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Gluten is a family of storage proteins found in various grains such as barley, rye, and wheat. Gluten is responsible for the soft and chewy texture of pastries and baked items. It also retains the moisture in bread, pasta, and cereal.  

Gluten intolerance and gluten sensitivity are two terms used interchangeably to describe a condition where the body recognizes gluten as an ‘enemy’ and initiates an immune response against it. 

Table of Contents

  1. Knowing the difference between gluten intolerance and celiac disease.
  2. What are the symptoms of gluten sensitivity?
  3. Is avoiding carbs to avoid gluten the best idea?
  4. Evolutionary significance: How did our ancestors respond to gluten?
  5. Gluten sensitivity among different ethnic groups.
  6. The genetics behind gluten sensitivity
    1. The HLA gene
    2. Non-genetic factors affecting gluten sensitivity
  7. Why get tested for gluten sensitivity?
  8. How to know if you are gluten-sensitive?
  9. Dietary recommendations to manage gluten sensitivity.
    1. Gluten-free foods
  10. Summary
  11. References

Knowing The Difference Between Gluten Intolerance And Celiac Disease

Gluten intolerance is also known as ‘non-celiac’ gluten sensitivity. 

Celiac disease is an exaggerated form of gluten intolerance. Upon consuming gluten, the immune system attacks the lining of the intestines. When the symptoms are more severe, the recovery is a lot harder.

Here, the body’s immune system, which is meant to protect it, mistakenly acts against it. This is known as an auto-immune response, which can be due to genetic reasons.

Since intestines play a big role in the absorption of essential nutrients, attacks on them over time can result in poor absorption of nutrients, putting you at risk for various deficiencies. When the gluten intolerance is non-celiac, the immune responses triggered do not damage the intestines but instead contribute to milder symptoms.

Gluten sensitivity symptoms are not restricted to just the digestive system. 

What are the symptoms of gluten sensitivity?

  1. Abdominal pain
  2. Diarrhea
  3. Bloating
  4. Constipation
  5. Nausea
  6. Headaches
  7. Fatigue
  8. Skin rashes
  9. Anxiety
  10. Depression
  11. Joint and muscle pain
  12. Numbness

Why Avoiding Carbs To Avoid Gluten May Not Be The Best Idea

All the fad about gluten-free diets has portrayed gluten-containing products, mainly wheat, in a bad light. While gluten is a big no-no for the gluten-sensitive, reduced consumption of whole grains may negatively impact your health. 

Whole grains like wheat, bran, and rye are rich sources of fiber. They also contain carbohydrates, proteins, and small amounts of B vitamins and minerals. 

Thus, avoiding gluten in the absence of an intolerance/sensitivity can end up being detrimental to your health.

Evolutionary Significance: How did our ancestors respond to gluten sensitivity?

Diana Gitig, a Ph. D. graduate from Cornell University, Massachusetts, mentions that celiac disease's first reported case dates back to 100 A.D. It was diagnosed by a Greek doctor, Aretaeus. Yet, the cause of the disease was never understood clearly. 

During the Dutch famine in the 1940s, when celiac patients received very little flour (wheat) for consumption, their symptoms started improving.

When fresh supplies of bread were reintroduced, the symptoms started worsening again. This was when wheat was isolated as the cause of the intestinal symptoms. 

Until the 1950s, only 1 out of 8000 were sensitive to gluten. Today, as high as 1 in every 100 individuals are gluten sensitive . 

Prof. David Sanders from the University of Sheffield takes help from the concept of evolution to answer this huge rise in cases. He claims that humans started eating wheat only recently, about 10,000 years ago. This is a very brief period considering that humans have walked on the planet for more than 2 million years. 

Humans initially consumed raw food, such as plants, fruits, and meat. Processed food (wheat, rye, and other grains), are relatively new in the evolutionary timeline. Prof. David acknowledges this fact and states that our body is still in the process of adapting, especially the food that contains gluten in it. With millions of years of having a gluten-free diet, it makes sense as to why gluten is considered a foreign body by our immune system.

Ethnicity And Gluten Sensitivity

Although a global analysis of gluten intolerance is yet to be done, a nationwide study was conducted in the United States. Over 400,000 biopsy results were examined to understand if ethnicity played a role in gluten intolerance and celiac disease. The following results were concluded after the study : 

It is also worth mentioning that gender studies showed that both men and women had equal chances of being gluten-sensitive. Hence it can be inferred that gender does not play a role in this intolerance.

Genetics And Gluten Sensitivity

The HLA gene

The Human Leukocyte Antigen (HLA) gene system plays a role in the production of the Major Histocompatibility Complex (MHC), which are proteins present on the cell surfaces. They play a role in regulating the immune system

Two classes of the HLA gene known as HLA-DQ2 (HLA-DQ2.2 and HLA-DQ2.5) and HLA-DQ8 are linked with gluten intolerance risk. 

Four types of the HLA gene, HLA DQ, HLA DQ 2.5, HLA DQ 2.2 (has three sub-types), and HLA DQ7, have been linked to gluten intolerance.

In a study conducted to assess the genetic influence on gluten intolerance, nearly all the patients with celiac disease had the risk allele in the HLA DQ2 and the HLA DQ8 genes. The absence of the same was found in 100% of people without celiac disease. In another study conducted to analyze the HLA gene types, people with the C allele in HLA DQ8, T allele in HLA DQ 2.5, the T, C and A alleles in different subtypes of HLA DQ 2.2 (M1, M2, and M3 respectively), and A allele in HLA DQ7 were shown to have an increased risk of reacting to gluten in their diets.

Non-Genetic Causes Of Gluten Sensitivity

Some of the non-genetic causes of gluten sensitivity are:

Not all people are born with gluten sensitivity. It is possible to acquire it during the course of life. This intolerance can be triggered after surgery, childbirth, or after a period of severe stress.

Commonly Associated Conditions With Gluten Sensitivity

Gluten Sensitivity Can Affect Hormone Levels

Gluten sensitivity increases the risk of an adrenal hormone imbalance.

The adrenal glands pick up on the stress levels.

Unstable sugar levels and inflammation of the digestive tract resulting from gluten intolerance cause the adrenal glands to secrete cortisol.

This leads to an increase in body fat, fatigue, and irritable mood.

Gluten Sensitivity Can Increase Fatigue

Fatigue is one of the most common symptoms of celiac disease and non-celiac gluten sensitivity.

In fact, fatigue and tiredness are the symptoms that last longest, even after the individual has shifted to a gluten-free diet.

Fatigue in gluten intolerant individuals occurs due to two main reasons:

  1. The inflammation in the digestive system results in improper absorption of nutrition, leaving the body deficient in certain nutrients.
  2. Gluten-allergy or sensitivity leads to diarrhea, characterized by loose, watery stools. This leads to lots of water and nutrients elimination from the body.

Dehydration is also a major cause of fatigue and tiredness in gluten intolerant people.

Gluten Sensitivity Can Cause Neurological Symptoms

Patients suffering from celiac and non-celiac forms of gluten intolerance have reported neurological symptoms such as headaches, brain fog, anxiety, depression, and peripheral neuropathy.

Gluten can also cause other disorders like insomnia, migraines, ADHD, epilepsy, schizophrenia, bipolar disorder, and in a minute number of cases, gluten ataxia (antibodies directed at gluten attacks the brain).

Gluten Sensitivity Can Cause Mood Disorders

Many studies have shown a correlation between gluten intolerance and depression, anxiety, and other neurological syndromes.

A study conducted by Christine Zioudrou and her colleagues at the National Institute of Mental Health in 1979 found that some gluten compounds can attach to the morphine receptors in the brain.

The morphine that is produced in the body is known as endorphins. These are released in our body for various reasons, for instance, to reduce/manage pain.

Certain compounds of gluten (exorphins) mimic the structure of endorphins and attach to the receptors. 

Thus, the endorphins have no place to attach to and are not activated. This can lead to mood-related disorders like depression and anxiety. 

Gluten Sensitivity Can Cause Insomnia

A large majority of the people who suffer from gluten-intolerance report lack of sleep and poor sleep quality.

Due to digestive symptoms, neurological symptoms, and generalized fatigue and tiredness, most people suffer from a lack of sleep or other related conditions.

How To Know If You Are Gluten Sensitive

If you think you have some of the symptoms of gluten sensitivity, talk to your doctor before jumping to any conclusions. The doctor can run tests and review your history to help reach a diagnosis.

Another way to find out if you have a risk for gluten allergy is to do a genetic test. If you already have your DNA raw data from any ancestry company like 23andMe, Ancestry DNA, Family Tree DNA or whole genome data, you can upload it to Xcode Life for a Gene Nutrition report.

In the Gene Nutrition report you can find an in-depth analysis of your genetic variants for gluten sensitivity and ways to manage or prevent it.

Dietary Recommendations For Gluten-Sensitive Individuals

A gluten-free diet seems pretty straightforward - just removing gluten from your diet. But completely avoiding gluten can be challenging as many ingredients added to food like soy sauce, mayonnaise, and roasted nuts also contain gluten. 

Whole grains like wheat and barley are well-known harbourers of gluten. So wheat-based bread, pasta, or baked goods should be avoided. 

What are the naturally gluten-free foods? 


  1. Gluten gluten sensitivity is a condition where the body recognizes gluten as an ‘enemy’ and initiates an immune response against it. 
  2. Celiac disease is an exaggerated form of gluten sensitivity.
  3. Evolutionarily, gluten could be considered foreign by the immune system since humans have gone millions of on a gluten-free diet.
  4. Studies have shown that individuals with with celiac disease had risk variants in the HLA DQ2 and the HLA DQ8 genes. Check you DNA raw data to know whether you have the risk variants.
  5. The absence of the same was found in 100% of people without celiac disease.
  6. Non-genetic causes of gluten sensitivity: gastrointestinal infections and abnormal gut bacteria.
  7. Conditions associated with gluten sensitivity: hormonal imbalance, depression, fatigue and insomnia.
  8. Genetic analysis is good way to prevent and manage gluten sensitivity effectively.
  9. You can use your 23andMe, AncestryDNA, Family Tree DNA, or whole genome data to check if you have the risk variants for gluten sensitivity.


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