The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 7 • November 2015

Safety Issues in the Use of Sweeteners as Alternatives to Sucrose

ERYTHRITOL —A recent paper (Chung, 2013) reported that, using the Ames test and a test for the formation of micronuclei in the bone marrow cells of male ICR mice, erythritol was not mutagenic to bacterial cells and did not cause chromosomal damage in mammalian cells either in vitro or in vivo.

STEVIA, SACCHARIN —The OAT (organic anion transporter) is involved in the elimination by the kidneys of certain drugs (Schiffman, 2012). Competition with this transporter can have serious effects if drug elimination is reduced. An example given in Schiffman, 2012 is the interaction at OATs between non-steroidal-anti-inflammatory drugs and methotrexate that can result in severe methotrexate toxicity. When SACCHARIN coexists in the plasma with drugs that are substrates of OATs, it is said to potentially compete for transport and modulate the drug’s pharmacokinetics (Schiffman, 2012). STEVIOL, the metabolite of steviol glycosides (stevioside and rebaudioside) are also excreted with the involvement of OATs. It is not known what the clinical significance is of the interaction of saccharin or steviol with OATs (Schiffman, 2012). Interestingly, the Schiffman paper notes that steviol is sold commercially (Sigma Aldrich, 2012) as an OAT inhibitor. Stevioside was also associated with DNA aberrations in the liver, spleen, and brain as detected by comet assays, though the effects were possibly due to steviol, a metabolite of stevioside.

The Schiffman paper also notes that studies in rodents have found that sucralose (Splenda®), acesulfame-K, and saccharin were shown to increase the expression of the Na+-glucose cotransporter SGLT1 and the glucose transporter GLUT2 via interaction with sweet taste receptors in the gastrointestinal tract. Schiffman reports that interaction of these same sweeteners with sweet taste receptors in pancreatic beta cells has been shown to induce insulin secretion. These and other effects discussed in the Schiffman paper indicate, the author says, that more research needs to be done on these sweeteners. For example, he notes, it was not known at that time (2012) whether these sweeteners passed the blood-brain barrier.

Another thing reported in the Schiffman paper was that neuroimaging studies had shown in a 2011 paper that routine use of artificial sweeteners altered responses to sucrose in the amygdala and insula as measured by fMRI scanning.

Another paper (Schiffman and Rother, 2013) provided a very lengthy (52 pages) discussion of the various effects of sucralose, including its alteration in the composition of the gut microbiota.

The safest sweeteners appear to be sugar in small amounts and sugar alcohols (such as erythritol, xylitol). In the case of sugar alcohols, it is useful to know that erythritol is by far the least likely of the sugar alcohols to cause diarrhea in excessive amounts and has almost no calories, being excreted largely unchanged in the urine. Another possibility for a safe sweetener is Palatinose™ (isomaltulose, a disaccharide composed of glucose and fructose linked by an alpha-1,6-glycosidic bond), a natural sugar found in honey and sugar cane extract that is digested only very slowly, has a low glycemic index, and increases insulin levels very little. Palatinose is also easy on teeth, as it is not usable by oral bacteria. (See “Isomaltulose” in Wikipedia.)


  • Abou-Donia, El-Masry, Abdel-Rahman, McLendon, Schiffman. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 71(21):1415-29 (2008).
  • Chung and Lee. Genotoxicity assessment of erythritol by using short-term assay. Toxicol Res. 29(4):249-55 (2013).
  • Schiffman. Rationale for further medical and health research on high-potency sweeteners. Chem Senses. 37:671-9 (2012).
  • Schiffman and Rother. Sucralose, a synthetic organochlorine sweetener: overview of biological issues. J Toxicol Environ Health B Crit Rev. 16:399-451 (2013).

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