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How we react to caffeine is dependent largely on genetics and varies between individuals.
- Gene “CYP1A2” is responsible for releasing the liver enzyme called “polymorphic cytochrome P450 1A2 (CYP1A2) enzyme” which breaks down caffeine.
- Gene “AHR” which controls if gene CYP1A2 switched on or off.
- Gene “ADORA2A” controls sensitivity to caffeine.
- 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 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:
- Increased heart beat;
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.
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;
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).
- Slow metabolizers who drink 4 cups of coffee 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 slow metabolizers, are planning to get pregnant and consume 2-3 cups of coffee per day (200-300mg caffeine) increase the risk of infertility.
- Pregnant women who are slow metabolizers and consume 2-3 cups of coffee per day (200-300mg caffeine) have an increased risk of miscarriage. (1, 4)
- Fast metabolizers have shown a 22% lower risk of heart attack by having 2-3 cups of coffee per day (200-300mg caffeine). For more technical explanation please click here.
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).
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 risk 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.
The risk 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)