Death by Chocolate
by Jeremy on Nov 24 2008 (2329 Views)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.
I have an 16 year old Bernese Mountain Dog (the typical life span of this breed is 12 years, and according to Wikipedia, that is .8 years longer then the record in the UK!). He gets chocolate quite often. He is still incredibly healthy, we jog 2-6 miles every day…depending on how tired I am and not him. He is wrong, you can feed a 100 pound dog chocolate safely; not a lot though.
Like every chemical and every poison, the dosage makes the poison.
Water is the mostly deadly chemical/poison in the world. No other chemical kills more people per year then water. It is all in the dosage.
I would not recommend feeding your dog pounds of chocolate, but a Hershey’s Kisses every now and then will not hurt a dog of reasonable size.
With humans and acetaminophen, after a certain dosage, your liver shuts down within ~3 days. There are well-tested dosages for humans of varying weights to establish what’s appropriate. I wouldn’t recommend experimenting with your beloved pet to find out what dosage of theobromine it is that’s going to do it. A Hershey’s Kiss for a 100 pound dog? .35 Kisses for a 50 pound dog? There are plenty of other treats they can enjoy.
Thank you both for your comments.
I’m more inclined to agree with bartel. Though, it doesn’t mean I think that Enahs is wrong (clearly, small amounts of chocolate have not been a problem for his/her dog).
I guess as with most situations it’s better to err on the side of caution. Personally, I think my two little princesses would prefer bacon (Beggin’ Strips) over chocolate anyway.
White chocolate is usually very low in theobromine, so fell free to toss the dog some of that.
Cool post! I hate gathering up courage to ask a question at a seminar only to get shot down. Grad student questions usually are the best ones, too.
Thanks for the comment!
I find grad student questions to be naturally inquisitive whereas (by contrast) Ph.D. questions tend to be more probing and have an feeling of “are you as smart as I am?” So much for education.
Really a cool post. I do agree with many about the low percent of theobromine. It’s interesting becoz., when many were wondering about the death of many vultures, finally they could arrive at a conclusion (the flesh they ate from the carcass, had diclofenac as pain killer)….
Because I worked for more than 30 years on Theobromine metabolism and its physiological effects, I want to say that Theobromine has no stimulant effect on CNS. There is no published study showing such an effect and our results on the contrary showed no dose-effect of Theobromine on the locomotor activity in the rat in contrast to caffeine. In addition, Paraxanthine and Theophylline which are caffeine metabolites are more potent than caffeine (Arnaud MJ. & Enslen M. The metabolism and role of paraxanthine in mediating the physiological effects of caffeine14th International Conference on Coffee Science, San Francisco/California-July 14-19, pp. 71-79, 1991). Although old Pharmacology Encyclopedia mention this CNS effect of Theobromine, it seems now clear that stimulant effects are associated with adenosine receptor antagonism and that the 1-methyl group is necessary to exhibit these effects.
In conclusion, toxicity and physiological effects of high dose of Theobromine and other Methylxanthines are associated to their metabolism and tissue levels due to specie-specific metabolic pathways as well as genetic variations of CYP and receptors.
Thank you for your comment Dr. Arnaud.
Theobromine is a phosphodiesterase inhibitor, meaning that it keeps cyclic AMP from activating. cAMP is an enzyme that has many functions, many involving the heart and blood. If the cAMP is kept from activation in sufficient amounts, blood pressure soars, platelets aggregate in the blood, and positive inotropic action in the heart decreases. This can lead to death if too much theobromine is ingested, even in humans, but dogs are most susceptible due to their slower metabolysis of theobromine because of their usually small size, along with their ability to taste sweetness (which makes them more susceptible than the smaller but unable cat).
Chemical equations for these processes are impossible to find… I’ve searched for hours and learned a ton, but still haven’t found one.
I meant inactivation, so all the effects are the opposite of what I said. (I’ve only been studying this a few days, give me a break)
Thank you so much for the article concerning Dr. Vinson. My husband, John, really enjoyed reading your material.
Thank you, Janice Soderquist