Health effects of caffeine

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Caffeine can be taken in tablet form

The health effects of caffeine have been extensively studied. Caffeine competitively inhibits different adenosine receptors, thereby producing mild central nervous system stimulant effects. Short term side effects such as headache, nausea, and anxiety have been shown as symptoms of mild caffeine consumption.[1] Caffeine also stimulates cardiac muscle, relaxes smooth muscle, increases gastric secretions, and produces diuresis.[2]

Toxicity and intoxication[edit]

Poisoning by caffeine
Classification and external resources
Specialty emergency medicine, psychiatry, psychiatry
ICD-10 F15, T43.6
ICD-9-CM 305.90, 969.71
eMedicine article/821863
Main symptoms of Caffeine overdose.png

Caffeine toxicity can present as a spectrum of clinical symptoms. Most of these originate in the central nervous and circulatory systems and can follow ingestion of 1g or more of caffeine. Insomnia, breathlessness and excitement progressing to mild delirium may be seen. Sensory disturbances, diuresis, tachycardia, extrasystoles, and elevated respirations as well as vomiting induced by potent gastric irritation can be present. Fatalities of caffeine poisoning are rare because the gastric irritation and vomiting develop before absorption of toxic amounts can occur. Normally, caffeine is rapidly and completely absorbed from the gastrointestinal tract with distribution in various tissues in approximate proportion to their water content. Convulsions result from the central stimulating effect with death caused by respiratory failure. Hyperglycemia and ketonuria associated with caffeine toxicity have been reported. These latter findings may be attributed to a stress reaction or the xanthine’s ability to mimic the metabolic effects of the cathecholamines including lipolysis, glycogenolysis and gluconeogenesis.[3] An acute overdose of caffeine usually in excess of about 300 milligrams, dependent on body weight and level of caffeine tolerance, can result in a state of central nervous system over-stimulation called caffeine intoxication,[4] or colloquially the "caffeine jitters". The median lethal dose (LD50) given orally, is 192 milligrams per kilogram in rats.[3] The LD50 of caffeine in humans is dependent on weight and individual sensitivity and estimated to be about 150 to 200 milligrams per kilogram of body mass, roughly 80 to 100 cups of coffee for an average adult taken within a limited time frame that is dependent on half-life.[citation needed] For additional information see: Caffeine.

Effects on different functions[edit]

Relationship between caffeine and adenosine[edit]

The predominant mechanism of action of caffeine is the antagonism of adenosine receptors. Adenosine is a locally released purine hormone that acts on different receptors (A1 and A2) that can increase or decrease cellular concentrations of cyclic AMP (cAMP). Adenosine inhibits adenyl cyclase via high affinity (A1) receptors and stimulates adenyl cyclase via low affinity (A2) receptors. Adenosine receptors are found throughout the body including the brain, in the cardiovascular, respiratory, renal and gastrointestinal system and in adipose tissue. Caffeine nonselectively blocks both adenosine receptors and competitively inhibits the actions of adenosine. Adenosine acts presynaptically to inhibit neuronal release of acetylcholine, norepinephrine, dopamine, gamma amino butyric acid and serotonin. Adenosine also reduces spontaneous firing of neurons in many regions of the brain which produces sedation and has anticonvulsant activity. Caffeine releases norepinephrine, dopamine, serotonin and glutamate in the brain and increases circulating catecholamines consistent with reversal of the inhibitory effects of adenosine on these systems.[5]

How caffeine wards off drowsiness[edit]


Caffeine antagonizes adenosine A2A receptors in the ventrolateral preoptic area (VLPO), thereby inducing inhibitory GABA neurotransmission to the tuberomammillary nucleus, a histaminergic projection nucleus that activation-dependently promotes sleep.[6]

Short-term effects[edit]

Caffeine can increase blood pressure;[7][8] long term consumption at sufficiently high doses has been associated with chronic arterial stiffness.[8] Blood pressure increases are mediated by adenosine receptor antagonism.[9] Caffeine can cause vasoconstriction.[10] It is unclear if caffeine causes increased heart rate as a side effect.[8][10] The ability for caffeine and theophylline to induce diuresis and natriuresis is well established.[11] Coffee and caffeine can affect gastrointestinal motility and gastric acid secretion.[12][13][14]

Other effects include:

  • Low doses of caffeine cause increased alertness and decreased fatigue.[15]
  • Caffeine increases the metabolic rate.[16][17][18]
  • Caffeine can increase blood pressure in non-habitual consumers.[19] High blood pressure is associated with an increase in strokes, and cerebral vascular disease, which in turn increase the risk of multi-infarct dementia.[19]
  • Caffeine may reduce control of fine motor movements (e.g. producing shaky hands)[15]
  • Caffeine can increase cortisol secretion, some tolerance is developed.[20]
  • Caffeine can contribute to increased insomnia and sleep latency.[15]
  • Dependence can occur with caffeine.[15][21]
  • High caffeine consumption may accelerate bone loss in postmenopausal women.[21][22]


The International Olympic Committee since the summer of 2000, no longer treats caffeine as a banned substance.[23]


The US National Institutes of Health states "too much caffeine can make you restless, anxious, and irritable. It may also keep you from sleeping well and cause headaches, abnormal heart rhythms, or other problems. If you stop using caffeine, you could get withdrawal symptoms. Some people are more sensitive to the effects of caffeine than others. They should limit their use of caffeine. So should pregnant and nursing women."[24]

Four caffeine-induced disorders are recognized by the American Psychiatric Association (APA) including: caffeine intoxication, caffeine-induced sleep disorder, caffeine-induced anxiety disorder, and caffeine-related disorder not otherwise specified (NOS).[4] The DSM-IV defines someone with caffeine-induced sleep disorder, as an individual who regularly ingests high doses of caffeine sufficient to induce a significant disturbance in their sleep, sufficiently severe to warrant clinical attention.[4] As of 2010, there is no known therapeutic effect of caffeine for ADHD.[25] Some studies have however found a modest protective against Alzheimer disease, but the evidence is inconclusive.[26][27][28]

According to a 2011 literature review, caffeine use is positively associated with anxiety and panic disorders.[29] Caffeine-induced anxiety symptoms occur in normal individuals and especially in vulnerable patients, like those with pre-existing anxiety disorders.[30] Caffeine withdrawal can also cause an increase in anxiety level.[25]

In moderate doses caffeine may reduce symptoms of depression and lower suicide risk.[25]

Long-term effects[edit]

Type II diabetes[edit]

Although the relationship between tea caffeine and diabetes mellitus has been a topic under study for many years,[31] there remains insufficient evidence to conclude any effect of tea or caffeine on diabetes or any other disease, such as cancer.[32][33]

Negative effects on diabetics[edit]

Coffee caffeine may have a negative effect on diabetes patients because it appears to be capable of reducing insulin sensitivity and makes it difficult for patients with diabetes to control their blood glucose levels.[34] Studies have shown that caffeine consumption increases blood glucose, but diabetes medication decreases blood glucose levels, indicating that the two may counter-interact.[34]


Research has shown that there is no significant association between caffeine consumption and cancer, including cancer of the mouth, pharynx, esophagus, stomach, liver, or pancreas.[32][33][35]


Caffeine withdrawal
Classification and external resources
Specialty emergency medicine, psychiatry, psychiatry
ICD-10 F15.1
ICD-9-CM 292.0


Caffeine use can lead to minor physical dependence. The most frequently seen withdrawal symptoms are headache and fatigue. Such symptoms affect consumers’ mood, but show no evidence of influencing ones’ performance. In prolonged caffeine drinkers, symptoms such as increased depression and anxiety, nausea, vomiting, physical pains and intense desire for beverages containing caffeine are also reported. The symptoms reflect consumers’ expectancy effects on caffeine to some degree.[15]

Withdrawal symptoms – including headache, irritability, inability to concentrate, drowsiness, insomnia, and pain in the stomach, upper body, and joints – may appear within 12 to 24 hours after discontinuation of caffeine intake, peak at roughly 48 hours, and usually last from 2 to 9 days.[36] Peer knowledge, support and interaction may aid withdrawal.[21]

Effect of genetics on withdrawal symptoms[edit]

Gene polymorphism could be associated with caffeine withdrawal symptoms and beta 1and beta-2 play roles in caffeine withdrawal.[37] For example, compared to people with homozygous Gly16 allele, consumers with the heterozygote ADR beta-2 Gly16 Arg gene polymorphism have a higher chance of feeling fatigue after 48 hours of caffeine withdrawal.[37] It has been suspected that beta2- adrenoceptors are the main cause for this increase in mental fatigue symptoms.[37] Beta 2- adrenoceptors are receptors that regulate glycogenolysis, secret insulin and intramuscularly transport glucose that is used for cerebral and muscle activity.[37] Another example is given by the genes ADRbeta1 Gly16 Arg and CYP1A2-163A>C polymorphisms.[37] They are associated with the consumers’ mood swings and increased depression level.[37] Among subjects homozygous for the CYP1A2 allele, ADRbeta1 Gly389 allele carriers are reported to have a higher percentage of depression level increase when compared to Arg389 homozygotes subjects.[37] Adrenergic receptors, again, play a key role in this symptom, as altered norepinephrine (an adrenoceptor agonist) neurotransmission contribute to the etiology of depression.[37] This symptom is often seen in faster caffeine metabolizers, because caffeine effects diminish quicker in these consumers and provide them less opportunity to adapt to caffeine loss.[37]



Health Canada has not developed definitive advice for adolescents 13 and older because of insufficient data. Nonetheless, Health Canada suggests that daily caffeine intake for this age group be no more than 2.5 mg/kg body weight. This is because the maximum adult caffeine dose may not be appropriate for light weight adolescents or for younger adolescents who are still growing. The daily dose of 2.5 mg/kg body weight would not cause adverse health effects in the majority of adolescent caffeine consumers. This is a conservative suggestion since older and heavier weight adolescents may be able to consume adult doses of caffeine without suffering adverse effects. For the rest of the general population of healthy adults, Health Canada advises a daily intake of no more than 400 mg.[38]

According to the US-based Waverly Health Center, three 8 oz cups of coffee (about 250 milligrams of caffeine) per day is considered an average or moderate amount of caffeine; ten 8 oz cups of coffee per day is considered an excessive intake of caffeine.[39]

Pregnant women[edit]

Caffeine's potential impact on female fertility, and its precise impact on pregnancy, is still being studied, but (as with many other substances in these circumstances) caution and moderation is warranted in any case until further information is known. For women of childbearing age, Health Canada recommends a maximum daily caffeine intake of no more than 300 mg, or a little over two 8 oz (237 mL) cups of coffee.[38]


In healthy children, caffeine intake produces effects that are "modest and typically innocuous".[40] For children age 12 and under, Health Canada recommends a maximum daily caffeine intake of no more than 2.5 milligrams per kilogram of body weight. Based on average body weights of children, this translates to the following age-based intake limits:[38]

Age range Maximum recommended daily caffeine intake
4-6 45 mg (slightly more than in 12 oz of a typical soft drink)
7-9 62.5 mg
10-12 85 mg (about ½ cup of coffee)

Relatedly, one study found that caffeine can be used to treat hyperkinetic children.[41] The research found that 200–300 mg of caffeine has a similar effect to methylphenidate in treating hyperkinetic impulse disorder. Moreover, the caffeine treatment did not show the side-effects caused by methylphenidate.[41] Moderate caffeine intake has been reported to help children with ADHD with their focus time. Most ADHD children have a focus time of less than a minute at a time. Giving a child with ADHD a drink with at least 50 mg of caffeine, mainly coffee without added sugar can help increase this focus time. It also is reported to help calm or slow down the hyperactive behaviors.[citation needed]

Labeling requirements[edit]

It is a regulatory requirement that the label of most prepackaged foods must declare a list of ingredients, including food additives such as caffeine, in descending order of proportion. However, there is no regulatory provision for mandatory quantitative labeling of caffeine, (e.g., milligrams caffeine per stated serving size). As for "natural caffeine", there are a number of food ingredients that naturally contain caffeine. These ingredients must appear in food ingredient lists. However, as is the case for "food additive caffeine", there is no requirement to identify the quantitative amount of caffeine in composite foods containing ingredients that are natural sources of caffeine. While coffee or chocolate are broadly recognized as caffeine sources, some ingredients (e.g. guarana, yerba maté) are likely less recognized as caffeine sources. For these natural sources of caffeine, there is no regulatory provision requiring that a food label identify the presence of caffeine nor state the amount of caffeine present in the food.[42]

Effect of alcohol on caffeine[edit]

According to DSST, alcohol provides a reduction in performance and caffeine has a significant improvement in performance.[43] When alcohol and caffeine are consumed jointly, the effects produced by caffeine are affected, but the alcohol effects remain the same.[44] For example, when additional caffeine is added, the drug effect produced by alcohol is not reduced.[44] However, the jitteriness and alertness given by caffeine is decreased when additional alcohol is consumed.[44] Alcohol consumption alone reduces both inhibitory and activational aspects of behavioral control. Caffeine antagonizes the activational aspect of behavioral control, but has no effect on the inhibitory behavioral control.[45]

Effect of orally administered birth control on caffeine[edit]

Consumption of caffeine while orally administering birth control can extend the half-life of caffeine; therefore, greater attention should be taken during caffeine consumption.[5]

See also[edit]


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