Theobromine

Source: Wikipedia, the free encyclopedia.
Not to be confused with bromine.
Theobromine
Clinical data
Other namesxantheose
diurobromine
3,7-dimethylxanthine
3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione
Dependence
liability		None
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: Unscheduled.
Pharmacokinetic data
MetabolismHepatic demethylation and oxidation
Elimination half-life6–8 hours[1][2]
ExcretionRenal (10% unchanged, rest as metabolites)
Identifiers
  • 3,7-dimethyl-1H-purine-2,6-dione
JSmol)
  • Cn1cnc2c1c(=O)[nH]c(=O)n2C
  • InChI=1S/C7H8N4O2/c1-10-3-8-5-4(10)6(12)9-7(13)11(5)2/h3H,1-2H3,(H,9,12,13) checkY
  • Key:YAPQBXQYLJRXSA-UHFFFAOYSA-N checkY
  (verify)
Theobromine
Identifiers
ECHA InfoCard
 100.001.359 Edit this at Wikidata
Properties
Appearance white solid
Density 1.524 g/cm3[3]
Melting point 351 °C (664 °F; 624 K)
330 mg/L)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Theobromine, also known as xantheose, is the principal alkaloid of Theobroma cacao (cacao plant).[4] Theobromine is slightly water-soluble (330 mg/L) with a bitter taste.[5] In industry, theobromine is used as an additive and precursor to some cosmetics.[4] It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut. It is a white or colourless solid, but commercial samples can appear yellowish.[5]

Structure

Theobromine is a flat molecule,

7-methylxanthine, each of which differ in the number or placement of the methyl groups.[5]

History

Theobromine was first discovered in 1841

Hermann Emil Fischer.[9][10][11]

Etymology

Theobromine is derived from

Greek roots theo ("god") and broma ("food"), meaning "food of the gods".[13]

Despite its name, the compound contains no bromine, which is based on Greek bromos ("stench").

Sources

A chocolate bar and molten chocolate. Chocolate is made from the cocoa bean, which is a natural source of theobromine.

Theobromine is the primary alkaloid found in cocoa and chocolate. Cocoa butter only contains trace amounts of theobromine. There are usually higher concentrations in dark than in milk chocolate.[14]

There are approximately 60 milligrams (1 grain) of theobromine in 28 grams (1 oz) of milk chocolate,[15] while the same amount of dark chocolate contains about 200 milligrams (3 grains).[16] Cocoa beans naturally contain approximately 1% theobromine.[17]

Plant species and components with substantial amounts of theobromine are:[18]

Theobromine can also be found in trace amounts in the

Ilex paraguariensis), Ilex vomitoria, Ilex guayusa,[19] and the tea plant.[20]

The mean theobromine concentrations in cocoa and carob products are:[21][22]

Item Mean theobromine per 100 g
Cocoa powder
 2060 mg
Cocoa beverages
 266 mg
Chocolate toppings 195 mg
Chocolate bakery products 147 mg
Cocoa cereals 69.5 mg
Chocolate ice creams 62.1 mg
Chocolate milks 22.6 mg
Carob products 0.00–50.4 mg

Biosynthesis

Theobromine is a purine alkaloid derived from xanthosine, a nucleoside. 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.[23]

Pharmacology

A diagram featuring 4 skeletal chemical formulas. Top (caffeine) relates to similar compounds paraxanthine, theobromine and theophylline.
Caffeine is metabolized in the liver into three primary metabolites: paraxanthine (84%), theobromine (12%), and theophylline (4%)[citation needed]

Even without dietary intake, theobromine may occur in the body as it is a product of the human metabolism of caffeine, which is metabolised in the liver into 12% theobromine, 4% theophylline, and 84% paraxanthine.[24]

In the liver, theobromine is metabolized into xanthine and subsequently into methyluric acid.[25] Important enzymes include CYP1A2 and CYP2E1.[26] The elimination half life of theobromine is between 6 and 8 hours.[1][2]

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.[27]

The primary mechanism of action for theobromine inside the body is inhibition of adenosine receptors.[5] Its effect as a phosphodiesterase inhibitor[28] is thought to be small.[5]

Effects

See also: Theobromine poisoning

Humans

Theobromine has no significant stimulant effect on the human central nervous system.[4] It is a bronchodilator and causes relaxation of vascular smooth muscle.[4] It is not currently used as a prescription drug.[5] The amount of theobromine found in chocolate is small enough that chocolate can, in general, be safely consumed by humans.

Compared with caffeine, theobromine is weaker in both its inhibition of

adenosine receptors.[4][29] 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.[30]

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.[31]

Also, chocolate may be a factor for

esophageal sphincter muscle in a way that permits stomach acids to enter the esophagus.[32]

Animals

Theobromine is the reason chocolate is poisonous to dogs. Dogs and other animals that

metabolize theobromine (found in chocolate) more slowly[33] can succumb to theobromine poisoning from as little as 50 g (1.8 oz) of milk chocolate
for a smaller dog and 400 g (14 oz), or around nine 44-gram (1.55 oz) small milk chocolate bars, for an average-sized dog. The concentration of theobromine in dark chocolates (about 10 g/kg (0.16 oz/lb)) is up to 10 times that of milk chocolate (1 to 5 g/kg (0.016 to 0.080 oz/lb)), meaning dark chocolate is far more toxic to dogs per unit weight or volume than milk chocolate.

The median lethal dose of theobromine for dogs is 100–200 mg/kg (0.0016–0.0032 oz/lb); therefore, a 10 kg (22 lb) dog would need to consume a minimum of 200 g (7.1 oz) of the most theobromine-rich (5 g/kg (0.080 oz/lb)) dark chocolate, or a maximum of 1 kg (2.2 lb) (of theobromine-rich milk chocolate), to have a 50% chance of receiving a lethal dose. However, even 40 g (1.4 oz) of milk chocolate may induce vomiting and diarrhea.[34]

The same risk is reported for cats as well,[35] although cats are less likely to ingest sweet food, as cats lack sweet taste receptors.[36] Complications include digestive issues, dehydration, excitability, and a slow heart rate. Later stages of theobromine poisoning include epileptic-like seizures and death. If caught early on, theobromine poisoning is treatable.[37] Although not common, the effects of theobromine poisoning can be fatal.

See also

References

  1. ^
    S2CID 10519385
    .
  2. ^
    PMID 3756065
    .
  3. ^
    doi:10.1107/S0108270198009469
    .
  4. ^ a b c d e "Theobromine". PubChem, US National Library of Medicine. 27 August 2022. Retrieved 3 September 2022.
  5. ^
    PMID 20859797
    .
  6. ISBN 978-0813331591
    .
  7. ISBN 978-0-89281-498-5. Archived
    from the original on 2019-09-18. Retrieved 2015-12-12.
  8. doi:10.1002/jlac.18420410117. Archived
    from the original on 2016-06-10. Retrieved 2015-12-12.
  9. ^ Thorpe TE (1902). Essays in Historical Chemistry. The MacMillan Company.
  10. doi:10.1002/cber.18820150194. Archived
    (PDF) from the original on 2019-05-05. Retrieved 2019-09-09.
  11. doi:10.1002/jlac.18822150302
    .
  12. ISBN 978-0-395-71146-0. Archived
    from the original on 2016-03-03. Retrieved 2007-02-23.
  13. ISBN 978-0-415-92723-9
    . (note: the book incorrectly states that the name "theobroma" is derived from Latin)
  14. ^ "AmerMed cocoa extract with 10% theobromine". AmerMed. Archived from the original on 2015-08-11. Retrieved 2008-04-13.
  15. ^ "USDA Nutrient database, entries for milk chocolate". Archived from the original on 2017-07-08. Retrieved 2012-12-29.
  16. ^ "USDA Nutrient database, entries for dark chocolate". Retrieved 2012-11-07.
  17. PMID 1586288
    .
  18. ^ "Theobromine content in plant sources". Dr. Duke's Phytochemical and Ethnobotanical Databases, United States Department of Agriculture. 6 February 2019. Archived from the original on 8 May 2019. Retrieved 9 March 2019.
  19. S2CID 52274913
    .
  20. ISBN 978-0-415-92746-8
    .
  21. ^ "FoodData Central". fdc.nal.usda.gov.
  22. doi:10.1111/j.1365-2621.1984.tb13737.x
    . Mean theobromine and caffeine levels respectively, were 0.695 mg/g and 0.071 mg/g in cocoa cereals; 1.47 mg/g and 0.152 mg/g in chocolate bakery products; 1.95 mg/g and 0.138 mg/g in chocolate toppings; 2.66 mg/g and 0.208 mg/g in cocoa beverages; 0.621 mg/g and 0.032 mg/g in chocolate ice creams; 0.226 mg/g and 0.011 mg/g in chocolate milks; 74.8 mg/serving and 6.5 mg/serving in chocolate puddings.... Theobromine and caffeine levels in carob products ranged from 0–0.504 mg/g and 0-0.067 mg/g, respectively.
  23. ISBN 9780124080614. {{cite book}}: |journal= ignored (help
    )
  24. ^ "Caffeine". The Pharmacogenetics and Pharmacogenomics Knowledge Base. Archived from the original on 2010-11-24. Retrieved 2011-01-08.
  25. PMID 13475320
    .
  26. PMID 10215755
    .
  27. S2CID 8405909
    .
  28. PMID 11692087
    .
  29. ISBN 978-0-07-135469-1
    .
  30. ^ "Theobromine". DrugBank.ca. Archived from the original on 13 November 2018. Retrieved 3 November 2018.
  31. ^ "3,7-Dimethylxanthine (Theobromine)". Toxnet, US National Library of Medicine. 1 December 2017. Archived from the original on 7 October 2018. Retrieved 13 November 2018.
  32. PMID 23462053
    .
  33. ^ "Chocolate – Toxicology – Merck Veterinary Manual". Archived from the original on 12 July 2014. Retrieved 23 December 2017.
  34. ^ Gwaltney-Brant S. "Chocolate Toxicosis in Animals". Merck Veterinary Manual. Merck & Co., Inc. Retrieved 24 December 2023.
  35. ^ Gwaltney-Brant S. "Chocolate intoxication" (PDF). aspcapro.org. ASPCA. Archived from the original (PDF) on 8 February 2017. Retrieved 23 December 2017.
  36. ^ "The Poisonous Chemistry of Chocolate". Wired. 14 February 2013. Archived from the original on 8 February 2017. Retrieved 12 March 2017.
  37. ^ "HEALTH WATCH: How to Avoid a Canine Chocolate Catastrophe!". The News Letter. Belfast, Northern Ireland. 2005-03-01.
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