selected foods (grouped according to chemical content), some only begin reacting after 4-5 days – for that reason our open food challenge protocol goes for up to 7 days for each group.
And in those who do suspect foods or ingredients, they often incriminate the wrong ones.
Q: A lot of Internet advice tells people that they can check for food intolerance by avoiding a food for a week or two – most often, the ‘food’ in question is gluten. Are there any problems with doing this?
A: People who eliminate gluten usually also unknowingly cut back on their intake of other things in their diet which are high in natural chemicals, e.g. ham, cheese, tomato and spreads on sandwiches, burgers, etc; tomato-based sauces and spices with pasta; and all the things that go on top of a pizza base. As a result they can mistakenly attribute any clinical improvement to the elimination of gluten, overlooking all the other changes they’ve made. Proof of the pudding is always in the eating – systematic challenges – but it needs to be done on a suitable low-chemical baseline diet to get reliable answers.
People can be misled in much the same way when they go on other diets such as ‘sugar-free’, ‘dairy-free’, ‘yeast-free’ etc. Hence the popularity of any number of other diet approaches, as well as various dodgy testing methods. Any major change in one aspect of a person’s diet inevitably alters their intake of various food chemicals to which they may be sensitive, so a degree of clinical improvement is common. In other words, some people can get the right answer for the wrong reasons. For people with mild intolerances, such changes may be sufficient to get their symptoms under control. However for the more severe/persistent intolerances, improvement is usually temporary, and more rigorous investigation is needed to get to the bottom of their problem.
Q: Many adults claim to be soy intolerant, and there is some talk on the Internet that people with gluten sensitivity will also be sensitive to soy. Is there anything behind this?
A: Some people with celiac disease and persistent symptoms despite sticking to their gluten free diet don’t tolerate soy. [These findings were published by Dr. Loblay and colleagues in 1999.].
Q: But outside of celiac disease and perhaps gluten intolerance, do you find that soy intolerance is something common in adults?
A: In people with irritable bowel symptoms, we eliminate wheat, soy, and milk in addition to natural and added chemicals initially; then we challenge with each in turn. People vary in their pattern of sensitivities, so at the end of the process each is prescribed an individualized diet based on their challenge responses. There is no single diet that suits everybody.
Soy is not really an issue in people with non-GI symptoms.
Thank you, Dr. Loblay.
If that you suspect that you have food intolerance, first see your doctor to rule out food allergies and other potential causes for your symptoms. Food intolerance is diagnosed through an elimination diet and food challenges, and it is best done with the help of a registered dietitian. Contact the professional dietitics association in your country to find a dietitian who is familiar with food intolerance or visit the directory of member dietitians on their website.
Let’s talk some more about whether it’s a good idea to try an elimination diet on your own to check for sensitivities to milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat and soybean. As I explained in an earlier post, these foods are known as the Big 8 food allergens in the US, and anyone who suspects that they have ever had an allergic reaction to one of these foods should talk with their doctor. As we saw, food allergies often diminish over time, but they will never cross over into a food sensitivity or intolerance.
With that established, we can move on to another issue: Can the Big 8 allergenic foods also cause intolerances? Well, it is true that wheat, milk, soy, and eggs can trigger flare-ups in people with irritable bowel syndrome (IBS), but to date, no one has established that this is related to allergy or to pharmacological food intolerance. We also know that lactose intolerance is real, and egg whites, soy sauce, and spoiling fish have the potential to cause adverse reactions by way of biogenic amines (including histamine). But, for the most part, the answer to my question is “No.”
This is not to say that people cannot have other problems with these foods. In fact, outside food allergies and the limited examples of food intolerance I just mentioned, doctors have identified several disorders in adults where the immune system unnecessarily reacts to certain food proteins – these are listed in the table below under ‘Other immune system reactions.’ These problems can be quite serious, so they are not something you should try to diagnose on your own.
Table 1. Possible reactions to the Big 8 food allergens in adults. When dealing with these foods, there are a lot of reasons to see a doctor and not many reasons to do an elimination diet on your own.
Foods
Allergic reactions
Other immune system reactions
Food intolerances
Milk
Cow’s milk protein allergy
Cow’s milk protein intolerance (unknown mechanism)
Soy protein intolerance (only in children) Possible aggravation in celiac disease (?)
Possible amine intolerance to soy sauce (?)
Eggs
Egg allergy (to whites, yolk, or both)
–
Egg white intolerance (histamine)
Crustacean shellfish
Shellfish allergy
Food protein induced entercolitis syndrome – FPIES (rare but serious)
–
Fish
Fish allergy
–
Scombroid poisoning (histamine)
Peanuts
Peanut allergy
–
–
Tree nuts
Tree nut allergy
–
–
Any food protein (varies by person)
–
Eosinophilic esophagitis (usually males)
–
One more thing: In the table above, I have classified reactions to the Big 8 foods as food allergy, food intolerance, and other immune system reactions; however, you might also run into the term ‘food sensitivity’ on the Internet. It’s important to be clear about what this phrase implies. In many contexts, ‘food sensitivity’ can be used as a generic term to describe any type of adverse reaction to food. I’m often guilty of using it this way. However, when someone recommends that you try an elimination diet or take a blood test to see whether you have ‘food sensitivities’ to the Big 8 foods, they are probably referring to something very specific – and very incorrect – namely, the idea that you may have some kind of chronic, low-level allergic reaction to food that is undermining your health. These IgG-based ‘food sensitivities’ don’t actually exist and so are not listed in my table of possible reactions.
To summarize, most reactions to the Big 8 foods are serious problems that require proper medical care; light-weight allergic ‘food sensitivities’ do not exist, so there is no need to test for them on your own. Even in the case of gluten sensitivity, you need to be checked for possible celiac disease before you go gluten free. And you certainly shouldn’t try to test yourself for egg white or fish/histamine intolerance without having properly ruled out allergies to eggs or fish. If you do feel that you are experiencing symptoms related to food, the best thing to do (after seeing your doctor) is talk to a registered dietitian about other foods that can cause food intolerance.
With so many Internet resources available on salicylate sensitivity and histamine intolerance – where fruits are a big culprit – it is easy to get the impression that adverse reactions to fruit are signs of food intolerance and not food allergy. But even though fruit are not included in the Big 8 list of allergenic foods (except for nuts, which technically are fruit), it is still possible to develop fruit allergies and even suffer anaphylaxis from fruit. In fact, since most allergy symptoms overlap with food intolerance symptoms and both types of reactions can be delayed, you should not try to distinguish between the two conditions on your own.
Fruits, vegetables & allergy
The following fruits and vegetables are most often implicated in allergy. This list is not exhaustive – other fruits are possible.
Primary fruit allergy is just like any other food allergy: specific proteins unique to fruits (lipid transfer proteins) bind to IgE antibodies and trigger the release of histamine and other chemicals. Symptoms are the same as classic allergy symptoms and develop along similar time frames.
Oral allergy syndrome (OAS), also known as pollen-food syndrome, is most common food allergy in adults. In order to suffer from OAS, you must have an existing allergy to pollen or latex. OAS occurs because certain proteins in fruit are similar enough to plant proteins that they can also bind to pollen-specific IgE antibodies and trigger symptoms. Symptoms arise rapidly – between 15 minutes to 1 hour after eating fruit – and typically include itching or hives in the mouth and throat. However, gastrointestinal and systemic symptoms are also possible, and foods related to birch pollen can also cause or aggravate chronic eczema in children and adults.
The worldwide prevalences for primary fruit allergy and for OAS are both around 5%. The prevalence rates and predominant types of fruits and vegetables involved vary from country to country. OAS is often regarded as a mild condition, but about 2% of people with OAS could experience anaphylactic shock. Taking ACE inhibitors for hypertension or congestive heart failure amplifies OAS symptoms, and this could lead to facial swelling that stops you from being able to breathe.
If you do have a fruit allergy or OAS, a doctor can answer your questions about managing your condition: Should you completely avoid your trigger foods? How much could you safely eat? Should it be cooked or peeled? Which varieties of troublesome fruits should you shop for?
If your doctor tells you that you do not suffer from a fruit allergy or OAS, then you can probably pursue a diet investigation for food intolerance with a registered dietitian – get your doctor’s OK. Remember, if you are a person who experiences laryngeal edema (swelling of the throat or upper airways), food challenges for food intolerance should be done only in a clinical (inpatient or outpatient) setting.
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Imagine that you are in a Chinese restaurant with your family. You’ll probably get a migraine later tonight (maybe from the amines in the soy sauce), but you’ve been craving Chinese food all week and you haven’t made the connection yet. Your daughter is drinking cup after cup of jasmine tea with her five spice stir fry, and this, combined with the other things she ate during the day, will give her hives again this evening. Your son asks you to read the fortune in his fortune cookie – “Knowledge is power,” it says, but it doesn’t warn you about the tartrazine in the cookie. He’ll be cranky tonight and distracted tomorrow morning. This is what you might experience if you suffer from food intolerance.
Lesson 1: What is food intolerance?
Is food intolerance real?
Yes. The existence of pharmacological food intolerance has been established by double blind placebo-controlled food challenges. The bulk of the research on food intolerance has been conducted in Australia, the UK, and Germany, and there is an increased awareness of food intolerance in these countries.
That said, two points should be kept in mind. First, even though food intolerance is real, it is relatively rare. These reactions are aptly categorized as ‘hypersensitivity‘ reactions, meaning that most people – perhaps 99% depending on the substance – will not experience any problems from food chemicals at normal amounts. Second, not all evidence carries equal weight when it comes to the different trigger chemicals, and many questions still need to be answered.
Food intolerance, as defined by the Allergy Unit at the Royal Prince Albert Hospital in Australia, is a sensitivity to chemicals found in a wide variety of foods. It is also known as pharmacological food intolerance, a type of non-allergic food hypersensitivity. Food intolerance does not involve the immune system.
The term ‘pharmacological’ is related of the nature of the substances that elicit food intolerance reactions. In addition to nutrients, foods contain chemicals that are foreign to our bodies (like benzoate in fruit or artificial colors in yogurt) or excess amounts of chemicals that our bodies normally produce (like tyramine or histamine in certain cheeses). This is obvious in the case of processed foods, but it is true for fresh or organic foods as well. The foreign or excess chemicals are processed in the body along the same lines as drugs, and in food intolerant people, they also produce drug-like effects. But why would such chemicals be present naturally in food? Because they are important to plants or because they are part of the normal ripening and aging processes.
Food intolerance is different in each person. Some people will be sensitive to certain trigger chemicals for their entire life, and these people will need to avoid foods that contain these chemicals in order to remain symptom-free. Others will only need to avoid their culprit foods for a time until they can resume eating them – perhaps in limited quantities – without seeing symptoms. Still others might only see problems when they eat large amounts of their offending foods or eat certain combinations of foods. But for everyone, the key to living life to the fullest is an accurate determination of which food chemicals are causing the problem. A registered dietitian or doctor can help you find your triggers through an elimination diet and food challenges.
Lesson 2: Food triggers linked to food intolerance
Table 1 contains the most commonly discussed food triggers linked to food intolerance. More than one trigger can be present in a given food, making it difficult to determine which foods contributed to your symptoms. Please be aware, though, that not all of the chemicals listed below are implicated in food intolerance by the same degree of evidence — for all the details, I recommend this recent open-access review:
Alcohol can modulate, for better or for worse, the effects of some food chemicals by increasing their absorption or altering their breakdown.
Lesson 3: Food intolerance symptoms
Food intolerance symptoms can arise hours or even days after eating a trigger food, and their severity depends on how much you ate, what you ate during the previous few days, and whether you have other health conditions. On top of this, symptoms can be aggravated by illness, environmental chemicals (like fragrances), medications, hormonal changes, or stress. The most common symptoms of food intolerance are given below.
System
Symptom
Skin
Hives (urticaria), swelling (angioedema), itching, aggravation of eczema
Migraine, vertigo, fatigue, muscle pain (myalgia), growing pains, behavioral changes in children
Generalized
Non-immune anaphylaxis
Lesson 4: Food intolerance as a food hypersensitivity
Adverse reactions like food intolerance and food allergy are classified as hypersensitivity reactions, where the concept of hypersensitivity has real meaning. Food hypersensitivities are reproducible reactions brought about by quantities of foods that most people can tolerate. In other words, to classify an adverse reaction as a food hypersensitivity, you must first think about the effect that a normal amount of that food would have on the average person.
Food hypersensitivities are divided into two main groups: those that are caused by the immune system (immune-mediated hypersensitivities) and those that aren’t (non-immune mediated hypersensitivities). If we consider food allergy – the poster child for immune-mediated food hypersensitivities – it is easy to see why hypersensitivity is an appropriate description. Allergies occur when the immune system overreacts to harmless proteins in foods, like milk, eggs, wheat, and soy, that lie at the heart of the Western diet. Only about 5% of the overall population is suffering from some type of food allergy, and the amount of food needed to trigger an allergic reaction can be much less than a typical portion.
There are more immune-mediated food hypersensitivities than just food allergies. These reactions involve other aspects of the immune system and may take a longer time to develop than a classic allergic reaction. Here I’m talking about problems like cow’s milk protein intolerance, soy protein intolerance and food protein induced entercolitis in children, celiac disease, and eosinophilic esophagitis — in some cases, asthma and eczema are also related to food. Notice that these conditions are occasionally lumped under food intolerance (and ‘intolerance’ even appears in a few of the labels), but strictly speaking, these are immune reactions.
The term food intolerance is used as the common name for non-immune mediated food hypersensitivities. The best-known type of food intolerance is lactose intolerance, the gastrointestinal discomfort that results from undigested lactose (milk sugar) in the colon. Roughly 75% of the world’s adults — 25% in the US and even fewer in northern Europe — do not produce enough lactase to digest all of the lactose they consume, but not all of these people will experience symptoms and, thus, lactose intolerance. In lactose intolerance, symptoms depend on a person’s gut bacteria and eating habits.
Pharmacological food intolerance, the focus of this primer, is also a non-immune mediated food hypersensitivity. For example, consider a person who has worked with their doctor to determine that their headaches and diarrhea are symptoms of histamine intolerance. In histamine intolerance, a person’s ability to break down histamine is impaired, so foods that are rich in histamine or that cause histamine to be released in the body can lead to symptoms. Histamine intolerance is a food hypersensitivity, because most people can tolerate normal quantities of histamine-rich or histamine-releasing foods.
That said, how do we gauge what “most people” can tolerate? As with food allergy and other immune-mediated food hypersensitivities, the non-immune hypersensitivities generally affect less than 10 or even less than 5% of the population. For example, less than 1% of adults are sensitive to food additives, at least 1% have histamine sensitivity, and around 6% suffer from food-induced migraines. This means that for any food hypersensitivity, perhaps 99% of people will experience no adverse reactions to those foods or food chemicals.
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