Artificial sweeteners

Your friends have a lot of opinions, don't they?

You're fine.

Honestly, artificial sweeteners are one of those YMMV (your mileage may vary) things... For some, they're a complete lifesaver. For others (like me) they could put someone in the hospital (allergic, not happy making figuring THAT out!). For even others, they can be sugar-binge triggers.

There aren't a lot of long term studies on Splenda in particular yet, but there are some shorter term ones out there if you dig.
If you're feeling okay using Splenda, then keep at it. If you're not, stop. Simple as that.
Your friend may be "concerned"... but it's your body-your science experiment!

Thought maybe I should provide a source for my claims. Keep in mind this is only a small fraction of research being reviewed and that there is also research that states the opposite, which is why I used the word 'could' in my previous post. The science is far from settled but since I don't see food and nutrition science as a religion but rather as possibilities, I try to keep an open mind.

The following excerpt comes from "Metabolic effects of non-nutritive sweeteners" published in 2015 by Yaninia Pepino in Physiology and Behaviour and is an analysis of several studies that seek to answer the question of the metabolic effect of non nutritive sweeteners (NNSs) on the human body. For those that can access it and would like to see the full article, the DOI is 10.1016/j.physbeh.2015.06.024

"2.2. NNSs interfere with gut microbiota and induce glucose intolerance

Perhaps the one unquestionable benefit of NNSs is that they help reduce dental cavities [38]. The anticavity effect of saccharin, sucralose, aspartame, and stevia is not only explained by the fact that these compounds are resistant to fermentation by oral bacteria, but also because of their demonstrated bacteriostatic effects [39], [40], [41]. Data from studies in vitro [42] and in animal models [43], [44], [45], and from a small study in human subjects [45], suggest that the effects of these NNSs are not limited to the microbial inhabitants of the mouth, but extend to those in the gut, thereby affecting the host metabolic phenotype and disease risk [46]. Pioneer work from the group of Schiffman showed that 12 weeks of exposure to Splenda (a NNS comprising 1% w/w sucralose with glucose (1% w/w) and maltodextrin (94% w/w) as fillers) significantly altered gut microbiota composition by decreasing beneficial bacteria and was associated with weight gain in rats [43]. In a recent work, Suez et al. confirmed and extend these findings by identifying a microbe-mediated mechanism by which NNSs might influence metabolism [45]. Suez et al. showed that 11 weeks of exposure to saccharin, sucralose, or aspartame induced higher glucose excursions after a glucose load than those in control animals not exposed to NNSs, and that such metabolic phenotype, at least for saccharin (which due to being the one NNS that more strongly affected glycemic responses in mice was studied further), was mediated by alteration of gut microbiota. Their elegant animal model truly determined causation because they demonstrated that saccharine induced hyperglycemia was transferable to germ-free mice that had never been exposed to saccharin in their life but that received a fecal transplant from saccharin-fed mice, or from microbiota incubated in vitro in the presence of saccharin [45]. Further, they exposed seven young healthy volunteers who were not regular users of NNSs, to one week of the FDA's maximum acceptable daily saccharin intake and evaluated their responses to an oral glucose tolerance test daily. They found that regular saccharin exposure in most subjects (i.e. responders), but not in all of them, increased glycemic responses to a glucose load. Congruent with findings from their animal model, the transplant of stool from human subjects of the responders group induced glucose intolerance in recipient germ-free mice [45]. Noteworthy, the inclusion of a control group for the exposure to saccharin in human subjects would have strengthened the conclusion of the study. Because such a control group was not included in the design, it is unclear whether some healthy individuals exposed to 7 consecutive oral glucose tolerance tests (i.e. daily consumption of 75 g of glucose) would have developed changes in glucose metabolism in the absence of saccharin, and whether transplant of stools from such a group would have caused glucose intolerance in germ-free mice.

Consistent with the findings from Suez et al., Palmnas and collaborators showed that 8 weeks of aspartame exposure (in a dose equivalent to human subjects consuming ~ 2–3 diet soft drinks per day) perturbed gut microbiota and resulted in elevated fasting glucose levels and impaired insulin tolerance in rats [44]. However, the mechanism by which aspartame perturbed gut microbiota is unclear, as aspartame is metabolized before reaching the colon by intestinal esterases and peptidases into amino acids and methanol [47].

2.3. NNSs interact with sweet-taste receptors in the digestive system that play a role in glucose absorption and trigger insulin secretion

2.3.1. Taste receptors are expressed in tissues beyond the tongue

One of the most exciting discoveries in recent years in the field of the chemical senses is the finding of taste receptors in non-taste tissues [48], [49], [50]. Data obtained from studies in mouse models in vivo and in vitro and human duodenal L cells in vitro [48], [49] strongly support the hypothesis that the sweet taste receptor subunit T1R3 coupled to the taste G protein alpha-gustducin, underlies at least one of the components of sugar sensing in the gut. Mice lacking alpha-gustducin or T1r3 show a severely blunted incretin response to glucose challenge [48], [51]. Incretins (GLP-1 and glucose dependent insulinotropic peptide: GIP) are gut hormones that once released into the bloodstream stimulate pancreatic beta-cells to secrete insulin, among other effects (reviewed in [52]). The so-called “incretin effect”, first described in the 60's refers to the fact that an oral glucose load elicits a remarkably greater insulin response than an intravenous glucose load even when both loads are matched to cause identical blood glucose levels [53]. That taste-signaling pathways in the gut intervene in the “incretin effect” is further supported by two observations. First, lactisole, a human sweet taste receptor antagonist, completely blocks GLP-1 release in vitro [48], [49], and significantly reduces GLP-1 secretion in response to intraduodenal or intagrastic glucose administration in human subjects [54], [55]. Second, alpha-gustducin knockout mice have significantly disrupted glucose homeostasis both after a glucose challenge and after post-fasting feeding on chow [48].

In addition to its important function of regulating GLP-1 secretion, sweet-taste signaling pathways in the gut may play a key role in the regulation of glucose absorption from the intestinal lumen into enterocytes. Data obtained in rodents suggest that intestinal sweet taste receptors control both active glucose absorption, by modulating expression of sodium-dependent glucose transporter isoform 1 (SGLT1) [49], and passive glucose absorption, by modulating apical glucose transporter 2 (GLUT2) insertion to the intestine [50]. Unlike wild type, knockout mice lacking either alpha-gustducin or T1r3 failed to up-regulate SGLT1 intestinal expression and glucose absorptive capacity when exposed to a high carbohydrate diet (70% sucrose) [49]. In fact, recent data suggest that sweet taste receptors may contribute to the incretin response by activating SGLT1 [56]. Consistent with findings from previous research that pharmacologically blocked SGLT1 activity [57], data from research studies using SGLT1 knockout mice determined that SGLT1 plays a critical role for intestinal glucose absorption and incretin release [56]."