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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? 

Summary

  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.

Reference

  1. https://www.sciencedaily.com/releases/2016/05/160509101719.htm
  2. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0002270
  3. https://www.ncbi.nlm.nih.gov/pubmed/18184122
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386975/
  5. https://www.celiac.com/articles.html/gluten-intolerance-affects-hormonal-balance-r4395/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641836/
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266949/

Research estimates that 18 million Americans have gluten sensitivity. It is characterized by adverse reactions to gluten, a protein found in wheat, barley, and rye. People who are gluten sensitive may experience common symptoms like bloating, diarrhea, fatigue, headaches, etc. upon consumption of gluten. Some genes, especially the HLA family contribute to the risk of developing gluten sensitivity. According to research, People with two copies of specific genes, such as HLA-DQ7 (a form of HLA-DQ3 that's similar to HLA-DQ8), risk very strong reactions to gluten. Upon confirmation of gluten sensitivity, the best way to go forward is opting for a gluten-free diet. 

Introduction

Gluten is a protein that is found in grains like wheat, rye, and barley.

Some people are inherently sensitive to gluten, which makes them gluten intolerant.

Gluten sensitivity is an autoimmune disease, and celiac disease is its most severe form.

About 0.5-13% of people have a non-celiac gluten sensitivity, which is a milder form of the disease.

Signs and symptoms of gluten sensitivity

There are many signs that indicate one might be suffering from gluten intolerance:

  1. Bloating is the most common symptom seen in gluten-intolerant people.
  2. Diarrhea and constipation.
  3. Foul-smelling feces due to poor nutrient absorption.
  4. Abdominal pain.
  5. Migraines
  6. Fatigue
  7. Muscle and joint pain due to an overly sensitive nervous system
  8. Individuals with celiac disease develop a condition called dermatitis herpetiformis.
  9. Other conditions that are relieved when on a gluten-free diet include psoriasis, chronic urticaria, and alopecia
  10. Weight loss that has no apparent cause, along with digestive troubles.

Gluten sensitivity can develop at any age

Yes. One can develop gluten sensitivity anytime during their lifetime.

Sometimes people test negative for the autoimmune condition but develop it later on in their lives.

One theory that could explain this is probably the change in the composition of the intestinal bacteria in people who are genetically predisposed to gluten sensitivity.

According to statistics, there has been a 5 fold increase in the prevalence of the disease, primarily in the elderly.

Your genes and sensitivity to gluten

The Human Leukocyte Antigen (HLA) system gene is associated with the synthesis of the Major Histocompatibility Complex (MHC), which are cell-surface proteins that are associated with the regulation of the immune system. 

There are six single nucleotide polymorphisms of this gene complex; HLA DQ, HLA DQ 2.5, HLA DQ 2.2 (3 SNPs), and HLA DQ7 which have been shown to be associated with gluten intolerance.

Association with Gluten Sensitivity

The HLA DQ genes have been shown to be strong genetic predictors of celiac disease.

In a study conducted to assess the genetic predisposition to gluten intolerance, nearly all the patients with celiac disease had the risk allele in the HLA DQ2 and the HLA DQ8 gene, with the absence of these variants in 100% of people without celiac disease.

In another study conducted to analyze the human leukocyte antigen alleles, people with the G variant of HLA DQ, T variant of HLA DQ 2.5, G variant of HLA DQ 2.2, T variant of HLA DQ 2.2, G variant of  HLA DQ 2.2, and A variant of HLA DQ7 were shown to be associated with predicting a reaction to gluten in the diet.

The 2 possible outcomes for gluten intolerance

The Gene Nutrition Report analyzes over 15 genetic variants that contribute to the risk of gluten sensitivity. 

Let’s explore the 2 outcomes with an example: HLA DQ 2.5

TT carriersIncreased risk for gluten sensitivity
CC carriersNormal risk for gluten sensitivity

Here, the T allele contributes to an increased risk for gluten sensitivity; the C allele carriers, on the other hand, are likely to not be sensitive to gluten. 

A similar analysis is performed for the other variants and an overall outcome is provided in the report.

How to go about it?

Increased risk for gluten sensitivity

Even if you carry the genetic markers associated with gluten sensitivity, it needs to be further confirmed by checking for symptoms.

It is important to consult with your physician and confirm gluten sensitivity before going on a gluten-free diet. 

Eliminating gluten from your diet

Before going for a gluten-free diet, it is important to know the foods which are high in gluten.

  1. Wheat
  2. Rye
  3. Barley
  4. Wheat Germ
  5. Bulgur
  6. Couscous
  7. Farina
  8. Triticale
  9. Semolina
  10. Graham flour
  11. Malt
  12. Malt vinegar
  13. Soups
  14. Ketchup
  15. Mayonaise
  16. Salad dressings
  17. Soy sauce
  18. Marinades, gravies
  19. Ice cream
  20. Energy bars
  21. Flavored Coffee
  22. Roasted nuts
  23. Burgers
  24. Oats (unless they are gluten-free)
  25. Many non-edible items such as shampoos, cosmetics, lip balm, Play-Doh, some medications, stamps, and also contain gluten.

What does gluten-free diet look like?

A gluten-free diet may sound simple - just eliminate gluten from your diet, right?

But here’s the truth: gluten is hidden in many foods where you might not expect to see it.

Locating gluten in some foods can be like trying to find a needle in a haystack.

Here’s a list of food items that are naturally gluten-free:

Normal risk for gluten sensitivity

Despite not having any genetic markers associated with gluten sensitivity, in a few cases, other factors like lifestyle and environment can contribute to the development of this condition.

Thus, it is important to consult a physician if you observe any symptoms upon consumption of gluten.

Is a gluten-free diet harmful?

Gluten-free food is increasingly becoming popular among people.

However, it is recommended only for those suffering from celiac disease who have no other option but to avoid the protein-containing grains.

But, if you are not gluten intolerant or sensitive, it is not advisable for you to go on a gluten-free diet.

Most gluten-free products that are available today are also stripped-off of other nutrients and therefore, are not healthy for those who can eat gluten-based foods.

Commonly associated conditions with gluten sensitivity

Gluten sensitivity and hormones

Gluten sensitivity can affect hormones, especially in women over 40 who are tending towards menopause.

The unpredictability of the ovaries along with the hormones estrogen and progesterone wreck havoc in the body.

If one is gluten intolerant, the problems can increase.

This is because if one is sensitive to gluten, there are high chances that they may have an adrenal hormone imbalance.

The adrenal glands pick up on the stress levels.

Unstable sugar levels and inflammation of the digestive tract as a result of gluten intolerance cause the adrenal glands to secrete cortisol.

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

Gluten Sensitivity and 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:

The inflammation in the digestive system due to which is unable to absorb nutrients. 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 and Anxiety

There are many studies that have demonstrated the effect of irritable bowels on the mood of an individual.

However, how gluten results in anxiety or depression in gluten-intolerant or gluten-sensitive individuals have not yet conclusively been proven.

Does gluten affect the brain?

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.

So, there is no doubt about gluten affecting the neurological system.

Gluten can cause other disorders like insomnia, migraines, ADHD, epilepsy, schizophrenia, bipolar disorder, and in a minute number of cases, gluten ataxia.

You can avoid the condition by moving to a strict gluten-free diet. 

Can gluten affect your mood?

Yes. There are many studies that have shown the correlation between gluten intolerance in people 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 the polypeptides contained in gluten can bind to the morphine receptors in the brain.

These receptor sites are responsible for how we feel.

But, due to the inability of available sites for morphine to bind to, it can lead to depression and mood-related disorders.

So, yes, gluten can affect one’s mood.

Gluten Sensitivity and Insomnia

There is no conclusive evidence available today that links gluten sensitivity or intolerance to insomnia or sleeplessness.

However, 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 related conditions.

Can gluten cause UTI’s?

There is a high incidence of UTIs reported in children with active untreated celiac diseases.

Gluten sensitivity and celiac disease

Though gluten sensitivity has similar symptoms to celiac disease, the two types of responses differ in terms of both longevity and consequences. While both cause a negative reaction to gluten, celiac disease comes with an inflammatory response, which is absent in gluten sensitivity. The negative effects in gluten sensitivity are also short-lived when compared to celiac disease. 

Updated 16 July, 2020

Going gluten-free? Pause and read. Gluten-free is the new buzz word. Most of us have anti-gluten friends who are moving mountains to make us join the “Go gluten-free!” movement. While what you eat is your choice, you might want to get some misconceptions cleared before you start allotting a fat budget for gluten-free foods. Also, find out how you can use your 23andMe DNA raw data to find out your gluten sensitivity status!

Gluten Sensitivity or Intolerance: What’s the big idea?

Is gluten sensitivity (GS) or gluten intolerance real?

This is a big debate and the scientific evidence for gluten sensitivity being a reality is strong.

A section of people are staunch supporters of the whole “gluten myth” and believe the whole gluten sensitivity thing to be a charade.

Yet the fact remains that there are now 0.5-6% of the world population has gluten sensitivity.

Before you make assumptions purely based on others' opinions, it is wise to do a simple home wheat intolerance test.

Family history is another way to find out if you are gluten sensitive.

Are celiac disease (CD) and gluten intolerance one and the same?

To begin with, they are both an exaggerated response by your system and involves gluten.

Yet there is a difference in the role that gluten plays.

In CD, gluten is like the manipulative villain who pitches two good soldiers, who are on the same side, against each other.

When gluten comes into your system your immune system releases an alarm that makes the white blood cells attack your intestinal lining.

In GS, however, gluten is the antagonist.

There is an inflammatory response towards gluten and not your intestine.

In both cases, a gluten-free diet vanishes the symptoms.

So why is our immune system perceiving gluten as an enemy?

Simply because humans have started eating wheat only from 10,000 years ago which is just 0.4% of our total time on this planet.

This means humans have been on a gluten-free diet for 99.6% of their time here. This makes gluten new to a process for our system.

For a major chunk of us, our immune system has accepted this in the diet but for about for a few people, gluten is still that manipulative malefactor.

I don’t have CD or GS. Can I still go gluten-free?

Like I said at the beginning of the article what you eat is completely your choice.

Feel free to go gluten-free!

Nevertheless be discrete in choosing your alternatives.

How are you going to make up for the fibers that make up 12-15% of the total dry weight of wheat?

Not to mention that you are going to suddenly deprive your body of important vitamins and minerals that you have been casually supplying through your regular consumption of wheat.

Switching to processed food labeled “gluten-free” which replace gluten-rich wheat flour with highly refined carbohydrates like potato starch, rice starch, and tapioca starch will wreak havoc on your blood sugar.

Some healthy options would be millets, soy flour, and coconut flour.

Buckwheat flour can be a good substitute for wheat in cookies and cakes.

You can also explore almond flour and sorghum flour.

There is active research going on to produce genetically modified versions of wheat that do not have gluten or specifically, the protein gliadin which is the primary constituent of gluten.

New Scientist reported recently that using a technique known as RNA interference, scientists are able to “remove” 90% of gliadin by silencing its expression.

You can find the study on the Plant Biotechnology Journal.

The final word: Gluten sensitivity is not a myth or a fad. It is real!

Gluten sensitivity is not a myth. It is most certainly not a fashion statement.

If wheat consumption makes you uncomfortable then nothing can stop you from investigating for yourself if you carry those genes.

To put all doubts to rest, it is wise to take a non-invasive genetic test and take necessary precautions if need be than to be in the dark about it all your life.

Have you done a genetic test from 23andme or AncestryDNA or FTDNA?
You can find out about your gluten sensitivity status from your raw data.

Updated 16 July, 2020

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