The sweet smell of research

The pharmacodynamics of asparagus pee

By Bart Braun

Leiden pharmacologists served their colleagues asparagus at an international conference and then asked them to assess the smell of their urine. “Some visitors were rather embarrassed.”

(Het Nederlandstalige origineel van dit artikel staat hier)
Two green asparagus stalks are in the urinals together. The one on the left sniffs and smells something strange. The caption reads “With horror, Arnie realized that standing beside him at the next urinal was the cannibal killer.”
Patt Kelley’s cartoon refers to a well-known phenomenon: eating asparagus makes your pee smell bad. It is an odour compared to rotting cabbage in scientific texts, to the stench of a skunk by the American press and to perfume by the French author Marcel Proust. “I find it difficult to describe precisely”, remarks pharmacologist Coen van Hasselt: “But believe me, it’s not pleasant.”
You are not alone if you are not familiar with this smell. Quite a large portion of the population lack the ability to detect it, although scientists are not sure how large that portion is. In 2011, American scientists traced a single altered DNA bead on chromosome number 1: a different 'DNA letter', or nucleotide base, there means that you can’t smell the stench.
The inability to detect one particular odour is not unique: the scientific name for it is “specific anosmia”. The scent of truffles – not to be confused with flavouring in truffle oil, which is made from petroleum – cannot be detected by some people: the most expensive mushroom in the world tastes and feels like putty to them. Another famous anosmia is part of the smell of coriander. If you don’t have the right olfactory receptor, the plant will only taste of soap.
However, in the case of asparagus, there are apparently non-excretors – people whose bodies do not turn the plant’s substances into smelly sulphuric compounds but into something else – as well as non-detectors. Scientists don’t yet know exactly which compounds are involved in the stink, although, in the eighties, a group of Britons attempted to create synthetic asparagus urinary odour. For science.
Van Hasselt continues: “Some work’s been done on asparagus, but there’s plenty we don’t know. We were looking for an experiment that could be conducted at an annual pharmacology conference and our American colleagues and we decided on an asparagus experiment.”
“We” are Van Hasselt, colleague Jeroen Elassaiss-Schaap and their professor Piet Hein van der Graaf. Their department at the Leiden Academic Centre for Drugs Research develops mathematical models to see how medicines act in our bodies. They and the American researchers set up an experiment to see how the human body processes asparagus.
The guests at the conference were given instructions, explains Van Hasselt: “We wanted them to eat varying quantities of asparagus because we wanted to learn about the dose-response relationship, so they had to keep track of how much asparagus they had eaten and whenever they went to the loo they had to smell how bad they thought it was. They were asked to express that in scores from one to five. I didn’t attend the conference myself, but I heard that some visitors were rather embarrassed.”
The aim was to conduct a clinical trial: a study to which new medicines must also comply. “If you set up a study like that, you have to adhere to very stringent rules and protocols. We and followed them all here: the proposal even passed Leiden’s ethical committee and we have collected all the information very systematically, as you would with a real trial.”
One problem with the setup of the experiment is that people obviously don’t give exactly the same marks to their urine’s odour. “It’s subjective: what might be a five to one person could be a three to another. We took that into account in our model.”
Van Hasselt: “At least, you can see that everyone who can smell it shows a similar progression: just after eating, their scores are relatively low still: one person will give it a zero and another will put down a one. Then the marks shoot up and after a few days, the smell score usually returns to the former level.”
Data reveals that the concentration of odorant in the urine is reduced, on average, by half every three 3.3 hours. Van Hasselt adds: “There are large differences between the subjects, which makes it difficult to consider other factors. We wondered whether age made any difference, or ethnicity, or whether you are male or female. I think that we could learn about that too if we had more data.”
It’s early days yet, but they wouldn’t be surprised if eventually the data comes pouring in all at once because the experiment’s setup is very suitable for citizen science: everyone can cook asparagus and everyone can sniff the loo. Van Hasselt explains: “Schools could do it as a practical biology lesson, medical or pharmacology students could do it as part of a course – they could design their own setup. All the data could be collected on a central website so we could acquire more understanding of the matter. But I’m not the person to do it. The Americans had something like that in mind and our department is seeing whether we could turn it into a practical for the Biopharmaceutical Sciences programme. It would be great to use this experiment for that.”
But isn’t it easier to do an experiment with a substance that everyone can excrete and smell? “You’re right; it wasn’t the easiest option as there are two elements that affect the dose response curve, which makes it more difficult. On the other hand, a simpler substance like caffeine would not have been as interesting, because far more work has been done on it. This experiment added a bit more to our knowledge.”

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