Many people suffer from unexplained symptoms like rashes, migraine, brain fog, and insomnia; some might never figure out the cause. Could common foods like dairy, wheat, eggs, and beans be responsible? And how do the experts think these sensitivities could work?
What is Food Sensitivity? What is Food Intolerance?
Food sensitivity and food intolerance are two very closely-related, but possibly distinct terms. They both describe non-allergic, bothersome reactions to food triggers.
Researchers generally seem to use “food intolerance” to describe non-immunologic reactions: for example, lactose intolerance is caused by a deficiency of the enzyme lactase. “Food sensitivity” is a nonspecific catch-all term used to describe a food reaction that is neither an allergy or intolerance .
However, the distinction between intolerance and sensitivity is not clear. According to the logic of the researchers cited above, food sensitivity must include all non-allergic immune responses to food. However, it has also been used to describe diseases that involve an allergic reaction by definition (such as eosinophilic gastrointestinal disease) [1, 2].
Food sensitivity and food intolerance may have so much overlap that they may describe a distinction without a difference. For the purposes of this article, we will use the terms interchangeably.
Food Sensitivity Symptoms
You may have already read a lot about inflammation and its complications. The best-known inflammatory condition is arthritis, but inflammation can be much less obvious than that. Here are the main symptoms food sensitivity can cause by raising inflammation.
If you have one or more of these symptoms and doctors haven’t been able to figure out why, you might want to ask if food sensitivity is a possible cause.
According to some researchers, digestive problems are among the most common symptoms of chronic inflammation from food sensitivity. The most common ones include bloating, nausea, diarrhea, and flatulence [3, 4].
“Brain fog” is what it sounds like: it describes a condition wherein mental function is slow and unclear, as if everything is happening through a fog. Brain fog reduces mental sharpness and clarity, learning, memory, and concentration .
According to some researchers, inflammation of the brain is the likely primary cause of brain fog. When inflammatory signals (such as histamine from mast cells) reach the brain, they activate the microglia, brain cells that act like white blood cells. Microglia activation has been associated with conditions like autism spectrum disorder [5, 6, 7, 8].
Migraine & Headache
Migraines and headaches can have a huge variety of triggers – everything from lights, sounds, and smells to the weather – so it can be difficult to tell whether they might be caused by food sensitivity .
Nevertheless, about a quarter of people who get migraines believe that food is the cause. In one study, all 56 migraineurs had unusually high IgG against between 6 and 30 foods; only 26% of healthy controls had unusually high IgG against a maximum of 4 foods .
Elimination diets based on these IgG results have had mixed results, however. In a study of 167 people, eliminating foods based on IgG reduced the number of migraines over the first four weeks, but the number rose back to near baseline at 12 weeks [9, 10].
In one study of people who believed that red wine triggered their migraines, drinking red wine did in fact trigger a migraine within about 3 hours. However, it’s difficult to create a placebo that looks, tastes, and smells like red wine, so the study could only compare wine with diluted vodka, serving them both cold and in dark bottles. Some of the observed effects may have been psychosomatic [9, 11].
A Connection with Histamine
Recently, one research team discovered that people who were prone to migraines had significantly lower than average levels of diamine oxidase (DAO), the enzyme that breaks down histamine. In their study, 87% of people with migraines were deficient in DAO, compared to 44% of people without migraines .
This result suggests that high histamine may cause or contribute to migraine headaches. Foods that are high in histamine (preserved, cured, or fermented foods) or that increase histamine release could trigger migraines .
Anxiety & Depression
Speaking of brain problems, inflammation and microglia activation can trigger anxiety and depression. Chronic inflammation decreases feelings of reward and motivation and increases sensitivity to perceived threats. In this way, inflammation can also worsen the symptoms of PTSD [7, 13, 14, 15].
Poor Sleep Quality & Insomnia
Chronic inflammation is associated with insomnia and shortened sleep duration, though its effect on sleep quality is less clear. It’s difficult to say whether inflammation causes poor sleep or vice versa. Currently, all we can say is that people (and especially teenagers) with insomnia have more inflammation than people who get a healthy amount of sleep [16, 17, 18].
Inflammation in the respiratory system causes symptoms like a runny nose, nasal congestion, cough, and difficulty breathing. Histamine is directly responsible for nasal congestion, so people with an inability to break down histamine could experience this symptom more than most [19, 20].
Some researchers believe that foods (fish, milk, eggs, and others) may contribute to asthma and other inflammatory symptoms of the airway. However, the relationship between food intolerance and asthma is not fully understood, and other researchers don’t buy into it .
Sensitivity to salicylates has been tentatively linked to the development of nasal polyps (abnormal tissue growth in the lining of the nose) .
Atopic dermatitis (eczema), rashes, and other symptoms of skin inflammation are common in food allergy and intolerance. In non-allergic reactions, skin inflammation can develop as late as 2-6 days after a sensitive person eats a trigger food [23, 24].
The most common food triggers for skin symptoms are milk (beta-casein) and egg whites (ovomucoid and ovalbumin) [23, 24, 25].
Possible Consequences of Food Sensitivity
At least one clinical trial has linked symptoms of food sensitivity to the complications or conditions in this section, but this is by no means an exhaustive list, and many people may react differently to foods and never develop these complications. In order to accurately assess your likelihood of developing neurodegenerative disease, cancer, and heart disease, talk to your doctor about your health status and risk factors.
Microglia activation may also drive neurodegeneration, as in the case of Alzheimer’s disease. One of the primary features of Alzheimer’s is the dysfunction of a protein called tau, which forms “tangles” inside neurons. According to some researchers, microglia activation – and, thus, inflammation in the brain – may be a driving force behind tau tangles [26, 27].
Like neurodegeneration, cancer isn’t a symptom to watch out for but rather a potential consequence of unmanaged inflammation.
Chronic inflammation and oxidative stress can damage DNA and prevent DNA repair. This can result in mutations, some of which can turn cells cancerous. Over a long enough period of time, inflammation can thereby directly cause cancer [28, 29].
According to some researchers, as many as a quarter of all cancers could be caused by inflammation and its complications [28, 29].
Inflammation and heart diseases have been connected for a long time. Inflammation and oxidative stress can damage the heart and blood vessels, opening the door for heart attack, coronary heart disease, and other serious health problems [30, 31, 32].
Researchers have long believed that high cholesterol causes heart disease. In the last year or so, some researchers have suggested that inflammation actually causes the problems attributed to cholesterol. However, cholesterol status contributes to inflammation, making this a potential “chicken and egg” situation .
Potential Dietary Offenders
Food sensitivity is relatively poorly understood, and many questions have yet to be answered. Some food components and additives have been observed to produce reactions in sensitive people, but the mechanisms for these reactions is often purely speculative. If you suspect that you are sensitive to a particular food or dietary component, talk to your doctor or dietitian about available tests and management strategies.
As Joe’s particular interests, lectin sensitivity and lectin avoidance have been heavily documented and discussed here at SelfDecode.
Lectins are a type of protein found in especially high amounts in legumes and whole grains (especially wheat). Check out Joe’s posts on lectin sensitivity for a detailed exploration of this poorly understood intolerance [33, 34].
Milk can produce inflammation in people in a few different ways. Some people don’t have enough of the lactase enzyme to break down lactose (milk sugar). Others are allergic to cow’s milk; they produce immunoglobulin E (IgE) against cow’s milk antigens and develop digestive, respiratory, skin, or anaphylactic symptoms [35, 24].
However, even with lactase and without allergy, some research suggests that cow’s milk may still cause problems. People with cow’s milk protein intolerance (CMPI) develop digestive or skin problems between 1 hour and several days after consuming milk. They do not have high IgE, IgG, or IgA against cow’s milk, and classic skin prick allergy tests come back negative .
CMPI typically causes nausea, bloating, diarrhea, and skin rashes. Some researchers suspect that Th1-mediated inflammation is responsible for the reaction .
The problem protein in CMPI is believed to be β-casein (beta-casein), which accounts for about 30% of all of the protein in cow’s milk [36, 37].
European and American dairy cows produce one of two variants of β-casein, called A1 and A2. A2 is the ancestral type; A1 is believed to have emerged between 5,000 and 10,000 years ago in European herds [36, 37].
A1 is the result of a single point mutation (SNP) that changed one amino acid from proline to histidine. According to multiple studies, many people with cow’s milk protein intolerance appear to react more strongly to A1 β-casein than to A2 β-casein. In one study, drinking milk that only contains the A2 protein completely resolved symptoms in some participants [36, 37, 38].
Some dairy farms have undergone testing and breeding programs to phase out cows that produce A1 β-casein from their herds. You can find A2 milk (and ghee) at many grocery chains and health food stores.
Multiple soy proteins can produce reactions in people who are sensitive to them. In many cases, this results in a soy allergy; however, soybeans also contain lectins, which some researchers believe may cause or exacerbate inflammatory conditions in sensitive people [39, 40, 41, 33].
According to one study, soy isoflavone intake is associated with Kawasaki disease, an inflammatory blood vessel disorder that is suspected to be autoimmune. Soy extracts have also triggered autoimmune antigen production in a cell study [42, 43].
In a study of mice with autoimmune disease, soy proteins considerably worsened kidney function compared to casein. Together, these results suggest a connection between soy and autoimmunity .
Egg allergies are relatively common, especially in children, and can be very severe. Children usually develop reactions to ovalbumin, ovomucoid protein, or both; the allergy often fades with age [25, 45].
Egg protein intolerance is not as well documented. However, some researchers believe that some cases of egg allergy may actually be sensitivity or intolerance: some people experience skin rashes (atopic dermatitis) 6-48 hours after consuming eggs, suggesting that IgE is not responsible for the reaction .
Whole-grain wheat contains a number of potential immunological triggers, including lectins and gluten. Some researchers believe that a lectin called wheat germ agglutinin (WGA) and a component of gluten called gliadin are the likely culprits behind most reactions to wheat .
Wheat Germ Agglutinin
Wheat germ agglutinin (WGA) is a lectin that protects wheat grains from insects and disease. In insects, for example, WGA damages and distorts the digestive tract. WGA kills some insects, thereby reducing the population of species that would otherwise eat the wheat grains [46, 47].
Most people can eat bread and other products containing wheat without any trouble. However, WGA doesn’t get broken down during digestion, and it has been linked to increased intestinal permeability. Some researchers have argued that, when WGA reaches the bloodstream, it may damage immune cells and blood vessels. In some studies, large quantities of WGA have been harmful even to healthy animals [34, 48].
Gluten & Gliadin
Celiac disease may not be the only cause of gluten intolerance. In recent years, non-celiac gluten intolerance has gained legitimacy and public awareness, though it remains controversial. Some researchers believe that gluten clearly causes inflammatory symptoms, while others believe that “non-celiac gluten intolerance” is a misdiagnosis of some other condition [49, 50].
Those who buy into the idea of non-celiac gluten sensitivity argue that it has a plausible mechanism: gliadin, a gluten protein, binds to the CXCR3 chemokine receptor in the gut. This may increase the expression of zonulin, which in turn decreases resistance in the gut’s tight junctions. Then, potentially dangerous toxins and inflammatory compounds (such as lipopolysaccharides) can cross the gut barrier into the bloodstream [51, 52, 53].
All that to say: some researchers believe that gliadin, a component of gluten, might increase gut permeability and allow inflammatory toxins to enter the bloodstream and cause the symptoms of non-celiac gluten sensitivity.
6) Vasoactive Amines
During the fermentation or decay of foods, bacteria produce vasoactive amines like tyramine, tryptamine, and histamine. Cured meats and fish, cheese, pickled vegetables, and fermented soy products are very high in amines for this reason. Spoiled fish can be so high in histamine that it produces symptoms of histamine poisoning in anyone who eats it [54, 55].
Histamine is one of the most common inflammatory compounds produced by the body. Human mast cells make and release it during inflammatory and allergic reactions, but it can also come from our food .
Histamine is inactivated by two major enzymes in the gut: diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). When there is too much histamine or too little DAO and HNMT, histamine causes inflammation in the body. People with strong reactions to histamine often have less DAO or HNMT than normal .
Other possible causes of histamine responses to food include overproduction of histamine by the gut flora and foods that cause histamine to be released elsewhere in the body, like sulfites in wine [57, 58, 59, 60].
In cell studies, saponins poke holes in cell membranes and allow other toxins to pass through the damaged gut barrier. Different saponins have had different effects in animals and humans, some of which may be beneficial, while others are inflammatory [61, 62, 63].
Legumes like soy, beans, peas, and lentils are the most significant source of dietary saponins. Other foods that contain significant amounts of saponins include garlic, onions, and asparagus. Many medicinal plants contain saponins, including green tea and ginseng [64, 65, 66, 67, 68, 69, 70].
At lower levels, some researchers believe that saponins appear to promote hormetic stress: that is, they challenge and activate the body’s defenses, creating an overall positive effect. Researchers have studied this potential benefit most extensively in ginseng saponins [71, 72, 73].
At higher levels, saponins might disrupt the gut barrier and increase intestinal permeability, though this mechanism is purely speculative and has yet to be observed in humans [62, 61].
8) Protease Inhibitors
Proteases are enzymes that, in the digestive system, break down proteins so their component parts can be used to build new proteins. Protease inhibitors are exactly what they sound like: compounds that can stop proteases from doing their work [74, 75].
Plants evolved to produce protease inhibitors mainly to defend against insects, but some researchers have argued that these may also inhibit efficient digestion in larger animals, including humans. Legumes, such as peas, contain protease inhibitors; these may prevent inflammatory proteins from being broken down [75, 76].
Some types of tannins (hydrolyzable tannins) can bind to certain enzymes and prevent them from breaking down inflammatory or toxic proteins. These tannins can also split into smaller compounds that cross the gut barrier and damage the liver and kidneys, though this effect has only been observed in fish so far .
Almost all plant-based foods contain tannins of some kind; these are responsible for bitter and astringent tastes, and many are considered beneficial. The foods highest in hydrolyzable tannins include :
- Pecans, walnuts, brazil nuts, peanuts, cashews
- Blue plums, pomegranates, red apples, peaches, brown and green pears, and kiwis
- Citrus fruit like navel oranges, grapefruit, tangerine & tangelo
- Grapes and oak-aged wines
- Beer (added for taste and color)
Salicylates are a group of chemicals related to salicylic acid. Some people can be very sensitive or even allergic to salicylates, and salicylic acid intolerance is relatively well documented [22, 78].
Salicylates include aspirin and are usually anti-inflammatory. However, in people with salicylate sensitivity, they can cause inflammation in the airway, skin, and digestive system. Many fruits and spices – such as sour apples, peaches, berries, ginger, cinnamon, cardamom, turmeric, and cumin – contain salicylates .
Oxalates are found naturally in the human body, but also in many plant-based foods like spinach, rhubarb, sweet potato, coffee, tea, soy, and nuts. When oxalate and related compounds build up in the body, they can contribute to kidney stones and a serious disease called hyperoxaluria [79, 80, 81, 82, 83, 84].
Oxalate typically binds to calcium in the gut, which may make them both more difficult to absorb. However, unabsorbed fat in the gut can also bind calcium, which may leave more oxalate free for absorption. Because of this complex relationship between calcium, oxalate, and fats, some researchers have suggested that people with difficulty absorbing fats are therefore at greater risk of oxalate disorders like oxalate crystal disease .
Poor fat absorption can be caused by, among other things, inflammatory bowel disease (IBD) and celiac disease. Both are marked by food sensitivity and autoimmunity, which suggests that oxalates could cause problems secondary to IBD and celiac disease [80, 85, 86, 87].
Your gut microbiome may also influence how much oxalate you absorb. A species of gut bacteria called Oxalobacter formigenes depends on oxalate as a food source and breaks it down in the intestine; this reduces the amount of oxalate absorbed into the blood .
Almost all babies have O. formigenes in their intestines, but only 60-80% of adults do, possibly because of antibiotic exposure. People without this species of gut bacterium may be more sensitive to oxalates .
Sulfites are small molecules containing sulfur. Some people (most frequently people with asthma) are sensitive to sulfite additives in food and red wine. When they consume sulfites, they may experience worse asthma symptoms, including airway narrowing [89, 90, 91].
The mechanism of this reaction is not well understood; one study suggests that sulfites activate mast cells in the lungs and increase the release of histamine. Sulfites seem to only produce a reaction in sensitive people, and only above a certain concentration threshold (about 300 parts per million or ppm in wine) [58, 91].
Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols – or, collectively, FODMAPs – are carbohydrates that can be fermented (but not readily absorbed) in the gut. People with irritable bowel syndrome (IBS) are often advised to avoid FODMAPs, as they will worsen IBS symptoms like bloating, pain, gas, and diarrhea .
FODMAPs may feed the gut bacteria that produce LPS, inflammatory toxins that weaken the gut barrier and produce inflammation [92, 93].
FODMAPs include such common offenders as fructose, fructans, and sorbitol [94, 95].
Glutamate is among the most important neurotransmitters for normal brain and nerve function. It is also responsible for the savory flavor of foods like parmesan cheese [96, 97].
An excess of glutamate may contribute to neurological disorders and increase the sensation of pain. Some researchers attribute this to a deficiency or defect in glutamic acid decarboxylase (GAD), the enzyme that converts glutamate into GABA. People with glutamate intolerance may also experience inflammation of the nose and airway about a day after consuming too much [98, 99, 100, 101].
Glutamate is found naturally in cheese, preserved meats, and fermented products. It is more abundant in processed foods than in fresh foods because of the addition of monosodium glutamate, or MSG [102, 101].
14) Additives & Sweeteners
Some chemical additives and artificial sweeteners may trigger inflammation and a dysfunctional immune response in sensitive people.
Tartrazine, a yellow food coloring, has been linked to worse symptoms in ADHD and may produce behavioral symptoms in sensitive children .
Sodium benzoate, a common preservative, may trigger allergic reactions and metabolic changes in some people [104, 105].
Sulfites, which are used as preservatives in food, wine, and pharmaceuticals, can cause rashes, flushing, low blood pressure, and digestive symptoms. In severe cases, sulfites have triggered anaphylactic and asthmatic reactions .
Aspartame, a common artificial sweetener used in sugar-free foods, may be linked to negative effects on mood and cognition. According to one study, people with lots of aspartame in their diets were more irritable and likely to be depressed and scored lower in spatial orientation tests. However, aspartame sensitivity is controversial; some researchers doubt its existence [106, 107].
This article is the second in a three-part series. In the next article, we’ll go over:
- How “food sensitivity tests” are supposed to work,
- Why they don’t work, and
- How to actually find and address food sensitivity.
Digestive problems, migraines, headaches, anxiety, depression, insomnia, breathing problems, and skin problems have been linked to various extents, to exposure to trigger foods. Some researchers believe that, over time, these inflammatory and autoimmune reactions can even lead to neurodegeneration, heart disease, and cancer.
Reactions are most commonly attributed to the proteins in milk (beta casein), eggs (ovalbumin and ovomucoid), and wheat (gluten and gliadin). Some people believe that they react badly to lectins, histamine, saponins, protease inhibitors, salicylates, oxalates, sulfites, FODMAPs, glutamate, and some food additives and artificial sweeteners.
This may look like a long, scary list, but if you have unexplained symptoms, it may be worth talking to your doctor about whether food might be the cause. Don’t rush to buy a food sensitivity test, though: the last post in this series will explain why they don’t work.
Learn more about food sensitivity tests with the CEO of SelfDecode Joe Cohen and Dr. Tommy Wood: