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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. 

Knowing The Difference Between Gluten Intolerance And Celiac Diseases

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. the symptoms are more severe, and 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 to it over a period of time can result in poor absorption of nutrients, putting you at risk for various deficiencies. 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.

The Story Behind 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. But the cause of the disease was never understood clearly. 

During the Dutch famine in the 1940s, when celiac patients received very less amounts of 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.

[what to do to maintain healthy levels- generally for everyone and specifically for your genotype]

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

Gluten intolerance or non-celiac gluten sensitivity occurs when the immune system sees gluten as an invader and attacks it. Certain types of the HLA gene family that mediate immune responses in our body play a role in putting an individual at risk of developing gluten intolerance. Gluten sensitivity has also been linked with other health conditions like hormonal imbalance and mental illnesses. Therefore, people who are sensitive to gluten are advised to switch to a gluten-free diet. However, it is important to keep in mind that a gluten-free diet is not everyone’s cup of tea. Most gluten-free products available in the market today are also stripped off of other nutrients and are advantageous only to the gluten-intolerant.

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/

MAO-A Gene: An introduction

The MAO-A gene, popularly nicknamed the “warrior gene,” is responsible for the production of an enzyme monoamine oxidase A. (MAOA)

It breaks down monoamine neurotransmitters (dopamine, epinephrine, and serotonin) through oxidation.

Thus, mutations in the MAO-A gene can directly affect the levels of these neurotransmitters, which can potentially lead to various behavior-associated disorders.

Importance of MAOA

MAOA is an essential regulator of brain function and is highly expressed in the cells of the brain and heart. It mainly assists in the breakdown of neurotransmitters such as

Because MAOA regulates the level of these “behavioral-hormones,” too little or too much of this enzyme plays a role in a number of psychiatric and neurological disorders like schizophrenia and ADHD. In fact, a class of drugs that inhibit this enzyme (MAOA inhibitors) is prescribed to treat depression.

The Types of MAO-A Gene

All of us have the MAO-A gene, but we have different versions (or types or variants) of them. There are two types of MAO-A genes: a  high-activity (MAOA-H) and a low-activity (MAOA-L) type, based on the number of times the sequence of the gene is repeated. One of the most frequently studied variants is MAOA-4R, which has four repeats and is associated with a high-activity of the MAOA enzyme. Other alternate forms of the MAO-A variants, including the 2-repeat (2R) and 3-repeat (3R) versions.

Monoamine Oxidase Deficiency

The monoamine oxidase A deficiency follows an X-Linked inheritance pattern. Thus, this disorder is majorly seen affecting males.

Lower levels of this enzyme typically result in the buildup of neurotransmitters in the brain.

Various studies have linked this buildup with unusual behavioral patterns involving aggressive outbursts and abnormal sexual behavior. The deficiency of this enzyme has also been associated with abnormal brain development, which can directly lead to intellectual disabilities. There are also other variants of this gene that increase the enzyme levels. 

Lower levels of the enzyme result in a slower breakdown of the neurotransmitters - (Worriers), and higher levels of the enzyme lead to a faster breakdown - (Warriors). Both decreased and increased levels of the enzyme have various implications.

Increased Risk For Depressive And Bipolar Disorders

A study on around 18,000 people with psychiatric issues identified an SNP rs1137070 associated with major depressive disorder and schizophrenia. People with the T allele had higher enzyme levels and, as a result, lower levels of the neurotransmitters.

Another study found that the G allele of rs6323 had the highest expression of the MAOA enzyme. “Subjects with major depressive disorder with the highest activity form of the enzyme (G or G/G)”

Increased Risk For ADHD

A study identified an SNP rs3027407 on the MAO gene associated with ADHD. This SNP affects dopamine-mediating action, which is related to the symptoms of ADHD in children. A allele was found in higher frequencies in people with ADHD. 

Increased Risk For Aggression

T allele of rs909525 in the MAO gene is associated with less aggressive behavior due to the higher activity of MAOA - the warriors. The C allele is associated with more aggressive behavior.

Increased Expression for Anger

A variation in the MAOA gene was associated with higher levels of anger expressed outwards. The A allele of rs2064070 was associated with increased expression of anger. 

The study also found two other variants, rs909525 - C allele, rs6323 - G allele, associated with increased anger. 

Symptoms of MAOA Deficiency

Diet and MAOA

A study found that a poor quality diet during adolescence can affect the verbal ability of individuals who have a low expression variant of the MAO-A gene. People who ate vegetables very rarely and included more junk food in their diet had verbal deficits in early adulthood. 

The “psychopathic” personality traits were also observed more in subjects who frequently consumed fast foods during their adolescence - this was seen only in people with a low expression variant of the MAO-A gene. 

Diet Recommendations for People on MAOA Inhibitors

MAOA inhibitors (MAOA-I) are a class of drugs that lower the enzyme MAOA levels. Higher MAOA levels have been linked to conditions like depression.

When on MAOA-I, it is important to limit high-tyramine foods. Tyramine is an amino acid that helps regulate blood pressure. MAOA enzyme is required to break down tyramine, the buildup of which is associated with migraine headaches and life-threatening blood pressure spikes. 

So if you are on MAOA-I, it is important that you reduce your tyramine consumption.

Some foods high in tyramine are:

  1. Aged cheese
  2. Pickled fermented foods
  3. Soybeans
  4. Sauces
  5. Dried or overripe fruits
  6. Alcoholic beverages
  7. Fava beans

Summary

References:

  1. https://www.sciencedirect.com/topics/neuroscience/monoamine-oxidase-inhibitors
  2. https://en.wikipedia.org/wiki/X-linked_recessive_inheritance
  3. https://pubmed.ncbi.nlm.nih.gov/26227907/
  4. https://pubmed.ncbi.nlm.nih.gov/19593178/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093913/table/T3/
  6. https://www.snpedia.com/index.php/Rs909525
  7. https://pubmed.ncbi.nlm.nih.gov/23111930/
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