Since the late 1800’s consumers have been enjoying artificial sweeteners as an additive to their food and beverage of choice. Whether from nature or the laboratory or both, the recent discovery of these tasty little molecules has made it possible to give an otherwise bland or boring menu item some flavor. With the advancement of science and technology, we are to expect more and more of these sweeteners to arrive on the scene. But as such, should we be excited… or cautious? For every new sweetener that gets discovered, there seems to be a wave of skeptics that question safety and other concerns. Here, we will explore a number of popular natural and artificial sweeteners with an in depth look at how they work and what types of health concerns are involved.
What’s on the Tongue
The human tongue is an interesting muscular organ that is sheathed by a moist tissue called mucosa. The tongue is covered in tiny bumps called papillae, of which each bump contains thousands of taste buds which contain gustatory cells. Each of these cells contain a plethora of gustatory receptors – which wait for chemicals to bind to them and tell the brain “yucky” or “yummy”. Regarding these gustatory receptors, they are nothing more than transmembrane proteins that have binding sites… little pockets within the protein’s “activation site” that sort of act like doorbells to the individual cell. When a chemical comes along and fits like a lock n’ key into the binding site of the gustatory receptor, a signal is transduced to the brain and interprets what it is we are tasting. Different chemical substrates have a marked binding capacity (or affinity) to its respective receptor. This affinity follows both a Michaelis constant or Km and a Binding Capacity or Bmax model, which describes, in this case, how long a substrate hangs on to its accompanying receptor. Usually when a chemical hangs onto its receptor for a long time within a gustatory cell, a signal to the brain is amplified as to that particular taste sensation. Conversely, when a chemical has a lower affinity to a given receptor, a shorter and weaker signal is transduced to the brain. This type of taste physiology is important in understanding how sweeteners work.
Sugars are water-soluble carbohydrates that exist as monosaccharides found in nature. Some di-and poly-saccharides found in nature are also classified as sugar and have similar characteristics. Some of the more popular monosaccharides we all know and love are glucose, fructose, and galactose, and are the main points of discussion here. These simple sugars have their own characteristic binding capacities to their respective gustatory receptors, and thus exhibit a given taste indices. For example, sucrose (table sugar) has a sweetness of 1.0, fructose has a sweetness of 1.17, and glucose has a sweetness of 0.741. The way in which these saccharides intramolecularly orient themselves plays a role in how sweet they are – either in the Fisher or Haworth projection formula. More on this important detail later.
Putting the aforementioned simple sugars aside, nature also has other types of sweeteners in its possession – sweet glycosides and sugar alcohols. In glycosides, a monosaccharide (glycone) is attached to a non-sugar molecule (aglycone), yet exhibits a sweetness factor of multiple times that of normal table sugar. From what we learned about affinity to gustatory receptors, these glycosides bind tightly to their associated receptors thus sending an amplified signal to the brain that is translated into an intensified sweetness. For this reason, sweet glycosides need to be diluted down to tolerable amounts so as not too overstimulate our taste buds.
The sugar alcohols on the other hand (maltitol, sorbitol, erythritol, etc.), exhibit their favorable low-calorie sweetness actions by another route. Sugar alcohols, found either in food or prepared industrially using natural sugar, are the result of an opened-ring configuration (Fisher projection formula) as opposed to a closed-ring configuration (Haworth projection formula) as in sugars typically found in their natural state. This is important because when certain sugars are in their opened-ring, or linear configuration, they have a lower glycemic index due to the inability of certain sections of the small intestine to translocate the monosaccharide from the lumen to the bloodstream2,3. Additionally, these unabsorbed alditols make their way to the colon where they get picked up by bacteria who will digest them and use them for their own metabolism3. The unfortunate side effect of this calorie-saving feature is the intense osmotic load in the small intestine that these polyols create, not only causing possible bloating and discomfort, but also impeding absorption of other nutrients4. However, some consumers don’t mind the trade off of having a low-calorie sweetener for a little gastric discomfort.
In addition to nature providing sweet molecules for our enjoyment, the laboratory has definitely not fallen short of providing a plethora of synthetically-prepared chemicals to manipulate our taste buds. Scientists have ways to tweak the molecular structure of existing natural sugars as well as just plain create new chemicals (sometimes by accident) for the purpose of patenting a new and exciting artificial sweetener. While beneficial on the taste buds, sometimes not so beneficial on the rest of our physiology. Here we will take a brief look at just a few popular artificial sweeteners.
Also known as NutriSweet™, aspartame is a synthetically-derived sweetener that has found its way into many popular foods and beverages. Discovered by accident back in the ‘60s, aspartame is a dipeptide comprised of phenylalanine and aspartic acid that has 180-250 times the sweetness of that of table sugar. One might say, well… a molecule simply comprising of two harmless amino acids. Don’t see a problem. The problem doesn’t lie in the weight loss aspect, as aspartame is a very low-calorie sugar substitute (although some might argue that it leads to weight gain), but in the potential side effects this dipeptide might cause. Excess of phenylalanine, aspartate, and one of aspartame’s metabolites diketopiperazine, have been shown to act as neurotoxins and possess carcinogenic activity5,7,8. Considering also that aspartame is actually a methyl ester of phenylalanylaspartate, when this “methoxy” group gets hydrolyzed it eventually turns into formaldehyde6, which can spell disaster in the human body in high amounts. Because aspartame contains a phenylalanine residue, a warning to PKU (phenylketonuria) sufferers is typically displayed on labels of products containing aspartame. PKU is a congenital disorder resulting from the incomplete metabolism of L-phenylalanine, leading to the accumulation of the amino acid to potentially toxic levels. This disorder however, only effects 1 out of every 10,000 people9. Although many, many studies have been performed on this particular sweetener as to its side effects, there is still much debate on how much is “too much”.
This popular aromatic chemical, also known as Sweet’n Low™, was developed in the late 1800’s following a simple 3-4 step reaction process, and like aspartame, was discovered by accident while working on a project that had nothing to do with its flavor. Saccharin has an almost zero caloric yield and possesses 300-400 times the sweetness of table sugar. The controversy with saccharin is its harmful side effects, or so the population thought. Saccharin was banned in 1981 and was considered carcinogenic because it supposedly produced bladder tumors in rats10. The ban has now been removed after further research and is now sold in over 100 countries. As with all scares, it usually boils down to dose-dependency – how much is “too much”… and the fact that the side effects were found in laboratory rats, not humans. One of the other fall backs of saccharin is its unfortunate aftertaste experienced by many consumers. When consumed in high concentrations, saccharin has been noted to have a strong bitter or metallic aftertaste.
A close cousin to saccharin is acesulfame potassium (or Ace K). This synthetically-derived sweetener was developed in the late 1960’s by Karl Clauss, a German chemist who, like many other researchers, discovered this molecule’s sweetness properties by accident. Acesulfame K is approximately 200 times sweeter than table sugar11 and like saccharin has a bitter aftertaste at high concentrations. Manufactures will often blend acesulfame K with other artificial sweeteners to mask its aftertaste. It has gained popularity as a food additive due to its heat and chemical stability12, therefore preventing its degradation in the oven and from other ingredients. Humans cannot metabolize acesulfame K and therefore it provides no caloric yield. There is an ionic bond to potassium, but this does not influence overall dietary intake of potassium due to the negligible amounts it contains13. In the late 1980s the FDA approved acesulfame K to be used in food and beverages and in 2003, approved for use as a general sweetener. All was well until a degradation product of acesulfame K was discovered and deemed toxic in large amounts. Needless to say, the FDA considered the amounts negligible in the average human diet and concluded that no further testing was necessary11.
Also known as Splenda™, sucralose is a very unique artificial sweetener due to the fact that its derivative is in fact table sugar (sucrose). Three chloride atoms are exchanged for three hydroxyl moieties on the sucrose molecule via a stepwise biocatalytic reaction. This just means that enzymes and microbial cultures do the chemistry instead of synthetic reagents. Although similar in structure to table sugar, sucralose possessed 450-650 times the sweetness of sucrose1 and has a pleasant sweet taste in which many of its characteristics are very close to that of sucrose14. Sucralose provides a caloric yield of zero in the human body. This is due to its ability to closely mimic sucrose, but as an organochloride, the body does not recognize it as sucrose. The majority of the sucralose ingested gets excreted in the feces, while the minority that makes it into the bloodstream ends up as waste in urine15 in which no further sucralose gets metabolized and used by any other organs or tissues. After much review by the FDA, it was determined that sucralose has little no evidence of toxicological effects and approved it as safe for human consumption in 1999. It is now estimated that the daily intake for consumers in America on average is 1.6mg per kg of body weight per day16. These statistics suggest that Splenda™ really seems to be the people’s sweetener of choice.
The Pros & Cons
Of course, natural and artificial sweeteners have their goods and bads. It is known that the majority of the artificial sweeteners have either little to no toxicological issues or have negative claims that have been dismissed by the FDA. Most natural sweeteners on the other hand, are blended or diluted to such degrees that the sweetener is in almost negligible amounts to have an effect on our physiology. One such effect would be the potential of a natural sweetener to initiate an insulin spike. This may be especially important to diabetics and hypoglycemics. Research has demonstrated that sweeteners such as saccharin, cyclamate, stevia, and acesulfame-K can potentiate an insulin surge in pancreatic islet cells, whereas others such as aspartame do not17,18. There have also been a number of studies that have observed a correlation between artificial sweeteners and weight gain, especially in children19-21. There is some controversy in this subject however, as to what the underlying cause of the degree of caloric compensation is when preloading with these sweeteners, but the statistics still stand. So, just because it’s not sugar doesn’t mean we can go crazy with its consumption and not expect to experience any adverse effects. The verdict is still out.
To Sum Up
Whether good or bad, neutral or indifferent, the food industry will continue to utilize the technology that is available to them to allow consumers to “have their cake and eat it too”. Further, as long as the Food and Drug Administration tells us it’s okay to consume certain sweeteners, whether natural or artificial, we most certainly will. The fact also remains that as long as there is further research to be done to draw conclusive results as to the potential side effects of such sweeteners, the subject will still remain controversial. One thing is for sure however, as more and more sweeteners continue to make their way from the R&D lab to the grocery store, this billion-dollar industry will continue to remain alive and well.
Author : Chad Brey, a California State University, Northridge alumnus, received his bachelors degree in Biochemistry in 2004 and has since worked as a chemist for various analytical and research facilities such as Amgen, Baxter, and Nusil Technology. Since 1997 he has worked in the dietary supplement industry for companies such as Earthwise Nutrition (formerly known as Great Earth Vitamins) and has earned a number of certificates as an IACET-certified dietary supplement specialist. Chad has written dozens of technical articles on the specifics of how certain dietary supplements work. Chad has formulated and developed small and large molecules in research and development laboratories since 2003 and continues to consult others in R&D today.
Joesten, Melvin D; Hogg, John L; Castellion, Mary E (2007). Sweetness Relative to Sucrose (table). The World of Chemistry: Essentials (4th ed.). Belmont, California: Thomson Brooks/Cole. p. 359. ISBN 0-495-01213-0. Retrieved 14 September 2010.
Hubert Schiweck, Albert Bär, Roland Vogel, Eugen Schwarz, Markwart Kunz, Cécile Dusautois, Alexandre Clement, Caterine Lefranc, Bernd Lüssem, Matthias Moser, Siegfried Peters (2012). Sugar Alcohols. Ullmann’s Encyclopedia of Industrial Chemistry. Weinheimdoi=10.1002/14356007.a25_413.pub3: Wiley-VCH.
Beaugerie L. et al., Clinical tolerance, intestinal absorption, and energy value of four sugar alcohols taken on an empty stomach. Gastroenterol Clin Biol. 1991;15(12):929-32.
Langkilde AM, Andersson H, Schweizer TF, Würsch P., Digestion and absorption of sorbitol, maltitol and isomalt from the small bowel. A study in ileostomy subjects. Eur J Clin Nutr. 1994 Nov;48(11):768-75.
Rycerz K, Jaworska-Adamu JE., Effects of aspartame metabolites on astrocytes and neurons. Folia Neuropathol. 2013;51(1):10-7.
Jacob SE, Stechschulte S., Formaldehyde, aspartame, and migraines: a possible connection. Dermatitis. 2008 May-Jun;19(3):E10-1.
Ashok I, Sheeladevi R, Wankhar D., Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain. J Biomed Res. 2015 Sep;29(5):390-6.
Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M., Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environ Health Perspect. 2007 Sep;115(9):1293-7.
Robin A Williams, Cyril DS Mamotte, and John R Burnett, Phenylketonuria: An Inborn Error of Phenylalanine Metabolism. Clin Biochem Rev. 2008 Feb; 29(1): 31–41.
M D Reuber, Carcinogenicity of saccharin. Environ Health Perspect. 1978 Aug; 25: 173–200.
Sanchari Chattopadhyay et al., Artificial sweeteners – a review. J Food Sci Technol. 2014 Apr; 51(4): 611–621.
Klug C, von Rymon Lipinski GW, Böttger D., Baking stability of acesulfame K. Z Lebensm Unters Forsch. 1992 May;194(5):476-8.
American Dietetic Association, Position of the American Dietetic Association: Use of nutritive and nonnutritive sweeteners. J Am Diet Assoc. 2004;104:255–275.
Arora S, Singh VP, Sharma V, Wadhwa BK, George V, Singh AK, Sharma GS. Analysis of sucralose and its storage stability in barfi. J Food Sci Technol. 2009; 46:114–117.
Roberts A, Renwick AG, Sims J, Snodin DJ., Sucralose metabolism and pharmacokinetics in man. Food Chem Toxicol. 2000;38 Suppl 2:S31-41.
US Food and Drug Administration (1999) Food additives permitted for direct addition to food for human consumption: sucralose. Fed Reg 64:43908–43909.
Malaisse WJ et al., Effects of artificial sweeteners on insulin release and cationic fluxes in rat pancreatic islets. Cell Signal. 1998 Nov;10(10):727-33.
Liang Y, Steinbach G, Maier V, Pfeiffer EF., The effect of artificial sweetener on insulin secretion. 1. The effect of acesulfame K on insulin secretion in the rat (studies in vivo). Horm Metab Res. 1987 Jun;19(6):233-8.
Blum JW, Jacobsen DJ, Donnelly JE. Beverage consumption patterns in elementary school aged children across a two-year period. J Am Coll Nutr. 2005;24(2):93–8.
Berkey CS, Rockett HR, Field AE, et al. Sugar-added beverages and adolescent weight change. Obes Res. 2004;12(5):778–88.
Johnson L, Mander AP, Jones LR, et al. Is sugar-sweetened beverage consumption associated with increased fatness in children? Nutrition. 2007;23(7–8):557–63.
Article originally appeared in HNN