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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.


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. 



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:


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

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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.

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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:



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

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

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