Sweet success

23 May 2022



Aspartame and other artificial sweeteners have been a staple of Western foods and beverages for over a century. But spurred on by the general enthusiasm for healthy living, scientists are increasingly interested in so-called rare sugars. Elly Earls speaks to Sreedevi Kakkad, a food and nutrition consultant at ChemBizR, to learn how research into these unusual products is progressing, and investigate the formulation and regulatory hurdles that scientists and manufacturers still need to overcome.


It is a well-known fact that too much traditional sugar is bad for the body. The growing prevalence of lifestyle conditions such as diabetes and obesity verify its continuing presence in individuals’ collective diets. The response has generally been to replace ‘bad’ sugars that might previously have been ladled into, say, tea, with Splenda tablets, or switch out full-fat Coca-Cola for Coke Zero, which gets its sweetness from the artificial sweetener aspartame.

But with evidence mounting about the potentially damaging effect of artificial sweeteners – aspartame being the most high profile – consumers are increasingly demanding natural alternatives. And the food and beverage industry is, albeit slowly, delivering. Natural sweetener stevia – which is derived from the South American plant of the same name – is an ingredient many people have likely heard of today. Rare sugar allulose, which occurs naturally in fruits like figs and raisins, perhaps, has crossed the public’s radars as well.

But these two ingredients are just the tip of the rare sugar iceberg. There are dozens of different ingredients found in small quantities in nature that have the potential to offer the sweetness of traditional sugars and artificial sweeteners without the negative health impacts.

Metabolic and probiotic benefits

The main difference between traditional and rare sugars is the way they are digested by our bodies. While traditional sugars cause an increase in blood glucose and insulin levels, according to the US Food and Drug Administration (FDA), some rare sugars are metabolised differently, including producing only very small changes in blood glucose and insulin.

“Almost half of consumers are now demanding less sugar in their products so they can manage lifestyle diseases like obesity and diabetes, which are associated with the consumption of traditional sugars,” says Sreedevi Kakkad, a food and nutrition consultant at ChemBizR, a boutique business research and consulting partner for chemical companies globally. “There is an increasing demand from the consumer side for food and beverage products that have lower sugar content but can maintain a similar taste and texture profile.”

Rare sugars allulose and isomaltulose so far have the most evidence from randomised controlled trials to support their benefits. “Allulose, with almost no caloric content, has been shown to reduce the postprandial glycemic response to other co-ingested carbohydrates and contributes to weight loss,” wrote John Sievenpiper, associate professor in the University of Toronto’s department of nutritional sciences, in a recent paper funded by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS). The paper, which summarised the metabolic and physiological properties of five rare sugars, continued: “While isomaltulose, also known as palatinose, has the same caloric content as sugar, it has been shown to have a low glycemic index and improve insulin resistance, with possible benefits for individuals with type 2 diabetes.”

Others, such as nigerose and inulin, which have been studied less, have shown probiotic benefits. The rapidly growing popularity of fermented drinks like kombucha points to consumer demand for products that contribute to improving gut health.

Manufacturing issues

One of the biggest challenges the industry faces when commercialising rare sugars, which also include fucose and cellobiose, is that they are in short supply. “While they are present in nature, their dosages are very small, so it’s challenging to extract them from these natural sources and incorporate them into food and beverage products,” Kakkad says.

Commercialisation of these ingredients also requires a much deeper understanding than currently exists about how to synthesise them, a process that involves using various modified enzymes and cultures. “The research into identifying the actual group of enzymes that can work for these kinds of conversions has been very limited,” Kakkad notes.

It is also not known how viable these kinds of ingredients would be in their ultimate product formulations. “You cannot simply replace traditional sugars with rare sugars because their sweetness intensities are different,” Kakkad explains. “In a case where you may use 1g of glucose, you may have to use 5g of the rare sugar to maintain that taste or texture of the product.”

The problem is that there will be a limiting dosage for the health benefits of rare sugars, above which they could provide negative impacts to people’s bodies. “Identifying those dosage cut off points or benchmark points above which we should limit the ingredient, needs to be extensively evaluated,” Kakkad stresses.

This would involve extensive human trials that have not yet been conducted. As Sievenpiper agreed: “If one wants to assess differences in hard clinical outcomes of clinical and public health importance such as diabetes, cardiovascular disease, cancer and death, then large, randomised trials involving thousands of participants over three to ten years will be required.”

Breakthrough research

Research into the production of rare sugars may be limited, but it is progressing slowly. Kakkad has been particularly encouraged by recent discoveries made at the University of Ghent. In 2019, Professor Tom Desmet at the faculty of bioscience engineering, discovered that the sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) can be used as a transglucosylase to produce rare sugar nigerose.

“That was a major breakthrough because previous research had looked at synthesising nigerose from bulk sugars using a very costly solvent,” Kakkad explains. But by synthesising nigerose from sucrose and glucose efficiently, Desmet and his team have added to the inventory of rare sugars that can conveniently be produced from bulk sugars.

Two years later, Swedish biotech company EnginZyme were able to use enzymes discovered by Desmet, in combination with its own technology platform, to make another breakthrough with rare sugar kojibiose, which is naturally present in honey.

The kojibiose pilot took place at the Bio Base Europe Pilot Plant in Ghent, Belgium, between April and August 2021 and wanted to show the feasibility of commercial-scale production of this rare sugar. The result showed that, compared with fermentation processes, the space-time yields of their process were significantly higher, successfully demonstrating the potential for highly cost-efficient manufacturing.

“We have made an important breakthrough as we can now demonstrate our ability to design, create and validate a commercial process on a large scale,” said EnginZyme CEO and co-founder Karim Engelmark Cassimjee. “Delivering these significant product volumes already, at our early stage of development, strengthens our leadership position in cell-free bioproduction and is an important step towards broad use of our technology.”

Smoothing the regulatory pathway

On top of manufacturing challenges, the regulatory pathway for rare sugar-containing products remains unclear. “A major problem for these kinds of ingredients is that they would be labelled as sugars,” Kakkad explains. “At present, according to most food regulations across the globe, any carbohydrate that is partially digested in the body must be labelled as a sugar.”

That said, the FDA has allowed the low-calorie sweetener allulose to be excluded from total and added sugars counts on nutrition and supplement facts labels when used as an ingredient. “It is different from other sugars in that it is not metabolised by the human body in the same way as table sugar,” the FDA wrote. “It has fewer calories, produces only negligible increases in blood glucose or insulin levels, and does not promote dental decay.”

As awareness continues to grow of the health benefits of rare sugars and how they are digested, Kakkad’s hope is that other regulators follow suit. Of course, this is predicated on the fact that scientists and manufacturers can overcome synthesis and formulation issues.

“Ingredients that can help consumers control their lifestyle diseases and symptoms of their lifestyle diseases are in demand, even if consumers are not yet aware of what those ingredients are,” she concludes. “Once ingredient manufacturers and food and beverage companies have solid information about the health benefits of these ingredients, and once those get published for the public to see, that’s when we believe they will begin to make a huge impact. At that point, the demand would be limitless.”


Sweeteners approved as food additives

The six high-intensity sweeteners approved for food additives:

  • Saccharin – first discovered and used in 1879, before the current food additive approval process came into effect in 1958. Brand names include Sweet‘N Low.
  • Aspartame – first approved for use in 1981. Brand names include Equal.
  • Acesulfame potassium (Ace-K) – first approved for use in 1988. Brand names include Sweet One.
  • Sucralose – first approved for use in 1998. Brand name is Splenda.
  • Neotame – approved for use in 2002. Brand name is Newtame.
  • Advantame – approved for use in 2014.

Source: FDA

The rarer, the better?

The Europe rare sugar market exceeded $200m in 2019 and is anticipated to register a growth rate of 3.5% between 2020 and 2026. Rare sugars are monosaccharides that rarely occur in nature such as D-allose, D-tagatose, D-allulose, xylitol, L-ribose, for example, and can be obtained from biochemical processes such as enzymatic conversion and fermentation. Rare sugars can suppress hyperglycemia and lipid accumulation that helps in preventing diabetes and obesity. Rare sugars contain fewer calories than normal sugars, therefore gaining popularity among consumers as substitutes for sugars and artificial sweeteners such as fructose, sucrose and HFS.

The utilisation of rare sugars has gained traction owing to rising consumer awareness on the use of sugar alternatives and reducing calorie content in diets, creating lucrative growth opportunities for the Europe rare sugar industry.

Source: Graphical Research

The rarer, the better?
A selection of different types of sugar and sweeteners are increasingly used as sugar substitutes.


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