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.
Sometimes it is easy to figure out food sensitivities – especially when they only involve one food or one kind of symptom. For example, lactose intolerance (a type of enzymatic food intolerance where people are deficient in the enzyme needed to digest milk sugar) is related only to milk and milk products, so it’s easy to notice the gastrointestinal symptoms after a nice bowl of ice cream with the kids. But other sensitivities are not so obvious.
Take pharmacological food intolerance, or just ‘food intolerance.’ This type of food sensitivity has always been hard to pin down, on both an individual level and in clinical studies. Symptoms can arise hours or even days after you eat a trigger food, and their severity depends on how much you ate, whether you ate any other trigger foods in prior days, and if you have other health conditions or environmental sensitivities. Furthermore, your symptoms may be different from those of someone else who reacts to the same foods.
On top of this, food intolerance is a reaction to chemicals that are found in a wide variety of foods. For example, if you were sensitive to histamine, you would need to watch out for fruits, meats, cheeses, chocolate, etc. If you were sensitive to artificial colors and preservatives, you would need to read every food label. This is different than food allergies, where people are oversensitive to the proteins found in specific foods. With food intolerance, your food journal wouldn’t be tracking the foods as much as the chemicals inside them. And that’s when things start to fall into place, because, as we’ll see, your symptoms aren’t always caused by the last thing that you ate.
The term ‘pharmacological food intolerance’ underscores the idea that foods, no matter how natural, can contain chemical compounds that are foreign substances in 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). These chemicals are referred to as xenobiotics, a term which also covers substances like medications, poisons, and environmental pollutants that enter our bodies. This means that pharmacological food reactions share characteristics that are already familiar to us from our experiences with other xenobiotics. In food intolerance:
The severity of your reaction depends on the dose. Below the threshold dose, no symptoms are observed.
Doses are additive across multiple meals. What you ate throughout the day, and even the previous day, counts towards your accumulated dose. Symptoms occur when the accumulated dose exceeds the threshold dose.
Multiple food chemicals can work together to exacerbate the effects of the others.
Withdrawal symptoms can occur.
You can become temporarily tolerant of a food chemical.
The most important of these ideas is the concept of a threshold dose. If you are very sensitive to a food chemical, you have a low threshold, and a small amount is all that is needed to produce symptoms. If you have a high threshold, eating small amounts of a substance will not produce any symptoms. And it’s not necessary to consume all of your food chemical in one meal in order to exceed the threshold dose – little bits can add up over a couple of days. If you were looking to see which food caused your symptoms, you might find that it was several foods over several meals that all contained the same trigger chemical.
In general, we can say that food intolerant people have lower dose thresholds than the rest of the population since most people do not react to food. This is partly due to differences in how well the body can rid itself of chemicals and partly due to how susceptible one is to experiencing adverse reactions – this is all part of the natural variations among people. However, it turns out that your personal threshold dose can also vary over time, depending on what else you have eaten, what medications you have taken, and other health-related factors.
An example of accumulated and threshold doses
The amount of chemical trigger in your body increases as successive meals are eaten.
Consider the chart on the right that tracks meals over four days – simplified, of course, for a hypothetical person. If you experienced symptoms on Day 4, would your first inclination be to blame the spaghetti dinner and perhaps the gluten-containing pasta in particular?
Our hypothetical person is actually sensitive to salicylate and amines, and she needs a mix of both to see symptoms – it turns out that honey, raspberries, guacamole, and tomato sauce all contain at least one of these chemicals. The chemicals accumulated in her body over the course of three days until her threshold dose (which, luckily for her, is rather high) was exceeded on the fourth day.
Our person had wondered about gluten sensitivity in the past, but didn’t seem to react reliably to wheat. Now that she is mindful of her trigger chemicals and her threshold dose, she can eat some of the foods she likes without adverse effects.
Food intolerance is a broad label that describes adverse reactions to food that do not involve the immune system. This site uses the term food intolerance as it has been defined by the Allergy Unit at the Royal Prince Albert Hospital in Australia, which corresponds to what some call pharmacological food intolerance.
What is food intolerance?
Food intolerance occurs when chemicals in food produce side effects, similar to the way that drugs produce side effects. Some people are more sensitive to these effects than others.
Food intolerance is not an allergy. A food allergy is an oversensitivity to a protein in a specific food, while food intolerance is a sensitivity to chemicals found in a wide variety of foods.
Organic, fresh, or processed foods can all cause adverse reactions – not all trigger chemicals are man-made.
Symptoms can be physical or behavioral, especially in children. Some people suffer from more than one symptom, and symptoms can change over time.
Food intolerance may affect up to 10% of the population when all food chemicals are considered, which is at least 2 times the prevalence of food allergy. Still, this means that food intolerance is relatively rare: for each food chemical, perhaps 99% of the population will experience no adverse effects.
Food intolerance is more common in adults than in children. Lifestyle factors may play a part in this. In comparison, more children suffer from food allergies than adults.
Children with food intolerance are more likely to be sensitive to food additives (artificial colors, flavors, and preservatives) than adults.
Food intolerance seems to run in families, although each family member may be sensitive to a different food chemical. More women experience food intolerance than men.
Food intolerant people are also likely to suffer from allergies. Food intolerance can make existing flare-ups of eczema and asthma worse, but cannot bring about these conditions on its own.
When do people experience food intolerance symptoms?
Symptoms can take hours to days to appear.
The severity of symptoms depends on how much of a food chemical was eaten, even over the course of several days.
Since symptoms are dose-dependent, they may seem unpredictable – sometimes they happen, sometimes they don’t. But if you think of food in terms of its chemical constituents, it all starts to make sense.
Some people are sensitive to more than one chemical and need to eat them in combination in order to see symptoms. Others only experience symptoms when they are under stress, sick, or have been exposed to chemicals in their environment.
Food intolerance should be considered only after your doctor has ruled out food allergies and other conditions and has given you the go ahead.
An elimination diet followed by food challenges is the only way to diagnose food intolerance.
Foods can contain more than one trigger chemical, making the order of the food challenges very important for ruling out all possible triggers. A registered dietitian can help.
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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