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?
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 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 for a food reaction that is neither 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 can accompany 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 the distinction is meaningless. 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 most well-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 consider food sensitivity as a possible cause.
“Brain fog” is what it sounds like: when you have brain fog, your 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 .
Inflammation of the brain is the 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 may be at the root of a lot of brain problems, including 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 they can be difficult to pin on 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].
Red wine triggers migraine within about 3 hours in people who believe that wine is a trigger. 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 get migraines often have significantly lower 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 directly causes nasal congestion, so people who are histamine intolerant may experience this symptom more than most [19, 20, 19].
Some foods (fish, milk, eggs, and others) trigger or contribute to asthma and other inflammatory symptoms of the airway. However, the relationship between food intolerance and asthma is not fully understood .
People who are sensitive to salicylates may develop 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].
Possible Consequences of Food Sensitivity
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. Microglia activation – and, thus, inflammation in the brain – may be the 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].
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 .
The Worst Dietary Offenders
Lectin sensitivity and lectin avoidance have been heavily documented here at SelfHacked.
Lectins are a type of protein found in especially high amounts in legumes and whole grains (especially wheat). Read Joe’s articles on lectin sensitivity for a detailed explanation 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, cow’s milk may 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 .
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 react more strongly to A1 β-casein than to A2 β-casein. Drinking milk that only contains the A2 protein can sometimes completely resolve symptoms [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 can trigger inflammation and autoimmunity in sensitive people [39, 40, 41, 33].
According to one study, soy isoflavones increase the risk of Kawasaki disease, an inflammatory blood vessel disorder that is suspected to be autoimmune. Soy intake has also been linked to autoimmune thyroid disease [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 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 .
Whole-grain wheat contains a number of potential triggers, including lectins and gluten. A lectin called wheat germ agglutinin (WGA) and a component of gluten called gliadin are probably responsible for 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 increases intestinal permeability. When it leaks into the blood, it proceeds to damage immune cells and blood vessels. Large quantities of WGA are harmful even to healthy animals [34, 48].
Gluten & Gliadin
Celiac disease isn’t 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].
Gliadin, a gluten protein, binds to the CXCR3 chemokine receptor in the gut. This increases 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].
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 a histamine intolerance often simply have too little DAO and HNMT .
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].
Saponins poke holes in cell membranes and allow other toxins to pass through the damaged gut barrier. Different saponins have different effects, some of which may actually 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, saponins are healthy for most people because of hormetic stress: saponins challenge and activate the body’s defenses, creating an overall positive effect. Researchers have studied this benefit most extensively in ginseng saponins [71, 72, 73].
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 stop proteases from doing their work [74, 75].
Plants evolved to produce protease inhibitors mainly to defend against insects, but these may also prevent 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) bind to enzymes in the gut 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 .
Almost all plant-based foods contain tannins of some kind, which are responsible for bitter and astringent taste. 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 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, which makes them both more difficult to absorb. However, unabsorbed fat in the gut can also bind calcium, freeing up oxalate for absorption. People with difficulty absorbing fats are therefore at greater risk of oxalate disorders .
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 be a secondary problem [80, 85, 86, 87].
Your gut microbiome can 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 at greater risk of oxalate disorders .
Sulfites are small molecules containing sulfur. Some people (most often people with asthma) are sensitive to sulfite additives in food and red wine. When they consume sulfites, they experience worsening 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 advised to avoid FODMAPs, as they will worsen IBS symptoms like bloating, pain, gas, and diarrhea .
Too much glutamate can contribute to neurological disorders and increase the sensation of pain. This is often caused by 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 can trigger inflammation and autoimmunity in sensitive people.
Tartrazine, a yellow food coloring, can worsen the symptoms of ADHD and may produce behavioral symptoms in sensitive children .
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 can trigger anaphylactic and asthmatic reactions .
Aspartame, a common artificial sweetener used in sugar-free foods, may have 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.
Joe developed the SelfHacked Lectin Avoidance Diet to help himself and clients with chronic inflammation and autoimmunity figure out which foods they are reacting to. Rather than spending thousands of dollars on tests that won’t yield definitive results, the SelfHacked Lectin Avoidance Diet can help you determine which foods you are sensitive to, since it’s an elimination-reintroduction protocol.
If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this inflammation DNA wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes. SelfDecode is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thanks for your support.
Foods can cause all kinds of symptoms even if you’re not allergic. Digestive problems, migraines, headaches, anxiety, depression, insomnia, breathing problems, and skin problems can all be the result of exposure to trigger foods.
Over time, these inflammatory and autoimmune reactions can even lead to neurodegeneration, heart disease, and cancer. It is important to be aware of possible food triggers in your diet and to eliminate them if necessary.
The most common triggers are the proteins in milk (beta casein), eggs (ovalbumin and ovomucoid), and wheat (gluten and gliadin). Some people may also 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’s worth figuring out 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.