Though on the rise, food allergies are fairly rare. If you have one, particularly a serious one, you may wonder why you got so lucky. While I can’t answer for the grand plans of the universe, I can provide a few insights on the subject. In this post I will be discussing the factors that make some proteins more likely to cause allergies and some of us more susceptible to them.

Do all proteins cause allergies?

Proteins are necessary for living cells to survive. They are ubiquitous and diverse with nearly 13,000 different protein families. Despite all that variety, just 0.16% of those families cause 80% of food allergies. Clearly, there is more to being an allergen than just being a protein.

What factors influence the potential of a protein to cause an allergic reaction?

1. Characteristics and structure of the protein

2. Amount of exposure to the protein

3. Genetic susceptibility of the person exposed

What types of proteins are more likely to cause allergic reactions?

Proteins provide countless essential roles in living organisms from balancing fluids to orchestrating chemical reactions. A protein’s function impacts its allergenicity. The majority of food allergies are caused by proteins involved in protection or storage.

Why protection and storage?

Protection proteins do exactly that. They protect plants from invasion by pests or pathogens. They are usually found in higher concentrations in seeds and tubers. These proteins are tough since they are designed to function even in hostile environments. Their ability to withstand aggressive atmospheres makes them perfect candidates for resistance to cooking and digestion. Profilins and Bet v 1, the main allergen in birch, are among defense proteins.

Storage proteins are found in seeds such as grains, nuts, and legumes. Their main purpose is to supply the nutrients required for the sprouting and developing of seedlings. There are two primary issues with these proteins. They are highly concentrated in seeds leading to greater exposure, and many of them are not damaged by heat. For example, globulins, which comprise over 50% of the protein in some species of nuts, are stable up to 200 degrees Fahrenheit. Albumins, like those found in soybeans and peanuts, are another family of storage proteins implicated in a large number of allergic reactions.

Beyond function, are there other protein properties that enhance allergenicity?

In order for a protein to initiate an allergic response, the allergenic component must be at least 20-25 amino acid residues long. Otherwise, it will be too short to bind properly to antibodies and the IgE system won’t respond.

Allergenicity is also dependent on stability. Sensitization through the gut, which is typical of many allergens like those in nuts, requires the protein to survive a number of onslaughts. It has to withstand cooking temperatures. It has to remain intact through the acidic conditions of the stomach. Additionally, it has to endure many enzymes and bile salts bombarding it throughout the digestive process. Most proteins are not up to the task. Some manage all too adeptly though.

Proteins make 3D structures by folding in and crosslinking. These arrangements look a bit like noodle blobs. As Giada De Laurentiis would tell you, not all noodles are created equal. Some protein configurations hold up better to cooking and digestion. For instance, beta structures are more resilient than alpha helices. Other structural components like links between different regions through disulfide bonds increase a protein’s hardiness. Plus, size does matter; smaller proteins are more able to withstand the heat of cooking.

Are certain protein sources more likely to cause allergies?

Immune responses, including allergies, are based on the body’s ability to distinguish between self and non-self. If a food protein is similar to our own proteins, it’s less likely our immune system will recognize it as different. Animal proteins, particularly from mammals, are much less prone to trigger allergic reactions for this reason.

Remarkably, a protein’s source may matter in other ways. Soy allergens usually elicit much milder reactions at much higher doses than many other allergenic foods. Research has suggested this might be due to the anti-inflammatory phytochemicals present in soy dampening the immune response to this ingredient.

What traits make a person more likely to develop allergies?

Some scientific studies indicate the risk of developing allergies is about 80% due to genetics. Inherited programming causes some immune systems to be unnecessarily sensitive. A genetic predisposition for an overly reactive immune system is known as atopy. Atopic diseases include eczema, asthma, pollen allergies and food allergies. If you have one parent with atopic disease, you have a 25% chance of also developing one. Those odds jump to 50% if both your parents have atopy.

The inherited immune system anomalies associated with allergies may have broader impact too. Research has shown the same genetic factors that increase vulnerability to allergies augment susceptibility to inflammatory and autoimmune disorders like Crohn’s disease and psoriasis.

That’s nature, but what about nurture?

Although genes clearly influence allergies, environment is decidedly also involved. Humankind’s genes haven’t changed in the last 50 years, but the incidence of atopic disease certainly has. In developed countries, the rates of asthma and allergies increased significantly in the last half of the 20^th century. For instance, in Australia, pollen allergies rose from 22.5% to 44% between 1982 and 1997.

One theory behind this surge is called the hygiene hypothesis. It speculates that modern environments have become too clean and our immune systems too sheltered from infections. Research has confirmed this hypothesis has merit, but no definitive conclusions can yet be made.

For my final part in this series, I will review how food allergies are diagnosed and treated. Come back to discover how to distinguish between an allergy that’s intolerable and an intolerance.

References:

1. Mills and Shewry. (2004). Plant Food Allergens. Blackwell Publishing.

2. Marenholz et al. (2017). Genome-Wide Association Study Identifies the SERPINB Gene Cluster as a Susceptibility Locus for Food Allergy. Nature Communications.

3. Masilamani et al. (2012). Determinants of Food Allergy. Immunology and Allergy Clinics of North America, 32(1), 11-33.

4. Thomsen. (2015). Epidemiology and Natural History of Atopic Diseases. European Clinical Respiratory Journal.

Cross-reactivity may sound like a description of your grandma’s irritation every time you walk through her pansies, but that’s not quite what it is.

As I mentioned in my previous post, 40% of those with pollen allergies have an associated plant food allergy due to cross-reactivity. Further, cross-reactivity is the predominant reason food allergies pop up in adulthood. While oral allergy syndrome is by far the most common way cross-reactivity presents, dangerous anaphylaxis can occur as well. Still, cross-reactivity perplexes both allergy sufferers and practitioners, which is why it will be the sole subject of this part in my allergies series.

What is cross-reactivity?

Cross-reactivity occurs when someone becomes sensitized to a particular allergen but then also reacts to separate species because of protein similarities.

Why do some proteins cause cross-reactivity reactions and others don’t?

As previously discussed, the bulk of food allergies are caused by proteins, and proteins are comprised of amino acids. One of the ways IgE antibodies recognize allergens is through amino acid sequences. If an unrelated protein has enough sequences in common with a substance we are allergic to, our IgE antibodies may flag it as an intruder as well. Yes, it may set our IgE Spidey sense and tongue tingling.

Why would two proteins be similar?

There are a couple reasons for likeness. Proteins from related species may share some components due to common genetics, but proteins from distinct species may also have commonalities because of similarities in function.

For instance, profilins are a group of proteins that are found in every plant part from fruit to nut. They perform essential functions like cell movement and, as they are present in almost every pollen, are a common pollen allergen. Roughly 10-30% of those with pollen allergies are sensitive to this family of proteins. Unfortunately, the uniformity between profilins from different plant sources is as high as 70-85%. What does this mean? Many people with pollen allergies will react when they encounter these proteins in food. Hence, profilins are involved in a high percentage of cross-reactivity cases.

Does the inhalant or food allergy come first?

Respiratory allergies are much more common than food allergies, impacting 10-30% of the world’s population. Therefore, in cases of cross-reactivity, the inhalant allergen is more often the primary sensitizer.

What are some of the common plants and foods that cause cross-reactivity reactions?

Which pollens and foods can cause cross-reactivity can be a bit confounding as the connections are not often obvious. Birch pollen and apple are the most frequently cross-reacting pollen and fruit pair. Birch pollen also causes cross-reactivity with carrots, pears, potatoes, and nuts.

Profilins, the protein family mentioned earlier, have been implicated in cross-reactivity with kiwis, apples, tomatoes, soybeans, celery, poppy seeds, and legumes. Fortunately, profilin allergy symptoms are typically mild involving a runny or stuffy nose in the case of pollens and oral allergy syndrome in the case of foods. On a side note, profilins are one of the allergens in birch pollen but are not the most common cause of birch allergies or cross-reactivity.

Many of those with a latex allergy will react to chestnuts, bananas, and avocados. This is because the protein involved in latex allergy, hevein, has 70% identical sequencing to proteins found in these fruits.

But cross-reactivity doesn’t stop with flora. People with a dust mite allergy can react to shrimp or other shellfish like mollusks.

Hopefully, how cross-reactivity connects the dissimilar is less confusing now. Next time, we will examine some of the properties of proteins and people that make allergies more likely to occur.

References:

1. Mills and Shewry. (2004). Plant Food Allergens. Blackwell Publishing.

2. Popescu. (2015). Cross-Reactivity Between Aeroallergens and Food Allergens. World Journal of Methodology, 5(2), 31–50.

When I was a kid, I used to tell people that I was allergic to beets so I wouldn’t have to eat them. Fortunately, I’ve learned to love beets over the years, therefore fibbing about that delicious veggie is no longer necessary. Yet, for a multitude of reasons, countless Americans may be guilty of their own allergy fibs. Allow me to keep you honest and informed.

As hard as it is to believe, many people restrict their diets unnecessarily based off erroneous self-diagnosed food allergies. While we’ve all encountered the occasional drama queen intent on making others accommodate imaginary dietary restrictions, I believe most people are justifiably baffled over allergies and are just trying to make the best decisions they can from the information they’ve encountered. With that in mind, let me add the synopses of some legitimate scientific research to your knowledge base. Over the next four posts, I will share some specifics I’ve learned about allergies through my years of being a food scientist. My studies have extended to literature written by some of the world’s leading experts on the subject, hundreds of pages of sensitivity sense. To restate, below you will find facts not propaganda, and more importantly, I hope you will find some answers.

How common are allergies?

Due mostly to confusion but perhaps sometimes delusion, 20% of the population believes they are allergic to at least one food. How close is that belief to reality? Only about one or two of every 100 adults and one in 10 children have a food allergy. What does this mean? Most kids outgrow their allergies and most adults are mistaken.

What causes allergies?

Allergies involve an immunological mechanism, usually a type I hypersensitivity reaction. This exaggerated response is mediated by IgE antibodies and can involve the skin, gastrointestinal tract, respiratory system, and cardiovascular system. It usually develops rapidly and doesn’t last long.

IgE antibodies are thought to have once been involved in defending our bodies against parasites. Our ancient ancestors may have had much need of their assistance, but modern living has largely eliminated the usefulness of their function. Since the only parasite currently in your life is that uncle that keeps borrowing money, your IgE are left bored and purposeless. Idle antibodies are the root of mischief in this case. In an attempt to stay relevant, these immunoglobulins have become the drama queens of the immune system. “Shellfish? Oh no you dit-ten!”

What are the most common food allergens?

The most widespread food allergies are milk, egg, peanut, tree nuts, fish, shellfish, soy, wheat, fruits, and legumes.

Is a food intolerance an allergy?

While intolerances are frequently mistaken for allergies, they are not allergies. Food allergies have an underlying immunological mechanism; food intolerances do not. Intolerances can be caused by deficiencies of certain digestive enzymes amongst other things. While intolerance can cause a great deal of discomfort, not to mention diarrhea, they do not pose a serious health threat.

Although there are a lot of reasons for adverse food reactions beyond the immune system, people tend to erroneously blame allergies. This leads to the overestimating of food allergies. If you and a certain food don’t get along, an allergy is just one of many possible explanations.

What specifically in foods causes allergies?

Proteins are generally the culprit though other substances like nickel can also cause responses. Proteins that resist digestion and are stable through cooking are more likely to cause allergic reactions as they are not broken down easily into their amino acid components.

Do you have to eat a food to have an allergic reaction to it?

No, allergic reactions to food ingredients can be caused by ingestion, skin contact, or inhalation. Yes, just touching a food or breathing its vapors can induce an allergic response in those susceptible.

What are the common skin symptoms of a food allergy?

Hives and swelling are typical demonstrations of a food allergy. Skin symptoms are the most common manifestations of a food allergy.

Skin reactions can occur from either consumption or direct skin contact. The foods usually associated with contact reactions are raw fish, shellfish, vegetables, and fruit.

What are the common gastrointestinal symptoms of a food allergy?

Anything from nausea, vomiting, abdominal pain, or diarrhea can mean a GI tract is dealing poorly with an allergen. These symptoms can be accompanied by issues in other organs or be the only indicators.

What are the common respiratory symptoms of a food allergy?

Respiratory reactions to a food allergen can occur due to inhalation or ingestion. Symptoms include stuffy nose, itchy eyes, bronchial swelling, bronchospasms, and bronchial hypersensitivity.

Some people allergic to fish, shellfish, or legumes may experience stuffy nose or sneezing when inhaling steam as these foods are cooking. Baker’s asthma, which is caused by the inhalation of flour, is one of the most pervasive occupational respiratory disorders. It impacts 15-30% of all millers, bakers, farmers, and pastry plant workers.

On a side note, the process of sensitization through the lungs is much more direct than sensitization through the gut. This is because inhaled proteins are in their native form not altered by digestion and cooking.

What is anaphylaxis?

Anaphylaxis is a potentially life-threatening expression of a food allergy that can simultaneously impact many body systems. It usually occurs within minutes of exposure and can cause itching, hives, swelling of the skin, swelling of the throat, difficulty breathing, abdominal cramps, vomiting, diarrhea, cardiac arrhythmias, hypotension, and shock. A third of all ER cases involving systemic anaphylaxis are a result of food allergies making those the most common cause. The foods most frequently implicated in ER visits are peanuts, tree nuts, fresh fruits, celery, seeds, legumes, seafood, eggs, and milk. Fatal anaphylaxis is more frequently observed in adults and adolescents; it seldom transpires with children. Acute asthma attacks associated with food-induced anaphylaxis can be particularly serious and are the most common reason for death in these instances.

How do the allergies of children vary from those of adults?

Allergies are most widespread during the first few years of life. Allergies that develop in infants are usually the result of proteins resisting digestion in the GI tract. Baby guts lack sophistication.

For children, the most common allergens are eggs and milk. These are usually outgrown, meaning a tolerance develops. However, kids allergic to peanuts, tree nuts, and shellfish typically remain allergic their entire lives.

In contrast, most food allergies that develop in adulthood are connected to pollens and other inhalant allergens and are a result of cross-reactivity. Cross-reactivity will be covered in my next post.

Are allergies region specific?

Peanut allergy is common in America whereas fish allergy is widespread in Japan. In Europe, many people are allergic to mustard seed. This demonstrates that the development of allergies is related to the degree of exposure.

Is there an association between atopic dermatitis, asthma, and food allergies?

The occurrence of allergies is greater in children with conditions like atopic dermatitis. Roughly 40% of children with mild-to-moderate dermatitis also have a food allergy. Further, childhood food allergies increase the likelihood of asthma and nasal allergies in adulthood.

What type of allergic response is most frequently experienced by adults?

Oral allergy syndrome is the most common way a food allergy presents itself in adults and seems to have become more ubiquitous in the last few decades. It involves contact hives, itching, and swelling restricted to the mouth and lips. It typically exhibits five to 15 minutes after consumption. This reaction is limited to the mouth because the proteins causing the allergy are broken down during the digestive process.

Oral allergy syndrome is regularly seen in adults and adolescents that are allergic to pollens of birch, ragweed, mugwort, or grasses. The triggering food is usually a fresh fruit or vegetable. Among those with pollen allergies, 40% have an associated plant food allergy. This is known as cross-reactivity. Cross-reactivity will be the subject of my next post in this four-part series. Tune in again soon for more overexcitement.

Reference: Mills and Shewry. (2004). Plant Food Allergens. Blackwell Publishing.