Back in the summer of 2001, I was obsessed with a certain regional brand of diet iced tea, and I would drink a few gallons of it a week. It was so good! That summer I also developed a problem with gas and diarrhea. My flatuence was so bad that I tried to keep people out of my cubicle at work because I was sure that the whole place had to stink. This coincided with a very stressful period in my life, so when I Googled my symptoms and read that irritable bowel syndrome could be caused by stress, I diagnosed myself with IBS. “Great,” I thought, “things are going badly and now I’m sick on top of it. That’s all I need.”
Fortunately, I wasn’t “sick” — I was just drinking too much sucralose sweetener. Sucralose feeds certain types of intestinal bacteria, which in turn produce the smelly gas, and it also pulls water into the intestines, causing diarrhea. The caffeine in the tea probably added to the diarrhea by moving my meals through my large intestine too quickly for even the usual amount of water to be absorbed from the stool. Later I would realize that my summer of embarassment did not constitute a chronic illness like IBS, which needs to be going on for at least 6 months to meet the Rome III diagnostic criteria [1] — I had simply eaten too much of something that would be hard for any body to handle, and the same thing could have happened with fructose if I had been drinking the same, excessive amount of regular cola or juice.
The point of my story is that sometimes a food will just do it to you. We might say that it “disagrees with you,” but if a food disagrees with you, odds are that it disagrees with a lot of other people, too. That’s why it’s important to understand that normal digestion varies, and it’s not always perfect. If you have a healthy gastrointestinal system — which puts you in only a modest majority, since almost a quarter of Americans suffer from digestive disorders [2] — this is good news. When the equipment is in working order, what you get out of it depends on what you put in. Leslie Bonci, MPH, RD, calls this an “investment in intestinal well-being” in the American Dietetic Association Guide to Better Digestion [3]:
“To make an investiment in intestinal well-being, one should consider food choices, portions, and meal timing. Food is one of the few things in life that we can control, and it is important to use food in a positive and intestinally friendly way. Experimenting with food choices as well as eating habits can help achieve a more balanced eating pattern, a healthier lifestyle, and very often, symptom relief.” (p. 4)
Notice that there is no mention here of food intolerance or food sensitivity: better digestion comes down to food choices and eating habits. In other words, no one can eat any amount of any food at any time without opening themselves up to the possibility of constipation, bloating, or gas. In her book, Ms. Bonci does an excellent job explaining the common effects of certain foods and supplements for anyone who wants a better handle on their digestive symptoms.
I am also struck by Ms. Bonci’s idea that “it is important to use food in a positive…way.” We too easily throw around the term “food sensitivity” — which actually isn’t a legitimate medical term — to describe the problems that food has caused. This recent habit doesn’t foster a positive relationship with food: it amounts to making a diagnosis, a claim that you have a disorder — that there is something wrong with you, not with what you have eaten. However, there is a big difference between being ill and making poor food choices.
The infographic
Some foods cause the same problems in everyone when we eat too much of them or in the wrong combination. Maybe for you it’s a pepperoni pizza that will sit like a lead weight in your stomach and then cause diarrhea later on, or maybe your attempts at eating healthier — like adding whole wheat, prebiotics, beans for protein, and lots of fruits and vegetables to your diet — have backfired with gas and bloating. This is not necessarily a sign of food intolerance. Your symptoms might be normal considering what you have eaten. You can see what I mean in my infographic, “What to expect with food and digestion.”
Hoekstra JH. Toddler diarrhoea: more a nutritional disorder than a disease. Arch Dis Child. 1998 Jul 1;79(1):2–5. http://dx.doi.org/10.1136/adc.79.1.2
Putting it together
Managing digestive symptoms requires planning, patience, and a lot of information on how different foods can affect digestion. Talking with your doctor is the best place to start so you know that you are not dealing with any serious medical issues. Do not try to diagnose yourself. An accurate diagnosis helps you to know whether you should just change your eating habits or whether you should avoid certain foods because of a food hypersensitivity.
To quote Leslie Bonci again, “it is important to find the correct balance regarding food choices and quantities, so that you can make a meal pleasurable and healthful, not painful.” A registered dietitian can help you restructure your eating so that food can always be a source of enjoyment.
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.
Author’s note: I have not been keeping up with the latest research on gluten sensitivity. This article was written in 2015, and while it still serves as a good example of how to evaluate scientific research, I cannot say whether it represents the current thinking on gluten sensitivity.
You’ve heard the Mark Twain quote, “There are three kinds of lies: lies, damned lies, and statistics” [1] – it refers to the way that numbers can be used to win arguments. Statistics can be used deliberately to deceive, but it can also lead us quite innocently to conclusions that overreach the data. Here I’m thinking about the most recent publication on non-celiac gluten sensitivity from Di Sabatino et al. [2], “Small Amounts of Gluten in Subjects with Suspected Nonceliac Gluten Sensitivity: a Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.”
At first glance, this study seems to say that gluten sensitivity is real. The abstract tells us:
“In a cross-over trial of subjects with suspected NCGS, the severity of overall symptoms increased significantly during 1 week of intake of small amounts of gluten, compared with placebo.”
This is the only conclusion that we see there. Later in the paper, though, we get some clarification:
“However, when we examined the individual patients’ overall scores we found that only a minority of the participants experienced a real worsening of symptoms under gluten.”
and
“If we look at the distribution of delta overall scores (gluten minus placebo), it is not surprising to note that a fair number of patients are victims of the nocebo effect…”
This sounds more like what we have been hearing from other gluten trials [3], and it certainly tempers the enthusiasm of the abstract. It even makes you wonder how the conclusion in the abstract could be so strong in light of the nocebo effect and negative gluten challenges. But there is no deliberate deception here, and, in fact, the authors caution that these results do not provide “crucial evidence in favor of the existence of this new syndrome.” It simply turns out that 3 of 59 participants – that’s 3 out of 59 people who had all originally believed that they were sensitive to low doses of gluten – reacted strongly enough during their gluten challenges to skew the group results in favor of gluten sensitivity. And how much stock can we place in these three individuals? Pretty much none. Let’s take a look at this in more detail.
Learning from the past
The gluten sensitivity debate has remained unsettled because of flaws in the previous studies. I have already discussed these problems in an article on Science-Based Medicine – essentially, either the baseline diets failed to exclude foods high in fermentable carbohydrates (FODMAPs), which are a source of considerable gastrointestinal discomfort, or the challenge capsules contained wheat instead of gluten. The Di Sabatino work seems to have taken this into account, and there are many good things about the way their study was carried out:
It was a randomized double blind placebo-controlled food challenge.
With its crossover design, data was obtained from 59 participants, which is a large group considering this type of study. A large group was needed because researchers were looking for a relatively small change (15 points) in symptom ratings relative to placebo over a collection of 15 intestinal and 13 extra-intestinal symptoms.
Unlike previous trials, this study did not focus on IBS sufferers, who may not be the best candidates for gluten sensitivity. Participants were recruited from patients who were referred to two celiac clinics for suspected gluten intolerance.
Patients were excluded if they showed signs of lactose intolerance or sensitivity to FODMAPs foods. Unfortunately, though, we don’t have any details on the criteria that was used to discover these sensitivities.
The placebo (rice starch) was selected to minimize fermentable carbohydrates in the intestine.
It seems that sufficient time was allowed for each of the challenges and the washout period in between (one week each).
Participants complied well with the baseline gluten-free diet, as evaluated using a standard questionnaire.
The study followed established statistical protocols.
I do have some misgivings about the baseline or ‘elimination’ diet, though. The elimination diet levels the playing field so that no effects from a participant’s regular diet are carried over into the study; it also serves as the baseline diet against which the effects of the placebo and gluten challenges should be measured. Ideally, the elimination diet would contain minimal food intolerance triggers, even going above and beyond the elimination of gluten. For example, histamine and other dietary amines can induce gastrointestinal symptoms and headaches (one of the extra-intestinal symptoms in this study) in some people [4], and either these people should be excluded from the trial or high-amine foods should be excluded from the baseline diet. Unfortunately, the Di Sabatino article gives us no details on the gluten-free diet that spanned the study, so I assume that the participants were allowed to select their own foods.
The plot thickens
Despite my misgivings, the effects of an uncontrolled elimination diet, as well as other random factors, can be accounted for by analyzing the challenge data on a group, not an individual, basis. Indeed, this study’s enthusiastic conclusion comes from the overall symptom scores for the group, which were greater for the gluten challenge than for the placebo (P = 0.034). Furthermore, the group symptom scores for many individual symptoms were also significantly higher for the gluten challenge than the placebo. However, the group data – although properly treated – does not give us the entire picture. As I mentioned earlier, it seems that the group response was skewed by three individuals who had an exceptionally high response to gluten compared with the placebo.
How can we know this? The article doesn’t offer that much in the way of details on individual patients, except for a very interesting scatter plot of the ‘delta weekly overall score’ for each person. (The delta score is overall weekly gluten score minus the placebo score.) In this plot we see what looks to my ruler and laser-beam eyes like a Gaussian distribution of points centered around an average delta score of 12.2. On both extremes – at a distance of more than two standard deviations beyond the average – we see a few lonely points, including three on the positive end and two on the negative. The authors identify the three points in the positive tail as the only “true gluten sensitive” participants in the study. I’ll repeat – only three participants were deemed gluten-sensitive.
Don’t worry if you can’t visualize what I just described – here are the two main ideas that we get from this graph. First, it seems that the placebo response rate in this study is somewhere around 50%, which isn’t surprising for gluten sensitivity, but which is higher than the 35% that is seen when double blind placebo-controlled food challenges are used to detect allergies [5]. This idea will come into play in a moment. Second, the three points being located more than two standard deviations (2 x 50.4) away from the average delta score means that there is only a 5% likelihood that these high scores would occur by chance. In other words, the math says that these three results probably aren’t a fluke – they’re a definite reaction. Again, everything is on the statistical up-and-up.
But the big question is, while being statistically correct, do these results really make a strong case for gluten sensitivity? I don’t think so. There are little things that don’t feel right, like the two people who reacted to the placebo to a similar degree as the “true gluten sensitive” (I prefer to call them ‘reactors’). On top of this, the reactors made up only 5% of a group of 59 people who believed that they suffered from gluten sensitivity. Could the 3 reactors be outliers in the sense that we have two distributions here – one random (meaning, gluten isn’t causing any real effect) and one related to some other type of food intolerance? My doubts about the uncontrolled elimination diet are coming back.
The preceding paragraph is just speculation, though. Here’s the real clincher. In this study, each participant took one gluten challenge and one placebo challenge. This is a fine thing to do when you are going to look at the group averages, which the researchers did. However, once you start to place more weight on the three gluten reactors, you are looking at things on an individual basis, and to diagnose food sensitivity in an individual, you need more than one set of challenges. (Think of it this way – in the group case, you do one test on multiple people, but in the individual case, you do multiple tests on one person.) Assuming a typical placebo response rate, an individual must go through three gluten and three placebo challenges in order for us to be 95% certain that they didn’t happen upon the three gluten challenges by luck [6]. Since the placebo response rate in this study is higher than normal, the three reactors really should have repeated the challenges even more than three times, but, unfortunately, we only have one set of results from them each. In a funky bit of irony, statistics tells us that we cannot conclude that these individuals have gluten sensitivity based on the limited data.
What’s next?
Life is full of compromises. Researchers look at things like group averages because double blind placebo-controlled food challenges are time consuming and difficult on the participants. To properly evaluate individual responses, participants would need to be on an extremely restrictive elimination diet (above and beyond excluding gluten) for months – just imagine the compliance problems and drop-out rates! Alternatively, the initial screening could be beefed up to identify likely placebo responders and to rule out more food intolerances, but imagine the costs! The current study addressed these issues in a reasonable way, and future researchers would do well to copy much of what Di Sabatino and colleagues have done…HOWEVER, we all must remember that gluten sensitivity cannot be identified in any individual without multiple gluten and placebo challenges.
1. Lies, damned lies, and statistics [Internet]. Wikipedia, the free encyclopedia. 2015 [cited 2015 Mar 3]. Available from: http://en.wikipedia.org/w/index.php?title=Lies,_damned_lies,_and_statistics&oldid=645997091
2. Di Sabatino A., Chiara Salvatore, Paolo Biancheri, Giacomo Caio, Roberto De Giorgio, Michele Di Stefano & Gino R. Corazza (2015). Small Amounts of Gluten in Subjects with Suspected Nonceliac Gluten Sensitivity: a Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial, Clinical Gastroenterology and Hepatology, DOI: http://dx.doi.org/10.1016/j.cgh.2015.01.029
3. Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR. No Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates. Gastroenterology. 2013 Aug;145(2):320–328.e3. http://dx.doi.org/10.1053/j.gastro.2013.04.051
4. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007 May 1;85(5):1185–96.
5. Gellerstedt M, Bengtsson U, Niggemann B. Methodological issues in the diagnostic work-up of food allergy: a real challenge. Journal of Investigational Allergology and Clinical Immunology. 2007;17(6):350.
6. Bindslev-Jensen C. Standardization of double-blind, placebo-controlled food challenges. Allergy. 2001;56(s67):75–7.
Paper: McQueen J, Loblay R, Swain AR, Anthony M, Lance J. A controlled trial of dietary modification in migraine. New advances in headache research. Smith-Gordom; 1989. p. 235–42.
Overview of paper: This trial follows on a study of food intolerance in 237 migraine patients presenting at a food allergy clinic [1]. In the original study (elimination diet/double blind placebo-controlled food challenges), 48% reacted to at least one chemical challenge, such as nitrates, preservatives, salicylate, amines, MSG, or tartrazine; four years later, a large number of these patients continued to follow an appropriately-restricted diet and considered themselves substantially improved.
In the current trial, participants were recruited from a migraine clinic instead of a food allergy clinic. Only 19 of 95 participants completed both the food challenge and the modified diet crossover trial (4 weeks normal diet, 1 week washout, 4 weeks trigger-free diet): “only half experienced a significant improvement on the appropriate [trigger-free] diet, and only three were headache-free altogether.”
The quote:
[E]ven in patients in whom dietary triggers may have been identified by double-blind challenge, long-term avoidance of the relevant foods is likely to be effective as a prophylactic measure only in a minority of patients. This should not be taken to mean that patients who incriminate particular foods as triggers must be mistaken. The situation is comparable to that in asthmatics where it has become abundantly clear that some patients are sensitive to the effects of salicylate, MSG and sulphite preservatives. Large doses may sometimes precipitate acute attacks, but regular avoidance of foods containing these substances does not usually produce measurable clinical improvements in the long term [2]. No doubt, in asthma as in migraine, this reflects the multitude of other intrinsic and extrinsic factors involved in the triggering of symptoms in predisposed individuals.
Significance of quote: This study has definite limitations, including a small sample size, a greater placebo response rate than normal, a short washout period (and possible order effect), and dietary compliance issues. The write-up is also short on experimental details, especially regarding the order of the two test diets. However, perhaps some of these problems mirror the real-life difficulties that people face when trying to manage migraines that can often be linked to food. Secondary triggers – lack of sleep, menstruation, bright lights, motion sickness, fragrances, etc. – can be at least as or even more important than food on any given day. This is not to say, though, that migraine (and asthma) sufferers should freely consume the foods that they know to be triggers, only that the complete avoidance of trigger foods may not be necessary for certain people.
2. “After 3 months on the restricted diet, four of 19 children on the MBS[metabisulfite]-free diet and one of six on the salicylate-free diet had objective signs of improvement, namely, reduction in asthma medications and/or improvement in lung function.”
Towns SJ, Mellis CM. Role of Acetyl Salicylic Acid and Sodium Metabisulfite in Chronic Childhood Asthma. Pediatrics. 1984 May 1;73(5):631–7.
Paper: Clarke L, McQueen J, Samild A, Swain A. The dietary management of food allergy and food intolerance in children and adults. Australian Journal of Nutrition and Dietetics. 1996;53(3):89–98.
Available from: https://www.sswahs.nsw.gov.au/rpa/allergy/research/daareview.pdf
Overview of paper: This review paper, written for dietitians, covers the definition, symptoms, and diagnosis of food allergies and (pharmacological) food intolerance. The only way to diagnose food intolerance is through an elimination diet and subsequent food challenges, and “all patients with suspected food intolerance need to be assessed by a physician to exclude any other disorder” before starting down this path.
The quote:
In most patients [on an elimination diet], clinical improvement occurs gradually over a two- to four-week period. If there is no change in symptoms after four weeks of strict adherence to the elimination diet, then food intolerance is unlikely to be the main factor in causing the patient’s symptoms. A normal diet should then be resumed by reintroducing one suspect food or chemical group at a time (e.g. milk, wheat, salicylate, amines, preservatives and colours) in gradually increasing amounts, up to high doses for three to seven days to determine if symptoms are exacerbated.
Significance of quote: Even though pharmacological food intolerance reactions are often delayed, elimination diets only need to last for four weeks to rule out food intolerance.
Paper: Schab DW, Trinh N-HT. Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled trials. J Dev Behav Pediatr. 2004 Dec;25(6):423–34.
Overview of paper: Many different studies have investigated the impact of artificial food colors (AFCs) on hyperactivity in children. Considering this prior work, this meta-analysis calculated an effect size of 0.283, which means that AFCs do seem to have a small but notable effect on behavior in some children. In comparison, this effect size is “approximately a third to a half the magnitude of the ESs [effect sizes] calculated in a meta-analysis of trials evaluating methylphenidate [Ritalin/Concerta] as a treatment of ADHD.”
The quote:
Neurochemical research into the basis of ADHD has strongly implicated defects in dopamine transmission. Both dopamine depletion and administration of AFCs create hyperactivity in developing rats. However, a theory on the contribution of AFCs to ADHD symptomatology must contend with two incongruities. First, the symptomatology of ADHD may differ from the pattern of symptoms induced by AFCs: as suggested by Rowe and Rowe, AFCs are associated more with irritability and insomnia than restlessness and inattention. Second, the patterns of behavior elicited by dopamine depletion in developing rats differs from the pattern elicited by administration of AFCs (or their metabolites). The sensitivity of developing rats also begs consideration of whether exposure to AFCs differentially affects the developing and developed organism.
Significance of quote: What is the nature of the behavioral changes caused by AFCs – do these chemicals cause ADHD or do they influence behavior in a way that aggravates ADHD? It seems that the effects of AFCs are slightly different than “true” ADHD symptoms, and the mechanisms behind them are likely to be different as well.
The debate over gluten is certainly confusing. While there have been several high-profile articles warning against gluten-free diets for the average healthy person (see this article on today.com for an example), it’s also not hard to find a friend or someone in the office who has some sort of gluten-free success story. Who should you believe? Does gluten really do all of the bad things that people say it does?
Gluten free diets are only medically needed by people who suffer from celiac disease, an immune disorder that attacks the small intestine. In contrast, the enormous popularity of going gluten free is not supported by medical need – instead, it’s bolstered by a number of medical-sounding gluten myths that speak to healthy people with common health concerns. In this article, we’ll pit these myths – which cover water weight, acne, rough skin, and hormonal problems – against established facts and learn why gluten is NOT behind them. We’ll also discuss the many benefits of wheat that you’d miss on a gluten-free diet.
Myth 1: Gluten causes water weight gain.
You may feel like you have less weight around the middle on a gluten-free diet, but carbs are actually behind this myth. Gluten is not a carbohydrate – it is a protein – and both carbs and protein are present in wheat. It naturally follows that if you avoid wheat bread, you are also avoiding the second largest source of carbs in the American diet (after soft drinks and next to cakes, cookies, pastries, and pies) [1].
The factors that influence how much water weight you carry – like hormones, your water intake, and your salt intake – are dynamic, so your weight can fluctuate by a few pounds each day. Carbohydrate consumption is another such factor. The short-term energy reserves in your liver are made up of carbs that have been converted into glycogen. The glycogen is ‘hydrated’ so that you retain about 2.5 grams of water for each gram of stored glycogen. When you eat fewer carbs, you store less glycogen and you retain less water. Reverse the process and you can also see why you initially lose water weight on a low-carb diet. [2]
The real question is, should you deliberately eat to avoid those few pounds of water, or is it healthier to invest in stretch denim? Losing water weight will only get you so far – eventually you need to further reduce calories to achieve sustainable weight loss, and a gluten-free diet is neither a good short-term nor a good long-term way to go about this. Gluten-free diets are not necessarily low in calories nor low in carbs if you eat processed foods or rice and potato flours, and, after a time, you are likely to become deficient in folate, calcium, iron, and zinc [3,4]. And if you’re thinking about adopting a typical low-carb diet instead, remember that while carb counting is important for diabetics, the benefit to others is unclear.
Myth 2: Gluten causes acne.
Carbs also seem to be responsible for this myth, too. After years of uncertainty as to whether sugar or chocolate really does cause acne, it is starting to look like refined carbohydrates and dairy aggravate or influence acne by way of insulin and insulin-like growth factor 1 (IGF-1). [5,6] IGF-1 is a growth hormone, but it continues to play a role in the body throughout adulthood.
Just as we discussed for water weight, avoiding wheat in order to (unnecessarily) avoid gluten can come with the side benefit of lowering your consumption of refined carbohydrates and reducing your acne. Now, does this necessarily mean that you should switch to a low-carb diet instead? No. As registered dietitian Jennifer Burris points out [5], the research to establish dietary guidelines for acne has yet to be conducted, and the best approach for managing acne is for each individual to work with their doctor and a dietitian to develop a solution that fits their particular situation.
Myth 3: Gluten causes “chicken skin” or keratosis pilaris.
Keratosis pilaris (KP) is a benign skin condition that looks a bit like permanent goose bumps on the arms, thighs, and buttocks [7], although the bumps are much rougher than goose bumps. In KP, excess keratin – a key protein in our outer layer of skin and in our hair and nails – plugs the hair follicule, sometimes trapping a small hair inside. [7] Keratosis pilaris is quite common – it affects around 50% of adolescents (80% of females) and 40% of adults – and seems to have a strong hereditary component. [8]
Keratosis pilaris is not caused by gluten-induced intestinal damage, as is claimed in this myth, and, in fact, keratosis pilaris is not common in celiac disease, the worst case scenario of gluten sensitivity. The only connection between KP and food seems to be a positive association with body mass index [9,10]. Less clear is a relationship between insulin resistance, IGF-1, and KP (also reported in the previous references), which is only speculation at this point.
Myth 4: Gluten causes hormone imbalances.
According to this myth, gluten produces intestinal inflammation that places stress on the adrenal glands, which in turn interferes with the sex hormones. Symptoms include water retention, acne, moodiness, extra body fat, migraines, fatigue, and many others – a little something for both younger and older women, and men, too. This myth is actually a new variant of an old idea from alternative medicine known as adrenal fatigue. In adrenal fatigue, the adrenal glands are called on to produce more and more of the stress hormone cortisol and eventually become exhausted. However, adrenal fatigue wasn’t true before gluten sensitivity came along, and it still isn’t true now.
But isn’t avoiding gluten just good sense?
To some, gluten-free dieting has its own sort of logic: since humans cannot fully digest gluten, and since modern wheat has been bred to have a high gluten content, then eating less wheat brings us back to the way things should be. But while longing for a low-gluten past may be a lovely bit of nostalgia, that’s all it is. Most people have no medical reason to avoid gluten, and no one has actually shown that the hybridization of modern wheat has led to a rise in any illness.
In fact, it is even wrong to think that the gluten content of wheat has been deliberately altered over the past several thousand years. [11] And true, many products today like supermarket breads contain an added gluten powder called vital gluten, and our consumption of vital gluten has tripled since 1977; however, this added gluten is still less than one-tenth of the overall gluten intake for most people. [11]
Despite wheat getting a bad rap today because of gluten (and earlier this century because of the high glycemic index of many foods based on white flour), there are actually health benefits to eating wheat – and possibly even gluten! Before you go gluten free by choice, take a look at some of wheat’s virtues:
Wheat contains a type of carb known as fructans, and one of these is the inulin that you’ll see listed in the ingredients of high fiber or prebiotic processed foods. Fructans help to support certain beneficial bacteria in the gut, which may in turn protect us against some cancers, some inflammatory conditions, and cardiovascular disease. [12] On the down side, fructans can make you gassy and bloated, but remember not to blame gluten for this.
Whole grains lower blood pressure, reduce the risk of type 2 diabetes, lower total and LDL cholesterol levels, and decrease the serum concentration of C-reactive protein, a marker of low grade inflammation. [13-15] Whole grains contain fiber, vitamins, minerals, and phytochemicals, but we don’t know which of these (or which combination) is responsible for their protective effects [14]; this makes it difficult to come up with a good substitute for whole grains, and whole wheat figures prominently into many whole grain foods.
Gluten itself may indirectly help boost the immune system and lower blood pressure. [12]
All things considered, a gluten-free diet is not really necessary for healthy people and may actually be detrimental.
Conclusion
Gluten myths seem to persist because of gluten’s association with carbohydrates – avoiding wheat to avoid gluten can also alleviate certain problems that are aggravated by carbs, giving the false impression that gluten is to blame. Don’t throw the baby out with the bathwater: for otherwise healthy individuals, a healthy, balanced diet will always be better than one that eliminates a staple food or an entire food group. If you do have health concerns, don’t go it alone. Speak with a doctor or a registered dietitian.
1. O’Neil C, Keast D, Fulgoni V, Nicklas T. Food Sources of Energy and Nutrients among Adults in the US: NHANES 2003–2006. Nutrients. 2012 Dec 19;4(12):2097–120. http://dx.doi.org/10.3390/nu4122097
2. Blackburn GL, Phillips JC, Morreale S. Physician’s guide to popular low-carbohydrate weight-loss diets. Cleveland Clinic journal of medicine. 2001;68(9):761–761.
3. Thompson T. Folate, iron, and dietary fiber contents of the gluten-free diet. J Am Diet Assoc. 2000 Nov;100(11):1389–96. http://dx.doi.org/10.1016/S0002-8223(00)00386-2
4. Shepherd SJ, Gibson PR. Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with coeliac disease. J Hum Nutr Diet. 2013 Aug;26(4):349–58. http://dx.doi.org/10.1111/jhn.12018
5. Burris J, Rietkerk W, Woolf K. Acne: The Role of Medical Nutrition Therapy. Journal of the Academy of Nutrition and Dietetics. 2013 Mar;113(3):416–30. http://dx.doi.org/10.1016/j.jand.2012.11.016
6. Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Experimental Dermatology. 2009 Oct;18(10):833–41. http://dx.doi.org/10.1111/j.1600-0625.2009.00924.x
7. Hwang S, Schwartz RA. Keratosis pilaris: A common follicular hyperkeratosis. Cutis. 2008;82(3):177–80.
8. Alai AN, Elston DM. Keratosis Pilaris Treatment & Management [Internet]. Medscape. [cited 2014 Jun 12]. Available from: http://emedicine.medscape.com/article/1070651-overview
9. Yosipovitch G, Mevorah B, Mashiach J, Chan YH, David M. High body mass index, dry scaly leg skin and atopic conditions are highly associated with keratosis pilaris. Dermatology (Basel). 2000;201(1):34–6.
10. Yosipovitch G, Hodak E, Vardi P, Shraga I, Karp M, Sprecher E, et al. The prevalence of cutaneous manifestations in IDDM patients and their association with diabetes risk factors and microvascular complications. Diabetes care. 1998;21(4):506–9.
11. Kasarda DD. Can an Increase in Celiac Disease Be Attributed to an Increase in the Gluten Content of Wheat as a Consequence of Wheat Breeding? Journal of Agricultural and Food Chemistry. 2013 Feb 13;61(6):1155–9. http://dx.doi.org/10.1021/jf305122s
12. Gaesser GA, Angadi SS. Gluten-Free Diet: Imprudent Dietary Advice for the General Population? Journal of the Academy of Nutrition and Dietetics. 2012 Sep;112(9):1330–3. http://dx.doi.org/10.1016/j.jand.2012.06.009
13. Brouns FJPH, van Buul VJ, Shewry PR. Does wheat make us fat and sick? Journal of Cereal Science. 2013 Sep;58(2):209–15. http://dx.doi.org/10.1016/j.jcs.2013.06.002
14. Belobrajdic DP, Bird AR. The potential role of phytochemicals in wholegrain cereals for the prevention of type-2 diabetes. Nutr J. 2013 May 16;12:62. http://dx.doi.org/10.1186/1475-2891-12-62
15. Hauner H, Bechthold A, Boeing H, Brönstrup A, Buyken A, Leschik-Bonnet E, et al. Evidence-Based Guideline of the German Nutrition Society: Carbohydrate Intake and Prevention of Nutrition-Related Diseases. Annals of Nutrition and Metabolism. 2012;60(s1):1–58. http://dx.doi.org/10.1159/000335326
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.
I have mixed emotions whenever I see an article on the Internet that instructs people on using an elimination diet to discover their food sensitivities. Of course, it’s not the idea of an elimination diet that bothers me – I have said many times that a properly done elimination diet and food challenges are the only way to diagnose food intolerance. These articles worry me when they suggest testing for sensitivities to foods that are on the list of Big 8 allergens. Simply put, don’t mess with these foods without consulting your doctor.
The Big 8 foods account for 90% of the food allergies in the US. (Interestingly, the most common food allergens vary by country.) The Big 8 foods are milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat and soybean. Other notable allergens include buckwheat, sesame, celery, mustard, and even corn. Fruits can also cause allergic reactions, and, quite frankly, it is possible to be allergic to any food, even if it isn’t commonly thought of as an allergen. Deadly anaphylactic reactions in adults are most often caused by peanuts, but any allergen can lead to a life-threatening reaction, even when your previous reactions were mild.
Adult-onset allergies
Did you know that it is possible for adults to develop food allergies after a lifetime of being able to eat anything? Allergies can start at any age, and adult-onset food allergies come with an increased risk for severe reactions.
Recently, doctors from Northwestern University [1] wanted to learn more about adult-onset food allergies, so they looked at the medical records of 1,111 patients from their allergy clinics. Fifteen percent of these patients were newly diagnosed as adults. In this group, the average age of onset was 31 years old, and 64% of patients were women. Shellfish and fish were the most common allergens, but all of the major allergens were represented.
If you think that you may have experienced an allergic reaction to a food in the past – even something as small as tingling in the mouth or a delayed reaction – ask your doctor for help in ruling out food allergies. For each person, the minimum amount of allergen required to produce a reaction is different. While the minimum amount for some foods is generally small (think peanuts), others often require larger amounts. When you ‘challenge’ yourself with a food to see whether you have a reaction, you don’t want to get into trouble by eating a large amount of something you wouldn’t normally eat. Even if your doctor allows you to do the food challenges on your own, it’s better to have asked than to be sorry later.
You might wonder why certain Internet MDs and nutritionists are giving out bad advice on testing for sensitivities to these allergenic foods. Unfortunately, they are basing their advice on misinformation from the alternative medicine community. Alternative medicine will have you believe that there is a lower grade of allergic reaction – originally referred to as food intolerance but now most often called a ‘sensitivity’ – that occurs when your IgG antibodies try to protect you from harmful foods. (A different antibody, IgE, is responsible for true allergic reactions.) As the story goes, IgG-based symptoms are delayed but never deadly. The truth is, these reactions don’t exist, and IgG antibodies are present in all of us as a sign that we can tolerate the foods that we commonly eat, like wheat, milk, eggs, soy, etc. Don’t mistake your mild but true allergic reactions for one of these ‘sensitivities.’ Even though food allergies often diminish over time, they will never cross over into a food sensitivity.
For more information on the common foods that produce allergic reactions (and for some interesting reading, too), check out these websites:
Stay tuned for a second article on this topic, where I will discuss the other conditions associated with these food allergens that you should talk to your doctor about.
1. Kamdar TA, Peterson S, Lau CH, Saltoun CA, Gupta RS, Bryce PJ. Prevalence and characteristics of adult-onset food allergy. The Journal of Allergy and Clinical Immunology: In Practice. 2015 Jan;3(1):114–115.e1.
Our bodies like to remind us that we aren’t as young as we used to be. The good news is that our digestive systems aren’t affected by aging as much as the other parts of us [1]. The bad news is that we can’t abuse our stomachs like we used to if we want to maintain the pleasure of eating. Does this mean that we have developed food intolerance? Not necessarily. To see why, let’s first look at the normal gastrointestinal signs of getting older, along with some age-related complications.
Age-related changes in digestion
Age brings with it certain changes in digestive function that some healthy people may notice more than others, including [2]:
Decreased lactase production. Older adults are more likely to be lactose intolerant and experience bloating, gas, or diarrhea after eating dairy products.
Decreased elasticity and slower emptying of the stomach. Some people cannot eat as much as they used to in one sitting without feeling fullness or bloating.
Overgrowth of certain bacteria in the small intestine. Our gut bacteria is mostly confined to the large intestine, and this is normal (although some bacteria are more desirable than others). As we age, the chance of bacterial overgrowth in the small intestine increases, producing pain, bloating, and weight loss.
Slowing or weakening of contractions in the large intestine. Constipation is more likely as we age.
If any of these points sound familiar, speak with your doctor to make sure that your symptoms are simply age-related and not part of a more serious problem. Be sure to discuss any signs of small intestinal bacterial overgrowth, because even though you can find plenty of Internet advice about “healing your gut” on your own, this condition may need medical treatment.
Other gastrointestinal symptoms are not caused by aging per se, but by things that go along with age [3], such as:
Medications. These can increase or decrease the time it takes for food to pass through us, resulting in either constipation or loose stools.
Age-related illnesses. Certain illnesses can also affect the proper functioning of the digestive system.
Obesity. Obesity makes heartburn more likely.
Continuing bad eating habits. Late-night fast food or too much coffee can cause heartburn and affect intestinal transit time.
In these cases, something as simple as a change in medication could provide much relief. As I said before, talk with your doctor about your concerns.
Relationship with food intolerance
If someone experiences a bad reaction after eating a certain food, it’s easy to understand why they might conclude that they have food intolerance – after all, it’s almost impossible to escape the association between food and digestion. But true food intolerance is a hypersensitivity reaction to food (emphasis on hyper-sensitivity) that most people will not encounter.
Continuing with our original question, are any age-related symptoms actually food intolerance? Well, there are three types of food intolerance [4,5]:
Enzymatic food intolerance – when the body does not make enough enzymes to digest or properly use a nutrient, as in lactose intolerance or phenylketonuria.
Toxic reactions – mainly histamine toxicity from spoiling fish (scombroid poisoning)
According to this classification, lactose intolerance is a type of food intolerance, but the other age-related digestive symptoms are not. This is an important distinction to make with regards to how we think about (and act on) our current state of health – in other words, do we continue to view ourselves as “normal” for our age, or do we start to feel like we have a “problem”?
What does this mean?
When food-related symptoms occur more frequently with age, this does not necessary mean that we have developed a medical problem – food intolerance – that needs to be treated by completely avoiding certain foods. It might just mean the we need to change our eating habits, like when we eat, how much we eat, and how much we can expect to indulge. For example, an adult with lactose intolerance may still be able to eat small amounts of dairy products (like yogurt) throughout the day, but they shouldn’t expect to go out after a soccer game and eat an ice cream sundae on an empty stomach like the rest of the kids. That said, if you are experiencing any of the symptoms mentioned in this article, see your doctor before attributing them to age.
1. Russell RM. Changes in gastrointestinal function attributed to aging. Am J Clin Nutr. 1992 Jun 1;55(6):1203S–1207S. PubMed
2. Effects of Aging on the Digestive System: Biology of the Digestive System: Merck Manual Home Edition [Internet]. [cited 2014 Apr 20]. Available from: http://www.merckmanuals.com/home/digestive_disorders/biology_of_the_digestive_system/effects_of_aging_on_the_digestive_system.html
3. Karen E. Hall, Wiley JW. Age-Associated Changes in Gastrointestinal Function. In: Hazzard W, et al. editors. Principles of Geriatric Medicine and Gerontology. 4th ed. New York: Mcgraw-Hill; 1998. p. 835–42.
4. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report. J Allergy Clin Immunol. 2010 Dec;126(6):1105–18. http://dx.doi.org/10.1016/j.jaci.2010.10.008
No blood test can detect food intolerance, not even the IgG/IgG4 ELISA tests that check for ‘hidden food intolerances’ to over a hundred common foods.
How do I get help, then?
Depending on where you live, it may be difficult to find a doctor or registered dietitian who has experience diagnosing food intolerance. Provided that your doctor has already ruled out other health problems, you can always contact the professional dietitics association in your country or visit their website. These associations maintain lists of dietitians by location and specialty. Depending on your medical history, some dietitians may be willing to consult with you from a distance.
Remember, the only way to diagnose food intolerance is through an elimination diet and food challenges. Even if you are concerned about a dairy or gluten sensitivity, IgG blood tests are of no value. (1-3)
In fact, allergy and immunology associations around the world have issued position statements warning against IgG blood tests, which they see as leading to potentially dangerous dietary restrictions, overlooked conditions (including true allergies), and unnecessary costs. Immunologists have found no evidence that IgG antibodies cause delayed food allergies or intolerances. As we’ll see later, it also turns out that the main demonstration of ‘successful’ IgG-based exclusion diets was not really so successful.
Still, you’re probably here because you have heard (from testing companies or the alternative medicine community, no doubt) that science supports not only the assumption behind IgG blood tests – that IgG antibodies are linked to delayed food sensitivities and chronic symptoms – but also the reported ability of IgG-based exclusion diets to relieve chronic illness. You may have also seen these tests in pharmacies or in the offices of doctors who practice functional or integrative medicine. You may be wondering, “Why are these tests being sold if they don’t work?”
“Why” involves motivation, so I’d rather focus on “how.” In the case of IgG blood tests, “how they can be sold” is an unfortunate melding of a few facts taken out of context plus some flawed research, with a few misrepresentations about how the immune system works thrown in. I must be clear, though – the problem isn’t one with consensus in the medical community. As I said, immunologists have not found any evidence of IgG-based food sensitivities, and it’s not as if they wouldn’t have noticed – for sure, IgG antibodies come up in research on immunotherapy, and this is a hot topic these days.
The alleged medical credibility of IgG blood tests is really coming from researchers in other specialties who hear about these tests and decide to give them a try for whatever condition they study (migraines, IBS, ADHD, etc.). This doesn’t seem particularly wise, but under the tenets of evidence-based medicine, a high-quality study should weed out bad ideas. However, in debunking the myths used to support food intolerance blood tests, we’ll see that not all studies are high quality.
Antibodies and allergies
Before we dive into the myths, let’s start with some background on antibodies and allergies. Antibodies, also known as immunoglobulins (Ig), are proteins produced by the immune system that help protect our bodies from foreign materials. There are several different classes of antibodies. For example, IgE antibodies bind to allergens (proteins from plants, animals, and fungi that should otherwise be of no threat to the body) and trigger histamine release from mast cells in what we think of as classical allergies (like to pollen or peanuts). Specialists refer to classical allergies as IgE-mediated reactions.
Allergy, intolerance, or sensitivity?
You may see different terms used to describe IgG blood tests – some say they detect food intolerance, others say delayed allergies, and others say food sensitivities. Since IgG antibodies are not involved in any adverse reactions to food, it doesn’t matter which label you choose – they’re all incorrect. Historically, though, these tests were advertised as detecting food intolerance, but the recent trend is to use the term food sensitivity. By medical convention, however, if IgG-based reactions were real, they would actually be a type of allergy. I prefer to speak of them as IgG-mediated reactions, but I do vary it a bit depending on the context.
The symptoms of IgE-mediated allergy come on rather abruptly after eating an offending food, often within 30 minutes to an hour. Other types of reactions – like cow’s milk protein intolerance – involve different aspects of the immune system and take longer to develop. Supporters of food intolerance blood tests believe that IgG antibodies cause yet another delayed type of allergic reaction, one which the medical community has failed to notice. Often this reaction is incorrectly labeled as food intolerance.
The IgG antibody class has several specialties, one of which is protective immunity. Protective immunity refers to our immune system’s ability to recognize and remove invaders like bacteria or viruses. This is also what keeps us from getting chicken pox twice. Blood is routinely screened for IgG antibodies to check for prior infections or vaccinations, but this is not the kind of blood test we’re talking about here.
IgG antibodies also support tolerance. Tolerance occurs when the immune system remembers to suppress its reaction to a foreign substance or to the body itself – in other words, tolerance is why the majority of us can eat whatever we want without fear of an allergic reaction. There are different mechanisms behind tolerance, but in many cases we have regulatory T cells to thank. Regulatory T cells invoke several helpers to suppress the immune response, and these include IgG antibodies. (4) IgG blocks IgE antibodies from combining with allergens and producing an allergic reaction, although the precise mechanics are under debate.
Even with this brief introduction, we can start to see that IgG antibodies are unlikely to be behind adverse reactions to food. The most advanced scientific knowledge points to the conclusion that food-specific IgG antibodies in our blood indicate exposure and tolerance, not in-tolerance, to those foods. (5) In other words, IgG antibodies are just a normal part of life. Unfortunately, commercial laboratories and alternative medicine still perpetuate the notion of IgG-mediated food reactions.
Taking on the myths behind IgG blood tests
We’ll debunk six myths that are used to support food intolerance blood tests:
Myths 1 and 2 cover the (lack of a) relationship between food-specific IgG antibodies and symptoms. Myths 3 through 5 get technical as they explore the mechanisms by which IgG antibodies (supposedly) cause illness. Myth 6 is the big one – it covers the claim that exclusion diets based on an individual’s food-specific IgG levels can successfully treat chronic symptoms. We’ll become amateur scientists to deal with this myth, and, in the process, we’ll see that sometimes it only takes a basic understanding of the scientific method and a little logic to evaluate medical studies.
Myth 1: High levels of IgG antibodies mean that you have a hidden or delayed reaction to food
Everyone produces IgG antibodies to food. Even though food intolerance blood tests rank your IgG antibody concentrations for various foods as low, medium, and high, there is actually no such thing as a ‘correct’ level. IgG concentrations vary from person to person and depend on diet – perhaps even on how one was fed as an infant (4) – so even healthy people will have high IgG levels for some foods. This means that a healthy person could get the same diet recommendations from an IgG blood test as a person with symptoms.
The same thing happens in classic food allergies, where there is no question that IgE antibodies are responsible. Some allergy-free people have elevated IgE levels, so doctors will not diagnose someone as having a classic (IgE-mediated) allergy without some sort of secondary evidence. This evidence could include a personal history, a physical exam, a skin-prick test, or an elimination diet and food challenge; of these, the strongest evidence is the elimination diet and food challenge.
Some supporters of IgG blood tests do acknowledge this situation indirectly by saying that the tests should only be used to “guide” a standard elimination diet and food challenge. So, then, how well do these tests perform as guides? Promotional materials almost always include testimonials by people who believe that an IgG blood test helped them find the foods behind their symptoms, and this is not surprising. As Brostoff and Gamlin (6) point out, alternative therapies could not make viable businesses if there were no successes. But these authors go on to explain that success stories are far from evidence that a test is worth your money:
“Given that the most common sources of food intolerance are wheat and milk, such therapists can achieve a reasonable success rate by diagnosing sensitivity to these two foods in all their patients. If eggs, oranges, chocolate, tea, and coffee are added to the list, they may well achieve success with 50 percent or more, and some patients will benefit from the placebo effect alone.” (p. 141)
So it seems that common sense would have about a 50% chance of finding at least some of the relevant foods for people who, we assume, actually have a food sensitivity. That’s the same odds as flipping a coin – any blood test would certainly need to do better than that. But in a 2001 survey of UK residents who had taken the YorkTest IgG blood test, only about 50% saw significant improvement in symptoms after eliminating their reported foods. (7) [The survey was repeated in 2007 (8), but its write-up contains a hole: it does not give us enough information to calculate an analogous success rate to compare with the first survey (9).] All in all, it looks like IgG blood tests, common sense, and luck offer about the same amount of help for guiding an elimination diet.
Myth 2: Food-specific IgG antibody levels correlate with chronic symptoms
You may be surprised to learn that no one has shown that food-specific IgG levels correlate with symptoms. The few studies that looked for a relationship gave mixed results – for example, testing of over 5,000 people with self-reported food reactions (10) found positive correlations for antibodies to certain foods and negative correlations for others. A negative correlation means that high antibody levels are associated with health, which certainly goes against pro-IgG claims. Most importantly, only one of these studies ensured that the participants actually had food sensitivities in the first place, and this small study found no relationship between IgG levels and, in their case, irritable bowel syndrome. (11)
Confirming up-front that participants have food sensitivities (and to which foods) is a fundamental requirement of any study on food allergy or intolerance – without it, all conclusions are meaningless. Moreover, the verification of food sensitivities must be done in some way that is independent of what is being researched. After all, you can’t diagnose someone as having food sensitivity using the IgG blood test when it is the blood test itself that you are investigating. And you can’t just ask someone if they experience adverse reactions to food, because more people think that they have a food sensitivity (up to 10 times more) than actually do. Food sensitivities can only be verified through careful elimination diets and food challenges.
In scientific terms, the strictest elimination diet/food challenge protocol is called the double blind placebo controlled food challenge (DBPCFC), because there is an additional requirement that both participants and researchers be ‘blind’ to whether a person is given a placebo or a real food challenge. The DBPCFC is the gold standard of food allergy and food intolerance diagnosis, which means that it is the standard to which the validity of any new test, like a blood test, must be compared. All good research on food sensitivities requires the DBPCFC, but most studies that look for IgG-mediated reactions fail to use it. This will come into play again when we consider Myth 6.
Myth 3: IgG antibodies degranulate basophils
Basophils and mast cells are closely-related immune cells that lie at the heart of allergic reactions. These cells are first ‘sensitized’ when IgE antibodies attach to their surface; later, when multiple IgE antibodies link up with an allergen, the cells ‘degranulate’ to release histamine and other chemicals that are responsible for allergy symptoms. Over 30 years ago, researchers entertained the possibility that IgG antibodies could also operate in this manner, but this was based on an observation that has since been discounted (12). That’s the short answer — IgG antibodies do not degranulate basophils. The long answer is more complex.
In 1982, Fagan et al. (13) observed that a subclass of IgG antibody (IgG4) degranulated basophils in vitro – this is why some food intolerance tests look at IgG4 levels specifically. After Fagan’s observation, IgG antibodies became a hot research topic. As the 1990s rolled around, immunologists had accepted that IgG was not a direct cause of allergic reactions, and IgG4 in particular was cleared of its alleged involvement; still, though, the initial observation needed to be explained. (14-16) In 1992, Lichtenstein et al. (17) revisited Fagan’s work and uncovered the reason why IgG had appeared to be a reagin.
Author’s note
I included this myth for people who want to pull out the old research and claim that IgG antibodies degranulate basophils. However, you shouldn’t read too much into this explanation of anti-IgE antibodies: there is nothing here to imply that IgG is a sign of classical (IgE-mediated) allergies.
It turned out that IgG did not degranulate the basophils directly. Using the blood of allergic donors, Lichtenstein showed that IgE antibodies were really responsible, as one would expect. However, the IgE antibodies had IgG antibodies attached to them, and this IgG had hidden the IgE in earlier experiments. It may sound strange, but it is possible to have antibodies against antibodies, and that is what these IgG antibodies were – anti-IgE antibodies. Hidden IgE antibodies are not uncommon: in certain tests, the presence of IgG anti-IgE antibodies can give the appearance of increased IgG levels and decreased IgE levels for the same allergen. (18)
Myth 4: IgG antibodies cause inflammation
To say that IgG antibodies cause inflammation is like trying to name a tune from just one note. There are four subclasses of IgG (IgG1 through IgG4), each with different roles. From the study of protective immunity, we know that some IgG antibodies have pro-inflammatory effects while others are anti-inflammatory. (19) However, the protective immune response involves a finely choreographed balance between these players, along with many other antibodies and cells. IgG4 antibodies help to wrap things up at the end of the immune response and have an anti-inflammatory effect. (19) Overall, IgG antibodies are necessary to keep our immune system in check, and singling out one type of IgG to conclude that IgG antibodies cause inflammation is a gross oversimplification – and just plain wrong.
Myth 5: IgG blood tests detect Type III hypersensitivities
Promotional materials from some laboratories will try to convince you of IgG’s role in food sensitivities by bringing up an unrelated point – that IgG antibodies are involved in Type III hypersensitivities. That is true, but it has nothing to do with what we are talking about here.
Type III hypersensitivities occur when immune complexes, made from IgG antibodies bound to other proteins, deposit in tissues like the kidneys, the joints, or blood vessel walls. This activates the immune system and leads to tissue damage. Type III hypersensitivities are caused by chronic infections, by inhaling dusts from hay or mold, or by your own body in autoimmune disorders, but not by foods. If you have a chronic Type III hypersensitivity reaction, you’re sick, you know it, and your doctor knows it – you might have a type of arthritis, breathing problems, or lupus.
Myth 6: Diets based on IgG levels have been shown to successfully treat symptoms
In debunking Myths 1 through 5, we have seen that there is no evidence to support the existence of IgG-mediated food reactions. In spite of this, a handful of clinical studies have attempted to determine whether diets based on IgG levels can reduce symptoms by looking at two specific groups of people – patients with migraine or patients with irritable bowel syndrome (IBS). Some studies found no benefit (see reference 20, for example), while others saw mild effectiveness (see reference 21).
These diet studies compare the effectiveness of test diets – ones that exclude the foods for which an individual has high IgG levels – against “sham” diets that serve as placebo controls. The best known of these studies, and the one regarded by alternative medicine as the pivotal study for legitimizing IgG blood tests, is a randomized controlled trial conducted by Atkinson et al. in 2004 (21). In order to blind participants to the nature of their diet, both diets in the Atkinson study excluded the same number of foods, but the control diets excluded foods for which a person did not have high IgG levels. Here, the group of IBS sufferers that received the test diet saw a 26% improvement in symptoms over the group that received the control diet.
The Atkinson study may look promising, but we’ll see that it suffers from inherent design flaws that essentially nullify its results. Before we get into this, though, we need to discuss how the scientific method is supposed to be applied to clinical studies. The scientific method is a procedure used to ensure that we make valid conclusions about the world around us. Observations are used to formulate a hypothesis about the way things work, and the hypothesis leads to predictions of cause and effect. This is where we hit the first problem with the Atkinson study – no one has observed that food-specific IgG antibodies are related to symptoms, so there should really be no hypothesis to proceed with.
When there is a reasonable hypothesis, it can be validated by testing its predictions in an experiment. Experiments are controlled situations where one and only one factor is varied and the outcome is recorded – if two or more factors are varied at one time, you would not know which is responsible for the outcome. If the outcome is the same as the prediction, and if the same result is obtained when other researchers repeat the experiment, then the hypothesis is true for that situation. In our case, if the Atkinson study really did have a valid hypothesis, it would only be true for IBS sufferers.
The scientific method is harder to apply in medicine than in branches of science like chemistry or physics where experimental conditions can be completely controlled. Some medical experiments that might seem ideal in terms of controlled conditions are unethical to perform on humans because the procedures might do harm. Moreover, people are people – participants in clinical studies have different histories, different environments, and different genes, and they don’t always follow directions. They are also susceptible to the placebo effect, where their own expectations of success or failure influence the outcome of a medical intervention.
To deal with human variability and unpredictability, medical science has developed its own arsenal of experimental techniques, the most notable of which is the use of a control group to serve as a reference for interpreting results. People in the control group might not have the illness in question or might not be subjected to the factor being studied. The selection of the control group can make or break an investigation, so care must be taken to match the characteristics of the people in the control group to those in the test group. When people are randomly assigned to each group, which is the ideal situation, the experiment is called a randomized controlled trial.
Getting back to the Atkinson study, we can see that it was not a well-designed experiment because multiple foods were excluded from the test diet or included in the control diet – in other words, more that one factor was varied at a time. Some might counter that this was necessary in order to see the full effects of the diets, and maybe that’s true, but the proper procedure would have been to conduct a DBPCFC on multiple and individual foods. While the test and control diets were both problematic, the most significant problem came from the control diet, as three independent researchers pointed out in letters to the journal that published the Atkinson results (22). One commenter noted, “regardless of IgG antibody status, the dietary restrictions in one group are not controlled for by the other group, and hence the conclusion may not be valid.” (23) Ironically, the control group added more uncertainty to the experiment than it took away.
Here is an example of this uncertainty. Most participants had high IgG levels for wheat and milk, so the test diets ended up being wheat-free and milk-free while the control diets generally contained these foods. This difference between the diets is significant because wheat and milk are known to aggravate IBS. Was the control group accidentally sabotaged by being given unfriendly foods? We just don’t know. It might be tempting to wonder whether IgG antibodies are the reason why wheat and milk aggravate IBS symptoms, but remember, there is no proof that IgG levels are related to any adverse effects. Moreover, Hunter (11) pointed out that significantly more participants in the Atkinson study had high IgG levels for milk than had been previously observed, so IgG levels are most likely not a factor in IBS.
The main lesson here is that experiments like the Atkinson study are too fraught with uncertainty for us to draw any conclusions from their results. One of the study’s investigators countered criticism of the control diets by arguing that the control diets did successfully compensate for the placebo effect because the test group improved on their diet to a statistically greater extent than the control group. (24) Statistical results are only as good as the experiment, though. The improvement of the control group may not have all been due to the placebo effect – their diet may have inadvertently removed some REAL food intolerance triggers, although we will never know because no one bothered to check the participants for food sensitivities using a DBPCFC.
Experimental flaws aside, it is also worthwhile to get a sense of just what a “26% improvement in symptoms” means for an IBS study. In a different measure of success, called the number needed to treat (NNT), the test diets in the Atkinson study performed much worse than other dietary interventions used in IBS. (11) The NNT is the number of people that need to be treated in order to find one who benefits from the treatment, calculated with respect to the control group. The NNT for this study was 9, while for most IBS diet studies, the NNT is around 2. Again, as we saw in Myth 1, diets based on IgG blood tests just don’t measure up.
Conclusions
In order to prove that food-specific IgG antibodies cause delayed reactions and chronic symptoms, one fundamental question would need to be answered: “do high levels of IgG against a food predict an adverse reaction to that food” (11). In debunking the myths used to justify food intolerance blood tests, we have seen that no research has provided a positive answer to that question. The evidence actually points to there being no association between IgG antibodies and adverse reactions, making IgG blood tests useless.
Some might personalize the argument against IgG-mediated food sensitivities and see it as dismissing their symptoms or delayed reactions in general. This is not true. The issue here is whether IgG blood tests are worth 500 to 1000 USD and the inconvenience, risk, and expense of modifying one’s diet – all possibly for nothing or for less improvement than could have been gained using a proper elimination diet and food challenges.
Remember that elimination diets and food challenges are already reliable means of diagnosing food sensitivities, even though spending a month or so tracking and testing your diet may not seem as attractive as a single blood test. Fortunately, the diet investigation process is not a shot in the dark – an experienced doctor or dietitian can use your personal history and your own suspicions to guide you through the process. Even though testing companies use rhetoric about ‘hidden food intolerances,’ there is usually nothing ‘hidden’ about food sensitivities at all.
1. Hochwallner H, Schulmeister U, Swoboda I, Twaroch TE, Vogelsang H, Kazemi-Shirazi L, et al. Patients suffering from non-IgE-mediated cow’s milk protein intolerance cannot be diagnosed based on IgG subclass or IgA responses to milk allergens. Allergy. 2011 Sep;66(9):1201–7. PubMed
2. Philpott H, Nandurkar S, Lubel J, Gibson PR. Alternative investigations for irritable bowel syndrome. J Gastroenterol Hepatol. 2013 Jan;28(1):73–7. PubMed
3. Carroccio A, Mansueto P, D’Alcamo A, Iacono G. Non-Celiac Wheat Sensitivity as an Allergic Condition: Personal Experience and Narrative Review. The American journal of gastroenterology. 2013;108(12):1845–52. PubMed
4. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. Journal of Allergy and Clinical Immunology. 2011 Jan;127(1):18–27. PubMed
6. Brostoff J, Gamlin L. Food Allergies and Food Intolerance: The Complete Guide to Their Identification and Treatment. Inner Traditions/Bear; 2000. 486 p.
7. Sheldon TA. Audit of the York Nutritional Laboratory Survey. Townsend Letter for Doctors and Patients [Internet]. [cited 2014 Mar 4];2002(August/September). Available from: http://webcache.googleusercontent.com/search?q=cache:QMG_H0UxZqIJ:www.drbralyallergyrelief.com/baf-report.doc
8. Hardman G, Hart G. Dietary advice based on food-specific IgG results. Nutrition & Food Science. 2007;37(1):16–23.
9. Are we missing something? 5,286 people responded to the 2007 survey of YorkTest users. Of these respondents, 75.8% indicated that they had experienced a ‘noticeable improvement’ in their condition after excluding foods from their diet. This may be true, but there are two things that are misleading about this figure. First, the definition of ‘noticeable improvement’ was expanded in the 2007 analysis to include people with only moderate improvement – this was not the case in the 2001 survey, so the 2007 results look better. More importantly, the 2007 survey does not tell us the total number of people who originally received the survey; in other words, we know how many people responded, but we don’t know how many people didn’t. When survey results are analyzed, it is important to have some idea of how non-respondents would have answered, because these people are more likely to have a negative attitude about the survey topic. As in the 2001 survey, the 2007 survey did include phone follow-ups with a sample of non-respondents, and, as expected, these people were less successful than the respondents with their diets after the YorkTest. In 2001, the inclusion of non-respondents in the analysis gave an overall success rate that was lower than the rate for respondents alone. The same would be true for the 2007 survey, but since the report did not tell us how many people failed to respond, we have no way of calculating the overall success rate. In other words, the 75.8% figure does not mean what we are led to think it means, and the true percentage would be lower.
10. Zeng Q, Dong S-Y, Wu L-X, Li H, Sun Z-J, Li J-B, et al. Variable Food-Specific IgG Antibody Levels in Healthy and Symptomatic Chinese Adults. PLoS One [Internet]. 2013 Jan 3 [cited 2014 Feb 16];8(1). Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536737/
11. Hunter JO. Food elimination in IBS: the case for IgG testing remains doubtful. Gut. 2005 Aug;54(8):1203. PubMed
12. Hamilton RG. Relevance of (IgG anti-IgE)-IgE complexes, IgG subclass and modern IgG antibody autoanalyzers in the dying IgG reagin story. Allergy. 2009 Feb;64(2):317–8. PubMed
13. Fagan DL, Slaughter CA, Capra JD, Sullivan TJ. Monoclonal antibodies to immunoglobulin G4 induce histamine release from human basophils in vitro. J Allergy Clin Immunol. 1982 Nov;70(5):399–404. PubMed
14. Van der Zee JS, Aalberse RC. The role of IgG in immediate-type hypersensitivity. Eur Respir J Suppl. 1991 Apr;13:91s–96s. PubMed
15. Shakib F, Smith SJ. In vitro basophil histamine-releasing activity of circulating IgG1 and IgG4 autoanti-IgE antibodies from asthma patients and the demonstration that anti-IgE modulates allergen-induced basophil activation. Clin Exp Allergy. 1994 Mar;24(3):270–5. PubMed
16. Aalberse RC, Van Milligen F, Tan KY, Stapel SO. Allergen-specific IgG4 in atopic disease. Allergy. 1993 Nov;48(8):559–69. PubMed
17. Lichtenstein LM, Kagey-Sobotka A, White JM, Hamilton RG. Anti-human IgG causes basophil histamine release by acting on IgG-IgE complexes bound to IgE receptors. J Immunol. 1992 Jun 15;148(12):3929–36. PubMed
18. Jensen-Jarolim E, de Weck AL, Stadler BM. Are allergen-specific IgG mainly IgG anti-IgE autoantibodies? Int Arch Allergy Appl Immunol. 1991;94(1-4):102–3. PubMed
19. Collins AM, Jackson KJL. A Temporal Model of Human IgE and IgG Antibody Function. Front Immunol [Internet]. 2013 Aug 9 [cited 2014 Feb 24];4. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738878/
20. Mitchell N, Hewitt CE, Jayakody S, Islam M, Adamson J, Watt I, et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches. Nutr J. 2011 Aug 11;10:85.
21. Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004 Oct;53(10):1459–64. PubMed
22. Gut – eLetters for Atkinson et al., 53 (10) 1459-1464 [Internet]. [cited 2014 March 30]. Available from: http://gut.bmj.com/cgi/eletters/53/10/1459 (Archived by WebCite® at http://www.webcitation.org/6Ojb0PjlN).
23. Sewell WAC. IgG food antibodies should be studied in similarly treated groups. Gut. 2005 Apr;54(4):566. PubMed
24. Whorwell PJ, Bentley KJ, Atkinson W, Sheldon TA. IgG antibodies to foods in IBS. Gut. 2005 Aug;54(8):1204. PubMed
Food intolerance blood tests measure a person’s levels of IgG antibodies to a wide variety of foods, but IgG antibodies do not have any proven link to illness. At best, these blood tests are a waste of money; at worst, they can lead to poor or even dangerous health decisions.
Despite their inherent ineffectiveness, IgG food intolerance tests have spread to the pharmacy and the doctor’s office, making it hard for the average patient to know where to turn for reliable information. To protect the public, professional medical associations in many countries asked the best minds in immunology to prepare position statements warning against these tests. Let’s take a look at some of the main points from these warnings in plain English.
From the Australasian Society of Clinical Immunology and Allergy [1]:
“IgG antibodies to food are commonly detectable in healthy adult patients and children, independent of the presence or absence of food-related symptoms. There is no credible evidence that measuring IgG antibodies is useful for diagnosing food allergy or intolerance, nor that IgG antibodies cause symptoms. In fact, IgG antibodies reflect exposure to allergen but not the presence of disease.” (full text)
What it means:
The most important thing to remember is that everyone produces IgG antibodies to food. The concentration of IgG antibodies in your blood depends on your genes, your diet, and maybe even on how you were fed as an infant [2]. There is simply no ‘correct’ IgG level. This means that a healthy person could get the same diet recommendations from an IgG blood test as a person with symptoms.
Looking at the entire body of available evidence, there is no correlation, let alone a causal link, between IgG antibodies and symptoms. In fact, using IgG test results to identify problem foods is no more successful than flipping a coin.
From the European Academy of Allergy and Clinical Immunology [2]:
“Food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints.” (full text)
What it means:
You might think that not being allergic to a food – in other words, being “tolerant” to that food – means that your immune system ignores it. Sometimes that happens, but tolerance is often an active process. Regulatory T cells keep the immune system from reacting to potential food allergens, and it is these cells that call in the IgG antibodies by secreting an anti-inflammatory messenger chemical known as IL-10. IgG antibodies are not the sign or cause of anything bad, but rather a sign that a person has eaten and has tolerated a certain food. IgG antibodies have nothing to do with food intolerance.
From the Canadian Society of Allergy and Clinical Immunology [3]
“The test is also being marketed to concerned parents, and may lead to exclusion diets which carry risks of poor growth and malnutrition for their children: for example, the elimination of dairy products, wheat, eggs, and/or other foods found in healthy balanced diets.” (full text)
What it means:
IgG blood tests often identify between 5 and 20 suspect foods, so the risk of nutritional deficiencies in children is real if too many foods are eliminated without proper medical support. The bigger issue is whether these tests are actually related to the conditions they are purported to treat, namely ADHD and autism spectrum disorder (ASD); let’s take a look at that.
ADHD. Some artificial colors have been shown to affect behavior in children with ADHD, but this reaction does not involve the immune system, so IgG blood tests are irrelevant for identifying which children might be affected. Other foods have also been shown to aggravate ADHD, but IgG levels could not accurately predict which foods. [4]
Autism spectrum disorder. Since IgG blood tests do not really detect adverse reactions to foods, it is unlikely that these tests would apply specifically to autism. While there is speculation that a ‘leaky gut’ increases the likelihood that IgG antibodies to wheat and milk proteins will be found in the blood of children with ASD, a much-touted paper on the topic actually showed that IgG levels did not correlate with intestinal permeability [5].
This doesn’t mean, though, that someone with autism couldn’t also suffer from food intolerance independent of IgG test results. For parents thinking about dietary interventions for autism, it might be helpful to consider the opinion of registered dietitian Zoe Connor, chair of the Dietitians in Autism group within the British Dietetic Association [6]:
“…[A]lthough there is insufficient evidence to recommend the use of any diet as a treatment for ASD, dietitians and other health professionals should provide support when an individual or their parents choose to try dietary changes. There are too many reports of children with ASD improving in behaviour and/or bowel habits after eliminating some foods for them to be discounted. However, the mechanism for this (until proven otherwise) is likely to be the same as for any general food intolerance, rather than any specific disorder that is particular to ASD, and so each case should be considered individually. For example, bowel problems such as diarrhoea or constipation can sometimes be caused by food intolerances, so individuals suffering from these might benefit from trying different food exclusions (medical causes should first be investigated by a doctor).” (p. 66)
From the American Academy of Allergy Asthma and Immunology [7]
“Additionally, and perhaps of greater potential concern, a person with a true immunoglobulin E (IgE)-mediated food allergy, who is at significant risk for life-threatening anaphylaxis, may very well not have elevated levels of specific IgG to their particular allergen, and may be inappropriately advised to reintroduce this potentially deadly item into their diet.” (full text)
What it means:
In true food allergies, IgE antibodies bind with allergen proteins to cause chemicals, like histamine, to be released in the body and trigger symptoms. IgG antibodies are not interchangable with IgE antibodies, and IgG blood tests do not detect food allergies.
We most often think of food allergies as beginning in childhood, but adults can also develop allergies at any time. Perhaps an old allergy returns, perhaps a mild allergy was there in the background all along, or perhaps the allergy is completely new. New allergies to pollen can also bring on food-related symptoms in the form of oral allergy syndrome. Adult food allergies must be taken seriously, because the risk for severe reactions becomes greater the later they develop [8].
Approaching food sensitivities the right way
The EAACI position statement [1] mentions another vulnerable market for food intolerance blood tests – people who see their doctor for a suspected food sensitivity that turns out not to be an allergy but cannot be explained. The doctor dismisses their symptoms, but not their suspicions of food. Feeling let down, they go outside the medical community for care or advice – which is understandable, but never the wise thing to do.
In a case like this, the safest thing is to get a doctor’s referral to see a registered dietitian and discuss doing a diet investigation. Alternative medicine may use rhetoric about ‘hidden food intolerances,’ but a knowledgable dietitian can use your personal history and diet log to guide you through the elimination diet and food challenges that check for food intolerance. In actuality, there is nothing ‘hidden’ about food intolerance, and there is no need to resort to blood tests to find your food sensitivities.
1. Australasian Society of Clinical Immunology and Allergy. Unorthodox Techniques for the Diagnosis and Treatment of allergy, Asthma and Immune Disorders – ASCIA Position Statement [Internet]. 2007 [cited 2014 Mar 10]. Available from: http://www.allergy.org.au/health-professionals/papers/unorthodox-techniques-for-diagnosis-and-treatment (Archived by WebCite® at http://www.webcitation.org/6OjZpQGNt).
2. Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S, Vieths S, et al. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Allergy. 2008;63(7):793–6. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2008.01705.x/abstract (Archived by WebCite® at http://www.webcitation.org/6OjZbB9va).
3. Carr S, Chan E, Lavine E, Moote W. CSACI Position statement on the testing of food-specific IgG. Allergy Asthma Clin Immunol. 2012 Jul 26;8(1):12. Available from: http://www.aacijournal.com/content/8/1/12 (Archived by WebCite® at http://www.webcitation.org/6OjZmUPVA).
4. Pelsser LM, Frankena K, Toorman J, Savelkoul HF, Dubois AE, Pereira RR, et al. Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial. The Lancet. 2011;377(9764):494–503.
5. De Magistris L, Picardi A, Siniscalco D, Riccio MP, Sapone A, Cariello R, et al. Antibodies against Food Antigens in Patients with Autistic Spectrum Disorders. BioMed Research International. 2013;2013:1–11.
6. Connor Z, Autism and autistic spectrum disorders. In: Skypala I, Venter C, editors. Food Hypersensitivity: Diagnosing and Managing Food Allergies and Intolerance. John Wiley & Sons; 2009. p. 63-68.
7. Bock SA. AAAAI support of the EAACI Position Paper on IgG4. Journal of Allergy and Clinical Immunology. 2010 Jun;125(6):1410. Available from: http://www.jacionline.org/article/S0091-6749(10)00512-9/fulltext (Archived by WebCite® at http://www.webcitation.org/6OjZkm9m9).
8. Kamdar TA, Peterson S, Lau CH, Saltoun CA, Gupta RS, Bryce PJ. Prevalence and characteristics of adult-onset food allergy. The Journal of Allergy and Clinical Immunology: In Practice. 2015 Jan;3(1):114–115.e1.
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.
How common is pharmacological food intolerance? Several million people are currently suffering from this problem in the West, and more – perhaps 5-10% – will have experienced it in their lifetime. You might see figures out there, however, that vary widely, from less than a percent to 20% and upwards, but this isn’t so surprising considering that it has also been difficult to get good prevalence estimates for food allergies (1,2). In this article we will sort through the available data and see why 5-10% is a fair estimate for the lifetime prevalence of food intolerance.
What is prevalence?
Prevalence tells us how many people are suffering from a disorder at a single point in time, given as a percentage of the total population. Since it is impossible to ask every person whether they have a certain condition, researchers work instead with a sample of people who will represent the entire population. The size of this sample will dictate the reliability of the results. The best studies also verify a person’s response by having them go through a medical examination or some other diagnostic procedure.
What data is out there on food intolerance?
For conditions like food intolerance, where the prevalence is expected to be only a few percent (or less than a percent), the most reliable data will come from studies where the sample size is in the hundreds (or thousands). From among these studies, we only want to consider the ones that use a double blind placebo-controlled food challenge (DBPCFC) to check whether a person really suffers from food intolerance. It turns out that just a handful of investigations meet our requirements (see Table 1), and four out of five of these focus only on the effects of food additives like artificial colors and sodium benzoate.
Table 1. Large-scale prevalence studies for food intolerance
Country
Study type
Population
Prevalence
Denmark (4) N = 4274
Additives DBPCFC
All children
1-2%
Denmark (5) N = 379
Additives OC, DBPCFC
Atopic children
2-7%
Denmark (6) N = 1094
Additives DBPCFC
22 year olds
0.5%
UK (7) N = 18,582
Additives DBPCFC
Adults
0.01%-0.23%
Germany (8) N = 4093
Foods, additives & salicylate DBPCFC
Adults
0.78-1.1%
N is the sample size
DBPCFC is double-blind placebo-controlled food challenge, an elimination diet and food challenge where the researchers and participants are unaware of who is receiving a real food challenge or a placebo
OC is open challenge, where the challenge food is known to all involved
Overall, it appears that food additive intolerance occurs in a few percent of children and a fraction of a percent of adults; when more foods are included, as in the German study, the prevalence increases to about one percent. The studies given in Table 1 also verify what has been observed elsewhere, namely that:
Food intolerance is more common in women than in men.
Children are more likely to suffer from food additive intolerance than adults.
Atopic individuals (people with allergies and often asthma) are more likely to see adverse reactions to food, which often exacerbate flare-ups of their existing conditions.
Unfortunately, the data that we have falls short in several ways, most notably in scope. As mentioned, the studies in Table 1 focused on food additives, not naturally-occurring trigger chemicals in food. Even in terms of additives, each study differed in the number and amounts of additives that were tested, and common preservatives, such as sulphites, were absent in many cases. Madsen (3) pointed out that these studies also differed in their inclusion criteria, that is, the symptoms that people could have and still participate in a study. Furthermore, many symptoms, including migraine, gastrointestinal symptoms, and hyperactivity in children, were not considered. Thus, the reported prevalence rates are slightly lower than what should be expected for pharmacological food intolerance when it is more completely defined.
Towards a more inclusive prevalence rate
Is there any other data that we can use to improve our estimate? Numerous smaller studies have been done on food intolerance in specific groups – like sufferers of chronic skin reactions, respiratory symptoms, and gastrointestinal problems – and it is tempting to extend the numbers found there to the rest of the population. Unfortunately, we cannot rely on studies that were not originally designed to establish prevalence rates because the results may be biased. For example, specialized clinics are likely to have reputations that attract specific types of patients, and these may or may not be representative of all patients with those conditions. This is called spectrum bias, a well-known cause of variation in clinical studies.
Alternatively, we could look at prevalence estimates for sensitivities to individual food chemicals, or at the co-occurrence of food intolerance and certain illnesses, and add it all up. For example, histamine intolerance, defined as two or more non-allergic symptoms that improve through antihistamine use and a low histamine diet, is thought to have a prevalence rate of at least 1% and perhaps higher (9). In the US alone, about 12% of the population suffers from migraines, and food triggers are involved in about half the cases (10). Indirect evidence (11) suggests that irritable bowel syndrome is aggravated by foods that contain or cause the release of histamine in the body – this could affect as much as 5-10% of the population, but this has not been clinically verified. The picture is even less clear for other food triggers and conditions, and we are missing information on sensitivities to naturally-derived salicylate and benzoate, other biogenic amines, etc.
Looking at the numbers that we do have, it seems reasonable, if not conservative, that the overall prevalence of food intolerance would be at least several percent. This consistent with the lifetime prevalence estimate of 5-10% from Loblay and Swain of the RPAH Allergy Clinic in Australia (12); they based this estimate on their experience with thousands of patients, although experience does not carry the same scientific weight as epidemiological studies. Still, we can double check if these numbers make sense by considering lifetime prevalence and self-reported prevalence rates.
Lifetime prevalence
When scientists give prevalence rates, they are actually talking about point prevalence, which is how I defined prevalence at the beginning of this article: the fraction of people suffering from a disorder at a single point in time. Lifetime prevalence is the fraction of people who will suffer from a disorder at some point in their lifetime. For life-long illnesses, the point prevalence and the lifetime prevalence will be equal; for disorders that last for relatively brief periods, the lifetime prevalence can be several or even many tens of times higher than the point prevalence, depending on exactly what it is that predisposes a person to developing a disorder. We can expect that the lifetime prevalence of food intolerance will be higher than the point prevalence values we have been discussing, but we don’t know by how much.
If we have some idea of how long food intolerance lasts, we can put some limits on how many times higher lifetime prevalence could be. Food intolerance is thought of as a transient and individualized problem (13, 14). Different people will experience food intolerance for different lengths of time, and, after undergoing a period of avoiding their personal triggers, will have varying success in reintroducing these food chemicals to their diet. There are limited follow-up reports on individuals who have undergone food intolerance testing. Swain (15) found that 81% of respondents to a follow-up questionnaire still experienced a recurrence of symptoms as much as five years after having identified their trigger chemicals. We can make some assumptions and use a probability calculation to estimate that for this group, food intolerance lasts for 14 years – this means that the lifetime prevalence for adults would be about three times higher than the point prevalence. (16) This keeps us in line with our lifetime prevalence estimate of 5-10%.
Self-reported rates
Doctors and researchers often note that people perceive more adverse reactions to foods than can be verified through double-blind placebo-controlled food challenges. Self-reported prevalence rates from surveys of the general population are as much as 10 times higher than the rates determined through controlled testing – this goes for all types of food reactions, even allergies. For example, in the German study included in Table 1, which also looked at food allergy, the self-reported lifetime prevalence for all food hypersensitivities was 34.9%, while the point prevalence was found to be 3.6% based on food challenges. (8) Surveys conducted in different countries give different self-reported rates (17), which can be explained by different diets, different genetic make-ups, and cultural differences.
The discrepancy between clinical and self-reported rates causes some medical professionals to be suspicious about the existence of food intolerance. But does this discrepancy really mean that food intolerance is, for the most part, ‘all in the mind?’ Let’s consider some possible reasons for the higher self-reported rates:
Depending on the survey questions, the self-reported rates could be representing the lifetime prevalence instead of the point prevalence – we need to be careful not to compare apples and oranges.
The respondents could simply be wrong about what caused their symptoms. Most of the self-reported rates were recorded before the current media focus on food allergies and food intolerance, but, today, heightened awareness is increasing the perception that food is the source of symptoms that are otherwise unexplained.
Food aversion is a real phenomenon – you begin to associate a food with an illness and then any exposure to that food makes you feel ill – and this could be mistaken for food intolerance.
Some people may experience a food sensitivity reaction once or twice in their lives, never to be repeated. Large-scale diagnostic studies like the ones listed in Table 1 do have procedures for screening out such events (for example, see reference 7) and only inviting individuals who have a history of reproducible food-related symptoms to participate in the food challenge phase. Studies that present only self-reported rates may or may not use such procedures, so we need to look carefully at each figure to see exactly what it includes.
Another possibility is that there is something about how food intolerance is verified in clinical studies that leads to an underestimation of the true prevalence. Next we will look at the difficulties involved in diagnosing food intolerance to see if this has any effect on point prevalence.
Diagnostic challenges
While it is possible to diagnose food intolerance by elimination diets alone and by open food challenges, only the double-blind placebo-controlled food challenge (DBPCFC) is viewed by researchers as providing a definitive result. This makes it the ‘gold standard’ among test procedures, but, unlike many other gold standard tests, the accuracy of the DBPCFC is not known. (18) In other words, since the process has not been standardized, the accuracy will vary from study to study depending on how the test was conducted.
The DBPCFC was developed with food allergies in mind, where a single food is expected to produce a fairly rapid reaction. These reactions are often easy to see – an asthmatic patient experiences a decrease in breathing ability or a patient develops hives. However, even with food allergies, the results are not always clear cut. (19-21) Take chronic eczema that has not cleared before the test – how much of a change in skin irritation is needed for a positive result? How long should you wait for a response? How do you grade subjective symptoms like headache? How many times should you repeat the test if the patient responds to the placebo? Should you stop medications during the test? Etc.
The diagnosis of food intolerance shares these uncertainties and more, and it can be difficult to reproduce positive food challenge results even in people with good evidence of food intolerance. (7) Several things come into play here:
It is not uncommon for someone to need to be exposed to a combination of food chemicals before they see symptoms. For example, Di Lorenzo et al. (22) found that few patients with chronic urticaria (hives) reacted to challenges with a single food additive but that many reacted to mixtures. Something like this could result from a true sensitivity to each of the triggers (12, 15) (even ones that are not chemically related) or from the unique effects that mixtures have on the processes that rid the body of foreign chemical substances.
Food intolerance reactions are dose-dependent, so a person will only see symptoms if the accumulated amount of food chemical in their body exceeds their threshold dose. Each person has a different threshold dose and this threshold can change over time. Researchers have trouble addressing these issues in food intolerance studies. For example, high challenge doses do not necessarily guarantee more positive reactions and, in any case, might not be representative of normal consumption. Incremental challenges might seem to mimic real life, but they could also lead a person to become more tolerant of a food chemical.
Similarly, some sufferers will be more sensitive to food triggers when they are also under stress, suffering from an illness, or exposed to certain chemicals (cleaning chemicals, fragrances, etc.) in their environment. (23) These additional factors may not be present at the time of the food challenge. Hormonal changes can also play a role in food sensitivity, but I have yet to see a study account for menstrual cycle, even though more women suffer from food intolerance than men.
Patients with chronic or allergic conditions need to be experiencing symptoms at the time of the food challenge in order for any worsening effect to be observed.
Researchers could simply be testing for sensitivity to the wrong chemicals. While salicylate or histamine intolerance is most often associated with fruit, German researchers reported that patients who failed to react to those substances still reacted to tomato extract, pointing to other unknown trigger chemicals. (24, 25). In another example, Lessof (26) pointed out years ago that a reaction to pesticide residue on unwashed fruit can also mimic food intolerance.
Trying to prove an association between food intolerance and a specific condition is like a shot in the dark if the condition that you are looking at is not uniform. As an example, consider the association between attention deficit hyperactivity disorder (ADHD) in children and food additives. For decades, scientists and the public have gone back and forth over whether behavior in these children is influenced by food chemicals. In 2010, one group of researchers found that food additives affected ADHD-like symptoms in children who possessed a gene that decreased their ability to break down histamine. (27) This result has yet to be replicated, but, if verified, it would go a long way to explaining why different studies had been finding different results – only a subgroup of children with ADHD (those with a certain gene) are sensitive to food chemicals. If a study did not happen to include any of these children, then it would have found no connection between behavior and food.
Right now we do not know the extent to which these diagnostic challenges might impact clinically-determined prevalence rates for food intolerance, but we can say that there is more uncertainty in these rates than is currently understood. From the examples that I have given, you might conclude that point prevalences could only go up if researchers addressed these issues; however, it all depends on how you define food intolerance and its impact on health. Increasing the specificity of the DBPCFC would certainly benefit individuals with hard-to-diagnose food sensitivities; at the same time, large-scale prevalence studies might also find more people who experience occasional reactions that do not lead to significant impairment. In the latter case, better diagnostics would not give us any more useful information on food intolerance as a public health problem.
Since self-reported prevalence rates vary more between countries than clinically-verified rates do (see ref 16 for examples), the inflation seen in self-reported rates is probably related more to cultural effects than to limitations of the DBPCFC. Based on self-reported rates, the real lifetime prevalence of food intolerance should never be more than 20-30%, which still supports our estimate of 5-10%. If we knew more about the mechanisms behind food intolerance, we could set upper limits on the prevalence rates for sensitivities to individual trigger chemicals; however, this will not necessarily be an easy task, because for each chemical sensitivity, there are still likely to be different mechanisms at work in different people.
Conclusions
A lifetime prevalence estimate of 5-10%, as given by Loblay and Swain, is probably a good, and perhaps conservative, estimate of the true prevalence of food intolerance. Better prevalence rates will not be available until researchers standardize the double blind placebo-controlled food challenge, define food intolerance consistently in terms of trigger chemicals and recognized symptoms, and make progress uncovering the mechanisms behind food intolerance.
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2. Kuznar W. Food Allergies May Not Be as Common as Reported. American Journal of Nursing. 2010 Aug;110(8):18.
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14. Hayder H, Mueller U, Bartholomaeus A. Review of Intolerance Reactions to Food and Food Additives. International Food Risk Analysis Journal. 2011;1.
15. Swain A. The role of natural salicylates in food intolerance [Internet] [PhD Dissertation]. University of Sydney; 1988.
16. Assumptions: The disappearance of symptoms follows a fixed probability and can be modelled by an exponential distribution; 81% still experience symptoms after 3 years. The rate of decline would be 0.07 events/year, which would lead to an expectation of 1/0.07 ≈ 14 years/event. For adults, assume a lifetime period of 40 years: 40/14 ≈ 3.
17. Skypala I. Other Causes of Food Hypersensitivity. In: Skypala I, Venter C, editors. Food Hypersensitivity: Diagnosing and Managing Food Allergies and Intolerance. John Wiley & Sons; 2009. p. 210–42.
18. Gellerstedt M, Bengtsson U, Niggemann B. Methodological issues in the diagnostic work-up of food allergy: a real challenge. Journal of Investigational Allergology and Clinical Immunology. 2007;17(6):350. PubMed
19. Niggemann B, Beyer K. Pitfalls in double-blind, placebo-controlled oral food challenges. Allergy. 2007 Jun 15;62(7):729–32. PubMed
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21. Niggemann B. When is an oral food challenge positive? Allergy. 2010 Jan;65(1):2–6. PubMed
22. Di Lorenzo G, Pacor ML, Mansueto P, Martinelli N, Esposito-Pellitteri M, Lo Bianco C, et al. Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria. Int Arch Allergy Immunol. 2005 Nov;138(3):235–42. PubMed
23. Allen DH, Van Nunen S, Loblay R, Clarke L, Swain A. Adverse reactions to foods. Med J Aust. 1984 Sep 1;141(5 Suppl):S37–42. PubMed
24. Henz BM, Zuberbier T. Most chronic urticaria is food-dependent, and not idiopathic. Exp Dermatol. 1998 Aug;7(4):139–42. PubMed
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27. Stevenson J, Sonuga-Barke E, McCann D, Grimshaw K, Parker KM, Rose-Zerilli MJ, et al. The role of histamine degradation gene polymorphisms in moderating the effects of food additives on children’s ADHD symptoms. Am J Psychiatry. 2010 Sep;167(9):1108–15. PubMed
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.
American College of Allergy, Asthma and Immunology (ACAAI). Oral allergy syndrome, high blood pressure medications can create lethal cocktail. [Internet] ScienceDaily; 2013 November 13. Available from: http://www.sciencedaily.com/releases/2013/11/131108090135.htm [Accessed 2014 January 18] (Archived by WebCite® at http://www.webcitation.org/6Oja4p5cB).
Breuer K, Wulf A, Constien A, Tetau D, Kapp A, Werfel T. Birch pollen-related food as a provocation factor of allergic symptoms in children with atopic eczema/dermatitis syndrome. Allergy. 2004;59(9):988–94. PubMed
Osterweil N. Foods That May Worsen Pollen Allergies. [Internet] WebMD. Available from: http://www.webmd.com/allergies/features/oral-allergy-syndrome-foods [Accessed 2014 January 18] (Archived by WebCite® at http://www.webcitation.org/6Oja92gwn).
Skypala I. Fruits and Vegetables. In: Skypala I, Venter C, editors. Food Hypersensitivity: Diagnosing and Managing Food Allergies and Intolerance. John Wiley & Sons; 2009. p. 147–65.
Non-celiac gluten sensitivity is not the same as food intolerance: gluten sensitivity may turn out to be a type of immune system reaction, while food intolerance is a non-allergic sensitivity to food chemicals. They do share one thing, though: the only proper way to diagnose them is through an elimination diet and food challenges.
Elimination diets and food challenges are not rocket science, but they do need to be done right. Here, I’d like to give you an example of how to do them WRONG. This comes from an episode of The Dr. Oz Show, in a segment titled “The New Warning Signs for Gluten Sensitivity.” Let’s look at why Dr. Oz’s advice is not a good way to go about investigating your diet.
“The New Warning Signs for Gluten Sensitivity”
In this episode, Dr. Oz warns that anyone who experiences migraine, brain fog, depression, joint pain, arthritis, or skin rashes could actually be suffering from gluten sensitivity (1). His guest, Dr. Amy Myers, agrees.
Dr. Myers is introduced as a specialist in functional medicine, which means that she is a licensed MD who practices alternative medicine. This is far from the first time that “America’s doctor” has promoted alternative medicine on his show; there are many good articles out there on his mixture of scientific and non-scientific beliefs – search on his name at Science-Based Medicine for more than a few – so I’m not going to get into that here. But I will say that much of what is said on his show should be taken with a grain of salt, including Dr. Myers’ thoughts on the prevalence of gluten sensitivity.
Dr. Myers first states that gluten sensitivity affects 18 million people in the US. She doesn’t explain this, but this figure corresponds to 6% of the US population, which is what some quote as the maximum possible prevalence for non-celiac gluten sensitivity (2). She then states that her personal suspicion is that 1 out of 2 people have gluten sensitivity, but this goes directly against what the researchers who originated the disorder think. She and Dr. Oz then tell us that people who suspect gluten sensitivity can do a gluten-free trial at home.
What’s wrong here?
The first problem with Dr. Oz’s advice is a matter of motivation. How likely is it that someone has gluten sensitivity? If the prevalence is 6%, then gluten sensitivity is a problem of similar size to food intolerance, but it’s not that likely for people who suffer from migraine, brain fog, depression, joint pain, or rashes – which are fairly common problems – to have gluten sensitivity. If the prevalence is 50%, as is presented on the show, then it’s quite a different story – you’d be crazy not to go gluten-free, right? And you might think, “Well, it’s only a two week diet. It won’t hurt and it might help.” But it could hurt, and it’s important to get it right.
Even for people who do have a deep suspicion that their symptoms are related to food, it is hard to know exactly which food or foods are causing the problem because we don’t eat single ingredients all day long. This leads me to the second problem with Dr. Oz’s advice – he doesn’t explain that an elimination diet and food challenges must be done in a systematic way.
Theoretically, you could just remove one food from your diet and keep the rest of your diet entirely the same. But this is difficult, if not impossible, to do in reality, especially with a foundation food like wheat. For example, if you stop eating pasta, you will probably also stop eating tomato sauce, and if you stop eating bread, you might also stop eating jam. You might still eat tomatoes and you might eat fruit, but tomato sauce and jam are concentrated versions of these foods and more likely to cause food intolerance. (3) Or you might inadvertently cut down on sugar and carbs or dairy or some other common trigger. (In fact, there is an idea floating around that high-sugar diets can lead to the same health effects as described by Dr. Oz.) So, if you started a two week gluten-free diet and felt better, could you really blame gluten for your symptoms? No.
All you can conclude from a poorly-done elimination diet is that your symptoms might be caused by something in your usual diet. Food challenges are the necessary second step to determine whether a specific food is causing your symptoms. After your symptoms subside, you must try eating that food again (the ‘challenge’) – if your symptoms return, then you can blame that food. But the food challenge is not as simple as it sounds, and you should be working with a doctor or dietitian on this. First, you should challenge with every food or trigger chemical that you excluded during the elimination diet phase – which, as I said, will probably include more substances than just gluten. Second, you should not only test yourself with the foods in question but also with a placebo. In an informal setting, a placebo could be any meal for which you do not know the ingredients (of course, you need to be working with someone else to pull this off). As you can see, coming up with the right foods or meals to challenge with does take some research and planning.
The placebo test is important to make sure that you find the truth and not just what you expect to find. In some cases, a doctor or dietitian might omit this step, especially in open challenges where it is obvious which food is being tested; however, the placebo effect could be significant for someone who goes into the process believing that they have a 50/50 chance of being sensitive to gluten. On top of this, specialists think that for patients with subjective symptoms (symptoms that can’t be measured by a third-party, like headache, brain fog, etc.), the food challenge and placebo tests should be repeated three times each, with a sufficient ‘wash out’ or break period in between, in order to get the best results.
So far I have been talking about avoiding results that are false positives – that is, thinking that you have gluten sensitivity when you don’t. It is also conceivable that you could get a false negative result, where you really are sensitive to gluten but your symptoms didn’t go away during the elimination diet. One way this could happen is if you also have a food intolerance – either you kept eating other foods that contributed to your symptoms or you added more of them to your diet through gluten substitutes. For example, sweet potato flour, sesame seeds, coconut flour, fava bean flour (and ‘garfava flour’), and almond flour are reported to be high in salicylate and/or amines. Most other grains and substitutes are not. Something similar could happen if you also suffer from a food allergy that you don’t know about (many gluten sensitive people also report food allergies). In order to avoid false negatives, the elimination diet should remove as many possible allergens or trigger chemicals as possible.
The price for getting it wrong
Those who suffer from celiac disease must to be extremely careful to avoid even trace amounts of gluten or else risk serious complications. This is a hard life to lead, to say the least, and not something to get into unnecessarily just because we are in the middle of a gluten-free fad. People on gluten-free diets also have problems meeting certain nutritional requirements, such as for folate and fiber. Doctors do not yet know whether gluten-sensitive people would need to follow the same level of adherence to a gluten-free diet as celiac suffers do.
Health problems should be approached more carefully than a 10 minute TV segment can convey. Doctors diagnose people with gluten sensitivity by ruling out all other causes and by looking at several different gastrointestinal test results that are easiest to interpret before you go gluten free. Self-diagnosis is dangerous because you can miss a serious medical problem; you also do yourself a disservice if you do have gluten sensitivity, because a doctor could provide you with ongoing advice as new risk factors, diagnostics, and treatments are discovered in this active area of research. You’ve waited long enough to sort out your symptoms – find a medical professional to help you get it right the first time.
1. The New Warning Signs for Gluten Sensitivity [Internet]. The Dr. Oz Show. 2013 [cited 2013 Dec 27]. Available from: http://www.doctoroz.com/episode/gluten-warning-signs-next-epidemic (Archived by WebCite® at http://www.webcitation.org/6OjaH1MXG).
2. Catassi C, Bai J, Bonaz B, Bouma G, Calabrò A, Carroccio A, et al. Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders. Nutrients. 2013 Sep 26;5(10):3839–53.
3. Swain A. The role of natural salicylates in food intolerance [PhD Dissertation]. University of Sydney; 1988. Available from: http://www.sswahs.nsw.gov.au/rpa/allergy/research/students/1988/AnneSwainPhDThesis.pdf
In this day and age, it’s hard to imagine medical tests that don’t draw blood or that don’t involve expensive, room-filling equipment; however, for food intolerance and some immune-mediated reactions, the tried and true diagnostic requires only a pencil, paper, and food. Doctors, dietitians, and medical researchers rely on elimination diets and food challenges to identify food sensitivities, which can be used regardless of the underlying mechanism – this is important because right now we have only rough ideas of how these some of these reactions might work.
Diet investigations are deceptively simple – start from scratch and add only one potential trigger at a time until the culprit is found – but they also require a detailed knowledge of food chemicals. For this and for safety reasons – after all, you need to rule out if you actually have an allergy or another condition – you should always undergo a diet investigation with the help of a doctor or a registered dietitian. To help you prepare, let’s look at the three phases of the process: the elimination diet, the food challenges, and the modified diet. Before you start, your dietitian may also ask you to briefly keep a food and symptom journal to provide a baseline on the severity and frequency of your symptoms.
The information here is provided to give you an idea of the diet investigation process; it is not a set of instructions to carry out the procedure yourself. Always check with a doctor or a registered dietitian before modifying your diet. The elimination diet/food challenge process is not appropriate for pregnant women. People with asthma or laryngeal edema (swelling in the throat/upper airways) should only undergo food challenges in a clinic where resuscitation facilities are available. People with Crohn’s disease should not try an elimination diet without medical supervision.
Phase 1: Elimination diet
The elimination diet consists of only a few foods that are unlikely to cause symptoms in most people; depending on your history, it might be less restrictive. You must adhere to the diet even if you think that you know which food chemical makes you ill because you might be sensitive to more than one chemical. In most people, symptoms improve after two to four weeks on the elimination diet. You may experience a withdrawal reaction (a flare-up of symptoms) after the first or second week.
The elimination diet is necessary for several reasons. First, it indicates whether you are on the right track: if there is no change in symptoms after four weeks of strict adherence to the diet, then food intolerance is unlikely. Second, it removes the variability (the ‘noise’) in your symptoms so that changes can be detected during the food challenge phase. Finally, it lowers the amount of trigger chemical that you need to eat in order to see symptoms.
The food challenges determine which food chemicals are triggering symptoms. After at least two weeks on the elimination diet, specific foods are reintroduced into your diet one at a time – these are the ‘challenges.’ If a reaction occurs after a challenge, then you must wait until the symptoms subside, plus a few days, before moving on to the next food. Such challenges are referred to as ‘open’ challenges because you are aware of what you are eating. In research studies, participants are given food chemicals in capsules so they do not know which chemical is being tested or whether they are getting a placebo – these ‘blind’ challenges provide the most reliable diagnosis.
Wheat and milk are often tested first because reactions to these foods are just as common as pharmacological food intolerance reactions; then salicylate, benzoate, amines, MSG, artificial colors, etc. are tested on the advice of your dietitian. Ideally, challenge foods would only contain one trigger chemical, but this is not always possible. When challenge foods contain more than one trigger, the ordering of the challenges is important to systematically rule out all possibilities.
Your dietitian will design a modified diet for you based on your challenge results. You will be reevaluated in 1 or 2 months to see how well the restricted diet is working and to decide whether it is safe to liberalize what you eat. In this part of the process, you will be checking to see whether you have a high or low dose threshold for symptoms; you may also be able to gradually increase the amount of triggers that you eat, but, for your safety, you should always work on this with a dietitian or doctor. Since threshold doses can decrease after avoiding a food chemical, sensitive people could experience dangerous reactions when reintroducing foods to their diet, even in amounts that previously did not cause symptoms.
More information
Consult these books if you are interested in learning more about diet investigations:
Brostoff J, Gamlin L. Food Allergies and Food Intolerance: The Complete Guide to Their Identification and Treatment. Inner Traditions/Bear; 2000. 486 p.
Clarke L, McQueen J, Samild A, Swain A. The dietary management of food allergy and food intolerance in children and adults. Australian Journal of Nutrition and Dietetics. 1996;53(3):89–98.
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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