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6 Cups a Day? How Genetics Affect Caffeine Tolerance

Article at a Glance
  • Genome-wide association studies (GWAS) have revealed certain variants of specific genes that are associated with increased coffee intake.
  • People with certain gene variants may need to drink up to 30 percent more coffee than those without the gene variants to get the same effects.
coffee and brain health

Coffee is one of the world’s most popular beverages, and caffeine the most popular drug. Millions of people drink caffeine in some form everyday.

But how much coffee do people really need to drink to get the benefits? And could our daily coffee habits be affected by genetics? Genome-wide association studies (GWAS) have revealed genetic variants that are associated with a tolerance for increased coffee and caffeine intake.

Genetically, some of us may need to drink more coffee to get the same benefits as those who don’t carry these genetic variants. So, if you’re wondering why you can’t seem to get the benefits of coffee no matter how much you drink, or why a cup of coffee before bed doesn’t seem to affect you, your genes may be to blame.

The Science of Coffee and Caffeine

Before we dive into how your genes affect your coffee habit, let’s take a closer look at the science behind coffee and caffeine metabolism.

Coffee beans contain caffeine, a stimulant that helps to increase alertness and reduce fatigue. Generally, the more caffeine the coffee contains, the more alert and energized you will feel. Caffeine has been studied for its potential to reduce risk for certain types of diseases, including some cancers and Parkinson’s disease. It has also been linked to improved cognitive function, as well as improved physical performance. That said, drinking too much caffeine can lead to negative side effects, such as anxiety, restlessness, and insomnia. It’s important not to overdo it with caffeine, as too much can have negative effects on your health, especially over the long-term.

People react differently to coffee because everyone’s body chemistry is unique and will affect the way they react to stimulants like caffeine. Also, different types of coffee contain different levels of caffeine, as well as other ingredients such as sugar, which can contribute to the varied reactions. Some people may be more sensitive to the effects of caffeine and develop a “caffeine tolerance” over time, while others may become more tolerant and find that it takes less and less coffee to get the same effect. Additionally, lifestyle, stress levels, health, and genetics all play a role in the way people react to coffee.

How Your Genes Affect Your Coffee Habit

While it may seem counterintuitive, your genes can play a significant role in how much coffee you need to drink to get that sought after “coffee buzz.”

Athletic Performance

I’ve written previously on the Gene Food blog about studies detailing the genetic variants that affect athletic performance after drinking caffeine.

Caffeine addiction

Genes play a role in coffee addiction. Certain genetic predispositions can increase the likelihood of addiction as well as the severity of its symptoms. Variants in genes involved in dopamine production and processing are included.

Caffeine metabolism

Studies have also shown that genetic variations in the enzyme responsible for metabolizing caffeine can cause some people to be more sensitive to its effects, leading to greater dependency. For more, see: How to tell if you are a slow caffeine metabolizer

Anxiety and mental health

Additionally, those with certain mental health disorders, such as anxiety and depression, are more likely to develop an addiction to coffee due to their increased sensitivity to its effects.1  Ultimately, an individual’s genetic makeup will influence their susceptibility to developing a coffee addiction.


Evidence suggests that the genes associated with coffee consumption may involve those related to taste and olfaction (smell), although specific genes involved have yet to be identified. Coffee taste preferences may have a genetic component, as suggested by a study which found an association between coffee preference and the TAS2R38 gene,2 which is thought to be involved in the detection of bitter tastes. Variants of this gene have also been associated with sensitivity to caffeine, suggesting a possible genetic component in preferences for caffeine concentrations in coffee.

The four big coffee consumption genes

A large meta-analysis published in Molecular Psychiatry looking at 91 462 coffee consumers of European ancestry pin-pointed four genes and their variants linked to higher coffee consumption.3 In this study, researchers looked at the genes that impact how our bodies respond to caffeine. Variants near GCKR, MLXIPL, BDNF and CYP1A2 (the caffeine metabolism gene) were associated with higher coffee consumption. They found that people with certain gene variants may need to drink up to 30 percent more coffee than those without the gene variants to get the same effects. This could mean the difference between needing two cups of coffee to feel energized and alert or needing three cups. Interestingly, these genes have also been associated with smoking initiation and/or smoking duration in other studies.

How your coffee habit affects your brain

We know that coffee affects our brain, but research has found that it can cause changes in its size as well. Keep in mind that these studies look at the high-end of coffee consumption (6+) and this is likely not a realistic situation for most people.

An in-depth study on coffee consumption and its effect on the brain involved over 600 participants, all between the ages of 45 and 85. It was found that higher coffee consumption was associated with a decrease in brain volume as well as an increased risk of dementia.4

The study also found that coffee consumption was linked to greater shrinkage in brain regions known as the mediotemporal lobe, which is considered to be one of the first regions of the brain to be directly affected by neurodegenerative diseases such as Alzheimer’s. In addition, it found that individuals who drank more than seven cups of coffee per day were more likely to experience greater brain volume loss and increased risk for dementia. It is likely that greater coffee intake contributes to the progression of neurodegenerative diseases due to its known ability to increase the activity of certain neurotransmitters in the brain.

Although research is ongoing, it’s important to be aware of the possible negative effects of increased caffeine intake on brain function and decrease your consumption accordingly if you are a “6 cups a day” type of caffeine drinker. 

The Coffee and Caffeine Debate

While the potential health benefits of coffee and caffeine are clear, the debate over the exact amount of coffee we should be drinking is ongoing. Some studies have suggested that drinking more than four cups of coffee a day could be dangerous, while other studies have suggested that even moderate amounts of caffeine can be beneficial.

It’s important to note, however, that everyone’s bodies are different. So, while the studies discussed above suggest that people with certain gene variants have decreased brain volume and need more coffee to get the same benefits as those without the gene variants, it’s important to listen to your body and take into account your individual response to caffeine. 

The Bottom Line

Your daily coffee habit may be affected by your genes. However, it is important to note that factors such as lifestyle, culture, and social environment also contribute to our individual coffee consumption habits. In other words, whether you require that extra cup of coffee might have something to do with both genetics and your environment.

Dr. Gina Leisching

Dr. Gina Leisching holds a BSc in Functional Human Biology, and Honours degree in Physiological Sciences, as well as a doctorate in human physiology from Stellenbosch University, South Africa. At Gene Food, Dr. Gina uses her expertise to provide evidence-pieces that readers may find helpful and informative.

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