Cheating with Stevia: Make it Sweet Without the Calories

Improving the nutritional value of what we eat, without sacrificing the flavors we’ve grown accustomed to and enjoy, is a complicated problem. Can something taste salty without salt? How would burgers make the barbecue sizzle without fat?

Many scientists are trying to find ways to get the best of both worlds (i.e., keep the flavor while dropping the bad stuff). For example, much research has been done to find substances that are sweet like sugar but not calorie dense. These sugar substitutes are aplenty and collectively termed low- and non-calorie sweeteners or LNCSs.¹ 

Stevia extracts contain well known LNCSs from Stevia rebaudiana Bertoni, a small shrub native to South America.² 

WHAT IS STEVIA? 

Like many plant extracts, stevia is a mixture of molecules and not just one thing. Specifically, the sweet tasting molecules are called steviol glycosides. The most abundant steviol glycoside in the stevia plant is called stevioside.³ On top of being a zero calorie sweetener, stevioside is 50-300 times sweeter than sugar.² 

There are many other steviol glycosides, but we’ll focus on stevioside here since these molecules behave mostly the same when ingested.

Nature is tricky. Despite not being a sugar, stevioside has three glucose molecules as part of its structure. Imagine you see a dog walker holding the leashes for two dogs. Now imagine that one of the dogs is biting on a leash of its own to walk a third dog.

In this example, each dog would be a sugar molecule tethered in place by something called a glycosidic bond (or the leash in our example) which can be broken in a process called hydrolysis.⁴  What kind of molecule is the dog walker? Well, I’m saving that for later so don’t jump to the end to find out. No cheating.

HOW IS STEVIA METABOLIZED? 

It stands to reason that the sugars on stevioside would hydrolyze off after consumption. After all, very few things survive the stomach’s acidic conditions without breaking down. Turns out, stevioside is such a molecule. It isn’t until the colon that stevioside breaks down, and  it’s only by the action of microbes and not your gut.² At this point it’s too late for your body to re-absorb the sugars, and in all likelihood, they are consumed by the bacteria that did the work to free them in the first place. 

IS STEVIA SAFE?

Like many good questions, this one has a long answer, but in a nutshell, it depends. Earlier I went over how stevioside is only one molecule in a mixture that can be extracted from the Stevia plant. Purified stevioside has been shown to be safe in both rats and humans.² In one study, two groups of people, one with type 2 diabetes and one without were given 250 milligrams of oral stevioside 3-times per day for 3 months. After conducting a battery of tests, such as measuring glucose levels and blood pressure, the authors report no significant changes when compared to the placebo in each group.⁵ The sample size in this study, and many like it, is small, yet the trend showing that stevioside is safe for human consumption is consistent. 

As for stevia leaf extracts, a study from 1968 had caused some initial concerns around the potential contraceptive effects in female rats.⁶ Another study showed fertility issues when giving stevia extracts to male rats.⁷ However, many of these negatively associated results have since received significant pushback from the scientific community as there were a few things skewed with these studies, whereas the rats had been given a dose so great it would be impossible for humans to consume anywhere close to the same amount. The rats in these studies could have likely been overdosed with the stevia molecules, later conceded by the professor who ran one of the studies. Newer studies have since tested against this, and even at large amounts of consumption, the results have shown no evidence of any potential dangers.

The bottom line is that isolated steviol glycosides like stevioside seem to be safe on their own, although we should always be aware that plants contain countless molecules, many of which need to be studied. Consider the excess amount of sugar we try to avoid at every turn, which also comes from plants. 

DOES STEVIA HAVE HEALTH BENEFITS?

In general, increased consumption of LNCSs at the expense of sugar could be a health benefit in itself because the negative effects caused by excessive sugar intake are reduced. Stevioside has also been shown to play an active role in decreasing hyperglycemia in mice.⁸ 

WHAT IS THE DOG WALKER? 

Earlier I promised to talk about the molecular scaffold or “dog walker” that holds the sugars in place in molecules like stevioside. That molecule is called kaurene, which is a terpene. Yes, the same kind of molecules which are commonly associated with cannabis. If you do a quick search for terpenes in your favorite browser, the top hits are almost always associated with cannabis containing products, but terpenes are everywhere. Limonene, the main component in orange peel oil; nootkatone extracted from grapefruit peel and an excellent insect repellent; Taxol the chemotherapy drug, and artemisinin the anti-malarial are all terpene derived.⁹   

Now you know. Purified steviol glycosides, the molecules that taste sweet, found in Stevia rebaudiana Bertoni, are made up of a terpene main scaffold and decorated with sugar molecules. 

References: 

1. Magnuson, B. A.;  Carakostas, M. C.;  Moore, N. H.;  Poulos, S. P.; Renwick, A. G., Biological fate of low-calorie sweeteners. Nutr Rev 2016, 74 (11), 670-689.
2. Samuel, P.;  Ayoob, K. T.;  Magnuson, B. A.;  Wölwer-Rieck, U.;  Jeppesen, P. B.;  Rogers, P. J.;  Rowland, I.; Mathews, R., Stevia Leaf to Stevia Sweetener: Exploring Its Science, Benefits, and Future Potential. J Nutr 2018, 148 (7), 1186S-1205S.
3. Makapugay, H. C.;  Nanayakkara, N. P. D.; Kinghorn, A. D., Improved high  performance liquid chromatographic separation of the Stevia rebaudiana sweet diterpene glycosides using linear gradient elution. J. Chromatogr., 1984; 283, 390-395.
4. Yuan, J. P.;  Li, X.;  Xu, S. P.;  Wang, J. H.; Liu, X., Hydrolysis kinetics of secoisolariciresinol diglucoside oligomers from flaxseed. J Agric Food Chem 2008, 56 (21), 10041-7.
5. Barriocanal, L. A.;  Palacios, M.;  Benitez, G.;  Benitez, S.;  Jimenez, J. T.;  Jimenez, N.; Rojas, V., Apparent lack of pharmacological effect of steviol glycosides used as sweeteners in humans. A pilot study of repeated exposures in some normotensive and hypotensive individuals and in Type 1 and Type 2 diabetics. Regul Toxicol Pharmacol 2008, 51 (1), 37-41.
6. Mazzei Planas, G.; Kuć, J., Contraceptive properties of Stevia rebaudiana. Science 1968, 162 (3857), 1007.
7. Melis, M. S., Effects of chronic administration of Stevia rebaudiana on fertility in rats. J Ethnopharmacol 1999, 67 (2), 157-61.
8. Philippaert, K.;  Pironet, A.;  Mesuere, M.;  Sones, W.;  Vermeiren, L.;  Kerselaers, S.;  Pinto, S.;  Segal, A.;  Antoine, N.;  Gysemans, C.;  Laureys, J.;  Lemaire, K.;  Gilon, P.;  Cuypers, E.;  Tytgat, J.;  Mathieu, C.;  Schuit, F.;  Rorsman, P.;  Talavera, K.;  Voets, T.; Vennekens, R., Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. Nat Commun 2017, 8, 14733.
9. Christianson, D. W., Structural and Chemical Biology of Terpenoid Cyclases. Chemical Reviews 2017, 117 (17), 11570-11648.