Caffeine: properties, uses, advantages, disadvantages, safety

Caffeine is a naturally occurring substance belonging to the methylxanthine family. It is present in numerous plants and is used in foods and beverages mainly for its stimulant effect on the central nervous system and, in some applications, as a flavouring substance because of its characteristic bitter taste.

It occurs naturally, among other sources, in coffee beans, tea leaves, guarana, kola nuts, yerba mate and, in smaller amounts, cocoa. EFSA describes caffeine as a compound naturally present in several plant materials and notes that, at moderate doses, it increases alertness and reduces drowsiness.

However, when the word “caffeine” appears separately in the ingredient list of a beverage, as frequently occurs in energy drinks and some cola beverages, it normally indicates purified caffeine deliberately added during formulation.

This added caffeine may be:

• extracted from plant materials;

• recovered, for example, during decaffeination processes;

• or manufactured by industrial chemical synthesis.

The simple declaration “caffeine” on the label does not reveal its origin. Purified natural caffeine and synthetically produced caffeine are chemically the same molecule when they meet equivalent purity specifications.

Description

Caffeine is a purine alkaloid and, more specifically, a trimethylxanthine.

Its common chemical name is:

1,3,7-trimethylxanthine

Its molecular structure contains three methyl groups attached to the xanthine skeleton.

Pure caffeine normally appears as:

• a white crystalline powder;

• white crystals or needles;

• a practically odourless substance;

• a distinctly bitter-tasting material.

Its molecular formula is C₈H₁₀N₄O₂, CAS number 58-08-2, and molecular weight approximately 194.19 g/mol.

Caffeine is sufficiently soluble in water for use in beverages, and its solubility increases with temperature.

Natural or industrially produced?

Caffeine differs from ingredients that exist only as industrial products.

Naturally occurring caffeine

Several plant species naturally produce caffeine as a secondary metabolite.

Major natural sources include:

• coffee – Coffea spp.;

• tea – Camellia sinensis;

• guarana – Paullinia cupana;

• yerba mate – Ilex paraguariensis;

• kola – Cola spp.;

• cocoa – Theobroma cacao.

The concentration depends on the species, variety, part of the plant, growing conditions and preparation method.

Caffeine added to foods

When caffeine appears as a separate ingredient, it is normally used in purified form.

Commercial caffeine may be obtained by:

• recovering it from coffee decaffeination processes;

• extracting it from tea or other caffeine-rich plant materials;

• purifying plant extracts;

• industrial chemical synthesis.

Therefore, the ingredient list alone does not justify stating either:

“this caffeine is natural”

or

“this caffeine is synthetic.”

The technically appropriate description is:

“purified caffeine added as an ingredient; natural or synthetic origin cannot be determined from the label alone.”

Production process

The manufacturing process depends on the origin of the caffeine.

Caffeine obtained by extraction

One important source is the decaffeination of coffee.

Caffeine removed from coffee beans may be:

• separated from the extraction medium;

• recovered;

• concentrated;

• purified;

• crystallised;

• dried;

• brought to the purity required for food use.

Different decaffeination and extraction systems have historically been used, including water, solvents and processes involving carbon dioxide.

Tea-processing fractions may also be used as sources for industrial caffeine extraction.

Synthetic caffeine

The same molecule can be manufactured through controlled chemical synthesis.

After synthesis, the product requires:

• purification;

• crystallisation;

• drying;

• analytical verification;

• impurity control;

• standardisation.

From a physiological standpoint, the human body does not distinguish between a caffeine molecule obtained from a plant and an identical molecule produced synthetically. What matters is the chemical identity, purity and dose.

Main substances contained

Unlike coffee, tea or guarana, purified caffeine is a chemically defined substance, not a complex plant mixture.

Its principal component is therefore caffeine itself.

A food-grade material may contain only:

• caffeine as the predominant substance;

• very small amounts of moisture;

• trace impurities within the applicable specification.

Other compounds naturally present in coffee or guarana should not be attributed to purified caffeine.

For example, a guarana extract can contain:

• caffeine;

• theobromine;

• polyphenols;

• tannins;

• carbohydrates;

• other plant-derived compounds.

Pure caffeine, by contrast, consists essentially of the single chemical substance.

This distinction becomes particularly important when a food contains both “caffeine” and “guarana extract”: part of the total caffeine has been added directly, while an additional amount may be naturally supplied by the botanical extract. Total caffeine exposure should therefore consider all sources present in the formulation.

Identification data and specifications

Mechanism of action

Caffeine readily crosses the blood-brain barrier and acts primarily as an adenosine receptor antagonist.

Adenosine is a neuromodulator that, among other functions, tends to reduce neuronal activity and promote drowsiness.

Caffeine occupies adenosine receptors without activating them normally, thereby reducing the physiological effects of adenosine.

At concentrations typically achieved through food consumption, the most relevant receptors are mainly:

• A₁;

• A₂A.

Other mechanisms, such as substantial phosphodiesterase inhibition or major effects on intracellular calcium, generally require concentrations much higher than those normally associated with dietary stimulant effects.

The resulting effects can include:

• increased alertness;

• reduced drowsiness;

• temporary improvement in attention;

• altered perception of fatigue;

• temporary increase in nervous-system activation.

Food use and safety evaluation

Amounts in foods and beverages

Caffeine may come both from naturally caffeine-containing ingredients and from added purified caffeine.

Indicative amounts often cited for common products include approximately:

• 60 ml espresso: 80 mg;

• 200 ml filter coffee: 90 mg;

• 220 ml black tea: 50 mg;

• 355 ml cola: 40 mg;

• 250 ml energy drink: 80 mg;

• 50 g dark chocolate: 25 mg;

• 50 g milk chocolate: 10 mg.

These are approximate values and can vary considerably according to formulation, raw material and preparation method.

A particularly important point is that total caffeine intake must include every source.

If a beverage contains:

• added caffeine;

• guarana;

• coffee;

• tea;

• mate;

• other caffeine-containing extracts;

actual exposure is the sum of caffeine contributed by all of them.

Caffeine in energy drinks

In energy drinks, caffeine is normally the principal ingredient responsible for the acute stimulant effect.

Other ingredients frequently present, such as:

• taurine;

• B vitamins;

• L-carnitine;

• botanical extracts;

should not automatically be considered equivalent to caffeine in stimulant activity.

The amount actually consumed depends both on concentration and on the volume of the serving or container.

For example:

32 mg/100 ml × 250 ml = 80 mg caffeine

32 mg/100 ml × 500 ml = 160 mg caffeine

Therefore, even when two beverages have the same concentration, the total dose can differ substantially according to package size.

European Union labelling requirements

The European Union has specific labelling requirements for beverages with a high caffeine content.

Beverages, other than certain coffee- or tea-based drinks whose name contains “coffee” or “tea”, containing caffeine from any source at more than 150 mg/L must carry the prescribed high-caffeine warning in the same field of vision as the name of the food.

The quantity of caffeine must also be stated in mg per 100 ml.

The expression “from any source” is particularly important.

It means that the threshold does not concern only purified caffeine added directly. Caffeine originating from guarana, coffee, tea, mate or other ingredients must also be included in the total.

For foods other than beverages to which caffeine is added for a physiological purpose, specific caffeine warning requirements also apply under EU food-information rules.

Use as a flavouring substance

Caffeine can also be used because of its flavouring properties, particularly its bitter taste.

In the EU it is listed as a flavouring substance with FL No. 16.016.

When caffeine is used specifically as a flavouring, category-specific maximum levels apply. For non-alcoholic beverages, the maximum is 150 mg/kg.

This application should be distinguished from the addition of caffeine specifically to obtain a physiological stimulant effect.

United Kingdom

UK food-information rules similarly require a warning for relevant beverages containing more than 150 mg/L of caffeine, together with an indication of the caffeine quantity.

The standard warning communicates that the product has a high caffeine content and is not recommended for children or pregnant or breast-feeding women.

As in the EU framework, the caffeine contribution of the complete formulation is relevant, rather than only the amount of purified caffeine added directly.

United States

In the United States, caffeine is recognised by the FDA as a food substance and is associated with 21 CFR §182.1180.

For cola-type beverages, the regulation allows caffeine at a tolerance of:

0.02%

when used according to good manufacturing practice.

For the general adult population, FDA commonly identifies 400 mg/day as an amount not generally associated with negative effects for most healthy adults.

However, individual sensitivity and caffeine metabolism vary considerably.

Safety

Caffeine is a physiologically active substance, and its safety is primarily related to total dose.

Healthy adults

EFSA considers that, for healthy adults:

single doses up to 200 mg

and

total daily intake up to 400 mg

generally do not raise safety concerns.

These values refer to caffeine from all sources combined.

A 400 mg/day reference should not be interpreted as a target intake or as a guarantee that every person can consume that amount without symptoms.

Individual sensitivity depends on factors such as:

• metabolism;

• habitual caffeine consumption;

• genetics;

• body size;

• timing of intake;

• medicines;

• individual physiological conditions.

Sleep

Even a single dose of approximately 100 mg may affect sleep duration or quality in some adults when consumed close to bedtime.

This means that a caffeine dose can be below toxicological safety limits while still producing undesirable effects on sleep quality.

Pregnancy

For pregnancy, EFSA considers total caffeine intake of up to:

200 mg/day

as not raising safety concerns for the fetus in its assessment.

All sources must be included:

• coffee;

• tea;

• cola;

• energy drinks;

• chocolate;

• supplements;

• other caffeine-containing products.

Children and adolescents

EFSA proposed:

3 mg/kg body weight/day

as a level that may be used when assessing caffeine exposure in children and adolescents.

For example:

• 30 kg → 90 mg/day;

• 40 kg → 120 mg/day;

• 50 kg → 150 mg/day.

These figures represent mathematical application of the EFSA reference and should not be interpreted as a recommendation for children to consume caffeine.

Effects of excessive intake

As caffeine dose increases, possible adverse effects include:

• agitation;

• nervousness;

• anxiety;

• insomnia;

• tremor;

• increased heart rate;

• palpitations;

• gastrointestinal discomfort;

• headache;

• restlessness.

At very high doses, far above normal food and beverage exposure, caffeine can become seriously toxic.

This risk is particularly relevant for:

• highly concentrated caffeine products;

• powders;

• incorrectly dosed supplements;

• accidental or deliberate ingestion of very large amounts.

These situations are different from moderate consumption of ordinary caffeinated beverages.

Tolerance, dependence and withdrawal

Regular caffeine consumption can lead to physiological adaptation to some of its effects.

Sudden discontinuation after habitual intake may produce temporary withdrawal symptoms, including:

• headache;

• sleepiness;

• fatigue;

• difficulty concentrating;

• irritability.

Caffeine therefore has genuine pharmacological activity and should not be considered merely a flavouring substance without biological effects.

Advantages

• Temporarily increases alertness.

• Reduces drowsiness.

• Can temporarily improve attention and ability to remain awake.

• Is active at relatively low doses.

• Is a chemically well-defined substance.

• Can be obtained from natural sources or industrial synthesis.

• Can be accurately standardised in beverages.

• Purified caffeine allows precise control of the added dose.

• Does not contribute nutritionally significant amounts of sugar, fat or sodium.

• Is intrinsically gluten-free.

• Is not a major regulated food allergen.

• Its safety has been extensively assessed by regulatory and scientific authorities.

Disadvantages

• It is not an essential nutrient.

• It has a real pharmacological effect on the central nervous system.

• It can disturb sleep at doses lower than the maximum levels considered safe.

• It may increase nervousness and anxiety in sensitive individuals.

• It can cause palpitations or a sensation of increased heart rate in some people.

• Individual sensitivity varies considerably.

• Habitual intake can result in adaptation and withdrawal symptoms.

• Total intake can easily be underestimated when several caffeine sources are consumed together.

• Guarana, tea, coffee or mate extracts may contribute additional caffeine.

• Energy drinks can be consumed rapidly, allowing a substantial dose to be ingested over a short period.

• Vitamins, taurine or other ingredients do not neutralise the effects of a high caffeine dose.

• “Natural” caffeine is not automatically safer than synthetic caffeine: the molecule has the same biological activity.

Natural caffeine and synthetic caffeine

When evaluating caffeine as a food ingredient, origin and chemical identity must be considered separately.

Caffeine extracted from coffee and caffeine manufactured synthetically have the same molecular formula:

C₈H₁₀N₄O₂

If identity, purity and specifications are equivalent, the human body is exposed to the same caffeine molecule.

Potential differences concern:

• manufacturing process;

• impurity profile;

• residues;

• certification;

• raw-material origin;

• sustainability;

• commercial “natural” status where legally applicable.

Determining the origin of the caffeine used in a specific food therefore requires:

• supplier specification;

• certificate of origin;

• technical documentation;

• manufacturing information.

The word “caffeine” alone does not provide this information.

Allergens and gluten

Pure caffeine:

• is not a protein;

• contains no gluten;

• is not inherently cereal-derived;

• contains no milk, egg, soy or tree-nut components in its molecular structure;

• is not itself a major regulated food allergen.

If caffeine is supplied as part of a commercial preparation or premix, however, the following may need to be assessed:

• carriers;

• excipients;

• anticaking agents;

• processing aids;

• other components of the preparation.

Supplier documentation should therefore be checked for the actual commercial raw material.

Storage

Purified caffeine should generally be stored:

• in a tightly closed container;

• in dry conditions;

• protected from contamination;

• away from excessive heat;

• according to the supplier's specification.

Caffeine itself is relatively stable as a dry substance.

In a finished beverage, stability can also depend on:

• pH;

• temperature;

• food matrix;

• heat treatment;

• shelf life;

• interactions with other formulation components.

In beverages, caffeine is generally sufficiently stable to allow accurate standardisation of the declared concentration.

Environment

The environmental profile of added caffeine depends partly on its origin.

For caffeine recovered during decaffeination, its use can represent the valorisation of a substance that would otherwise be removed during production.

For plant-extracted caffeine, relevant factors include:

• cultivation;

• transport;

• extraction;

• water use;

• solvents or CO₂;

• purification;

• energy consumption.

For synthetic caffeine, relevant factors include:

• chemical raw materials;

• reagents;

• energy;

• purification;

• management of process residues.

It is therefore not possible to state generally that natural caffeine necessarily has a lower environmental impact than synthetic caffeine without comparing the complete production chains.

Conclusion

Caffeine is a chemically defined methylxanthine with molecular formula C₈H₁₀N₄O₂, CAS 58-08-2 and molecular weight approximately 194.19 g/mol.

It occurs naturally in coffee, tea, guarana, kola, mate and cocoa, but it may also be added to foods and beverages as a purified ingredient.

When “caffeine” appears separately in an ingredient list, it should normally be interpreted as purified caffeine deliberately added during formulation. It may have been extracted from plant sources or produced synthetically; the label alone does not establish its origin.

Physiologically, caffeine is a central nervous system stimulant whose principal mechanism at ordinary dietary doses is antagonism of adenosine receptors. It can increase alertness and reduce drowsiness.

For healthy adults, EFSA considers single doses up to 200 mg and total daily intake of up to 400 mg not to raise safety concerns. However, even about 100 mg close to bedtime may affect sleep in some adults. During pregnancy, total intake of up to 200 mg/day from all sources is the relevant EFSA reference, while for children and adolescents EFSA uses 3 mg/kg body weight/day as a safety-based reference.

In the European Union, relevant beverages containing more than 150 mg/L of caffeine from any source must carry the prescribed high-caffeine warning and indicate the caffeine content. This means that caffeine contributed by guarana, coffee, tea, mate and similar ingredients must also be considered, not just purified caffeine added directly.

Caffeine has no E-number, is not an essential nutrient and, in energy drinks, its principal role is normally a physiological stimulant effect. A proper evaluation of a caffeinated product should therefore consider caffeine concentration, total caffeine per container or serving, additional natural caffeine sources, frequency and timing of consumption, and individual sensitivity.

Studies

High doses of caffeine, product intolerance or drug use can have serious consequences on the body (1).

It can be addictive.

The high and increasing consumption of so-called energy drinks over the last few years is taken into consideration by this in-depth study on 2097 publications and the relationship between caffeine (present in such beverages) and adverse events in the cardiovascular and neurological system is discussed (2 ) and here the negative effects of these drinks are analyzed (3).

Caffeine is used in the following products:

• cosmetics
• personal care products
• perfumes and fragrances

It is likely that there will be emissions of this substance into the environment from:

• washing liquids
• machine detergents
• car care products
• paints
• coatings or adhesives
• fragrances and deodorants

Caffeine studies

Molecular Formula: C₈H₁₀N₄O₂

Molecular Weight: 194.194 g/mol

UNII: 3G6A5W338E

CAS: 58-08-2  71701-02-5  95789-13-2

EC Number: 200-362-1

FEMA Number: 2224

PubChem Substance ID 24277682

MDL number MFCD00005758

Beilstein Registry Number 17705

Synonyms:

• 1,3,7-Trimethylpurine-2,6-dione
• Theobromine, 1-methyl-
• Propoxyphene Compound 65
• SK-65 Compound
• teina
• Ercatab
• Lanorinal
• 1,3,7-trimethyl-1,3,7-trihydropurine-2,6-dione
• 3,7-Dihydro-1,3,7-trimethyl-1H-purin-2,6-dion
• 1,3,7-trimethyl-2,6-dioxo-1,2,3,6-tetrahydropurine
• 1-methyltheobromine
• 1H-Purine-2,6-dione, 3,7-dihydro-1,3,7-trimethyl-
• 1,3,7-Trimethyl-3,7-dihydro-1H-purine-2,6-dione
• 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione
• 1,3,7-trimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
• Theophylline Me
• Xanthine, 1,3,7-trimethyl
• Methylxanthine theophylline
• Theobromine Me
• Phensal
• 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
• Caffeine, synthetic
• Quick-Pep
• Durvitan
• Wigraine
• 1,3,7-Trimethyl-2,6-dioxopurine
• Theophylline, 7-methyl
• DHCplus
• Tri-Aqua
• Kofein
• Miudol
• Caffeine, anhydrous
• Tirend
• Cafecon
• Caffine
• Dexitac
• Nodaca
• Caffedrine
• Stim
• Methyltheobromine
• Koffein
• Mateina
• Theine
• Alert-pep