Waking up to coffee

Opinion has long been divided over whether coffee is beneficial or harmful to health. Most recent research suggests the beverage is good for us – at least in moderation, as Maria Burke reports

Drinking coffee in moderation is safe. Three to four cups/day has few harmful side-effects for most people, according to a major review of over 200 meta-analyses back in 2017.[1] Yet another review in 2020 concluded that consumption of three to five cups/day is associated with a reduced risk of several chronic diseases – but notes that high caffeine intake can be harmful, particularly in pregnant or lactating women.[2] It also cautions that individuals vary widely when it comes to metabolism of, and sensitivity to, coffee.

Other recent observational studies have found that coffee may actually extend life and reduce the risk of a host of diseases including Type 2 diabetes, chronic liver disease and some types of cancer. It’s also been shown to help irregular heartbeats (arrhythmias) and prevent heart disease. The 2021 European Society of Cardiology guidelines now describe coffee consumption of three to four cups/day as moderately beneficial. Historically, many doctors recommended patients with cardiovascular disease (CVD) or arrhythmias avoid coffee.

So why is coffee good for you? Coffee is chemically complex and contains large numbers of bioactive components. The type of bean, degree of roasting, and preparation method all have an influence on the biochemical composition of the final cup. As well as caffeine, coffee contains polyphenols such as chlorogenic acids (CGAs) and lignans, the alkaloid trigonelline and modest amounts of magnesium, potassium, and vitamin B3 (niacin) along with melanoidins, formed during roasting. These complex molecules contain a wide range of antioxidants, such as CGAs and phenolic acids including hydroxycinnamic acids such as ferulic, caffeic, and p-coumaric acids.

Drinking coffee in moderation is associated with a lower risk of dementia, but the highest risk of dementia is associated with heavy coffee consumption.
David Llewellyn University of Exeter, UK

Polyphenols

The fact that coffee is rich in polyphenols – some of the most powerful antioxidant molecules known in food – could explain its health benefits. Research suggests that CGAs – the most common polyphenolic compounds found in coffee – have antioxidant and anti-inflammatory effects and play pivotal roles in glucose and lipid metabolism regulation and in related disorders, such as diabetes, CVD, obesity and cancer.[3]

A team from the University of Dusseldorf, Germany, suggested recently that the phenolic phytochemicals in coffee have similar beneficial properties to those found in many fruits and vegetables. This is because they all trigger the upregulation of proteins involved in cell protection, notably antioxidant, detoxifying and repair enzymes. The key to this response is the activation of a particular system – nuclear factor erythroid 2-related factor-2 – which induces the expression of cell defence genes.[4]

What’s more, the German team speculates that polyphenols and other non-digestible constituents of coffee like polysaccharides and melanoidins share the ability to modify the composition and metabolic function of gut microbiota, just like similar components of other plant foods.

The antioxidant properties, however, depend on how coffee is prepared, report Bożena Bukowska and colleagues at the University of Lodz, Poland. This team looked at how effective coffee-related polyphenols are at reducing reactive oxygen species and oxidative stress – an imbalance of free radicals and antioxidants – in cells.[5] They found the coffee roasting process influences both polyphenol content and oxidative activity. The lowest levels of active compounds such as CGA and caffeine are found in roasted coffee beans. On the other hand, light coffee roasted for less time and green coffee (raw beans) show the strongest antioxidant properties.

Of course, to produce a physiological effect, polyphenols need to be bioavailable. Several studies have highlighted that about two-thirds of ingested CGAs are intact when they reach the lower intestine, where they are metabolised by gut microbiota, resulting in a wide range of chemical modifications and breakdowns that could account for their biological properties.[6] Other evidence suggests that, similarly to dietary fibres, the coffee melanoidins escape digestion to be eventually metabolised in the colon by different microbial species, resulting in the hydrolytic release of antioxidants, mainly CGAs.[7]

A team from the University of Naples, Italy, has studied the changes occurring in polyphenol composition and the relative differences in antioxidant and anti-inflammatory properties of coffee brews after simulated gastrointestinal digestion using a human colon cancer cell model. They found that levels of polyphenols in the digested coffee brews were higher than those in the non-digested ones.[8] All samples decreased the levels of intracellular reactive oxygen species when compared with untreated cells, while digested coffee samples exhibited higher antioxidant capacity and total phenolic content than non-digested coffee samples. Digested coffee samples also showed a higher reduction in levels of the immune protein interleukin-6 (IL-6) than the non-digested samples; IL-6 stimulates inflammatory and auto-immune processes in many diseases such as multiple sclerosis. Overall, they suggest their findings show that the digestion process may be able to release compounds with higher bioactivity.

Role of caffeine

Another important component of coffee is caffeine, known for its powers to boost concentration and reaction times, and keep us awake. But does it have a role to play in health-promoting effects?

Caffeine is a methylxanthine as is adenosine, which relaxes and dilates blood vessels and also affects the electrical activity of the heart. Caffeine blocks adenosine from binding to the adenosine A1 receptor, which enhances release of the neurotransmitter acetylcholine and inhibits the effects of adenosine.

Caffeine is absorbed almost completely within 45 minutes after consumption, when it spreads throughout the body and crosses the blood-brain barrier. The half-life of caffeine in adults is typically 2.5-4.5 hours but varies largely between people; the activity of caffeine-metabolising enzymes is partly inherited. A variety of factors affect its breakdown such as smoking, which reduces half-life by up to half; and oral contraceptives, which double it. Half-life can hit 15 hours in pregnant women, especially those in the third trimester; while drugs such as certain antibiotics, cardiovascular drugs, bronchodilators and antidepressants can also slow caffeine clearance.

The impact of decaffeinated and caffeinated coffee has not been widely investigated. But now a recent study has focused specifically on the role of caffeine in cardiovascular outcomes. The team, led by Peter Kistler of the Baker Heart and Diabetes Research Institute in Melbourne, Australia, followed almost 450,000 men and women recruited from the UK Biobank who were free of arrhythmias, coronary heart disease, congestive heart failure and ischaemic stroke, for over 12 years on average. Coffee drinkers were compared with non-drinkers after accounting for other factors such as age, sex, diabetes and alcohol consumption.[9] The study found that drinking two to three cups of coffee/day is linked with a longer lifespan. This applied to ground coffee (27% reduction in death from any cause), instant (11%) and decaffeinated (14%). All coffee types were also associated with a reduced likelihood of CVD which was diagnosed in around a tenth of participants. Again, the lowest risk was observed with two to three cups/day; ground coffee was associated with a 20% decreased likelihood, instant 9% and decaffeinated 6%.

It’s a common perception that coffee, or more particularly caffeine, triggers arrhythmias or makes them worse. But the study found that ground and instant coffee, but not decaffeinated, were associated with a reduction in arrhythmias including atrial fibrillation. An arrhythmia was diagnosed in 7% of participants. The lowest risks were observed with four to five cups/day for ground coffee and two to three cups/day for instant coffee, with 17% and 12% reduced risks, respectively.

‘Caffeine is the most well-known constituent in coffee, but the beverage contains more than 100 biologically active components,’ says Kistler. ‘It is likely that the non-caffeinated compounds were responsible for the positive relationships observed between coffee drinking, cardiovascular disease and survival. Our findings indicate that drinking modest amounts of coffee of all types should not be discouraged but can be enjoyed as a heart healthy behaviour.’

However, the study was not able to allow for all factors linked to cardiovascular health, such as socioeconomic status and physical activity. Could it be that it is not necessarily coffee making people healthy, it’s that inherently healthier people consume coffee?

Most research exploring the associations between coffee and heart issues has relied on self-reported coffee consumption. That is, they tend to be observational studies rather than randomised trials. A team from the University of California, San Francisco, US, used a technique called Mendelian randomisation – a type of genetic analysis – to help mitigate these limitations when considering coffee consumption and irregular heartbeat (tachyarrhythmias). Because other behaviour or circumstances cannot affect the genotype, such factors should not confound the result.

Like the Australian team, the UCSF group found no evidence that caffeinated coffee made arrhythmias worse. In fact, their results suggest that coffee intake may in fact reduce the risk, with the strongest evidence associated with developing atrial arrhythmias and supraventricular tachycardia.[10] They also didn’t identify any changes in arrhythmia risk related to different genetic determinants of coffee metabolism, but they point out that there may be other genes related to arrhythmia risk that could affect this association.

The team suggests there are several possible explanations for their findings. For example, caffeine blocks adenosine receptors and high doses of adenosine are known to trigger atrial fibrillation. Coffee’s antioxidant and anti-inflammatory properties may also play a role. Even the properties of caffeine related to neurotransmitters – including dopamine, adrenaline and noradrenaline – could help protect against some arrhythmias.

Too much coffee?

But can coffee be bad for you? Adenosine is responsible for feeling of sleepiness and brings on sleep. Because caffeine can bind to and block adenosine receptors in the brain, drinking coffee can contribute to insomnia and induce anxiety, particularly at high doses and in susceptible people.

Caffeine has also been linked to migraines because it can induce tightening of the body’s blood vessels. Without coffee, blood vessels in a habitual coffee drinker can dilate, increasing blood flow to the head and causing headaches. Caffeine can also be addictive in high doses, especially in teenagers and young adults (pubmed.ncbi.nlm.nih.gov/28174076/).

What’s less well known, perhaps, is coffee’s effect on brain health. In the largest study of its kind, researchers found that high coffee consumption is associated with smaller total brain volumes and an increased risk of brain diseases such as dementia and stroke. The study assessed the effects of coffee on the brain among 17,702 UK Biobank participants aged 37-73.[11]

‘Drinking coffee in moderation is associated with a lower risk of dementia, but the highest risk of dementia is associated with heavy coffee consumption,’ said team member David Llewellyn, Professor of Epidemiology and Digital Health at the University of Exeter, UK. ‘We found that drinking more than six cups of coffee/day was associated with 53% increase in dementia risk in comparison with people drinking one or two cups/day. In theory people who don’t drink coffee at all may benefit from starting to drink in moderation, and heavy consumers may benefit from drinking less. Whether this really makes a difference to the risk of developing dementia is not yet known.’

An observational study of 20,000 participants in the Norwegian city of Tromsø has linked coffee with higher blood cholesterol levels.[12] Åsne Lirhus Svatun and colleagues at the Arctic University of Norway found that espresso coffee consumption was associated with increased levels of blood cholesterol with a significantly stronger association for men, compared with women. Boiled/plunger coffee was associated with increased levels in both sexes and with similar magnitude; filtered coffee was associated with a small increase in levels in women. However, there were no data on the type of cholesterol or risk of heart disease.

‘It’s well known that terpenoids (kahweol and cafestol) found in coffee increase blood cholesterol quite substantially,’ comments Tom Sanders, Professor Emeritus of Nutrition and Dietetics, King’s College London. ‘In the past, people in TromsØ used to drink large amounts of boiled coffee, which was high in these compounds. The levels are lower in expresso coffee, which is often more popular with men. Levels in coffee made in a cafetière are similar to those in boiled coffee. The levels are low in instant coffee. However, it does not really matter what type of coffee you drink if you only have one or two cups/day, but it is important if you drink more.’

References
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6 A. Stalmach, et al; Arch. Biochem. Biophys., 2010, 501, 98
7 N. Aljahdali, et al; Nutrients, 2020, 12, 241
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