Curious about coffee

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Some people take a nice break and recover, others shake and shudder. Nobody can escape the effects of a cup of coffee. This is a cause for concern for researchers, but so far they have not found any good reason to stop slurping.

Every day millions of people take a drug to boost their energy levels to go to work. Or they drink their first dose of the day when they reach the workplace, sometimes together with colleagues in the same situation. The dose needs to be tested carefully or there will be unpleasant side effects. 

For some reason people in Nordic countries such as Sweden and Finland drink the most amount of coffee.

“The best explanation I’ve heard is that we have terribly dark, gloomy, depressing winters. Maybe we need something to get through them”, says Bertil Fredholm, Professor emeritus of Pharmacology at Karolinska Institutet who was one of the first to describe how caffeine, the psychoactive substance in coffee which is also found in tea and chocolate, affects the body.

A cup of coffee can do a lot of things depending on how much caffeine it contains, but also depending on who drinks it and when. Some people get a boost, recover and perform at their best, others mainly feel jittery. Caffeine can heighten our senses when we need it the most. But if you drink coffee at the wrong time it can mess with your sleep and transform you into a hollow-eyed zombie.

How can such a small molecule such as caffeine lead to all this? Well, it does this by neutralising another molecule – adenosine.

Bertil Fredholm“Adenosine is released from our cells during the day and has a subduing, tiring effect which leads to us eventually falling asleep. It is also released during strenuous work, which results in a feeling of tiredness later”, says Bertil Fredholm.

In the 1970s together with colleagues he discovered that caffeine binds to the receptors in the body which are intended for adenosine, which makes them inaccessible for adenosine. However, as caffeine is not adenosine, the signals which normally make us tired do not occur, so we become more energetic than we would have been until the caffeine is broken down.

According to Bertil Fredholm, referring to caffeine as a drug, in fact the world’s most used drug, is correct if by drug you mean a substance which stimulates the nervous system, is addictive and can lead to withdrawal symptoms. It is certainly true that many people feel that they need to have their daily cup (at least) to function, and that if they stop then they will instead get a headache and generally feel grouchy for a few days. However, stronger drugs are naturally part of a completely different league.

“The craving and feeling of reward is completely different from that of, for example, nicotine, morphine or alcohol. I don’t think that people drink coffee mainly to combat withdrawal symptoms, they do it because they want to and it generally makes them feel good”, says Bertil Fredholm.

Those who are particularly sensitive or drink too much coffee may experience side effects, such as sleeping problems, palpitations and anxiety. Considering that caffeine affects basic physiological processes in the body, combined with the enormous amounts which are consumed by the population, researchers have also suspected that coffee could have an impact on the risk of slightly more serious illnesses.

In the 1970s and 1980s researchers reported that they had seen signs of a higher risk of cardiovascular diseases as well as bladder cancer and pancreatic cancer among coffee drinkers. In 1991 the popular drink ended up on the World Health Organization’s list of “possibly causes cancer” dietary factors and it got a very bad reputation.

However, researchers continued to investigate the alleged risks in larger and more long-term studies. It was eventually found that the cancer risks were not at all caused by drinking coffee, but other factors such as smoking. However, there is a link between coffee and cardiovascular diseases, but this has been adjusted and explained.

“In previous studies it was found that coffee contributes to bad blood lipids which can increase the risk of cardiovascular diseases. We now know that this is only true for unfiltered coffee such as, for example, boiled coffee, which we used to drink a lot in Sweden in the past”, says Susanna Larsson, Senior researcher of nutritional epidemiology at the Institute of Environmental Medicine, Karolinska Institutet, who has conducted several studies on the link between coffee and different illnesses.

The reason is that unfiltered coffee, such as Swedish boiled coffee, Arabic coffee and, to a lesser degree espresso, contain cholesterol-raising substances, diterpenes. Filter coffee is virtually free of these substances as they get trapped in the coffee filter. 

Pregnant women are advised not to drink more than three cups of coffee per day as it is suspected that high doses of caffeine increase the risk of miscarriage. Apart from this, current research does not support the notion that drinking coffee poses any serious health risks, according to Susanna Larsson.

Coffee has been removed from the World Health Organization’s list of carcinogens. However, there is a warning about drinking very hot coffee (or other beverages) as the temperature may probably increase the risk of oesophageal cancer. 

On the contrary the health effects mainly appear to be positive. A recently published study on over half a million people in ten European countries showed that coffee drinkers had lower mortality rates linked to cardiovascular diseases, primarily stroke, compared to those who do not drink any coffee at all. The safest link is seen for type 2 diabetes. Those who drink 5-6 cups of coffee per day have roughly 30 per cent lower risk of getting type 2 diabetes, according to Susanna Larsson.

“In this context the research is unusually unanimous, study after study shows that coffee consumption is linked to a lower risk of diabetes. There is also a good physiological explanation, as we know that caffeine increases insulin sensitivity with lower blood glucose levels as a result”, she says.

In different studies, including those of Susanna Larsson and her colleagues, coffee has also been linked to a lower risk of different forms of cancer such as uterine, liver and gallbladder cancer. However, the studies on cancer are somewhat contradictory.

“For example, other researchers have seen a link between coffee consumption and lower risk of colon cancer, but we haven’t been able to confirm this in our Swedish data”, says Susanna Larsson.

Even for cancer there are ideas on which mechanisms may be involved. Coffee contains a large amount of antioxidants which can protect the cells from injuries, but this may also be linked to caffeine.

“Some tumours release a lot of adenosine, which inhibits the body’s immune cells that can destroy tumour cells. As caffeine in turn inhibits adenosine, it is possible that there is a cancer prevention effect”, says Bertil Fredholm.

As if this was not enough, there is also research which connects coffee drinking to a lower risk of Alzheimer’s disease and Parkinson’s disease.

“In terms of Parkinson’s disease, there are good studies on physiological mechanisms which, together with clinical trials of substances similar to caffeine verify the conclusions of several major epidemiological studies”, says Bertil Fredholm.

So coffee has made a complete U-turn and now seems to rank highly in all camps. A delicious everyday drug which may save lives – can it get any better? However, Susanna Larsson points out that research support for the positive effects varies significantly, and it is easy to believe them a little too early.

“I also thought that there was quite good evidence for coffee reducing the risk of Alzheimer’s disease. That was the impression I got, even in the research sphere. But when I started to develop an interest in the issue, I found out that only three small studies had been published. This is too little to say that there is any real support for this claim. But it’s definitely interesting to continue studying  the issue”, says Susanna Larsson. 

Patrik Magnusson, foto: Ann SvalanderAccording to Patrik Magnusson, Senior researcher of medical genetics at the Department of Medical Epidemiology and Biostatistics, proving how a dietary factor impacts health is more difficult than you would imagine. He points out that it is completely natural that a drink such as coffee, which tampers with our nervous system and is consumed by millions, appears to have a strong link with different diseases in the research. The difficult part is proving that it is really caused by drinking coffee. 

Every research question has its pitfalls, which may be more or less easy to control. For example, studies on coffee consumption and reduced type 2 diabetes need to take into account what Patrik Magnusson refers to as the ‘cream roll effect.’

“In Sweden we take a lot of breaks to fika and have coffee or tea. But do we know whether coffee drinkers eat exactly the same amount of cake and cookies as everyone else around the table? It might be the case that coffee drinkers don’t feel the same sort of craving for cake and cookies, in which case that would contribute to a lower risk of diabetes for this group. I don’t think that we really know the answer to this question”, he says.

If the positive findings turn out to be true, it is a welcome bonus for the world’s coffee drinkers, but the most important thing is perhaps that we are able to say that coffee is not lethal after all.  Neither Susanna Larsson nor Patrik Magnusson, who both like coffee, think that the health considerations need to control the choice to drink coffee.

“No, I think that you should drink coffee if it makes you feel good. There is still a lot which we don’t know about the potential health effects. But at least there are not any major risks, that has been clarified by the research”, says Susanna Larsson.

However, based on his personal experience Patrik Magnusson advises people with sleeping problems to review their coffee consumption.

“I stopped drinking coffee after 2pm and it made a huge difference to how I sleep at night, now I sleep as though someone has knocked me out with a bat”, he says.

Whether he cut down on drinking coffee based on his own free will can be discussed. According to his research results, genes largely govern the coffee drinking habits of people, an idea which tends to be slightly astonishing for many people.

“That sounds completely strange, of course I decide whether I should drink coffee and not my genes. That is how most people react when we present the results, but us twin researchers aren’t that surprised”, says Patrik Magnusson.

Research on twins has showed that they often have the same coffee habits even if they grow up separately – if one of them drinks coffee then it is highly likely that the other one will also drink it. Results of twin studies show that 40 percent of the variation of coffee drinking in the population is explained by genetic differences.

The background is that caffeine is broken down in the body to several metabolites which impact the body in slightly different ways. The enzyme system which controls this process, including the rate at which metabolites break down, differs between different individuals depending on their genes. Thus there is a genetically controlled variation in how we are impacted by a cup of coffee. For example, not everyone finds it difficult to sleep after a cup of coffee in the evening.

“For coffee drinkers it’s simply a matter of choosing to drink coffee if it makes you feel good, and stopping if it makes you feel bad. But it’s interesting that theoretically we can predict these choices based on a genetic test”, says Patrik Magnusson.

However, first the genes involved need to be identified. Together with international colleagues, Patrik Magnusson has recently compared genetic data of almost 10,000 people with plasma levels of caffeine and their different break down products as well as the coffee consumption of individuals. Several genes which affect coffee consumption were identified. Among other things, researchers found that genes which break down caffeine slowly are linked to reduced consumption of coffee. 

The genetic knowledge gives rise to an interesting opportunity for future research on the health effects of coffee. As genes are not linked to other underlying associations, such as the ‘cream roll effect’, or reverse causation, such as that an illness may cause lower coffee drinking rather than the opposite, researchers would be able to use them to get a clearer view of the causal links.  

However, before we go and get tested for the coffee gene, researchers need to identify some more coffee genes. While we are waiting, researchers suggest that we enjoy our coffee breaks.

3 things you did not know about…

  • Coffee and time: No, it is perhaps not enough to skip your evening coffee if you have sleeping problems. It takes 3-7 hours for half of the caffeine in your body to break down, so coffee consumption of the entire day affects the caffeine level when you go to bed.
  • Coffee and urine: No, coffee is not diuretic. Caffeine stimulates the kidneys to produce urine, but this only means that you feel the urge to urinate faster, not that you lose more fluid.
  • Coffee and death: No, you do not drink coffee with your life at stake. Or for that matter, if you manage to consume the deadly dose of caffeine by drinking roughly 100 cups of coffee at once, then you will die. But that is difficult.

Source: Bertil Fredholm

Text: Ola Danielsson, first published in Medicinsk Vetenskap nr 3 2017