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A better bitter blocker

With millions of adults and children avoiding nutritious foods because of the bitter taste, and gagging or vomiting when forced to take bitter liquid medicines, Givaudan has expanded on its new bitter blocker at the annual National Meeting & Expo of the American Chemical Society (ACS) in Anaheim, California, this week.

“A lot of people are very sensitive to bitter taste in medicines, calorie-free sweeteners, and foods,” said Ioana Ungureanu, who described the new substance at the ACS meeting, one of the largest scientific US conferences of 2011. “We’d like to be able to make their diets more enjoyable by masking the off-putting flavours of bitterness. Blocking these flavours we call off-notes could help consumers eat healthier and more varied diets. It could encourage them to switch to non-calorie soft drinks and help children and seniors swallow bitter-tasting medications.”

Ungureanu, a research scientist with Givaudan Flavours in Cincinnati, Ohio, noted, for instance, that green, leafy vegetables like spinach and broccoli are excellent sources of calcium and other nutrients important for good health. But calcium, magnesium, zinc and other key minerals and vitamins in nutritious foods unfortunately have a taste that people find unpleasantly bitter. Though it is unlikely that the bitterness of these fresh vegetables will be masked any time soon, there are many other food and beverage products that are becoming much more palatable.

Taste cells with specific receptors blanket the tongue. Scientists have identified 27 receptors for different shades of bitterness, which along with salty, sweet, sour and savoury (or umami), make up the human taste palate. The new bitterness blocker, known only at this point as GIV3616, works by blocking some of the bitterness receptors.

Givaudan scientists previously discovered the first commercially feasible substance capable of blocking bitter taste in humans. Called GIV3727, it inhibited taste receptors involved in people’s ability to detect the bitter aftertaste from artificial sweeteners, including saccharin and sucralose. But Givaudan scientists immediately realised that it could be used as the model for developing blockers for other taste receptors, including substances that might make liquid medicines or bitter foods more palatable.

The new compound, Ungureanu said, is more potent and can dissolve more quickly in foods and beverages. “It works at levels on the order of parts per million and blocks flavours using 10 times less material than what was needed previously.”

“Sensitivity to many foods is partly due to genetics,” Ungureanu said. “Recent studies have estimated that a large portion of the population — almost 25 percent, or 75 million people — are known as supertasters who have heightened sensitivity to bitter foods. “Our compound could one day make supertasters’ coffee more smooth or their veggies more appetising.”

Givaudan published the molecule’s structure in Current Biology on May 27, 201.

Our bitter past

The race to create these taste molecules at Givaudan and other biotechnology companies is a battle against the 400 million years of evolution that make the human tongue what it is today.

The tongue is packed with 10,000 taste buds, each as wide across as a human hair. Every taste bud contains an assortment of 50-150 taste cells, each of which is specialised for one of the five basic tastes: salty, sweet, sour, bitter, or savoury. Food particles stick to the tiny taste receptors on these cells, triggering a chain of events inside the cell that lead to experience of tasting in the brain.

The first creature with bitter taste receptors similar to ours lived about 400 million years ago. Modern humans, birds, fish, and other mammals all carry similar genes from this shared ancestor, genes that allow our bodies to make taste receptors.

Scientists first identified taste receptor molecules in 1998, when Charles Zucker of the University of California, San Diego found that rats lacking a single gene were unable to taste sugar. After the Human Genome Project in 2003, Zucker identified all human genes that code for our specialised taste receptors.

Humans have one type of receptor devoted to sweet, one for salt, one for sour, and one for savoury – but, at the latest count, there are 25 different receptors for bitterness. Scientists believe this variety of bitter receptors capable of detecting thousands of different compounds helps to protect us since poisons and toxins found in nature tend to be bitter tasting.

“It’s a very old evolutionary principle,” says Wolfgang Meyerhof, geneticist at the German Institute of Human Nutrition in Potsdam-Rehbruecke who worked with Givaudan. “Taste helps us to avoid noxious substances and gives an attractiveness to nutrients.”

The sweet future

Many foods and drinks – especially diet drinks made with artificial sweeteners – also have a bitter taste or aftertaste that the food industry would like to eliminate.

“We wanted to develop a bitter blocker that targets a single receptor,” says Meyerhof.

To find GIV3727, Givaudan recruited millions of tiny tongue-like taste testers – cells genetically engineered to be covered in human bitter receptors. These cells glow when exposed to bitter compounds and can be used to check the effectiveness of hundreds of thousands of potential bitter blockers much more quickly and cheaply than human taste testers.

Givaudan screened more than 170,000 molecules to find GIV3727, a bitter “antagonist” that sticks to several different bitter receptors and blocks bitter food compounds from attaching.

After passing safety tests and being certified by the FDA as “Generally Recognized as Safe” (GRAS), the molecule was tested on human volunteers. People who tried the bitter blocker along with artificial sweeteners acesulfame K and saccharin, which are hundreds of time sweeter than sugar, reported tasting much less bitterness but just as much sweetness.

Years ago, scientists discovered another taste compound – adenosine monophosphate – which interferes with the molecular pinball inside of our taste cells to prevent both bitter and sweet tastes. It is used to dull the bitterness of some drugs, which is why some medicines taste so sweet: manufacturers add concentrated sweeteners to overcome the effects that it has on sweetness.

But Danielle Reed, a geneticist at the Monell Chemical Senses Center in Philadelphia who was not involved in the research, says that Givaudan’s achievement was a first.

“There’s never been a demonstration that there is a specific bitter blocker that acts as an antagonist to a bitter receptor,” said Reed.

Givaudan says that several major food companies have purchased GIV3727, which may be coming to supermarket shelves in the future in everything from diet drinks to mouthwash to sugar-free bubblegum.

Source: Science Daily & Inside Science

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