Theobromine, also known as xantheose, is the principal
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
of ''
Theobroma cacao'' (cacao plant).
Theobromine is slightly water-
soluble
In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution.
The extent of the solubi ...
(330 mg/L) with a bitter taste.
In industry, theobromine is used as an
additive and precursor to some
cosmetics
Cosmetics are constituted mixtures of chemical compounds derived from either natural sources, or synthetically created ones. Cosmetics have various purposes. Those designed for personal care and skin care can be used to cleanse or protect ...
.
[ It is found in ]chocolate
Chocolate is a food made from roasted and ground cacao seed kernels that is available as a liquid, solid, or paste, either on its own or as a flavoring agent in other foods. Cacao has been consumed in some form since at least the Olmec civ ...
, as well as in a number of other foods, including the leaves of the tea
Tea is an aromatic beverage prepared by pouring hot or boiling water over cured or fresh leaves of ''Camellia sinensis'', an evergreen shrub native to East Asia which probably originated in the borderlands of southwestern China and north ...
plant, and the kola nut. It is a white or colourless solid, but commercial samples can appear yellowish.[
]
Structure
Theobromine is a flat molecule, a derivative of purine. It is also classified as a di methyl xanthine
Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine ...
. Related compounds include theophylline
Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
, caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...
, paraxanthine
Paraxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine, structurally related to caffeine.
Production and metabolism
Paraxanthine is not known to be produced by plants but is observed in nature as a metabolite of caffeine in a ...
, and 7-methylxanthine, each of which differ in the number or placement of the methyl groups.[
]
History
Theobromine was first discovered in 1841 in cacao beans by Russian chemist Aleksandr Voskresensky
Aleksandr Abramovich Voskresensky (Russian: Александр Абрамович Воскресенский; 25 November 1808 – 21 January 1880) was a Russian chemist who served as rector of Saint Petersburg Imperial University in 1861–1863 ...
. Synthesis of theobromine from xanthine
Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine ...
was first reported in 1882 by Hermann Emil Fischer.
Etymology
''Theobromine'' is derived from '' Theobroma'', the name of the genus
Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nom ...
of the cacao tree, with the suffix ''-ine'' given to alkaloids and other basic nitrogen-containing compounds. That name in turn is made up of the Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
roots ''theo'' ("god
In monotheistic thought, God is usually viewed as the supreme being, creator, and principal object of faith. Swinburne, R.G. "God" in Honderich, Ted. (ed)''The Oxford Companion to Philosophy'', Oxford University Press, 1995. God is typically ...
") and ''broma'' ("food"), meaning "food of the gods".[ (note: the book incorrectly states that the name "theobroma" is derived from Latin)]
Despite its name, the compound contains no bromine
Bromine is a chemical element with the symbol Br and atomic number 35. It is the third-lightest element in group 17 of the periodic table ( halogens) and is a volatile red-brown liquid at room temperature that evaporates readily to form a simi ...
.
Sources
Theobromine is the primary alkaloid found in cocoa and chocolate
Chocolate is a food made from roasted and ground cacao seed kernels that is available as a liquid, solid, or paste, either on its own or as a flavoring agent in other foods. Cacao has been consumed in some form since at least the Olmec civ ...
. Cocoa butter only contains trace amounts of theobromine. There are usually higher concentrations in dark than in milk chocolate.
There are approximately of theobromine in of milk chocolate, while the same amount of dark chocolate contains about . Cocoa beans naturally contain approximately 1% theobromine.
Plant species and components with substantial amounts of theobromine are:
* '' Theobroma cacao'' – seed and seed coat
A seed is an embryonic plant enclosed in a protective outer covering, along with a food reserve. The formation of the seed is a part of the process of reproduction in seed plants, the spermatophytes, including the gymnosperm and angiosperm p ...
* '' Theobroma bicolor'' – seed coat
* ''Ilex paraguariensis
''Ilex'' (), or holly, is a genus of over 570 species of flowering plants in the family Aquifoliaceae, and the only living genus in that family. ''Ilex'' has the most species of any woody dioecious angiosperm genus. The species are evergreen o ...
'' – leaf
* '' Camellia sinensis'' – leaf
Theobromine can also be found in trace amounts in the kola nut, the guarana
Guaraná ( from the Portuguese ''guaraná'' ), ''Paullinia cupana'', syns. ''P. crysan, P. sorbilis'') is a climbing plant in the family Sapindaceae, native to the Amazon basin and especially common in Brazil. Guaraná has large leaves and c ...
berry, yerba mate ( ''Ilex paraguariensis''), ''Ilex vomitoria
''Ilex vomitoria'', commonly known as yaupon () or yaupon holly, is a species of holly that is native to southeastern North America. The word ''yaupon'' was derived from the Catawban ''yą́pą'', from ''yą-'' tree + ''pą'' leaf. Another com ...
'', '' Ilex guayusa'', and the tea plant.
The mean theobromine concentrations in cocoa and carob products are:
Biosynthesis
Theobromine is a purine alkaloid derived from xanthosine, a nucleoside
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleoti ...
. Cleavage of the ribose and N-methylation yields 7-methylxanthosine. 7-Methylxanthosine in turn is the precursor to theobromine, which in turn is the precursor to caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...
.
Pharmacology
Even without dietary intake, theobromine may occur in the body as it is a product of the human metabolism of caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...
, which is metabolised in the liver into 12% theobromine, 4% theophylline
Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
, and 84% paraxanthine
Paraxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine, structurally related to caffeine.
Production and metabolism
Paraxanthine is not known to be produced by plants but is observed in nature as a metabolite of caffeine in a ...
.
In the liver, theobromine is metabolized into xanthine
Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine ...
and subsequently into methyluric acid. Important enzymes include CYP1A2
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene.
Function
...
and CYP2E1. The elimination half life of theobromine is between 6 to 8 hours.
Unlike caffeine, which is highly water soluble, theobromine is only slightly water soluble and is more fat soluble, and thus peaks more slowly in the blood. While caffeine peaks after only 30 minutes, theobromine requires 2-3 hours to peak.
"The main mechanism of action for methylxanthines has long been established as an inhibition of adenosine receptors".[ Its effect as a phosphodiesterase inhibitor] is thought to be small.[
]
Effects
Humans
Theobromine has no significant stimulant effect on the human central nervous system.[ It is a ]bronchodilator
A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lung ...
and causes relaxation of vascular smooth muscle
Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels.
Structure
Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood ve ...
.[ It is not currently used as a prescription drug.][ The amount of theobromine found in chocolate is small enough that chocolate can, in general, be safely consumed by humans.
Theobromine and ]caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...
are similar in that they are related alkaloids. Theobromine is weaker in both its inhibition of cyclic nucleotide
A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate groups. Like other nucleotides, cyclic nucleotides are composed of three functional groups: a sugar, a nitrogenous base, a ...
phosphodiesterases and its antagonism of adenosine receptors. The potential phosphodiesterase inhibitory effect of theobromine is seen only at amounts much higher than what people normally would consume in a typical diet including chocolate.
Toxicity
At doses of 0.8–1.5 g/day (50–100 g cocoa), sweating, trembling and severe headaches were noted, with limited mood effects found at 250 mg/day.
Also, chocolate may be a factor for heartburn
Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid (gastric reflux) into the esophagus. It is the m ...
in some people because theobromine may affect the esophageal sphincter muscle in a way that permits stomach acids to enter the esophagus
The esophagus ( American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to ...
.
Animals
Theobromine is the reason chocolate is poisonous to dogs. Dogs and other animals that metabolize theobromine (found in chocolate) more slowly can succumb to theobromine poisoning from as little as of milk chocolate for a smaller dog and , or around nine small milk chocolate bars, for an average-sized dog. The concentration of theobromine in dark chocolates (approximately ) is up to 10 times that of milk chocolate () – meaning dark chocolate is far more toxic to dogs per unit weight or volume than milk chocolate.
The same risk is reported for cats as well, although cats are less likely to ingest sweet food, with most cats having no sweet taste receptors. Complications include digestive issues, dehydration, excitability, and a slow heart rate. Later stages of theobromine poisoning include epileptic
Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
-like seizure
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
s and death. If caught early on, theobromine poisoning is treatable. Although not common, the effects of theobromine poisoning can be fatal.
See also
* Health effects of chocolate
* History of chocolate
The history of chocolate began in Mesoamerica. Fermented beverages made from chocolate date back to at least 1900 BC to 1500 BC. The Mexica believed that cacao seeds were the gift of Quetzalcoatl, the god of wisdom, and the seeds once had so muc ...
* Theodrenaline
References
{{Phosphodiesterase inhibitors
Adenosine receptor antagonists
Bitter compounds
Components of chocolate
IARC Group 3 carcinogens
Phosphodiesterase inhibitors
Xanthines