Why Is Caffeine Not Affecting Me?


Caffeine is one of the world’s most consumed drugs. It can be found in numerous forms of food as well as beverages such as coffee, energy drinks, soda, and chocolate.1,2 A study suggested that coffee and tea are the most widely consumed caffeine-containing beverages worldwide.3 Roughly 89% of the adults in the USA consume caffeine-containing drinks regularly, with an average daily intake of about 180mg/day or two cups of coffee.

Meanwhile, adults and children in the UK consume about 130mg/day and 35mg/day of caffeine, respectively.6 This suggests that many people love caffeine. Even if you are not a coffee drinker yourself, surely you will see people around you drinka cup of coffee. 

But what is so special about this caffeinated drink? 

First of all, caffeine is widely known for its stimulant effect. It is consumed to increase focus and reduce sleepiness and fatigue.13 

How does caffeine promote wakefulness?

Adenosine is a neurotransmitter that helps to regulate your sleep-wake cycle. In other words, it acts as a messenger and tells your brain you are sleepy. Given its similar shape to adenosine, caffeine will bind to adenosine receptors and block them.12 Thus, you can say that caffeine is an adenosine imposter or scientifically known as an adenosine antagonist.39 

A study suggested that caffeine intake (up to 4.3mg/kg) can block up to 50% of adenosine receptors in our brain.30 Thus, it prevents adenosine from acting on its receptor, blunting the fatigue effect of adenosine. As a result, you will become less sleepy, and you will be more awake.12 No wonder some people feel less energetic if they do not sip their coffee first thing in the morning. 

However, some people can fall asleep or still feel the same even after drinking their coffee. It feels like caffeine has no effect  on them. Why? 

This article will discuss why some people are not affected by caffeine. 

Benefits of Caffeine

Many people consume caffeine daily. Thus, it is vital to know its effect on our health. A plethora of studies have shown the beneficial impact of caffeine consumption on our health. Older studies suggested that caffeine consumed in low doses can lower your anxiety levels and improve your mood.7,8 

Furthermore, caffeine is also shown to enhance your memory and effective learning. A study in 2016 demonstrated that students who consumed caffeinated coffee performed significantly better in an explicit memory task than the ones who drank decaffeinated coffee.9 However, there were no differences when the participants did the implicit memory test or when they performed the memory test in the late afternoon.9 

Another interesting study also demonstrated similar findings. A study by Smith suggested that caffeine consumption can improve people’s memory but only in extroverts. Introverts performed better with decaffeinated coffee.10 

Side effects of Caffeine

Despite its beneficial effects on our health, caffeine can also contribute to several adverse effects. Its side effects can be mild to severe. The negative impact of caffeine is generally due to the dose consumed and the individual’s sensitivity to it. The mild side effects include anxiety.11

Moreover, several scientists have extensively studied the role of caffeine on the risk of developing cardiovascular disease. A review published by Frontiers in Psychiatry explained that caffeine or coffee consumption can increase blood pressure.2 .

What stops caffeine from working?

Several factors that could contribute to the ineffectiveness of caffeine are listed below.


Genetics might be the culprit here as they play an important role in an individual’s response to caffeine. 

Primarily, caffeine metabolism occurs in the liver and is broken down by an enzyme called CYP1A2.2 CYP1A2 also occurs naturally in coffee beans.36 It exists in two different forms.34 One of them tends to metabolize caffeine faster than the other. Thus, individuals who have this form of CYP1A2 are commonly classified as “fast caffeine metabolizers”, making them feel less responsive to the stimulant’s effects of the caffeine.35 

Likewise, NAT2 is another enzyme that breaks down caffeine. The rate of caffeine metabolism also depends on this NAT2 gene which is also influenced by ethnicity.39 


Another reason your coffee does not give you the "kick" anymore is that you develop a caffeine tolerance. 

It occurs when the effect of the caffeine eventually decreases after regular consumption. According to research, caffeine tolerance develops in individuals who consume 1.5 to 3.0 mg/kg per day of caffeine for 28 consecutive days.32 A study discussed that daily caffeine intake might lead to the creation of new adenosine receptors, which allow adenosine to bind to it. Caffeine could not block all the receptors and thus, reduce its effectiveness in promoting wakefulness.31 

Extreme fatigue

Caffeine may not affect you because you’re fatigued and suffer from sleep deprivation. It might be a sign that you should rest. 

As mentioned before, adenosine is a messenger that urges you to sleep. Although caffeine temporarily blocks the adenosine receptor, it does not mean that it prevents the production of adenosine. Adenosine levels will increase the more time that you are awake. As a result, the build-up of adenosine production might make you more tired. When you sleep, the adenosine concentration in your body will decrease.40 Thus, it is better for you to get some sleep.

Low dosage of caffeine

Maybe the reason why you can’t feel the full effects of caffeine is that the dosage is too low for you. You could increase the amount of caffeine to make you feel awake. However, be mindful not to exceed the recommended dosage or develop a caffeine addiction.

Lifestyle and medical conditions

How fast the caffeine is metabolized is also affected by your lifestyle, such as smoking. Experts explained that smoking can increase caffeine metabolism due to the properties of nicotine in the cigarette.37,38 Therefore, smokers have to increase their caffeine intake to feel the buzz/rush. 

Furthermore, Pharmacological Reviews Journal also discussed the impact of diet on caffeine clearance. The journal explained that grapefruit juice intake will slow the breakdown of caffeine. On the other hand, your body will metabolize caffeine faster when you eat a lot of broccoli and brassica vegetables as well as a high amount of Vitamin C.39 Therefore, the reason why you barely feel anything after your morning coffee might be due to your diet. 

Medications might be another reason why your coffee is not affecting you. Drugs or treatments with some medications might influence CYP1A2 activity, which will impact the speed of caffeine metabolism in your body.39 

Alternatives to feel energised

Drinking coffee is not the only way that can help you to combat tiredness. Several alternatives can make you feel energetic, mentioned below.


World Health Organization (WHO) suggests that doing some physical exercise is better than none.16 They also emphasize that all adults should exercise regularly and aim to do at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity physical activity per week.17 Meanwhile, children and adolescents should do moderate-to-vigorous intensity exercise for an average of 60 min per day.

Doing exercise can make you feel energized. A study by de Vries et al.  investigated the effect of exercise in reducing study-related fatigue in university students. The study demonstrated that students in the exercise condition were less tired and less exhausted than those in the control condition. Furthermore, there was an improvement in sleep quality among students who exercised. In the long run, the exercisers have improved their sleep quality, fatigue, and emotional exhaustion.14 

Moreover, a recent meta-analysis also demonstrated that physical activity reduces fatigue in patients with multiple sclerosis (MS).15

Limit screen time before bed

A healthy adult should get 7 or more hours of sleep per night.19 Meanwhile, school-age children (6-13 years) and teenagers (14-17 years) should obtain 9-11 hours and 8-10 hours of sleep per night, respectively.18 However, with the growth of social media and technology, we tend to neglect our good night’s sleep and spend more time with our gadgets before bed.

Scientists said the ubiquitous use of smartphones and the normalization of portable electronic devices in the bedroom increase the prevalence of sleep loss among school-age children, adolescents and adults.18,20 Sleep loss can result in tiredness and fatigue.21 A review elucidated that long screen time before bed can disrupt sleep quality and increase daytime tiredness among children and adolescents.22 Therefore, it is vital to reduce your screen time before bed.

Sleep hygiene

Sleep is optimal for promoting health and preventing tiredness.21 Therefore, having good sleep habits, also called sleep hygiene, is a must. Most common and evidently supported sleep hygiene recommendations include23:

  1. Avoid nicotine and alcohol before bedtime:lLike caffeine, nicotine makes you feel awake. Excessive smoking and regular nicotine administration can disrupts your sleep. 
  2. Avoid daytime naps
  3. Exercise regularly
  4. Consistent sleep timing
  5. Reduce bedroom noises


Water is essential to keep us energised. Lack of water can cause dehydration which is detrimental to our body. 

Benton and Young elucidated that reduced body mass by >2% due to dehydration are linked to increased fatigue and lower alertness.24 Another study also concluded that an increased intake of water in people who drink less water (<1.2 L/day) makes them less tired.25 Therefore, it is crucial to drink enough water in a day. 


Getting enough nutrition can boost your body’s energy levels and provide fuel for us to perform physical activity.26 

All the B vitamins except folate are essential for energy production.26 You can get vitamin B from animal products such as red meat, dairy and eggs.27 Another top source of vitamin B is whole grains and legumes. 

Vitamin C, which can be found abundantly in citrus fruit and leafy vegetables, is also a good source of energy.29 Apart for vitamin C, iron and magnesium are also essential in making us more awake.26 

Spending time outdoors

Getting kissed by the sun is another way to increase your energy. A study in 2017 demonstrated that high exposure to morning light might improve your sleep quality and make you fall asleep faster at night.33 Therefore, you might feel better the next day!


Caffeine makes you feel awake and energized. However, some of you might barely feel anything after your coffee. This article explained several reasons you are not achieving the desired effect of caffeine. But then again, coffee is not the only way to unleash your chaotic energy. There are various ways to make yourself feel more awake and energetic. 


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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Sentia Racha Keyulong

Bachelor of Science - BSc, Psychology, The University of Edinburgh, Scotland, Scotland

Sentia is an experienced Research Assistant and Medical Writer.

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