Death by Chocolate

For those of you who don’t know, Dr. Joe Vinson is iconic to the chemical community (believe it or not, even more so than Soderquist).  The American Chemical Society frequently hosts his seminars on some of life’s guilty little pleasures, coffee and chocolate.  I recently had the chance to sit in on his “Science of Chocolate” seminar.  And after and hour of lecturing about the history and chemical make up of chocolate, he took questions from the audience.  When I used to housesit for my aunt, I remember her telling me to be careful not to feed the dog chocolate because it could kill them.  I also recall coming across a warning by the ASPCA about the dangers of cocoa bean fertilizer. 

With my curiosity, I decided to ask the expert.  “Why is chocolate toxic to dogs?”  There was a bit of laughter behind me after I posed the question.  Vinson claimed that the theobromine was responsible.  “You would think that for a 100 pound dog it would be okay to feed them chocolate safely.  But you can’t.”  He then took the next question while I sat there completely unsatisfied with the response. 

So (like my daschund and miniature pinscher) I went digging.  Despite the name, theobromine has nothing to do with halogens.  Theobromine (or more IUPAC-y, 3,7-dimethylxanthine) is a structural derivative of caffeine.  In fact, several species of plants synthesize caffeine by converting xanthosine into theobromine.  The biosynthesis is concluded by N-methylation of theobromine by caffeine synthase (using S-adenosyl-L-methionine or SAM).  Recently, Crozier and co-workers mentioned that several groups have reported identical biosynthetic routes to caffeine (Coffea Arabica – coffee; Camellia sinensis – tea; Theobroma cacao – cacao; see Phytochemistry 2008, 69, 841-856).  At any rate, both theobromine and caffeine are stimulants (caffeine much more so). 

It appears that theobromine metabolism has only been moderately studied in the scientific community; most research has revolved around human metabolism.  Arnaud and Welsch (two research chemists at Nestlé in Switzerland) used ¹⁴C-labeled theobromine to determine the metabolic breakdown of the alkaloid in rats (J. Agric. Food Chem., 1979, 27, 524-527).  They determined that theobromine and methyl uracil were the major radioactive components in the urine (accounting for 85% of total radioactivity).  Other side products included 7-methylxanthine, 7-methyluric acid, 3-methyluric acid and several others.  Interestingly, they noted large similarities in the chemical composition of urine samples in both humans and rats that had been given theobromine.  However, there were quantitative differences between the two species.  Along with their paper, they actually printed pictures of 2D-TLC plates of urine samples of humans and rats.

By comparison, it appears that the canid (or canine) biochemistry for metabolizing theobromine is strangely unique relative to humans (and rats for that matter).  The consensus opinion appears to be that dogs are unable to metabolize and then excrete theobromine efficiently.  Upon ingestion of a theobromine-containing substance, dogs have been reported to excrete “small quantities of an unidentified but apparently unique metabolite” (Drug Metab. Disposition 1984, 12, 154-160).  It also appears that the toxicity associated with the inability to metabolize theobromine causes an increased concentration of intercellular free calcium, which is consistent with significant CNS stimulation and tachycardia (J. Agric. Food Chem., 2005, 53, 4069-4075).  Physiologically, theobromine ingestion in dogs is linked to epileptic seizures, heart attacks and death. 

Bottom line: stick to the peanut butter.  It’s much safer.

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