Theobromine

Theobromine, formerly known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. 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 classified as a xanthine alkaloid, others of which include theophylline and caffeine. Caffeine differs from these compounds in that it has an extra methyl group (see under Pharmacology section).
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 "broma" ("food"), meaning "food of the gods") with the suffix "-ine" given to alkaloids and other basic nitrogen-containing compounds.
Theobromine is a slightly water-soluble (330 mg/L), crystalline, bitter powder. Theobromine is white or colourless, but commercial samples can be yellowish. It has an effect similar to, but lesser than, that of 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 Aleksandr Voskresensky. Synthesis of theobromine from xanthine was first reported in 1882 by Hermann Emil Fischer.
Sources.
Theobromine is the primary alkaloid found in cocoa and chocolate. Cocoa powder can vary in the amount of theobromine, from 2% theobromine, up to higher levels around 10%. Cocoa butter only contains trace amounts of theobromine. There are usually higher concentrations in dark than in milk chocolate. Theobromine can also be found in trace amounts in the kola nut, the guarana berry, yerba mate ("Ilex paraguariensis"), Ilex vomitoria, Ilex guayusa, and the tea plant. 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:
The mean theobromine concentrations in cocoa and carob products are:
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.
Pharmacology.
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.
In the liver, theobromine is metabolized into xanthine and subsequently into methyluric acid. Important enzymes include CYP1A2 and CYP2E1.
"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.
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. 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.
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. The potential inhibitory effect of theobromine on phosphodiesterases is seen only at amounts much higher than what people normally would consume in a typical diet including chocolate.
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-like seizures and death. If caught early on, theobromine poisoning is treatable. Although not common, the effects of theobromine poisoning can be fatal.
In 2014, four American black bears were found dead at a bait site in New Hampshire. A necropsy and toxicology report performed at the University of New Hampshire in 2015 confirmed they died of heart failure caused by theobromine after they consumed of chocolate and doughnuts placed at the site as bait. A similar incident killed a black bear cub in Michigan in 2011.