TheobromineBy Mariah BakerToxins Biol 445

Introduction• I had always heard that dogs were “allergic” to

chocolate. I wanted to find

1. if this was true, and

2. what substance in chocolate could be responsible for this.

• This lead me to find Theobromine and heightened my curiosity of how it can be harmful to animals, yet useful to humans.

In this presentation I will include…

• Where Theobromine is found and how it is classified.

• The history of Theobromine and how it is currently

being used.

• It’s toxicity towards animals.

• The mechanisms of toxicity.

• Ways that theobromine is used in medical treatment.

What is Theobromine?

• Chemical formula: C7H8N4O2

• Also known as: Xantheose

• IUPAC name: 3,7-dimethyl-1H-purine-2,6-dione

• Classification: Xanthine alkaloid

• Similar to: Theophylline, Caffeine• Fun fact: Theobromine doesn’t actually contain any bromine. It gets it’s

common name from the plant not the element.

Where is Theobromine found?

• Theobromine is mainly found in cacao beans from the plant, Theobroma cacao.

-Theobroma cacao can be found in Guatemala, Mexico, Caracas, Mexico, and India.

• It has also been found in the leaves of the tea plant, the kola nut, yerba mate, and the guarana berry.

• Theobromine is most commonly found in chocolate that we consume. This is due to chocolate coming from cacao beans.

Chocolate and Theobromine

• The levels of theobromine in chocolate vary based on how the chocolate is processed.

• Milk chocolate has about 60 mg of Theobromine per 1 oz, but dark chocolate has about 200 mg of Theobromine per 1 oz (USDA Nutrient databases for milk and dark chocolate).

• Cocao beans are made up of about 1% Theobromine.

History of Theobromine• Theobromine was

discovered in 1841 by Alexander Woskresensky, who was a Russian chemist (Woskresenky 1842).• The first synthesis of

theobromine from xanthine was done by Hermann Emil Fischer in 1882 (Thorpe 1902).

Toxicity of Theobromine• Theobromine can be toxic to any animal, but cats and dogs

are the ones most worried about.

• Dogs are most commonly known for being at risk because they are most likely to eat chocolate.

- Cats are also at risk, but are less likely to eat chocolate because they cannot sense sweetness.

• Cats and dogs are at a higher risk because they metabolize theobromine much slower than other animals.

• A lesser known fact is that Theobromine is also toxic to bears.

Toxicity in Animals• Consumption can happen by several

different means. Animals can eat chocolate meant for humans, but can also ingest it from other sources such as, food that is made form cocoa by-products or mulch made from the hulls of cocoa beans.

• The LD50 for Theobromine in animals is between 100-200 mg/kg, but signs of toxicity have occurred at lower doses.

"Chocolate." : Food Hazards: Merck Veterinary Manual. N.p., n.d. Web. 24 Apr. 2015.

Mechanism of Theobromine• Theobromine is a competitive

inhibitor of cellular adenosine receptors. This stimulates the central nervous system and causes an increase in neurotransmitter release. • Theobromine inhibits

phosphodiesterase and therefore, causes an increase in the levels of cyclic AMP causing increased respiratory rate, vasoconstriction, and bradycardia.

"DrugBank: Theobromine (DB01412)." DrugBank: Theobromine (DB01412). N.p., n.d. Web. 24 Apr. 2015.

Photo Credit: http://journal.frontiersin.org/article/10.3389/fendo.2012.00113/full

Mechanism of Theobromine (Cont.)• Theobromine also

increases intracellular calcium levels, causing increased strength and contractility of skeletal and cardiac muscles.

• Specifically in the heart, blockage of adenosine receptors lead to accelerated and stronger heart beats.

This is the structure of Adenosine. The blockage of it’s receptor causes the main problem within Theobromine toxicity.

Here are a few charts to warn dog owners of chocolate consumption.

"My Dog Ate Chocolate ... What Should I Do?" My Dog Ate Chocolate ... What Should I Do? N.p., n.d. Web. 24 Apr. 2015.

"Chocolate Toxicity." BRVC Blog. N.p., n.d. Web. 24 Apr. 2015.

Symptoms of Theobromine Toxicity in animals• Vomiting• Polydipsia (excessive

thirst)• Diarrhea• Restlessness• Bloating• Polyuria (excessive

passage of urine)• Ataxia (lack of muscle

coordination)• Tremors and seizures• Tachycardia• Hypertension• Hyperthermia• Comas• And eventual death due to

cardiac arrhythmias or respiratory failure.

Gwaltney-Brant, Sharon, DVM,PhD. "Chocolate Intoxication." www.aspcapro.org. N.p., n.d. Web. 24 Apr. 2015.

Treatment of Theobromine Toxicity• To treat theobromine toxicity in animals the main focus is decreasing

symptoms and getting the toxin out of their bodies.

• Initially gastrointestinal decontamination is done and supportive care is followed.

• Diazepam can be given to stop seizures and arrhythmias should be treated if necessary. One should also watch for hyperthermia and treat as needed, although aggressive treatments are discouraged.

• If treatment is done quickly after ingestion, the survival rate is usually high. Gwaltney-Brant, Sharon, DVM,PhD. "Chocolate Intoxication." Www.aspcapro.org. N.p., n.d. Web. 24 Apr. 2015.

Positive uses of Theobromine in Humans• Theobromine can be used as a diuretic, heart

stimulant, and vasodilator (widens blood vessels) (Drugbank).

-Due to these properties, theobromine can be used to treat high blood pressure.• It can also be used as a respiratory stimulant in

premature babies with respiratory issues (Drugbank).• Studies are currently being done on if Theobromine

and caffeine can help inhibit coughs, but further research is required (Usmani 2004).

An interesting find!• In January of 2015 in

Concord N.H. four bears (two adult and two cubs) were found dead after eating 90 pounds of chocolate that a hunter had put out as bait. The toxicology reports proved that their deaths were due to heart failure caused by theobromine intoxication (msn.com).

Photo credit: MSN.com

Conclusion• Chocolate is toxic to animals, but it depends largely on

the type and amounts ingested.

• Theobromine is the culprit in chocolate and it’s blockage of adenosine receptors causes the biggest problems.

• Dogs, cats, bears, and possibly birds are all fairly sensitive to chocolate, whereas humans, rats, and mice are not.

• Theobromine does have clinical uses, mostly relating to lowering high blood pressure.

Works Cited• "4 Bears Die of Chocolate Overdoses; Expert Proposes Ban." 4 Bears Die of Chocolate

Overdoses; Expert Proposes Ban. N.p., n.d. Web. 24 Apr. 2015.• "Chocolate Toxicity." BRVC Blog. N.p., n.d. Web. 24 Apr. 2015.• "Chocolate." : Food Hazards: Merck Veterinary Manual. N.p., n.d. Web. 24 Apr. 2015.• "My Dog Ate Chocolate ... What Should I Do?" My Dog Ate Chocolate ... What Should I Do?

N.p., n.d. Web. 24 Apr. 2015.• Bibra, Ernst, and Jonathan Ott. "Chocolate (Theobroma Cacao)." Plant Intoxicants: A Classic

Text on the Use of Mind-altering Plants. Rochester, VT: Healing Arts, 1995. N. pag. Print.• Gwaltney-Brant, Sharon, DVM,PhD. "Chocolate Intoxication." Www.aspcapro.org. N.p., n.d.

Web. 24 Apr. 2015.• http://ndb.nal.usda.gov/• Thomas Edward Thorpe (1902). Essays in Historical Chemistry. The MacMillan Company.• Usmani, Omar S., et al. "Theobromine inhibits sensory nerve activation and cough." The FASEB

journal 19.2 (2005): 231-233.• Woskresensky A (1842). "Über das Theobromin".Liebigs Annalen der Chemie und

Pharmacie 41: 125–127. doi:10.1002/jlac.18420410117.