Nutrition Myths
Caffeine sensitivity depends on your genes


  • DNA plays a big part in how much coffee or other caffeinated beverages we can drink, to the point that some of us should avoid or at least reduce their intake.
  • There are several genes that determine how well we can take a caffeine hit, since they influence the rate of breaking down caffeine, the sensitivity and tolerance to caffeine and  the rate of breaking down other harmful substances induced in the body by caffeine.
  • Fast metabolizers benefit from having 200-300mg of caffeine per day, while slow metabolizers increase the risk of heart attack, women who are slow metabolizers increase a risk of infertility and if pregnant, increase a risk of miscarriage.


Caffeine sensitivity depends on your genes

What is caffeine sensitivity?

How we react to caffeine is dependent largely on genetics and varies between individuals.

Depending on what variant of the genes we have, can determine how fast caffeine is broken down in our bodies and how sensitive and tolerant we are to the effects of caffeine.

Some caffeine sensitive people may experience unpleasant symptoms by drinking as little as one cup of coffee or even tea per day. For those people regular caffeine intake leads to adverse health effects and drinking caffeinated beverages is not advisable.

Those who are not caffeine sensitive and built up caffeine tolerance may have more than 5 cups of coffee per day and barely notice the effects.

NOTE: caffeine sensitivity is not the same as caffeine intolerance (caffeine allergy).

There are a few genes responsible for how efficiently we deal with caffeine in our diet. (1, 2)

  1. Gene “CYP1A2” is responsible for releasing the liver enzyme called “polymorphic cytochrome P450 1A2 (CYP1A2) enzyme” which breaks down caffeine.
  2. Gene “AHR” which controls if gene CYP1A2 switched on or off.
  3. Gene “ADORA2A” controls sensitivity to caffeine.
  4. Gene “COMT” which controls the breakdown of catecholamines.

Please note that the studies of these genetic factors related to caffeine and catecholamine metabolism are very recent, so many previous studies that measured the effects of caffeine on our bodies did not consider these factors.


  • Caffeine sensitivity relates to how we react to caffeine.
  • Caffeine sensitivity is dependent largely on genetics and varies between individuals.
  • How sensitive to caffeine is are depends mainly on four genes.

Caffeine Sensitivity symptoms

People who are sensitive to caffeine and those who cannot break down caffeine efficiently usually feel the effects after drinking one or two coffees.

Common caffeine sensitivity symptoms:

  • Jitteriness;
  • Increased heart beat;
  • Nausea;
  • Sweating;
  • Dizziness;
  • Diarrhea;
  • Insomnia;
  • Headache;


  • Caffeine sensitive people may experience negative symptoms even after ingesting a small amount of caffeine.

Gene CYP1A2 and the rate of breaking down caffeine

After drinking a cup of coffee, most of the caffeine gets absorbed by the body and circulates for a few hours while slowly degrading in our system.

95% of caffeine (along with some drugs and carcinogens) is broken down inside the liver using an enzyme called “polymorphic cytochrome P450 1A2 enzyme”. (3, 4)

How long the caffeine stays in the body is measured by the half-life of the substance. Half-life indicates how long it takes for half of the substance to be broken down and excreted from the body.

The half-life of caffeine depends on several factors:

  • Levels of enzymes that break down caffeine;
  • Amount of ingested caffeine;
  • Liver and overall health;
  • What drugs or medications are taken at the time of caffeine intake;
  • Pregnancy.

The half-life of caffeine in healthy adults is about four hours. The gene CYP1A2 is responsible for releasing the enzyme that breaks down caffeine. It is not responsible, however, for the tolerance of caffeine.

There are two variations of this gene – one that helps metabolize caffeine faster and another that helps metabolize it slower.

Every person has two copies of this gene, one inherited from each parent.  A combination of two of the fast variant copies (fast+fast) will make you a fast caffeine metabolizer.

Any other combinations (fast + slow) or (slow+slow) will make you a slow caffeine metabolizer.


  • Slow metabolizers have an increased risk of non-fatal heart attack when they drink daily 2-3 cups of coffee (200-300mg caffeine).
  • Those who drink 4 coffees per day have 4 times the risk of heart attack comparing with those that drink about 1 cup (100mg caffeine) per day.
  • Women, who are planning to get pregnant and consume 2 coffees per day increase the risk of infertility.
  • Pregnant women consume 2 coffees per day have an increased risk of miscarriage. (1, 4)


  • Fast metabolizers have shown a 22% lower risk of heart attack by having 3-4 cups of coffee per day. For more technical explanation please click here.


  • Our genes responsible for releasing the enzyme that breaks down caffeine.
  • Fast metabolizers have a variation of this gene that helps metabolize caffeine faster, and slow metabolizers have another variation that metabolize it slower.
  • 2-3 coffees per day is beneficial for fast metabolizers, while detrimental to health in slow metabolizers.

Gene AHR and switching on gene CYP1A2

The gene called AHR is another gene associated with the rate of caffeine breakdown. It does this indirectly by regulating gene CYP1A2. (5)

Gene ADORA2A and sensitivity to caffeine

As mentioned above, caffeine attaches to the receptor A(2a).

Gene ADORA2A variations are responsible for receptor A(2a) which is associated with caffeine sensitivity. (6, 7, 8)

Technically speaking, people who carry two copies of the C allele of ADORA2A are more sensitive to the effects of caffeine and suffer from sleep disturbances.

People with two copies of the T allele of ADORA2A experience greater anxiety after caffeine. (6)

Gene COMT and the breaking down of catecholamines

Caffeine increases the release of catecholamines.

When in high concentrations, catecholamines damage cells in the muscular tissue of the heart leading to an increased probability of heart attack.

An enzyme called Catechol-0-Methyl Transferase (COMT) breaks down catecholamines.

The less active that the COMT enzyme is, the bigger the concentration of catecholamines and the more probability of damage to the heart and a resulting increased risk of a heart attack.

The gene responsible for making this enzyme more active is the “COMT gene”.

COMT has a number of variations.

Therefore, if you have a COMT rs4680 variant, which causes low COMT activity, by drinking coffee you are increasing the risk of a heart attack. (6, 9)

The probability of a heart attack grows if you are a slow metabolizer and have low COMT activity.

Receptor A1 and caffeine tolerance

Caffeine attaches to two receptors in the cells surface A(1) and A(2a). Drinking coffee or caffeinated beverages frequently is associated with increased tolerance to caffeine. This occurs since chronic caffeine intake increases the density (number) of receptors. The more receptors that get produced, the more we crave caffeine. (6)


You will find a summary of the most common nutrition myths and evidence-based nutrition facts here.

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