Coffee: The Curse of four cups

Daria Spasskaya

We at N+1 like to talk about scientific research on the benefits of coffee and the caffeine contained in it. According to some scientific articles, regular coffee consumption protects against the development of diabetes, heart attack, Parkinson's disease, cirrhosis, impotence and generally prolongs life. However, caffeine is an addictive stimulant of the nervous system, and people suffering from hyperexcitability, insomnia and cardiovascular diseases are usually not recommended to use it. This dual nature of coffee confuses many and even makes scientists writing about the benefits of coffee suspect of receiving grants from coffee companies. Let's figure out why they write so much about coffee, and whether it's worth starting to drink it in order to improve health.

The coffee market is growing from year to year, and coffee is being consumed in places where it was not particularly loved before – for example, in Asia. It is quite natural that scientists want to know what the national coffee craze will turn out to be in the long term, so the number of articles about the health effects of coffee and the molecular mechanisms of caffeine action is growing along with the market. At the same time, coffee is still a relatively unpopular drink in Russia. In 2017, one Russian per year accounted for 1.69 kilograms of coffee consumed, while the average in Europe is 7.8 kilograms per person per year, and in the United States – 4.4 kilograms. Probably also for this reason, such an abundance of information about coffee seems to us to be outright propaganda.

In scientific articles, coffee consumption is often measured in conventional cups, but this, of course, is not the most accurate way to convey the amount of substance. It should be noted that caffeine is not the only biologically active component of coffee. About 1000 compounds are responsible for the taste and aroma of the drink, including diterpene alcohols, caffeic acid and its derivatives, flavonoids and tocopherols. Many of them work as antioxidants or change the density of the lipid fraction of the blood and, thus, also have an impact on the health of consumers.

The concentration of all these substances depends on the type of coffee, growing conditions, the method of roasting the beans, the method of preparation and a bunch of other factors. As a result, a cup of coffee can contain from 50 to 300 milligrams of caffeine. In many sources, the average caffeine content in a cup of coffee beans is taken as 100 milligrams (in an average cup of tea, the caffeine is 2-4 times less). Thus, three to four cups of coffee a day correspond to 300-400 milligrams of caffeine – the maximum amount that healthy people do not associate with side effects. However, personal experience tells us that coffee has different effects on different people. Someone has a cup of strong coffee that causes a rapid heartbeat, and someone has a desire to take a nap.

Caffeine, entering our body, like most drugs, undergoes transformation in the liver, and its concentration in the blood depends on the activity of liver enzymes. The main enzyme that metabolizes caffeine is cytochrome CYP1A2 – it decomposes 90 percent of the substance. Different variants of this enzyme, determined by polymorphisms in the CYP1A2 gene, have different activity and cause people to metabolize caffeine at a higher or lower rate. For people with low activity of CYP1A2, slowly decomposing caffeine, the substance acts more strongly and for a long time, which increases the likelihood of side effects. People with high cytochrome activity, on the contrary, need to consume more caffeine to show at least some effect.

Caffeine metabolism in the liver (Wikimedia Commons)

Many polymorphisms in the CYP1A2 gene are known – for example, the activity of the enzyme is affected by the nucleotide substitution in the first intron of the gene at position 734 of adenine (A) for cytosine (C). Carriers of the AA genotype are able to metabolize caffeine quickly, while carriers of the AC or CC genotype do it slowly. The rate of caffeine metabolism is directly related to the effect of drinking coffee on health. It has been shown that carriers of the C allele have regular coffee consumption (more than 2 cups) increases the risk of myocardial infarction, and in carriers of the AA genotype, the same amount, on the contrary, improves the state of the cardiovascular system. Thus, from the point of view of risk to the heart, for some people, conditional four cups of coffee will be useful, and for some – harmful.

In addition to polymorphisms, other alleles play a role in CYP1A2, for example, variants of adenosine receptor genes – targets of caffeine. In addition to genetic features, the expression of the CYP1A2 gene is influenced by external factors, such as smoking. In smokers, caffeine is metabolized in the liver at a rate 50 percent higher than in non-smokers (this may explain why the combination of coffee and cigarettes is so popular in modern culture). Some drugs, such as oral contraceptives, on the contrary, slow down the metabolism of caffeine. In pregnant women, the metabolism of caffeine also slows down, which leads to certain risks for the fetus.

Summing up, we can say that the effect of coffee on each person is individual and depends on his genetics and habits, so it is quite difficult to predict whether you personally will benefit from increasing coffee consumption. Of course, you don't have to run to sequence your genome to understand whether you are at risk of an increase or decrease in the risk of a heart attack by 30 percent from an extra cup. Listen to yourself – if coffee makes you feel good, drink to your health, and if it's bad, don't force it in, nothing good will come of it.

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