Theobromine
Encyclopedia
Theobromine also known as xantheose, is a bitter alkaloid
of the cacao plant, with the chemical formula C7
H8
N4
O2
. It is found in chocolate
, as well as in a number of other foods, including the leaves of the tea
plant, and the kola
(or cola) nut. It is in the methylxanthine
class of chemical compounds, which also includes the similar compounds theophylline
and caffeine
. (In caffeine, the only difference is that the NH group of theobromine is an N-CH3 group.) Despite its name, the compound contains no bromine
—theobromine is derived from Theobroma
, the name of the genus
of the cacao tree, (which itself is made up of the Greek roots theo ("God
") and brosi ("food"), meaning "food of the gods") with the suffix -ine given to alkaloids and other basic
nitrogen-containing compounds.
Theobromine is a water
-slightly-soluble
(330 mg/L), crystalline, bitter powder; the colour has been listed as either white
or colourless. It has a similar, but lesser, effect to caffeine in the human nervous system, making it a lesser homologue
. Theobromine is an isomer
of theophylline, as well as paraxanthine
. Theobromine is categorized as a dimethyl xanthine.
Theobromine was first discovered in 1841 in cacao beans by Russian chemist Alexander Woskresensky. Theobromine was first synthesized from xanthine
by Hermann Emil Fischer
.
Theobromine is the primary alkaloid found in cocoa and chocolate
. Cocoa powder can vary in the amount of theobromine, from 2% theobromine to at least 10% usually having higher concentrations in "dark" than "milk" chocolate. Theobromine can also be found in small amounts in the kola nut
(1.0-2.5%), the guarana
berry, ilex guayusa
, ilex paraguariensis
(yerba mate), and the tea plant
.
The plant
species
with the largest amounts of theobromine are:
The mean theobromine concentrations in cocoa and carob products are:
, theobromine is used as a vasodilator (a blood vessel widener), a diuretic
(urination aid), and heart stimulant
.
Theobromine increases urine production. Because of this diuretic
effect, and its ability to dilate blood vessels, theobromine has been used to treat high blood pressure. The American Journal of Clinical Nutrition notes that historic use of theobromine as a treatment for other circulatory problems including arteriosclerosis
, certain vascular disease
s, angina pectoris, and hypertension
should be considered in future studies.
Following its discovery in the late 19th century, theobromine was put to use by 1916, where it was recommended by the publication Principles of Medical Treatment as a treatment for edema
(excessive liquid in parts of the body), syphilitic
angina attacks, and degenerative angina.
"In the human body, theobromine levels are halved between 6-10 hours after consumption."
Theobromine has also been used in birth defect
experiments involving mice
and rabbit
s. A decreased fetal
weight was noted in rabbits following forced feeding, but not after other administration of theobromine. Birth defects were not seen in rats. Possible future uses of theobromine in such fields as cancer
prevention have been patented.
, which is metabolised
in the liver into 10% theobromine, 4% theophylline
, and 80% paraxanthine
.
In the liver, theobromine is metabolized into xanthine
and subsequently into methyluric acid. Important enzymes include CYP1A2
and CYP2E1
.
Like other methylated xanthine derivatives
, theobromine is both a
As a phosphodiesterase inhibitor
, theobromine helps prevent the phosphodiesterase
enzymes from converting the active cAMP to an inactive form. cAMP works as a second messenger in many hormone
- and neurotransmitter
-controlled metabolic systems, such as the breakdown of glycogen
. When the inactivation of cAMP is inhibited by a compound such as theobromine, the effects of the neurotransmitter or hormone that stimulated the production of cAMP are much longer-lived. In general, the net result is a stimulatory effect.
The amount of theobromine found in chocolate is small enough that chocolate can, in general, be safely consumed by human
s. However, theobromine poisoning
may result from the chronic or acute consumption of large quantities, especially in the elderly.
While theobromine and caffeine are similar in that they are related alkaloids, theobromine is weaker in both its inhibition of cyclic nucleotide
phosphodiesterases and its antagonism
of adenosine receptors. Therefore, theobromine has a lesser impact on the human central nervous system
than caffeine. However, theobromine stimulates the heart to a greater degree. While theobromine is not as addictive, it has been cited as possibly causing addiction
to chocolate. Theobromine has also been identified as one of the compounds contributing to chocolate's reputed role as an aphrodisiac.
As it is a myocardial stimulant as well as a vasodilator, it increases heartbeat, yet it also dilates blood vessels, causing a reduced blood pressure
. However, a recent paper published suggested that the decrease in blood pressure may be caused by flavanols. Furthermore, its draining effect allows it to be used to treat cardiac failure, which leads to and is exacerbated by an excessive accumulation of fluid in the body.
A 2004 study published by Imperial College London
concluded that theobromine has an antitussive
(cough-reducing) effect superior to codeine
by suppressing vagus nerve
activity. In the study, theobromine significantly increased the capsaicin
concentration required to induce coughs when compared with a placebo. A drug, called BC1036, is being developed by the private UK company SEEK and it uses theobromine to treat persistent cough. In addition, theobromine is helpful in treating asthma
, since it relaxes the smooth muscle
s, including the ones found in the bronchi
.
A study conducted in Utah between 1983 and 1986, and published in 1993, showed a possible association between theobromine and an increased risk of suffering from prostate cancer
in older men. This association was not found to be linear for aggressive tumors. While the association may be spurious, it is plausible. Prenatal and infant exposure to theobromine appeared possibly associated with hypospadias
and testicular cancer in one population study.
As with caffeine, theobromine can cause sleeplessness, tremors, restlessness, anxiety, as well as contribute to increased production of urine
. Additional side effects include loss of appetite
, nausea
, and vomiting
.
s, can succumb to theobromine poisoning
from as little as 50 grams of chocolate for a smaller dog and 400 grams for an average-sized dog. The same risk is reported for cat
s as well, although cats are less likely to ingest sweet food, having no sweet taste receptors. Complications include digestive issues, dehydration, excitability, and a slow heart rate. Later stages of theobromine poisoning include epileptic
-like seizure
s and death. If caught early on, theobromine poisoning is treatable. Although not usual, the effects of theobromine poisoning, as stated, can become fatal.
The toxicity for (pet) birds is not known, but it is typically assumed that it is toxic to birds.
mutation
s in lower eukaryote
s and bacteria
. At the time of a 1991 report, further updated in 1997, by the IARC
, genetic mutations had been found in higher eukaryotic cells, specifically cultured mammalian cells, but the compound was still listed as having inadequate evidence for classification of human carcinogenicity.
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
of the cacao plant, with the chemical formula C7
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
H8
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
N4
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
O2
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
. It is found in chocolate
Chocolate
Chocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...
, as well as in a number of other foods, including the leaves of the tea
Tea
Tea is an aromatic beverage prepared by adding cured leaves of the Camellia sinensis plant to hot water. The term also refers to the plant itself. After water, tea is the most widely consumed beverage in the world...
plant, and the kola
Kola nut
Kola Nut is the nut of the kola tree, a genus of trees native to the tropical rainforests of Africa, classified in the family Malvaceae, subfamily Sterculioideae . It is related to the South American genus Theobroma, or cocoa...
(or cola) nut. It is in the methylxanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....
class of chemical compounds, which also includes the similar compounds theophylline
Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
and caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
. (In caffeine, the only difference is that the NH group of theobromine is an N-CH3 group.) Despite its name, the compound contains no bromine
Bromine
Bromine ") is a chemical element with the symbol Br, an atomic number of 35, and an atomic mass of 79.904. It is in the halogen element group. The element was isolated independently by two chemists, Carl Jacob Löwig and Antoine Jerome Balard, in 1825–1826...
—theobromine is derived from Theobroma
Theobroma
Theobroma is a genus of flowering plants in the mallow family, Malvaceae, that is sometimes classified as a member of Sterculiaceae. It contains roughly 20 species of small understory trees native to the tropical forests of Central and South America...
, the name of the genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
of the cacao tree, (which itself is made up of the Greek roots theo ("God
God
God is the English name given to a singular being in theistic and deistic religions who is either the sole deity in monotheism, or a single deity in polytheism....
") and brosi ("food"), meaning "food of the gods") with the suffix -ine given to alkaloids and other basic
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
nitrogen-containing compounds.
Theobromine is a water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
-slightly-soluble
Solubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
(330 mg/L), crystalline, bitter powder; the colour has been listed as either white
White
White is a color, the perception of which is evoked by light that stimulates all three types of color sensitive cone cells in the human eye in nearly equal amounts and with high brightness compared to the surroundings. A white visual stimulation will be void of hue and grayness.White light can be...
or colourless. It has a similar, but lesser, effect to caffeine in the human nervous system, making it a lesser homologue
Homologous series
In chemistry, a homologous series is a series of compounds with a similar general formula, possessing similar chemical properties due to the presence of the same functional group, and showing a gradation in physical properties as a result of increase in molecular size and mass...
. Theobromine is an isomer
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...
of theophylline, as well as paraxanthine
Paraxanthine
Paraxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine, structurally related to caffeine. Like caffeine, paraxanthine is a psychoactive central nervous system stimulant...
. Theobromine is categorized as a dimethyl xanthine.
Theobromine was first discovered in 1841 in cacao beans by Russian chemist Alexander Woskresensky. Theobromine was first synthesized from xanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....
by Hermann Emil Fischer
Hermann Emil Fischer
Hermann Emil Fischer, Emil Fischer was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He developed the Fischer projection, a symbolic way of drawing asymmetric carbon atoms.-Early years:Fischer was born in Euskirchen, near Cologne,...
.
Sources
Chocolate
Chocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...
. Cocoa powder can vary in the amount of theobromine, from 2% theobromine to at least 10% usually having higher concentrations in "dark" than "milk" chocolate. Theobromine can also be found in small amounts in the kola nut
Kola nut
Kola Nut is the nut of the kola tree, a genus of trees native to the tropical rainforests of Africa, classified in the family Malvaceae, subfamily Sterculioideae . It is related to the South American genus Theobroma, or cocoa...
(1.0-2.5%), the guarana
Guarana
Guarana , Paullinia cupana, syn. P. crysan, P. sorbilis) is a climbing plant in the maple family, Sapindaceae, native to the Amazon basin and especially common in Brazil. Guarana features large leaves and clusters of flowers, and is best known for its fruit, which is about the size of a coffee bean...
berry, ilex guayusa
Ilex guayusa
Ilex guayusa is an Amazonian tree of the holly genus, native to the Ecuadorian Amazon Rainforest. One of three known caffeinated holly trees, the leaves of the guayusa tree are dried and brewed like a tea for their stimulative effects....
, ilex paraguariensis
Yerba mate
Maté, yerba maté or erva maté , Ilex paraguariensis, is a species of holly native to subtropical South America in northeastern Argentina, Bolivia, southern Brazil, Uruguay and Paraguay...
(yerba mate), and the tea plant
Camellia sinensis
Camellia sinensis is the species of plant whose leaves and leaf buds are used to produce Chinese tea. It is of the genus Camellia , a genus of flowering plants in the family Theaceae. White tea, green tea, oolong, pu-erh tea and black tea are all harvested from this species, but are processed...
.
The plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
with the largest amounts of theobromine are:
- Theobroma cacao
- Theobroma bicolor
- Ilex paraguariensisYerba mateMaté, yerba maté or erva maté , Ilex paraguariensis, is a species of holly native to subtropical South America in northeastern Argentina, Bolivia, southern Brazil, Uruguay and Paraguay...
- Camellia sinensisCamellia sinensisCamellia sinensis is the species of plant whose leaves and leaf buds are used to produce Chinese tea. It is of the genus Camellia , a genus of flowering plants in the family Theaceae. White tea, green tea, oolong, pu-erh tea and black tea are all harvested from this species, but are processed...
- Cola acuminataCola acuminataCola acuminata belongs to the family Sterculiaceae and its fruits are harvested from the forests of the Democratic Republic of Congo. The fruits are rough, mottled and up to 8 inches long and contain large, flat and bright red coloured seeds...
- Theobroma angustifolium
- GuaranaGuaranaGuarana , Paullinia cupana, syn. P. crysan, P. sorbilis) is a climbing plant in the maple family, Sapindaceae, native to the Amazon basin and especially common in Brazil. Guarana features large leaves and clusters of flowers, and is best known for its fruit, which is about the size of a coffee bean...
- Coffea arabicaCoffea arabicaCoffea arabica is a species of Coffea originally indigenous to the mountains of Yemen in the Arabian Peninsula, hence its name, and also from the southwestern highlands of Ethiopia and southeastern Sudan. It is also known as the "coffee shrub of Arabia", "mountain coffee" or "arabica coffee"...
The mean theobromine concentrations in cocoa and carob products are:
| Item | Mean theobromine content (mg/g) |
|---|---|
| Cocoa | 20.3 |
| Cocoa cereals | 0.695 |
| Chocolate bakery products | 1.47 |
| Chocolate toppings | 1.95 |
| Cocoa beverages | 2.66 |
| Chocolate ice creams | 0.621 |
| Chocolate milks | 0.226 |
| Carob products | 0-0.504 |
Therapeutic uses
In modern medicineMedicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, theobromine is used as a vasodilator (a blood vessel widener), a diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
(urination aid), and heart stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
.
Theobromine increases urine production. Because of this diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
effect, and its ability to dilate blood vessels, theobromine has been used to treat high blood pressure. The American Journal of Clinical Nutrition notes that historic use of theobromine as a treatment for other circulatory problems including arteriosclerosis
Arteriosclerosis
Arteriosclerosis refers to a stiffening of arteries.Arteriosclerosis is a general term describing any hardening of medium or large arteries It should not be confused with "arteriolosclerosis" or "atherosclerosis".Also known by the name "myoconditis" which is...
, certain vascular disease
Vascular disease
Vascular disease is a form of cardiovascular disease primarily affecting the blood vessels.Some conditions, such as angina and myocardial ischemia, can be considered both vascular diseases and heart diseases .Cigarette smoking is the major risk factor....
s, angina pectoris, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
should be considered in future studies.
Following its discovery in the late 19th century, theobromine was put to use by 1916, where it was recommended by the publication Principles of Medical Treatment as a treatment for edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
(excessive liquid in parts of the body), syphilitic
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
angina attacks, and degenerative angina.
"In the human body, theobromine levels are halved between 6-10 hours after consumption."
Theobromine has also been used in birth defect
Teratology
Teratology is the study of abnormalities of physiological development. It is often thought of as the study of human birth defects, but it is much broader than that, taking in other non-birth developmental stages, including puberty; and other non-human life forms, including plants.- Etymology :The...
experiments involving mice
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
and rabbit
Rabbit
Rabbits are small mammals in the family Leporidae of the order Lagomorpha, found in several parts of the world...
s. A decreased fetal
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
weight was noted in rabbits following forced feeding, but not after other administration of theobromine. Birth defects were not seen in rats. Possible future uses of theobromine in such fields as cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
prevention have been patented.
Pharmacology
Even without dietary intake, theobromine may occur in the body as it is a product of the human metabolism of caffeineCaffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, which is metabolised
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
in the liver into 10% theobromine, 4% theophylline
Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
, and 80% paraxanthine
Paraxanthine
Paraxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine, structurally related to caffeine. Like caffeine, paraxanthine is a psychoactive central nervous system stimulant...
.
In the liver, theobromine is metabolized into xanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....
and subsequently into methyluric acid. Important enzymes include CYP1A2
CYP1A2
Cytochrome P450 1A2 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body...
and CYP2E1
CYP2E1
Cytochrome P450 2E1 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. In humans, the CYP2E1 enzyme is encoded by the CYP2E1 gene...
.
Like other methylated xanthine derivatives
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....
, theobromine is both a
- competitive nonselective phosphodiesterase inhibitorPhosphodiesterase inhibitorA phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase , therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate by the respective PDE...
, which raises intracellular cAMPCyclic adenosine monophosphateCyclic adenosine monophosphate is a second messenger important in many biological processes...
, activates PKACAMP-dependent protein kinaseIn cell biology, Protein kinase A refers to a family of enzymes whose activity is dependent on cellular levels of cyclic AMP . PKA is also known as cAMP-dependent protein kinase...
, inhibits TNF-alphaTNF inhibitorTumor necrosis factor promotes the inflammatory response, which in turn causes many of the clinical problems associated with autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, hidradenitis suppurativa and refractory asthma. These disorders are...
and leukotrieneLeukotrieneLeukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
synthesis, and reduces inflammationAnti-inflammatoryAnti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
and innate immunity and - nonselective adenosine receptorAdenosine receptorThe adenosine receptors are a class of purinergic receptors, G protein-coupled receptors with adenosine as endogenous ligand.-Pharmacology:...
antagonist.
As a phosphodiesterase inhibitor
Phosphodiesterase inhibitor
A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase , therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate by the respective PDE...
, theobromine helps prevent the phosphodiesterase
Phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
enzymes from converting the active cAMP to an inactive form. cAMP works as a second messenger in many hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
- and neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
-controlled metabolic systems, such as the breakdown of glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
. When the inactivation of cAMP is inhibited by a compound such as theobromine, the effects of the neurotransmitter or hormone that stimulated the production of cAMP are much longer-lived. In general, the net result is a stimulatory effect.
Humans
Human
Humans are the only living species in the Homo genus...
s. However, theobromine poisoning
Theobromine poisoning
Theobromine poisoning or chocolate poisoning is an adverse reaction to the alkaloid theobromine, found in chocolate, tea, cola beverages, açaí berries, and some other foods. Cacao beans contain about 1.2% theobromine by weight, while processed chocolate, in general, has smaller amounts...
may result from the chronic or acute consumption of large quantities, especially in the elderly.
While theobromine and caffeine are similar in that they are related alkaloids, theobromine is weaker in both its inhibition of cyclic nucleotide
Cyclic nucleotide
A cyclic nucleotide is any nucleotide in which the phosphate group is bonded to two of the sugar's hydroxyl groups, forming a cyclical or ring structure.These include:* cyclic AMP* cyclic GMP* cyclic ADP-ribose...
phosphodiesterases and its antagonism
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
of adenosine receptors. Therefore, theobromine has a lesser impact on the human central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
than caffeine. However, theobromine stimulates the heart to a greater degree. While theobromine is not as addictive, it has been cited as possibly causing addiction
Substance use disorder
Substance use disorders include substance abuse and substance dependence. In DSM-IV, the conditions are formally diagnosed as one or the other, but it has been proposed that DSM-5 combine the two into a single condition called "Substance-use disorder"....
to chocolate. Theobromine has also been identified as one of the compounds contributing to chocolate's reputed role as an aphrodisiac.
As it is a myocardial stimulant as well as a vasodilator, it increases heartbeat, yet it also dilates blood vessels, causing a reduced blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
. However, a recent paper published suggested that the decrease in blood pressure may be caused by flavanols. Furthermore, its draining effect allows it to be used to treat cardiac failure, which leads to and is exacerbated by an excessive accumulation of fluid in the body.
A 2004 study published by Imperial College London
Imperial College London
Imperial College London is a public research university located in London, United Kingdom, specialising in science, engineering, business and medicine...
concluded that theobromine has an antitussive
Cough medicine
A cough medicine is a medicinal drug used in an attempt to treat coughing and related conditions. For dry coughs, treatment with cough suppressants may be attempted to suppress the body's urge to cough...
(cough-reducing) effect superior to codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
by suppressing vagus nerve
Vagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
activity. In the study, theobromine significantly increased the capsaicin
Capsaicin
Capsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...
concentration required to induce coughs when compared with a placebo. A drug, called BC1036, is being developed by the private UK company SEEK and it uses theobromine to treat persistent cough. In addition, theobromine is helpful in treating asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, since it relaxes the smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
s, including the ones found in the bronchi
Bronchus
A bronchus is a passage of airway in the respiratory tract that conducts air into the lungs. The bronchus branches into smaller tubes, which in turn become bronchioles....
.
A study conducted in Utah between 1983 and 1986, and published in 1993, showed a possible association between theobromine and an increased risk of suffering from prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
in older men. This association was not found to be linear for aggressive tumors. While the association may be spurious, it is plausible. Prenatal and infant exposure to theobromine appeared possibly associated with hypospadias
Hypospadias
Hypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus...
and testicular cancer in one population study.
As with caffeine, theobromine can cause sleeplessness, tremors, restlessness, anxiety, as well as contribute to increased production of urine
Polyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
. Additional side effects include loss of appetite
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
.
Danger for animals
Animals that metabolize theobromine more slowly, such as dogDog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
s, can succumb to theobromine poisoning
Theobromine poisoning
Theobromine poisoning or chocolate poisoning is an adverse reaction to the alkaloid theobromine, found in chocolate, tea, cola beverages, açaí berries, and some other foods. Cacao beans contain about 1.2% theobromine by weight, while processed chocolate, in general, has smaller amounts...
from as little as 50 grams of chocolate for a smaller dog and 400 grams for an average-sized dog. The same risk is reported for cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
s as well, although cats are less likely to ingest sweet food, having no sweet taste receptors. Complications include digestive issues, dehydration, excitability, and a slow heart rate. Later stages of theobromine poisoning include epileptic
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
-like seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s and death. If caught early on, theobromine poisoning is treatable. Although not usual, the effects of theobromine poisoning, as stated, can become fatal.
The toxicity for (pet) birds is not known, but it is typically assumed that it is toxic to birds.
Other
Theobromine is known to induce geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in lower eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s and bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. At the time of a 1991 report, further updated in 1997, by the IARC
International Agency for Research on Cancer
The International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organisation of the United Nations....
, genetic mutations had been found in higher eukaryotic cells, specifically cultured mammalian cells, but the compound was still listed as having inadequate evidence for classification of human carcinogenicity.
Further reading
- http://toxnet.nlm.nih.gov/index.html from the Hazardous Substances Data BankHazardous Substances Data BankThe Hazardous Substances Data Bank is a toxicology database on the U.S. National Library of Medicine's Toxicology Data Network . It focuses on the toxicology of potentially hazardous chemicals, and includes information on human exposure, industrial hygiene, emergency handling procedures,...