Requested DocAlert: How Does Coffee/Caffeine Affect Brain Health and Disease?

Information sourced from BMJ:

Pract Neurol 2016;16:89-95
[Free full-text Pract Neurol article PDF | PubMed® abstract]


Effects of coffee/caffeine on brain health and disease: What should I tell my patients?

Astrid Nehlig

Correspondence to Dr Astrid Nehlig, INSERM U 1129; Faculty of Medicine; 11 rue Humann, 67085 Strasbourg, France;



Over the last decade, Food Regulation Authorities have concluded that coffee/caffeine consumption is not harmful if consumed at levels of 200 mg in one sitting (around 2½ cups of coffee) or 400 mg daily (around 5 cups of coffee). In addition, caffeine has many positive actions on the brain. It can increase alertness and well-being, help concentration, improve mood and limit depression. Caffeine may disturb sleep, but only in sensitive individuals. It may raise anxiety in a small subset of particularly sensitive people. Caffeine does not seem to lead to dependence, although a minority of people experience withdrawal symptoms. Caffeine can potentiate the effect of regular analgesic drugs in headache and migraine. Lifelong coffee/caffeine consumption has been associated with prevention of cognitive decline, and reduced risk of developing stroke, Parkinson’s disease and Alzheimer’s disease. Its consumption does not seem to influence seizure occurrence. Thus, daily coffee and caffeine intake can be part of a healthy balanced diet; its consumption does not need to be stopped in elderly people.


Coffee is the most frequently consumed drink worldwide after water. It is a very complex drink comprising >1000 compounds, many of which are not yet identified. A main component is caffeine, also found in many other sources such as drinks (tea, soft drinks, energy drinks, hot chocolate, mate, guarana), in foods (mainly chocolate) and in medications (painkillers, slimming creams and pills).

What is a safe daily consumption?

A low dose of caffeine (50–200 mg in one sitting) can have positive effects: increasing alertness and energy, well-being, relaxation, good mood and improved memory. However, high doses of caffeine (400–800 mg in one sitting) may have negative effects: anxiety, nervousness, jitteriness, insomnia, tachycardia and trembling. There is a consensus that the daily ingestion of 300–400 mg caffeine (around 4–5 cups of coffee) does not raise any health concern.

Several countries have assessed the safe limits of caffeine consumption. Among the most recent ones, the Belgium Superior Health Council based its recommendations on the assessments conducted previously by the Food Standards of Australia and New Zealand, Health Canada and the UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. The Belgium Superior Health Council considered that a caffeine intake of 5.7 mg/kg per day (400 mg/day for a 70 kg adult) was not linked to adverse effects in relation to general toxicity, altered behaviour, decreased male fertility, cardiovascular or cancer risk. The council recommended a maximum daily intake of caffeine of 2.5 mg/kg for children and adolescents, noting an increased risk of anxiety and altered behaviour beyond this dose, and advised to women of childbearing age not to exceed 200–300 mg per day.

The very recent European Food Safety Authority report on the safety of caffeine considered that “single doses of caffeine up to 200 mg (about 3 mg/kg) from all sources have no safety concerns for the general adult population, even if consumed less than two hours before intense physical exercise under normal environmental conditions. Caffeine intakes from all sources up to 400 mg per day (about 5.7 mg/kg) do not raise safety concerns for adults in the general population, except pregnant women”. In the latter subgroup, they considered that “caffeine intakes from all sources up to 200 mg per day do not raise safety concerns for the fetus”. Finally, “owing to the limited information available for children and adolescents, caffeine intakes derived from acute consumption in adults (3 mg/kg per day) may serve as a basis to derive daily caffeine intakes of no concern”.

These data are in line with previous reports from the literature that had reached consensus on dose-dependent effects.

Effects of caffeine on a healthy brain

Coffee/caffeine, alertness and sleep

Caffeine ingestion is well known to give a dose-dependent increase in energetic arousal, to improve hedonic tone, and to help concentration, mainly by eliminating distractors. Caffeine (75 mg) can shorten reaction time and improve visual attention and sustained attention mainly in long, demanding tasks. It seems particularly effective in improving alertness in situations of reduced arousal, such as the post-lunch attention decline, regular colds, night shift work and driving at night.

Caffeine readily affects sleep, and this is the function most sensitive to caffeine. Doses as low as 100 mg (around one single cup of coffee) can prolong sleep latency, shorten total sleep time and prolong light sleep phases while shortening deep sleep. Rapid eye movement (REM) sleep is not much affected.

These effects clearly depend on caffeine being consumed before going to bed, but even caffeine ingested in the morning may detrimentally affect sleep. For example, 200 mg caffeine (around 2–2½ cups of coffee) in the morning reduces total sleep time by about 10 min, sleep efficiency by about 3% and increases the latency to stage 2 sleep. These effects occur in low consumers but not in habitual ones. There is no age-related difference.

However, there are clear differences in individual sensitivity to caffeine effects on sleep. Those may be partly linked to the polymorphism of CYP1A2, but more importantly, a polymorphism of the brain adenosine A2A receptor (ADORA2A) modulates the susceptibility to subjective and objective effects of caffeine on sleep. In sensitive individuals, insomnia almost doubles with caffeine consumption compared with no caffeine.

[Coffee/caffeine,] mood and mood disorders

Caffeine in low doses (150–200 mg) has been repeatedly reported to improve mood states. These effects explain why coffee and tea are widely used as breakfast beverages. Its positive effects on mood can be enhanced by the co-consumption of bread and by the presence of blue light (which has positive effects on mood). The effects are more pronounced in the elderly; in addition, non-consumers are influenced by caffeine expectancy.

Several studies on large cohorts have associated daily coffee drinking with a decreased risk of depression. In the Nurses’ Health Study concerning 50 730 women followed up for 10 years, the risk of depression was reduced by 15% in those drinking 2–3 cups of coffee daily, and by 20% in those drinking over cups [sic] per day. A recent study on a population of 263 923 elderly Americans from the NIH-AARP Diet and Health Study showed a 9% reduced risk of depression with the daily intake of ≥4 cups of coffee. Several other studies on young and middle-aged populations confirmed this observation, which also occurs with tea or caffeine alone.

Coffee consumption also appears to be associated with decreased suicide risk. In a cohort of 43 599 men from the Hea[l]th Professionals Follow-up Study and 73 820 women from the Nurses’ Health Study, the suicide risk was 45% lower in those consuming 2–3 cups of coffee daily and 53% lower with >4 cups daily.

Coffee/caffeine and anxiety

High doses of caffeine can cause anxiety feelings, though this does not usually occur with low doses. Animal models of anxiety have confirmed caffeine’s anxiogenic effect. Two studies in humans reported a caffeine-related increase in self-ratings of anxiety for social threat words (ie, hated and lonely) and negative facial expressions (ie, angry and fearful faces). One study reported that the dose-dependent increase in anxiety after 75–300 mg caffeine occurred in men but not in women.

In a caffeine challenge test (480 mg caffeine given acutely), panic disorder patients and their healthy first-degree relatives were more sensitive than healthy volunteers to panic attack symptoms. This response concords with the finding that a variant of the ADORA2A gene modulates caffeine-induced anxiety in people who habitually consume little caffeine. Frequent consumption of caffeine leads to centrally mediated tolerance to its anxiogenic effect, even in genetically susceptible people.

Caffeine and dependence

The possibility of caffeine dependence questions many people. While caffeine in coffee is a mild central nervous system stimulant, preclinical studies showed that caffeine does not stimulate dopaminergic transmission in the shell of the nucleus accumbens, which would be the characteristic and specific feature of drugs of dependence. Likewise, human imaging studies show that caffeine does not activate the brain circuit of dependence and reward. Many data suggest that moderate coffee drinkers do not develop a physical dependence to caffeine.

However, the American Psychiatric Association has added caffeine withdrawal to the list of symptoms in Diagnostic and Statistical Manual of Mental Disorders, 5th edn. Some people experience symptoms after abruptly stopping caffeine. Those tend to occur 12–24 h after stopping caffeine and translate mainly into headaches, drowsiness and feeling of fatigue, but usually do not last >48 h. They can be avoided by gradually reducing intake.

Caffeine acts as a reinforcer, meaning it is able to wipe out unpleasant effects due to withdrawal. However, the underlying mechanisms are not clearly understood. The doses of caffeine in tea and coffee appear high enough to act as reinforcers since people look for them in case of withdrawal symptoms, and a dose of 25–50 mg caffeine per cup of coffee already acts as a reinforcer. However, the possible reinforcing effects of coffee unrelated to caffeine—but related to smell, taste and social environment that usually accompany coffee consumption—may be everyday motivators for consumption of caffeine-containing or caffeine-free coffee drinks.


In conclusion, coffee/caffeine consumed at moderate levels (not more than 200 mg caffeine in one setting or 400 mg over the day) does not appear to present any harmful effects for human health. Caffeine increases vigilance and helps concentration but because of that may disturb the quality of sleep. In some people, caffeine also raises the level of anxiety. For migraine and headaches, caffeine potentiates the effect of common analgesic drugs. In non-randomised observational cohort studies, the lifelong consumption of coffee/caffeine is associated with reduced rate of age-related cognitive decline, reduced risk of developing Parkinson’s disease or Alzheimer’s disease and lower risk of stroke. Its regular consumption does not affect patients with epilepsy. Thus, daily coffee and caffeine intake can be part of a healthy balanced diet and their consumption should not be stopped in elderly people.

Key points
Coffee/caffeine [does] not present any harmful effects if consumed at levels of 200 mg in one sitting (2½ cups of coffee) or 400 mg daily (5 cups of coffee).
Caffeine increases alertness and well-being and helps concentrating.
Caffeine may disturb sleep.
Caffeine improves mood and reduces depression.
Caffeine may raise anxiety in some individuals.
Caffeine does not lead to dependence.
Caffeine potentiates the effect of regular analgesic drugs in headache and migraine.
Lifelong coffee/caffeine consumption prevents cognitive decline.
Lifelong coffee/caffeine consumption decreases the risk of stroke, Parkinson’s disease and Alzheimer’s disease.

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