The sweetner source plays a big role in defining how safe it is, for example if the source is chemical base then big question marks must sorround it in regards how much safe it is, its always being discovered that when certain sweetner is being considered legally approved after couple of years we can hear or read an article showing us how much damage it caused for the consumers, it might help in diabetic cases but can damage in other organs, such as stevia was considered once safe and later on it was shown that it might cause infertility, and the list goes on, the solution is by moderation, instead of substitution, if a person knows this will cause damage this is for them must be enough sign to stop consuming it, and replace sugar by pure honey, as for honey has chemical structure that will help relieve many sugar related deseases as long as its consumed in moderation and with the right quantity for ones case.

Natural sugar is better. Artificial sweeteners may alter the gut microbiome and lead to impaired glucose tolerance.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615743/pdf/kgmi-06-02-1017700.pdf

https://www.ncbi.nlm.nih.gov/pubmed/18800291

There is a tendency for people to have mistrust in substances that have been chemically altered. Regarding your question, this alteration is from sucrose to sucralose. People place too much trust in the “appeal to nature” which is the rhetorical tactic which proposes that something is good because it is ‘natural’ or bad because it is ‘unnatural.’ However, there are plenty of things occurring naturally which are poisonous (i.e., arsenic, strychnine, curare alkaloids, etc.). With this in mind, it is inconsequential whether or not sucralose is chemically altered from sucrose.

The over consumption of sugar is much more detrimental than the over consumption of sucralose. From an epidemiological stance, there is enough evidence to link the consumption of sugared beverages (and essentially increased sugar consumption) to the causation of obesity. This evidence includes a consistent positive association between sugar intake and long-term weight gain in both prospective cohort studies and randomized controlled trials (RCTs). Additionally, there is enough evidence to indicate that sugar intake is a causal link to obesity as indicated through temporality and a dose-response relationship (Hu, 2013). Furthermore, meta-analyses have provided evidence linking sugared beverages to the risk of diabetes, metabolic syndrome, and cardiovascular disease (Bray & Popkin, 2014).

In regards to sucralose, the study cited by the above researcher (Abou-Donia et al., 2008) which suggested that sucralose alters intestinal microflora and potentially alters p-glycoprotein and cytochrome p-450 was reported to be flawed. An Expert Panel undertook a rigorous investigation of the study and found that, the study was deficient in “several critical areas” and the results were “not consistent with published literature and not supported by the data presented” (Brusick et al., 2009). A review of the current literature on sucralose reported that the substance is safe for its intended use as a non-caloric sugar alternative (Magnuson, Roberts & Nestmann, 2017).

While it is most likely true that excessive consumption of sucralose would have negative health effects, these would pale in comparison to those experienced from excessive consumption of sucrose. Your anecdotal evidence that your grandparents consume vast quantities of sugar with no ill effect should not dictate that sugar is safer than sucralose. Sucralose is safer, but as with everything, moderation is the key.

References:

Abou-Donia MB, El-Masry EM, Abdel-Rahman AA< McLendon RE, Schiffman SS. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71(21):1415-29. doi:10.1080/15287390802328630.

Bray GA, Popkin BM. Dietary sugary and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: health be damned! Pour on the sugar. Diabetes Care. 2014;37(4):950-6. doi:10.2337/dc13-2085.

Brusick D, Borzelleca JF, Gallo M, et al. Expert panel report on a study of Splenda in male rats. Regul Toxicol Pharmacol. 2009;55(1):6-12. doi:10.1016/j.yrtph.2009.06.013.

Hu FB. Resolved: There is sufficient scientific evidence that decreasing sugar-sweetened beverage consumption will reduce the prevalence of obesity and obesity-related diseases. Obes Rev. 2013;14(8):606-19. doi:10.1111/obr.12040.

Magnuson BA, Roberts A, Nestmann ER. Critical review of the current literature on the safety of sucralose. Food Chem Toxicol. 2017;106(Pt A):324-55. doi:10.1016/j/fct.2017.05.047

Thank you all for great answers. I believe this topic will be discussed for a long time.  

Re Safety of Sucrolose Sweetener in Humans

Logan, above, has provided a valuable contribution to this question, deserving of close attention. I will take a more specific, targeted look - I have reviewed the safety of sucralose as to claimed potential cancer promotion effects, a brief summary of which follows:

The most recent (2016) systematic review of all relevant studies across MEDLINE, TOXFILE, BIOSIS Toxline, FOODLINE, CAB Abstracts, Food Science and Technology Abstracts (FSTA), NTIS, and EMBASE [Berry C, Brusick D, Cohen SM, Hardisty JF, Grotz VL,  Williams GM. Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale. Nutr Cancer 2016 Nov-Dec; 68(8):1247-1261.], concluded that there are no sucralose-related metabolites of carcinogenic potential, and both in vitro and in vivo assays have uncovered no confirmed genotoxic activity, with long-term carcinogenicity studies failing to discover any carcinogenic potential.

And in human clinical studies, no evidence of toxicity or metabolic or physiological changes suggesting carcinogenic potential were found. This comprehesive review - and dozens of others - therefore counseled that  sucralose is without any demonstrable carcinogenic activity, even atexposure levels several orders of magnitude greater than the range of customary and anticipated daily ingestion levels. 

In all of these, the systematic review of the evidence from international regulatory bodies (US FDA, the Joint Food and Agricultural Organization/World Health Organization (FAO/WHO) Expert Committee on Food Additives, Health Canada, the Japanese Ministry of Health and Welfare, the Scientific Committee on Food, the European Union, and the Food Standards of Australia and New Zealand) and toxicology experts unambiguously confirm that sucralose is noncarcinogenic and safe to ingest.

I note that two studies - conducted by the same investigators - of sucralose (the Ramazzini Institute (RI)) are widely cited as supporting a safety concern, via an observed increased incidence of certain tumors, hematopoietic tumors in particular (leukemias or lymphomas), in male Swiss mice [Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WC, et al. Consumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. Am J Clin Nutr 2012; 96:1419–1428, 2012.] [Soffritti M, Padovani M, Tibaldi E, Falcioni L, Manservisi F, et al.: Sucralose administered in feed, beginning prenatally through lifespan, incudes hematopoietic neoplasias in male swiss mice. Int J Occup Env Health 2016; 22:7–17] but these are isolated studies and against the  cumulative evidence, and moreover the design of the studies posed certain severe methodological difficulties, among them:

• the accuracy of histopathologic diagnosis of hematopoietic neoplasms,
• and the significant uncertainty of the relevance to humans of such findings in mice (few hematological malignancy data translate to the human clinical domain), and along with study's many additional methodological defects, rob its conclusions of evidentiary integrity, to wit:
• There was no dose-response effect between the dose of sucralose to which mice had been exposed and the incidence of these cancers; this is a known sign of a non-causal relationship, as dose-dependency is a constant fact  of all carcinogenic and mutagenic agents to date, no exceptions.

Study design was poor, given that the mice were exposed from gestation to death but wholly without any adequate control group.

• Only male mice were affected, another signal of compromised methodological design and control.

The vast database of well-designed animal studies on sucralose is absent any evidence of a connection between the sweetener and cancer.

Constantine Kaniklidis

Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)

Oncology Reviewer, Current Oncology [journal]

Society for Integrative Oncology (SIO)

Member, European Association for Cancer Research (EACR)