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In an ancient village perched on a Sicilian mountaintop, Gary K. Beauchamp tasted something unexpected. He’d come to the hamlet of Erice, with its medieval castles and cobblestone lanes, for a 1999 meeting on molecular gastronomy. But after sampling extra-virgin olive oil fresh-pressed by a colleague from Italy’s University of Palermo, he returned home with a hunch that’s fueled a decade’s worth of research.
When Beauchamp (pronounced BEACH-am), a biopsychologist at Philadelphia’s Monell Chemical Senses Center, tasted the olive oil—his first taste of it alone, outside the context of food—he noticed an irritating sensation in a very specific spot: the back of his throat. And it just so happened he’d felt that sensation before, tasting a liquid form of the over-the-counter painkiller ibuprofen. “I was dumbfounded that the burn was exactly the same,” he says. “It struck me that maybe the similarity of the throat irritation signaled pharmacological similarity.”
It’s a decades-old idea in the taste field that a compound’s taste properties might predict its drug potency in the body, Beauchamp explains. On a team with Monell colleague Paul A. S. Breslin, who already was studying ibuprofen’s sensory properties, and Monell and University of Pennsylvania chemist Amos B. Smith III, Beauchamp found a possible connection. They confirmed that a specific compound in extra-virgin olive oil, which they dubbed oleocanthal, is responsible for the oil’s sting, and they found that like ibuprofen, oleocanthal blocks cyclooxygenase enzymes, which are players in inflammation and pain (Nature, DOI: 10.1038/437045a; C&EN, Sept. 5, 2005, page 15). “The idea is if oleocanthal is an anti-inflammatory compound like ibuprofen, then maybe it helps explain some of the beneficial effects of consuming olive oil over a lifetime,” Beauchamp says.
But those experiments didn’t resolve all of the team’s questions about olive oil. “We still had no idea why the sensation was restricted to the throat,” Beauchamp says. Most foods with kick, such as wasabi or chili peppers, don’t trigger such a localized sensation. At last month’s American Association for the Advancement of Science meeting in Washington, D.C., Beauchamp talked about how he and his colleagues solved that mystery. It turns out that oleocanthal specifically activates a single sensory protein called transient receptor potential cation channel A1 (TRPA1), and that protein largely resides in one spot: the back of the throat. Ibuprofen, the team learned, also selectively activates that channel over other sensory receptors (J. Neurosci., DOI: 10.1523/jneurosci.1374-10.2011).
“I always find it fascinating when you can provide a molecular explanation for sensation or behavior,” says Craig Montell, who studies TRPA1 in fruit flies at Johns Hopkins University. The channel seems to play an “irritant sensor” role in much of the animal kingdom, he adds. It helps flies detect noxious tastes and smells, and even excessive heat.
The discovery still doesn’t explain a few things, such as the nature of the connection between the throat irritation and anti-inflammatory activity, Beauchamp says. It also doesn’t help determine whether activating TRPA1, as both ibuprofen and oleocanthal do, is an alternative way to fight inflammation. But many teams are exploring oleocanthal’s protective effects. For example, in collaboration with neurobiologist William L. Klein at Northwestern University, Breslin found that low doses of oleocanthal altered the structure of neurotoxic amyloid-β proteins thought to contribute to Alzheimer’s disease (Toxicol. Appl. Pharmacol., DOI: 10.1016/j.taap.2009.07.018).
What’s more, the work doesn’t explain why other substances that activate TRPA1, such as allyl isothiocyanate from mustard oil, irritate tissues throughout the throat and mouth, not just the back of the throat. It may be that the localized sting arises from how oleocanthal activates TRPA1, Beauchamp speculates. Whereas mustard oil activates the channel through covalent interactions with cysteines, the new study suggests oleocanthal works in a different way. By virtue of its different mechanism, oleocanthal may be more specific for TRPA1, whereas mustard oil and other irritants would act on multiple channels, he says. However, the data don’t rule out another possibility: that oleocanthal activates an as-yet-unknown variant of TRPA1, Beauchamp says.
Perhaps most intriguing are the anthropological implications of olive oil’s throaty bite, Beauchamp adds. The irritation is thought to be a hallmark of premium olive oils, and in taste tests, people raised in Mediterranean cultures do not mind the sting, on average, as much as Americans do. It’s possible, he muses, that people unconsciously come to equate the sensation with nutritional or health benefits, which lessens olive oil’s sting, so to speak.
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