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/

What does the CYP1A2 gene do? 

CYP1A2 codes for the production of 21-hydroxylase, which is part of the cytochrome P450 family of enzymes.

This family of enzymes is quite important as it is a part of many processes, that include breaking down drugs, production of cholesterol, hormones, and fats.

The adrenal glands secrete the enzyme, 21-hydroxylase.

Situated on the top of the kidneys, the adrenal glands also produce hormones like epinephrine and cortisol.

Incidentally, 21-hydroxylase plays a role in the production of cortisol and another hormone named aldosterone.

Cortisol is a stress-related hormone and plays a role in protecting the body from stress, as well as reducing inflammation.

Cortisol also helps in maintaining blood sugar levels.

Aldosterone, also known as the salt-retaining hormone, regulates the amount of salt retained in the kidneys.

This has a direct consequence on blood pressure, as well as fluid retention in the body. 

There seems to be an interesting trend in the activity of the CYP1A2 gene and caffeine intake.

The consequence of being a “rapid” or a “slow” metabolizer of caffeine can have effects on an individual’s cardiovascular health.

This article explains the wide-ranging effects of this gene, caffeine intake,  cardiovascular health, hypertension, and even pregnancy!

What is the association between CYP1A2 and caffeine metabolism?

In the body, CYP1A2 accounts for around 95% of caffeine metabolism.

The enzyme efficiency varies between individuals.

A homozygous, that is, AA genotype represents individuals that can rapidly metabolize caffeine.

Some individuals have a mutation in this locus and thus have the AC genotype.

These individuals are “slow” caffeine metabolizers.

CYP1A2 and cardiovascular health

There seems to be a link between CYP1A2, the incidence of myocardial infarction (MI), and coffee intake.

The positive effects of coffee include lowering a feeling of tiredness and increasing alertness; however, it can also narrow the blood vessels.

This increases blood pressure and could lead to cardiovascular disease risk.

Rapid metabolizers of coffee have the AA genotype and may unravel the protective effects of caffeine in the system.

However, the individuals that are slow metabolizers have a higher risk of MI.

This suggests that the intake of caffeine has some role in this association. 

Yet another study associated DNA damage due to mutagens found in tobacco smoking could contribute to MI.

The study included participants who were genotyped at the CYP1A2 gene.

They found a group of ‘highly inducible’ subjects that had a CYP1A2*1A/*1A genotype.

These individuals have a greater risk for MI, independent of their smoking status.

This also means that there is some intermediary substrate that the CYP1A2 gene decomposes, and if this gene has a mutation, it could lead to a higher risk of MI. 

In a study conducted on 2014 people, people who were slow metabolizers of caffeine (C variant) and who consumed more than 3 cups of coffee per day had an association with increased risk for myocardial infarction. 

In a similar study on 513 people, increased intake of coffee, among slow metabolizers, has an association with an increased risk for hypertension.

The association between smoking and hypertension

Smoking is capable of inducing the CYP1A2 enzyme. Smokers exhibit increased activity of this enzyme.

In a study conducted on 16719 people, people with the A variant, and who were non-smokers, were 35% less likely to be hypertensive than people with the C variant.

In the same study, CYP1A2 activity had a negative association with blood pressure among ex-smokers.

But for people who were still smoking, the same gene expressed an association with increased blood pressure.

The gene CYP1A2 also has an association with caffeine metabolism and smoking.

A study aimed to tie these concepts together to find the relationship between this gene and blood pressure (BP).

The main measurements of the study were caffeine intake, BP, and the activity of the CYP1A2 gene.

In non-smokers, CYP1A2 variants (having either a CC, AC, or AA genotype) were associated with hypertension.

Higher CYP1A2 activity was associated with people who quit smoking and had lower BP compared to the rest but had a higher BP while smoking.

In non-smokers, CYP1A2 variants (having either a CC, AC or AA genotype) were associated with high caffeine intake, and also had low BP.

This means that caffeine intake plays some role in protecting non-smokers from hypertension, by inducing CYP1A2.

The effect of the CYP1A2 on pregnancy and caffeine intake

The intake of caffeine during pregnancy has an association with the risk of reduced fetal growth.

High caffeine intake shows a link to decreased birth weight.

The babies are also at risk of being too small during the time of pregnancy.

This was also observed in a study conducted on 415 Japanese women.

Women with the A variant who drank more than 300 mg of coffee per day were shown to be at an increased risk of giving birth to babies with low birth weight.

Summary

In conclusion, there are a lot of effects that the CYP1A2 gene has on the body. Many studies, as noted above, seem to link the activity of this gene to caffeine intake.

A variant at the CYP1A2 gene can determine whether an individual is a fast or slow metabolizer of caffeine, and this has some effect on the blood pressure and cardiovascular health of an individual.

The gene also plays a role in regulating an infant’s weight during the pregnancy of a woman,  and this has a link with caffeine intake. It is thus interesting to analyze the effect of the variants of the CYP1A2 gene on an individual, based on their caffeine intake. 

References

  1. https://ghr.nlm.nih.gov/gene/CYP21A2
  2. https://jamanetwork.com/journals/jama/fullarticle/202502
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474926/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1735605/
  5. https://www.researchgate.net/publication/223974368_Caffeine_intake_and_CYP1A2_variants_associated_with_high_caffeine_intake_protect_non-smokers_from_hypertension
  6. https://www.nature.com/articles/pr201770#:~:text=Maternal%20caffeine%20intake%20may%20increase,8%2C%209%2C%2010)

Do you have your DNA raw data from 23andMe, AncestryDNA, FTDNA, LivingDNA, etc.?

Upload it to Xcode Life to know about your CYP1A2 caffeine metabolism and caffeine sensitivity variants.

Published on 18 June, 2020

Caffeine acts as a stimulant of the Central Nervous System (CNS), causing increased alertness.

It is the world's most widely consumed legal psychoactive drug.

Caffeine offers a range of benefits from something as small as over an afternoon slump to reducing the risk of some serious health conditions like heart diseases.

Some common food sources of caffeine include:

How does caffeine affect your body?

Up to 400 milligrams of caffeine appears to be safe for most healthy adults.

Anything exceeding that can be harmful to the body.

The effect of caffeine on various systems of the body are as follows:

Central Nervous System (CNS)

Caffeine is a stimulant and causes mental alertness once it reaches the brain.

It is a common ingredient in medications that are meant to treat drowsiness, migraines, and headaches.

Digestive and excretory systems

Caffeine stimulates the production of stomach acid and can cause heartburn, acid reflux, or stomach upset.

Excess caffeine is stored in the liver, which exits through urine.

Hence, drinking excessive coffee or tea increases the urge for urination.

Respiratory and circulatory systems

Caffeine intake increases adrenaline production.

This, in turn, increases your blood pressure for some time.

When consumed in excess quantities, caffeine can lead to irregular heartbeat and breathing.

Skeletal system

Excess caffeine interferes with the absorption and utilization of calcium.

Reduced calcium levels in the body can lead to osteoporosis.

Muscular system

Muscle twitching is often a visible symptom of excess caffeine consumption.

Reproductive system

A little caffeine during pregnancy appears to be safe in most cases.

However, it is important to note that caffeine can cross the placental barrier, and therefore, can affect the fetus.

It can increase the fetus's heart rate and, in some cases, may even lead to a miscarriage.

CYP1A2: How does this gene affect caffeine consumption?

CYP1A2 codes for a protein that belongs to the Cytochrome P450 family.

This protein is involved in the breakdown of stimulants, drugs, nutrients, and other xenobiotics.

The CYP1A2 gene regulates the synthesis of the enzyme, and small variations in this gene are associated with the efficiency of caffeine metabolism.

Some people are genetically predisposed to produce very little of CYP1A2 enzyme while others may generate a sufficient amount.

Approximately 10% of the population is found to be rapid caffeine metabolizers, showing a high tolerance to caffeine.

This enzyme is also essential for removing toxic chemicals from our body and processing hormones and other products of metabolism.

Both increased and decreased enzyme activity have been linked to an increased risk of cancer.

It is a significant protein family in the human body, as it majorly decides how an individual responds to drugs and nutrients.

Variations in this gene broadly divide people into two groups of metabolizers:

CYP1A2: Gene polymorphism:

In particular, two Single Nucleotide Polymorphisms (SNP) are found to influence caffeine metabolism:

rs762551

The haplotype CYP1A2*1F is associated with this variation.

[table id=100 /]

rs2472297

Individuals who have the TT genotype in this specific polymorphism of the CYP1A2 gene may be fast metabolizers of caffeine.

study conducted on 553 individuals found that people with this genotype had a 70% reduction in the risk of a heart attack on increased consumption of caffeine.

[table id=101 /]

Why should you know your genetic predisposition to consume caffeine?

People of certain genetic types have a genetic predisposition to drink more cups of coffee.

Identification of this tendency will help in moderating coffee consumption, taking into account the individual's caffeine metabolism status.

Genetic tests can help identify such parameters.

After all, it would be good to know if you are prone to guzzling down a little too much, especially when your caffeine sensitivity scale is tipped at the wrong end.

CYP1A2: Caffeine tolerance

Caffeine tolerance in an individual is gene deep.

The enzyme CYP1A2 is responsible for metabolizing caffeine in the body and determines whether the individual is a slow or a fast caffeine metabolizer.

Fast metabolizers of caffeine may have a high caffeine tolerance.

Such people have two copies of the fast variant.

Some people have one slow and one fast copy of the variant and are said to be moderately tolerant to caffeine.

However, those individuals who have two copies of the slow variant are slow metabolizers of caffeine and are said to be poorly tolerant of it.

How does caffeine affect your metabolism?

Resting metabolic rate describes the rate at which you burn calories at rest.

A lot of studies vouch for caffeine boosting the RMR. 

Early research also suggests that caffeine supports fat-burning during exercise.

This increase in fat-burn is what majorly contributes to the increase in metabolism.

Initially, the increase in metabolism upon caffeine consumption can be evident. 

However, this effect can diminish in long-term coffee drinkers due to the developed tolerance.

If you're primarily interested in coffee for the sake of fat loss, it may be wise not to consume it excessively and end up making your body more tolerant of caffeine.

Effects of excessive caffeine intake

Caffeine is a component in many plants, including coffee and tea.

The primary purpose of it is to act as a toxin to defend the plants against herbivores.

Caffeine in limited quantities is beneficial to our health, but in excessive amounts, harmful.

The effects of excessive caffeine intake (more than 4-5 cups of strong tea or coffee) include:

  1. Tremors
  2. Increased urination
  3. Increased heart rate
  4. Nervousness
  5. Stomach upset
  6. Anxiety
  7. Increased blood pressure
  8. It can cause restlessness in unborn babies and hyperactivity in kids

How do you remove caffeine from your body?

Excessive caffeine consumption does come with a set of undesirable effects.

During such times, the following remedies can help flush out caffeine from the system:

If nothing else works, just wait! The half-life of caffeine in the human body is roughly 4-6 hours, which means caffeine naturally starts to breakdown after that time. 

What is caffeine withdrawal?

If your body is dependent on caffeine, eliminating caffeine from your diet may cause symptoms of withdrawal.

This occurs typically 12-24 hours after stopping caffeine.

The symptoms of caffeine withdrawal are:

Ways to reduce caffeine withdrawal symptoms:

References:

  1. https://www.ncbi.nlm.nih.gov/gene/1544
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346273/

Do you have your DNA raw data from 23andMe, AncestryDNA, FTDNA, MyHeritage?

Upload your DNA raw data to Xcode Life. Our Gene Nutrition Report analyses caffeine sensitivity and metabolism, gluten sensitivity, lactose intolerance, vitamin needs, and 33 more such categories.

Updated on 09 June, 2020

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

Our affinity for alcohol is not new; in fact, we developed it ten million years ago, even before we evolved into humans! The natural source of alcohol is fruits, with usually less than 1% of ethanol in ripe fruits and up to 8% in overripe fruits. The presence of alcohol was beneficial both for our primate ancestors as well as the plants that bore the fruits. The strong smell of alcohol traveled far and wide, attracting primates. This helped primates reach food sources while they helped the plants by dispersing the seeds. Alcohol was considered highly beneficial when fruits were its major source. In the present time, where alcoholic drinks are available in large quantities and are consumed in higher concentrations, they tend to do more harm than good.

Alcohol flush reaction: What is it?

The consumption of alcohol in some individuals causes blotches of erythema on their face and neck region, and sometimes on the entire body. Such an event is called an alcohol flush reaction.

Most of the time, it happens as a result of improper digestion of alcohol.

Accumulation of acetaldehyde in the body after alcohol consumption leads to this reaction.

When you consume alcohol, it gets metabolized to its byproduct acetaldehyde.

In typical cases, acetaldehyde gets metabolized further.

An enzyme called aldehyde dehydrogenase, coded by the gene ALDH2, is responsible for this metabolism.

However, some individuals have a defective gene that prevents the further metabolism of acetaldehyde.

This causes its accumulation in the body resulting in an alcohol flush reaction.

More about the enzyme

There are two types of enzymes responsible for the breakdown of alcohol: alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. Acetate is synthesized with the help of aldehyde dehydrogenases (ALDH), mostly by ALDH2, a mitochondrial enzyme, but also by ALDH1, the cytosolic enzyme. 

There are five different types of ADH enzymes based on structural similarity and kinetic properties. 

Class I enzymes: The class I enzymes are coded by the ADH1A, ADH1B, and ADH1C genes, which are associated with about 70% of the total ethanol oxidizing capacity.

II: The class II enzymes are coded by the ADH4 gene, which is associated with about 30% ethanol oxidizing capacity. 

III: The class III enzymes are coded by the ADH5 gene and is the only class of enzyme that is detected in the brain. 

IV: The class IV enzymes are coded by the ADH7 gene and are found mainly in the upper digestive tract, where it oxidizes ethanol at high concentrations. 

V: The class V enzymes coded ADH6 gene are found in a variety of substrates, including retinol but are less efficient in ethanol metabolism.

Who is more prone to alcohol flush?

People of Asian descent, especially the East Asian descent, are more susceptible to have an alcohol flush reaction.

In fact, this red face phenomenon is also called the "Asian flush or "Asian glow."

According to some studies, over 70% of East Asians have genetic polymorphisms in either ADH or ALDH2, leading to intense flushing with ethanol consumption.

What happens during an alcohol flush reaction?

Other than the primary flushing red face, the other symptoms include:

Is the reaction dangerous?

While the flushing by itself may not to be dangerous, the reaction may have other health-related implications.

A 2013 study reported that people who experience an alcohol flush reaction on drinking might have a higher chance of developing hypertension, or high blood pressure.

Another study done on East Asian men in 2017 found an association between high risk of cancer, especially esophageal cancer, and flushing reaction.

This can be due to the high levels of acetaldehyde, which can trigger the growth of cancer cells.

How's it diagnosed?

When you report with suspected alcohol flush reaction, your doctor may first perform a physical examination. Other confirmatory tests also help with the diagnosis.

Skin test 

It detects your allergy, if any, to a substance in alcoholic beverages such as grains like maize, rye, and wheat. 

A little amount of the substance is injected into your skin, and the reaction is studied. If the skin appears red and raised, you are noted positive for the test.

Blood test

A blood test is done to detect the presence of antibodies like IgE that are found in the blood when there is an allergic reaction to a substance in alcohol.

Enzyme test

Measuring the amount of alcohol metabolizing enzymes, alcohol dehydrogenase and aldehyde dehydrogenase, can predict the intensity of reaction that one may experience.

Genetic test

The gene responsible for acetaldehyde metabolism in the body is ALDH2 that produces the enzyme ALDH2 or Aldehyde Dehydrogenase 2. 

Individuals who suffer from an alcohol flush reaction may have a faulty or deficient ALDH2 gene, and this can be identified using genetic testing.

Treating alcohol flush reaction

There is no definitive treatment for the root cause of this reaction, ALDH2 deficiency.

However, there are options when it comes to managing the symptoms.

  1. Antihistamines or histamine blockers can help control facial flushing.
  2. Another treatment, brimonidine, approved by the FDA for treating rosacea (a skin condition that causes redness in your face), can be effective for managing the flushing as well.
  3. Some laser-based therapies are also helpful to control the redness in the face.

Alcohol flush prevention

The only foolproof way to prevent this reaction is to avoid or limit your alcohol intake.

A lot of people tend to use OTC antihistamines to manage the reaction, but this is strongly not advisable.

The first and foremost step is to recognize your risk for this condition by studying your ALDH2 gene variants.

Check your 23andMe raw data or your Ancestry DNA raw data to find out the variant you carry

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According to the variant you carry, you might need to limit or discontinue alcohol consumption.

Other unwanted reactions to alcohol consumption addressed

Why do I bleed after a night of drinking?

Alcohol irritates the gastric lining.

When you drink alcohol, even a small quantity of it, it causes your stomach to produce acid.

Consumption of excess alcohol leads to increased production of stomach acid, which can lead to gastritis.

In many cases, due to excess alcohol, it triggers pain in the stomach, causes diarrhea, vomiting, and even bleeding.

Why do my ears burn when I drink alcohol?

Alcohol affects almost all parts of our body.

Consumption of excess alcohol affects the part of the brain that controls hearing.

In fact, alcohol consumption affects ears and hearing in more than one way.

When we drink alcohol, it also gets absorbed in the fluid of our ears and causes a burning sensation.

Does alcohol cause hot flashes?

Alcohol causes hot flashes in women, especially those going through menopause.

Does alcohol increase body temperature?

Having even a few sips of alcohol can make you feel warmer.

This is because alcohol makes the blood vessels underneath your skin dilate and increases the blood flow in them, which can induce the 'warm feeling.'

But in reality, alcohol reduces your core temperature.

What are some steps to reduce alcohol consumption?

Reducing alcohol consumption can immensely improve your health. Here is a list of a few things you can do to help you reduce drinking:

  1. Keep track of your drinking habits, and change them if warranted
  2. Drink slowly and hydrate yourself with water between drinks
  3. Switch to low alcohol alternatives
  4. Avoid salty snacks such as peanuts, as they make you more thirsty leading you to consume more alcohol
  5. Space out your drinks along with lots of food
  6. Watch out for peer-pressure and avoid any triggers
  7. Don't be shy to reach out for support

Do you have your DNA raw data from 23andMe, AncestryDNA, MyHeritage, FTDNA, LivingDNA, etc.?

Upload the file to Xcode Life to get insights into 700+health-related traits!

Updated 05 May 2020

It is hard to believe that caffeine, a stimulant that holds popularity in battling fatigue and improving creativity, can do any harm.

1. Caffeine Sensitivity

Caffeine sensitivity is a term that describes the efficiency of the human body to process caffeine and to metabolize it.

We have all heard of co-workers who drink 6 cups of coffee, the recreational drink for nearly 60% of Americans, every day, and friends who guzzle a cup an hour before bedtime.

Yet there are some of us who feel jittery, anxious, or even restless after a single cup.

So, is caffeine a scourge, a tonic, or a mix of both?

Is coffee good for you?

For starters, coffee has a few benefits.

A large research study showed that Americans get more antioxidants from coffee than from any other dietary source.

Other studies have shown that there are several nutrients in a cup of brewed coffee, like Magnesium, Niacin, and Potassium, depending on the soil nutrients and the type of processing.

2. How caffeine works

Adenosine is an organic compound that inhibits arousal and promotes sleepiness upon binding to its receptor.

Caffeine has a structure similar to adenosine and works as an adenosine receptor antagonist.

It competes with adenosine to bind to the adenosine receptor.

This process promotes wakefulness.

Though this can affect the quality of sleep among certain people, it could help in situations like driving at night or averting jet lag, where mental alertness is critical.

Analyze Your Genetic Variants For Caffeine Sensitivity

According to the U.S. Food and Drug Administration (FDA), 300 milligrams of caffeine are consumed every day by the average American. The Mayo Clinic states that drinking up to 400 milligrams per day is safe, which is approximately 4 cups.

A good cup of coffee is the most popular caffeine delivery mechanism that comes with a few health benefits like being a good source of antioxidants, warding off liver disease, and protecting against Parkinson’s.

The health risks and benefits have been understood, over the years, however, caffeine and metabolism, or the way in which our body processes the chemical, varies on several key factors.

3. Caffeine content in popular beverages

BeverageCaffeine content (mg)
Coffee8 oz cup - 95 mg
Espresso1 oz shot - 63 mg
Green tea8 oz cup - 28 mg
Black tea8 oz cup - 26 mg
Energy drinks8 oz cup - 91 mg
Sodas (Cola)16 oz cans - 49 mg
Coffee liqueur1.5 oz shot - 14 mg
Dark chocolate1 oz square 24 mg

4. Caffeine Metabolism: What CYP1A2 gene says

Caffeine, an alkaloid, is also known as  1,3,7-trimetilksantin.

It is acidic in its pure crystalline form and is found in over 60 plant species.

The enzyme CYP1A2 is responsible for the metabolism of caffeine in the liver.

Due to potentially ineffective CYP1A2 enzyme activity, some people can experience issues like caffeine jitters after 2-3 cups of coffee per day.

Such slower metabolizers of caffeine may experience problems with blood pressure, headaches, etc.

Learn More

<strong>Coffee and <em>CYP1A2</em>: 3 ways high caffeine intake can affect you!</strong>

5. More about the CYP1A2 gene

The CYP1A2 gene regulates the synthesis of the enzyme, and small variations in this gene have an association with the efficiency of caffeine metabolism.

Some people have a genetic predisposition to produce very little of CYP1A2 enzyme while others may produce a large amount.

Approximately 10% of the population is found to be rapid caffeine metabolizers, which rates them high on caffeine sensitivity.

Analyze Your Genetic Variants For Caffeine Sensitivity

Approximately 10% of the population are found to be rapid caffeine metabolizers, which rates them high on caffeine sensitivity.

6. Slow metabolizer variant

The polymorphism associated with caffeine metabolism is rs762551.

Studies have shown that individuals with AC or CC genotypes are slow metabolizers of caffeine.

These individuals have a high caffeine sensitivity.

They tend to have a slightly increased risk for heart attack upon consumption of more than 2 cups of coffee every day.

7. Rapid metabolizer variant

Individuals who have the A.A. genotype in the specific polymorphism of the CYP1A2 gene may be fast metabolizers.

These individuals have a low caffeine sensitivity.

study conducted on 553 individuals found that people with this genotype had a 70% reduction in the risk of a heart attack on increased caffeine consumption.

8. How many cups of coffee should you consume? Genetic testing for Caffeine metabolism

The polymorphism in the CYP1A2 gene is well studied and is useful to determine the caffeine metabolism status.

This, in turn, can shine some light on the tendency to consume caffeine. 

9. 23andMe caffeine results

The 23andMe reports provide caffeine metabolizer status.

There are other well known 23andMe third-party tools, like Xcode Life, that can provide a better understanding.

Upload your 23andMe raw data to find out your caffeine metabolism status.

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23andMe DNA raw data is the genetic information obtained after a genetic test, and it is usually provided as a text file.

This information can be downloaded after utilizing the 23andMe login provided to all 23andMe customers.

10. Using your Ancestry DNA raw data to identify your caffeine metabolizer status

There is a wealth of information provided by ancestry DNA that can be used to identify a number of health and nutrition-based traits.

Use your ancestry DNA login to download your Ancestry DNA raw data.

You can then upload your Ancestry DNA raw data onto our site to identify the caffeine metabolizer status.

11. 23andme vs. AncestryDNA vs. Xcode Life

23andme vs. AncestryDNA vs. Xcode Life pertaining to caffeine metabolizer status

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12. Your genetic predisposition to consume caffeine

People of certain genetic types tend to have a genetic predisposition to drink more cups of coffee.

Identification of this tendency will help in moderating coffee consumption, taking into account the caffeine metabolism status of the individual.

Genetic tests can help identify such parameters.

After all, it would be good to know if you are prone to guzzling down a little too much, especially when your caffeine sensitivity scale is tipped at the wrong end.

Updated on 10 June, 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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