Coffee: Benefits based on your genes

Coffee: good or bad for you? Coffee is one of the most popular beverages in the world, second only to tea. However, it is sometimes controversial because of its caffeine content.

Large population studies have shown many benefits of coffee consumption, including a reduced risk of heart disease, endometrial cancer, diabetes, Parkinson’s disease, liver cancer, cirrhosis, prostate cancer, and stroke. On the other hand, large population studies often fail to account for an individual’s response to a substance, and the benefits of coffee may vary based on your genes.

Table of Contents

Drinking Coffee: Good or Bad?

Studies have shown many benefits of coffee consumption, including decreased risk of:

endometrial cancer
diabetes
Parkinson’s disease,
liver cancer
cirrhosis
prostate cancer
stroke
heart disease

Antioxidants found in coffee:

Coffee is actually the “number one source of antioxidants in the U.S diet, according to a new study by researchers at the University of Stanton”.[ref]

In brewed coffee, several micronutrients, including potassium, magnesium, and niacin, are available in somewhat significant levels, but variations in soil nutrients, processing, and brewing do make a difference in the micronutrient levels per cup.[ref]

Caffeine affects people differently

Whether you start your morning with a cup of coffee or tea, caffeine remains the most popular ‘drug’ of choice for a large percentage of the population.

Caffeine wakes us up by blocking the adenosine receptor.

Caffeine also acts as a central nervous system stimulant, increasing reaction time.

Genetics determine how quickly your body processes and eliminates caffeine, and whether it makes you jittery or anxious.

Adenosine Receptors:

Adenosine is a molecule used in the body for a variety of purposes. One action of adenosine is that it makes us sleepy at the end of the day. Adenosine builds up in the brain over the course of the day and then is cleared out more quickly at night while we sleep. Higher levels of adenosine make us feel sleepy, driving us to go to sleep at night.

Caffeine can also bind to the adenosine receptors in the brain. When caffeine attaches to the adenosine receptor, it blocks the receptor, making you feel more alert.

Changes to the adenosine A2A receptor gene (ADORA2A) also give rise to variations in how we respond to caffeine.

Changes in how the adenosine receptor functions due to genetic variants (see the genotype report below) can alter a person’s response to caffeine, including whether coffee increases anxiety.[ref]

Caffeine Metabolism: CYP1A2

CYP1A2 is a phase I detoxification enzyme that breaks down caffeine, as well as several other important toxins such as aflatoxin B1 from mold.

When you consume caffeine, it undergoes a process called biotransformation, which involves several enzymatic reactions to break it down. CYP1A2 is the primary enzyme responsible for metabolizing caffeine in the liver, although other enzymes also contribute to a lesser extent.

CYP1A2 enzyme activity can vary between individuals due to genetic variants (below in the genotype report) and environmental factors. Some people may have a highly active CYP1A2 enzyme, which means they metabolize caffeine quickly, while others may have a less active enzyme, resulting in slower caffeine metabolism.

Will coffee cause your kidneys harm?

A 2023 study made headlines by saying that people with slower coffee metabolism were at a 3-fold increased risk of kidney failure when drinking 3 or more cups of coffee a day. When digging into the details, the study was conducted in ~600 people who had high blood pressure. The kidney function measurements were done in 22 people with slower CYP1A2 variants who drank 3 cups or more of coffee a day, and the results were compared to 17 people with fast CYP1A2 variants who also drank 3+ cups a day.[ref]

The kidney function measurements did decrease faster over the course of 7 years in those with the slow CYP1A2 variants. However, I’m not sure that these results warrant the scary headlines of being at a 3-fold risk of kidney failure for people drinking more coffee. The sample size was small, and CYP1A2 also breaks down other substances, such as mold toxins.

Coffee: Genotype Report

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CYP1A2 gene:

This gene codes for the enzyme that metabolizes or breaks down caffeine in the body.

If you are a slower metabolizer, you will feel the effects of caffeine for a longer period of time.
If you are a fast metabolizer, you will break down and get rid of caffeine more quickly from your system.

Check your genetic data for rs762551 (23andMe v4, v5; AncestryDNA):

C/C: Slower metabolizer of caffeine
A/C: Intermediate metabolizer of caffeine
A/A: Fast metabolizer of caffeine[ref] heavy coffee drinkers have a decreased risk of a heart attack.

Members: Your genotype for rs762551 is —.

Slow metabolizers of caffeine (rs762551 A/C or C/C) might have a slightly increased risk of a heart attack when drinking more than 2 cups of coffee per day. Fast metabolizers (A/A) may have a decreased risk of heart attack with coffee consumption, with heavy coffee drinkers shown to have a significantly decreased risk that is about 70% less than average.[ref][ref] The results on this aren’t completely clear, with some showing a risk and others not finding a risk.[ref]

ADORA2A Gene (Adenosine 2A receptor):

This gene codes for the adenosine receptor protein, which, among other things, plays a role in regulating dopamine and glutamine release in the brain. Caffeine partially blocks the receptor. Both of the variants listed below are very common.

Check your genetic data for rs5751876 (23andMe v4, v5)

C/C: no increase in anxiety from caffeine; higher sensitivity to the alerting effects of normal caffeine consumption.[ref]
C/T: no increase in anxiety from caffeine
T/T: high caffeine doses are more likely to make you anxious[ref][ref]

Members: Your genotype for rs5751876 is —.

Check your genetic data for rs2298383 (23andMe v5):

T/T: no increase in anxiety from caffeine
C/T: no increase in anxiety from caffeine
C/C: high caffeine dose more likely to make you anxious[ref][ref]

Members: Your genotype for rs2298383 is —.

Interesting studies on these ADORA2A variants:

Anxiety: While the two variants above are tied to increased anxiety with caffeine, they are also found to correspond with increased anxiety in general (not linked to caffeine).[ref]
Have dry eyes? These two ADORA2A variants lead to slightly increased tear volume with caffeine consumption.[ref]
Caffeine intake: A study found that those who were more susceptible to anxiety from caffeine were also likely to have a higher habitual caffeine intake. Those drinking more coffee tended to build up a tolerance to the anxiety-inducing effects regardless of genotype.
BRCA1 and Breast Cancer: For those with a BRCA1 mutation, one study found that coffee consumption before age 35 for those with the rs5751876 C-allele reduced their risk of breast cancer by 64%.[ref]
Wake-up effect of caffeine: People with the rs5751876 C/C genotype showed a higher sensitivity to the alerting effects of normal caffeine consumption.[ref]

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