Coffee and health

The relationship between coffee and health is a common topic. On the internet, we can find a lot of recommendations and suggestions about it. Testimonials from people, tell us why they’ve stopped drinking coffee, especially related to the cardiovascular world, particularly as it relates to hypertension, towards which coffee has always been regarded as a kind of poison. The last few years have been riddled with a myriad of studies that have shown the opposite and suggested that coffee has strictly health-promoting properties, with the potential to be beneficial, especially in cardiovascular and metabolic diseases.

Answering the doubts (once again) comes a review of studies on the subject, just published in the New England Journal of Medicine (1), in which epidemiologists and nutritionists from the schools of public health of Singapore and Harvard universities analyzed the most reliable research.

In summary, the results suggest that the benefits of coffee outweigh the risks. With the caveats - moderate consumption, good health, little in pregnancy, zero as a child. Let’s start by reviewing the positive findings and then discuss how a gene variation might counter some of these benefits.

Caffeine increases lucidity

Caffeine acts on the central nervous system by increasing lucidity and reducing tiredness and sleepiness. Fifteen to twenty minutes after drinking espresso, cappuccino, or American-style coffee, it reaches the brain and binds to the receptors of a neurotransmitter, adenosine, involved in the sleep cycle. It takes its place and inhibits the urge to sleep.

Not only that, a 2014 study published in The Journal of Nutrition (2) found that caffeine could improve mental function (in the short term) and help consolidate new memories. But it certainly can't compensate for the decrease in performance if there are successive late nights.

Not too hot!

The idea that dark drink is connected to dangerous drug comes from research in the 1970s that linked them to increased rates of cancer and heart disease. In 2016, however, the World Health Organization reversed these assumptions and clarified that there is no evidence of an increased risk of cancer.

On the contrary, statements by the World Cancer Research Fund indicate that coffee appears to protect against some cancers, such as cancers of the liver and endometrium (the mucous membrane covering the uterus). The advice rather is to let the liquid get a little cooler. It appears that the temperature of any very hot drink is responsible for increasing the probability of oesophagal cancer.

Antioxidant effects

Coffee contains several hundred biologically active phytocompounds, including antioxidants such as polyphenols and small amounts of magnesium, potassium, and vitamin B3 (niacin).

As stated in the New England Medical Journal (1) meta-analysis, this cocktail of molecules could reduce oxidative stress in cells by fighting excess free radicals and modulating glucose and fat metabolism. However, obesity and type 2 diabetes do not disappear if coffee is highly sweetened and added to a diet rich in sweets and junk food.

No harm to the heart

What about the effects of caffeine on the heart? Arrhythmia? Fibrillation? Previous investigations already tended to rule out a negative effect on cardiovascular disorders, so the latest review of studies confirms that no evidence drinking coffee increases the risk of death from heart disease or any other cause. As for blood pressure, it can rise immediately after a cup, but with regular consumption, according to research, the body develops a form of tolerance that protects against the danger of developing hypertension from coffee. Mitigating the effect on blood pressure could be a compound, chlorogenic acid. The way caffeine is absorbed, however, is an individual matter, so each person should decide for himself, especially if he has health problems.

Variability

Studies have shown that there is a selection of patients who are “responders” to caffeine. Hence, there is a population of patients who are predisposed to a greater effect of caffeine, which increases systolic and diastolic blood pressure values, as can be seen in Figure 1, which means that there is a kind of predisposition to be affected by the blood pressure effects of caffeine and decaffeinated coffee.

This has nothing to do with the effects of coffee, but much more with an individual’s response.

Figure 1:Pressure reactivity against caffeine, six hours after its ingestion in hypertensive responders and non-responders’ patients (3)

There is an extremely high variability to caffeine; even among us, there are individuals who are unable to tolerate caffeine even at very low concentrations because they experience symptoms such as anxiety, nausea, nervousness, or insomnia even if they drink just one coffee.

What lies behind this variability in caffeine? The influence of genes!

There is a polymorphism that is in the gene, that codes for cytochrome P450-1A2, this is a gene that codes for an enzyme, which is responsible for the process of detoxification of caffeine, it performs a series of demethylations of caffeine, which transform caffeine into other metabolites that can then be excreted (Figure 2)

Figure 2. Metabolites of caffeine demethylations

At the level of this gene, there is a polymorphism that presents an AC substitution that can determine the effectiveness of this enzyme, i.e. carriers of the AA genotype are fast metabolizers (subjects, where, the enzyme works at full capacity), while the presence of even a single substitution, i.e. AC or CC, means that subjects are slow metabolizers, the caffeine will remain in the bloodstream for longer, and will therefore be responsible for the effects of caffeine such as alertness, attention, nervousness for longer (figure 3)

Figure 3: Polymorphism is localized in the gene that codes for cytochrome P450-1A2, this is a gene that codes for an enzyme, which is responsible for the detoxification process of caffeine

Given the nature of caffeine's physiological effects, some researchers have wondered if it could be related to an increased risk of cardiovascular disease in all subjects or only in these “fast or slow metabolizers”. This study was carried out in Costa Rica, the “Costa Rica hearth study” (4), involved around 4000 subjects, which measured the risk of cardiovascular pathology in subjects who were “fast metabolizers” versus subjects who were “slow metabolizers”, also distinguishing the amount of coffee that was consumed to understand whether coffee consumption could modulate this association (figure 4)

“Figrue 4: Costa Rica hearth study” (4). Costa Rica Hearth Study (n=4,028) [observational].Cases (n = 2,014) with a first acute non-fatal MI and population-based controls (n = 2,014) were genotyped. A food frequency questionnaire was used to assess coffee intake.

What emerged from this study (see above) is that in subjects who are “fast metabolizers” (left columns), low coffee consumption was even protective, compared to those who did not consume it, against various CV diseases. But if we look at what was happening in “slow metabolizers” (right columns), caffeine consumption, especially when it went beyond two to three cups per day, induced an increased CV risk. So, from here we understand how the difference in tolerance to this substance, can affect health.

How to test for the CYP1A2 gene? Depending on your reaction to caffeinated drinks, you have probably already intuited whether you are a fast or slow metabolizer of caffeine. But how do you test to find out for sure? You can test for the presence of the caffeine gene through a simple saliva or blood test that analyses DNA. For it to be meaningful, nutrigenetic information should be filtered by a qualified specialist who is able to give it the correct value!

How many cups a day

With all the good that can be said about it, nobody should drink too much coffee. The European Food Safety Authority (EFSA) (5) stated in 2015 that “caffeine intake of up to 400 milligrams per day, consumed throughout the day, raises no safety concerns for healthy adults”.

Going beyond that, one risks suffering the unwanted consequences of the substance, from nervousness to tachycardia.

How to regulate? Caffeine sources are varied (Figure 6), from chocolate (around 18 milligrams in 30 grams of dark chocolate) to energy drinks and some fizzy drinks (40 milligrams in a cola-type can). Caffeine is contained in green and black tea: also called theine, it is the natural pesticide that the plant develops to protect itself and, in a cup, (220 millilitres) there are about 50 milligrams. In an espresso, on the other hand, the quota is around 80. So, with two or three cups of coffee and a cup of tea, you will keep away from that maximum which, on a mean average, it is best not to exceed during the day. It is likely that those who are sensitive to caffeine, already self-regulate their consumption, because the negative effects of too much caffeine are not enjoyable. Those who have problems sleeping should not drink coffee in the late afternoon: the half-life of caffeine, i.e., the time required for the body to remove 50 per cent of it, is on about four hours on average, varying from two to eight hours.

In conclusion, a curiosity: the activity of the enzymes involved in caffeine is partly inherited, in the sense that a slower metabolism of the substance can be genetically determined.

This article is the summary of the final thesis entitled “Coffee and health: from a Nutrigenomic and Cardiovascular Perspective”, submitted by the author at the end of the advanced course at the University of Camerino named “Molecular Aspects of Nutrition: from Nutrigenomics to Functional Nutrition”, with Prof. Gianni Sagratini as the thesis supervisor.

References:

Van Dam, R. M., Hu, F. B., & Willett, W. C. (2020). Coffee, Caffeine, and Health. N Engl J Med, 383, 369-78.

Beydoun, M. A., Gamaldo, A. A., Beydoun, H. A., Tanaka, T., Tucker, K. L., Talegawkar, S. A., ... & Zonderman, A. B. (2014). Caffeine and alcohol intakes and overall nutrient adequacy are associated with longitudinal cognitive performance among US adults. The Journal of nutrition, 144(6), 890-901.

Cornelis, M. C., El-Sohemy, A., Kabagambe, E. K., & Campos, H. (2006). Coffee, CYP1A2 genotype, and risk of myocardial infarction. Jama, 295(10), 1135-1141.

https://www.efsa.europa.eu/en/topics/topic/caffeine (2015).