Several protein-based high potency sweeteners (HPS) are being explored for possible commercialization beyond stevia to protein sweeteners. “The requirements for any new sweetener include regulatory approval, good taste, practical utility and acceptable cost,” said John C. Fry, Ph.D., Director, Connect Consulting. Fry explored these factors in his Global Food Forums 2022 Clean label Conference presentation, “Beyond Stevia: Are Protein Sweeteners the Next Big Thing?”
Regulatory approval is the absolute requirement for commercial success. Paradoxically, the toxicological testing that is the foundation of such approval is seldom the first action in a program of sweetener development. This is because such tests are costly and only likely to be applied to substances that have already shown some practical promise as potential HPS.
Consumers generally prefer natural products, as it is widely assumed these are inherently safer than synthetic additives. However, this is not always true. Fry quoted the example of monatin, a natural amino acid derived from the root of a shrub that grows in Africa. It is a high-potency sweetener with an excellent taste and a history of human use—attributes that recommend it for commercial development. Initial toxicology studies were promising, but further research revealed that, in high doses, monatin affects the heart rate of healthy human volunteers. Commercial development of monatin was abandoned as a result.
In the case of proteins, it is assumed they will be digested into amino acids and metabolized normally. However, this cannot merely be taken for granted and needs to be verified for possible new sweeteners. Secondly, unlike other categories of ingredients, proteins are more likely to be allergenic. This adds another safety testing hurdle. Finally, as a class, proteins include some famously toxic materials, such as snake venom, and proposed novel protein additives must also be screened for their toxic potential.
However, taste is generally the first thing to consider in practical terms. For a sweetener, good taste has two key elements. Firstly, we look for a clean sweetness with no unwanted side tastes. The latter include bitter, metallic and licorice tastes that bedevil some sweeteners. Secondly, the sweetness should be delivered on a timescale similar to sucrose. Ideally, the sweet taste should appear (onset) and decline (linger), similar to sucrose. Currently, no HPS exactly matches the dynamics of sucrose, and both slower onset and longer linger are common issues. Of these, delayed onset is, anecdotally, the greater negative for consumers.
Practical Considerations Beyond Sweetness
Practical utility involves solubility and stability. Solubility is not generally a problem, as high-potency sweeteners are typically used at concentrations of only a few to a few hundred parts per million. Nevertheless, it can be challenging to make liquid concentrates if these are required. For example, some steviol glycosides are limited in use because of poor solubility.
A candidate sweetener must also be stable through its isolation, storage and transport stages as a raw material. Subsequently, it must survive common processing steps—especially pasteurization and possibly baking or canning. Finally, it must be adequately stable in the finished consumer product.
Potential sweeteners must also have an acceptable cost, essentially a function of potency. Potency is the effectiveness of a sweetener on a weight basis compared to sucrose. All HPS have a curved concentration-response relationship, where sweet intensity tends to plateau as concentration increases. In other words, potency depends on the concentration at which it is measured. As the concentration increases, the potency declines. (See chart “Cost in Use of Reb A”) This, in turn, means that the cost-in-use rises with rising concentration.
Another common effect of increasing concentration is that unwanted side tastes are more likely to be perceived. This and the impact on cost are powerful reasons not to use HPS near their concentration-response plateau.
Potency values range from about 30 (for cyclamate, the weakest of the global commercial HPS) to thousands for sweeteners such as neotame and advantame. A good target for a new sweetener would be several hundred or above.
There is a surprisingly short list of sweetener candidate proteins. Most are from plant sources; one (lysozyme) is animal, but there is growing interest in customized synthetic proteins. Many protein sweeteners of natural origin have defects that make them unsuitable for commercialization. After eliminating the candidates with significant flaws, four remain and have received some attention: thaumatin, miraculin, brazzein and designer proteins.
Thaumatin is derived from the katemfe fruit that grows wild in Western Africa. There are five isoforms, but the sweetener is mainly in forms I and II. There are widely differing potency estimates, but most agree that it is several thousand. Thaumatin has a prolonged onset and a long linger. At 5% sucrose equivalent, some individuals can still taste thaumatin 30 minutes later. However, thaumatin is commercially successful and widely used as a flavor modifier rather than a sweetener.
There has been much recent attention paid to miraculin. This protein is present in the miracle fruit that grows wild in Western Africa but can be grown commercially in many parts of the world. Miraculin is only sweet when exposed to acids. In neutral saliva, miraculin is tasteless and blocks the sweetness of other sweeteners. When exposed to acid, miraculin’s structure changes and triggers a very sweet taste. Miraculin remains bound to the sweetness receptor for 20 minutes to an hour. The EU has approved miraculin as a novel food, but a recent USA GRAS notification has been withdrawn because of insufficient safety data. Owing to the need for acid; the unpredictability of the sweet response; and the long-lasting effects, the practicality of miraculin as a sweetener is dubious.
Brazzein is a potently sweet protein obtained from the pulp of the Oubli fruit (Pentadiplandra brazzeana Baillon) that also grows wild in Western Africa. Its potency is around 1800 at 5% sucrose equivalent. It has a high-quality sweetness, and this is one of the rare HPS that can reach 10% sucrose equivalent on its own, which is a level typically found in carbonated beverages or fruit juice. Its dynamics are still an issue, as brazzein takes four to five seconds to reach peak sweetness. It needs to be blended with another sweetener that has a faster onset to achieve more sugar-like dynamics. Several groups are working on the commercialization of brazzein.
Designer proteins start with a protein from nature, and the structure is changed with modern computational protein design. The subsequent molecule can be produced by fermentation. The technique can improve properties, such as greater stability or higher potency. The result is also currently called a “mutant” protein, as it does not exist in nature. Fry suggests that the industry should develop a more consumer-friendly name. Although potentially attractive, these novel proteins represent regulatory approval and marketing challenges. Ultimately, they will probably be considered artificial sweeteners.
Of these four HPS, thaumatin is already a commercial success—but more as a flavor modifier. Miraculin would seem to have little prospect of being more than a curiosity, while brazzein and designer proteins are under active development.
“Beyond Stevia: Are Protein Sweeteners the Next Big Thing?” John C. Fry, Ph.D., CChem, FRSC, FIFST, Director, Connect Consulting