Caffeine sensitivity is determined by the efficiency of the human body to process and metabolize caffeine.
This shouldn’t be confused with caffeine tolerance, which describes how the body responds to caffeine over time.
Sensitivity has more to do with a person’s unique genetic makeup as this determines to what degree a given amount of caffeine will affect a person.
Genetic Link to Caffeine Sensitivity
Caffeine is metabolized by the liver using the enzyme CYP1A2. The ability to produce this enzyme is regulated by the CYP1A2 gene. Slight changes in the DNA sequence of this gene determine how efficiently a person can metabolize caffeine and thus eliminate it from the body.¹
Some people genetically produce very little of this enzyme while others produce a large amount. The majority of humans are somewhere in the middle.
The AHR gene also plays a role in caffeine sensitivity in that it regulates the turning on and off of the CYP1A2 gene. 10% of the population are rapid caffeine metabolizers and thus not very caffeine sensitive. ²
The third genetic link to caffeine sensitivity involves the type of adenosine receptors a person has in his/her brain. Those lacking the correct adenosine receptors in their brains are unresponsive to the awakening effects of caffeine because the caffeine molecule cannot properly bind to the receptors. ³
Determine your caffeine sensitivity by taking a DNA test (such as the 23andMe Health + Ancestry test).
6 More Genetic Links
The most recent research from The Harvard School of Public Health found 6 new genetic variants associated with the way people metabolize and form an addiction to caffeine.4
The 120,000 person study revealed:
- 2 genes related to how caffeine is metabolized.
- 2 genes associated with how we feel rewarded from ingesting caffeine.
- 2 genes that regulate fat and sugar in the bloodstream as a response to caffeine.
More research in Italy and the Netherlands have shown the gene PDSS2 may also be responsible for the speed of metabolism. People with a specific variation drink less coffee than others. It is thought that the PDSS2 dictates sensitivity at lower levels of consumption, while CYP1A2 determines consumption at higher caffeine levels.
Three Levels of Caffeine Sensitivity
Based on the genetic data we have to date, we can identify people with 3 distinct levels of caffeine sensitivity, which in turn determines to what degree the effects of caffeine will be realized.
1. Hypersensitive to Caffeine
These people react to very small amounts of caffeine. Even at amounts less than 100 mg, people who are hypersensitive to caffeine can experience overdose symptoms such as insomnia, jitters, and an increased heartbeat.
For these people, it can take as much as twice as long for caffeine to metabolized.
2. Normal Sensitivity to Caffeine
People who show normal sensitivity to caffeine can usually have 200-400 mg of caffeine daily without any adverse reactions. These people have no trouble sleeping as long as the caffeine is consumed early enough in the day.
The majority of humans fall under this category and this group is what the recommended daily safe dose of caffeine has been established for.
3. Hyposensitive to Caffeine
About 10% of the human population are hyposensitive to caffeine. They process caffeine so efficiently that these people report taking large doses ( >500 mg) without much effect at all. Those hyposensitive can also consume caffeine shortly before bedtime and still get a good night’s sleep.
These people are more prone to consuming large doses of caffeine in order to get the desired effects.
Determining Your Level
In order to safely use caffeine, it’s important to understand your level of caffeine sensitivity.
Based on the three descriptions above, you should be able to identify your level of caffeine sensitivity and then follow our recommendations below.
- For those hypersensitive to caffeine, we recommend that they cautiously consume caffeine and avoid highly caffeinated beverages like coffee and energy drinks. Black tea or green tea is probably a wise choice for this group. Quitting caffeine altogether may be an even better option.
- Those with normal sensitivity should be aware of how much caffeine they are consuming and keep this within the daily safe dose guidelines of between 300-400 mg. This equates to 2-3 cups of brewed coffee (not Starbucks), two 16 fl.oz. energy drinks, 7-8 cups of black tea.
- Hyposensitive people should evaluate the necessity of caffeine. If large amounts of caffeine do not create the desired effects such as wakefulness, alertness, and productivity, then we would question the benefits of consuming it. Since caffeine is toxic, large doses daily could be doing damage over time, which isn’t yet fully understood.
Caffeine Sensitivity Isn’t Exactly Black and White
While the above guidelines and caffeine sensitivity levels may apply to many, there are some that could fall somewhere in the middle.
Some people could be normal but lean toward the hypersensitive category or learn toward the hyposensitive category. Human genetics are complex and people are unique with many subtle genetic variations.
Also, some people can develop caffeine hypersensitivity as they age instead of having it from birth. Our gene expression changes as we age.
If you don’t align perfectly in one of the sensitivity categories above, it’s okay! It’s just important that you understand how caffeine interacts with your unique set of DNA.
- 1. GenePlanet.com
- 2. http://www.gbhealthwatch.com/Trait-Caffeine-Consumption.php
- 3. Genetics of caffeine consumption and responses to caffeine
- 4. Cornelis, M. C., Byrne, E. M., Esko, T., Nalls, M. A., Ganna, A., Paynter, N., ... & Xue, L. (2014). Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Molecular psychiatry. link
- 5. Pirastu, N. et al. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption. Sci. Rep. 6, 31590; doi: 10.1038/srep31590 (2016).