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. http://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/

The Human Leukocyte Antigen system (HLA) gene is associated with the synthesis of 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(rs7454108), HLA DQ 2.5 (rs2187668), HLA DQ 2.2 (rs7775228, rs2395182, rs4713586) and HLA DQ7 (rs4639334) which have been shown to be associated with gluten intolerance.

Association with Gluten Intolerance:

Farming and agriculture introduced humans to new proteins about 10,000 years ago. Gluten is one such protein present in wheat, which makes bread light and springy as it traps steam and carbon-di-oxide when the dough rises during baking. However, this protein cannot be completely broken down into amino acids like other proteins are. Instead it is broken down to the peptides- gliadin and glutenin. People with certain variants of the gene have been shown to react to these peptides, giving rise to classic symptoms of gluten intolerance like diarrhea, stomach cramps, tiredness and abdominal bloating.

Celiac disease is a severe form of gluten intolerance and it is found to affect 1% of the population. Non-celiac gluten sensitivity is a mild form of gluten intolerance. In India, more than 10% of the population has gluten intolerance.

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 a study conducted to analyze the human leukocyte antigen alleles, people with the G variant of HLA DQ(rs7454108), T variant of HLA DQ 2.5 (rs2187668), G variant of HLA DQ 2.2 (rs7775228), T variant of HLA DQ 2.2 (rs2395182), G variant of  HLA DQ 2.2 (rs4713586) and A variant of HLA DQ7 (rs4639334) were shown to be associated with predicting a reaction to gluten in the diet.

Does your 23andme, Ancestry DNA, FTDNA raw data have HLA DQ gene variant information?

CHIP VersionHLA DQ SNPs
23andMe (Use your 23andme raw data to know your HLA DQ Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your HLA DQ Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your HLA DQ Variant)
OmniExpress microarray chipPresent
Genotype    HLA DQ(rs7454108)    Phenotype
AA[Advantage] More likely to be gluten tolerant
AGModerate risk for gluten intolerance
GG[Limitation] More likely to be gluten intolerant
Genotype HLA DQ 2.5 (rs2187668)Phenotype
CC[Advantage] More likely to be gluten tolerant
CTModerate risk for gluten intolerance
TT[Limitation] More likely to be gluten intolerant
Genotype HLA DQ 2.2 (rs7775228)Phenotype
AA[Advantage] More likely to be gluten tolerant
AGModerate risk for gluten intolerance
GG[Limitation] More likely to be gluten intolerant
Genotype HLA DQ 2.2 (rs4713586)Phenotype
AA[Advantage] More likely to be gluten tolerant
AGModerate risk for gluten intolerance
GG[Limitation] More likely to be gluten intolerant
Genotype    HLA DQ7 (rs4639334)  Phenotype
GG[Advantage] More likely to be gluten tolerant
AGModerate risk for gluten intolerance
AA[Limitation] More likely to be gluten intolerant

How can this information be used?

It is important to choose an appropriate diet based on the genetic profile

For people with Risk Variant (Gluten Intolerant)  People with gluten intolerance should completely avoid gluten in their food. There are many gluten free products available in the market. Rice is gluten free, which could be the reason behind the low prevalence of gluten intolerance among South Indians. People with moderate risk should watch out for symptoms associated with gluten intolerance and avoid it from the diet, only if there are symptoms.
For people with Normal Variant (Gluten Tolerant)  Continue to include gluten in the diet as there is minimal risk associated with developing gluten intolerance.


References
:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386975/
  2. http://celiacindia.org.in/
  3. https://www.ncbi.nlm.nih.gov/pubmed/26603490
  4. https://www.ncbi.nlm.nih.gov/pubmed/27278238
  5. http://www.grupoaran.com/mrmUpdate/lecturaPDFfromXML.asp?IdArt=4621240&TO=RVN&Eng=1
  6. https://www.geneticliteracyproject.org/2015/07/14/facts-behind-celiac-disease-and-gluten-intolerance/
  7. https://www.ncbi.nlm.nih.gov/pubmed/18184122
  8. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0002270

Related Links:

  1. https://www.xcode.life/dna-and-health/world-osteoporosis-day-2016-osteoporosis-could-be-linked-to-gluten-intolerance
  2. https://www.xcode.life/product/gluten-intolerance-genetic-assessment

Nutrigenetics, fitness genetics, health genetics are all nascent but rapidly growing areas within human genetics. The information provided herein is based on preliminary scientific studies and it is to be read and understood in that context.”

[idea]Osteoporosis affects 200 million women worldwide[/idea]

 

Osteoporosis is a condition in which the bone mass is lowered, resulting in weak bones that are prone to fractures. This condition is often associated with people over 50 years of age, especially in women post menopause. The propensity for people with osteoporosis to fracture their bones is alarmingly high, with estimates stating that every 3 seconds there is an osteoporotic fracture that occurs across the world.

There are no symptoms associated with the condition until there is a fracture, which is a painful indicator of poor bone health. The brittleness of the bone and the higher chance of fracture forces older people to remain in their homes, worrying about possible falls that could lead to a fracture. This is a significant psychological symptom associated with the condition.

Children with osteoporosis also exhibit poor bone health which not only increases their risk for fractures but could also stunt their growth.

World Osteoporosis Day 2016:[hr height="30" style="default" line="default" themecolor="1"]

This World Osteoporosis Day 2016, there is a need to explore causes for this condition in order to provide effective solutions. The theme for this year’s World osteoporosis Day 2016 is “Love your bones, Protect your future”

[idea]World Osteoporosis Day was started in October 1996[/idea]

 

Association with Gluten Intolerance[hr height="30" style="default" line="default" themecolor="1"]


Gluten intolerance is a condition in which the body is unable to metabolize gluten, found in wheat, barley and rye. The condition is caused due to a mutation in the gene HLA DQ and it leads to a range of gastrointestinal symptoms that include nausea, diarrhea, bloating, abdominal cramps and pain. There are certain other extra-intestinal symptoms associated with gluten intolerance that include depression, inability to focus, foggy mind and – possibly osteoporosis. In a gluten intolerant individual, the body is unable to digest the gluten in the diet and this triggers an autoimmune condition where the body’s immune cells attack the lining of the small intestine, where important nutrients like calcium are absorbed. This leads to malabsorption and the resultant
lowering of bone density and osteoporosis.

[idea]Gluten intolerance found in 10% of the population[/idea]

 

But, here’s the good news:[hr height="30" style="default" line="default" themecolor="1"]

Studies have shown that eating a gluten free diet will aid in regaining bone mass, both in children as well as in adults. The tricky part is to identify the condition before it leads to considerable loss in bone density or a fracture.

In a study on school children in Ludhiana, 6 children were identified to have gluten intolerance and none of them showed any other symptom, including gastro intestinal, except stunted growth.

It is difficult to assess intolerance in children based on symptoms as they rarely understand the enormity of the situation and will fail to acknowledge it. The process of eliminating specific food from the diet is also difficult as it can take many months before there is a clear association that is found. Instead gene testing affords a quick and cost-effective solution that detects the mutation in the HLA DQ gene, allowing dietary modification that will limit the risk of osteoporosis.

This World Osteoporosis day, get tested for gluten intolerance and safeguard bone health.

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