Coffee Metabolism

April 5, 2023

Coffee is a beverage prepared using the brewed seeds of coffee plants. Coffee is enjoyed worldwide. It is one of the top three drinks in the world. Coffee is available in all stores and breweries and is typically derived from both Coffea arabica and Coffea canephora. Arabica is considered a milder form of coffee with more flavours and aromas. While Robusta the main variety of canephora is strong in flavours. ( )

Sometimes, variation is displayed by many individuals in terms of coffee metabolism. There are some individuals who are slow coffee metabolisers, on the other hand, few individuals can metabolise coffee at a faster rate. This has raised questions in many people's minds. “Why is there a variation in coffee metabolism in populations”? 

Let us try to delve deeper and gain a better understanding of the situation.

Mechanism of Coffee Metabolism

One of the main compounds found in coffee is caffeine. The caffeine molecule is the one that stimulates our nervous system. Individuals do consume coffee in order to improve their performance and get a boost as soon as they wake up in the morning. 

Caffeine, on the whole, is metabolised entirely by the body. Only 3 per cent or slightly less of the caffeine is passed through the urine without being metabolised. The route of caffeine metabolism (70-80 per cent) in humans is through N-3-demethylation to paraxanthine. This reaction is carried out in the liver by CYP1A2. (Cytochrome P450 family 1; subfamily A member 2) The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. Since coffee is a form of xenobiotics, it is metabolised by CYP1A2 in the liver for the same reason.


In order to study this, human liver microsomes were studied in labs, and it was found that 1-N-demethylation to theobromine accounts for 7 to 8 percent (percent) of caffeine metabolism. While caffeine metabolism with 7-N-demethylation to theophylline accounts for 8 per cent. 1,3,7-trimethyluric acid is formed from C-8 hydroxylation, which adds up to 15 percent percent of caffeine metabolism.


Previous studies conducted to understand coffee metabolism have elucidated that on average coffee has a half-life of 2.5 to 5 hours in the system. Similarly, half-lives from 2.5 to 9.9 hours have been recorded based on interindividual variations. 

Individual variation in coffee metabolism 

As discussed in the above paragraphs, CYP1A2 carries out the conversion of caffeine in the liver. However, there are individual variations observed. These individual variations make a person either a slow or fast metaboliser. An SNP (Single Nucleotide Polymorphism) from A to C at the 163rd of the CYP1A2 gene plays a role in this. Those individuals who have “C” are slow metabolisers, which means caffeine would take 10-12 hours to get metabolised in their system. This causes dizziness and jitteriness in these individuals. On the other hand, individuals with type “A” will metabolise caffeine within 3–4 hours and don’t experience dizziness and jitteriness symptoms. 

Effects of various factors on caffeine metabolism 

There are various factors that affect the coffee metabolism of individuals. Age, hormones, liver diseases, genetics and even diet could play a role in how caffeine is metabolised. Let's go over these elements in more detail below. 


In neonates (under 28 days old), it is observed that caffeine clearance is slightly slower compared to adults. It is shown that their coffee metabolism takes 65 to 105 hours. This could be the fact that the organs are still developing in neonates. In humans, age does not appear to affect caffeine clearance, whereas, in rats, the caffeine half-life increases in an age-related manner.


Sex and Hormones: 

Studies have shown that the CYP1A2 enzyme is more active in males compared to females. However, there is no difference in the urinary metabolites observed in terms of the metabolites excreted from the urine.

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Along this, it is observed that during pregnancy, the metabolism of coffee is slowed down. Once the pregnancy is over, the metabolism returns to its preconception state. This is because the CYP1A2 CYP1A2 activity decreases during late pregnancy.


Liver Diseases: 

Individuals with hepatitis B, C, or cirrhosis take longer to clear coffee from their systems. This is primarily due to the synthesis of paraxanthine in the liver. This is primarily due to the fact that these diseases affect the various activities of the liver, and since CYP1A2 activity is highest in liver there is increased half-life of coffee which can go upto 50-160 hours. Thus, the synthesis of paraxanthine is hampered which is the first step in caffeine breakdown.



Caffeine clearance and its half-life are quite significantly affected by grapefruit consumption. The difference that is observed is 23% increase in clearance and 31% increase in half-life. Consumption of foods rich in vitamin C helps increase the clearance of coffee. Apiaceous vegetables (such as carrots, celery, parsley, caraway, fennel, etc) decrease CYP1A2 activity.

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In South Asian countries, the activity of CYP1A2 is significantly decreased since they cook their foods with ingredients containing curcumin, which downregulates the activity of CYP1A2.



Similarly, it is advisable to consume coffee 60-90 minutes after waking up in the morning. This is because once we wake up there are still adenosine receptors which need to be cleared out and caffeine acts as an adenosine blocker. If this is not followed, the remaining adenosine receptors are blocked. These will get activated in the afternoon, or the caffeine effects will be washed off, causing “the afternoon crash” observed by many coffee drinkers. Thus, it again depends on individuals genetic make up and well being. 

To sum up the discussion, we can say that there are various interindividual differences that dictate the way in which coffee will be metabolised in the system. It is advisable to discuss with your healthcare healthcare provider or nutritionist the ups and downs of coffee for yourself in particular. 

Krishna Mesta
Functional Nutritionist- R & D division

Krishna has a Master's in Nutrition and Dietetics with a specialisation in Nutrigenomics. He believes that Research is like a solving puzzle by finding the missing pieces and arranging them together in such a way that it makes easy for others to understand.

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