International Coffee Day – Your Guide to Caffeine: Its History, Biology, Genetics and Smarter Caffeine Habits in the Precision Health Era

Dr. Adam Jameson | Precision Health Executive | Pharmacist | REVIV Global

Coffee is a ritual, social glue, and a daily part of life - yet beneath all that, it’s the world’s longest-running biochemical experiment. On International Coffee Day, as billions of us brew our favourite cup, it’s worth asking: why does caffeine affect each of us so differently? Two people can drink the same coffee and have completely different experiences (1) – with one getting laser focus, and the other getting the jitters and being wide awake until midnight. The answer lies at the intersection between chemistry, genetics, and lifestyle. In this article, we’ll explore the origins of coffee, the science underpinning caffeine, and how to enjoy coffee in the precision health era – using genetic insights to guide your caffeine kicks.

Coffee originated in Ethiopia, spread via Yemen and the Ottoman Empire, and later took Europe by storm as it became a global commodity. Coffeehouses became hubs for trade, politics, and ideas, as caffeine-fuelled conversations powered innovation and progress. Today, coffee is one of the most traded agricultural products worldwide. Originally, coffee beans were chewed or pressed, then later soaked, roasted, and brewed into the aromatic drink we have become familiar with (2). The arrival of coffee in London sparked controversy, with a royal ban on coffeehouses being issued in 1675 – prompting public backlash and ultimately a withdrawal of the order (3).

But what drove humanity’s obsession with coffee? Caffeine, of course. Caffeine is a methylxanthine compound that is rapidly absorbed in the gut and can cross the blood-brain barrier, making its effects felt quickly. Typically caffeine blood concentration peaks within 30-60 minutes after consumption (4). Caffeine’s mechanism of action is primarily through its ability to block adenosine receptors (A1/A2A). Adenosine accumulates throughout the day as a by-product of ATP use (ATP is the body’s primary cellular energy currency). The gradual build-up of adenosine prepares the body for sleep by reducing neuronal firing in the brain and promoting sleepiness via A1/A2A signalling. As caffeine blocks this effect, it can leave you feeling more alert and less tired. Caffeine therefore does not create energy, but rather masks tiredness and dials down the body’s natural sleep-pressure signalling (5).

The benefits of coffee are not all down to caffeine. Coffee contains many bioactive compounds, so although you might feel the effects of caffeine, the positive effects of coffee go further. This is sometimes referred to as coffee’s ‘entourage effect’. Coffee beans are packed with polyphenols, antioxidants, and are even a source of fibre – all of which enable coffee to support metabolism, reduce oxidative stress and inflammation, and improve gut health (5). Hence why even decaffeinated coffee (which may still contain up to 15mg of caffeine per cup) provides consumers with health benefits and similar long-term positives to caffeinated coffee.

There is a range of effects that coffee can have. In the short-term caffeine increases alertness, speeds up reaction time, and even reduces perceived exertion during endurance exercise. Pre-workout caffeine is a useful tool to improve physical performance (6). In the longer term, large studies have found that coffee consumption is associated with more benefits than harm

when considering multiple outcomes, including lower all-cause mortality and reduced risk of diabetes and some liver conditions (7). This likely reflects polyphenols, antioxidants, and fibre-like compounds in coffee that support metabolic, vascular, liver, and gut health (8,9). It must be stressed that these are findings from observational studies across cohorts and do not necessarily prove causation. That said, the findings are consistent and have been repeated across several large studies (10).

Despite these benefits there are some potential consequences. For example, research demonstrates that blood pressure can temporarily rise in some individuals, and unfiltered coffee may raise LDL cholesterol (11,12). This highlights how brewing techniques can impact outcomes from coffee. Timing is also key – the half-life of caffeine is around 5-6 hours (range 3-10+ hours depending on the person), meaning that if you drink a coffee at 4pm, you can expect around half of the caffeine dose to still be circulating in your blood at 10pm (5). Drinking coffee later in the day has been found to reduce total sleep time and impair sleep quality (13). This underscores the fine balance between deriving benefits from coffee, versus the potential downsides.

When we factor in genetics, our relationship with coffee begins to unfold. Firstly, the way in which our body handles caffeine can differ between individuals. A enzyme in the liver called CYP1A2 is the body’s primary route for breaking down and clearing caffeine. Caffeine is continuously metabolised by the CYP1A2 enzyme in the liver to produce metabolites. As levels fall, caffeine’s effects subside, at a rate that varies dependent on the individual. The evidence about caffeine metabolism points to differences in how quickly we can break down caffeine – translating broadly into three categories often grouped as fast, intermediate, or slow CYP1A2 metabolisers (14).

Slow metabolisers may see caffeine linger for longer, as their bodies, or more specifically their CYP1A2 enzymes, are slower to process and metabolise caffeine. Conversely, fast metabolisers possess the ability to process and clear caffeine quicker. Intermediate metabolisers sit somewhere in-between. Our CYP1A2 metaboliser profile influences caffeine tolerance and may modify some health associations of coffee. In the short-term, slower metabolisers may see a greater effect of caffeine on their sleep or blood pressure (5,13). In the longer-term, some studies report higher cardiovascular risk with high coffee intake in slow metabolisers (15), however the evidence is context-dependent. This points to an interaction between our genes, the amount of coffee we consume, and the outcomes we experience.

Secondly, the way in which coffee exerts its effects on our bodies can also differ. As mentioned, caffeine works by blocking adenosine receptors and evidence suggests that variation in the genetic code for the A2A adenosine receptor (ADORA2A) can alter how sensitive we are to caffeine. Two people consuming the same dose of caffeine can therefore have quite different initial responses. Certain ADORA2A gene variants are linked to stronger caffeine-induced anxiety and greater sleep disturbance from the same dose (16,17) This helps to explain why some people can have a 5pm espresso and still achieve great sleep, while others have a midday latte and feel jittery for the rest of the afternoon.

Use your genetics and lifestyle to time and dose caffeine so that it works for you and not against your sleep and focus:

• Slow CYP1A2 metabolisers: shift caffeine intake to earlier in the day, set a coffee curfew 8-10 hours before bedtime (or even earlier if sleep is impaired), cap coffee intake to one cup per day, and consider decaf coffee thereafter.
• Fast CYP1A2 metabolisers: you may tolerate later intake of coffee and multiple coffees per day, but be mindful to still protect sleep by keeping most coffee intake to before mid-afternoon.
• ADORA2A gene variability: your genotype may mean you are more sensitive to the effects of caffeine therefore consider using smaller, earlier doses, and pair with food to reduce jitters and anxiety.
• Decaffeinated coffee: although a great option, be wary that some decaf coffee options have been washed with chemicals that, if ingested, require detoxification via the body’s detox pathways. Although exposure is low, if you prefer to avoid exposure completely, opt for Swiss water or CO2 process decaf coffee, which are solvent-free. Despite this, decaf coffee still has benefits, as it contains the polyphenols and fibre-like compounds that regular coffee does.
• Athletes: you may benefit from caffeine 30-60 minutes pre-workout at a dose of 1-3mg/kg. Start with a low dose and gradually build up. Be aware of the impact this may have on sleep (and therefore recovery) if you’re working out later in the day.

Our genetic blueprint helps to explain the differences we see in how people consume and respond to coffee. Be mindful though, other factors such as medicines, liver function, and pregnancy can all affect CYP1A2 activity.

Being armed with information about caffeine is one thing, but knowing insights into your personal relationship with caffeine is another. This is where precision health can bring data to life, translating individual-level data and existing evidence into actionable lifestyle changes that you can utilise in everyday life to promote healthier living (18). Learning about your CYP1A2 genotype, through a genetic test like the 10X Health Precision Genetic Test available from REVIV, helps predict whether you are a fast or slow caffeine metaboliser. With this information, among all the other genetic insights the test offers (including how well you detoxify for decaf coffee drinkers), you can personalise your coffee routine and utilise coffee as a tool to help you achieve your health and wellness goals.

Being able to predict response to caffeine is one thing, but having data to validate predictions and generate a feedback loop is now possible due to wearables (19). Coffee is loved for its energising effects, yet we know caffeine can affect how our bodies rest and recover (20). Some wearable devices can highlight these effects, by tracking sleep patterns, recovery, and heart rate. Metrics such as total sleep time, sleep stage duration, and nocturnal heart rate can reveal how caffeine may delay sleep onset or reduce sleep quality. Some wearables now offer personalised ‘caffeine windows’ to suggest the latest safe time to enjoy coffee without impairing sleep. These recommendations are developed based on dynamic recovery data and nudge users towards healthier caffeine habits that align with optimal rest and performance.

Not all energy boosts need to come from caffeine. In the precision health era, we are rapidly improving how well we understand the impact of sleep, nutrition, hydration, and exercise on energy levels. At REVIV we offer IV therapies to complement these different lifestyle factors. Pairing a precision coffee routine with positive lifestyle changes, plus an appropriate IV therapy from REVIV clinics globally, can help you feel and function better.

On International Coffee Day, level up your coffee routine, and instead of reaching for another top-up, consider starting a personal caffeine experiment. Set your coffee curfew, decide on a caffeine dose, and be mindful of how brewing techniques can influence caffeine outcomes. If LDL cholesterol is on your radar, be sure to use paper-filtered brews to remove LDL-raising compounds from your coffee. To supercharge your sleep, try decaf coffee after your curfew and see what happens. In the precision health era and the rise of wearables – it really is possible to track your relationship with caffeine and alter your routine to make coffee a tool for good and not just a quick energy fix. Remember though, caffeine simply masks tiredness, it does not replace the foundational things we can do to sustain energy like sleep, hydration, nutrition, and exercise.

If you want to go a step further, bring genetics into the conversation. Understanding your CYP1A2 profile can help you time and tailor your coffee intake with confidence, by removing the guesswork. And if you want to explore non-caffeine support, REVIV can help you build energy from the inside out – through nutrition and hydration to support energy metabolism at the cellular level – ensuring your daily brew complements a body already set up to perform. However you drink your coffee on International Coffee Day, let coffee be an informed choice that helps you reach your health goals.

This blog is for educational purposes only and does not replace medical advice. Always consult your healthcare provider if you have any health concerns.

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