ON THIS PAGE
- Before the caffeine tolerance starts developing
- What is caffeine tolerance? How does it develop?
- Building tolerance has a limit – caffeine sensitivity
- People with high tolerance to caffeine may develop Caffeinism
- Physical dependence on caffeine
- Caffeine withdrawal symptoms
- Difference between caffeine tolerance and caffeine sensitivity
- How caffeine affects the brain?
Before the caffeine tolerance starts developing
Caffeine is a drug that acts on the central nervous system and significantly affects other organs such as the heart, blood vessels, kidneys and adrenal hormones.
The following are temporary physiological reactions that occur in the body when an individual is caffeine-naive, takes caffeine for the first time or hasn’t had caffeine for a long time (1):
- Increase in blood pressure
- Increase in heart rate
- Increase in adrenalin (epinephrine) in the blood
- Increase in noradrenaline (norepinephrine) in the blood
- Increase in renin activity
- Increase in catecholamines in urine
These internal physiological changes manifest though the following symptoms, mostly pleasurable:
- Better concentration
- Euphoria – like feeling
- Positive and optimistic feeling
- Good mood
- Increased energy
NOTE: the pleasurable and beneficial effects of caffeine intake come at a price, since negative effects can also occur, such as difficulty sleeping and occasional exhaustion from increased adrenal hormones.
An individual that either never had coffee or any caffeinated drinks or had a long period of caffeine abstinence, experiences the most intense reactions to the first dose of caffeine.
At this point, the build-up of caffeine tolerance hasn’t started and the tolerance to caffeine is at its initial stage.
NOTE: “Caffeine intolerance” is used by scientists to refer to a “caffeine allergy” rather than to describe the stage before caffeine tolerance. The correct term used by scientists is “caffeine-naive”.
Some layman sources use “zero tolerance” which can be also confusing because it can be associated with “not being allowed” to consume caffeine.
- The first caffeinated drink after a long period of abstinence usually causes some temporary physiological reactions which can manifest manifest though familiar (mostly pleasurable and stimulation-like) symptoms.
- The symptoms may be negative if you are caffeine-sensitive.
What is caffeine tolerance? How does it develop?
Caffeine tolerance refers to how an individual adapts to the effects of an increased dose of caffeine.
To achieve the same stimulation-like effects, as with the first dose of caffeine after a period of abstinence (caffeine naive), the dose needs to increase.
If you use caffeine on a regular basis, the body needs to make certain adjustments (described in the image below) in order to maintain the normal physiological equilibrium (as it was before caffeine intake). If you are caffeine sensitive, your body may be unable to adjust (see section below).
The balancing of the physiological changes reduces the symptoms of caffeine. These effects tend to disappear within 1-4 days of the same dose of continuous caffeine intake, which indicates that tolerance to caffeine is regained.
This is what building caffeine tolerance means.
However, if the daily dose is increased again, the side-effects of caffeine intake return, although in a milder form than in caffeine naïve people.
- Tolerance to caffeine can be built with a regular use of the same dose of caffeine.
- With a regular intake of caffeine your body adjusts to maintain a normal physiological equilibrium.
Building tolerance has a limit – caffeine sensitivity
Caffeine tolerance can only increase to a certain point. This limit is set by the maximum amount of enzymes that the body can produce to breakdown caffeine in the liver. This amount depends on each individual.
Therefore, by exceeding a certain dose of caffeine, you will experience a set of unpleasant caffeine overdose symptoms.
Tolerance can be built only up to that personal maximum sensitivity limit.
People who are very sensitive to caffeine, experience overdose symptoms with the smallest amount of caffeine and are not able to build tolerance.
On the other hand, people who are the least sensitive to caffeine are able to build their tolerance up to the point of over-consumption and dependency. This state is called caffeinism (see below).
Most of the population (moderate to high caffeine users), however, can tolerate about 400mg of caffeine daily without experiencing any negative symptoms.
- Each person has a different caffeine sensitivity limit, and the tolerance to caffeine can only be built up to that limit.
People with high tolerance to caffeine (fast metabolizers) may develop Caffeinism
A small percentage of the population can handle caffeine very well and their threshold limit is extremely high, allowing them to build the tolerance up to the point of caffeine overuse.
If they don’t control the intake, it may lead to caffeine over-consumption and to a dependency syndrome called caffeinism.
Caffeinism is associated with a daily intake of between 1000mg to 1500mg (or even more) of caffeine (equivalent to on average 10-15 coffees).
Long term caffeinism leads to serious health issues such as peptic ulcers and GERD.
Symptoms of caffeinism are similar to those of anxiety disorder which is thought to be due to the increased levels of lactate (used as fuel) in the brain.
The following are the symptoms of caffeinism: (2)
Central nervous system:
- Difficulty sleeping
- Overactive reflexes
- Tingling sensation around the mouth, hands and feet
- Chest pain
- Palpitations or increased heart rate
Digestive tract system:
- Pain in the abdomen
To prevent reaching a state of over-consumption (caffeinism), the best method for individuals who can handle large amounts of caffeine is to consciously limit drinking caffeine to optimal amounts for maximum health benefits (400mg of caffeine or 4-5 coffees per day.)
- People with extremely high threshold limit may build the tolerance up to the point of caffeine overuse and develop a caffeine dependency syndrome called caffeinism.
- Long term caffeinism leads to serious health issues such as peptic ulcers and GERD.
Physical dependence on caffeine
Physical dependence on caffeine can develop with amounts as small as 100mg of caffeine per day (about 1 coffee).
Physical dependence means craving for drugs which relieve the withdrawal symptoms and seeking the positive effects that the drugs can provide.
- When you start craving the positive effects of caffeine including a relief of caffeine withdrawal symptoms you become physically dependent.
Caffeine withdrawal symptoms
The body adapts to regular caffeine intake. If this intake suddenly stops, we get affected by a number of symptoms called withdrawal symptoms.
These symptoms start within 12 and 24 hours after the discontinuation, with the peak occurring anywhere between 20-48 hours.
For some individuals, these symptoms can start after only 3 to 6 hours and last for an entire week.
However, they usually disappear on the third day, depending on various factors, such as the daily doses and the frequency of caffeine intake.
Some studies show that the severity of the withdrawal symptoms doesn’t seem to have any relationship with the amount of daily caffeine usage, meaning that heavy and light caffeine users can experience similar symptoms.
Withdrawal symptoms usually tend to be more severe in the afternoons, rather than in the mornings, and on the second day, rather than on the first day of abstinence.
The studies on this subject are not consistent and report incidences of withdrawal symptoms in between 11%-100% of the cases. Severe withdrawal symptoms are not common.
- Flu-like feeling
- Headache (more common in women than in men and less with increasing age)
- Increased heart rate
- Lack of concentration
- Muscle tension
- Stomach ache
- Stomach upset
- Upper body and joint pain
To relieve the caffeine withdrawal symptoms, an aspirin or a small amount of caffeine can be taken. The intensity of the caffeine withdrawal symptoms is mild in comparison to other drugs such as heroin, or cocaine.
- Caffeine withdrawal symptoms usually start from 3 to 6 hours and last for an entire week and peak within 20-48 hours.
- The intensity of withdrawal symptoms of caffeine are much milder in comparison to other drugs.
- To relieve caffeine withdrawal symptoms have a smaller than usual amount of caffeine or aspirin.
Difference between caffeine tolerance and caffeine sensitivity
Caffeine tolerance is sometimes confused with caffeine sensitivity, which refers to our body’s genetic ability to produce enzymes that break down caffeine.
For instance, if you are unable to produce enough enzymes to break down caffeine from three coffees in a day, you may suffer from caffeine overdose symptoms after having a third coffee.
If you stick to two coffees per day, then you will not experience negative symptoms.
This limit of how much caffeine you can have per day or in one dose refers to caffeine sensitivity.
On the other hand, if you have enough enzymes to break down caffeine from three or more coffees and regularly have only two coffees per day, when you drink the third coffee you may experience a positive reaction to that extra dose of caffeine, such as increased energy, acute focus, etc.
After drinking that third coffee, your tolerance starts building up, meaning that with regular consumption of the same dose of caffeine, those positive sensations are being neutralized.
Having three coffees per day on consecutive days, fully builds your tolerance to that amount of caffeine.
- Sensitivity to caffeine refers to our ability to produce enzymes that break down caffeine, while caffeine tolerance refers to the body’s ability to balance physiological effects of regular intake of the same dose of caffeine.
How caffeine affects the brain?
This section describes what happens on a physiological level after caffeine intake. It explains the reasons for how we feel from the time we drink our first coffee, through building up of tolerance to caffeinism and what happens when we stop using caffeine regularly.
Building tolerance to caffeine as well as caffeine withdrawal symptoms are related to the brain inhibitory neurotransmitter called adenosine.
Adenosine has a tranquilizer function in the brain. It slows down the brain function, inhibits the transmission of messages between brain nerves and tells the brain that we are tired and should rest. Adenosine exerts this action only when it is attached to the adenosine receptors.
From the first coffee (caffeine-naive)
The caffeine molecule has a very similar shape to the adenosine molecule, allowing it to fit nicely in the adenosine receptors on neurotransmitters in the brain without activating them. It simply occupies the adenosine spot without doing anything.
If many caffeine molecules get attached to these receptors, adenosine will be unable to exert any of the above mentioned physiological effects.
This means that the tranquilizing actions of adenosine and all of the other functions that adenosine is responsible for, don’t come into effect and we stay alert and energetic.
Caffeine tolerance starts developing
Each time the caffeine dose is increased, caffeine molecules take up more adenosine receptors and the euphoric effects return temporarily.
In response to the blocked adenosine receptors and to maintain the equilibrium, the body produces more receptors so that adenosine molecules are able to resume their normal functions.
This increased number of adenosine receptors allows the adenosine molecules to start exerting their usual physiological functions. After a while, everything returns to normal and the effects of caffeine (as per the list above) disappear. The caffeine tolerance is built.
Going too far – Caffeinism
The more caffeine is consumed, the more adenosine receptors that are produced. Other body changes also occur such as the release of hormones, such as epinephrine (adrenaline), creating imbalances that can lead to serious long term medical conditions.
The mechanism of the caffeine withdrawal symptoms is not well understood, yet but a number of findings give some possible reasons why it may occur.
Caffeine is a good remedy for headaches caused by a blood pressure drop, since it constricts blood vessels in the brain.
A large amount of adenosine causes the dilation of blood vessels, leading to a decrease in blood pressure. The dilation of blood vessels is known to cause headaches.
If caffeine intake is suddenly stopped, after regular use, a number of changes occur in the brain that may explain symptoms such as headache or fatigue. (6):
- Brain electrical activity, measured by an electroencephalogram (EEG), shows an increased theta rhythm which is linked to fatigue, tiredness and sluggishness.
- Cerebral blood flow velocity increases causing headaches.
These effects are thought to be linked to the interaction of caffeine with the adenosine receptors.
Due to a constant build-up of tolerance with regular caffeine intake, the number of adenosine receptors is elevated.
By stopping caffeine intake, the number of adenosine receptors is too high in comparison with the circulating adenosine molecules.
A higher amount of adenosine suddenly has access to the receptors. The increased number of adenosine molecules attached to the receptors, instantly multiplies its normal physiological effects such as sleepiness, vasodilation and resulting lowered blood pressure.
These sudden physiological changes lead to some unpleasant symptoms known as withdrawal symptoms.
Fortunately, the body quickly detects that there is no need for an excessive amount of adenosine receptors and starts reducing their numbers. This process can last from 1-5 days which is also the time it takes for all of the withdrawal symptoms to subside.
- Adenosine (brain neurotransmitter) slows down the brain function, and tells the brain that we are tired and should rest.
- The caffeine molecule has a very similar shape to the adenosine.
- Caffeine molecules occupy adenosine receptors, and so adenosine’s effects are inhibited.
- Caffeine withdrawal symptoms, building tolerance to caffeine, caffeine symptoms and caffeinizm are all related to action of this neurotransmitter.
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