Hello everyone!

 As one of the three most popular drinks in the world, coffee first became popular in Western countries. In recent years, it has become very popular in China. Quite a number of students, white-collar workers, and middle-aged and elderly people cannot live without coffee every day.

However, although some friends like to drink coffee very much, they often get stomachache every time they drink it, or they can't sleep all night after drinking a little during the day, but others are fine. Why is that? With this question, the editor searched PubMed and found that this may actually be related to our innate genes . Let's talk about how to drink coffee well today!

Pay attention: Coffee is not only delicious, but also has health benefits

The coffee tree is an evergreen tree belonging to the Rubiaceae family. The coffee we drink daily is made from coffee beans and a variety of cooking utensils, and then baked using appropriate methods. It is known as one of the three major beverages in the world along with tea and cocoa.

Coffee contains a lot of bioactive substances , the most commonly mentioned of which is caffeine, a psychoactive molecule that also has physiological effects such as anti-oxidation and anti-apoptosis. In addition, coffee also contains many lipid molecules, such as cafestol and kahweol, which are also bioactive substances that help DNA repair, anti-oxidation, and scavenging free radicals.

In 2017, the British Medical Journal published a study titled “Coffee and Health”[3], which evaluated the relationship between coffee drinking and up to 67 health outcomes. It involved a total of 201 high-quality meta-analyses and tens of millions of observational populations, causing a sensation in the academic community and giving people a new understanding of coffee, a common yet mysterious food. Below, I will briefly present the results of this study.

The research results in the above figure are divided into two parts according to the red box of the editor, both of which compare people with high coffee drinking (5-6 cups, about 1200 ml-1400 ml) and people with low coffee drinking (0-1 cup, less than 240 ml). The first part is the 10 health outcomes that are most harmful to health due to high coffee drinking, and the second part is the 10 health outcomes that are most protected by high coffee drinking.

From the research results, it can be basically summarized as follows:

High coffee drinking is risky for some people with special physiological conditions , such as pregnant women and children. It may increase the adverse outcomes of low birth weight or premature birth, and children may increase the risk of leukemia. The risk of lung cancer may be caused by the excessive promotion of lung cancer by smoking, according to the rigorous analysis of researchers. On the other hand, it is not suitable to drink coffee if you are in a special period of diarrhea, taking cold medicine, fever, etc.

On the other hand, for adults who are not in special physiological conditions , drinking coffee is a good way to prevent many chronic metabolic diseases, cancers, and other diseases, such as cardiovascular and cerebrovascular diseases (including coronary heart disease, cerebral infarction, stroke, etc.).

The researchers also explored the health effects from two perspectives: drinking coffee and never drinking coffee; and drinking one extra cup of coffee (about 240 ml). The overall health effects were similar to the analysis results in the above figure.

Finally, through dose-effect analysis, the researchers concluded that drinking 2-3 cups of black coffee (approximately 480 ml-720 ml) a day is the dosage range with the greatest health protective effect.

Well, what is the reason why our friends feel uncomfortable after drinking? Let’s reveal it to you next!

The factor that makes you uncomfortable is the stimulant in coffee

First of all, caffeine, the bioactive substance with the highest content in coffee, which is also the main ingredient for refreshing the brain, is actually metabolized by specific enzymes in the body. Therefore, the body must have the "ability" to produce this enzyme, and to produce this enzyme, the corresponding gene must be present.

The special coding on the corresponding gene can specifically produce proteins with specific functions (enzymes are also a type of protein), which enter the circulation and play the corresponding physiological functions. Therefore, the author began to explore what gene-controlled enzymes affect the metabolism of caffeine?

Magical metabolic enzyme

The editor found an authoritative article published in the journal Pharmaceutical Review last year [1]. In fact, this enzyme is a protein called liver microsomal cytochrome P-450-dependent drug metabolizing enzyme , which is responsible for more than 90% of caffeine metabolism. If caffeine is not metabolized in time, gastrointestinal irritation symptoms or continuous excitement and insomnia will occur.

But what's amazing is that the rs762551 gene site that encodes this enzyme may mutate, producing a "second-rate" enzyme, which is actually an enzyme with a significantly reduced ability to break down caffeine.

So the more important question is, is the probability of this gene mutation very high in Asians?

The answer is yes!

The editor retrieved two relevant studies. The first article explored the content of hepatic microsomal cytochrome P-450-dependent drug-metabolizing enzymes in different ethnic groups in China and in America (as shown in the figure below) [2].

We can find that the level of this "powerful enzyme" in the Han ethnic group is very low . Although there is no statistically significant difference with the American people, it may be due to the small number of people surveyed. So the editor retrieved another article.

This article is a meta-analysis [3] that studies the relationship between the presence or absence of mutations in this “powerful enzyme” and the amount of coffee consumed. The three included articles that used Asians as research subjects all found that the activity of this enzyme in Europeans and Americans is significantly higher than that in Asians (Japanese/Koreans/Chinese).

How can we drink coffee happily?

Haha, the whole story becomes clearer now. Some of us are born with limited ability to metabolize caffeine, but does that mean we can’t drink coffee because of this “congenital defect”?

Actually not! So I would like to remind those who are still addicted to coffee:

1. If you haven't drunk it for a long time, drink it in small amounts when you drink it again to see if your body has any uncomfortable reactions (such as diarrhea, stomach pain, etc.)
2. If you can't fall asleep easily after drinking coffee and you like coffee very much, try to drink a small amount in the morning.
3. For those who want to drink coffee but cannot fall asleep easily and want to drink more, you can choose latte coffee with a larger proportion of milk, which can satisfy your craving without taking in too much caffeine at one time.

Generally speaking, the "powerful enzyme" mentioned by the editor can be induced, that is, its content will slowly increase if it is slowly guided, so if you drink it carefully according to steps 1-3, your body will slowly adapt over time! In general, coffee is a healthy drink, and long-term healthy drinking of black coffee has a very good preventive and protective effect on our cardiovascular and cerebrovascular (especially cerebral infarction) effects!

 References:
 [1] Nehlig Astrid,Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption.[J] .Pharmacol. Rev., 2018, 70: 384-411.
 [2] Li Guo-Fu, Zheng Qing-Shan, Yu Yichao et al. Impact of Ethnicity-Specific Hepatic Microsomal Scaling Factor, Liver Weight, and Cytochrome P450 (CYP) 1A2 Content on Physiologically Based Prediction of CYP1A2-Mediated Pharmacokinetics in Young and Elderly Chinese Adults.[J] .Clin Pharmacokinet, 2019, 58: 927-941.
 [3] Denden S, Bouden B, Haj Khelil A et al. Gender and ethnicity modify the association between the CYP1A2 rs762551 polymorphism and habitual coffee intake: evidence from a meta-analysis. [J] .Genet. Mol. Res., 2016, 15: undefined.