Synthetic Sweeteners Pt. 2 – Sucralose, Neotame, Saccharin and Special Natural Guest, Stevia

This is the second part of a discussion on synthetic sweeteners. The first part focused on aspartame since that’s the sweetener most commonly found in diet drinks (at least the ones that I drink) and, consequently, the one that gets questioned about the most. In this part, we’ll look at 4 others – sucralose, neotame, stevia (the odd one out – it’s not synthetic), and saccharin.

Just to start things off – I found a neat, and obviously very dated, little youtube video on taste buds that’s relevant.


Sucralose (marketed as “Splenda”) is a derivative of sucrose, substituting three alcohols (O-H) with chlorine atoms.  Again, this sweetener was discovered through serendipitous taste-testing – a student was asked to “test” the compound but misinterpreted this request as “taste.”

Sucralose is a chlorinated analogue of sucrose. The tagline "made from sugar so it tastes like sugar" can be a bit misleading - aspartame's like a protein but it certainly doesn't taste like a protein, after all

Sucralose is a chlorinated analogue of sucrose. The tagline “made from sugar so it tastes like sugar” can be a bit misleading – aspartame’s like a protein but it certainly doesn’t taste like a protein, after all

Sucralose is about 600 times sweeter than sucrose. Sucralose has been eating away at the market share of aspartame, due to its favorable taste, safety, and stability profile (phenylketonurics don’t need to worry about this one). Animal studies on the health effects of sucralose showed that the sweetener is benign, much like aspartame. For an independent review, see: Grotz, V. L. and Munro, I. C. Regulatory Toxicology and Pharmacology 2009 55:1-5. Importantly, sucralose doesn’t accumulate all that much in the body and gets excreted in a timely manner. The small (2-3%) amount that gets accumulated is metabolized much like sucrose such that it’s converted into a form that’s more easily excreted in urine (it’s glucuronidated). This is quite contrary to recent claims made by Dr. Mercola (you may have seen him on The Dr. Oz show), who recently wrote on his website, “Splenda [or sucralose] is actually more similar to DDT than sugar”. I don’t think you need a chemistry degree to see that the chemical structure of sucralose appears to be more similar to that of sucrose and very different from DDT  (as shown below). A blogging peer of ours, Nicholas Tesla of Kentucky Chemistry, recently wrote a post that completely debunks Mercola’s statement along with a bunch of other content on Mercola’s ‘sucralose is similar to DDT’ page.No, it is not!



Neotame is structurally very similar to aspartame with an extra hydrophobic group highlighted in red. This group, in addition to modifying neotame’s taste profile, also inhibits the same metabolic pathway as aspartame.

 Neotame is structurally very similar to aspartame and is many orders of magnitude sweeter than sucrose. Neotame includes a big greasy hydrocarbon chain added to the aspartic acid nitrogen (presumably to fit better in the receptor, but that’s just my guess – a lot of the details are in the proprietary abyss of patent literature). The neat thing is that this hydrocarbon chain renders this dipeptide immune to the action of the body’s proteases, enzymes which break down proteins. Our bodies’ proteases will break aspartame down to the constituent aspartic acid and phenylalanine, but can’t touch neotame (if anyone else just had “Can’t Touch This” play in their heads, you’re not alone). Since no phenylalanine is released, neotame is considered safer for consumption by phenylketonurics. However, since neotame is a new development in artificial sweeteners, there’s continuing testing for safety.

Then there’s Stevia. Stevia is not a synthetic sweetener, but it is worth mentioning since it is a popular alternative to table sugar (i.e. sucrose). Stevia is a genus of herbs that is known for its sweet leaves. The leaves contain steviol glycosides, natural molecules that contain glucose. These glycosides are potent sweeteners that are roughly 300 times sweeter than sucrose. Stevia has been used for a few decades in Japan to sweeten teas and has been marketed there since 1971. As a result, there is a large amount of data that Stevia is relatively safe for consumption. However, adoption in European and Western countries has been slow, even though the US FDA has determined that it’s safe for consumption even at similarly high doses to aspartame (New York Medical College (15 January 2009). “Notice to the U.S. Food and Drug Administration (FDA) that the use of Rebiana (Rebaudioside A) derived from Stevia rebaudiana, as a Food Ingredient is Generally Recognized as Safe (GRAS)). Many critics of aspartame and the like laud Stevia as the all-natural sweetener, which surely it is, but natural doesn’t necessarily mean safer as our own Dorea Reeser recently discussed in her recent Guest Blog post for the Scientific American, “Natural versus Synthetic Chemicals is a Gray Matter” . The JECFA conducted a similar review on Stevia as they did on aspartame and concluded that Stevia is safe for consumption with one caveat – they suggested that there is a negative effect on hypertension at high doses and, thus, recommended a relatively low recommended daily intake (although still above what one would reasonably consume in a day). Benford, D.J.; DiNovi, M., Schlatter, J. (2006). “Safety Evaluation of Certain Food Additives: Steviol Glycosides” (PDF). WHO Food Additives Series (World Health Organization Joint FAO/WHO Expert Committee on Food Additives (JECFA)) 54: 140.)

Steviol glycoside

Steviol glycoside is an active sweetener isolated from the stevia genus of herbs. It consists of a steviol core, highlighted in red, bound to molecules of glucose.

The last sweetener I’ll talk about is saccharin. It may seem odd that I’ll leave it to last, considering that it was discovered in 1878. And it is – I have no good reason to put it last. Saccharin, marketed as “Sweet’n’Low,” is a very simple and stable compound derived from coal tar. Because of its stability, saccharin will pass through the body unmetabolized, thus providing no energy to the body. There was some controversy regarding its discovery – you can read more about that on the Wiki article. Saccharin is a really interesting artificial sweetener. It has been around for over a century and still has a significant market share. After some initial safety concerns, the EPA removed saccharin from the list of chemicals hazardous to human beings. Oddly enough, higher animal models such as primates showed increased incidence of cancer in some studies, but the same correlation wasn’t found in humans. The only problem with it is that it gives a slightly bitter aftertaste, which is why things like aspartame were developed. It’s also a compound that strikes me as totally weird – it looks completely different from the other compounds mentioned, but it still triggers the same effect. I’ll look into it in more detail and I’ll write about it if I find something.


Saccharin, extracted from tar, looks as if it absolutely does not taste sweet. And yet it makes millions of dollars doing exactly that! SCIENCE!


That’s it for now. I really want to discuss some of the hits you’ll get when you search “Aspartame safety” and things like that. It’s downright fascinating, what comes up. Fascinating and a little depressing.

Images are from Wikimedia Commons, Dorea, I drew them or they’re pictures of things.


  1. lynnk says:

    You might pose that sweet taste/chemical structure question to these folks:

  2. rwwh says:

    Sweetness is weird. I studied some sweet compounds for my PhD, and learned some strange sweetness facts:
    – Chloroform is sweet
    – Hydrogen sulphide at very high doses “tastes” sweet (before you pass out, apparently).
    – Thaumatin is a sweet tasting protein. Molecule for molecule it is much sweeter than any small molecule. It is used as a sweetener sometimes, but it has the disadvantage that its taste lingers on for minutes.
    – There are compounds that are countering sweet taste: after a small dose of such a (slightly bitter) compound, taking a handful of sugar crystals in your mouth feels like eating sand….

    In the end, if you talk to a pharmacologist, he will tell you that at the concentrations at which sugar is “active”, it is no surprise that such different reactions take place. Anything will stick to anything at such high concentrations….

  3. Dorea Reeser says:

    Thank you for sharing this! All of this is REALLY interesting! I would never have known that chloroform is sweet, and I didn’t know what thaumatin is. How do you study the “sweetness” of compounds?

  4. rwwh says:

    I didn’t do a lot of tasting: what I did during my PhD studies is develop modeling techniques to study the structure of sweet tasting compounds, in the hope that we could learn to predict sweetness. In fact, the modeling techniques proved to be more valuable later than the actual results on sweet tasting compounds!

    There are ways of testing how sweet compounds are: you can let a group of people compare the sweetness of a dilute solution of the new compound with a standard sugar solution. The result is unfortunately very dependent of the concentration of the sugar solutions. The scores of some artificial sweeteners that are “hundreds of times sweeter than sugar” were measured at very low sweetness. This means that when you compare to just a little bit of sugar in water, a solution of the artificial sweetener is equally sweet already even if it is hundreds of times less concentrated. At higher concentrations the “sweetness ratio” of a lot of these compounds quickly gets smaller, and at the top of the scale nothing can beat the sweetness of a concentrated sugar solution.

    How to test the sweetness of lethal compounds like beryllium salts, hydrogen sulphide or chloroform: I have absolutely no idea…. maybe they only did these by measuring the nerve response of sweet papilla from a cow’s tongue…..

  5. Hasan Khan says:

    That’s awesome, thanks for sharing. So sweetness is a non-linear function of concentration, is that right? Very interesting. I’d like to try something that counters sugar like that.

  6. Rob Hooft says:

    Yup, that is right. Sweet compounds have a sweetness saturation level, and those are all different for different compounds. At low concentration the effect may be linear (as far as you can define that for a subjective experience), but at higher concentrations the additional sweetness is always sublinear.

  7. Pat Free says:

    is regular sugar the best sweetener if you use it in moderation?

  8. Hasan Khan says:

    I think so, for taste purposes anyway. The artificial sweeteners are heat stable, but I’ve heard people argue that the taste is different when baking with artificial sweeteners. If you’re not too worried about taste and you don’t need to heat something, consider using some sweetener to cut down on the sugar content.

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