The compounds could not only help drug companies make bitter-tasting medicines more palatable, they could also help food manufacturers reduce the vast amounts of sugar, salt and fat they add to most processed foods. Part of the reason these additives make food taste better is that they mask bitter tastes.
Biotech firm Linguagen of New York last month received patent protection for the family of blockers it has discovered, and it says there is already interest from food and drug companies. "A major food ingredient company is testing them, and a major pharmaceutical company," says chief operating officer Shawn Marcell.
"This has been a real breakthrough," says Linda Bartoshuk of Yale University, who studies taste perception. "For most of the stuff you hear out there, they almost never have data and they almost never publish anywhere reliable. But this is good solid science."
Linguagen was founded by Robert Margolskee of the Mount Sinai School of Medicine in New York, who discovered the particular cascade of reactions that leads to bitterness perception. When taste receptor cells in the mouth detect bitter compounds such as naringin, found in grapefruit, caffeine and the painkiller ibuprofen, they release a protein called gustducin (see Graphic). This triggers a series of reactions that finally results in a nerve impulse being sent to the brain saying "bitter".
Researchers at Linguagen tested a huge range of compounds from chemical libraries to see if any could block gustducin release. In test tubes they mixed the compounds one by one with a dye and the relevant components found in the mouth. When the dye turned blue, it signalled that gustducin had been produced. If it did not turn blue, the researchers assumed that the compound was blocking gustducin production. The team confirmed that the potential blockers really did prevent bitterness being perceived when lab mice could not distinguish a bitter solution doped with the blocker from plain water.
Then the researchers tried the best ones themselves, sipping coffee and grapefruit juice containing the compounds. Stephen Gravina, who carried out the experiments, said the coffee's flavour was "milder and more mellow".
Usefully, all the compounds that blocked bitterness are nucleotides, the family of molecules that includes the building blocks for DNA and RNA. All of them are naturally occurring and already found in various foods. That means the compounds will not require FDA approval when small amounts are added to food and drugs.
"We don't know exactly how it works," admits Gravina. But the researchers think that by bonding to the mouth's bitter taste receptors in place of the bitter compounds, they inhibit the release of gustducin.
Trying to block bitter flavours is far more practical than, say, trying to remove any of the vast range of compounds that can make food taste unpleasant. And only tiny amounts of bitter blockers are required to stop the bitter signal reaching the brain. The reason is evolutionary: some bitter substances are highly poisonous, so we need to detect compounds like them at very low concentrations.
If Linguagen's blockers are proven safe and effective, they could go a long way to making food healthier. At the moment, vast amounts of sugar, fat and salt, which are known to contribute to obesity, high blood pressure and the risk of strokes, are added to processed foods. One tin of soup can contain half the recommended daily intake of salt. Bitter blockers would avoid the need to mask unpleasant flavours and could also make bitter-tasting, healthy foods such as broccoli and soya more palatable.
Adding bitter blockers will not stop us detecting food that is rotten, adds Linguagen scientist Richard McGregor. Bad smells and sour tastes, conveyed to the brain through a different set of receptors and chemical messenger, warn us when food has gone off.
As well as working to develop more potent blockers to work in extremely bitter medicines, such as HIV drugs, Linguagen also hopes to tackle entirely different messengers and reaction pathways to produce artificial sweeteners and salt substitutes.
Written by Celeste Biever, Boston
New Scientist issue: 1 March 2003
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