For something curative and healing, most medicines have a surprisingly noxious taste. From bitter-tasting syrups to the persistent metallic aftertaste of certain tablets, why do many of our best treatments taste so bad — and how much does this actually matter?
The majority of modern drugs were developed from or inspired by compounds found in nature, particularly in static species such as plants and marine invertebrates like sponges and corals.
"They cannot move. They cannot escape. So the only tool that they have to defend themselves from predators is to produce chemicals and they are usually compounds that are, to some extent, toxic for humans or other animals,' Orazio Taglialatela Scafati, a pharmaceutical biologist at the University of Naples Federico II in Italy, told Live Science.
Over millions of years, these plants and animals evolved to produce compounds which interact with different receptors in their predator species, whether it's heart-stopping cardiac glycosides in foxgloves, hallucinogenic alkaloids in belladonna, or toxic taxane compounds in yew berries.
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In response, humans (and many other animals, too) evolved taste receptors to detect these harmful compounds, with the bitter taste serving as a clear signal to avoid those potential foods. The bitter taste is therefore a warning sign that a particular chemical is likely to change the normal chemistry of the body.
Fast forward a few tens of thousands of years and modern science began helping us understand specifically how these compounds interact with our bodies, enabling us to harness their potent physiological effects in safe and effective medicines. Relatively few medications use these compounds exactly as they are produced by the organism, rare examples being antibiotics such as penicillin and painkillers like morphine. The majority instead draw inspiration from the chemical structure of the natural products, mimicking their biological activity with a few targeted improvements.
"A drug must have several features: it must have a good way of administration, it must be absorbed, must reach the target, and must be active," Taglialatela Scafati said. "So sometimes it's necessary to modify the structure of the drug in order to achieve this."
However, said Bahijja Raimi-Abraham, a pharmaceutical scientist and practicing pharmacist at King's College London, when thinking about medicines it's important to draw a distinction between the active drug compound and the dosage form which the patient actually takes.
In the medication the patient receives, the active ingredient is combined with biologically inactive components known as excipients, which both regulate drug properties like absorption and stability, and enable the medication to be processed into syrups, tablets and capsules which are easy to administer.
Theoretically, then, adding flavoring excipients should help to tackle the unpleasant taste of the active ingredient in tablets and syrups. But how patients perceive medications is in fact much more complex than just the flavor, Raimi-Abraham told Live Science. "People focus a lot on the taste but we should actually be focused on palatability," she explained. "We're not just thinking about taste, we're thinking about smell, we're thinking about aftertaste, texture, appearance. These factors determine if somebody is going to accept a medicine."
This is a particularly important consideration when working with pediatric and geriatric patients — if a medication is not palatable, there's a real risk that children and elderly patients will refuse (or struggle) to take the required dose. Not only does this potentially endanger the health of more vulnerable patients, but failing to complete a prescribed course of medication can also contribute to the more widespread phenomenon of drug resistance, especially with regard to antibiotics.
Striking a balance between the different aspects of palatability is consequently extremely important but incredibly difficult. Improving one factor may often adversely affect another and part of the challenge here is the human body's physical mechanism for taste.
"The main taste sensors that people think about are in the tongue, but you also have taste receptors in other parts of the body, including the esophagus and in the stomach," Raimi-Abraham said. A flavored formulation which masks bitterness in the mouth can therefore leave a nasty aftertaste when the active ingredient dissolves in the stomach.
Despite these difficulties, pharmaceutical companies invest millions every year in trying to address this palatability problem. "There are lots of different strategies: sweeteners and flavorings, coatings, tweaking the chemical structure, adding modifiers to change the mouth feel and mask the bitterness. And all this, taking into account patient differences such as age that influence taste," Raimi-Abraham said. "I think the reason why some medicinal products still have a bitter taste is because it's an art as well as a science to get that formulation strategy for the overall taste right."
