The Chemistry of Chocolate: An Allergy Understood

When I was little, I'd get cold sores if I ate too much chocolate. I thought it was just some kind of mild allergy, passed down to me from my dad, who had the same reaction. Together, we avoided direct sunlight, citrus, chocolate, and a few other things that triggered the onset of these painful sores. On those rare occasions when we forgot to wear SPF lip balm or binged on chocolate, some Tylenol and a couple of L-lysine vitamins prevented a cold sore from appearing.

A couple years ago, I started getting cold-sore-like blisters on my arms, legs, chest and face. The blisters would appear, last several weeks, and then disappear again, leaving circular pink scars in their place. In an attempt to find out what was causing this skin reaction, I began carefully examining what I'd recently eaten whenever the rash began to appear.

Chocolate. It was chocolate.

Instead of getting cold sores from eating too much chocolate, a single Cadbury mini-egg became enough to incite a rash from my forehead to ankles.

After watching others enjoy consequence-free chocolate binges during the past holiday seasons (Christmas, Valentine's Day, Easter...), I decided that it was time to find out why I suddenly was having such a bad physical reaction to chocolate.

Chocolate, seemingly so deliciously simple, is actually a complex substance that contains over 300 different chemical compounds with names ranging from the pronounceable and familiar substance caffeine and element calcium to the tongue-twisting P-hydroxyphenylacetic-acid, Leucocyanidins, and Stearodiolein.

Fortunately, the important chemical components of chocolate aren't quite as linguistically frightening as some of those listed above. This guilty pleasure in its simplest form is composed of theobromine, a chemical structurally similar to caffeine, a well-known neurotransmitter called serotonin, a less-well-known neurotransmitter called anandamide (an active ingredient in marijuana), phenylethylamine, antioxidants, and a tiny bit of straight-up caffeine.

Theobromine: Chocolate's caffeine-like "buzz"

When I began to research the chemistry of chocolate, most of the information I found dealt with only one of its over-300 constituents, theobromine.

Theobromine has the chemical formula C₇H₈N₄O₂, meaning that it is composed of seven carbon atoms (C₇), eight Hydrogen atoms (H₈), four nitrogen atoms (N₄) and two oxygen atoms (O₂). This structure is very similar to the chemical structure of caffeine, C₈H₁₀N₄O_2, which is also contained in small amounts in chocolate. The similarities between theobromine and caffeine help to explain why chocolate, which is comprised of two percent theobromine (chocolate's largest single component), sometimes gives people a "buzz."

Theobromine acts similarly to caffeine as a myocardinal stimulant, or a chemical agent that temporarily arouses or accelerates the activity of heart tissue. Unlike caffeine, the effects of theobromine, which is responsible for a slightly elevated heartbeat and that lovely "buzzed" feeling some get from eating chocolate, are relatively mild and long-lasting. Caffeine, on the other hand, is a strong stimulant that is immediately effective, increasing both heart rate and awareness.

Neurotransmitters: Bringing it down a notch

My friends jokingly call me masochistic, but when it comes to my body sometimes I think they're right. Every month, without fail, just before "that time," I crave chocolate. And I don't mean the random "Oh, that'd be yummy right now," thoughts that might flit through your head when you see a television ad for Hershey's kisses. I'm talking about the wake-up-in-the-middle-of-the-night, can't-stop-thinking-about-the-luscious-goodness-of-it kind of chocolate cravings. The kind of cravings that most premenstrual women can solve with a couple of chocolate bars. Unfortunately, I'm not so lucky.

So why do so many women crave chocolate during their premenstrual period? Apparently, the "calming" effect women want during "that time of the month" or in times of increased stress and anxiety is due to the serotonin found in chocolate.

Serotonin is a compound found in human and animal tissue, especially in the brain where it acts as a neurotransmitter. Neurotransmitters are specialized chemical messengers that carry information from one nerve to another, aiding in the most basic way processes like thinking and moving.

Serotonin has the chemical formula C₁₀H₁₂N₂O, making it yet another component of chocolate comprised of nothing more than carbon, hydrogen, nitrogen and oxygen (just like both theobromine and caffeine). Whether we realize it or not, we've all been introduced to serotonin to some extent by the television ads that have popped up during the last decade for products made by large pharmaceutical companies. Companies that now market prescription drugs directly to viewers rather than going through doctors and insurance companies as they did in the past.

Advertisements for pharmaceuticals began to appear after 1997, when the FDA (Food and Drug Administration) relaxed its requirements. Who hasn't heard of Paxil, an SSRI marketed by the pharmaceutical company GlaxoSmithKline? Paxil ads encourage consumers to seek treatment for "feelings of depression" with the phrase "Your Life is Waiting." While Paxil has virtually disappeared from television advertising over the past several years, other antidepressants stepped in to take its place. The most prominent now is Eli Lilly and Company's Cymbalta, which is marketed using the "Depression Hurts" advertisement campaign, which features those ads that show people sitting alone with painful looks on their faces while a disembodied female voice asks, "Where does depression hurt? ...Everywhere. Who does depression hurt? ...Everyone."

With all of these multi-million dollar ad campaigns for antidepressant medications, who hasn't heard of SSRIs, a common type of pharmaceutical drug used to treat depression, anxiety and bipolar disorder?

Although most people have heard of these types of drugs (usually as part of a laundry list of antidepressants that includes MAOIs and TCAs), most don't know what this acronym actually stands for. SSRI is short for "Selective Serotonin Reuptake Inhibitor."

According to research conducted in the area of psychobiology, many cases of depression are the result of significantly high or low levels of serotonin in the brain. This is why serotonin-related products like SSRIs are so important for treating depression. And why chemists and psychiatrists alike theorize that the consumption of chocolate, and the serotonin that it contains, may actually work in the brain to alter mood.

Chocolate Allergy or Serotonin Sensitivity?

What first piqued my interest in the serotonin component of chocolate was a case report about a chocolate-serotonin interaction.

The report detailed the case of a man who was taking an SSRI called Fluoxetine (a generic form of Prozac and the same SSRI that I happen to take daily) to treat symptoms of depression. According to the Swedish scientists that studied this man's case, he exhibited signs of a rare serotonin sensitivity that caused the patient to break out in a dermal rash after he consumed chocolate.

Okay, so this guy took Fluoxetine... I take Fluoxetine.

And this guy broke out in a skin rash after eating chocolate... and I break out in a skin rash after eating chocolate... Hmmmm.

According to the case report, a plausible explanation for a chocolate-induced skin rash like the one I often experience while taking an SSRI like Fluoxetine is "that SSRI together with serotonin-containing chocolate has increased serotonin concentration to a level where 5-HT receptors system at the dermal and epidermo-dermal junctional area are affected."

It has long been known that antidepressants that work with serotonin, such as Fluoxetine, can lead to skin irritations and rashes. This is why those inserts that the pharmacy gives you with all of your prescriptions listing the warnings includes in its list of side effects for such antidepressants states the following: "During premarketing testing of more than 5600 patients given Fluoxetine, approximately 4% developed a rash and/or [hives]."

This rash can occur because human skin contains not only a system for producing serotonin, but also serotonin receptors, making it very sensitive to serotonin levels in the body. When we ingest an SSRI, the active ingredients don't go directly to our brain, where they're needed. No, the antidepressant must travel the same route as any other medication that we ingest, first being digested in the stomach and then traveling through the small and large intestine where it is absorbed into our bloodstream, eventually making its way to the brain.

On its way to the brain, the digested SSRI travels through your bloodstream, first reaching in numerous places the largest organ in the human body: our skin.

Here's where the indecipherable scientific mumbo-jumbo quoted above comes into play. Basically, the scientists and psychiatrists that published this case report came to the preliminary conclusion (preliminary because it's a case report and not an actual scientific study) that an SSRI-medication like Fluoxetine may interact with ingested chocolate, which contains serotonin, raising the overall level of serotonin in the skin beyond what our serotonin receptors can naturally handle, resulting in a skin rash.

But why would only some patients be affected?

While the scientists who published the case report did not come up with a definitive answer to this question, they believe that individuals who experience symptoms of a chocolate-SSRI interaction, people like me, may be more sensitive to serotonin levels in their body than everyone else.