Sweeteners - A review of this chemical class

Glucose is a vital component of life on Earth. It is the power that drives the majority of biological life systems. This importance is evident in the fact that Glucose, as an intravenous sugar solution, is on the World Health Organization's List of Essential Medicines[1].

Plants and most algae make glucose via photosynthesis from water and carbon dioxide from energy from sunlight[2]. Within plants, it is used to make cellulose and by all living organisms to produce adenosine triphosphate (ATP), where this energy is created to drive cells[3].

Sugar is one chemical in the sugars (saccharides) families [4]. Within the sugars group, they exist as monosaccharides (glucose, fructose, and galactose), disaccharides(sucrose (glucose + fructose), lactose (glucose + galactose), and maltose (two molecules of glucose). Oligosaccharides or polysaccharides. (Starch and complex carbohydrates, like cellulose)[5]. Monosaccharides and disaccharides are much easier to digest and get the quick energy needed.

As humans, we establish a taste for sweetness?taste receptors at the tip of the tongue with a direct route to the brain [4]. With some theorists, this activates the dopamine response[6]

An evolutionary trait of all animals was the ability to quickly absorb energy sources (sugars and carbohydrates) and convert them to energy to ensure long-term food sources and to keep warm during cooler climates. This was fine as we had limited access, but this is no longer true. Food is easy to access now, and the amounts of sugar can allow for overconsumption, which increases your risk of obesity and diabetes[8,9].

How did sugar become so common?

The history of the sugar industry started thousands of years ago in India, sometime after the first century AD[10] (with some documentation of its use between 1500 and 500 BC)[11], when sugarcane was used. Fun fact: the etymology of the word sugar comes from the Sanskrit word??arkarā[4,11], though the use of sugarcane was concurrently cultivated in China, Taiwan, and New Guinea. By the sixth century AD, this cultivation and processing had reached Persia[12]. This was then spread as part of the arab caliphates to Al-Andalus (the Iberian Peninsula countries of Peninsular Spain, Continental Portugal and Gibraltar) and became a significant trade as part of the "Fine spices.[13]" This is noted by increasing reference to sugar in the literature; however, at this point, its availability was still low due to high prices. Between 1500 - the 1800s, the European colonies (Portugal, Spain, Netherlands, the United Kingdom and France) spread sugarcane and sugar production across the Americas and the Caribbean. The increase in supply helped to bring the cost down, and by the 18th century, the demand for sugar skyrocketed (it was one of Britain's most valuable imports). Sugar was still a luxury item in Europe before the early 19th century. In the late 18th Beet sugar was discovered as a method of producing sugar in the cooler climates in Prussia (and by extension Europe) by Andreas Sigismund Marggraf,[4] and later Franz Karl Achard (his student) began breading and developed one of the first industrial plants.

Due to the Napoleonic Wars, beat-based sugar production spread across France. Jean-Baptiste Quéruel and Benjamin Delessert led industrialization effects. In the United Kingdom, by the start of the 20th century, the British Sugar (Subsidy) Act of 1925 supported sugar production ramp-up and helped lower costs.

In 1900, the world's sugar production was approximately 10 million tons, which increased to 150 million tons in 2005. About 60% of the world's sugar production is from cane, and 40% is from beets[4].

As of 2024, British Sugar Plc produces around?1.2 million tonnes?of white sugar every year (something we should be proud of and helps to support farmers and the people of East Anglia and parts of the East Midlands)[14]. One of the favourite facts about the UK sugar industry is that we now slice as many beets in a day as we did in the entire first campaign (A campaign is a term used for the period where sugar is produced in a year.)

This lower cost and availability drove more consumption of jams, sweets, tea, coffee, cocoa/chocolate, processed foods, soft drinks and desserts. This led to a vast increase in the number of products in this space, including brands that still exist today.

With the increased living standards, more disposable income, and the availability of sugary foods, increased consumption and overconsumption have had a knock-on effect on obesity. This has led to an increased focus on sugar reduction and "diet" versions of these products using alternatives known as sweeteners. However, for many reasons, this group of different chemicals has become subject to numerous claims of being unsafe despite evidence showing them to be safe.

What are sweeteners?

Sweeteners (sugar substitutes) are chemicals that provide sweetness without a Caloric response and are often used as an alternative to sugars. They can either be produced via chemical synthesis or extracted from plants. They can be found standalone in small pills, powders, and packets or as part of other formulations.

Typical food sweeteners include saccharin, cyclamate, aspartame, acesulfame potassium (ace-K) monk fruit extract, sucralose and stevia.

Sugar alcohols such as erythritol, xylitol, and sorbitol are used mainly in chewing gum and dentistry products.

Saccharin

Saccharin was the first artificial sweetener developed in the late 19th century by German chemists Remsen and Fahlberg, who accidentally discovered it[15]. Commercial production started not long after its discovery but became widely available during WWI's reduction in sugar surplus.

It is 300 to 500 times sweeter than sucrose but has a bitter aftertaste[16,17].

Since the 1960s, saccharin has been the subject of health concerns. This was following a study on rats that showed that Saccharin could lead to bladder cancer, which nearly led to a ban. However, it was later discovered that rats involved in the studies were highly susceptible to bladder cancer. There is a mechanism found in rats and not in humans. High doses in rats cause a precipitate, which irritates cells lining the bladder, leading to cancer. World Health Organization noted, "This mechanism is not relevant to humans because of critical interspecies differences in urine composition".[18] The EPA stated in 2010 that it was not seen as a potential hazard to human health. Despite this, it is still banned in Canada. This is often where the safety scare of sweeteners begins.

Cyclamate

Cyclamate was the subsequent significant discovery in this area. It was first found (again by accident) by Michael Sveda and developed by DuPont and then Abbott Laboratories. Initially intended as a way to reduce the bitterness of antibiotics. It is 30–50 times sweeter than sucrose, one of the least potent variants.

Studies in 1966 and 1969 showed links to cancer, which led to a Ban in 1970. However, the 1969 studies used dose levels equivalent to ingesting 550 cans of diet fizzy drinks daily[19]. The study's results could not be repeated; in the 1980s, the FDA reviewed all available evidence and showed it was not a carcinogen but kept the ban in place. The EU examined and removed the ban in 1996. A later long-term study in 2000 on monkeys proved no causal link to cancer.

Aspartame

Aspartame was first discovered in 1965 by James M. Schlatter at the G.D. Searle company when he was looking for an anti-ulcer drug. Again, it was found by accident (becoming a theme). It is 200 times sweeter than sucrose[20], and its sweetness lasts longer than sucrose's (so it is often blended with Acesulfame potassium). Because it is so sweet, you only need a small dose to achieve the desired outcome.

It is one of the most studied chemicals due to constant claims of toxicity, but it is constantly being found safe.

Aspartame contains two naturally occurring amino acids, phenylalanine and aspartic acid. Because of this, if you have the rare inherited condition phenylketonuria (PKU), you must avoid Aspartame. Which cannot be metabolised if you have PKU.

Acesulfame potassium

Acesulfame potassium was first discovered in 1967 by Karl Clauss and Harald Jensen at Hoechst AG. It is 200 times sweeter than sucrose but has a bitter aftertaste. It is often blended with Aspartame.

Acesulfame potassium has excellent heat stability, which makes it perfect for baking products; however, shelf life has to be considered as it can degrade to acetoacetate (which is toxic in high doses). Like other sugar alternatives, it has been wildly studied and found to be safe in the doses used.

An interesting side note: the kidneys excrete acesulfame K, which is used to determine the amount of urine in swimming pools.

Mogroside

Mogroside,?extracted from monk fruit and commonly called?luo han guo,?is 250 times sweeter than sucrose. It is not a permitted sweetener in the European Union but is?allowed as a flavour. It is not widely used.

Sucralose

Sucralose, the most common sugar substitute, was discovered in 1976 by Tate & Lyle scientists. Unlike other alternatives, it is derived from chlorinating sucrose. Most of the ingested sucralose is not metabolized by the body. Sucralose is about 600 times sweeter than sucrose. Sucralose is highly insoluble in fat and can't accumulate in fatty tissues. Only 15% is absorbed, with most passing through.

Most controversy around Sucralose is linked to its marketing, which states it is like sugar.

Steviol glycosides (stevia)

Stevia is a natural extract from Stevia Rebaudiana. It is 50 to 300 times sweeter than sucrose. Stevia has been widely used as a sweetener in Japan since the 1970s, but it has only recently been accepted as safe in large parts of the world.

Sugar alcohol/polyols

Sugar alcohol/polyols are a class of sweeteners usually derived from sugars. Their structure contains one hydroxyl group (?OH) attached to each carbon atom. Their sweetness range from 30 - 100. The lower levels mean they are often used to mask the bitter aftertaste of other sugar substitutes. Oral bacteria do not metabolize sugar alcohol/polyols and do not contribute to tooth decay. Xylitol has been found to deter tooth decay.

While they are safe, they have a side effect: if overconsumed, they can cause bloating, diarrhoea, and flatulence.

Are they toxic?

In short, no.

As shown in the last section. Time and time again, sweeteners have not been found to cause cancer. There is also no causation link to mortality as similar or more significant increases occurred with similar sugar-sweetened beverages.

Some limited studies show that sweeteners might increase obesity; however, this has not been studied comprehensively. Though theory shows it shouldn't, this could be due to behavioural issues.

The WHO doesn't recommend sweeteners as a method for weight reduction. However, in this author's view, switching to sweeteners at the start of a weight loss journey can only be a good thing to show one can be in control before moving to better methods (more balanced diets, consumption reduction and exercise).

The history of sugar production is fascinating, and despite all the misinformation about sweeteners, it is enjoyable for a chemical scientist.

Despite the noise around sweeteners, they are constantly found safe at the doses used.

Declaration of interest

Worked for British Sugar Newark in 2012-13 and did work experience at Britsh Sugar Washington in 2011

References

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2. https://www.rsb.org.uk/images/15_Photosynthesis.pdf
3. https://www.acs.org/molecule-of-the-week/archive/a/adenosine-triphosphate.html
4. Asadi, Mosen, Beet-sugar handbook.
5. Flitsch SL, Ulijn RV (January 2003). "Sugars tied to the spot". Nature. 421 (6920): 219–220. Bibcode:2003Natur.421..219F. doi:10.1038/421219a. PMID?12529622. S2CID?4421938.
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13. Salobre?a: Rutas y senderos / Countryside Paths and Walks, ed. by Juan Manuel Pérez, trans. by Deborah Green (Salobre?a: Ayuntamiento de Salobre?a, 2009), ISBN?8487811132, pp. 9-10.
14. https://www.abf.co.uk/our-businesses/sugar#:~:text=British%20Sugar%20is%20the%20sole,the%20East%20Midlands%20each%20year.
15. Fahlberg's account of how he discovered the sweetness of saccharin appears in: Anon. (July 17, 1886). "The inventor of saccharine". Scientific American. new series. 60 (3): 36. Archived from the original on 2017-03-14
16. von Rymon Lipinski GW; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (2010). NY, NY: John Wiley & Sons; Sweeteners. Online Posting Date: June 15, 2000
17. https://www.sciencedirect.com/topics/medicine-and-dentistry/nutritive-sweetener#:~:text=Saccharin%20is%20the%20oldest%20artificial,but%20has%20a%20bitter%20aftertaste.
18. IARC Monograohs on the Evaluation of Carcinogenic Risks to Humans: Some Chemicals that Cause Tumours of the Kidney or Urinary Bladder in Rodents and Some Other Substances. Vol.?73. Lyon, France: International Agency for Research on Cancer. 1999. p.?607. ISBN?978-92-832-1273-7.
19. Taubes G (2017). The Case against Sugar. London, England: Portobello books. pp.?143–144. ISBN?9781846276378.
20. Aspartame". EFSA. Archived from the original on 10 March 2011. Retrieved 23 September 2010.